Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-br...Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.展开更多
BACKGROUND Attention-deficit/hyperactivity disorder(ADHD)is one of the most common disorders in child and adolescent psychiatry,with a prevalence of more than 5%.Despite extensive research on ADHD in the last 10 to 20...BACKGROUND Attention-deficit/hyperactivity disorder(ADHD)is one of the most common disorders in child and adolescent psychiatry,with a prevalence of more than 5%.Despite extensive research on ADHD in the last 10 to 20 years,effective treatments are still lacking.Instead,the concept of ADHD seems to have become broader and more heterogeneous.Therefore,the diagnosis and treatment of ADHD remains challenging for clinicians.AIM To investigate the effects of a multimodal integrated intervention for children with ADHD.METHODS Between March 2019 and September 2020,a total of 100 children with ADHD who were diagnosed and treated at our hospital were assessed for eligibility,two of whom revoked their consent.A case-control study was conducted in which the children were equally assigned,using a randomized number table,to either a medication group(methylphenidate hydrochloride extended-release tablets and atomoxetine hydrochloride tablets)or a multimodal integrated intervention group(medication+parent training+behavior modification+sensory integration therapy+sand tray therapy),with 49 patients in each group.The clinical endpoint was the efficacy of the different intervention modalities.RESULTS The two groups of children with ADHD had comparable patient characteristics(P>0.05).Multimodal integrated intervention resulted in a significantly higher treatment efficacy(91.84%)than medication alone(75.51%)(P<0.05).Children who received the multimodal integrated intervention showed lower scores in the Conners Parent Symptom Questionnaire and the Weiss Functional Impairment Rating Scale than those treated with medication alone(P<0.05).The Sensory Integration Scale scores of children in the multimodal integrated intervention group were higher than those of children in the medication group(P<0.05).Children who received the multimodal integrated intervention had higher compliance and family satisfaction and a lower incidence of adverse events than those treated with medication alone(P<0.05).CONCLUSION Multimodal integrated intervention effectively alleviated symptoms associated with ADHD in children.It enhanced their memory and attention with high safety and parental satisfaction,demonstrating good potential for clinical promotion.展开更多
Spectral classification plays a crucial role in the analysis of astronomical data.Currently,stellar spectral classification primarily relies on one-dimensional(1D)spectra and necessitates a sufficient signal-to-noise ...Spectral classification plays a crucial role in the analysis of astronomical data.Currently,stellar spectral classification primarily relies on one-dimensional(1D)spectra and necessitates a sufficient signal-to-noise ratio(S/N).However,in cases where the S/N is low,obtaining valuable information becomes impractical.In this paper,we propose a novel model called DRC-Net(Double-branch celestial spectral classification network based on residual mechanisms)for stellar classification,which operates solely on two-dimensional(2D)spectra.The model consists of two branches that use 1D convolutions to reduce the dimensionality of the 2D spectral composed of both blue and red arms.In the following,the features extracted from both branches are fused,and the fused result undergoes further feature extraction before being fed into the classifier for final output generation.The data set is from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope,comprising 15,680 spectra of F,G,and K types.The preprocessing process includes normalization and the early stopping mechanism.The experimental results demonstrate that the proposed DRC-Net achieved remarkable classification precision of 93.0%,83.5%,and86.9%for F,G,and K types,respectively,surpassing the performance of 1D spectral classification methods.Furthermore,different S/N intervals are tested to judge the classification ability of DRC-Net.The results reveal that DRC-Net,as a 2D spectral classification model,can deliver superior classification outcomes for the spectra with low S/Ns.These experimental findings not only validate the efficiency of DRC-Net but also confirm the enhanced noise resistance ability exhibited by 2D spectra.展开更多
BACKGROUND Long-term treatment of attention deficit/hyperactivity disorder(ADHD)is associated with adverse events,such as nausea and vomiting,dizziness,and sleep disturbances,and poor maintenance of late ADHD medicati...BACKGROUND Long-term treatment of attention deficit/hyperactivity disorder(ADHD)is associated with adverse events,such as nausea and vomiting,dizziness,and sleep disturbances,and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients’social functioning.AIM To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD.METHODS A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group(methylphenidate hydrochloride and tomoxetine hydrochloride)or the non-pharmacological group(parental training,behavior modification,sensory integration therapy,and sand tray therapy),with 45 cases in each group.Outcome measures included treatment compliance,Swanson,Nolan,and Pelham,Version IV(SNAP-IV)scores,Conners Parent Symptom Questionnaire(PSQ)scores,and Weiss Functional Impairment Rating Scale(WFIRS)scores.RESULTS The non-pharmacological interventions resulted in significantly higher compliance in patients(95.56%)compared with medication(71.11%)(P<0.05).However,no significant differences in SNAP-IV and PSQ scores,in addition to the learning/school,social activities,and adventure activities of the WFIRS scores were observed between the two groups(P>0.05).Patients with non-pharmacological interventions showed higher WFIRS scores for family,daily life skills,and self-concept than those in the pharmacological group(P<0.05).CONCLUSION Non-pharmacological interventions,in contrast to the potential risks of adverse events after longterm medication,improve patient treatment compliance,alleviate patients’behavioral symptoms of attention,impulsivity,and hyperactivity,and improve their cognitive ability,thereby improving family relationships and patient self-evaluation.展开更多
Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the me...Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic(5 XFAD; Jackson Laboratory) mice and their littermates(wild-type, controls) were used in this study. Additional 6-weekold and 10-week-old 5 XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For10-week-old 5 XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5 XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5 XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University,China on December 17, 2015(approval No. AEEI-2015-182).展开更多
AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/a...AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,展开更多
Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with ...Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion. Results Profiling analysis demonstrated that an 11.6kDa protein was significandy elevated in lung cancer patients, compared with the control groups （P〈0.001）. The level and percentage of 11.6kDa protein progressively increased with the clinical stages Ⅰ-Ⅳ and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6kDa peak. Further identification showed that 2177Da was a fragment of serum amyloid A （SAA, MW 11.6kDa）. Two of the new peaks, 1550Da and 1611Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6kDa protein and MS analysis. Conclusion SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.展开更多
As an extension of the wavelet approach to vi- bration control of piezoelectric beam-type plates developed earlier by the authors, this paper proposes a hybrid active- passive control strategy for suppressing vibratio...As an extension of the wavelet approach to vi- bration control of piezoelectric beam-type plates developed earlier by the authors, this paper proposes a hybrid active- passive control strategy for suppressing vibrations of lami- nated rectangular plates bonded with distributed piezoelec- tric sensors and actuators via thin viscoelastic bonding lay- ers. Owing to the low-pass filtering property of scaling func- tion transform in orthogonal wavelet theory, this wavelet- based control method has the ability to automatically filter out noise-like signal in the feedback control loop, hence re- ducing the risk of residual coupling effects which are usu- ally the source of spillover instability. Moreover, the exis- tence of thin viscoelastic bonding layers can further improve robustness and reliability of the system through dissipating the energy of any other possible noise induced partially by numerical errors during the control process. A simulation procedure based on an advanced wavelet-Galerkin technique is suggested to realize the hybrid active-passive control pro- cess. Numerical results demonstrate the efficiency of the pro- posed approach.展开更多
Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxyt...Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM(5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that(5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that(5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for(5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases.展开更多
Liver is the most common site of metastases of colorectal cancer,and liver metastases present with distinct histopathological growth patterns(HGPs),including desmoplastic,pushing and replacement HGPs and two rare HGPs...Liver is the most common site of metastases of colorectal cancer,and liver metastases present with distinct histopathological growth patterns(HGPs),including desmoplastic,pushing and replacement HGPs and two rare HGPs.HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics.Many studies have revealed the association of HGPs with carcinogenesis,angiogenesis,and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications.These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making,and a target of imaging observation for patient screening.Of note,it is crucial to determine the underlying mechanism shaping HGP,for instance,immune infiltration and extracellular matrix remodeling in desmoplastic HGP,and aggressive characteristics and special vascularization in replacement HGP(rHGP).We highlight the importance of aggressive features,vascularization,host immune and organ structure in formation of HGP,hence propose a novel"advance under camouflage"hypothesis to explain the formation of rHGP.展开更多
We mainly investigate the variable-coefficient 3-coupled nonlinear Schrodinger(NLS)system,which describes soli- ton dynamics in the three-spineα-helical protein with inhomogeneous effect.The variable-coefficient NLS ...We mainly investigate the variable-coefficient 3-coupled nonlinear Schrodinger(NLS)system,which describes soli- ton dynamics in the three-spineα-helical protein with inhomogeneous effect.The variable-coefficient NLS equation is transformed into the constant coefficient NLS equation by similarity transformation firstly.The Hirota method is used to solve the constant coefficient NLS equation,and then we get the one-and two-breather solutions of the variable-coefficient NLS equation.The results show that,in the background of plane waves and periodic waves,the breather can be transformed into some forms of combined soliton solutions.The influence of different parameters on the soliton solution and the collision between two solitons are discussed by some graphs in detail.Our results are helpful to study the soliton dynamics inα-helical protein.展开更多
AIM: To identify the difference in gene expression of microphage (Mφ) between normal spleen and portal hypertensive spleen using cDNA microarrays and find new gene functions associated with hypersplenism in portal hy...AIM: To identify the difference in gene expression of microphage (Mφ) between normal spleen and portal hypertensive spleen using cDNA microarrays and find new gene functions associated with hypersplenism in portal hypertension. METHODS: The Biostar-H140s chip containing 14 112 spots of cDNAs were used to investigate the difference of the expression. The total RNA extracted from macrophages isolated from both normal spleen and portal hypertensive spleen was reversely transcribed to cDNA with the incorporation of fluorescent (cy3 and cy5) labeled dCTP to prepare the hybridization probes. After hybridization, the gene chip was scanned for the fluorescent intensity. The differentially expressed genes were screened. That was repeated three times, and only the genes which had differential expression in all three chips were considered to be associated with hypersplenism in portal hypertension. RESULTS: Eight hundred and ninety-six, 1330 and 898 genes were identified to be differentially expressed in three chips, respectively. One hundred and twenty-one genes (0.86%) were identified to be differentially expressed in all three chips, including 21 up-regulated genes and 73 down-regulated genes. The differentially expressed genes were related to ionic channel and transport protein, cyclin, cytoskeleton, cell receptor, cell signal conduct, metabolism, immune, and so on. These genes might be related to the hypersplenism in portal hypertension.CONCLUSION: The investigations based on cDNA microarray can screen differentially expressed genes of macrophages between normal spleen and portal hypertensive spleen, thus may provide a new idea in studying the pathogenesis of hypersplenism in portal hypertension.展开更多
BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that ofte...BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.展开更多
