N-doped graphite carbon sphere coated cobalt nanoparticle catalyst(Co@C-N-900),prepared by solvothermal-calcination method,is applied to activate peroxymonosulfate(PMS)for bisphenol A(BPA)elimination.The outcomes demo...N-doped graphite carbon sphere coated cobalt nanoparticle catalyst(Co@C-N-900),prepared by solvothermal-calcination method,is applied to activate peroxymonosulfate(PMS)for bisphenol A(BPA)elimination.The outcomes demonstrate that the Co@C-N-900 could effectively activate PMS,thereby causing efficient removal of BPA in water.In addition,the Co@C-N-900/PMS system also has the advantages of low metal leaching,applicability in high salinity environments,good selectivity and stability.Further investigations using electron paramagnetic resonance,chronoamperometry,and quenching experiments demonstrated that the Co@C-N-900/PMS system is a typical non-radical route with singlet oxygen(^(1)O_(2))as the main reactive oxygen species(ROS).Density functional theory calculations(DFT)indicate that N-doping can effectively regulate the charge distribution on the catalyst surface,generating acidic/alkaline sites favorable for PMS adsorption and activation.Furthermore,it also can enhance the interaction and charge transfer capacity between the Co@C-N-900 and PMS.Lastly,LC-QTOF-MS/MS analysis revealed two possible BPA degradation pathways:(1)^(1)O_(2)attacked the isopropyl group in BPA between the two phenyl groups,causingβ-scission to occur.(2)Following the oxidation of the hydroxyl group in the aromatic ring of BPA,^(1)O_(2)could cause furtherβ-scission.The prepared Co@C-N-900 catalyst is a very promising catalyst,which would offer a workable remedy for treating water pollution.展开更多
Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury.Clinical and experimental evidence demonstrates that liver injury involves complex inter-orga...Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury.Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain,eye,liver,intestine,and kidney.Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury,particularly those associated with bilirubin,reactive oxygen species,ammonia,bile acid,and inflammatory factors.Notably,the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood.Additional research is necessary to fully comprehend these effects and their therapeutic implications.The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs,including both traditional Chinese and Western medicines,to patients with liver dysfunction.This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions.Furthermore,when utilizing transporter inducers or inhibitors clinically,consideration of their long-term effects on transporters and subsequent therapeutic impact is essential.Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters.Similarly,prudent use of inducers or inducertype therapeutic drugs is necessary to prevent enhanced drug resistance.This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.展开更多
Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism ...Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.展开更多
Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal...Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.Methods:A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included.Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio(NLR).High systemic inflammation was defined as NLR≥3,and underweight was defined as BMI<18.5 kg/m2.Results:Among 2,542 patients,NLR≥3 and underweight were common[627(25%)and 349(14%),respectively].In the entire cohort,NLR≥3 or underweight independently predicted overall survival(OS)[hazard ratio(HR):1.236,95%confidence interval(95%CI):1.069–1.430;and HR:1.600,95%CI:1.350–1.897,respectively]and recurrence-free survival(RFS)(HR:1.230,95%CI:1.054–1.434;and HR:1.658,95%CI:1.389–1.979,respectively).Patients with both NLR≥3 and underweight(vs.neither)had much worse OS(HR:2.445,95%CI:1.853–3.225)and RFS(HR:2.405,95%CI:1.802–3.209).Furthermore,we observed similar results in subgroup analyses according to pathological stage,age,and postoperative chemotherapy.Conclusions:Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival.Underweight combined with severe inflammation could enhance prognostication.Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.展开更多
Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation....Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids(oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation. We found that cell surface LRP6 in bone marrow mesenchymal stromal cells(MSCs) decreased rapidly in response to increased oxPLs in marrow microenvironment. LRP6 directly bound and mediated the uptake of oxPLs by MSCs. oxPL-LRP6 binding induced LRP6 endocytosis through a clathrin-mediated pathway, decreasing responses of MSCs to osteogenic factors and diminishing osteoblast differentiation ability. Thus, LRP6 functions as a receptor and molecular target of oxPLs for their adverse effect on MSCs, revealing a potential mechanism underlying atherosclerosis-associated bone loss.展开更多
Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene dise...Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent manner.The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model.Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.展开更多
Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing a...Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis.Methods:Sonographic EHR data were obtained from the EHR database.Pathological reports were used as the gold standard for diagnosing thyroid cancer.We developed thyroid cancer diagnosis based on natural language processing(THCaDxNLP)to interpret unstructured sonographic text reports for thyroid cancer diagnosis.We used the area under the receiver operating characteristic curve(AUROC)as the primary metric to measure the performance of the THCaDxNLP.We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs.those without THCaDxNLP using 5 independent test sets.Results:We obtained a total number of 788,129 sonographic radiological reports.The number of thyroid sonographic data points was 132,277,18,400 of which were thyroid cancer patients.Among the 5 test sets,the numbers of patients per set were 439,186,82,343,and 171.THCaDxNLP achieved high performance in identifying thyroid cancer patients(the AUROC ranged from 0.857–0.932).Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy(93.8%vs.87.2%;one-sided t-test,adjusted P=0.003),precision(92.5%vs.86.0%;P=0.018),and F1 metric(94.2%vs.86.4%;P=0.007).Conclusions:THCaDxNLP achieved a high AUROC for the identification of thyroid cancer,and improved the accuracy,sensitivity,and precision of thyroid ultrasound radiologists.This warrants further investigation of THCaDxNLP in prospective clinical trials.展开更多
In this work,a strategy of"etching-modification filling-graft copolymerization"was proposed to load the acidic ionic polyionic liquid on the smooth ceramic surface.In this way,commercial ceramic Raschig ring...In this work,a strategy of"etching-modification filling-graft copolymerization"was proposed to load the acidic ionic polyionic liquid on the smooth ceramic surface.In this way,commercial ceramic Raschig rings were successfully transformed into the supported catalytic packing for the reactive distillation,and were further evaluated with esterification reaction of ethyl acetate by means of the fully mixed reactor,the ultrasonic destruction,the cyclic catalysis reaction and the lab-scale distillation column experiment.This catalyst coating has good adhesion with the substrate.It can withstand 24 h of ultrasound damage and shows good stability in three cycle catalytic experiments.This kind of coated catalyst has better catalytic activity than the commercial Amberlyst 15 dry.In the lab-scale reaction distillation,the supported catalyst Raschig ring can achieve a higher conversion in comparison with the tea bag catalytic packing of Amberlyst 15 dry under some conditions.展开更多
Background: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out i...Background: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Methods: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univariate and multivariate linear regression on log PSA values. Results: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). Conclusions: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.展开更多
Although cytochrome P450 enzymes are the most versatile biocatalysts in nature,there is insufficient comprehension of the molecular mechanism underlying their functional innovation process.Here,by combining ancestral ...Although cytochrome P450 enzymes are the most versatile biocatalysts in nature,there is insufficient comprehension of the molecular mechanism underlying their functional innovation process.Here,by combining ancestral sequence reconstruction,reverse mutation assay,and progressive forward accumulation,we identified 5 founder residues in the catalytic pocket of flavone 6-hydroxylase(F6H)and proposed a"3-point fixation"model to elucidate the functional innovation mechanisms of P450s in nature.According to this design principle of catalytic pocket,we further developed a de novo diffusion model(P450Diffusion)to generate artificial P450s.Ultimately,among the 17 non-natural P450s we generated,10 designs exhibited significant F6H activity and 6 exhibited a 1.3-to 3.5-fold increase in catalytic capacity compared to the natural CYP706X1.This work not only explores the design principle of catalytic pockets of P450s,but also provides an insight into the artificial design of P450 enzymes with desired functions.展开更多
