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Background: Although ERAS Program had some advantages in laparoscopic distal gastrectomy (LDG), its efficacy and safety remained unclear. We conducted a systematic review and meta-analysis to assess the efficacy and safety of the ERAS group and the traditional care (TC) group in LDG. Methods: Multiple databases were retrieved from 1 January 2000 to 30 April 2023. The risk ratio (RR), standardized mean difference (SMD) and their 95% confidence interval (CI) were used to estimate the results. Results: Our meta-analysis contained 17 randomized controlled trials (RCTs) studies, which comprised 1468 patients. Regarding efficacy, the ERAS group had significantly shorter postoperative time to first flatus (SMD=-1.29 [95% CI: -1.68, -0.90]), shorter time to first defecation (SMD=-1.26 [95% CI: -1.90, -0.61]), shorter hospital stays (SMD=-0.99 [95% CI: -1.34, -0.63]), and lower hospitalization costs (SMD=-1.17 [95% CI: -1.86, -0.48]) compared to the TC group. Furthermore, in the ERAS group, C-reactive protein levels were lower on postoperative days 1, 3 or 4, and 7; albumin levels were higher on postoperative days 3 or 4 and 7; and interleukin-6 levels were lower on postoperative days 1 and 3. Regarding safety, the overall postoperative complication rate was lower in the ERAS group (RR: 0.76 [95% CI: 0.60, 0.97]), but there was no significant difference in the individual postoperative complication rate. Other indicators were also not statistically significant. Conclusion: The combination of ERAS Program with laparoscopy surgery was safe and effective for the perioperative management of patients with distal gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice. Methods: A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool. Results: A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant. Conclusion: The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common form of dementia. There are two main types of AD: familial and sporadic. Familial AD is linked to mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). On the other hand, sporadic AD is the more common form of the disease and has genetic, epigenetic, and environmental components that influence disease onset and progression. Investigating the epigenetic mechanisms associated with AD is essential for increasing understanding of pathology and identifying biomarkers for diagnosis and treatment. Chemical covalent modifications on DNA and RNA can epigenetically regulate gene expression at transcriptional and posttranscriptional levels and play protective or pathological roles in AD and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, which is clinically identified with irregular and rapid heartbeat rhythm. AF puts a patient at risk of forming blood clots, which can eventually lead to heart failure, stroke, or even sudden death. Electrocardiography (ECG), which involves acquiring bioelectrical signals from the body surface to reflect heart activity, is a standard procedure for detecting AF. However, the occurrence of AF is often intermittent, costing a significant amount of time and effort from medical doctors to identify AF episodes. Moreover, human error is inevitable, as even experienced medical professionals can overlook or misinterpret subtle signs of AF. As such, it is of critical importance to develop an advanced analytical model that can automatically interpret ECG signals and provide decision support for AF diagnostics. Methods: In this paper, we propose an innovative deep-learning method for automated AF identification using single-lead ECGs. We first extract time-frequency features from ECG signals using continuous wavelet transform (CWT). Second, the convolutional neural networks enhanced with residual learning (ReNet) are employed as the functional approximator to interpret the time-frequency features extracted by CWT. Third, we propose to incorporate a multi-branching structure into the ResNet to address the issue of class imbalance, where normal ECGs significantly outnumber instances of AF in ECG datasets. Results and Discussion: We evaluate the proposed Multi-branching Resnet with CWT (CWT-MB-Resnet) with two ECG datasets, i.e., PhysioNet/CinC challenge 2017 and ECGs obtained from the University of Oklahoma Health Sciences Center (OUHSC). The proposed CWT-MB-Resnet demonstrates robust prediction performance, achieving an F1 score of 0.8865 for the PhysioNet dataset and 0.7369 for the OUHSC dataset. The experimental results signify the model’s superior capability in balancing precision and recall, which is a desired attribute for ensuring reliable medical diagnoses. [ABSTRACT FROM AUTHOR]

Pinus massoniana Lamb. is an important, common afforestation and timber tree species in China. Species of Pestalotiopsis are well-known pathogens of needle blight. In this study, the five representative strains were isolated from needle blight from needles of Pi. massoniana in Nanjing, Jiangsu, China. Based on multi-locus phylogenetic analyses of the three genomic loci (ITS, TEF1, and TUB2), in conjunction with morphological characteristics, a new species, namely Pestalotiopsis jiangsuensis sp. nov., was described and reported. Pathogenicity tests revealed that the five representative strains of the species described above were pathogenic to Pi. massoniana. The study revealed the diversity of pathogenic species of needle blight on Pi. massoniana. This is the first report of needle blight caused by P. jiangsuensis on Pi. massoniana in China and worldwide. This provides useful information for future research on management strategies of this disease. [ABSTRACT FROM AUTHOR]