BACKGROUND Chimeric antigen receptor T-Cell(CAR-T)therapy is an effective new treatment for hematologic malignancies.Cytokine release syndrome(CRS)and neurologic toxicity are main toxicities.CRS-induced rhabdomyolysis...BACKGROUND Chimeric antigen receptor T-Cell(CAR-T)therapy is an effective new treatment for hematologic malignancies.Cytokine release syndrome(CRS)and neurologic toxicity are main toxicities.CRS-induced rhabdomyolysis(RM)followed by CART therapy treatment has not been previously reported.CASE SUMMARY We report a case of a 22-year-old woman with relapsed acute lymphoblastic leukemia obtained sequential cluster of differentiation(CD)19 and CD22 CAR-T infusion.This patient experienced grade 3 CRS with RM,mild hypotension requiring intravenous fluids,and mild hypoxia and was managed effectively with the IL-6 receptor antagonist tocilizumab.This patient had no signs of immune effector cell-associated neurologic syndrome.Restaging scans 30 d postCAR-T therapy demonstrated a complete remission,and the symptoms of muscle weakness improved through rehabilitation.CONCLUSION Myalgia is an easily overlooked symptom of severe CRS after CAR-T therapy.It is necessary to monitor myoglobin levels when a patient presents with symptoms of myalgia or acute renal insufficiency.展开更多
Objective: To study the protective effect and molecular mechanism of glucagon-like peptide-1 (GLP-1) on the high glucose-induced endothelial cell injury. Methods: Endothelial cells HUVECs were cultured and divided int...Objective: To study the protective effect and molecular mechanism of glucagon-like peptide-1 (GLP-1) on the high glucose-induced endothelial cell injury. Methods: Endothelial cells HUVECs were cultured and divided into three groups, control group were treated with serum-free low-glucose culture medium, high glucose group were treated with serum-free culture medium containing 40 mmol/L glucose and GLP-1 group were treated with serum-free culture medium containing 10 mmol/L GLP-1 and 40 mmol/L glucose. 24 h after treatment, the expression of apoptosis genes and autophagy genes as well as the levels of oxidative stress products and antioxidants were measured. Results: JAK2, STAT3, Bax, Caspase-9, Caspase-3, Nrf2, NQO1, HO1 and GSH-Px mRNA expression as well as ROS, gp91phox, MDA and ox-LDL levels in high glucose group of cells were significantly higher than those in control group while STSQM1, Atg-5 and LC-3 mRNA expression were significantly lower than those of control group;JAK2, STAT3, Bax, Caspase-9 and Caspase-3 mRNA expression as well as ROS, gp91phox, MDA and ox-LDL levels in GLP-1 group of cells were significantly lower than those in high glucose group while Nrf2, NQO1, HO1, GSH-Px, STSQM1, Atg-5 and LC-3mRNA expression were significantly higher than those in high glucose group. Conclusion:GLP-1 can reduce the high glucose-induced endothelial cell injury by inhibiting apoptosis, reducing oxidative stress and enhancing autophagy.展开更多
LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is the most promising cathode for high-energy Li-ion batteries,despite its poor cycling stability that originates from the reactions that occur with the electrolyte.Herein,to sol...LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is the most promising cathode for high-energy Li-ion batteries,despite its poor cycling stability that originates from the reactions that occur with the electrolyte.Herein,to solve this interfacial issue,a facile electrolytic electrochemical polymerization process was introduced in this paper,and a uniform conductive electrolyte interface(polyaniline)was successfully constructed on the surface of the NCM811 porous electrode(PANI-NCM),which facilitated the charge transfer during charge/discharge.The side reactions at the interface between the cathode and the electrolyte are suppressed,and thereby,the cycling performance and rate capability are considerably improved.PANI-NCM delivers an initial capacity of 157.2 mAh·g^(-1)as well as excellent cyclability(capacity retention of 88%after 500 cycles at 2C),whereas the capacity of the bare NCM811 has dropped to 31.3 mAh·g^(-1).In addition,polypyrrole and polythiophene also can be formed through electrolytic electrochemical polymerization process,which provides a practicable tactic to modify the interfacial stability of cathodes for high-energy Li-ion batteries.展开更多
Background:Parkinson’s disease(PD)is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions(Lewy bodies)within some remaining neurons in the substantia nigra.Recently,ast...Background:Parkinson’s disease(PD)is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions(Lewy bodies)within some remaining neurons in the substantia nigra.Recently,astroglial inclusion body has also been found in some neurodegenerative diseases including PD.However,the underlying molecular mechanisms of how astroglial protein aggregation forms remain largely unknown.Here,we investigated the contribution ofαB-crystallin(CRYAB),a small heat shock protein,inα-synuclein inclusion formation in astrocytes.Methods:Small interfering RNA(siRNA)-mediated CRYAB(siCRYAB)knockdown or CRYAB overexpression was performed to investigate the impact of CRYAB on the autophagy in human glioblastoma cell line U251 cells.Coimmunoprecipitation(co-IP)and immunoblotting were used to dissect the interaction among multiple proteins.The clearance ofα-synuclein in vitro was evaluated by immunocytochemistry.CRYAB transgenic mice and transgenic mice overexpressing A30P mutant form of humanα-synuclein were used to examine the influence of CRYAB toα-synuclein accumulation in vivo.Results:We found that knockdown of CRYAB in U251 cells or primary cultured astrocytes resulted in a marked augmentation of autophagy activity.In contrast,exogenous CRYAB disrupted the assembly of the BAG3-HSPB8-HSC70 complex via binding with BAG3,thereby suppressing the autophagy activity.Furthermore,CRYAB-regulated autophagy has relevance to PD pathogenesis.Knockdown of CRYAB remarkably promoted cytoplasmic clearance ofα-synuclein preformed fibrils(PFFs).Conversely,selective overexpression of CRYAB in astrocytes markedly suppressed autophagy leading to the accumulation of α-synuclein aggregates in the brain of transgenic mice expressing humanα-synuclein A30P mutant.Conclusions:This study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies.展开更多
A series of the electrochemical and long-term corrosion tests was carried out in a 3.5 wt% Na2SO4 solution on thermal-sprayed WC-17Co and WC-10Co-4Cr cermet coatings in order to examine the effect of composition of bi...A series of the electrochemical and long-term corrosion tests was carried out in a 3.5 wt% Na2SO4 solution on thermal-sprayed WC-17Co and WC-10Co-4Cr cermet coatings in order to examine the effect of composition of binder materials on the corrosion behavior. The results reveal that the overall corrosion resistance of the WC-17Co coating is inferior to that of the WC-Co-Cr coatings due to the corrosion of binder materials which induce WC particles to fall off. CoO and WO3 oxide films form on the surface of WC-17Co coating in Na2SO4 solution electrochemical corrosion process, which will protect the coating in the process of corrosion. Cr2O3 oxide film formed on the WC-10Co-4Cr coating surface has a strong hindered role to corrosion. The corrosion mechanism of WC-17Co coating in Na2SO4 solution is entire corrosion of Co matrix, while it is film-hole corrosion mechanism for WC-10Co-4Cr coating.展开更多