In this paper,a series of calibration-free temperature measurement methods based on light-induced thermoelastic spectroscopy(LITES)are proposed for the first time.These techniques utilize the steady-state and transien...In this paper,a series of calibration-free temperature measurement methods based on light-induced thermoelastic spectroscopy(LITES)are proposed for the first time.These techniques utilize the steady-state and transient response characteristics of the quartz tuning fork(QTF),namely,the calibration-free LITES(CF-LITES)and calibration-free heterodyne LITES(CF-H-LITES)methods.Four methods,first harmonic(1f)difference signal to normalize the second harmonic(2f)fundamental signal(method Ⅰ,2f_(fund)/1f_(diff)),1f overtone signal to normalize the 2f fundamental signal(method Ⅱ,2f_(fund)/1f_(over)),1f heterodyne difference signal to normalize the 2f heterodyne fundamental signal(method Ⅲ,2f-H_(fund)/1f-H_(diff)),and 1f heterodyne overtone signal to normalize the 2f heterodyne fundamental signal(method Ⅳ,2f-H_(fund)/1f-H_(over)),for simultaneously detecting 1f and 2f within the frequency response range of the QTF are proposed to achieve calibration-free measurement.A self-designed T-shaped QTF with low fundamental and overtone frequencies was used to increase the energy accumulation time,thereby enhancing the sensor signal level.A 3-stage tube furnace was adopted to verify the performance of these 4 methods.Experimental results showed that the errors for the 4 methods were less than 4%,with a standard deviation below 11℃.Furthermore,the calibration-free method,which employs normalization of the 2f signal with the 1f signal,effectively mitigates the impact of laser beam jitter and power fluctuations on detection performance.A superior performance can be obtained by adopting the CF-H-LITES technique based on method Ⅳ.It not only has excellent detection performance but also reduces the measurement period to 4 s,which is about 5 times faster.This development shows substantial promise for expanding the application of the CF-LITES and CF-H-LITES techniques in harsh environments.展开更多
Organofluorine compounds have consistently played a pivotal role in chemical synthesis,materials development,and drug discovery.Among these,chiral organofluorine compounds have emerged as a significant focus of resear...Organofluorine compounds have consistently played a pivotal role in chemical synthesis,materials development,and drug discovery.Among these,chiral organofluorine compounds have emerged as a significant focus of research.Gem-difluoroalkenes and difluoroenoxysilanes,owing to their high reactivity and modifiability,are extensively employed in the synthesis of chiral organofluorine compounds.This review summarizes recent research progress in the use of these molecules in asymmetric synthesis.Their application in synthesizing biologically active chiral molecules could open new possibilities and lead to unexpected breakthroughs in medicinal chemistry.展开更多
The global pandemic of COVID-19 has underscored the huge potential of nucleic acid drugs in effective and rapid vaccine development.Hence,it is significant to accelerate the research and clinical transformation of nuc...The global pandemic of COVID-19 has underscored the huge potential of nucleic acid drugs in effective and rapid vaccine development.Hence,it is significant to accelerate the research and clinical transformation of nucleic acid drugs.However,when administered systemically,nucleic acid molecules are vulnerable to degradation by nucleases,and their structural hydrophilicity hampers cellular entry,limiting their efficacy.Moreover,free nucleic acid drugs may cause some side effects in vivo,and the application of small nucleic acid drugs is largely restricted by intratumoral or peritumoral administration.Currently,the design and preparation of nucleic acid delivering systems face many scientific problems and technical challenges.Breaking through the technical bottlenecks in intraneous delivery of nucleic acid molecules is anticipated to open a new era of efficient,precise and safe nucleic acid drugs.This program,based on the new advances in nanotechnology and biomedical engineering,aims to advance the nucleic acid nano drug delivery systems(NDDS)and overcome intraneous delivery barriers.This review explores the barriers in nucleic acid drug delivery and presents methods for enhancing intracellular uptake,offering guidance for the design of nucleic acid carriers.Furthermore,it discusses the latest advancements in applying NDDS to nucleic acid drugs.展开更多
