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
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
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
A highly sensitive carbon dioxide(CO_(2))sensor based on light-induced thermoelastic spectroscopy(LITES)utilizing a selfdesigned low-frequency quartz tuning fork(QTF)and a fiber-coupled multipass cell(MPC)is reported ...A highly sensitive carbon dioxide(CO_(2))sensor based on light-induced thermoelastic spectroscopy(LITES)utilizing a selfdesigned low-frequency quartz tuning fork(QTF)and a fiber-coupled multipass cell(MPC)is reported in this paper.The QTF with a low resonant frequency of 8675 Hz and a high Q factor of 11,675.64 was used to improve its energy accumulation time and the sensor’s signal level.The MPC with the fiber-coupled structure and optical length of 40 m was adopted to significantly increase the gas absorbance and reduce the optical alignment difficulty as well as improve the robustness of the sensor system.A distributed feedback(DFB),near-infrared diode laser with an emission wavelength of 1.57μm was used as an excitation source.The experimental results showed that this CO_(2)-LITES sensor had an excellent linear response to CO_(2) concentrations.The minimum detection limitation(MDL)of this CO_(2)-LITES sensor was obtained to be 445.91 ppm,and it could be improved to 47.70 ppm(parts per million)when the integration time of the system reached 500 s.Further improvement methods for the detection performance of such sensors were also discussed.展开更多
Paclitaxel(Taxol)stands out as a tetracyclic diterpenoid natural product derived from the endangered plant Taxus.Recognized as a pivotal broad-spectrum anticancer drug,it has garnered widespread attention due to its l...Paclitaxel(Taxol)stands out as a tetracyclic diterpenoid natural product derived from the endangered plant Taxus.Recognized as a pivotal broad-spectrum anticancer drug,it has garnered widespread attention due to its low yield,intricate structure,unique anticancer mechanism,and remarkable efficacy(Tong et al.,2021).Although chemists achieved the total synthesis of paclitaxel 30 years ago,after decades of research,the natural biosynthetic pathway for its production remains an enigma(Ajikumar et al.,2010;Malci et al.,2023).A recent breakthrough,published in Molecular Plant by Alisdair R.Fernie's team,unveils a minimal gene set of 18 genes required for paclitaxel biosynthesis(Zhang et al.,2023),representing a significant mark toward unraveling the entire biosynthetic pathway and enhancing paclitaxel production efficiency.展开更多
Monoterpenoids are typically present in the secretory tissues of higher plants,and their biosynthesis is catalyzed by the action of monoterpene synthases(MTSs).However,the knowledge about these enzymes is restricted i...Monoterpenoids are typically present in the secretory tissues of higher plants,and their biosynthesis is catalyzed by the action of monoterpene synthases(MTSs).However,the knowledge about these enzymes is restricted in a few plant species.MTSs are responsible for the complex cyclization of monoterpene precursors,resulting in the production of diverse monoterpene products.These enzymatic reactions are considered exceptionally complex in nature.Therefore,it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid products.In our study,we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene products.By focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic,monocyclic and bicyclic products in MTSs,we observed that even a single amino acid mutation can change the specificity and diversity of MTS products,which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation changing.Notably,residues N340,I448,and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene cations.Alterations in these residues,either directly or indirectly,can impact the synthesis of single monoterpenes or their mixtures.By revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs,it will be possible to reasonably design and engineer different catalytic activities into existing MTSs,laying a foundation for the artificial design and industrial application of MTSs.展开更多
Dear Editor,As one of the most important crops to supply the majority of plant oil and protein for the whole world,soybean is facing an increasing global demand.The reference genome of accession"Williams82"o...Dear Editor,As one of the most important crops to supply the majority of plant oil and protein for the whole world,soybean is facing an increasing global demand.The reference genome of accession"Williams82"opened the gate of genomics research in soybean(Schmutz et al.,2010).After that,vast multi-omics data were generated,thereby providing valuable resources for functional study and molecular breeding.Parts of these data have been collected in different soybean databases(see details in Supplemental Table 1),such as Soybase(Grant et al.,2010)and SoyKB(Joshi et al.,2012),which made valuable efforts to facilitate the wide utility of these data.Nevertheless,these existing databases poorly tackled multi-omics data integration and interactivity for soybean,provoking tremendous challenges for researchers to deal with these big omics data,particularly considering the unprecedented rate of data growth(Yang et al.,2021).Thus,constructing an integrated multi-omics database for soybean that provides a one-stop solution for big data mining with friendly interactivity is highly desired.展开更多
