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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative Medicine 2024年第2期22卷 188-198页

作者： Meng li Yang Zhou Hui Zhu lie-ming Xu jian Ping Institute of liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of Traditional Chinese Medicine Shanghai 201203China Key Laboratory of liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in chol

关键词： liver cirrhosis biliary Long non-coding RNA H19 Danhongqing formula Cholangiocyte Hepatic stellate cells STAT3 transcription factor

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Male reproductive function before and after theadjustment of the COVID-19 prevention policy:amulticenter study in China

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Asian Journal of Andrology 2024年第3期26卷 308-314页

作者： jian-Zheng li Han Wu li Wang Yun-Shan Wang Feng Kong Long-Qiao Cao ming liang Xiong Wang ming-Zhen Yuan Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan 250000China Institute of Women Children and Reproductive HealthShandongUniversityJinan 250012China Engineering Laboratory of Urinary Organ and Functional Reconstruction of Shandong Province Jinan 250000China The First People’sHospital of Jining Jining 272000China Department of Reproductive Medicine The Second Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250000China Reproductive Medicine Center Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityYantai 264000China.

At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.

关键词： COVID-19 multicenter study reproduction SARS-CoV-2 semen analysis

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Oscillation properties of eigenfunctions for Sturm-liouville problems with interface conditions via Prufer transformation

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Applied Mathematics(A Journal of Chinese Universities) 2024年第2期39卷 191-200页

作者： li Zhi-yu li Kun CAI Jin-ming QIN jian-fang ZHENG Zhao-wen School of Mathematical Sciences Qufu Normal UniversityQufu 273165China College of Mathematics and Systems Science Guangdong Polytechnic Normal UniversityGuangzhou 510665China

A class of Sturm-liouville problems with discontinuity is studied in this paper.The oscillation properties of eigenfunctions for Sturm-liouville problems with interface conditions are obtained.The main method used in this paper is based on Prufer transformation,which is different from the classical ones.Moreover,we give two examples to verify our main results.

关键词： Sturm-liouville problem interface condition oscillatory solution

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Integrating machine learning and CALPHAD method for exploring low-modulus near-β-Ti alloys

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Rare Metals 2024年第1期43卷 309-323页

作者： Hao Zou Yue-Yan Tian li-Gang Zhang Ren-Hao Xue Zi-Xuan Deng ming-ming Lu jian-Xin Wang li-Bin liu School of Computer Science and Engineering Central South UniversityChangsha 410083China School of Materials Science and Engineering Central South UniversityChangsha 410083China State Key Laboratory of Powder Metallurgy Central South UniversityChangsha 410083China

Traditional theoretical and empirical calculation methods can guide the design of β-and metastable β-alloys for bio-titanium. However, it is still difficult to obtain novel near-β-Ti alloys with low modulus. This study developed a method that combines machine learning with calculation of phase diagrams(CALPHAD) to facilitate the design of near-β-Ti alloys. An elastic modulus database of Ti–Nb–Zr–Mo–Ta–Sn system was constructed first, and then three features(the electron to atom ratio, mean absolute deviation of atom mass, and mean electronegativity) were selected as the key factors of modulus by performing a three-step feature selection. With these features, a highly accurate model was built for predicting the modulus of near-β-Ti alloys. To further ensure the accuracy of modulus prediction, machine learning with the elastic constants calculated was leveraged by CALPHAD database. The root mean square error of the well-trained model can be as low as 6.75 GPa. Guided by the prediction of machine learning and CALPHAD, three novel near-β-Ti alloys with elastic modulus below 50 GPa were successfully designed in this study. The best candidate alloy(Ti–26Nb–4Zr–4Sn–1Mo–Ta) exhibits an ultra-low modulus(36.6 GPa) after cold rolling with a thickness reduction of 20%. Our method can greatly save time and resources in the development of novel Ti alloys, and experimental verifications have demonstrated the reliability of this method.

关键词： Near-β-Ti alloy Machine learning Calculation of phase diagram Low-modulus alloy Feature selection

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A general synthetic strategy for N, P co-doped graphene supported metal-rich noble metal phosphides for hydrogen generation

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Green Energy & Environment 2024年第1期9卷 152-162页

作者： Jingwen Ma Xiang li Guangyu Lei Jun Wang Juan Wang jian liu ming Ke Yang li Chunwen Sun School of Chemical and Environmental Engineering China University of Mining and Technology(Beijing)Beijing100083China State Key Laboratory of Heavy Oil Processing China University of PetroleumBeijing102249China Lab of Advanced Nano-structures&Transfer Processes Department of Chemical EngineeringTianjin UniversityTianjin300354China PetroChina Planning and Engineering Institute Beijing100083China