Nanorods(NRs)hold promise for surpassing the theoretical external quantum efficiency limit of light-emitting diodes(LEDs)based on spherical quantum dots(QDs)due to their linearly polarized emission and high photon out...Nanorods(NRs)hold promise for surpassing the theoretical external quantum efficiency limit of light-emitting diodes(LEDs)based on spherical quantum dots(QDs)due to their linearly polarized emission and high photon out-coupling efficiency.Compared with the most studied dot-in-rod NRs,rod-in-rod NRs have higher degree of polarization.However,due to the difficulties in achieving uniform NR seeds,synthesizing rod-in-rod NRs that cover the entire visible spectrum remains a significant challenge,especially for green and blue ones.In this study,high-quality and uniformly sized green CdSeS NRs were successfully synthesized by systematically optimizing the S/Se ratio,the nucleation temperature and the amount of ligand.Based on these high-quality NR seeds,CdSeS/CdZnS/ZnS core–shell NRs were further prepared with narrow emission bandwidths(28 nm at 540 nm),high photoluminescence(PL)quantum yield(75%),and high linear polarization(the PL anisotropy(r)=0.3).This study provides a new possibility for the application of NRs in LEDs,lasers,and other optoelectronic devices.展开更多
基金the financial support from Sichuan Science and Technology Program(No.2023NSFSC0847)Scientific Research and Innovation Team Program of Sichuan University of Science and Technology(No.SUSE652A003)+3 种基金Talent Introduction Project of Sichuan University of Science and Engineering(No.2021RC03)Talent Introduction Project of Sichuan University of Science and Engineering(No.2021RC05)the Undergraduate Training Program for Innovation and Entrepreneurship(No.CX2024042)The Innovation Fund of Postgraduate,Sichuan University of Science&Engineering(No.Y2024094)。
文摘N-doped graphite carbon sphere coated cobalt nanoparticle catalyst(Co@C-N-900),prepared by solvothermal-calcination method,is applied to activate peroxymonosulfate(PMS)for bisphenol A(BPA)elimination.The outcomes demonstrate that the Co@C-N-900 could effectively activate PMS,thereby causing efficient removal of BPA in water.In addition,the Co@C-N-900/PMS system also has the advantages of low metal leaching,applicability in high salinity environments,good selectivity and stability.Further investigations using electron paramagnetic resonance,chronoamperometry,and quenching experiments demonstrated that the Co@C-N-900/PMS system is a typical non-radical route with singlet oxygen(^(1)O_(2))as the main reactive oxygen species(ROS).Density functional theory calculations(DFT)indicate that N-doping can effectively regulate the charge distribution on the catalyst surface,generating acidic/alkaline sites favorable for PMS adsorption and activation.Furthermore,it also can enhance the interaction and charge transfer capacity between the Co@C-N-900 and PMS.Lastly,LC-QTOF-MS/MS analysis revealed two possible BPA degradation pathways:(1)^(1)O_(2)attacked the isopropyl group in BPA between the two phenyl groups,causingβ-scission to occur.(2)Following the oxidation of the hydroxyl group in the aromatic ring of BPA,^(1)O_(2)could cause furtherβ-scission.The prepared Co@C-N-900 catalyst is a very promising catalyst,which would offer a workable remedy for treating water pollution.
基金the National Natural Science Foundation of China(No.82173884).
文摘Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury.Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain,eye,liver,intestine,and kidney.Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury,particularly those associated with bilirubin,reactive oxygen species,ammonia,bile acid,and inflammatory factors.Notably,the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood.Additional research is necessary to fully comprehend these effects and their therapeutic implications.The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs,including both traditional Chinese and Western medicines,to patients with liver dysfunction.This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions.Furthermore,when utilizing transporter inducers or inhibitors clinically,consideration of their long-term effects on transporters and subsequent therapeutic impact is essential.Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters.Similarly,prudent use of inducers or inducertype therapeutic drugs is necessary to prevent enhanced drug resistance.This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
基金supported by the National Natural Science Foundation of China(No.82172408,81772314,and 81922045)the Original Exploration project(22ZR1480300)+5 种基金Outstanding Academic Leaders(Youth)project(21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100)China Postdoctoral Science Foundation(2023M742347).
