Search

IntroductionEnteric dysbacteriosis is strongly associated with nonalcoholic fatty liver disease (NAFLD). However, the underlying causal relationship remains unknown. Thus, the present study aimed to investigate the relationship between gut microbiota and NAFLD using Mendelian randomization (MR) and analyze the target genes potentially regulated by specific microbiota.MethodsBidirectional two-sample MR analysis was performed using inverse variance weighted (IVW) supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Data were pooled from gut microbiota and NAFLD association studies. The least absolute shrinkage, selection operator regression, and the Support Vector Machine algorithm were used to identify genes regulated by these intestinal flora in NAFLD. The liver expression of these genes was verified in methionine choline-deficient (MCD) diet-fed mice.ResultsIVW results confirmed a causal relationship between eight specific gut microbes and NAFLD. Notably, the order Actinomycetales, NB1n, the family Actinomycetaceae, Oxalobacteraceae and the genus Ruminococcaceae UCG005 were positively correlated, whereas Lactobacillaceae, the Christensenellaceae R7 group, and Intestinibacter were negatively correlated with NAFLD onset. In NAFLD, these eight bacteria regulated four genes: colony-stimulating factor 2 receptor β, fucosyltransferase 2, 17-beta-hydroxysteroid dehydrogenase 14, and microtubule affinity regulatory kinase 3 (MAPK3). All genes, except MARK3, were differentially expressed in the liver tissues of MCD diet-fed mice.DiscussionThe abundance of eight gut microbiota species and NAFLD progression displayed a causal relationship based on the expression of the four target genes. Our findings contributed to the advancement of intestinal microecology-based diagnostic technologies and targeted therapies for NAFLD.

Abstract Background and aim Hemostasis profile is often complicated in liver cirrhosis. Thromboelastography is a global viscoelastic test recommended by the current practice guideline and consensus. This cross-sectional study aimed to evaluate the association of thromboelastography profile with severity of liver cirrhosis and presence of portal venous system thrombosis (PVST). Methods Overall, 116 and 50 cirrhotic patients were included in the Shenyang and Xi’an cohorts, respectively. Thromboelastography parameters were compared between cirrhotic patients with Child–Pugh class A and B/C, those with and without decompensated events, and those with and without PVST. Hypercoagulability would be considered if at least two of the following thromboelastography parameters were met: shortened reactive time (R), shortened coagulation time (K), increased angle, and increased maximum amplitude (MA). Results In the Shenyang cohort, 16 patients had shortened R, of whom seven (43.75%) had prolonged K and 11 (68.75%) decreased MA. In the Xi’an cohort, 24 patients had shortened R, of whom seven (29.17%) had prolonged K and 15 (62.50%) decreased MA. In the Shenyang cohort, the prevalence of hypercoagulability was not significantly different between cirrhotic patients with Child–Pugh class A and B/C (3.85% vs. 6.25%, P = 0.873), those with and without decompensated events (5.49% vs. 4.00%, P = 1.000), and those with and without PVST (4.17% vs. 5.88%, P = 1.000), which were similar to the results obtained in the Xi’an cohort. Conclusion There is a high rate of discordance between R and other thromboelastography parameters. In addition, hypercoagulability may not be related to more advanced stage of liver cirrhosis or presence of PVST.

Spontaneous portosystemic shunt (SPSS) refers to collateral vessels that communicate between the portal vein system and systemic circulation. SPSS mainly includes esophageal varices, gastric varices, left gastric vein, recanalized paraumbilical vein, abdominal wall varices, and spontaneous splenorenal shunt. SPSS contributes to the development of hepatic encephalopathy caused by portal vein inflow bypassing and carries a higher risk of death in liver cirrhosis. Abdominal contrast-enhanced computed tomography is a major imaging approach to establish a diagnosis of SPSS and evaluate its location and feature. This review primarily describes the main contrast-enhanced CT features of SPSS in liver cirrhosis.

Acute portomesenteric vein thrombosis is potentially lethal. In the present paper, a cirrhotic patient with a previous history of esophageal variceal bleeding presented with acute occlusive portomesenteric vein thrombosis, but achieved complete recanalization by low-molecular-weight heparin followed by rivaroxaban. Notably, no bleeding episode occurred during anticoagulation therapy. This case supported early initiation of anticoagulation in such patients.