Dear Editor,Plant UDP-dependent glycosyltransferases(UGTs),belonging to the carbohydrate-active enzyme glycosyltransferase 1 family(Louveau and Osbourn,2019),not only play important roles in adaptation to various envi...Dear Editor,Plant UDP-dependent glycosyltransferases(UGTs),belonging to the carbohydrate-active enzyme glycosyltransferase 1 family(Louveau and Osbourn,2019),not only play important roles in adaptation to various environments(Cai et al.,2020;Pastorczyk-Szlenkier and Bednarek,2021)but also endow plant natural products with great pharmaceutical and ecological significance(Margolin et al.,2020).In recent years,an increasing number of plant UGTs have been characterized to function in the biosynthesis of many bioactive compounds such as ginsenosides(Wei et al.,2015),breviscapine(Liu et al.,2018),and rubusoside(Xu et al.,2022).展开更多
As a new energy source,hydrogen(H_(2))detection is a hot topic in recent years.Because of the weak absorption characteristic,laser spectroscopy-based H_(2)detection is challenging.In this paper,a highly sensitive H_(2...As a new energy source,hydrogen(H_(2))detection is a hot topic in recent years.Because of the weak absorption characteristic,laser spectroscopy-based H_(2)detection is challenging.In this paper,a highly sensitive H_(2)sensor based on light-induced thermoelastic spectroscopy(LITES)technique is demonstrated for the first time.A continuous-wave,distributed feedback diode laser with emission in the 2.1μm region was adopted as the excitation source to target the strongest H_(2)absorption line of 4,712.90 cm^(−1).A Herriott multipass cell with an optical length of 10.1 m was chosen to further improve the H_(2)absorption.With the feature of processing the raw input data without data preprocessing and extracting the desired features automatically,the robust shallow neural network(SNN)fitting algorithm was brought in to denoise the sensor.For the LITES-based H_(2)sensor,the concentration response was tested,and an excellent linear response to H_(2)concentration levels was achieved.A minimum detection limit(MDL)of~80 ppm was obtained.On the basis of implementation of the H_(2)-LITES sensor,a heterodyne H_(2)-LITES sensor was further constructed to realize a fast measurement of resonance frequency of quartz tuning fork and H_(2)concentration simultaneously.The resonance frequency can be retrieved in several hundred milliseconds with the measurement accuracy of±0.2 Hz,and the result of 30,713.76 Hz is exactly same as the experimentally determined value of 30,713.69 Hz.After the SNN algorithm was applied,an MDL of~45 ppm was achieved for this heterodyne H_(2)-LITES sensor.展开更多
This paper proposes a branch-independence-based reliability assessment approach for transmission systems.The approach consists of branch decoupling and state-space partition techniques.By integrating an impact-increme...This paper proposes a branch-independence-based reliability assessment approach for transmission systems.The approach consists of branch decoupling and state-space partition techniques.By integrating an impact-increment-based reliability index calculation model and the proposed branch decoupling technique,a proportion of sampled contingency states no longer need to be analyzed using the time-consuming optimal power flow(OPF)algorithm.In this way,the technique speeds up the calculation of reliability indices.Since first-order contingency states have a high probability of being sampled,we propose a state-space partition technique to replace first-order contingency state simulation with first-order contingency state enumeration.Consequently,the calculation of reliability indices is further accelerated by avoiding a large amount of repetitive OPF analyses during simulation process without affecting reliability index accuracy.The validity and applicability of our approach are verified using the IEEE 118-bus and IEEE 145-bus systems.Numerical results indicate that the proposed approach can improve computational efficiency without decreasing accuracy.展开更多
Taxus,commonly known as yew,is a well-known gymnosperm with great ornamental and medicinal value.In this study,by assembling a chromosome-level genome of the Himalayan yew(Taxus wallichiana)with 10.9 Gb in 12 chromoso...Taxus,commonly known as yew,is a well-known gymnosperm with great ornamental and medicinal value.In this study,by assembling a chromosome-level genome of the Himalayan yew(Taxus wallichiana)with 10.9 Gb in 12 chromosomes,we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome,resulting in the main genes for paclitaxel biosynthesis,i.e.those encoding the taxadiene synthase,P450s,and transferases,being clustered on the same chromosome.The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization.Furthermore,we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway.The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodi-versity of taxoids in gymnosperms.展开更多
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supported by the National Natural Science Foundation of China(Nos.62335006,62022032,and 62275065)the Key Laboratory of Opto-Electronic Information Acquisition and Manipulation(Anhui University)+1 种基金Ministry of Education(No.OEIAM202202)the Fundamental Research Funds for the Central Universities(No.HIT.OCEF.2023011).