As highly social animals, Indo-Pacific humpback dolphins (Sousa chinensis) exhibit community differentiation. Nevertheless, our understanding of the external and internal factors influencing these dynamics, as well as their spatiotemporal variations, is still limited. In the present study, variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay, China, were monitored over two distinct periods (2007–2010 and 2017–2019) to analyze the effects of habitat utilization and the composition of individuals within the population. In both periods, the population demonstrated a strikingly similar pattern of social differentiation, characterized by the division of individuals into two main clusters and one small cluster. Spatially, the two primary clusters occupied the eastern and western waters, respectively, although the core distribution area of the eastern cluster shifted further eastward between the two periods. Despite this distribution shift, the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected. A subset of 16 individuals observed in both periods, comprising 51.6% and 43.2% of the population in each respective period, emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability, especially during the 2007–2010 period. These observations suggest that the composition of dominant individuals, an internal factor, had a more substantial influence on the formation of the social network than changes in habitat use, an external factor. Consequently, the study proposes distinct conservation measures tailored to each of the two main clusters. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma lacks ideal diagnostic biomarkers. There is a lack of scientific evaluation of relevant promising biomarkers as well. Therefore this study reanalyzes the related studies of 11 blood biomarkers of HCC, and compares the diagnostic value of these biomarkers for HCC systematically. The relevant literatures on the diagnostic value in HCC of 11 blood indexes in recent 5 years were searched in PubMed, Embase, and Cochrane libraries. Data were extracted and analyzed. Finally, 83 literature studies were brought into meta-analysis. The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The AUC and sum of sensitivity and specificity of the combination of AFP and other biomarkers were all significantly higher than that of AFP, including AFP + AFP-L3 + DCP, AFP + DCP, AFP/DCP, AFP + GPC3. Among other biomarkers, the AUC and sum of sensitivity and specificity of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN were significantly higher than that of AFP. In this study, GP73 had the highest sum of sensitivity and specificity (1.78) and AUC (0.95). The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The combination of AFP and other biomarkers improved the diagnostic efficiency. The diagnostic value of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN was higher than that of AFP. GP73 had the best diagnostic value for HCC with the highest sum of sensitivity and specificity (1.78) and AUC (0.95). The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The combination of AFP and other biomarkers improved the diagnostic efficiency of HCC. The diagnostic value of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN was higher than that of AFP. GP73 had the best diagnostic value for HCC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic lower back pain (CLBP) is one of the most common disorders worldwide. Flash cupping has the ability to relieve CLBP; nevertheless, its impact on CLBP and the likely mechanism of action have not been studied. OBJECTIVE: The goal of this study was to assess the impact of a single, brief cupping session on CLBP and low back muscle activity using multichannel surface electromyography (sEMG). METHODS: In this randomized controlled trial, 24 patients with CLBP were enrolled and randomly assigned to the control group (treated by acupuncture) and cupping group (treated by acupuncture and flash cupping). Acupuncture was applied on the shen shu (BL23), dachang shu (BL25), and wei zhong (BL40) acupoints in both the groups. A brief cupping treatment was applied to the shen shu (BL23), qihai shu (BL24), dachang shu (BL25), guanyuan shu (BL26), and xiaochang shu (BL27) acupoints on both sides of the lower back in the cupping group. The numeric rating scale (NRS) was used to assess therapy efficacy for lower back pain (LBP) before and after treatment. Surface EMG data collected during symmetrical trunk flexion-extension movements were utilized to measure lower back muscle activity and the effectiveness of LBP therapy. RESULTS: There was no statistically significant difference (P = 0.63) in pain intensity between the two groups before and after treatment. There was a statistically significant difference (P = 0.04) between the control group and the cupping group in the sEMG topographic map parameter CoGx-To-Midline. CONCLUSION: This study established a connection between the action mechanism of flash cupping and enhanced horizontal synchronization of lower back muscular activity. [ABSTRACT FROM AUTHOR]

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Water level rise is considered an environmental filter for the growth and reproduction of aquatic plants in lakes. Some emergent macrophytes can form floating mats, enabling them to escape from the negative effects of deep water. However, an understanding of which species can be uprooted and form floating mats easily and what factors affect these tendencies remains greatly elusive. We conducted an experiment to determine whether the monodominance of Zizania latifolia in the emergent vegetation community in Lake Erhai was related to its floating mat formation ability and to try to find the reasons for its floating mat formation ability during the continuous increase in water level over the past few decades. Our results showed that both the frequency and biomass proportion of Z. latifolia were greater among the plants on the floating mats. Furthermore, Z. latifolia was more likely to be uprooted than the other three previously dominant emergent species due to its smaller angle between the plant and the horizontal plane, rather than the root:shoot or volume:mass ratios. The dominance of Z. latifolia in the emergent community in Lake Erhai is due to its easier ability to become uprooted, allowing it to outperform other emergent species and become the single dominant emergent species under the environmental filter of deep water. The ability to uproot and form floating mats may be a competitive survival strategy for emergent species under the conditions of continuous significant water level rise. [ABSTRACT FROM AUTHOR]