Background and Aims: The intersphincteric resection (ISR) is beneficial for saving patients' anus to a large extent and restoring original bowel continuity. Laparoscopic ISR (L-ISR) has its drawbacks, such as two-dimensional images, low motion flexibility, and unstable lens. Recently, da Vinci robotic ISR (R-ISR) is increasingly used worldwide. The purpose of this article is to compare the feasibility, safety, oncological outcomes, and clinical efficacy of R-ISR vs. L-ISR for low rectal cancer.Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to identify comparative studies of R-ISR vs. L-ISR. Demographic, clinical, and outcome data were extracted. Mean difference (MD) and risk ratio (RR) with their corresponding confidence intervals (CIs) were calculated.Results: Five studies were included. In total, 510 patients were included, of whom 273 underwent R-ISR and 237 L-ISR. Compared with L-ISR, R-ISR has significantly lower estimated intraoperative blood loss (MD = −23.31, 95% CI [−41.98, −4.64], P = 0.01), longer operative time (MD = 51.77, 95% CI [25.68, 77.86], P = 0.0001), hospitalization days (MD = −1.52, 95% CI [−2.10, 0.94], P < 0.00001), and postoperative urinary complications (RR = 0.36, 95% CI [0.16, 0.82], P = 0.02).Conclusions: The potential benefits of R-ISR are considered as a safe and feasible alternative choice for the treatment of low rectal tumors.

Portal venous system thrombosis (PVST), a common complication of liver cirrhosis, is closely associated with thrombophilia. To explore the association of homocysteine (Hcy), anticardiolipin antibody (aCL), and anti-β2 glycoprotein I antibody (aβ 2 GPI), which are possible thrombophilic factors, with PVST in liver cirrhosis. Overall, 654 non-malignant patients (219 with and 435 without liver cirrhosis) admitted between January 2016 and June 2020 were retrospectively evaluated. Presence of PVST, degree of main portal vein (MPV) thrombosis, and clinically significant PVST were identified. Hcy level, hyperhomocysteinemia (HHcy), aCL positivity, and aβ 2 GPI positivity were compared according to the presence of liver cirrhosis and PVST. Positive aβ 2 GPI was significantly more frequent in patients with liver cirrhosis than those without, but Hcy level and proportions of HHcy and positive aCL were not significantly different between them. PVST could be evaluated in 136 cirrhotic patients. Hcy level [10.57 μmol/L (2.71-56.82) versus 9.97 μmol/L (2.05-53.44); P = 0.796] and proportions of HHcy [4/44 (9.1%) versus 13/81 (16.0%); P = 0.413] and positive aCL [1/23 (4.3%) versus 10/52 (19.2%); P = 0.185] and aβ 2 GPI [9/23 (39.1%) versus 21/52 (40.4%); P = 0.919] were not significantly different between cirrhotic patients with and without PVST. There was still no significant association of Hcy level, HHcy, aCL, or aβ 2 GPI with PVST based on Child-Pugh classification, MPV thrombosis >50%, and clinically significant PVST. Hcy, aCL, and aβ 2 GPI may not be associated with PVST in liver cirrhosis, suggesting that routine screening for Hcy, aCL, and aβ 2 GPI should be unnecessary in such patients.

Background and Aims. Left-sided portal hypertension (LSPH) is a rare type of portal hypertension, which occurs due to obstruction, stenosis, or thrombosis within the splenic vein. Pancreatic diseases are the most common etiology of LSPH. This study is aimed at reporting our experiences and discussing the presentation, management, and prognosis of LSPH secondary to pancreatic diseases. Patients and Methods. We retrospectively reviewed five patients who were diagnosed with LSPH secondary to pancreatic diseases at our department. We collected the demographic information, history, comorbidities, clinical presentations, laboratory tests, esophagogastroduodenoscopy (EGD), images, and outcome data. Results. Three elderly patients (>60 years old) were diagnosed with pancreatic cancer, of whom one underwent laparoscopic radical distal pancreatectomy and splenectomy, one received chemotherapy, and another one chose conservative management due to multiple systemic metastases. Two younger patients (

Abstract Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initiating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously uncharacterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice. NPYDRN/vlPAG neurons are rapidly activated by various stressful stimuli. Inhibiting these neurons exacerbated hypophagic and anxiety responses during stress, while activation significantly ameliorates acute stress-induced hypophagia and anxiety levels and transmits positive valence. Furthermore, NPYDRN/vlPAG neurons exert differential but synergic anxiolytic effects via inhibitory projections to the paraventricular thalamic nucleus (PVT) and the lateral hypothalamic area (LH). Together, our findings reveal a feedforward inhibition neural mechanism underlying stress resistance and suggest NPYDRN/vlPAG neurons as a potential therapeutic target for stress-related disorders.

