Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve she...Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.展开更多
Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(...Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.展开更多
Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gr...Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety.Notably,more than half of patients with DPN can be asymptomatic,which tends to delay early detection.Furthermore,the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration,gangrene and nontraumatic amputation,which decreases quality of life.Thus,it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention.It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes.The pathogenesis of both disorders involves vascular endothelial dysfunction.Emerging evidence indicates that traditional and novel cardiovascularrelated biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction.Additionally,beyond traditional cardiovascular-related biomarkers,novel cardiovascular-related biomarkers have been linked to diabetes and its complications.In this review,we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN,such as cardiac troponin T,B-type natriuretic peptide,Creactive protein,myeloperoxidase,and homocysteine,and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.展开更多
The quality indicators of cotton will change during storage.Taking the 5.89 million t of Xinjiang cotton from 2016 to 2021 as a sample,this paper analyzed the main fiber quality indicator data of warehouse-in and ware...The quality indicators of cotton will change during storage.Taking the 5.89 million t of Xinjiang cotton from 2016 to 2021 as a sample,this paper analyzed the main fiber quality indicator data of warehouse-in and warehouse-out cotton for storage of 1.5,3.0,4.0,5.0,6.0,and 7.0 years.It was found that the color grade of cotton decreased with the extension of storage time.The cotton with storage time of 5.0 years mainly changed from white cotton grade 2 and white cotton grade 3 to light yellow stained cotton grade 1 and yellow stained cotton grade 1.Among them,the increase of light yellow stained cotton grade 1 was the largest,and the change to yellow stained cotton grade 1 was the largest at the storage 6.0-7.0 years.In addition,there were no significant changes in moisture regain,Micronaire value,upper half mean length,length uniformity index and fiber strength.展开更多
Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashi...Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashimoto’s thyroiditis,and presented with progressively enlarging neck mass.The first two cases were confirmed by surgical biopsy to be diffuse large B cell lymphoma,and received radiotherapy combined with chemotherapy,or received only chemotherapy.The third case was confirmed by core needle biopsy to be mucosa-associated lymphoid tissue lymphoma,and received radiotherapy.In summary,confirmation of PTL diagnosis is essential for further clinical decisions.Core biopsy should be one of the most important methods to make the diagnosis of PTL,while the use of fine needle aspiration cytology alone is still limited in diagnosing PTL.展开更多
The distance-based outlier detection method detects the implied outliers by calculating the distance of the points in the dataset, but the computational complexity is particularly high when processing multidimensional...The distance-based outlier detection method detects the implied outliers by calculating the distance of the points in the dataset, but the computational complexity is particularly high when processing multidimensional datasets. In addition, the traditional outlier detection method does not consider the frequency of subsets occurrence, thus, the detected outliers do not fit the definition of outliers (i.e., rarely appearing). The pattern mining-based outlier detection approaches have solved this problem, but the importance of each pattern is not taken into account in outlier detection process, so the detected outliers cannot truly reflect some actual situation. Aimed at these problems, a two-phase minimal weighted rare pattern mining-based outlier detection approach, called MWRPM-Outlier, is proposed to effectively detect outliers on the weight data stream. In particular, a method called MWRPM is proposed in the pattern mining phase to fast mine the minimal weighted rare patterns, and then two deviation factors are defined in outlier detection phase to measure the abnormal degree of each transaction on the weight data stream. Experimental results show that the proposed MWRPM-Outlier approach has excellent performance in outlier detection and MWRPM approach outperforms in weighted rare pattern mining.展开更多