文摘A highly sensitive carbon dioxide(CO_(2))sensor based on light-induced thermoelastic spectroscopy(LITES)utilizing a selfdesigned low-frequency quartz tuning fork(QTF)and a fiber-coupled multipass cell(MPC)is reported in this paper.The QTF with a low resonant frequency of 8675 Hz and a high Q factor of 11,675.64 was used to improve its energy accumulation time and the sensor’s signal level.The MPC with the fiber-coupled structure and optical length of 40 m was adopted to significantly increase the gas absorbance and reduce the optical alignment difficulty as well as improve the robustness of the sensor system.A distributed feedback(DFB),near-infrared diode laser with an emission wavelength of 1.57μm was used as an excitation source.The experimental results showed that this CO_(2)-LITES sensor had an excellent linear response to CO_(2) concentrations.The minimum detection limitation(MDL)of this CO_(2)-LITES sensor was obtained to be 445.91 ppm,and it could be improved to 47.70 ppm(parts per million)when the integration time of the system reached 500 s.Further improvement methods for the detection performance of such sensors were also discussed.
基金National Natural Science Foundation of China(no.32371499)for supporting their research.
文摘Paclitaxel(Taxol)stands out as a tetracyclic diterpenoid natural product derived from the endangered plant Taxus.Recognized as a pivotal broad-spectrum anticancer drug,it has garnered widespread attention due to its low yield,intricate structure,unique anticancer mechanism,and remarkable efficacy(Tong et al.,2021).Although chemists achieved the total synthesis of paclitaxel 30 years ago,after decades of research,the natural biosynthetic pathway for its production remains an enigma(Ajikumar et al.,2010;Malci et al.,2023).A recent breakthrough,published in Molecular Plant by Alisdair R.Fernie's team,unveils a minimal gene set of 18 genes required for paclitaxel biosynthesis(Zhang et al.,2023),representing a significant mark toward unraveling the entire biosynthetic pathway and enhancing paclitaxel production efficiency.
基金supported by the National Key R&D Program of China(2020YFA0908000)the National Natural Science Foundation of China(31901015)Science and Technology Partnership Program,Ministry of Science and Technology of China(KY202001017).
文摘Monoterpenoids are typically present in the secretory tissues of higher plants,and their biosynthesis is catalyzed by the action of monoterpene synthases(MTSs).However,the knowledge about these enzymes is restricted in a few plant species.MTSs are responsible for the complex cyclization of monoterpene precursors,resulting in the production of diverse monoterpene products.These enzymatic reactions are considered exceptionally complex in nature.Therefore,it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid products.In our study,we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene products.By focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic,monocyclic and bicyclic products in MTSs,we observed that even a single amino acid mutation can change the specificity and diversity of MTS products,which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation changing.Notably,residues N340,I448,and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene cations.Alterations in these residues,either directly or indirectly,can impact the synthesis of single monoterpenes or their mixtures.By revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs,it will be possible to reasonably design and engineer different catalytic activities into existing MTSs,laying a foundation for the artificial design and industrial application of MTSs.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24000000,XDA19050302,and XDA24040201)the Science and Technology Innovation 2030-Major Project(2022ZD04017)+5 种基金the National Natural Science Foundation of China(32030021,32000475,and 32201775)the National Key Research and Development Program of China(2021YFF1001201)the Taishan Scholars Programthe Xplorer Prize Awardthe Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y2021038)the China National Postdoctoral Program for innovative Talents(BX2021354).
文摘Dear Editor,As one of the most important crops to supply the majority of plant oil and protein for the whole world,soybean is facing an increasing global demand.The reference genome of accession"Williams82"opened the gate of genomics research in soybean(Schmutz et al.,2010).After that,vast multi-omics data were generated,thereby providing valuable resources for functional study and molecular breeding.Parts of these data have been collected in different soybean databases(see details in Supplemental Table 1),such as Soybase(Grant et al.,2010)and SoyKB(Joshi et al.,2012),which made valuable efforts to facilitate the wide utility of these data.Nevertheless,these existing databases poorly tackled multi-omics data integration and interactivity for soybean,provoking tremendous challenges for researchers to deal with these big omics data,particularly considering the unprecedented rate of data growth(Yang et al.,2021).Thus,constructing an integrated multi-omics database for soybean that provides a one-stop solution for big data mining with friendly interactivity is highly desired.
