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Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1532-1546页

作者： Jin Liu Si-Cong Zeng An Wang Hai-Ying Cheng Qian-jun zhang Guang-xiu Lu Hunan Guangxiu Hospital Hunan Normal UniversityChangsha 410000Hunan ProvinceChina Scientific Research Department Reproductive and Genetic Hospital of Citic-XiangyaChangsha 410000Hunan ProvinceChina

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11(STK11/LKB1)gene mutations.Preimplantation genetic testing can protect a patient’s offspring from mutated genes;however,some variations in this gene have been interpreted as variants of uncertain significance(VUS),which complicate reproductive decision-making in genetic counseling.AIM To identify the pathogenicity of two missense variants and provide clinical guidance.METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya.Software was employed to predict the protein structure,conservation,and pathogenicity of the two missense variation sites in patients with PJS.Additionally,plasmids were constructed and transfected into HeLa cells to observe cell growth.The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry.Statistical analysis was performed using one-way analysis of variance.PG(p.Arg297Gly)and c.733C>T(p.Leu245Phe)]in 9 unrelated PJS families who were seeking reproductive assistance.The two missense VUS were located in the catalytic domain of serine/threonine kinase,which is a key structure of the liver kinase B1(LKB1)protein.In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase(AMPK)at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells.In addition,the two missense STK11 variants promoted the proliferation of HeLa cells.Subsequent immunohistochemical analysis showed that phosphorylated-AMPK(Thr172)expression was significantly lower in gastric,colonic,and uterine polyps from PJS patients with missense variations than in non-PJS patients.Our find

关键词： Missense STK11 Peutz-Jeghers syndrome Rare disease Genetic counseling Assisted reproductive technique

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A bifunctional POM-based Cu-viologen complex with mixed octamolybdate clusters for rapid oxidation desulfurization and effective photogeneration of hydrogen

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Rare Metals 2024年第1期43卷 236-246页

作者： Lin Yang Zhong zhang Chao-Nan zhang xiu-Li Wang College of Chemistry and Materials Engineering Bohai UniversityJinzhou 121013China Professional Technology Innovation Center of Liaoning Province for Conversion Materials of Solar Cell Bohai UniversityJinzhou 121013China

The design and synthesis of catalysts for the oxidation desulfurization and production of hydrogen are extremely important for solving environmental pollution and energy shortage.Herein,a novel bifunctional [α-Mo_(8)O_(26)]^(4-)/[β-Mo_(8)O_(26)]^(4-)-based Cu-viologen complex H_(4)[Cu_(2)~ⅠCl_(2)(Hbcbpy)_(4)] [α-Mo_(8)O_(26)] [β-Mo8O_(26)]·H_(2)O(BHU-2,Hbcbpy=1-(4-carboxybenzyl)-4,4'-bipyridinium) was synthesized and characterized by single-crystal X-ray diffraction(XRD),infrared radiation spectra,powder X-ray diffraction(PXRD) and X-ray photoelectron spectroscopy(XPS) spectra.The structural characteristic of BHU-2 is the presence of two types of octamolybdate clusters [α-Mo_(8)O_(26)]^(4-)/[β-Mo_(8)O_(26)]^(4-)and a new binuclear Cu~Ⅰ-Hbcbpy complex linked by Cl-bridges[Cu_(2)ⅠCl_(2)(Hbcbpy)_(4)]^(4+).BHU-2 as a heterogeneous catalyst exhibits excellent activities to the oxidation desulfurization and photocatalytic hydrogen production.At room temperature,BHU-2 can catalyze 96% conversion of methyl phenyl sulfide with 98% selectivity,and the process obeys the pseudo-first-order reaction kinetic with the half-life of9.6 min.The notorious 2-chloroethyl ethyl sulfide can achieve 99% conversion with 98% selectivity within only1 min at the presence of BHU-2,and the turnover frequency(TOF) is up to 7400 h^(-1).BHU-2 also exhibits high catalytic activity for the oxidation of other aromatic and aliphatic thioethers within short time at room temperature.Furthermore,BHU-2 shows a high catalytic activity for visible-light-driven hydrogen evolution with an H_(2) evolution rate of 1677.85 μmol·g^(-1)·h^(-1) within 10 h.Moreover,the catalytic activities do not decrease evidently after three cycles,revealing the prominent structural stability and recyclability.

