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Abstract Background Quality caregiver-infant interaction is crucial for infant growth, health, and development. Traditional methods for evaluating the quality of caregiver-infant interaction have predominantly relied on rating scales or observational techniques. However, rating scales are prone to inaccuracies, while observational techniques are resource-intensive. The utilization of easily collected medical records in conjunction with machine learning techniques offers a promising and viable strategy for accurate and efficient assessment of caregiver-infant interaction quality. Methods This study was conducted at a follow-up outpatient clinic at two tertiary maternal and infant health centers located in Shanghai, China. 68 caregivers and their 3-15-month-old infants were videotaped for 3–5 min during playing interactions in non-threatening environment. Two trained experts utilized the Infant CARE-Index (ICI) procedure to assess whether the caregivers were sensitive or not in a dyadic context. This served as the gold standard. Predictors were collected through Health Information Systems (HIS) and questionnaires, which included accessible features such as demographic information, parental coping ability, infant neuropsychological development, maternal depression, parent-infant interaction, and infant temperament. Four classification models with fivefold cross-validation and grid search hyperparameter tuning techniques were employed to yield prediction metrics. Interpretable analyses were conducted to explain the results. Results The score of sensitive caregiver-infant interaction was 6.34 ± 2.62. The Random Forest model gave the best accuracy (83.85%±6.93%). Convergent findings identified infant age, care skills of infants, mother age, infant temperament-regulatory capacity, birth weight, positive coping, health-care-knowledge-of-infants, type of caregiver, MABIS-bonding issues, ASQ-Fine Motor as the strongest predictors of interaction sensitivity between infants and their caregiver. Conclusions The proposed method presents a promising and efficient approach that synergistically combines rating scales and artificial technology to detect important features of caregiver-infant interactions. This novel approach holds several implications for the development of automatic computational assessment tools in the field of nursing studies.

Abstract Background Psoriasis is a chronic inflammatory skin disorder associated with various comorbidities. The role of nutrition and dietary antioxidants in psoriasis management has gained attention. The Composite Dietary Antioxidant Index (CDAI) quantifies overall dietary antioxidant intake, but its association with psoriasis remains unclear. This study aimed to investigate the association between the CDAI and psoriasis, as well as the relationship between individual components of CDAI and psoriasis risk. Methods Data from the US National Health and Nutrition Examination Survey (NHANES) were analyzed. Baseline characteristics, CDAI scores, and psoriasis status were assessed. Multivariable logistic regression and restricted cubic splines were employed to analyze the association. Results The study included 23,311 participants, with 621 diagnosed with psoriasis. Higher CDAI scores were associated with a lower odds ratio (OR) of psoriasis occurrence (OR = 0.72, 95% CI 0.56–0.92, P = 0.009 in Model 3). Vitamin E intake exhibited an inverse correlation with psoriasis risk (OR = 0.76, 95% CI 0.60–0.96, P = 0.039 in Model 3). Other CDAI components did not show significant associations with psoriasis. Conclusion This study demonstrates a significant inverse association between CDAI and psoriasis, indicating that higher dietary antioxidant intake is associated with a reduced risk of psoriasis. Specifically, higher vitamin E intake was associated with a lower likelihood of psoriasis. These findings underscore the potential role of dietary antioxidants in psoriasis management. Further research is warranted to elucidate the underlying mechanisms and explore targeted dietary interventions.

Abstract Objectives The purpose of this study was to investigate fatigue, mental workload, and burnout among health care workers (HCWs) and explore the possible underlying factors. Materials and methods An online cross-sectional survey design was used to collect data from HCWs in Chongqing, China. The online survey included the Fatigue Severity Scale, NASA Task Load Index, and Chinese version of the Maslach Burnout Inventory-General Survey to assess fatigue, mental workload, and burnout, respectively, and was conducted from February 1 to March 1, 2023. Results In this study, the incidence of fatigue and burnout among HCWs was 76.40% and 89.14%, respectively, and the incidence of moderate to intolerable mental workloads was 90.26%. Work–family conflict, current symptoms, number of days of COVID-19 positivity, mental workload, burnout and reduced personal accomplishment were significantly associated with fatigue. Mental workload was affected by fatigue and reduced personal accomplishment. Furthermore, burnout was influenced by marital status and fatigue. Moreover, there was a correlation among mental workload, fatigue, and burnout. Conclusions Fatigue, mental workload and burnout had a high incidence and were influenced by multiple factors during COVID-19 public emergencies in China.