基金supported by grants from the National Key R&D Program of China(no.2019YFA0905700)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-CXRC-015)+1 种基金China Postdoctoral Science Foundation(No.2019M661032)National Natural Science Foundation of China(No.31901026).
文摘Dear Editor,Plant UDP-dependent glycosyltransferases(UGTs),belonging to the carbohydrate-active enzyme glycosyltransferase 1 family(Louveau and Osbourn,2019),not only play important roles in adaptation to various environments(Cai et al.,2020;Pastorczyk-Szlenkier and Bednarek,2021)but also endow plant natural products with great pharmaceutical and ecological significance(Margolin et al.,2020).In recent years,an increasing number of plant UGTs have been characterized to function in the biosynthesis of many bioactive compounds such as ginsenosides(Wei et al.,2015),breviscapine(Liu et al.,2018),and rubusoside(Xu et al.,2022).
基金the National Natural Science Foundation of China(grant nos.62275065,62022032,61875047,and 61505041)Fundamental Research Funds for the Central Universities.
文摘As a new energy source,hydrogen(H_(2))detection is a hot topic in recent years.Because of the weak absorption characteristic,laser spectroscopy-based H_(2)detection is challenging.In this paper,a highly sensitive H_(2)sensor based on light-induced thermoelastic spectroscopy(LITES)technique is demonstrated for the first time.A continuous-wave,distributed feedback diode laser with emission in the 2.1μm region was adopted as the excitation source to target the strongest H_(2)absorption line of 4,712.90 cm^(−1).A Herriott multipass cell with an optical length of 10.1 m was chosen to further improve the H_(2)absorption.With the feature of processing the raw input data without data preprocessing and extracting the desired features automatically,the robust shallow neural network(SNN)fitting algorithm was brought in to denoise the sensor.For the LITES-based H_(2)sensor,the concentration response was tested,and an excellent linear response to H_(2)concentration levels was achieved.A minimum detection limit(MDL)of~80 ppm was obtained.On the basis of implementation of the H_(2)-LITES sensor,a heterodyne H_(2)-LITES sensor was further constructed to realize a fast measurement of resonance frequency of quartz tuning fork and H_(2)concentration simultaneously.The resonance frequency can be retrieved in several hundred milliseconds with the measurement accuracy of±0.2 Hz,and the result of 30,713.76 Hz is exactly same as the experimentally determined value of 30,713.69 Hz.After the SNN algorithm was applied,an MDL of~45 ppm was achieved for this heterodyne H_(2)-LITES sensor.
基金supported by the China Postdoctoral Science Foundation (No.2020TQ0222)。
文摘This paper proposes a branch-independence-based reliability assessment approach for transmission systems.The approach consists of branch decoupling and state-space partition techniques.By integrating an impact-increment-based reliability index calculation model and the proposed branch decoupling technique,a proportion of sampled contingency states no longer need to be analyzed using the time-consuming optimal power flow(OPF)algorithm.In this way,the technique speeds up the calculation of reliability indices.Since first-order contingency states have a high probability of being sampled,we propose a state-space partition technique to replace first-order contingency state simulation with first-order contingency state enumeration.Consequently,the calculation of reliability indices is further accelerated by avoiding a large amount of repetitive OPF analyses during simulation process without affecting reliability index accuracy.The validity and applicability of our approach are verified using the IEEE 118-bus and IEEE 145-bus systems.Numerical results indicate that the proposed approach can improve computational efficiency without decreasing accuracy.
基金the National Key R&D Program of China(2020YFA0908000)National Science Fund for Excellent Young Scholars(31922047)+1 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-002)the China Postdoctoral Science Foundation(No.2019M661032)。
文摘Taxus,commonly known as yew,is a well-known gymnosperm with great ornamental and medicinal value.In this study,by assembling a chromosome-level genome of the Himalayan yew(Taxus wallichiana)with 10.9 Gb in 12 chromosomes,we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome,resulting in the main genes for paclitaxel biosynthesis,i.e.those encoding the taxadiene synthase,P450s,and transferases,being clustered on the same chromosome.The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization.Furthermore,we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway.The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodi-versity of taxoids in gymnosperms.