The exploitation of electrocatalysts with high activity and durability for HER is desirable for future energy systems,but it is still a challenge.NMPs have attracted increasing attentions,but the preparation process often needs toxic regents or dangerous reaction conditions.Herein,we develop a general green method to fabricate metal-rich NMPs anchored on NPG through pyrolyzing DNA cross-linked complexes.The obtained Ru_(2) P-NPG exhibits an ultrasmall overpotential of 7 mV at 10 mA cm^(2) and ultralow Tafel slope of 33 mV dec^(-1) in 1.0 mol L?1 KOH,even better than that of commercial Pt/C.In addition,Ru 2 P-NPG also shows low overpotentials of 29 and 78 mV in 0.5 mol L^(-1) H_(2)SO_(4) and 1.0 mol L^(-1) PBS,respectively.The superior activity can be attributed to the ultrafine dispersion of Ru 2 P nanoparticles for more accessible sites,more defects formed for abundant active sites,the two-dimensional plane structure for accelerated electron transfer and mass transport,as well as the regulation of electron distribution of the catalyst.Moreover,the synthetic method can also be applied to prepare other metal-rich noble metal phosphides(Pd_(3)P-NPG and Rh_(2)P-NPG),which also exhibits high activity for HER.This work provides an effective strategy for designing NMP-based electrocatalysts.

关键词： Noble metal phosphides Electrocatalyst Deoxyribonucleic acid Hydrogen evolution pH universal

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METTL5 promotes gastric cancer progression via sphingomyelin metabolism

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1925-1946页

作者： Ya-Qiong Zhang jian li Zhe Qin De-ming li Fang-Zhou Ye Song-Hua Bei Xiao-Hong Zhang li Feng Endoscopy Center Minhang Hospital Affiliated to Fudan UniversityShanghai 201100China

BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expr

关键词： Gastric cancer METTL5 Sphingomyelin metabolism Cisplatin

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Development in oxide metallurgy for improving the weldability of high -strength low-alloy steel-Combined deoxidizers and microalloying elements

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1263-1284页

作者： Tingting li jian Yang State Key Laboratory of Advanced Special Steel School of Materials Science and EngineeringShanghai UniversityShanghai 200444China

The mechanisms of oxide metallurgy include inducing the formation of intragranular acicular ferrite(IAF)using micron-sized inclusions and restricting the growth of prior austenite grains(PAGs)by nanosized particles during welding.The chaotically oriented IAF and refined PAGs inhibit crack initiation and propagation in the steel,resulting in high impact toughness.This work summarizes the com-bined effect of deoxidizers and alloying elements,with the aim to provide a new perspective for the research and practice related to im-proving the impact toughness of the heat affected zone(HAZ)during the high heat input welding.Ti complex deoxidation with other strong deoxidants,such as Mg,Ca,Zr,and rare earth metals(REMs),can improve the toughness of the heat-affected zone(HAZ)by re-fining PAGs or increasing IAF contents.However,it is difficult to identify the specific phase responsible for IAF nucleation because ef-fective inclusions formed by complex deoxidation are usually multiphase.Increasing alloying elements,such as C,Si,Al,Nb,or Cr,con-tents can impair HAZ toughness.A high C content typically increases the number of coarse carbides and decreases the potency of IAF formation.Si,Cr,or Al addition leads to the formation of undesirable microstructures.Nb reduces the high-temperature stability of the precipitates.Mo,V,and B can enhance HAZ toughness.Mo-containing precipitates present good thermal stability.VN or V(C,N)is ef-fective in promoting IAF nucleation due to its good coherent crystallographic relationship with ferrite.The formation of the B-depleted zone around the inclusion promotes IAF formation.The interactions between alloying elements are complex,and the effect of adding dif-ferent alloying elements remains to be evaluated.In the future,the interactions between various alloying elements and their effects on ox-ide metallurgy,as well as the calculation of the nucleation effects of effective inclusions using first principles calculations will become the focus of oxide metallurgy.

关键词： oxide metallurgy technology heat affected zone high-strength low-alloy steel intragranular acicular ferrite microalloying element

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Vertical two-dimensional WS_(2)flakes grown on flexible CNT film for excellent electrochemical performance

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Rare Metals 2024年第1期43卷 164-174页

作者： Qian Gong Jing-Yun Zou ming Ren Si-Qi Zhu Yu-Rong Zhou li-ming Zhao jian Chen Yu-Long Wu jiang-Tao Di li-Xing Kang Qing-Wen li School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaHefei 230026China Key Laboratory of Multifunctional Nanomaterials and Smart Systems Division of Advanced MaterialsSuzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhou 215123China jiangsu Key Laboratory of Micro and Nano Heat Fluid Flow Technology and Energy Application School of Physical Science and TechnologySuzhou University of Science and TechnologySuzhou 215009China