Harvesting clean energy from water evaporation has been extensively investigated due to its sustainability.To achieve high efficiency,energy conversion materials should contain multiple features which are difficult to...Harvesting clean energy from water evaporation has been extensively investigated due to its sustainability.To achieve high efficiency,energy conversion materials should contain multiple features which are difficult to be simultaneously obtained from single-component materials.Here we use composite laminar membranes assembled by nanosheets of graphene oxide and mica,and find a sustained power density induced by water evaporation that is two orders of magnitude larger than that from membranes made by either of the components.The power output is attributed to selective proton transport driven by water evaporation through the interlayer nanochannels in the membranes.This process relies on the synergistic effects from negatively charged and hydrophilic mica surfaces that are important for proton selectivity and water transport,and the tunable electrical conductivity of graphene oxide that provides optimized internal resistance.The demonstrated composite membranes offer a strategy of enhancing power generation by combining the advantages from each of their components.展开更多
Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiti...Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.展开更多
Dear editor,Cas13,a class Ⅱ type Ⅵ CRISPR‒Cas endonuclease with two higher eukaryotes and prokaryotes nucleotide-binding(HEPN)domains,exclusively binds to and cleaves single-stranded RNA by a complementary guide RNA...Dear editor,Cas13,a class Ⅱ type Ⅵ CRISPR‒Cas endonuclease with two higher eukaryotes and prokaryotes nucleotide-binding(HEPN)domains,exclusively binds to and cleaves single-stranded RNA by a complementary guide RNA(gRNA)(Makarova et al.,2020).RfxCas13d(also known as CasRx)is an ortholog of CRISPR‒Cas13 with a relatively small size and robust RNA knockdown capability in mammalian cells(Konermann et al.,2018).Owing to its simplicity and high efficiency,CasRx has been applied for RNA targeting in various types of cells and organisms.Nevertheless,most of these studies failed to control the nuclease activity of CasRx spatiotemporally.The re-engineered split-Cas9 system enables inducible genome editing and epigenetic modulation through chemical-induced reassembly of the Cas9 protein(Zetsche et al.,2015).However,tools that allow for efficient and controllable RNA knockdown by a split-Cas13 system remain to be established.展开更多
Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,here...Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG,calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer.RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H.pylori infection sites,and then effectively destroyed the architecture of H.pylori biofilms,killed dispersed H.pylori and inhibited the re-adhesion of residual bacteria(called biofilms eradication tetralogy).Moreover,RHL/Cl-Ch-cal activated the host immune response to H.pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells.Finally,RHL/Cl-Ch-cal killed the intracellular H.pylori through recovering the lysosomal acidification and assisting degradation.In experiments,RHL/Cl-Ch-cal demonstrated prominent anti-H.pylori efficacy in the classical H.pylori-infected mice model.Therefore,the study provides a“comprehensive attack”strategy for anti-H.pylori therapies including biofilms eradication tetralogy,immune activation and intracellular bacteria killing.展开更多
Two novel three-dimensional (3-D) coordination polymers, [Pb(HTDA)]n (1) and [Co5(TDA)2(H2TDA)2(H2O)8]n (2) [H3TDA = 1H-1,2,3-triazole-4,5-dicarboxylic acid], have been prepared by hydrothermal reactions and character...Two novel three-dimensional (3-D) coordination polymers, [Pb(HTDA)]n (1) and [Co5(TDA)2(H2TDA)2(H2O)8]n (2) [H3TDA = 1H-1,2,3-triazole-4,5-dicarboxylic acid], have been prepared by hydrothermal reactions and characterized by elemental analysis, infrared spectroscopy and single-crystal X-ray diffraction. Compound 1 is constructed from rod-shaped secondary building units (SBUs) and exhibits a 3-D network with (410·65)(410·63·82) topology. Compound 2 is built up from ligands bridging three different cobalt ions and exhibits a 3-D network with (4·82)3(4·82·103) topology. In addition, the thermal stabilities of the two compounds, the photoluminescence properties of compound 1 and the magnetic properties of compound 2 have been studied.展开更多