The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia (Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver (P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content (P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue (P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish (P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue. [ABSTRACT FROM AUTHOR]

l‐homoserine, a nonprotein amino acid, is used to synthesize many active substances in the industry. Here, to develop a robust l‐homoserine‐producing strain, Escherichia coli W3110 was used as a chassis to be engineered. Based on a previous construct with blocked competing routes for l‐homoserine synthesis, five genes were overexpressed by promoter replacement strategy to increase the l‐homoserine production, including enhancement of precursors for l‐homoserine synthesis (ppc, thrA, and asd), reinforcement of the NADPH supply (pntAB) and efflux transporters (rhtA) to improve the l‐homoserine production. However, the plasmid losing was to blame for the wildly fluctuating fermentation performance of engineered strains, ranging between 2.1 and 6.2 g/L. Then, a hok/sok toxin/antitoxin system was introduced into the free plasmid expression cassette to maintain the genetic stability of the episomal plasmid; consequently, the plasmid‐losing rate sharply decreased, resulting in the engineered strain SHL17, which exhibited excellent stability in l‐homoserine production, with 6.3 g/L in shake flasks and 44.4 g/L in a 5‐L fermenter without antibiotic addition. This work verified the effective use of the hok/sok toxin/antitoxin system combined with promoter engineering to improve the genetic stability of E. coli episomal plasmids without antibiotics. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the intervention effect of curcumin in myocardial infarction rodent models. Methods: A systematic retrieval of relevant studies on curcumin intervention in rats or mice myocardial infarction models was conducted, and the data were extracted. The outcome indicators included biochemical blood indicators, such as creatine kinase (CK), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA), lactate dehydrogenase (LDH) and superoxide dismutase (SOD), as well as cardiac tissue structure indicators, such as left ventricular weight to body weight ratio (LVW/BW), apoptosis index, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), and myocardial infarction area, and hemodynamic indexes, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), maximum rate of left ventricular pressure rise (+dp/ dtmax), and maximum rate of left ventricular pressure decline (–dp/dtmax). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle’s bias risk tool. Results: A total of 24 studies were included in the meta-analysis. The quality assessment of included studies revealed that the evidence was low quality and none of studies was judged as having a low risk of bias across all domains. The results revealed that curcumin could reduce CK-MB, CK, LDH, and MDA levels. They also revealed that it could lower SBP, DBP, LVEDP, LVW/BW, apoptosis index, LVEDD, LVESD, and myocardial infarction area and increase LVEF, LVFS, +dp/dtmax, and–dp/dtmax. However, it had no significant impact on the heart rate and the levels of SOD in the models. Conclusion: Curcumin alleviates myocardial injury and oxidative stress in myocardial infarction rodent models in terms of blood biochemistry indicators, improves the diastolic and systolic capacity of the ventricle in terms of hemodynamic indexes, and reduces the necrosis and apoptosis of cardiomyocytes in terms of tissue structure. The methodological quality of the studies was low and additional research is warranted. [ABSTRACT FROM AUTHOR]

Objectives Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing. Methods We generated Emx1-Cre:Ulk4flox/flox conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus. Results The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3α/β were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1α (PP1α). Indeed, the reduction of p-Akt and p-GSK-3α/β was rescued by administration of inhibitor acting on PP2A and PP1α in CKO mice. Conclusions Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice. [ABSTRACT FROM AUTHOR]

Indirubin is a bisindole compound for the treatment of chronic myelocytic leukemia. Here, we presented a structure-guided method to improve the activity of a flavin-containing monooxygenase (bFMO) for the efficient production of indirubin in Escherichia coli. A flexible loop interlocked with the active pocket through a helix and the substrate tunnel rather than the active pocket in bFMO were identified to be two reconfigurable structures to improve its activity, resulting in K223R and N291T mutants with enhanced catalytic activity by 2.5- and 2.0-fold, respectively. A combined modification at the two regions (K223R/D317S) achieved a 6.6-fold improvement in catalytic efficiency (kcat/Km) due to enhancing π–π stacking interactions stabilization. Finally, an engineered E. coli strain was constructed by metabolic engineering, which could produce 860.7 mg/L (18 mg/L/h) indirubin, the highest yield ever reported. This work provides new insight into the redesign of FMOs to boost their activities and an efficient approach to produce indirubin. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circ-CSNK1G3 in cancer research deserve further investigation. [ABSTRACT FROM AUTHOR]

