BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical tec...BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.展开更多
Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context...Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.展开更多
The purpose of this study was to assess the differences in clinical and sonographic features of papillary thyroid carcinoma（PTC） between cervical lymph node metastatic（CLNM） and nonmetastatic groups.Clinical data ...The purpose of this study was to assess the differences in clinical and sonographic features of papillary thyroid carcinoma（PTC） between cervical lymph node metastatic（CLNM） and nonmetastatic groups.Clinical data of PTC patients（414 patients with 624 malignant nodules） who underwent a preoperative ultrasonography and surgery between June 2010 and March 2015 at Renmin Hospital of Wuhan University were retrospectively analyzed.Clinical factors,preoperative ultrasound features and the final pathological findings were obtained.The differences in the sonographic features of PTC between the CLNM group and the non-CLNM group were analyzed.There were 187 CLNM and 227 non-CLNM patients.The median age at the diagnosis of this cohort was 45.4 years old（ranging from 18 to 77 years）.Ultrasonographic parameters that were significantly associated with CLNM [OR=2.569（1.502,4.393）,P〈0.001）] were as follows：the mulifocality of the nodules,size over 2 cm,the presence of microcalcifications,the distance ratio（DR） pattern showing the contact of the nodules with the thyroid capsule,and the extracapsular spread of the nodules.No significant differences in age,gender,thyroid stimulating hormone（TSH） levels and other ultrasonography parameters were found between the CLNM and the non-CLNM groups.Therefore,our results suggest that a larger size,microcalcifications,mulifocality,and the DR pattern showing the contact of the nodules with the thyroid capsule and extracapsular spread are significantly more indicative of CLNM in PTC.展开更多
BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma that is mainly involved in the gastrointestinal tract. Thesynchronous occurrence of colonic MALT lymphoma and adenocarc...BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma that is mainly involved in the gastrointestinal tract. Thesynchronous occurrence of colonic MALT lymphoma and adenocarcinoma in thesame patient is extremely rare. We here report a case of synchronous colonicMALT lymphoma found on surveillance colonoscopy five months after surgeryand chemotherapy for sigmoid adenocarcinoma.CASE SUMMARY A 67-year-old man was admitted because of hematochezia for two months.Colonoscopy suggested a colonic tumor before hospitalization. Abdominalcomputed tomography (CT) revealed local thickening of the sigmoid colon. Thepatient underwent a left hemicolectomy with local lymph node dissection. Thehistopathology revealed moderately differentiated adenocarcinoma and partiallymucinous adenocarcinoma. The pTNM stage was T3N1Mx. The patient receivedchemotherapy with six cycles of mFOLFOX6 after surgery. Colonoscopy wasperformed five months later and revealed single, flat, polypoid lesions of thecolon 33 cm away from the anus. Subsequently, the patient underwent endoscopic mucosal resection for further diagnosis. The pathological diagnosis was MALTlymphoma. Positron emission tomography /CT suggested metastasis. The patientrefused further treatment and died ten months later.CONCLUSION Colonic MALT lymphoma may occur after surgery and chemotherapy foradenocarcinoma as a synchronous malignancy. Regular surveillance colonoscopyand careful monitoring after surgery are critical.展开更多
Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides...Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.展开更多
Compared with organic solar cells(OSCs) adopting conventional architecture,inverted OSCs have offered generally better stability,where Zn O is the most widely used electron transporting layer(ETL) material.For ZnO-bas...Compared with organic solar cells(OSCs) adopting conventional architecture,inverted OSCs have offered generally better stability,where Zn O is the most widely used electron transporting layer(ETL) material.For ZnO-based inverted OSCs,a welltuned interface of organic(active layer)-inorganic(Zn O film) with matched surface energy(γS) is critical for both high performance and high stability.In this work,two typical calixarenes,C4A and Bu C4A,were employed as the tuning agents to adjust this organic-inorganic interface for ZnO-based inverted OSCs.As a result,with PM6:L8-BO as the