Background This study explored the diagnostic performance of visceral adiposity to predict the degree of intestinal inflammation and fibrosis.Methods The patients with Crohn’s disease(CD)who underwent surgical small ...Background This study explored the diagnostic performance of visceral adiposity to predict the degree of intestinal inflammation and fibrosis.Methods The patients with Crohn’s disease(CD)who underwent surgical small bowel resection at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2007 and December 2017 were enrolled.We evaluated the intestinal imaging features of computed tomography enterography(CTE),including mesenteric inflammatory fat stranding,the target sign,mesenteric hypervascularity,bowel wall thickening,lymphadenopathy,stricture diameter,and maximal upstream diameter.We used A.K.software(Artificial Intelligence Kit,version 1.1)to calculate the visceral fat(VF)and subcutaneous fat(SF)volumes at the third lumbar vertebra level.Pathological tissue information was recorded.Diagnostic models were established based on the multivariate regression analysis results,and their effectiveness was evaluated by area under the curve(AUC)and decision curve analyses.Results Overall,48 patients with CD were included in this study.The abdominal VF/SF volume ratio(odds ratio,1.20;95%confidence interval,1.05–1.38;P=0.009)and the stenosis diameter/upstream intestinal dilatation diameter(ND)ratio(odds ratio,0.90;95%confidence interval,0.82–0.99;P=0.034)were independent risk factors for the severe fibrosis of the small intestine.The AUC values of the VF/SF ratio,the ND ratio,and their combination were 0.760,0.673,and 0.804,respectively.The combination of the VS/SF volume ratio and ND ratio achieved the highest net benefit on the decision curve.Conclusion The VF volume on CTE can reflect intestinal fibrosis.The combination of the VF/SF volume ratio and ND ratio of CD patients assessed using CTE can help predict severe fibrosis stenosis of the small intestine.展开更多
基金supported financially by grants from the National Natural Science Foundation of China(No.81771793).
文摘Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.
基金supported by the National Natural Science Foundation of China(No.81100581)the Beijing Bethune Charitable Foundation(No.2021).
文摘Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.
基金National Natural Science Foundation of China,No.82100922.
文摘Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety.Notably,more than half of patients with DPN can be asymptomatic,which tends to delay early detection.Furthermore,the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration,gangrene and nontraumatic amputation,which decreases quality of life.Thus,it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention.It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes.The pathogenesis of both disorders involves vascular endothelial dysfunction.Emerging evidence indicates that traditional and novel cardiovascularrelated biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction.Additionally,beyond traditional cardiovascular-related biomarkers,novel cardiovascular-related biomarkers have been linked to diabetes and its complications.In this review,we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN,such as cardiac troponin T,B-type natriuretic peptide,Creactive protein,myeloperoxidase,and homocysteine,and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.
基金Supported by 2021 Science and Technology Project of China Grain Reserves Group Limited Company(Sinograin)"Research on Natural Variation Law of Reserve Cotton Quality"(2021-11).
文摘The quality indicators of cotton will change during storage.Taking the 5.89 million t of Xinjiang cotton from 2016 to 2021 as a sample,this paper analyzed the main fiber quality indicator data of warehouse-in and warehouse-out cotton for storage of 1.5,3.0,4.0,5.0,6.0,and 7.0 years.It was found that the color grade of cotton decreased with the extension of storage time.The cotton with storage time of 5.0 years mainly changed from white cotton grade 2 and white cotton grade 3 to light yellow stained cotton grade 1 and yellow stained cotton grade 1.Among them,the increase of light yellow stained cotton grade 1 was the largest,and the change to yellow stained cotton grade 1 was the largest at the storage 6.0-7.0 years.In addition,there were no significant changes in moisture regain,Micronaire value,upper half mean length,length uniformity index and fiber strength.
文摘Primary thyroid lymphoma(PTL)is an exceptionally rare and highly aggressive potentially curable malignant disease.We report three typical cases of PTL referred to our hospital.All three cases had long history of Hashimoto’s thyroiditis,and presented with progressively enlarging neck mass.The first two cases were confirmed by surgical biopsy to be diffuse large B cell lymphoma,and received radiotherapy combined with chemotherapy,or received only chemotherapy.The third case was confirmed by core needle biopsy to be mucosa-associated lymphoid tissue lymphoma,and received radiotherapy.In summary,confirmation of PTL diagnosis is essential for further clinical decisions.Core biopsy should be one of the most important methods to make the diagnosis of PTL,while the use of fine needle aspiration cytology alone is still limited in diagnosing PTL.