The wick is the most crucial element of loop heat pipes (LHPs). At present, wick materials are limited to copper, stainless steel, nickel, and so on. Little research has been carried out on new wick materials. This paper reports the fabrication of aluminum wicks and performance tests of LHPs using aluminum wicks. Experimental data show that this LHP is capable of transferring a heating load of 130 W, while the thermal resistance is only approximately 0.04 K/W. Then, the experimental data were compared with those for LHPs using a polytetrafluoroethylene (PTFE) wick. Based on the SIMPLE algorithm, a 2-D unsteady-state heat transfer model and a 2-D steady-state flow model of the wicks are established to analyze the effects of wick material, pore size and porosity on the performance of the evaporator. The experimental data for LHPs with PTFE wicks are from the literature. The simulation results show that a PTFE wick can effectively reduce heat leakage, while an aluminum wick has better temperature uniformity and a lower casing temperature. However, wicks with large porosities have lower flow resistance. [ABSTRACT FROM AUTHOR]

Background: Many factors were reported associated with the pregnancy rate of intrauterine insemination (IUI), which played key role is still debated. Aims: The aim of this study was to explore related clinical pregnancy outcome factor in IUI cycles of non-male factor. Settings and Design: The clinical data of 1232 IUI cycles in 690 couples experiencing infertility who attended the Reproductive Center of Jinling Hospital between July 2015 and November 2021 were retrospectively analysed. Materials and Methods: Female and male age, body mass index (BMI), anti-Miillerian hormone (AMH), male semen parameters before and after wash, endometrial thickness (EMT), artificial insemination timing and ovarian stimulation (OS) protocols were compared between the pregnant group and the non-pregnant group in order to explore any correlation. Statistical Analysis Used: Continuous variables were analysed using independent-samples t-test, and Chi-square test was used for comparison of measurement data between the two groups. P <0.05 was considered statistical significance. Results: There were statistically significant differences in female AMH, EMT and duration of OS between the two groups. The AMH was higher in the pregnant group than in the non-pregnant group (P < 0.01), the stimulated days was significantly longer (P < 0.05) and EMT was significantly greater (P < 0.01) in the pregnant group than in the non-pregnant group. Further analysis showed that when patients with IUI had the following conditions: AMH > 4.5 ng/ml, EMT between 8 and 12 mm and letrozole + human menopausal gonadotropin stimulation with higher clinical pregnancy. However, there were no differences between the pregnant group and the non-pregnant group amongst the female and male age, BMI, hormones on baseline and day of human chorionic gonadotrophin, number of ovulated oocytes, sperm parameters before and after wash, treatment protocols and the timing of IUI (P > 0.05). Furthermore, there were 240 couples who not pregnant received one or more cycles of in vitro fertilisation/ intracytoplasmic sperm injection/ pre-implantation genetic technology treatment, and another 182 couples forgo follow-up treatment. Conclusion: The results of the present study demonstrate that the clinical IUI pregnancy rate is correlated with the factors of female AMH, EMT and OS protocol; more studies and samples are necessary to evaluate whether other factors affect pregnancy rate. [ABSTRACT FROM AUTHOR]

Fatigue, including cognitive fatigue, is one of the most debilitating symptoms reported by persons with multiple sclerosis (pwMS). Cognitive fatigue has been associated with disruptions in striato-thalamo-cortical and frontal networks, but what remains unknown is how the rate at which pwMS become fatigued over time relates to microstructural properties within the brain. The current study aims to fill this gap in knowledge by investigating how cognitive fatigue rate relates to white matter and basal ganglia microstructure in a sample of 62 persons with relapsing-remitting MS. Participants rated their level of cognitive fatigue at baseline and after each block (x7) of a within-scanner cognitive fatigue inducing task. The slope of the regression line of all eight fatigue ratings was designated as "cognitive fatigue rate." Diffusional kurtosis imaging maps were processed using tract-based spatial statistics and regional analyses (i.e., basal ganglia) and associated with cognitive fatigue rate. Results showed cognitive fatigue rate to be related to several white matter tracts, with many having been associated with basal ganglia connectivity or the previously proposed "fatigue network." In addition, cognitive fatigue rate was associated with the microstructure within the putamen, though this did not survive multiple comparisons correction. Our approach of using cognitive fatigue rate, rather than trait fatigue, brings us closer to understanding how brain pathology may be impacting the experience of fatigue in the moment, which is crucial for developing interventions. These results hold promise for continuing to unpack the complex construct that is cognitive fatigue. [ABSTRACT FROM AUTHOR]