Abstact Background DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. Results At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was − 8.2 days for erenumab and − 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: − 1.57 [95%CI: − 2.83, − 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (− 5.34 vs − 4.66) and mMIDAS scores (− 14.67 vs − 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). Conclusion DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. Trial registration NCT03867201

In view of the main contradiction between traditional topology optimization for basic theory research and the actual requirements of comprehensive performance for modern industrial products, a feature-integrated structural optimization design method with an appropriate reliability, a light weight, and excellent mechanical properties for continuum structures was established based on the reliability-based topology optimization of modified minimum weight with a displacement constraint (RBTO-MMWDC) model. Taking hollow slab structures as an example, a graphical user interface based on the optimization code was developed for practical applications. Furthermore, the topological layout of β =3.0 was selected for geometric model reconstruction and mechanical property evaluations were performed using the finite element method (FEM) and experiments. Compared with those of the traditional structure, the compression resistance and bending resistance properties of the optimized structure are improved by 29% and 75%, respectively, and the first-order natural frequency is increased by 101%. In addition, the results of the experiments are consistent with the simulation in terms of tendency. The bending resistance strength and stiffness of the optimized structure are improved by 61% and 55%, respectively. This study provides a theoretical reference and feasible solution for the feature-integrated design of continuum structures in engineering applications.

Cache-enabled heterogeneous networks (HetNets) have recently emerged as an attractive solution to meet the exponentially increasing demand on mobile data traffic. However, the power consumption and the backhaul limitation of small base stations (SBSs) have become bottlenecks to deploy HetNets. How to relieve the burden of backhauls via wireless caching and enable the HetNets to operate in an energy-efficient way are still open issues. Aiming to minimize the power consumption while guaranteeing QoS requirements of users, in this paper, we address the problem of joint user association (UA) and resource allocation (RA) for coded cache-enabled HetNets. First, based on the many-to-many matching game between the virtual SBSs and users (VSU), we propose a low-complexity joint UA and power allocation (PA) algorithm (JUPVA). Then, considering the unequal BA, we design a three-phase optimization algorithm (JURVA), which makes a joint decision on UA, PA, and BA iteratively. The simulation results demonstrate that the proposed algorithms yield significant performance improvement in terms of power consumption.

Both the jejunum and colon release cytokines that interact with intestinal microbiota. However, it is largely unclear which cytokines and microbial populations are involved in the homeostasis of the intestinal ecosystem for sheep health. To address this, we collected contents for isolating microbiota and tissues for determining cytokines from the jejunum and colon of 7-month-old Altay sheep. We used the techniques of 16S rRNA sequencing and ELISA to detect microbial population and cytokine level, respectively. Correlations between microbial population and cytokines were analyzed by Spearman correlation coefficient. The correlation analysis revealed higher populations of Bacteroides, Fibrobacteres and Spirochetes in the colon than in the jejunum, and IL-6 and IL-12 levels were higher in the jejunum than in the colon. Association analysis further revealed a positive association between IL-10 level and both Ruminococcus_2 and norank_f_Bifidobacteriaceae population in the jejunum. The analysis also revealed positive associations between IL-6 level and Ruminococcaceae_UCG-014 and Ruminococcaceae_UCG-013 population, IL-10 and Prevotellaceae_UCG-004, as well as TNF-α and Prevotellaceae_UCG-003 in the colon. These results indicate a potential interaction between the intestinal microbiota and the host immune system that needs to be further clarified for considering dietary formulations to maintain animal health and disease prevention.

For greater sustainability in construction, coarse recycled aggregate concrete (RAC) is becoming popular as a replacement for natural aggregate concrete (NAC) in structures. The elastic modulus of concrete (E) is a fundamental parameter in structure design. However, the empirical equations for E of NAC cannot apply to RAC because E of RAC is lower than NAC of equal strength, which hinders the widespread use of RAC to a certain extent. This paper provides a practical equation for E of RAC based on a comprehensive statistical analysis of 1383 mixes from 154 publications, allowing designers to easily estimate E of RAC by known parameters at the design stage, such as compressive strength, replacement rate and quality of recycled aggregate. This equation is developed by introducing a reduction factor η into the empirical equation for NAC and verified by the additional experimental results. Compared with JGJ/T443-2018 (a Chinese standard), this paper provides a more reasonable and accurate estimate by analysing much more data and taking into account other factors, such as aggregate type and the volume ratio of aggregate to paste.