文摘Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.
基金supported by the National Major Research and the Innovation Program of China(Grant No.2016YFC1303200)the National Key R&D Program of China(Grant No.2017YFC0908300)the National Natural Science Foundation of China(Grant No.81972761)。
文摘Objective:The systemic inflammation index and body mass index(BMI)are easily accessible markers that can predict mortality.However,the prognostic value of the combined use of these two markers remains unclear.The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.Methods:A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included.Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio(NLR).High systemic inflammation was defined as NLR≥3,and underweight was defined as BMI<18.5 kg/m2.Results:Among 2,542 patients,NLR≥3 and underweight were common[627(25%)and 349(14%),respectively].In the entire cohort,NLR≥3 or underweight independently predicted overall survival(OS)[hazard ratio(HR):1.236,95%confidence interval(95%CI):1.069–1.430;and HR:1.600,95%CI:1.350–1.897,respectively]and recurrence-free survival(RFS)(HR:1.230,95%CI:1.054–1.434;and HR:1.658,95%CI:1.389–1.979,respectively).Patients with both NLR≥3 and underweight(vs.neither)had much worse OS(HR:2.445,95%CI:1.853–3.225)and RFS(HR:2.405,95%CI:1.802–3.209).Furthermore,we observed similar results in subgroup analyses according to pathological stage,age,and postoperative chemotherapy.Conclusions:Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival.Underweight combined with severe inflammation could enhance prognostication.Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.
基金supported by the National Institutes of Health grant DK083350the American Heart Association#15GRNT25280000
文摘Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids(oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation. We found that cell surface LRP6 in bone marrow mesenchymal stromal cells(MSCs) decreased rapidly in response to increased oxPLs in marrow microenvironment. LRP6 directly bound and mediated the uptake of oxPLs by MSCs. oxPL-LRP6 binding induced LRP6 endocytosis through a clathrin-mediated pathway, decreasing responses of MSCs to osteogenic factors and diminishing osteoblast differentiation ability. Thus, LRP6 functions as a receptor and molecular target of oxPLs for their adverse effect on MSCs, revealing a potential mechanism underlying atherosclerosis-associated bone loss.
基金supported by Medical University of Silesia research grants,No.PCN-1-129/N/2/O(to AS)。
文摘Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent manner.The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model.Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31801117 to Dr.X.Li and 82073287 to Dr.Zhang)the Program for Changjiang Scholars and Innovative Research Team in University in China(Grant No.IRT_14R40 to Dr.K.Chen)the Chinese National Key Research and Development Project(Grant No.2018YFC1315601).
文摘Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis.Methods:Sonographic EHR data were obtained from the EHR database.Pathological reports were used as the gold standard for diagnosing thyroid cancer.We developed thyroid cancer diagnosis based on natural language processing(THCaDxNLP)to interpret unstructured sonographic text reports for thyroid cancer diagnosis.We used the area under the receiver operating characteristic curve(AUROC)as the primary metric to measure the performance of the THCaDxNLP.We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs.those without THCaDxNLP using 5 independent test sets.Results:We obtained a total number of 788,129 sonographic radiological reports.The number of thyroid sonographic data points was 132,277,18,400 of which were thyroid cancer patients.Among the 5 test sets,the numbers of patients per set were 439,186,82,343,and 171.THCaDxNLP achieved high performance in identifying thyroid cancer patients(the AUROC ranged from 0.857–0.932).Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy(93.8%vs.87.2%;one-sided t-test,adjusted P=0.003),precision(92.5%vs.86.0%;P=0.018),and F1 metric(94.2%vs.86.4%;P=0.007).Conclusions:THCaDxNLP achieved a high AUROC for the identification of thyroid cancer,and improved the accuracy,sensitivity,and precision of thyroid ultrasound radiologists.This warrants further investigation of THCaDxNLP in prospective clinical trials.