By using the coupling method and the localization technique, we establish non-uniform gradient estimates for Markov semigroups of diffusions or stochastic differential equations driven by pure jump Lévy noises, where the coefficients only satisfy local monotonicity conditions. [ABSTRACT FROM AUTHOR]

Purpose: The poor prognosis of hepatocellular carcinoma (HCC) urgent us to discover early and effective biomarkers. In this study, we applied tandem mass tag (TMT)-based proteomic analysis to discover potential protein markers for HCC identification and differentiation. Patients and Methods: Fifteen patients, well-differentiated (G1, N = 5), moderate-differentiated (G2, N = 5), and poorly differentiated (G3, N = 5), with 30 matched pair tissues (both tumor and adjacent non-tumor tissues derived from the same patient) were enrolled. All samples were subjected to TMT labeling and LC−MS/MS analysis. The identified proteins were subsequently assigned to GO and KEGG for predicting function. The identified protein candidates were validated using immunohistochemistry (IHC). Results: A total of 1010 proteins were identified. Of these, 154 differentially expressed proteins (DEPs), 100 up-regulated and 54 down-regulated, were found between tumor and adjacent non-tumor tissues; 12 DEPs, 9 up-regulated and 3 down-regulated, were found between G1 and G3 tissues; 8 DEPs, 5 up-regulated and 3 down-regulated, were found between G1 and G2 tissues; 11 DEPs, 8 up-regulated and 3 down-regulated, were found between G2 and G3 tissues. Among them, ASS1 and CPS1 were significantly up-regulated while UROD and HBB were significantly down-regulated in G3 compared with G1 and G2 tumors. Three proteins, CYB5A, FKBP11 and YBX1, were significantly up-regulated in G1 compared with both G2 and G3 tumors. The 7 biomarker candidates were further verified by IHC. Conclusion: A variety of DEPs related to the histological differentiation of HCC were identified, among which ASS1, CPS1, URPD and HBB proteins were potential biomarkers for distinguishing poorly differentiated HCC, while CYB5A, FKBP11 and YBX1 were potential biomarkers for distinguishing well-differentiated HCC. Our findings may further provide a new insight facilitating the diagnosis and prognosis of HCC. [ABSTRACT FROM AUTHOR]

3-Phosphoinositide-dependent protein kinase-1 (PDK1) plays a critical role in the development of mammalian brain. Here, we investigated the role of PDK1 in Purkinje cells (PCs) by generating the PDK1-conditional knock-out mice (cKO) through crossing PV-cre or Pcp2-cre mice with Pdk1fl/fl mice. The male mice were used in the behavioral testing, and the other experiments were performed on mice of both sexes. These PDK1-cKO mice displayed decreased cerebellar size and impaired motor balance and coordination. By the electrophysiological recording, we observed the reduced spontaneous firing of PCs from the cerebellar slices of the PDK1-cKO mice. Moreover, the cell body size of PCs in the PDK1-cKO mice was time dependently reduced compared with that in the control mice. And the morphologic complexity of PCs was also decreased after PDK1 deletion. These effects may have contributed to the reduction of the rpS6 (reduced ribosomal protein S6) phosphorylation and the PKCγ expression in PDK1-cKO mice since the upregulation of pS6 by treatment of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-1, the agonist of mTOR1, partly rescued the reduction in the cell body size of the PCs, and the delivery of recombinant adeno-associated virus-PKCγ through cerebellar injection rescued the reduced complexity of the dendritic arbor in PDK1-cKO mice. Together, our data suggest that PDK1, by regulating rpS6 phosphorylation and PKCγ expression, controls the cell body maintenance and the dendritic development in PCs and is critical for cerebellar motor coordination. [ABSTRACT FROM AUTHOR]