关键词： Polyoxometalate Metal-organic complex Viologen Oxidation desulfurization Photocatalytic hydrogen production

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A Detailed Thermal Resistance Network Analysis of FCBGA Package

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Journal of Thermal Science 2024年第1期33卷 18-28页

作者： DANG Hao LU Yang DU Yanzheng zhang xiu zhang Qian MA Weigang zhang Xing Key Laboratory for Thermal Science and Power Engineering of Ministry of Education Department of Engineering MechanicsTsinghua UniversityBeijing 100084China Zhongxing Telecom Equipment Corporation Shanghai 201203China

Using thermal models to describe the heat dissipation process of FCBGA is a significant topic in the field of packaging.However,the thermal resistance model considering the structure of each part of the chip is still ambiguous and rare,but it is quite desirable in engineering.In this work,we propose a detailed thermal resistance network model,and describe it by using thermal conduction resistance and thermal spreading resistance.For a striking FCBGA case,we calculated the thermal resistance of each part of the structure according to the temperature field simulated by COMSOL.The thermal resistance network can be used to predict the temperatures in the chip under different conditions.For example,when the power changes by 40%,the relative error of junction temperature prediction is only 0.24%.The function of the detailed thermal resistance network in evaluating the optimization space and determining the optimization direction is clarified.This work illustrates a potential thermal resistance analysis method for electronic devices such as FCBGA.

关键词： FCBGA package thermal resistance network thermal spreading resistance junction temperature

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Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/m TOR Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 251-259页

作者： YAO jun-peng FENG xiu-mei WANG Lu LI Yan-qiu ZHU Zi-yue YAN Xiang-yun YANG Yu-qing LI Ying zhang Wei Acupuncture and Tuina School Chengdu University of Traditional Chinese MedicineChengdu611137China Department of Rehabilitation Medicine Guanghan People’s HospitalGuanghanSichuan Province618399China Academic Affairs Office Chengdu University of Traditional Chinese MedicineChengdu611137China

Objective:To explore the mechanism of electroacupuncture(EA) in promoting recovery of the facial function with the involvement of autophagy,glial cell line-derived neurotrophic factor(GDNF),and phosphatidylinositol-3-kinase(PI3K)/mammalian target of rapamycin(mTOR) signaling pathway.Methods:Seventy-two male Sprague-Dawley rats were randomly allocated into the control,sham-operated,facial nerve injury(FNI),EA,EA+3-methyladenine(3-MA),and EA+GDNF antagonist groups using a random number table,with 12 rats in each group.An FNI rat model was established with facial nerve crushing method.EA intervention was conducted at Dicang(ST 4),Jiache(ST 6),Yifeng(SJ 17),and Hegu(LI 4) acupoints for 2 weeks.The Simone’s 10-Point Scale was utilized to monitor the recovery of facial function.The histopathological evaluation of facial nerves was performed using hematoxylin-eosin(HE) staining.The levels of Beclin-1,light chain 3(LC3),and P62 were detected by immunohistochemistry(IHC),immunofluorescence,and reverse transcriptionpolymerase chain reaction,respectively.Additionally,IHC was also used to detect the levels of GDNF,Rai,PI3K,and mTOR.Results:The facial functional scores were significantly increased in the EA group than the FNI group(P<0.05 or P<0.01).HE staining showed nerve axons and myelin sheaths,which were destroyed immediately after the injury,were recovered with EA treatment.The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats(P<0.01);however,EA treatment reversed these abnormal changes(P<0.01).Meanwhile,EA stimulation significantly increased the levels of GDNF,Rai,PI3K,and mTOR(P<0.01).After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist,the repair effect of EA on facial function was attenuated(P<0.05 or P<0.01).Conclusions:EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI.EA may exert this neuroreparative effect through mediating the release of GDNF,activating the PI3

关键词： electroacupuncture facial nerve injury autophagy glial cell line-derived neurotrophic factor phosphatidylinositol-3-kinase/mammalian target of rapamycin Chinese medicine

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Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes:A Meta-Regression of Acupuncture Randomized Controlled Trials

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Chinese Journal of Integrative Medicine 2024年第3期30卷 260-266页

作者： xiu Wen-cui GANG Wei-juan ZHOU Qi SHI Lan-jun HU Xiang-yu MING Tian-yu LUO Zhen zhang Yu-qing JING Xiang-hong Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing100700China China Center for Evidence-Based Traditional Chinese Medicine China Academy of Chinese Medical SciencesBeijing100700China Department of Health Research Methods Evidenceand ImpactMcMaster UniversityHamiltonOntarioL8S 4L8Canada Center for Evidence-Based Integrative Medicine-Clarity Collaboration Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China