基金financial support provided by the National Natural Science Foundation of China(No.21978243)。
文摘In this work,a strategy of"etching-modification filling-graft copolymerization"was proposed to load the acidic ionic polyionic liquid on the smooth ceramic surface.In this way,commercial ceramic Raschig rings were successfully transformed into the supported catalytic packing for the reactive distillation,and were further evaluated with esterification reaction of ethyl acetate by means of the fully mixed reactor,the ultrasonic destruction,the cyclic catalysis reaction and the lab-scale distillation column experiment.This catalyst coating has good adhesion with the substrate.It can withstand 24 h of ultrasound damage and shows good stability in three cycle catalytic experiments.This kind of coated catalyst has better catalytic activity than the commercial Amberlyst 15 dry.In the lab-scale reaction distillation,the supported catalyst Raschig ring can achieve a higher conversion in comparison with the tea bag catalytic packing of Amberlyst 15 dry under some conditions.
文摘Background: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Methods: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univariate and multivariate linear regression on log PSA values. Results: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). Conclusions: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.
基金funding from the National Key R&D Program of China(grant no.2019YFA0905700 and 2021YFC2103500)the National Natural Science Foundation of China(no.32371499)+3 种基金the China Postdoctoral Science Foundation(grant no.2019M661032)the National Natural Science Foundation of China(NSFC,grant nos.31901026 and 32171418)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(nos.TSBICIP-KJGG-002-02 and TSBICIP-CXRC-015)the Tianjin Science Fund for Distinguished Young Scholars(no.18JCJQJC48300).
文摘Although cytochrome P450 enzymes are the most versatile biocatalysts in nature,there is insufficient comprehension of the molecular mechanism underlying their functional innovation process.Here,by combining ancestral sequence reconstruction,reverse mutation assay,and progressive forward accumulation,we identified 5 founder residues in the catalytic pocket of flavone 6-hydroxylase(F6H)and proposed a"3-point fixation"model to elucidate the functional innovation mechanisms of P450s in nature.According to this design principle of catalytic pocket,we further developed a de novo diffusion model(P450Diffusion)to generate artificial P450s.Ultimately,among the 17 non-natural P450s we generated,10 designs exhibited significant F6H activity and 6 exhibited a 1.3-to 3.5-fold increase in catalytic capacity compared to the natural CYP706X1.This work not only explores the design principle of catalytic pockets of P450s,but also provides an insight into the artificial design of P450 enzymes with desired functions.
基金supported by the National Natural Science Foundation of China(Grant Nos.62335006,62022032,62275065,62405078,and 61875047)the Key Laboratory of Opto-Electronic Information Acquisition and Manipulation(Anhui University),the Ministry of Education(Grant No.OEIAM202202)the Fundamental Research Funds for the Central Universities(Grant No.HIT.OCEF.2023011).
文摘In this paper,a series of calibration-free temperature measurement methods based on light-induced thermoelastic spectroscopy(LITES)are proposed for the first time.These techniques utilize the steady-state and transient response characteristics of the quartz tuning fork(QTF),namely,the calibration-free LITES(CF-LITES)and calibration-free heterodyne LITES(CF-H-LITES)methods.Four methods,first harmonic(1f)difference signal to normalize the second harmonic(2f)fundamental signal(method Ⅰ,2f_(fund)/1f_(diff)),1f overtone signal to normalize the 2f fundamental signal(method Ⅱ,2f_(fund)/1f_(over)),1f heterodyne difference signal to normalize the 2f heterodyne fundamental signal(method Ⅲ,2f-H_(fund)/1f-H_(diff)),and 1f heterodyne overtone signal to normalize the 2f heterodyne fundamental signal(method Ⅳ,2f-H_(fund)/1f-H_(over)),for simultaneously detecting 1f and 2f within the frequency response range of the QTF are proposed to achieve calibration-free measurement.A self-designed T-shaped QTF with low fundamental and overtone frequencies was used to increase the energy accumulation time,thereby enhancing the sensor signal level.A 3-stage tube furnace was adopted to verify the performance of these 4 methods.Experimental results showed that the errors for the 4 methods were less than 4%,with a standard deviation below 11℃.Furthermore,the calibration-free method,which employs normalization of the 2f signal with the 1f signal,effectively mitigates the impact of laser beam jitter and power fluctuations on detection performance.A superior performance can be obtained by adopting the CF-H-LITES technique based on method Ⅳ.It not only has excellent detection performance but also reduces the measurement period to 4 s,which is about 5 times faster.This development shows substantial promise for expanding the application of the CF-LITES and CF-H-LITES techniques in harsh environments.