Background: To investigate the construction situation, costs and charges associated with pharmacy intravenous admixture services (PIVAS) to provide references for the construction and development of PIVAS in mainland China.Methods: A multi-center cross-sectional survey was conducted via a WeChat Group targeting PIVAS leaders in hospitals to investigate the basic situation of PIVAS, including opening time, area, number of PIVAS, equipment, management mode, PIVAS costs and charges, as well as numbers of beds, open wards, and staff, and analyze differences in PIVAS construction at different provincial and hospital levels.Results: 137 questionnaires were collected from 29 provinces, representing a response rate of 99.3%. Most participants (88.4%) were from Level III Hospitals. The number of years of operations of PIVAS ranged from 1 to 22 (median: 6). PIVAS site area ranged between 100 and 1973 m2; daily average infusion volume was concentrated in the ranges 0-1000 bags (29.9%, 41/137) and 1001-2000 bags (26.3%, 36/137). In terms of PIVAS management mode, the vast majority used separate pharmacy management (65.0%, 89/137). Only 52.6% (72/137) of PIVAS have standardized charges, and 70.1% (96/137) operate at a loss. The median costs of mixed tumor chemotherapy drugs, total parenteral nutrition, general medicine, antibiotics were 20, 35, 4 and 5 RMB, respectively. With the exception of a few features, PIVAS construction does not obviously differ among different regions and hospital levels.Conclusions: In recent years, PIVAS in China has developed rapidly and become relatively large. The main problems are that most provinces lack standards for charges and PIVAS construction differs among hospitals. Therefore, standards for PIVAS construction and charges should be developed to provide a reference for the future development of PIVAS. [ABSTRACT FROM AUTHOR]

Background: During disc degeneration, inflammatory cytokine tumor necrosis factor (TNF)-α is correlated with nucleus pulposus (NP) cell apoptosis. Transforming growth factor (TGF)-β1 has the potential to regenerate degenerative disc. Objective: To investigate the protective role of TGF-β1 against TNF-α-mediated NP cell apoptosis and the underlying mechanism. Methods: Rat NP cells were treated with TNF-α (100 ng/ml) for 48 h. TGF-β1 was added into the culture medium to investigate its protective effects against TNF-α-induced NP cell apoptosis. Exogenous FasL was used to investigate the potential role of the Fas/FasL pathway in this process. Flow cytometry assay was used to analyze NP cell apoptosis. Real-time PCR andWestern blotting were used to analyze gene and protein expression of apoptosis-related molecules. Results: In TNF-α-treated NP cells, TGF-β1 significantly decreased NP cell apoptosis, declined caspase-3 and -8 activity, and decreased expression of Bax and caspase-3 (cleaved-caspase-3) but increased expression of Bcl-2. However, exogenous FasL partly reversed these effects of TGF-β1 in NP cells treated with TNF-α. Additionally, expression of Fas and FasL in TNF-α-treated NP cells partly decreased by TGF-β1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-β1 and TNF-α. Conclusion: TGF-β1 helps to inhibit TNF-α-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-β1 may be effective to retard inflammation-mediated disc degeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epidemiological evidence remains equivocal on the associations between environmentally relevant levels of per-/polyfluoroalkyl substances (PFASs) and human semen quality. OBJECTIVES: We aimed to test whether the potential effects on semen quality could be better observed when seminal PFAS levels were used as an exposure marker compared with serum PFAS levels. METHODS: Matched semen and serum samples from 664 adult men were collected from a cross-sectional population in China from 2015 to 2016. Multiple semen parameters were assessed, along with measurement of 16 target PFASs in semen and serum. Partitioning between semen and serum was evaluated by the ratio of matrix-specific PFAS concentrations. Regression model results were expressed as the difference in each semen parameter associated with the per unit increase in the ln-transformed PFAS level after adjusting for confounders. RESULTS: Perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and emerging chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were detected at their highest concentrations in both semen and serum, with median concentrations of 0.23, 0.10, and 0:06 ng/mL in semen, respectively, and a semen-to-serum ratio of 1.3:3.1. The between-matrix correlations of these PFAS concentrations were high (푅 =0.70-0.83). Seminal PFOA, PFOS, and 6:2 Cl-PFESA levels were significantly associated with a lower percentage of progressive sperm and higher percentage of DNA fragmentation (false discovery rate-adjusted 혱-values of <0:05). Associations between serum PFAS levels and semen parameters were generally statistically weaker, except for DNA stainability, which was more strongly associated with serum-based PFASs than with semen-based PFASs. CONCLUSIONS: Our results suggest the potential for deleterious effects following exposure to 6:2 Cl-PFESA and other PFASs. Compared with serum PFAS levels, the much clearer association of seminal PFAS levels with semen parameters suggests its advantage in hazard assessment on semen quality, although the potential for confounding might be higher. Exposure measurements in target tissue may be critical in clarifying effects related to PFAS exposure. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical outcomes of reconstruction of maxillary class III defect using 3D-printed titanium mesh. Methods: Twelve patients with maxillary class III defect from April 2015 to December 2016 were retrospectively studied. A 3D individualized maxillary stereo model based on mirror images of the unaffected maxilla was obtained to fabricate an anatomically adapted titanium mesh using computer-assisted design and manufacture. The individual titanium mesh was inserted into the maxillary class III defect after total maxillectomy. The incidence of postoperative complications was evaluated. The postoperative orbital volume and protrusion degree of eye were measured. Results: All patients were satisfied with their postoperative facial symmetry, without developing diplopia or endophthalmos. The postoperative orbital volumes were 26.41 ± 0.52 mL on the affected side and 26.55 ± 0.45 mL on the unaffected side. The postoperative protrusion degrees of affected and unaffected eyes were 16.21 ± 0.48 and 16.82 ± 0.79 mm, respectively. Titanium mesh exposure was observed in 2 patients and mild limitation of mouth opening was observed in 4 patients who underwent postoperative radiotherapy. Conclusion: Reconstruction of maxillary class III defect with 3D-printed titanium mesh can achieve successful clinical outcomes, which recovered orbital volume and protrusion degree of eye. [ABSTRACT FROM AUTHOR]