Proton exchange membrane fuel cell(PEMFC)has important implications for the success of clean transportation in the future.One of the key factors affecting the cost and performance of PEMFC is the cathode electrocataly...Proton exchange membrane fuel cell(PEMFC)has important implications for the success of clean transportation in the future.One of the key factors affecting the cost and performance of PEMFC is the cathode electrocatalyst for the oxygen reduction reaction(ORR)to overcome sluggish kinetics and instability in an acidic environment.As an essential component of the electrocatalyst,the support material largely determines the activity,mass transfer,charge transfer,and durability of the electrocatalyst.Thereby,the support material plays a critical role in the overall performance of the electrocatalyst.Carbonbased materials are widely used as electrocatalyst supports because of their high porosity,conductivity,chemical stability,and tunable morphology.Recently,some new carbon-based materials with excellent structure have been introduced,such as carbon nanotubes,carbon nanowires,graphene,metal-organic framework(MOF)-derived carbon,and biomass-derived carbon materials.Combined with a variety of strategies,such as controllable construction of porous structures and surface defects,proper doping heteroatoms,the ingenious design of model electrocatalysts,and predictive theoretical calculation,a new reliable path was provided for further improving the performance of electrocatalysts and exploring the catalytic mechanism.Based on the topic of carbon-based materials for ORR in acidic medium,this review summarizes the up-to-date progress and breakthroughs,highlights the factors affecting the catalytic activity and stability of ORR electrocatalysts in acids,and discusses their future application and development.展开更多
Objective Poly（rC）-binding protein 1 （PCBP1） belongs to the heterogeneous nuclear ribonucleoprotein family and participates in transcriptional and translational regulation. Previous work has identified transcripts...Objective Poly（rC）-binding protein 1 （PCBP1） belongs to the heterogeneous nuclear ribonucleoprotein family and participates in transcriptional and translational regulation. Previous work has identified transcripts targeted by both knockdown and overexpression of PCBP1 in SH-SY5Y neuroblastoma cells using a microarray or ProteomeLabTM protein fractionation 2-dimensions （PF-2D） and quadrupole time-of-flight mass spectrometer. The present study aimed to further determine whether these altered transcripts from major pathways （such as Wnt signaling, TGF-β signaling, cell cycling, and apoptosis） and two other genes, H2AFX and H2BFS （screened by PF-2D）, have spatial relationships. Methods The genes were studied by qRT-PCR, and dynamic Bayesian network analysis was used to rebuild the coordination network of these transcripts. Results PCBP1 controlled the expression or activity of the seven transcripts. Moreover, PCBP1 indirectly regulated MAP2K2, FOS, FST, TP53 and WNT7B through H2AFX or regulated these genes through SAT. In contrast, TP53 and WNT7B are regulated by other genes. Conclusion The seven transcripts and PCBP1 are closely associated in a spatial interaction network.展开更多
基金supported by the National Key Research and Development Program of China,Nos.2016YFC1306300(to XMW),2016YFC1306000the National Key R&D Program of China-European Commission Horizon 2020,No.2017YFE0118800-779238(to YXW)+15 种基金the Notional Natural Science Foundation of Chino,Nos.81970992(to WZ),81571229(to WZ),81071015(to WZ),30770745(to WZ)Capital's Funds for Health Improvement and Research(CFH),No.2022-2-2048(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.kz201610025030(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Project of the Natural Science Foundation of Beijing,No.4161004(to WZ)Capitol Clinical Characteristic Applicotion Research,No.Z121107001012161(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)High Level Technical Personnel Training Project of Beijing Health System of China,No.2009-3-26(to WZ)Excellent Personnel Training Project of Beijing,No.20071D0300400076(to WZ)Important National Science&Technology Specific Project,No.2011ZX09102-003-01(to WZ)Beijing Healthcare Research Project,No.JING-15-2(to WZ)Basic-Clinicol Research Cooperation Funding of Capitol Medical University of China,Nos.2015-JL-PT-X04(to WZ),10JL49(to WZ),14JL15(to WZ)the Natural Science Foundation of Capital Medical UniversityBeijingChina,No.PYZ2018077(to PG)Youth Research Fund of Beijing Tianton Hospital of Capital Medical University of China,Nos.2015-YQN-14(to PG),2015-YQN-15,2015-YQN-17。
文摘Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.
基金Supported by Ningbo Medical Key Fostering Discipline Child Health Science,No.2022-F26Ningbo Science and Technology Plan Project Public Welfare Plan,No.2019C50099.
文摘BACKGROUND Attention-deficit/hyperactivity disorder(ADHD)is one of the most common disorders in child and adolescent psychiatry,with a prevalence of more than 5%.Despite extensive research on ADHD in the last 10 to 20 years,effective treatments are still lacking.Instead,the concept of ADHD seems to have become broader and more heterogeneous.Therefore,the diagnosis and treatment of ADHD remains challenging for clinicians.AIM To investigate the effects of a multimodal integrated intervention for children with ADHD.METHODS Between March 2019 and September 2020,a total of 100 children with ADHD who were diagnosed and treated at our hospital were assessed for eligibility,two of whom revoked their consent.A case-control study was conducted in which the children were equally assigned,using a randomized number table,to either a medication group(methylphenidate hydrochloride extended-release tablets and atomoxetine hydrochloride tablets)or a multimodal integrated intervention group(medication+parent training+behavior modification+sensory integration therapy+sand tray therapy),with 49 patients in each group.The clinical endpoint was the efficacy of the different intervention modalities.RESULTS The two groups of children with ADHD had comparable patient characteristics(P>0.05).Multimodal integrated intervention resulted in a significantly higher treatment efficacy(91.84%)than medication alone(75.51%)(P<0.05).Children who received the multimodal integrated intervention showed lower scores in the Conners Parent Symptom Questionnaire and the Weiss Functional Impairment Rating Scale than those treated with medication alone(P<0.05).The Sensory Integration Scale scores of children in the multimodal integrated intervention group were higher than those of children in the medication group(P<0.05).Children who received the multimodal integrated intervention had higher compliance and family satisfaction and a lower incidence of adverse events than those treated with medication alone(P<0.05).CONCLUSION Multimodal integrated intervention effectively alleviated symptoms associated with ADHD in children.It enhanced their memory and attention with high safety and parental satisfaction,demonstrating good potential for clinical promotion.