Abstract Background Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor. Results The direct growth of free-standing Cu-Co-Ni-S on the interconnected three-dimensional (3D) network of CP boosted the active site of the composites, improved ion diffusion kinetics, and significantly promoted the electron transfer rate. The multiple oxidation states and synergistic effects among Co, Ni, Cu, and S further promoted glucose electrooxidation. The well-architected Cu-Co-Ni-S/CP presented exceptional electrocatalytic properties for glucose with satisfied linearity of a broad range from 0.3 to 16,000 μM and high sensitivity of 6829 μA mM− 1 cm− 2. Furthermore, the novel sensor demonstrated excellent selectivity and storage stability, which could successfully evaluate the glucose levels in human serum. Notably, the novel Cu-Co-Ni-S/CP showed favorable biocompatibility, proving its potential for in vivo glucose monitoring. Conclusion The proposed 3D hierarchical morphology self-supported electrode sensor, which demonstrates appealing analysis behavior for glucose electrooxidation, holds great promise for the next generation of high-performance glucose sensors.

Abstract Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

Abstract Background Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. Methods We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. Results There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, − 1.88; 95% CI = − 2.60 to − 1.15), azithromycin (MD, − 1.74; 95% CI = − 2.52 to − 0.95), doxycycline (MD, − 1.53; 95% CI = − 2.05 to − 1.00), ceftriaxone (MD, − 1.22; 95% CI = − 1.89 to − 0.55), penicillin (MD, − 1.22; 95% CI = − 1.80 to − 0.64), and penicillin or ampicillin (MD, − 0.08; 95% CI = − 1.01 to − 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch–Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). Conclusions Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. Systematic review registration PROSPERO CRD42022354938.

Abstract Oil-based drilling cutting pyrolysis residues (ODCPRs), bauxite, and sintering additives were applied to manufacture ceramic proppants with low density and high strength in this work. The effect of ODCPRs ratio, sintering temperature, holding time, and the content of additives on the performance of the proppants was comprehensively investigated, respectively. And the sintering mechanism of proppants was also discussed according to the phase, microstructure, and thermal behavior analyses. The results revealed that at the best sintering condition (1280 °C, holding for 60 min), and a mass ratio (ODCPRs: bauxite: MnO2 at 3:7:0.1), the well-developed granular corundum and acicular mullite formed inside the proppants and interspersed with each other to form a dense structure. The proppants presented low density and high strength as the bulk density of 1.48 g/cm3, the apparent density of 2.94 g/cm3, a breakage ratio of 5.25% under 52 MPa closed pressure, and the acid solubility of 4.80%, which could well meet the requirement of the standards of SY/T 5108-2014. This work provided a new pathway for recycling ODCPRs and the fabrication of high-performance proppants.

Gansu Province in China has the characteristics of an underdeveloped economy, low forest carbon sink, and rich non-fossil energy, making it a typical area for research to achieve the “double carbon” target. In this paper, the primary energy consumption and carbon emissions and their development trends in Gansu Province during the “double carbon” target period were predicted by the fixed-base energy consumption elasticity coefficient method, and the possibility of achieving the “double carbon” target in Gansu Province was explored. In the three hypothetical scenarios, it was estimated that the total primary energy consumption of Gansu Province will be 91.9–94.81 million tons of standard coal by 2030 and 99.35–110.76 million tons of standard coal by 2060. According to the predicted share of different energy consumption in Gansu Province, the CO2 emissions of Gansu Province in the three scenarios were calculated and predicted to be between 148.60 and 153.31 million tons in 2030 and 42.10 and 46.93 million tons in 2060. The study suggests that Gansu Province can reach the carbon peak before 2030 in the hypothetical scenarios. However, to achieve the goal of carbon neutrality by 2060, it was proposed that, in addition to increasing carbon sinks by afforestation, it is also necessary to increase the share of non-fossil energy. As long as the share is increased by 0.3% on the basis of 2030, the goal of carbon neutrality by 2060 in Gansu Province can be achieved. The results show that the increase in the share of non-fossil energy consumption is the most important way to achieve the goal of carbon neutrality in Gansu Province, and it also needs to be combined with the optimization of industrial structure and improvement of technological progress. Based on the research results, some countermeasures and suggestions are put forward to achieve the goal of carbon neutrality in Gansu Province.