Quantitative measurement of the orbital soft tissue volume plays a very important role in the study of orbital diseases. The purpose of this study is to establish a computed tomography- (CT-) based three-dimensional (3D) reconstruction model and measure the orbital soft tissue volume in Chinese adults. We collected data from 103 Chinese adults (52 males and 51 females) who underwent orbital CT. The CT images of these adults were used to reconstruct a 3D model of the orbital bony cavity, orbital fat, extraocular muscle, and intraorbital optic nerve using Mimics software, and their respective volumes were measured. The mean (±SD) orbital bony cavity volume (OV), orbital fat volume (FV), extraocular muscle volume (MV), and intraorbital optic nerve volume (iONV) of the males were 22.2 ± 2.2 cm3, 8.9 ± 1.8 cm3, 1.9 ± 0.34 cm3, and 0.41 ± 0.08 cm3, respectively. The mean OV, FV, MV, and iONV of the females were 20.2 ± 1.5 cm3, 8.1 ± 1.7 cm3, 1.6 ± 0.3 cm3, and 0.36 ± 0.074 cm3, respectively, which were all significantly lower than those in males (all p<0.05). FV (r = 0.370; p<0.001) and MV (r = 0.283; p=0.007) were significantly correlated with body mass index (BMI), while iONV was not correlated with BMI (r = −0.070; p=0.480). This study shows that FV, MV, and iONV were higher in males than in females. With increasing BMI, FV and MV both increased, but iONV did not exhibit this trend. [ABSTRACT FROM AUTHOR]

Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ. [ABSTRACT FROM AUTHOR]

Introduction: Salivary adenoid cystic carcinoma (SACC) is a frequent type of salivary gland cancer which is characterized by slow growth but high incidence of distant metastasis. We aimed to identify therapeutic targets which are associated with metastasis of SACC.Material and Methods: Total RNA was isolated from a low metastatic SACC cell line (ACC-2) and a highly metastatic SACC cell line (ACC-M), which was screened from ACC-2 by combination of in vivo selection and cloning in vitro. Then the total RNA was subjected to microarray analysis. Differentially expressed genes (DEGs) were screened from ACC-M compared with ACC-2, followed by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Function annotation for DEGs also was performed. A protein-protein interaction network (PPI) was constructed for DEGs.Results: A total of 1128 DEGs were identified from ACC-M cells compared with ACC-2 cells. Both up- and down-regulated DEGs were enriched in different functions in biological process (BP), cellular component (CC) and molecular function (MF). Additionally, down-regulated DEGs were mainly enriched in "Apoptosis" and "Cytokine-cytokine receptor interaction" pathways which involved IFN-α1, NTRK1 and TGF-β1. In the PPI network, PIK3CA, PTPN11 and PIK3R1 had a number of nodes greater than 10.Conclusions: Transforming growth factor β1 might play a pivotal role during lung metastasis of SACC and be selected as a candidate target for treatment of metastatic SACC. IFNA1, NTRK1 and PIK3CA were also associated with tumor metastasis. [ABSTRACT FROM AUTHOR]

A plantation of 5-year-old poplar Populus × euramericana cv. ‘Neva’ was used to study the regulatory effects of root pruning on nutrients, photosynthetic characteristics, and water-use efficiency (WUE) of leaves and growth rates of diameter at breast height (DBH; 1.3 m), tree height, and volume. Six root-pruning treatments were conducted with different combinations of intensity (at a distance of six, eight or ten times DBH from the trunk) and orientation (on two or four sides of the trees). Results showed that the N, P, K, photosynthetic rate, transpiration rate, and stomatal conductance of leaves were all significantly decreased by root pruning over the initial period following root pruning (30 days), but increased in the subsequent investigations. The values of the above indexes peaked in 8–2 treatment (i.e., eight times DBH distance on two sides). The leaf WUE in 8–2 treatment, and average growth rates of DBH, tree height and volume, were the highest among all treatments within 3 years of root pruning. The results indicated that the root pruning based on the appropriate selection of intensity and orientation had significant positive effects on leaf nutrients, photosynthesis, and growth of trees in a closed-canopy poplar plantation. [ABSTRACT FROM AUTHOR]