基金supported by the Natural Science Foundation of Tianjin Municipality(22JCYBJC00410)the National Natural Science Foundation of China-Chinese Academy of Sciences Joint Fund for Astronomy(U1931134)。
文摘Spectral classification plays a crucial role in the analysis of astronomical data.Currently,stellar spectral classification primarily relies on one-dimensional(1D)spectra and necessitates a sufficient signal-to-noise ratio(S/N).However,in cases where the S/N is low,obtaining valuable information becomes impractical.In this paper,we propose a novel model called DRC-Net(Double-branch celestial spectral classification network based on residual mechanisms)for stellar classification,which operates solely on two-dimensional(2D)spectra.The model consists of two branches that use 1D convolutions to reduce the dimensionality of the 2D spectral composed of both blue and red arms.In the following,the features extracted from both branches are fused,and the fused result undergoes further feature extraction before being fed into the classifier for final output generation.The data set is from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope,comprising 15,680 spectra of F,G,and K types.The preprocessing process includes normalization and the early stopping mechanism.The experimental results demonstrate that the proposed DRC-Net achieved remarkable classification precision of 93.0%,83.5%,and86.9%for F,G,and K types,respectively,surpassing the performance of 1D spectral classification methods.Furthermore,different S/N intervals are tested to judge the classification ability of DRC-Net.The results reveal that DRC-Net,as a 2D spectral classification model,can deliver superior classification outcomes for the spectra with low S/Ns.These experimental findings not only validate the efficiency of DRC-Net but also confirm the enhanced noise resistance ability exhibited by 2D spectra.
基金Supported by Ningbo Science and Technology Plan Project Public Welfare Plan(Municipal Level),No:2019C50099Ningbo Medical Key Supporting Discipline Child Health Science,No:2022-F26。
文摘BACKGROUND Long-term treatment of attention deficit/hyperactivity disorder(ADHD)is associated with adverse events,such as nausea and vomiting,dizziness,and sleep disturbances,and poor maintenance of late ADHD medication compromises treatment outcomes and prolongs the recovery of patients’social functioning.AIM To evaluate the effect of non-pharmacological treatment on the full recovery of social functioning in patients with ADHD.METHODS A total of 90 patients diagnosed with ADHD between May 2019 and August 2020 were included in the study and randomly assigned to either the pharmacological group(methylphenidate hydrochloride and tomoxetine hydrochloride)or the non-pharmacological group(parental training,behavior modification,sensory integration therapy,and sand tray therapy),with 45 cases in each group.Outcome measures included treatment compliance,Swanson,Nolan,and Pelham,Version IV(SNAP-IV)scores,Conners Parent Symptom Questionnaire(PSQ)scores,and Weiss Functional Impairment Rating Scale(WFIRS)scores.RESULTS The non-pharmacological interventions resulted in significantly higher compliance in patients(95.56%)compared with medication(71.11%)(P<0.05).However,no significant differences in SNAP-IV and PSQ scores,in addition to the learning/school,social activities,and adventure activities of the WFIRS scores were observed between the two groups(P>0.05).Patients with non-pharmacological interventions showed higher WFIRS scores for family,daily life skills,and self-concept than those in the pharmacological group(P<0.05).CONCLUSION Non-pharmacological interventions,in contrast to the potential risks of adverse events after longterm medication,improve patient treatment compliance,alleviate patients’behavioral symptoms of attention,impulsivity,and hyperactivity,and improve their cognitive ability,thereby improving family relationships and patient self-evaluation.
基金supported by the National Natural Science Foundation of China,No.81571038,81771145(both to YZ)
文摘Mounting evidence suggests that synaptic plasticity provides the cellular biological basis of learning and memory, and plasticity deficits play a key role in dementia caused by Alzheimer's disease. However, the mechanisms by which synaptic dysfunction contributes to the pathogenesis of Alzheimer's disease remain unclear. In the present study, Alzheimer's disease transgenic mice were used to determine the relationship between decreased hippocampal synaptic plasticity and pathological changes and cognitive-behavioral deterioration, as well as possible mechanisms underlying decreased synaptic plasticity in the early stages of Alzheimer's disease-like diseases. APP/PS1 double transgenic(5 XFAD; Jackson Laboratory) mice and their littermates(wild-type, controls) were used in this study. Additional 6-weekold and 10-week-old 5 XFAD mice and wild-type mice were used for electrophysiological recording of hippocampal dentate gyrus. For10-week-old 5 XFAD mice and wild-type mice, the left hippocampus was used for electrophysiological recording, and the right hippocampus was used for biochemical experiments or immunohistochemical staining to observe synaptophysin levels and amyloid beta deposition levels. The results revealed that, compared with wild-type mice, 6-week-old 5 XFAD mice exhibited unaltered long-term potentiation in the hippocampal dentate gyrus. Another set of 5 XFAD mice began to show attenuation at the age of 10 weeks, and a large quantity of amyloid beta protein was accumulated in hippocampal cells. The location of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor and N-methyl-D-aspartic acid receptor subunits in synaptosomes was decreased. These findings indicate that the delocalization of postsynaptic glutamate receptors and an associated decline in synaptic plasticity may be key mechanisms in the early onset of Alzheimer's disease. The use and care of animals were in strict accordance with the ethical standards of the Animal Ethics Committee of Capital Medical University,China on December 17, 2015(approval No. AEEI-2015-182).