Abstract CD47 blockade has emerged as a promising immunotherapy against liver cancer. However, the optimization of its antitumor effectiveness using efficient drug delivery systems or combinations of therapeutic agents remains largely incomplete. Here, patients with liver cancer co‐expressing CD47 and CDC7 (cell division cycle 7, a negative senescence‐related gene) are found to have the worst prognosis. Moreover, CD47 is highly expressed, and senescence is inhibited after the development of chemoresistance, suggesting that combination therapy targeting CD47 and CDC7 to inhibit CD47 and induce senescence may be a promising strategy for liver cancer. The efficacy of intravenously administered CDC7 and CD47 inhibitors is limited by low uptake and short circulation times. Here, inhibitors are coloaded into a dual‐targeted nanosystem. The sequential release of the inhibitors from the nanosystem under acidic conditions first induces cellular senescence and then promotes immune responses. In an in situ liver cancer mouse model and a chemotherapy‐resistant mouse model, the nanosystem effectively inhibited tumor growth by 90.33% and 85.15%, respectively. Overall, the nanosystem in this work achieved the sequential release of CDC7 and CD47 inhibitors in situ to trigger senescence and induce immunotherapy, effectively combating liver cancer and overcoming chemoresistance.

Background: The COVID-19 pandemic has required teachers and students to suddenly transition from face-to-face formats to distance education (DE). The uniqueness of nursing discipline is that it requires both theoretical and skills-based learning. Therefore, it is necessary to explore the influencing factors and effectiveness of DE in nursing education. This exploration can guide teaching practice and provide a basis for the future application of DE in nursing education. Aims: To describe the current distance education readiness and depth of learning among undergraduate nursing students and explore possible influencing factors. To determine the relationship between students’ distance education readiness and the depth of learning. Design: This is a descriptive and cross-sectional online study. Settings: School of Nursing in a traditional Chinese medicine university, Beijing, China. Participants: A total of 222 undergraduate nursing students from a traditional Chinese medicine university were recruited. Methods: A questionnaire, which is composed of information form, the Online Learning Readiness Scale, and the Scale of Students Making Deep Learning, was used for data collection. Frequency, percentage, arithmetic mean, standard deviation, t-test, one-way ANOVA, and Pearson correlations were used in the analysis of the data. Result: Undergraduate nursing students have lower averages in distance education readiness and higher averages in the depth of learning. Significant differences in distance education readiness and depth of learning between different grade groups. A positive correlation was found between distance education readiness and depth of learning (r = 0.894, p

Summary: Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.

Introduction Liver disease causes 2 million deaths annually, accounting for 4% of all deaths worldwide. Liver surgery is one of the effective therapeutic options. Bleeding is a major complication during liver surgery. Perioperative bleeding and allogeneic blood transfusion may deteriorate the prognosis. Terlipressin (TP), a synthetic analogue of the antidiuretic hormone, may reduceblood loss during abdominal surgery. Several clinical centres have attempted to use TP during liver surgery, but the evidence for its effectiveness in reducing blood loss and the need for allogeneic blood transfusion, as well as its safety during the perioperative period, remains unclear. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of TP in reducing blood loss and allogeneic blood transfusion needs during liver surgery.Methods and analysis We will search PubMed, EMBASE, the Cochrane Library and Web of Science for studies on perioperative use of TP during liver surgery from inception to July 2023. We will limit the language to English, and two reviewers will independently screen and select articles. The primary study outcomes are estimated blood loss and the need for allogeneic blood transfusion. Secondary outcomes include operating time, intensive care unit stay, length of stay, intraoperative urine output, acute kidney injury rate, postoperative complications, hepatic and renal function during follow-up, and TP-related adverse effects. We will include studies that met the following criteria: (1) randomised controlled trials (RCTs), cohort studies or case-control studies; (2) the publication time was till July 2023; (3) adult patients (≥18 years old) undergoing elective liver surgery; (4) comparison of TP with other treatments and (5) the study includes at least one outcome. We will exclude animal studies, case reports, case series, non-original articles, reviews, paediatric articles, non-controlled trials, unpublished articles, non-English articles and other studies that are duplicates. We will use Review Manager V.5.3 software for meta-analysis and perform stratification analysis for the study quality of RCTs based on the Jadad score. For cohort or case-control studies, the study quality will be analysed based on Newcastle-Ottawa Scale scores. Grading of Recommendations, Assessment, Development and Evaluation will be used to assess confidence in the cumulative evidence. For primary outcomes, we will conduct subgroup analyses based on meta-regression. We will also perform leave-one-out sensitivity analyses to evaluate the effect of each individual study on the combined results by removing the individual studies one by one for outcomes with significant heterogeneity. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines.Ethics and dissemination This study is a secondary analysis of existing data; therefore, it does not require ethical approval. We will disseminate the results through peer-reviewed publications.PROSPERO registration number CRD42023450333.