The use of custom implants has recently gained increasing importance in craniofacial surgery in order to optimize preoperative planning and reduce operative time. The design of patient-specific implants plays an important role to restore craniofacial bone. Nevertheless, the design method has become the bottleneck. In this study, a new design method of a maxillofacial prosthesis based on the topology optimization was proposed to realize lightweight custom implants. At first, parametric predesign of the optimized model was carried out to ensure that the optimized model conformed to the main physiological anatomical structure and recover basic function structure. Then, the design region is defined under given load and boundary conditions. The material interpolation technique of SIMP with the penalization factor is adopted to get the final optimized 3D model. Finally, the experimental results verify that the method of topology optimization for the maxillofacial prosthesis proposed is efficient. [ABSTRACT FROM AUTHOR]

Iridium-containing liquid-crystalline polymers were obtained by graft copolymerisation using poly (methylhydrogeno)siloxane, 1-methyl-4-(4-(4-vinylcyclohexyl)cyclohexyl)benzene (M1) and an iridium complexes monomer (Ir-M2). The series of polymers contained different molecular fractions of Ir-M2 from 0% to 1.2%. All of these polymers showed mesomorphic behaviours. The introduction of small amount of iridium ions endowed liquid-crystalline polymers with luminescent properties. The chemical structures were characterised by IR and 1H NMR. The mesomorphic properties and phase behaviour were investigated by differential scanning calorimetry, thermal gravimetric analysis, polarising optical microscopy and X-ray diffraction. With an increase of iridium complexes units in the polymers, the glass transition temperature (Tg) did not change significantly; the isotropic temperature (Ti) decreased. All polymers showed typical nematic marble textures, which was confirmed by X-ray diffraction. The temperatures at which 5% weight loss occurred (Td) were greater than 300°C for the polymers. The introduction of iridium complexes units did not change the liquid-crystalline state of polymer systems. With Ir3+ ion contents ranging between 0.6 and 2.4 mol%, luminescent intensity of polymers gradually increased. [ABSTRACT FROM AUTHOR]

The article discusses a study that determined whether there are living Indo-Pacific humpback dolphins or Chinese white dolphin Sousa chinensis in Southeast China, including Ningde, Fuzhou and Yuqing. Forty-two boat surveys were conducted in the region from October 2009 to June 2010. The dolphin was sighted six times in Ningde, representing the current northernmost distribution area of the species in China and the world. The encounter rate was 0.47 sightings per 100-kilometer survey route and 0.79 dolphins per 100-kilometer.

This study aimed to determine the effects of root pruning on the physicochemical characteristics and microbial activities of poplar rhizosphere soil. The root systems of 5-year-old poplar (Populus×euramericana cv. ‘Neva’) trees were manually pruned at 6, 8, or 10 times diameter at breast height (DBH) from the trunk (severe, moderate, and light, respectively) along both inter-row sides. Moderate root pruning significantly increased the concentrations of amino acids, organic acids, and total sugars in the root exudates and decreased the pH of rhizosphere soil. This treatment also increased the contents of available nitrogen, phosphorus, potassium, and total organic carbon as well as high-, medium-, and low-activity organic carbon in rhizosphere soil. Moreover, moderate pruning increased the contents of microbial biomass carbon and nitrogen, and enhanced basal respiration, in addition to decreasing the metabolic quotients in rhizosphere soil by 8.9%, 5.0%, and 11.4% compared with control, light, and severe root pruning treatments, respectively. Moderate pruning increased the growth rates of DBH, tree height, and volume to the highest levels. Furthermore, these indices were not significantly different between the light root pruning and control groups, but varied significantly between severe and moderate root-pruning treatments. Thus, root pruning, depending on the distance from the trunk, significantly influences the physicochemical properties and microbial activities in poplar rhizosphere soil. [ABSTRACT FROM AUTHOR]

Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA adenine modification, N(6)-methyladenine (6mA), has recently been found in mammalian cells. However, the presence and function(s) of 6mA in the mammalian brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in response to environmental stress. We find that overall 6mA levels are significantly elevated upon stress. Genome-wide 6mA and transcriptome profiling reveal an inverse association between 6mA dynamic changes and a set of upregulated neuronal genes or downregulated LINE transposon expression. Genes bearing stress-induced 6mA changes significantly overlap with loci associated with neuropsychiatric disorders. These results suggest an epigenetic role for 6mA in the mammalian brain as well as its potential involvement in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]