active layer,significantly promoted power conversion efficiencies(PCEs) from 17.14%(for ZnO) to 18.25%(for ZnO/C4A) and 17.80%(for ZnO/Bu C4A) were achieved.Photodynamic studies indicate that the enhanced performance is due to the faster charge extraction process,the suppressed recombination and more ideal internal electric field in ZnO/calixarene-based devices.In addition,wellmatched interface energy and more ordered molecular aggregation in active layer effectively improved photostability and thermal stability for ZnO/calixarene-based devices.These results indicate that calixarenes could act as effective modifying agents of ZnO to improve inverted OSCs’ performance and stability simultaneously,and likely also stimulate calixarenes’ and other macromolecules’ broader studies in other organic electronic devices.展开更多
Disk burst accidents sometimes happen in aeroengines.To avoid tragic consequences,aeroengine casings must have sufficient containment capability.Experiments and simulations need to be conducted to study the impact,dis...Disk burst accidents sometimes happen in aeroengines.To avoid tragic consequences,aeroengine casings must have sufficient containment capability.Experiments and simulations need to be conducted to study the impact,distortion,and perforation caused by disk burst and which may give important clues to potential failure mechanisms.This paper presents some containment tests of high-speed rotating disk fragments,in which the original disks were burst into three equal fragments within a predetermined rotating speed range.The failure modes of the containment casing varied significantly with the thickness of the containment casing.Shearing,tearing,tensile fracture,and large plastic stretching deformation occurred in a thin-walled containment casing,while a thick-walled casing could contain disk fragments and withstand large plastic deformation.Numerical simulations were carried out to study the impact process and failure modes further.Good agreement was found between the results of the simulations and the tests.展开更多
A series of novel 1,2,4-triazoles containing 1,2,3-thiadiazole derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, 1H NMR, and elemental analysis and ESI-MS or HRMS. Preli...A series of novel 1,2,4-triazoles containing 1,2,3-thiadiazole derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, 1H NMR, and elemental analysis and ESI-MS or HRMS. Preliminary bioassays indicated that these compounds exhibited very good insecticidal activity against Aphis laburni at 100 μg/mL, with mortality no less than 95%. Compounds 6a, 6c, 6f, 61 showed higher curative activity against TMV and compound 6h showed a higher induction effects against TMV in vivo at 100 μg/mL. Collectively, our data demonstrate a new strategy for control of insects and viruses.展开更多
To investigate the ballistic resistance and failure pattern of aeroengine casing following the impact of disk fragments, and to determine the optimum case structure, the phenomena of a 1/3rd disk fragment impact on si...To investigate the ballistic resistance and failure pattern of aeroengine casing following the impact of disk fragments, and to determine the optimum case structure, the phenomena of a 1/3rd disk fragment impact on single and double-layered thin plate targets were simulated using nonlinear dynamical analysis software MSC.Dytran. Strain rate effect was introduced in a Johnson-Cook (JC) material model for the disk fragment and the plate. Impact modeling was based on the Arbitrary Lagrange-Eulerian method, and simulated using explicit finite element method (FEM). Simulation results showed that the major failure pattern of the plate is shearing and tensile fracture with large plastic deformation. It was also concluded that the ballistic limit velocity increases with the standoff distance when it is beyond a certain value, and that greater resistance is obtained when the front plate has either a proportionately low or high thickness. The impact resistance of a double-layered plate may exceed that of a single plate if the thicknesses and standoff distance of the two plates are set appropriately.展开更多
文摘BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.
基金supported by the Fundamental Research Funds for the Central Universities(2042021kf0102,2042021kf0083)supported by two National Natural Science Foundation of China(NSFC)Grants(81903166,82203629)+1 种基金a Natural Science Foundation of Hubei(2018CKB916)sponsored by Shanghai Pujiang Program(22PJD054).
文摘Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.