Abstract Background Clarifying the effectiveness of co-teaching in medicine and nursing (CMN) is important as it is crucial in clinical practice to improve the quality of patient care and prognosis. In this study, we aimed to determine the efficacy of CMN in nurse anesthetist training. Method The study comprised a 6-month training session and a before-and-after controlled study. In total, 59 nurses were recruited. The first 30 nurses were enrolled in the conventional single-teaching in nursing (SN) group and only took nursing-related courses. The next 29 students were enrolled in the CMN group and received both general medical and nursing-specific curricula. Before and after training, medical and nursing collaboration competency scores and knowledge scores were compared between the two groups. At the end of the study, qualitative comments on teaching satisfaction and clinical reasoning skills improvement were queried, and content analysis was performed. Results Participants in the CMN group outperformed those in the SN group in tests of medical and nursing collaboration abilities as well as knowledge. The CMN group outperformed the SN group in terms of teaching satisfaction evaluation, particularly in terms of fostering learning in the anesthetist specialty, improving clinical practice, fostering motivation, and influencing how people think about challenges at work. Furthermore, participants in the CMN group felt that their clinical reasoning abilities had improved. Conclusion In comparison to the SN group, the CMN group had enhanced outcomes of patient care, medical and nursing collaboration, and clinical reasoning skills.

TGA transcription factors belong to Group D of the bZIP transcription factors family and play vital roles in the stress response of plants. Brassica napus is an oil crop with rich economic value. However, a systematic analysis of TGA gene family members in B. napus has not yet been reported. In this study, we identified 39 full-length TGA genes in B. napus, renamed TGA1~TGA39. Thirty-nine BnTGA genes were distributed on 18 chromosomes, mainly located in the nucleus, and differences were observed in their 3D structures. Phylogenetic analysis showed that 39 BnTGA genes could be divided into five groups. The BnTGA genes in the same group had similar structure and motif compositions, and all the BnTGA genes had the same conserved bZIP and DOG1 domains. Phylogenetic and synteny analysis showed that the BnTGA genes had a close genetic relationship with the TGA genes of the Brassica juncea, and BnTGA11 and BnTGA29 may play an important role in evolution. In addition, qRT-PCR revealed that three genes (BnTGA14/17/23) showed significant changes in eight experimental materials after drought treatment. Meanwhile, it can be inferred from the results of drought treatment on different varieties of rapeseed that the stress tolerance of parental rapeseed can be transmitted to the offspring through hybridization. In short, these findings have promoted the understanding of the B. napus TGA gene family and will contribute to future research aimed at B. napus resistant breeding.

