The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

JR东日本公司的新干线综合运输管理系统(COSMOS)

介绍了JR东日本旅客公司开发的新干线综合运输管理系统(COSMOS)的各种功能。该系统包括运输计划、运行管理、车站作业管理、维修作业管理、车辆管理、设备管理、信息集中管理和电力系统控制等子系统。

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Rates, predictors, and causes of readmission after transcatheter aortic valve replacement in patients with chronic kidney disease

BACKGROUND Transcatheter aortic valve replacement(TAVR)is a revolutionary procedure for severe aortic stenosis.The coexistence of chronic kidney disease(CKD)and TAVR introduces a challenge that significantly impacts patient outcomes.AIM To define readmission rates,predictors,and causes after TAVR procedure in CKD stage 1-4 patients.METHODS We used the national readmission database 2018 and 2020 to look into readmission rates,causes and predictors after TAVR procedure in patients with CKD stage 1-4.RESULTS Out of 24758 who underwent TAVR and had CKD,7892(32.4%)patients were readmitted within 90 days,and had higher adjusted odds of being females(adjusted odds ratio:1.17,95%CI:1.02-1.31,P=0.02)with longer length of hospital stay>6 days,and more comorbidities including but not limited to diabetes mellitus,anemia,and congestive heart failure(CHF).CONCLUSION Most common causes of readmission included CHF(18.0%),sepsis,and complete atrioventricular block.Controlling readmission predictors with very close followup is warranted to prevent such high rate of readmission.

Do changes in intracoronary pressure aid coronary spasm diagnosis using the spasm provocation test?

BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their occurrence.AIM To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the SPT.METHODS Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery pressure.During each SPT,the pressure wire was advanced into the distal portion of the right coronary artery(RCA)and left anterior descending coronary artery,and the ratio of intracoronary pressure to aortic pressure(Pd/Pa)was monitored.Coronary spasm was defined as an arterial narrowing of>90%in response to the administration of acetylcholine(ACh),with chest symptoms and/or ischemic electrocardiographic changes.ACh was administered to the RCA at low,moderate,or high doses of 20,50,or 80μg,respectively,and to the left coronary artery(LCA)at low,moderate,or high doses of 50,100,or 200μg,respectively.Coronary arteries with coronary spasms at low doses of ACh were defined as group L,and those with coronary spasms at moderate or high doses were defined as group MH.Those who did not occur coronary spasms at any ACh dose were designated as group N.RESULTS Among the 132 coronary arteries assessed using a pressure wire,there were 49 in group N,25 in group L,and 58 in group MH.Baseline Pd/Pa was the lowest in group L(P=0.001).The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N(P<0.001).A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95,with a sensitivity of 0.600(15/25)and a specificity of 0.713(76/107)and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was−0.04,with a sensitivity of 0.741(43/58)and a specificity of 0.694(34/49).CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for predicting the occurrence of coronary spasms.

Geothermo-mechanical alterations due to heat energy extraction in enhanced geothermal systems: Overview and prospective directions

Geothermal energy from deep underground (or geological) formations,with or without its combination with carbon capture and storage (CCS),can be a key technology to mitigate anthropogenic greenhouse gas emissions and meet the 2050 net‐zero carbon emission target.Geothermal resources in low‐permeability and medium‐and high‐temperature reservoirs in sedimentary sequence require hydraulic stimulation for enhanced geothermal systems (EGS).However,fluid migration for geothermal energy in EGS or with potential CO_(2) storage in a CO_(2)‐EGS are both dependent on the in situ flow pathway network created by induced fluid injection.These thermo‐mechanical interactions can be complex and induce varying alterations in the mechanical response when the working fluid is water (in EGS) or supercritical CO_(2)(in CO_(2)‐EGS),which could impact the geothermal energy recovery from geological formations.Therefore,there is a need for a deeper understanding of the heat extraction process in EGS and CO_(2)‐EGS.This study presents a systematic review of the effects of changes in mechanical properties and behavior of deep underground rocks on the induced flow pathway and heat recovery in EGS reservoirs with or without CO_(2) storage in CO_(2) ‐EGS.Further,we proposed waterless‐stimulated EGS as an alternative approach to improve heat energy extraction in EGS.Lastly,based on the results of our literature review and proposed ideas,we recommend promising areas of investigation that may provide more insights into understanding geothermo‐mechanics to further stimulate new research studies and accelerate the development of geothermal energy as a viable clean energy technology.