基金supported by the National Natural Science Foundation of China(No.81471781,No.81502665 and No.81302314/H1622)the Fundamental Research Funds of Health and Family Planning Commission of Hubei Province(No.JS-20110118)the Fundamental Research Funds for the Central Universities of China(No.2042014kf0189)
文摘The purpose of this study was to assess the differences in clinical and sonographic features of papillary thyroid carcinoma（PTC） between cervical lymph node metastatic（CLNM） and nonmetastatic groups.Clinical data of PTC patients（414 patients with 624 malignant nodules） who underwent a preoperative ultrasonography and surgery between June 2010 and March 2015 at Renmin Hospital of Wuhan University were retrospectively analyzed.Clinical factors,preoperative ultrasound features and the final pathological findings were obtained.The differences in the sonographic features of PTC between the CLNM group and the non-CLNM group were analyzed.There were 187 CLNM and 227 non-CLNM patients.The median age at the diagnosis of this cohort was 45.4 years old（ranging from 18 to 77 years）.Ultrasonographic parameters that were significantly associated with CLNM [OR=2.569（1.502,4.393）,P〈0.001）] were as follows：the mulifocality of the nodules,size over 2 cm,the presence of microcalcifications,the distance ratio（DR） pattern showing the contact of the nodules with the thyroid capsule,and the extracapsular spread of the nodules.No significant differences in age,gender,thyroid stimulating hormone（TSH） levels and other ultrasonography parameters were found between the CLNM and the non-CLNM groups.Therefore,our results suggest that a larger size,microcalcifications,mulifocality,and the DR pattern showing the contact of the nodules with the thyroid capsule and extracapsular spread are significantly more indicative of CLNM in PTC.
文摘BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma that is mainly involved in the gastrointestinal tract. Thesynchronous occurrence of colonic MALT lymphoma and adenocarcinoma in thesame patient is extremely rare. We here report a case of synchronous colonicMALT lymphoma found on surveillance colonoscopy five months after surgeryand chemotherapy for sigmoid adenocarcinoma.CASE SUMMARY A 67-year-old man was admitted because of hematochezia for two months.Colonoscopy suggested a colonic tumor before hospitalization. Abdominalcomputed tomography (CT) revealed local thickening of the sigmoid colon. Thepatient underwent a left hemicolectomy with local lymph node dissection. Thehistopathology revealed moderately differentiated adenocarcinoma and partiallymucinous adenocarcinoma. The pTNM stage was T3N1Mx. The patient receivedchemotherapy with six cycles of mFOLFOX6 after surgery. Colonoscopy wasperformed five months later and revealed single, flat, polypoid lesions of thecolon 33 cm away from the anus. Subsequently, the patient underwent endoscopic mucosal resection for further diagnosis. The pathological diagnosis was MALTlymphoma. Positron emission tomography /CT suggested metastasis. The patientrefused further treatment and died ten months later.CONCLUSION Colonic MALT lymphoma may occur after surgery and chemotherapy foradenocarcinoma as a synchronous malignancy. Regular surveillance colonoscopyand careful monitoring after surgery are critical.
基金supported by the National Key R&D Program of China(nos.2019YFA0904200 and 2018YFA0507600)the Tsinghua University Spring Breeze Fund(no.2020Z99CFY042)+1 种基金the National Natural Science Foundation of China(nos.92053108 and 31961143004)NCC Fund(no.NCC2020FH04).
文摘Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.