Background:The effects of acupuncture have varied in different randomized controlled trials(RCTs),and there are many factors that influence treatment effect of acupuncture in different outcomes,with conflicting results.Objective:To identify factors and their impact on the treatment effect of acupuncture in different outcomes.Methods:Acupuncture RCTs were searched from 7 databases including Medline(Pub Med),Embase,Cochrane Central Register of Controlled Trials,China National Knowledge Infrastructure,Wanfang Database,VIP Database,and China Biology Medicine disc between January 1st,2015 and December 31st,2019.Eligible studies must compare acupuncture to no acupuncture,sham acupuncture,or waiting lists,and report at least 1patient-important outcome.A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables,even those excluded from the multivariable model due to collinearities.We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences(SMDs),categorising them as small(0.4) effects.Results:The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables.High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude,the difference of adjusted SMDs 0.46,95% confidence interval(CI) 0.07 to 0.84;P=0.02].The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables.Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture(0.30,95% CI 0.06 to 0.53;P=0.01).The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables.Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects,compared to non-penetrating acupuncture and fixed regimen,respectively(0.40,95% CI 0 to 0.80;P=0.05;0.29,95% CI 0.06 to 0.53;P=0.01).

关键词： acupuncture randomized controlled trial patient-important outcome meta-regression

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Deep Guided Attention Network for Joint Denoising and Demosaicing in Real Image

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Chinese Journal of Electronics 2024年第1期33卷 303-312页

作者： Tao zhang Ying FU jun zhang School of Computer Science and Technology Beijing Institute of Technology Advanced Reasearch Institute of Multidisciplinary Science Beijing Institute of Technology

Denoising(DN) and demosaicing(DM) are the first crucial stages in the image signal processing pipeline. Recently, researches pay more attention to solve DN and DM in a joint manner, which is an extremely undetermined inverse problem. Existing deep learning methods learn the desired prior on synthetic dataset, which limits the generalization of learned network to the real world data. Moreover, existing methods mainly focus on the raw data property of high green information sampling rate for DM, but occasionally exploit the high intensity and signalto-noise(SNR) of green channel. In this work, a deep guided attention network(DGAN) is presented for real image joint DN and DM(JDD), which considers both high SNR and high sampling rate of green information for DN and DM, respectively. To ease the training and fully exploit the data property of green channel, we first train DN and DM sub-networks sequentially and then learn them jointly, which can alleviate the error accumulation. Besides, in order to support the real image JDD, we collect paired raw clean RGB and noisy mosaic images to conduct a realistic dataset. The experimental results on real JDD dataset show the presented approach performs better than the state-of-the-art methods, in terms of both quantitative metrics and qualitative visualization.

关键词： Image denoising Image demosaicing Joint processing Guided attention Paired real dataset

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Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei zhang Yongguo zhang Yinglin Xia jun Sun Division of Gastroenterology and Hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer Center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown VA Medical Center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 phase.Long CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized duration.Anyone infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early.People with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental models.Here,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long CovID.We highlight the potential mechanisms and possible treatment based on Gl health and microbiome.Finally,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

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Accelerating Asteroidal Period and Pole Inversion from Multiple Lightcurves Using Parallel Differential Evolution and Cellinoid Shape Model

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Research in Astronomy and Astrophysics 2024年第4期24卷 271-286页

作者： Yong-Xiong zhang Wen-xiu Guo Xiao-Ping Lu Hua Zheng Hai-Bin Zhao jun Tian Wei-Lin Wang School of Engineering Guangzhou College of Technology and BusinessGuangzhou 510850China School of Computer Science and Engineering Macao University of Science and TechnologyTaipaMacao 999078China School of Mathematics and Statistics Shaoguan UniversityShaoguan 512099China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao 999078China Key Laboratory of Planetary Sciences Purple Mountain ObservatoryCASNanjing 210023China

Determining asteroid properties provides valuable physical insights but inverting them from photometric lightcurves remains computationally intensive.This paper presents a new approach that combines a simplified Cellinoid shape model with the Parallel Differential Evolution(PDE)algorithm to accelerate inversion.The PDE algorithm is more efficient than the Differential Evolution algorithm,achieving an extraordinary speedup of 37.983 with 64 workers on multicore CPUs.The PDE algorithm accurately derives period and pole values from simulated data.The analysis of real asteroid lightcurves validates the method’s reliability:in comparison with results published elsewhere,the PDE algorithm accurately recovers the rotational periods and,given adequate viewing geometries,closely matches the pole orientations.The PDE approach converges to solutions within 20,000 iterations and under one hour,demonstrating its potential for large-scale data analysis.This work provides a promising new tool for unveiling asteroid physical properties by overcoming key computational bottlenecks.