The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be determined.Heterotopicossification(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues.Hypoxia andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote HO.However,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to beelucidated.Here,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell fate.Usingsingle-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in MPCs.Zeugopod mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in vivo.ScRNA-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of HO.Importantly,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1αdeletion.From a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic metabolism.This suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC fate.These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

Porosity and bedding controls on bio-induced carbonate precipitation and mechanical properties of shale and dolomitic rocks: EICP vs MICP

Biocementation is an emerging field within geotechnical engineering that focuses on harnessing microbiological activity to enhance the mechanical properties and behavior of rocks. It often relies on microbial-induced carbonate precipitation (MICP) or enzyme-induced carbonate precipitation (EICP) which utilizes biomineralization by promoting the generation of calcium carbonate (CaCO3) within the pores of geomaterials (rock and soil). However, there is still a lack of knowledge about the effect of porosity and bedding on biocementation in rocks from a mechanistic view. This experimental study investigated the impact of porosity and bedding orientations on the mechanical response of rocks due to biocementations, using two distinct biocementation strategies (MICP and EICP) and characteristically low porosity but interbedded rocks (shale) and more porous but non-bedded (dolostone) rocks. We first conducted biocementation treatments (MICP and EICP) of rock samples over a distinct period and temperature. Subsequently, the rock strength (uniaxial compressive strength, UCS) was measured. Finally, we analyzed the pre- and post-treatment changes in the rock samples to better understand the effect of MICP and EICP biocementations on the mechanical response of the rock samples. The results indicate that biocementations in dolostones can improve the rock mechanical integrity (EICP: +58% UCS;MICP: +25% UCS). In shales, biocementations can either slightly improve (EICP: +1% UCS) or weaken the rock mechanical integrity (MICP: -39% UCS). Further, results suggest that the major controlling mechanisms of biogeomechanical alterations due to MICP and EICP in rocks can be attributed to the inherent porosity, biocementation type, and bedding orientations, and in few cases the mechanisms can be swelling, osmotic suction, or pore pressurization. The findings in this study provide novel insights into the mechanical responses of rocks due to MICP and EICP biocementations.

Clinical,pathological,and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers

Background:Colon cancers are categorized into mismatch repair deficient/microsatellite unstable(MSI-H)and mismatch repair proficient/microsatellite stable(MSS)cancers.This study aims to compare the disease char-acteristics and trends in the utilization of cancer therapies across different age groups and stages in these two groups.Methods:MSI-H and MSS colon adenocarcinomas from 2010 to 2016 were identified using the National Can-cer Database.We compared patient and disease characteristics between the two groups and evaluated the use of adjuvant chemotherapy across age groups and cancer stages.Within MSI-H and MSS groups,we conducted a land-mark analysis after propensity score matching for adjuvant chemotherapy versus no chemotherapy to determine its effect on survival.Results:Of the 542,368 patients that met inclusion criteria,120,751(22%)had mismatch repair results avail-able-out of these 96,928(80%)had MSS colon cancers while 23,823(19.7%)had MSI-H cancers.MSI-H disease had a bimodal age distribution(<40 years=22%;≥75 years=26%)and was frequent among females(22%)and non-Hispanic Whites(20%).Among those<65 years,15%of low-risk stage 2 MSI-H patients and 40%of high-risk stage 2 MSI-H patients received adjuvant chemotherapy.More than two-thirds of stage 3 patients<65 years received adjuvant chemotherapy in both groups.After conducting propensity-score matching for age,gender,and co-morbidities,we found that adjuvant chemotherapy use had a trend towards lower overall survival(OS)in low-risk stage 2 MSI-H(HR=1.8[95%CI,0.8-4.02])and high-risk stage 2 MSI-H(HR=1.42[95%CI,0.96-2.12])groups.Adjuvant chemotherapy significantly improved OS in stage 3 colon cancer patients irrespective of microsatellite status or risk category of disease.Conclusions:MSI-H colon cancer had bimodal age distribution.Among stage 2 MSI-H patients<65 years,a notable proportion received adjuvant chemotherapy.Among MSI-H stage 2 patients,adjuvant chemotherapy use was associated with lower survival while it significantly improved survival for stage 3 patients,irrespective of MSI status.