Fine morphological reconstruction of individual neurons across the entire brain is essential for mapping brain circuits. Inference of presynaptic axonal boutons, as a key part of single-neuron fine reconstruction, is critical for interpreting the patterns of neural circuit wiring schemes. However, automated bouton identification remains challenging for current neuron reconstruction tools, as they focus mainly on neurite skeleton drawing and have difficulties accurately quantifying bouton morphology. Here, we developed an automated method for recognizing single-neuron axonal boutons in whole-brain fluorescence microscopy datasets. The method is based on deep convolutional neural networks and density-peak clustering. High-dimensional feature representations of bouton morphology can be learned adaptively through convolutional networks and used for bouton recognition and subtype classification. We demonstrate that the approach is effective for detecting single-neuron boutons at the brain-wide scale for both long-range pyramidal projection neurons and local interneurons.

Summary: Parsing diverse nerve cells into biological types is necessary for understanding neural circuit organization. Morphology is an intuitive criterion for neuronal classification and a proxy of connectivity, but morphological diversity and variability often preclude resolving the granularity of neuron types. Combining genetic labeling with high-resolution, large-volume light microscopy, we established a single neuron anatomy platform that resolves, registers, and quantifies complete neuron morphologies in the mouse brain. We discovered that cortical axo-axonic cells (AACs), a cardinal GABAergic interneuron type that controls pyramidal neuron (PyN) spiking at axon initial segments, consist of multiple subtypes distinguished by highly laminar-specific soma position and dendritic and axonal arborization patterns. Whereas the laminar arrangements of AAC dendrites reflect differential recruitment by input streams, the laminar distribution and local geometry of AAC axons enable differential innervation of PyN ensembles. This platform will facilitate genetically targeted, high-resolution, and scalable single neuron anatomy in the mouse brain. : Wang et al. combine mouse genetic labeling with high-resolution, large-volume light microscopy and establish a single-neuron anatomy platform. They show that cortical axo-axonic cells, a GABAergic interneuron type that innervates pyramidal neurons at axon initial segments, consist of multiple subtypes distinguished by laminar position and dendritic and axonal arborization. Keywords: GABAergic interneurons, axo-axonic cells, AACs, chandelier cells, ChCs, neuron subtypes, genetic single neuron anatomy, gSNA, fMOST

Antarctica is a sensitive area of global temperature change. Analyzing the temperature change in Antarctica can provide a basis for the analysis of global climate change The shared data provided by the automatic weather station plan are analyzed, and the relatively complete January temperature of Antarctic 8905 station from 1981 to 2020 is selected for analysis. Using the multi-scale analysis function of wavelet analysis, Morlet wavelet function is selected to carry out continuous wavelet transform on the daily temperature data, and the real part, modulus square and variance of continuous wavelet change are analyzed. It is found that the daily temperature of Antarctica is There are 14, 27, 72, 268, 380 and 665 day main periods for temperature changes. The trend analysis of wavelet transform coefficients under each period shows that the Antarctic temperature is in a high temperature period of 14, 27, 72, 268, 380 and 665 day periods in the years after 2021. The maximum temperature in January in Antarctica has a 20-year main period, and the minimum temperature has a 14-year and 23-year main period, The average value has a main cycle of 6 years, 14 years and 24 years.

Over the last years, inulin, a fructan mixture consisting of oligosaccharides and polysaccharides, has attracted more and more attention from both food industry and researchers, due to its unique functional properties as a natural resource. Therefore, there is an increased interest in the extraction and quantification of inulin for its valorization from inulin rich plants, wastes and by-products. In this work, ultrasonic treatment was applied for inulin extraction, observing a great impact of extraction temperature and ultrasonic power on the inulin content in the obtained extracts. A combined process including trifluoroacetic acid (TFA)-assisted hydrolysis and analysis with high performance liquid chromatography equipped with evaporative light scattering detector (HPLC-ELSD) was developed to quantify inulin content. The effect of hydrolysis parameters was investigated, obtaining the optimal conditions after using TFA at a concentration of 1 mg/mL, hydrolysis temperature of 90 °C, and hydrolysis duration of 60 min. The good linearity (>0.995), precision, recovery (100.27%), and stability obtained during the validation process showed that this developed method allows the quantification of total inulin content in the samples analyzed. This combined method may also contribute to the investigation of the functional properties of inulin (e.g., as prebiotic).