Coffee is one of the most popular beverages worldwide, and there is an increasing concern of the health risk of coffee consumption in pregnancy. Preeclampsia (PE) is a serious pregnancy disease that causes elevated blood pressure and proteinuria in pregnant women and growth restriction of fetuses due to poorly developed placental vasculature. The aim of our study is to investigate the possible effect of coffee intake during pregnancy in rats with potential underlying vasculature conditions. The endothelial nitric oxide synthase inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) at a high dose (125 mg/kg/d) was used to induce PE in pregnant rats, which were used as the positive control group. In addition, low-dose L-NAME (10 mg/kg/d) was used to simulate the compromised placental vasculature function in pregnant rats. Coffee was given together with low-dose L-NAME to the pregnant rats from gestational day 10.5–18.5. Our results show that the pregnant rats treated with low-dose L-NAME + coffee, but not low-dose L-NAME alone, developed PE symptoms such as prominent fetal growth restriction, hypertension, and proteinuria. Therefore, our findings suggest that coffee intake during pregnancy may cause an increased risk of PE in susceptible women.

Boundary layer transition prediction has always been a hot and difficult research topic in the field of fluid mechanics. Among them, the crossflow induced transition plays a crucial role in the transition phenomenon on the surface of the aircraft, which is affected by the freestream disturbance, wall surface roughness, wall pressure gradient, local sweep angle, crossflow characteristic Reynolds number, Mach number, wall curvature and temperature. All those factors make the prediction of the cross-flow transition very complicated and difficult. In recent years, many research institutions have proposed various prediction methods for this problem, which are basically divided into two categories: one is to establish the critical transition Reynolds number criterion, and to determine whether transition occurs; the other type is the modeled linear stability theory, which calculates the cross-flow disturbance amplification factor and compares it with the transition threshold to determine whether transition occurs. Several typical prediction models of crossflow dominated transition based on local variables of low-speed boundary layer and high-speed boundary will be systematically reviewed and summarized, and the future research directions will be prospected.

Satellites should be equipped with more and more deployable, large, flexible appendages to improve their service efficiency and reduce launch costs. The spring-driven deployment method of flexible appendages has been widely applied and generates great instantaneous shock loads on satellites, maybe affecting the safety of other flexible appendages, but the current related investigations for satellites with multiple large flexible appendages are insufficient. In this study, the deployment test of the antenna itself was conducted, and the attitude changes in a satellite during antenna deployment were telemetered. Then, a related dynamical model of the satellite was established and verified by the telemetry values of the satellite. Finally, the shock mechanism transmitted to solar arrays was analyzed, and the effect of solar array attitude was discussed. The results show that the simulated method of antenna deployment equivalent to the shock loads tested was thought to be efficient, though it could cause a small non-zero constant of the simulated angular velocities in the antenna deployment direction. The shock-induced moments, except the rotation direction of the solar array drive assembly (SADA), should be highlighted for the antenna deployment dynamic design of satellites, and the solar array attitude has few effects on the shock-induced loads at the SADA.

Abstract Background The high incidence of intraoperative glucose dysregulations in liver transplantation (LT) is related to the lack of highly orchestrated control of intraoperative blood glucose. Glucose monitoring based on a single arterial blood gas test can only provide a simple glucose profile and is insufficient in monitoring intraoperative glycemic variability (GV), which is not conducive to controlling GV and may have a lag in the management of hyper/hypoglycemia. Continuous glucose monitor (CGM), which has been successfully applied in the management of chronic disease in diabetes, provides more detailed blood glucose records and reflect GV parameters such as coefficient of variation (CV%). However, its effectiveness and accuracy for guiding blood glucose management in major surgeries remains unclear. Methods This is a single-center, randomized, controlled, superiority trial. One hundred and eighty patients scheduled for orthotopic LT will be recruited and randomized into two groups. All patients are monitored for intraoperative glucose using CGM combined with arterial blood gas (ABG). In the intervention group (group CG), ABG will be performed when CGM value is 10.0 mmol/L, or the rate of change of CGM value > 1.67 mmol/(L·min). In the control group (group G), intraoperative ABG tests will be performed every 2 h, and the frequency of ABG tests will be adjusted based on the previous arterial glucose result. Patients in both groups will have their blood glucose adjusted according to arterial glucose values and a uniform protocol. Surgical and other anesthetic management is completed according to standard LT practices. Discussion This study intends to investigate the effectiveness of CGM-based intraoperative glucose management and its impact on the prognosis of LT patients by comparing the GV, mean glucose values, and the incidence of hypo/hypoglycemic events guided by the above two glucose monitoring methods. Trial registration This study is registered at www.chictr.org.cn on January 4, 2022, under the registration number ChiCTR2200055236.