一氧化氮在亚细胞结构精确照射诱导旁效应中的作用

研究了肿瘤细胞的亚结构在荷能离子照射下所诱导的旁效应及其信号分子。以氦离子微束装置所产生的精确数量离子定位照射神经胶质瘤细胞T98G细胞核或细胞质,检测细胞染色体损伤和胞内一氧化氮(Nitric Oxide,NO)自由基的产额,探索NO清除剂对它们的影响,并以(Diethylamine nitric oxide,DEANO)研究NO的细胞效应。结果表明,无论是细胞核照射还是细胞质照射,只要1个细胞受到1个离子的照射,就可通过损伤的级联放大形成辐射旁效应,引起周围数十个细胞的损伤。对比核、质照射的生物效应,细胞核照射比细胞质照射具有更加显著的直接作用,但这两种照射所诱导的旁效应程度却相当。而NO自由基清除剂c-PTIO(2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide)可抑制旁效应的产生。NO分子探针DAF-FM(4-amino-5-methylamino-2',7'-difluorofluorescein diacetate)原位检测表明,即使只有1%的细胞核或细胞质受到单离子照射,具有NO阴性表达的细胞百分数增加了30%,使NO引起的细胞荧光密度增加15%。DEANO实验表明,NO可引起细胞微核的产生。因此,NO是亚细胞结构照射引起旁效应的一个重要信号因子。

腋淋巴结阳性乳腺浸润性导管癌差异蛋白的质谱分析

目的筛选可能用于判断乳腺浸润性导管癌发生腋淋巴结转移的血清蛋白标志物。方法收集2015年3月—2016年5月天津市宝坻区人民医院收治的乳腺浸润性导管癌患者血清样本24份,按照是否发生腋淋巴结转移分为两组,每组各12份。将每组的12份血清等量混合,利用双向凝胶电泳(2D-PAGE)和基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)技术鉴定差异蛋白质,对2D-PAGE图谱与MALDI-TOF-MS质谱进行分析。结果 2D-PAGE图谱分析筛选出差异蛋白点11个;经MALDI-TOF-MS质谱分析鉴定出高可信度的蛋白5种,表达上调的为T淋巴瘤侵袭转移诱导因子1(Tiam1)、组织蛋白酶K(Cat K)、血管内皮生长因子B(VEGF-B)、肌动蛋白相关蛋白复合物3(ARPC3),表达下调的为抑癌蛋白Necdin(覆盖率分别为Tiam1蛋白29%,Cat K蛋白12%,VEGF-B蛋白34%,ARPC3蛋白26%,Necdin蛋白18%)。结论乳腺浸润性导管癌发生腋淋巴结转移后其蛋白质表达谱也发生了变化,所鉴定出的差异蛋白有可能成为判断其是否发生腋淋巴结转移的血清蛋白标志物。