基金support from the Sichuan University of Science&Engineering(2024RC042)and HKBU RC-SFCRG/23-24 for financial support.
文摘Organofluorine compounds have consistently played a pivotal role in chemical synthesis,materials development,and drug discovery.Among these,chiral organofluorine compounds have emerged as a significant focus of research.Gem-difluoroalkenes and difluoroenoxysilanes,owing to their high reactivity and modifiability,are extensively employed in the synthesis of chiral organofluorine compounds.This review summarizes recent research progress in the use of these molecules in asymmetric synthesis.Their application in synthesizing biologically active chiral molecules could open new possibilities and lead to unexpected breakthroughs in medicinal chemistry.
基金the Jilin University Research Initiation Fund(419080600207).
文摘The global pandemic of COVID-19 has underscored the huge potential of nucleic acid drugs in effective and rapid vaccine development.Hence,it is significant to accelerate the research and clinical transformation of nucleic acid drugs.However,when administered systemically,nucleic acid molecules are vulnerable to degradation by nucleases,and their structural hydrophilicity hampers cellular entry,limiting their efficacy.Moreover,free nucleic acid drugs may cause some side effects in vivo,and the application of small nucleic acid drugs is largely restricted by intratumoral or peritumoral administration.Currently,the design and preparation of nucleic acid delivering systems face many scientific problems and technical challenges.Breaking through the technical bottlenecks in intraneous delivery of nucleic acid molecules is anticipated to open a new era of efficient,precise and safe nucleic acid drugs.This program,based on the new advances in nanotechnology and biomedical engineering,aims to advance the nucleic acid nano drug delivery systems(NDDS)and overcome intraneous delivery barriers.This review explores the barriers in nucleic acid drug delivery and presents methods for enhancing intracellular uptake,offering guidance for the design of nucleic acid carriers.Furthermore,it discusses the latest advancements in applying NDDS to nucleic acid drugs.
基金supported by the National Natural Science Foundation of China(Nos.22179009,U22A2072,22379017,52372135).
文摘Nanorods(NRs)hold promise for surpassing the theoretical external quantum efficiency limit of light-emitting diodes(LEDs)based on spherical quantum dots(QDs)due to their linearly polarized emission and high photon out-coupling efficiency.Compared with the most studied dot-in-rod NRs,rod-in-rod NRs have higher degree of polarization.However,due to the difficulties in achieving uniform NR seeds,synthesizing rod-in-rod NRs that cover the entire visible spectrum remains a significant challenge,especially for green and blue ones.In this study,high-quality and uniformly sized green CdSeS NRs were successfully synthesized by systematically optimizing the S/Se ratio,the nucleation temperature and the amount of ligand.Based on these high-quality NR seeds,CdSeS/CdZnS/ZnS core–shell NRs were further prepared with narrow emission bandwidths(28 nm at 540 nm),high photoluminescence(PL)quantum yield(75%),and high linear polarization(the PL anisotropy(r)=0.3).This study provides a new possibility for the application of NRs in LEDs,lasers,and other optoelectronic devices.