Soft electrochemical actuators that can generate mechanical motions in response to electrical stimuli can be used as artificial muscles in microscale robots.The electrode materials are the key component of the electrochemical actuator because they limit the ion diffusion and accumulation processes and thus affect the deformation in fast response-time and potential engineering applications.Low-dimensional materials,such as one-dimensional(1D)CNT and two-dimensional(2D)vertically stood WS_(2),are great electrode due to their good electrochemical stability and high surface-to-volume ratios,but show limited performances when being used on their own in the actuators because of low reconstruction or low conductivity.A combination of 1D CNT and 2D WS_(2)could form a heterojunction with both high electrochemical activity and great mechanical stability.Herein,by depositing highly disordered graphene nanosheets(HDGNs)on CNT films and then WS_(2)on the formed low-dimensional nanocarbon film,a hybrid WS_(2)/HDGN/CNT film was synthesized through a multistep CVD method.Vertically grown WS_(2)nanosheets were achieved by taking advantage of HDGNs which limits CNTs sliding.So,the volume expansion caused by the transition from WO_(3)to WS-2can force the vertical growth of WS_(2).This hybrid film shows excellent electrochemical properties,such as high specific capacitance and high rate performance.Soft actuators based on the WS_(2)/HDGN/CNT films show good actuating performance,including stability and reconfigurability.

关键词： CNT Graphene Vertically growth WS_(2) Electrochemical actuators

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Multidisciplinary comprehensive treatment of massive hepatocellular carcinoma with hemorrhage:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2225-2232页

作者： Xian-Shuai Kou Fan-Fan li Yun Meng jian-ming Zhao Sheng-Fen liu Lan Zhang The First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina Department of Thoracic Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Department of Orthopedics Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC),a major contributor to cancer-related deaths,is particularly prevalent in Asia,largely due to hepatitis B virus infection.Its prognosis is generally poor.This case report contributes to the medical literature by detailing a unique approach in treating a large HCC through multidisciplinary collaboration,particularly in patients with massive HCC complicated by ruptured bleeding,a scenario not extensively documented previously.CASE SUMMARY The patient presented with large HCC complicated by intratumoral bleeding.Treatment involved a multidisciplinary approach,providing individualized care.The strategy included drug-eluting bead transarterial chemoembolization,sorafenib-targeted therapy,laparoscopic partial hepatectomy,and standardized sintilimab monoclonal antibody therapy.Six months after treatment,the patient achieved complete radiological remission,with significant symptom relief.Imaging studies showed no lesions or recurrence,and clinical assessments confirmed complete remission.This report is notable as possibly the first docu-mented case of successfully treating such complex HCC conditions through integrated multidisciplinary efforts,offering new insights and a reference for future similar cases.CONCLUSION This study demonstrated effective multidisciplinary treatment for massive HCC with intratumoral bleeding,providing insights for future similar cases.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Sintilimab Sorafenib Translational therapy Multidisciplinary team Case report

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Exploring changes of precipitation extremes under climate change through global variable-resolution modeling

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Science Bulletin 2024年第2期69卷 237-247页

作者： Wei Sun jian li Rucong Yu Nina li Yi Zhang State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China Institute of Tibetan Plateau Meteorology China Meteorological AdministrationChengdu 610072China Department of Atmospheric Science Yunnan UniversityKunming 650091China National Meteorological Center China Meteorological AdministrationBeijing 100081China 2035 Future Laboratory PIESAT Information Technology Co.Ltd.Beijing 100105China

Understanding the responses of precipitation extremes to global climate change remains limited owing to their poor representations in models and complicated interactions with multi-scale systems.Here we take the record-breaking precipitation over China in 2021 as an example,and study its changes under three different climate scenarios through a developed pseudo-global-warming(PGW)experimental framework with 60-3 km variable-resolution global ensemble modeling.Compared to the present climate,the precipitation extreme under a warmer(cooler)climate increased(decreased)in intensity,coverage,and total amount at a range of 24.3%-37.8%(18.7%-56.1%).With the help of the proposed PGW experimental framework,we further reveal the impacts of the multi-scale system interactions in climate change on the precipitation extreme.Under the warmer climate,large-scale water vapor transport converged from double typhoons and the subtropical high marched into central China,enhancing the convective energy and instability on the leading edge of the transport belt.As a result,the mesoscale convective system(Mcs)that directly contributed to the precipitation extreme became stronger than that in the present climate.On the contrary,the cooler climate displayed opposite changing characteristics relative to the warmer climate,ranging from the large-scale systems to local environments and to the Mcs.In summary,our study provides a promising approach to scientifically assess the response of precipitation extremes to climate change,making it feasible to perform ensemble simulations while investigating the multi-scale system interactions over the globe.

关键词： Precipitation extreme Climate change Pseudo-global-warming experiment Variable-resolution modeling Multi-scale system interaction

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