全国产化单纤高功率光纤激光器的研究

报道了采用国产双包层掺镱光纤搭建的高功率光纤激光器。此光纤激光器采用中国电子科技集团公司第四十六研究所最新研制的20/400双包层掺镱光纤,激光器采用谐振腔振荡方式输出,激光器中心波长为1080 nm,最高输出激光功率为758 W,输出光斑直径6~8 mm,接近准单模输出,光束β因子为1.3。电光转换效率36.7%,光-光转换效率71%,经过32 h的满功率激光输出,平均输出功率波动范围小于2%。

羽毛球颠球练习对小学生视力的即时干预效果研究

目的:为探讨羽毛球颠球练习对小学生视力的即时效果,找到一套方便实施的小学生预防近视的运动方法。方法:采用随机对照试验,将54名小学生随机分为羽毛球颠球练习组、羽毛球对打组和跳绳组,分别进行40分钟的练习,观察三组受试者运动前后视力变化。结果:羽毛球颠球组和羽毛球对打组的视力前后比较,双眼视力改善均有非常显著性差异(P<0.01),跳绳组干预前后,双眼视力无显著性变化。再对颠球组进行皮尔逊相关性分析,年龄越小,颠球后的视力改善越明显(r=-0.389,P<0.05)。结论:颠球具有较好的即时改善视力效果,且年龄越小,改善效果越好。

正六棱型MoO_(3-x)微米柱光催化剂的制备及性能

首先采用低温水相合成法制备了正六棱型MoO_(3)微米柱,然后以抗坏血酸为还原剂一步还原法制备了一种表面氧空位可控的MoO_(3-x)光催化材料。MoO_(3-x)具有较窄的禁带宽度和较大的光吸收范围。以罗丹明B为模拟污染物的光催化降解实验表明,随着氧空位的增加,MoO_(3-x)的催化活性明显增加。对于Mo^(5+)摩尔分数为20.1%的MoO2.799样品,降解90%的初始质量浓度为10 mg/L的罗丹明溶液只需要60 min。本研究为高性能半导体光催化材料的制备提供了一种新思路。

基于状态空间模型的飞行器装配误差敏感度研究

飞行器具有零部件多、结构复杂和装配精度要求高等特点,其装配有安全性装配、少可逆性装配等要求。根据飞行器相关的关键产品特性(Key product characteristic,KPC)和关键控制特性(Key control characteristic,KCC)参数,提出一种基于状态空间模型的装配误差敏感度量化分析方法,将飞行器多舱段精密装配过程中的误差敏感度分为3级指标,并进行阐述和定义。通过联立飞行器状态空间模型和输出方程,得到输入向量和输入矩阵的关系,进而求出状态转换矩阵,得到不同级别误差敏感度的理论表达式。将随机产生服从正态分布的装配特征误差代入系统矩阵,运用蒙特卡洛(Monte Carlo)仿真对不同装配特征的敏感度指标进行计算,并对比分析理论计算和蒙特卡洛仿真求得的特征级敏感度指标值。研究表明,将动态系统灵敏度分析方法应用到多工位装配过程可行,所提出的基于状态空间模型的飞行器装配误差敏感度分析方法合理,对飞行器舱段精密装配过程的精度评估具有参考意义。

Effects of cereal fiber on bowel function: A systematic review of intervention trials

AIM: To comprehensively review and quantitatively summarize results from intervention studies that examined the effects of intact cereal dietary fiber on parameters of bowel function. METHODS: A systematic literature search was conducted using Pub Med and EMBASE. Supplementary literature searches included screening reference lists from relevant studies and reviews. Eligible outcomes were stool wet and dry weight, percentage water in stools, stool frequency and consistency, and total transit time. Weighted regression analyses generated mean change(± SD) in these measures per g/d of dietary fiber. RESULTS: Sixty-five intervention studies among generally healthy populations were identified. A quantitative examination of the effects of non-wheat sources of intact cereal dietary fibers was not possible due to an insufficient number of studies. Weighted regression analyses demonstrated that each extra g/d of wheat fiber increased total stool weight by 3.7 ± 0.09 g/d(P < 0.0001; 95%CI: 3.50-3.84), dry stool weight by 0.75 ± 0.03 g/d(P < 0.0001; 95%CI: 0.69-0.82), and stool frequency by 0.004 ± 0.002 times/d(P = 0.0346; 95%CI: 0.0003-0.0078). Transittime decreased by 0.78 ± 0.13 h per additional g/d(P < 0.0001; 95%CI: 0.53-1.04) of wheat fiber among those with an initial transit time greater than 48 h.CONCLUSION: Wheat dietary fiber, and predominately wheat bran dietary fiber, improves measures of bowel function.