Abstract Background Chronic inflammation and oxidant/antioxidant imbalance are two main pathological features associated with lipopolysaccharide (LPS)-induced acute lung injury (ALI). The following study investigated the protective role of hydrogen (H2), a gaseous molecule without known toxicity, in LPS-induced lung injury in mice and explored its potential molecular mechanisms. Methods Mice were randomly divided into three groups: H2 control group, LPS group, and LPS + H2 group. The mice were euthanized at the indicated time points, and the specimens were collected. The 72 h survival rates, cytokines contents, pathological changes, expression of Toll-like receptor 4 (TLR4), and oxidative stress indicators were analyzed. Moreover, under different culture conditions, RAW 264.7 mouse macrophages were used to investigate the potential molecular mechanisms of H2 in vitro. Cells were divided into the following groups: PBS group, LPS group, and LPS + H2 group. The cell viability, intracellular ROS, cytokines, and expression of TLR4 and nuclear factor kappa-B (NF-κB) were observed. Results Hydrogen inhalation increased the survival rate to 80%, reduced LPS-induced lung damage, and decreased inflammatory cytokine release in LPS mice. Besides, H2 showed remarked anti-oxidative activity to reduce the MDA and NO contents in the lung. In vitro data further indicated that H2 down-regulates the levels of ROS, NO, TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages and inhibits the expression of TLR4 and the activation of nuclear factor kappa-B (NF-κB). Conclusion Hydrogen gas alleviates lipopolysaccharide-induced acute lung injury and inflammatory response most probably through the TLR4-NF-κB pathway.

Abstract Advanced liver cancer is the most fatal malignant cancer, and the clinical outcomes of treatment are not very satisfactory due to the complexity and heterogeneity of the tumor. Combination therapy can efficiently enhance tumor treatment by stimulating multiple pathways and regulating the tumor immune microenvironment. Nanodrug delivery systems have become attractive candidates for combined strategies for liver cancer treatment. This study reports a nano ultrasound contrast agent (arsenic trioxide (ATO)/PFH NPs@Au‐cRGD) to integrate diagnosis and treatment for efficient ultrasound imaging and liver cancer therapy. This nanodrug delivery system promotes tumor‐associated antigens release through ATO‐induced ferroptosis and photothermal‐induced immunogenic cell death, enhancing the synergistic effects of ATO and photothermal therapy in human Huh7 and mouse Hepa1–6 cells. This drug delivery system successfully activates the antitumor immune response and promotes macrophage M1 polarization in tumor microenvironment with low side effects in subcutaneous and orthotopic liver cancer. Furthermore, tumor metastasis is inhibited and long‐term immunological memory is also established in orthotopic liver cancer when the nanodrug delivery system is combined with anti‐programmed death‐ligand 1 (PD‐L1) immunotherapy. This safe nanodrug delivery system can enhance antitumor therapy, inhibit lung metastasis, and achieve visual assessment of therapeutic efficacy, providing substantial potential in clinic applications for liver cancer.

Cardiomyocyte apoptosis has been characterized as one of the major mechanisms underlying doxorubicin (DOX)-induced cardiomyopathy. MicroRNA-21-5p (miR-21-5p) was reported to mitigate ischemia-induced cardiomyocyte apoptosis and cardiac injury. However, to our knowledge, the functional role of miR-21-5p in DOX-induced cardiomyopathy is unclear. In this study, we explored the role of miR-21-5p in DOX-induced cardiac injury. The expression level of miR-21-5p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Dual luciferase reporter assay was used to verify the potential target gene of miR-21-5p. The apoptosis rate of NRCMs was detected by TUNEL staining assay. Western blot analysis was used to detect the protein expression levels of Bax, Bcl-2, Caspase3, cleaved-Caspase3 and BTG2. For animal studies, mice were injected with AAV9-miR-21-5p or AAV9-Empty viruses, and treated with DOX at a dose of 5 mg/kg per week through intraperitoneally administration. After 4 weeks of DOX treatment, mice were subjected to echocardiography to measure the left ventricular ejection fraction (EF) and fractional shortening (FS). Results showed that miR-21-5p was upregulated in both DOX-treated primary cardiomyocytes and mouse heart tissues. Interestingly, enhanced miR-21-5p expression inhibited DOX-induced cardiomyocyte apoptosis and oxidative stress, while decreased miR-21-5p expression promoted cardiomyocyte apoptosis and oxidative stress. Furthermore, cardiac overexpression of miR-21-5p protected against DOX-induced cardiac injury. The mechanistic study indicated that BTG2 was a target gene of miR-21-5p. The anti-apoptotic effect of miR-21-5p could be inhibited by BTG2 overexpression. Conversely, inhibition of BTG2 rescued the pro-apoptotic effect of miR-21-5p inhibitor. Taken together, our study showed that miR-21-5p could prevent DOX-induced cardiomyopathy by downregulating BTG2.