基金Supported by Innovation Fund of Fujian Province,No.2007-CXB-7Key Science and Technology Project of Xiamen,No.3502Z20077045
文摘AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,
基金This work was supported by the National Natural Science Foundation of China (Grant No.30370712)Beijing Key Project (Grant No. 7051002)+1 种基金 Beijing Science Technology Committee Project (No.Y0204002040111)a grant of Majon State Basic Research Program of China (No. 2006CB 910100).
文摘Objective To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. Method Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion. Results Profiling analysis demonstrated that an 11.6kDa protein was significandy elevated in lung cancer patients, compared with the control groups （P〈0.001）. The level and percentage of 11.6kDa protein progressively increased with the clinical stages Ⅰ-Ⅳ and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6kDa peak. Further identification showed that 2177Da was a fragment of serum amyloid A （SAA, MW 11.6kDa）. Two of the new peaks, 1550Da and 1611Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6kDa protein and MS analysis. Conclusion SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.
基金supported by the National Natural Science Foundation of China (11032006,11072094,11121202)a grant fromthe Ph.D. Program Foundation of Ministry of Education of China(20100211110022)the Program for New Century Excellent Talents in University (NCET-10-0445)
文摘As an extension of the wavelet approach to vi- bration control of piezoelectric beam-type plates developed earlier by the authors, this paper proposes a hybrid active- passive control strategy for suppressing vibrations of lami- nated rectangular plates bonded with distributed piezoelec- tric sensors and actuators via thin viscoelastic bonding lay- ers. Owing to the low-pass filtering property of scaling func- tion transform in orthogonal wavelet theory, this wavelet- based control method has the ability to automatically filter out noise-like signal in the feedback control loop, hence re- ducing the risk of residual coupling effects which are usu- ally the source of spillover instability. Moreover, the exis- tence of thin viscoelastic bonding layers can further improve robustness and reliability of the system through dissipating the energy of any other possible noise induced partially by numerical errors during the control process. A simulation procedure based on an advanced wavelet-Galerkin technique is suggested to realize the hybrid active-passive control pro- cess. Numerical results demonstrate the efficiency of the pro- posed approach.
基金supported by the National Natural Science Foundation of China,No.81402932(to YQC)
文摘Many studies have shown that(5R)-5-hydroxytriptolide is the optimal modified analogue of triptolide, possessing comparable immunosuppressive activity but much lower cytotoxicity than triptolide. Whether(5R)-5-hydroxytriptolide has preventive effects on neuroinflammation is unclear. This study was designed to pretreat primary astrocytes from the brains of neonatal Sprague-Dawley rats with 20, 100 and 500 nM(5R)-5-hydroxytriptolide for 1 hour before establishing an in vitro neuroinflammation model with 1.0 μg/mL lipopolysaccharide for 24 hours. The generation of nitric oxide was detected by Griess reagents. Astrocyte marker glial fibrillary acidic protein was measured by immunohistochemical staining. The levels of tumor necrosis factor-α and interleukin-1β in the culture supernatant were assayed by enzyme linked immunosorbent assay. Nuclear factor-κB/p65 expression was examined by immunofluorescence staining. The phosphorylation of inhibitor of nuclear factor IκB-α and the location of nuclear factor-κB/P65 were determined using western blot assay. Our data revealed that(5R)-5-hydroxytriptolide inhibited the generation of nitric oxide, tumor necrosis factor-α and interleukin-1β from primary astrocytes activated by lipopolysaccharide, decreased the positive reaction intensity of glial fibrillary acidic protein, reduced the expression of tumor necrosis factor alpha and interleukin-1β in culture supernatant, inhibited the phosphorylation of IκB-α and the translocation of nuclear factor-κB/P65 to the nucleus. These results have confirmed that(5R)-5-hydroxytriptolide inhibits lipopolysaccharide-induced glial inflammatory response and provides cytological experimental data for(5R)-5-hydroxytriptolide in the treatment of neurodegenerative diseases.
基金Supported by National Nature Science Foundation,No.81873111,No.82174454,and No.82074182Natural Science Foundation of Beijing,No.7202066。
文摘Liver is the most common site of metastases of colorectal cancer,and liver metastases present with distinct histopathological growth patterns(HGPs),including desmoplastic,pushing and replacement HGPs and two rare HGPs.HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics.Many studies have revealed the association of HGPs with carcinogenesis,angiogenesis,and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications.These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making,and a target of imaging observation for patient screening.Of note,it is crucial to determine the underlying mechanism shaping HGP,for instance,immune infiltration and extracellular matrix remodeling in desmoplastic HGP,and aggressive characteristics and special vascularization in replacement HGP(rHGP).We highlight the importance of aggressive features,vascularization,host immune and organ structure in formation of HGP,hence propose a novel"advance under camouflage"hypothesis to explain the formation of rHGP.
基金supported by the Scientific and Technological Innovation Programs of Higher Education Institution in Shanxi,China(Grant Nos.2020L0525 and 2019L0782)the National Natural Science Foundation of China(Grant Nos.11805141 and 12075210)+2 种基金Applied Basic Research Program of Shanxi Province,China(Grant No.201901D211424)“1331 Project”Key Innovative Research Team of Taiyuan Normal University(Grant No.I0190364)Key Research and Development program of Shanxi Province,China(Grant No.201903D421042).