Role of endoscopic ultrasound during hospitalization for acute pancreatitis

Endoscopic ultrasound(EUS)is often used to detect the cause of acute pancreatitis(AP)after the acute attack has subsided.The limited data on its role during hospitalization for AP are reviewed here.The ability of EUS to visualize the pancreas and bile duct,the sonographic appearance of the pancreas,correlation of such appearance to clinical outcomes and the impact on AP management are analyzed from studies.The most important indication for EUS appears to be for detection of suspected common bile duct and/or gall bladder stones and microlithiasis.Such an approach might avoid diagnostic endoscopic retrograde cholangio-pancreatography with its known complications.The use of EUS during hospitalization for AP still appears to be infrequent but may become more frequent in future.

日本铁路客票预订和发售综合系统(MARS)

介绍了日本铁路客票预订和发售综合系统(MARS)的发展简史、现状,并作了展望。

Management and prevention of acute and chronic lateral ankle instability in athletic patient populations

Acute and chronic lateral ankle instability are common in high-demand patient populations. If not managed appropriately, patients may experience recurrent instability, chronic pain, osteochondral lesions of the talus, premature osteoarthritis, and other significantlong-term disability. Certain populations, including young athletes, military personnel and those involved in frequent running, jumping, and cutting motions, are at increased risk. Proposed risk factors include prior ankle sprain, elevated body weight or body mass index, female gender, neuromuscular deficits, postural imbalance, foot/ankle malalignment, and exposure to at-risk athletic activity. Prompt, accurate diagnosis is crucial, and evidence-based, functional rehabilitation regimens have a proven track record in returning active patients to work and sport. When patients fail to improve with physical therapy and external bracing, multiple surgical techniques have been described with reliable results, including both anatomic and nonanatomic reconstructive methods. Anatomic repair of the lateral ligamentous complex remains the gold standard for recurrent ankle instability, and it effectively restores native ankle anatomy and joint kinematics while preserving physiologic ankle and subtalar motion. Further preventative measures may minimize the risk of ankle instability in athletic cohorts, including prophylactic bracing and combined neuromuscular and proprioceptive training programs. These interventions have demonstrated benefit in patients at heightened risk for lateral ankle sprain and allow active cohorts to return to full activity without adversely affecting athletic performance.

Coronary spasm: It's common, but it's still unsolved

Coronary spasm is caused by a transient coronary nar -rowing due to the constriction of epicardial coronary artery, which leads to myocardial ischemia. More than 50 years have passed since the first recognition of coronary spasm, and many findings on coronary spasm have been reported. Coronary spasm has been considered as having pivotal roles in the cause of not only rest angina but also exertional angina, acute coronary syndrome, and heart failure. In addition, several new findings of the mechanism of coronary spasm have emerged recently. The diagnosis based mainly on coronary angiography and spasm provo-cation test and the mainstream treatment with a focus on a calcium-channel blocker have been established. At a glance, coronary spasm or vasospastic angina(VSA) has become a common disease. On the contrary, there are several uncertain or unsolved problems regarding coronary spasm, including the presence of medically refractory coronary spasm(intractable VSA), or an appropriate use of implantable cardioverter defibrillator in patients with cardiac arrest who have been confirmed as having coronary spasm. This editorial focused on coronary spasm, including recent topics and unsolved problems.