关键词： methods:numerical minor planets asteroids:general techniques:photometric astrom

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Host plant traits play a crucial role in shaping the composition of epiphytic microbiota in the arid desert,Northwest China

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Journal of Arid Land 2024年第5期16卷 699-724页

作者： zhang jun zhang Yuanming zhang Qi State Key Laboratory of Desert and Oasis Ecology Key Laboratory of Ecological Safety and Sustainable Development in Arid LandsXinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China Xinjiang Key Laboratory of Biodiversity Conservation and Application in Arid Lands Xinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China Xinjiang Field Scientific Observation Research Station of Tianshan Wild Fruit Forest Ecosystem Yili Botanical GardenXinjiang Institute of Ecology and GeographyChinese Academy of SciencesUrumqi 830011China College of Life Sciences Shihezi UniversityShihezi 832003China

Phyllosphere microorganisms are a crucial component of environmental microorganisms,highly influenced by host characteristics,and play a significant role in plant health and productivity.Nonetheless,the impact of host characteristics on shaping phyllosphere microbial communities of plants with different life forms remains ambiguous.Utilizing high-throughput sequencing technology,this study analyzed the diversity and community composition of phyllosphere epiphytic microorganisms(e.g.,bacteria and fungi)of various plant life forms in the hinterland of the Gurbantunggut Desert,Northwest China.Functional annotation of prokaryotic taxa(FAPROTAX)and fungi function guild(FUNGuild)were employed to assess the ecological functions of microorganisms and to investigate the role of stochastic and deterministic processes in shaping phyllosphere microbial communities.Result showed a diverse array of phyllosphere epiphytic microorganisms in the desert plants,with Proteobacteria,Cyanobacteria,and Actinobacteriota dominating bacterial community,while Ascomycota and Basidiomycota were prevalent in fungal community.Comparison across different plant life forms highlighted distinct microbial communities,indicating strong filtering effects by plant characteristics.FAPROTAX prediction identified intracellular parasites(accounting for 27.44%of bacterial community abundance),chemoheterotrophy(10.12%),and phototrophy(17.41%)as the main functions of epiphytic bacteria on leaves of different life form plants.FUNGuild prediction indicated that phyllosphere epiphytic fungi primarily served as Saprotrophs(81.77%),Pathotrophs(17.41%),and Symbiotrophs(0.82%).Co-occurrence network analysis demonstrated a predominance of positive correlations among different microbial taxa.Raup-Crick dissimilarity index analysis revealed that deterministic processes predominantly influenced phyllosphere bacterial and fungal community assembly.Variance partitioning analysis and random forest modeling suggested that plant leaf functional traits significantly impacted

关键词： phyllosphere epiphytic bacteria phyllosphere epiphytic fungi community structure community diversity functional diversity plant life form plant functional traits

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Probiotics intervention in colorectal cancer:From traditional approaches to novel strategies

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Chinese Medical Journal 2024年第1期137卷 8-20页

作者： Suki Ha Xiang zhang jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status.These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis,metabolism,and immune response.The disruption of microbiota,known as dysbiosis,has been implicated in many intestinal diseases,including colorectal cancer(CRC).As the third most common cancer and the second leading cause of cancer-related death worldwide,CRC poses a significant health burden.There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes.Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment.Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC,alleviating treatment-related side effects,and potentiating the efficacy of anticancer therapy,which is the key to successful translation to clinical practice.This paper aims to review the traditional probiotics and new interventions,such as next-generation probiotics and postbiotics,in the context of CRC.The underlying mechanisms of probiotic anti-cancer effects are also discussed,including the restoration of microbial composition,reinforcement of gut barrier integrity,induction of cancer cell apoptosis,inactivation of carcinogens,and modulation of host immune response.This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy.Despite all the promising findings presented in studies,the evaluation of potential risks,optimization of delivery methods,and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

关键词： colorectal cancer probiotics gut microbiota dysbiosis adjuvant therapy immune modulation gut barrrier

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