文摘We mainly investigate the variable-coefficient 3-coupled nonlinear Schrodinger(NLS)system,which describes soli- ton dynamics in the three-spineα-helical protein with inhomogeneous effect.The variable-coefficient NLS equation is transformed into the constant coefficient NLS equation by similarity transformation firstly.The Hirota method is used to solve the constant coefficient NLS equation,and then we get the one-and two-breather solutions of the variable-coefficient NLS equation.The results show that,in the background of plane waves and periodic waves,the breather can be transformed into some forms of combined soliton solutions.The influence of different parameters on the soliton solution and the collision between two solitons are discussed by some graphs in detail.Our results are helpful to study the soliton dynamics inα-helical protein.
基金Supported by the National Natural Science Foundation of China,No. 30170909
文摘AIM: To identify the difference in gene expression of microphage (Mφ) between normal spleen and portal hypertensive spleen using cDNA microarrays and find new gene functions associated with hypersplenism in portal hypertension. METHODS: The Biostar-H140s chip containing 14 112 spots of cDNAs were used to investigate the difference of the expression. The total RNA extracted from macrophages isolated from both normal spleen and portal hypertensive spleen was reversely transcribed to cDNA with the incorporation of fluorescent (cy3 and cy5) labeled dCTP to prepare the hybridization probes. After hybridization, the gene chip was scanned for the fluorescent intensity. The differentially expressed genes were screened. That was repeated three times, and only the genes which had differential expression in all three chips were considered to be associated with hypersplenism in portal hypertension. RESULTS: Eight hundred and ninety-six, 1330 and 898 genes were identified to be differentially expressed in three chips, respectively. One hundred and twenty-one genes (0.86%) were identified to be differentially expressed in all three chips, including 21 up-regulated genes and 73 down-regulated genes. The differentially expressed genes were related to ionic channel and transport protein, cyclin, cytoskeleton, cell receptor, cell signal conduct, metabolism, immune, and so on. These genes might be related to the hypersplenism in portal hypertension.CONCLUSION: The investigations based on cDNA microarray can screen differentially expressed genes of macrophages between normal spleen and portal hypertensive spleen, thus may provide a new idea in studying the pathogenesis of hypersplenism in portal hypertension.
基金Supported by Special Research Project of Capital Health Development 2016,No.2020-2-2048.
文摘BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.
文摘BACKGROUND Chimeric antigen receptor T-Cell(CAR-T)therapy is an effective new treatment for hematologic malignancies.Cytokine release syndrome(CRS)and neurologic toxicity are main toxicities.CRS-induced rhabdomyolysis(RM)followed by CART therapy treatment has not been previously reported.CASE SUMMARY We report a case of a 22-year-old woman with relapsed acute lymphoblastic leukemia obtained sequential cluster of differentiation(CD)19 and CD22 CAR-T infusion.This patient experienced grade 3 CRS with RM,mild hypotension requiring intravenous fluids,and mild hypoxia and was managed effectively with the IL-6 receptor antagonist tocilizumab.This patient had no signs of immune effector cell-associated neurologic syndrome.Restaging scans 30 d postCAR-T therapy demonstrated a complete remission,and the symptoms of muscle weakness improved through rehabilitation.CONCLUSION Myalgia is an easily overlooked symptom of severe CRS after CAR-T therapy.It is necessary to monitor myoglobin levels when a patient presents with symptoms of myalgia or acute renal insufficiency.
基金Surface Project of National Natural Science Foundation of China,No:81570440Shanghai Leading Talent Fund Project,No.:035.
文摘Objective: To study the protective effect and molecular mechanism of glucagon-like peptide-1 (GLP-1) on the high glucose-induced endothelial cell injury. Methods: Endothelial cells HUVECs were cultured and divided into three groups, control group were treated with serum-free low-glucose culture medium, high glucose group were treated with serum-free culture medium containing 40 mmol/L glucose and GLP-1 group were treated with serum-free culture medium containing 10 mmol/L GLP-1 and 40 mmol/L glucose. 24 h after treatment, the expression of apoptosis genes and autophagy genes as well as the levels of oxidative stress products and antioxidants were measured. Results: JAK2, STAT3, Bax, Caspase-9, Caspase-3, Nrf2, NQO1, HO1 and GSH-Px mRNA expression as well as ROS, gp91phox, MDA and ox-LDL levels in high glucose group of cells were significantly higher than those in control group while STSQM1, Atg-5 and LC-3 mRNA expression were significantly lower than those of control group;JAK2, STAT3, Bax, Caspase-9 and Caspase-3 mRNA expression as well as ROS, gp91phox, MDA and ox-LDL levels in GLP-1 group of cells were significantly lower than those in high glucose group while Nrf2, NQO1, HO1, GSH-Px, STSQM1, Atg-5 and LC-3mRNA expression were significantly higher than those in high glucose group. Conclusion:GLP-1 can reduce the high glucose-induced endothelial cell injury by inhibiting apoptosis, reducing oxidative stress and enhancing autophagy.
基金financially supported by the National Natural Science Foundation of China(Nos.52172227 and Z190010)。
文摘LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is the most promising cathode for high-energy Li-ion batteries,despite its poor cycling stability that originates from the reactions that occur with the electrolyte.Herein,to solve this interfacial issue,a facile electrolytic electrochemical polymerization process was introduced in this paper,and a uniform conductive electrolyte interface(polyaniline)was successfully constructed on the surface of the NCM811 porous electrode(PANI-NCM),which facilitated the charge transfer during charge/discharge.The side reactions at the interface between the cathode and the electrolyte are suppressed,and thereby,the cycling performance and rate capability are considerably improved.PANI-NCM delivers an initial capacity of 157.2 mAh·g^(-1)as well as excellent cyclability(capacity retention of 88%after 500 cycles at 2C),whereas the capacity of the bare NCM811 has dropped to 31.3 mAh·g^(-1).In addition,polypyrrole and polythiophene also can be formed through electrolytic electrochemical polymerization process,which provides a practicable tactic to modify the interfacial stability of cathodes for high-energy Li-ion batteries.