基金supported by Fundamental Research Funds for the Central Universities (No. 2018XD004)
文摘The distance-based outlier detection method detects the implied outliers by calculating the distance of the points in the dataset, but the computational complexity is particularly high when processing multidimensional datasets. In addition, the traditional outlier detection method does not consider the frequency of subsets occurrence, thus, the detected outliers do not fit the definition of outliers (i.e., rarely appearing). The pattern mining-based outlier detection approaches have solved this problem, but the importance of each pattern is not taken into account in outlier detection process, so the detected outliers cannot truly reflect some actual situation. Aimed at these problems, a two-phase minimal weighted rare pattern mining-based outlier detection approach, called MWRPM-Outlier, is proposed to effectively detect outliers on the weight data stream. In particular, a method called MWRPM is proposed in the pattern mining phase to fast mine the minimal weighted rare patterns, and then two deviation factors are defined in outlier detection phase to measure the abnormal degree of each transaction on the weight data stream. Experimental results show that the proposed MWRPM-Outlier approach has excellent performance in outlier detection and MWRPM approach outperforms in weighted rare pattern mining.
基金support from the National Key Research and Development Program of China(No.2019YFA0705400)the National Natural Science Foundation of China(Nos.21972121 and 22021001)the Fundamental Research Funds for the Central Universities(No.20720210017).
文摘Harvesting clean energy from water evaporation has been extensively investigated due to its sustainability.To achieve high efficiency,energy conversion materials should contain multiple features which are difficult to be simultaneously obtained from single-component materials.Here we use composite laminar membranes assembled by nanosheets of graphene oxide and mica,and find a sustained power density induced by water evaporation that is two orders of magnitude larger than that from membranes made by either of the components.The power output is attributed to selective proton transport driven by water evaporation through the interlayer nanochannels in the membranes.This process relies on the synergistic effects from negatively charged and hydrophilic mica surfaces that are important for proton selectivity and water transport,and the tunable electrical conductivity of graphene oxide that provides optimized internal resistance.The demonstrated composite membranes offer a strategy of enhancing power generation by combining the advantages from each of their components.
基金supported by the National Natural Science Foundation of China (Grants 31771549 to Y.C.,82103251 to J.Z.,82203153 to K.Z.,and 82203574 to S.W.)the 1.3.5 Project for Disciplines of Excellence (Grants ZYGD18021,ZYJC18009,ZYJC21002,and ZYJC21015)+1 种基金the China Postdoctoral Science Foundation (Grants 2020TQ0210 and 2021M692268 to J.Z.)Natural Science Foundation of Sichuan Province (Grant 2022NSFSC1438 to J.Z.).
文摘Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.
基金supported by the National Natural Science Foundation of China(82203444 and 82273161)the Natural Science Foundation of Jiangsu Province(BK20220672)。
文摘Dear editor,Cas13,a class Ⅱ type Ⅵ CRISPR‒Cas endonuclease with two higher eukaryotes and prokaryotes nucleotide-binding(HEPN)domains,exclusively binds to and cleaves single-stranded RNA by a complementary guide RNA(gRNA)(Makarova et al.,2020).RfxCas13d(also known as CasRx)is an ortholog of CRISPR‒Cas13 with a relatively small size and robust RNA knockdown capability in mammalian cells(Konermann et al.,2018).Owing to its simplicity and high efficiency,CasRx has been applied for RNA targeting in various types of cells and organisms.Nevertheless,most of these studies failed to control the nuclease activity of CasRx spatiotemporally.The re-engineered split-Cas9 system enables inducible genome editing and epigenetic modulation through chemical-induced reassembly of the Cas9 protein(Zetsche et al.,2015).However,tools that allow for efficient and controllable RNA knockdown by a split-Cas13 system remain to be established.