基金supported by the Ministry of Science and Technology of China(MoST,2019YFA0705900)the National Natural Science Foundation of China(21935007,52025033,51873089)+1 种基金Tianjin city(20JCZDJC00740)111 Project(B12015)。
文摘Compared with organic solar cells(OSCs) adopting conventional architecture,inverted OSCs have offered generally better stability,where Zn O is the most widely used electron transporting layer(ETL) material.For ZnO-based inverted OSCs,a welltuned interface of organic(active layer)-inorganic(Zn O film) with matched surface energy(γS) is critical for both high performance and high stability.In this work,two typical calixarenes,C4A and Bu C4A,were employed as the tuning agents to adjust this organic-inorganic interface for ZnO-based inverted OSCs.As a result,with PM6:L8-BO as the active layer,significantly promoted power conversion efficiencies(PCEs) from 17.14%(for ZnO) to 18.25%(for ZnO/C4A) and 17.80%(for ZnO/Bu C4A) were achieved.Photodynamic studies indicate that the enhanced performance is due to the faster charge extraction process,the suppressed recombination and more ideal internal electric field in ZnO/calixarene-based devices.In addition,wellmatched interface energy and more ordered molecular aggregation in active layer effectively improved photostability and thermal stability for ZnO/calixarene-based devices.These results indicate that calixarenes could act as effective modifying agents of ZnO to improve inverted OSCs’ performance and stability simultaneously,and likely also stimulate calixarenes’ and other macromolecules’ broader studies in other organic electronic devices.
基金Project supported by the Chinese Aviation Propulsion Technology Development Program (No. APTD-11)the Zhejiang Provincial Natural Science Foundation of China (No. Y1090245)
文摘Disk burst accidents sometimes happen in aeroengines.To avoid tragic consequences,aeroengine casings must have sufficient containment capability.Experiments and simulations need to be conducted to study the impact,distortion,and perforation caused by disk burst and which may give important clues to potential failure mechanisms.This paper presents some containment tests of high-speed rotating disk fragments,in which the original disks were burst into three equal fragments within a predetermined rotating speed range.The failure modes of the containment casing varied significantly with the thickness of the containment casing.Shearing,tearing,tensile fracture,and large plastic stretching deformation occurred in a thin-walled containment casing,while a thick-walled casing could contain disk fragments and withstand large plastic deformation.Numerical simulations were carried out to study the impact process and failure modes further.Good agreement was found between the results of the simulations and the tests.
基金funded in part by the NSF of Tianjin (No. 10JCZDJC17500)the National Key Project for Basic Research (No. 2010CB126105)+2 种基金National Key Technology Research and Development Program (No. 2011BAE06B02)the Foundation of Achievements Transformation and Application of Tianjin Agricul-tural Science and Technology (No. 201002250)Tianjin Key Technology Research and Development Program (No. 11ZCGYNC00100)
文摘A series of novel 1,2,4-triazoles containing 1,2,3-thiadiazole derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, 1H NMR, and elemental analysis and ESI-MS or HRMS. Preliminary bioassays indicated that these compounds exhibited very good insecticidal activity against Aphis laburni at 100 μg/mL, with mortality no less than 95%. Compounds 6a, 6c, 6f, 61 showed higher curative activity against TMV and compound 6h showed a higher induction effects against TMV in vivo at 100 μg/mL. Collectively, our data demonstrate a new strategy for control of insects and viruses.
基金Project (No. 1104-03) supported by the Aviation Propulsion Technology Development Program, China
文摘To investigate the ballistic resistance and failure pattern of aeroengine casing following the impact of disk fragments, and to determine the optimum case structure, the phenomena of a 1/3rd disk fragment impact on single and double-layered thin plate targets were simulated using nonlinear dynamical analysis software MSC.Dytran. Strain rate effect was introduced in a Johnson-Cook (JC) material model for the disk fragment and the plate. Impact modeling was based on the Arbitrary Lagrange-Eulerian method, and simulated using explicit finite element method (FEM). Simulation results showed that the major failure pattern of the plate is shearing and tensile fracture with large plastic deformation. It was also concluded that the ballistic limit velocity increases with the standoff distance when it is beyond a certain value, and that greater resistance is obtained when the front plate has either a proportionately low or high thickness. The impact resistance of a double-layered plate may exceed that of a single plate if the thicknesses and standoff distance of the two plates are set appropriately.