基金This work was supported by grants from the Natural Science Foundation of China(31430036,91742116,U1801681)National Key Basic Research Program of China(2015CB553500)+3 种基金Key Research Program of Frontier Sciences(QYZDJ-SSW-SMC002)Strategic Priority Research Program of Chinese Academy of Science(XDB32020100)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Shanghai Municipal Science and Technology Commission(17ZR1435300 to SZZ).
文摘Background:Parkinson’s disease(PD)is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions(Lewy bodies)within some remaining neurons in the substantia nigra.Recently,astroglial inclusion body has also been found in some neurodegenerative diseases including PD.However,the underlying molecular mechanisms of how astroglial protein aggregation forms remain largely unknown.Here,we investigated the contribution ofαB-crystallin(CRYAB),a small heat shock protein,inα-synuclein inclusion formation in astrocytes.Methods:Small interfering RNA(siRNA)-mediated CRYAB(siCRYAB)knockdown or CRYAB overexpression was performed to investigate the impact of CRYAB on the autophagy in human glioblastoma cell line U251 cells.Coimmunoprecipitation(co-IP)and immunoblotting were used to dissect the interaction among multiple proteins.The clearance ofα-synuclein in vitro was evaluated by immunocytochemistry.CRYAB transgenic mice and transgenic mice overexpressing A30P mutant form of humanα-synuclein were used to examine the influence of CRYAB toα-synuclein accumulation in vivo.Results:We found that knockdown of CRYAB in U251 cells or primary cultured astrocytes resulted in a marked augmentation of autophagy activity.In contrast,exogenous CRYAB disrupted the assembly of the BAG3-HSPB8-HSC70 complex via binding with BAG3,thereby suppressing the autophagy activity.Furthermore,CRYAB-regulated autophagy has relevance to PD pathogenesis.Knockdown of CRYAB remarkably promoted cytoplasmic clearance ofα-synuclein preformed fibrils(PFFs).Conversely,selective overexpression of CRYAB in astrocytes markedly suppressed autophagy leading to the accumulation of α-synuclein aggregates in the brain of transgenic mice expressing humanα-synuclein A30P mutant.Conclusions:This study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies.
基金financially supported by the Fundamental Research Funds for the Central Universities (Nos.SWJTU11BR203 and SWJTU12CX047)the National Key Technology R&D Program of the Ministry of Science and Technology (No. 2012BAE06B02)
文摘A series of the electrochemical and long-term corrosion tests was carried out in a 3.5 wt% Na2SO4 solution on thermal-sprayed WC-17Co and WC-10Co-4Cr cermet coatings in order to examine the effect of composition of binder materials on the corrosion behavior. The results reveal that the overall corrosion resistance of the WC-17Co coating is inferior to that of the WC-Co-Cr coatings due to the corrosion of binder materials which induce WC particles to fall off. CoO and WO3 oxide films form on the surface of WC-17Co coating in Na2SO4 solution electrochemical corrosion process, which will protect the coating in the process of corrosion. Cr2O3 oxide film formed on the WC-10Co-4Cr coating surface has a strong hindered role to corrosion. The corrosion mechanism of WC-17Co coating in Na2SO4 solution is entire corrosion of Co matrix, while it is film-hole corrosion mechanism for WC-10Co-4Cr coating.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U1710256 and U1810115)the Shanxi Science and Technology Major Project(Grant Nos.20181102019 and 20201101016)。
文摘Proton exchange membrane fuel cell(PEMFC)has important implications for the success of clean transportation in the future.One of the key factors affecting the cost and performance of PEMFC is the cathode electrocatalyst for the oxygen reduction reaction(ORR)to overcome sluggish kinetics and instability in an acidic environment.As an essential component of the electrocatalyst,the support material largely determines the activity,mass transfer,charge transfer,and durability of the electrocatalyst.Thereby,the support material plays a critical role in the overall performance of the electrocatalyst.Carbonbased materials are widely used as electrocatalyst supports because of their high porosity,conductivity,chemical stability,and tunable morphology.Recently,some new carbon-based materials with excellent structure have been introduced,such as carbon nanotubes,carbon nanowires,graphene,metal-organic framework(MOF)-derived carbon,and biomass-derived carbon materials.Combined with a variety of strategies,such as controllable construction of porous structures and surface defects,proper doping heteroatoms,the ingenious design of model electrocatalysts,and predictive theoretical calculation,a new reliable path was provided for further improving the performance of electrocatalysts and exploring the catalytic mechanism.Based on the topic of carbon-based materials for ORR in acidic medium,this review summarizes the up-to-date progress and breakthroughs,highlights the factors affecting the catalytic activity and stability of ORR electrocatalysts in acids,and discusses their future application and development.
基金supported in part by the National Basic Research Program of China (2011CB504100)the National Natural Science Foundation of China (81072858)the "973" project(2007CB511902) from the Ministry of Science and Technology of the People’s Republic of China
文摘Objective Poly（rC）-binding protein 1 （PCBP1） belongs to the heterogeneous nuclear ribonucleoprotein family and participates in transcriptional and translational regulation. Previous work has identified transcripts targeted by both knockdown and overexpression of PCBP1 in SH-SY5Y neuroblastoma cells using a microarray or ProteomeLabTM protein fractionation 2-dimensions （PF-2D） and quadrupole time-of-flight mass spectrometer. The present study aimed to further determine whether these altered transcripts from major pathways （such as Wnt signaling, TGF-β signaling, cell cycling, and apoptosis） and two other genes, H2AFX and H2BFS （screened by PF-2D）, have spatial relationships. Methods The genes were studied by qRT-PCR, and dynamic Bayesian network analysis was used to rebuild the coordination network of these transcripts. Results PCBP1 controlled the expression or activity of the seven transcripts. Moreover, PCBP1 indirectly regulated MAP2K2, FOS, FST, TP53 and WNT7B through H2AFX or regulated these genes through SAT. In contrast, TP53 and WNT7B are regulated by other genes. Conclusion The seven transcripts and PCBP1 are closely associated in a spatial interaction network.