基金supported by National Natural Science Foundation of China (Nos. 81773659 and 81973264)Guangdong Basic and Applied Basic Research Foundation (Nos. 2019A1515011954, 2020A1515010593 and 2021A1515012621, China)Guangdong Provincial Key Laboratory of Construction Foundation (No. 2019B030301005, China)
文摘Helicobacter pylori(H.pylori),creating a global infection rate over 50%,presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo.To improve the eradication efficacy,herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG,calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer.RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H.pylori infection sites,and then effectively destroyed the architecture of H.pylori biofilms,killed dispersed H.pylori and inhibited the re-adhesion of residual bacteria(called biofilms eradication tetralogy).Moreover,RHL/Cl-Ch-cal activated the host immune response to H.pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells.Finally,RHL/Cl-Ch-cal killed the intracellular H.pylori through recovering the lysosomal acidification and assisting degradation.In experiments,RHL/Cl-Ch-cal demonstrated prominent anti-H.pylori efficacy in the classical H.pylori-infected mice model.Therefore,the study provides a“comprehensive attack”strategy for anti-H.pylori therapies including biofilms eradication tetralogy,immune activation and intracellular bacteria killing.
基金supported by the National Natural Science Foundation of China (20703008)Chang Jiang Scholars Program (2006),Department of Science and Technology of Jilin Province (20082103)+2 种基金the Training Fund of NENU’s Scientific Innovation Project (NENU-STC07017,-STC08005,and-STC08012)the Fundamental Research Funds for the Central Universities (Project No. 09SSXT123)Open Project Program of the State Key Laboratory of Supramolecular Structure and Materials,Jilin University
文摘Two novel three-dimensional (3-D) coordination polymers, [Pb(HTDA)]n (1) and [Co5(TDA)2(H2TDA)2(H2O)8]n (2) [H3TDA = 1H-1,2,3-triazole-4,5-dicarboxylic acid], have been prepared by hydrothermal reactions and characterized by elemental analysis, infrared spectroscopy and single-crystal X-ray diffraction. Compound 1 is constructed from rod-shaped secondary building units (SBUs) and exhibits a 3-D network with (410·65)(410·63·82) topology. Compound 2 is built up from ligands bridging three different cobalt ions and exhibits a 3-D network with (4·82)3(4·82·103) topology. In addition, the thermal stabilities of the two compounds, the photoluminescence properties of compound 1 and the magnetic properties of compound 2 have been studied.
基金supported by the National Natural Science Foundation of China[grant numbers 81772699,81472999,81272350]the Guangzhou People’s Livelihood Science and Technology Project[grant number 201803010052].
文摘Background This study explored the diagnostic performance of visceral adiposity to predict the degree of intestinal inflammation and fibrosis.Methods The patients with Crohn’s disease(CD)who underwent surgical small bowel resection at the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2007 and December 2017 were enrolled.We evaluated the intestinal imaging features of computed tomography enterography(CTE),including mesenteric inflammatory fat stranding,the target sign,mesenteric hypervascularity,bowel wall thickening,lymphadenopathy,stricture diameter,and maximal upstream diameter.We used A.K.software(Artificial Intelligence Kit,version 1.1)to calculate the visceral fat(VF)and subcutaneous fat(SF)volumes at the third lumbar vertebra level.Pathological tissue information was recorded.Diagnostic models were established based on the multivariate regression analysis results,and their effectiveness was evaluated by area under the curve(AUC)and decision curve analyses.Results Overall,48 patients with CD were included in this study.The abdominal VF/SF volume ratio(odds ratio,1.20;95%confidence interval,1.05–1.38;P=0.009)and the stenosis diameter/upstream intestinal dilatation diameter(ND)ratio(odds ratio,0.90;95%confidence interval,0.82–0.99;P=0.034)were independent risk factors for the severe fibrosis of the small intestine.The AUC values of the VF/SF ratio,the ND ratio,and their combination were 0.760,0.673,and 0.804,respectively.The combination of the VS/SF volume ratio and ND ratio achieved the highest net benefit on the decision curve.Conclusion The VF volume on CTE can reflect intestinal fibrosis.The combination of the VF/SF volume ratio and ND ratio of CD patients assessed using CTE can help predict severe fibrosis stenosis of the small intestine.