Introduction: It has been proven that hydrogen has obvious anti-inflammatory effects in animal experiments and clinical practice. However, the early dynamic process of the inflammatory response caused by lipopolysaccharide (LPS) and the anti-inflammatory effect of hydrogen has not been definitively reported. Methods: Inflammation in male C57/BL6J mice or RAW264.7 cells was induced with LPS, for which hydrogen was immediately administered until samples were taken. Pathological changes in lung tissue were assessed using hematoxylin and eosin (HE) staining. Levels of inflammatory factors in serum were determined using liquid protein chip. The mRNA levels of chemotactic factors in lung tissues, leukocytes, and peritoneal macrophages were measured by qRT-PCR. The expression levels of IL-1α and HIF-1α were measured by immunocytochemistry. Results: Hydrogen alleviated LPS-induced inflammatory infiltration in the lung tissues of mice. Among the 23 inflammatory factors screened, LPS-induced upregulation of IL-1α etc. was significantly inhibited by hydrogen within 1 hour. The mRNA expression of MCP-1, MIP-1α, G-CSF, and RANTES was inhibited obviously by hydrogen at 0.5 and 1 h in mouse peritoneal macrophages. In addition, hydrogen significantly blocked LPS or H2O2-induced upregulation of HIF-1α, and IL-1α in 0.5 h in RAW264.7 cells. Discussion: The results suggested that hydrogen is potentially inhibitive against inflammation by inhibiting HIF-1α and IL-1α release at early occurrence. The target of the inhibitive LPS-induced-inflammatory action of hydrogen is chemokines in macrophages in the peritoneal cavity. This study provides direct experimental evidence for quickly controlling inflammation with the translational application of a hydrogen-assisted protocol.

Abstract Background Gut microbiota plays important roles in health maintenance and diseases. Physical exercise has been demonstrated to be able to modulate gut microbiota. However, the potential role of gut microbiome in exercise protection to myocardial infarction (MI) remains unclear. Results Here, we discovered exercise training ameliorated cardiac dysfunction and changed gut microbial richness and community structure post-MI. Moreover, gut microbiota pre-depletion abolished the protective effects of exercise training in MI mice. Furthermore, mice receiving microbiota transplants from exercised MI mice had better cardiac function compared to mice receiving microbiota transplants from non-exercised MI mice. Mechanistically, we analyzed metabolomics in fecal samples from exercised mice post-MI and identified 3-Hydroxyphenylacetic acid (3-HPA) and 4-Hydroxybenzoic acid (4-HBA), which could be applied individually to protect cardiac dysfunction post-MI and apoptosis through NRF2. Conclusions Together, our study provides new insights into the role of gut microbiome in exercise protection to MI, offers opportunities to modulate cardiovascular diseases by exercise, microbiome and gut microbiota-derived 3-HPA and 4-HBA. Video Abstract

The “One Belt and One Road” strategy provides a new opportunity for deepening oil and gas energy cooperation between China and Central-North Asian countries. This paper systematically studies the supply and demand characteristics, interdependence and cooperation prospects of oil and gas between them using relevant oil and gas energy data of these countries from 2016 to 2021. The objective of this research is to provide a basis for the overall planning of oil and gas energy cooperation between China and Central-North Asian countries in the future. The results show that the proven reserves of oil and gas in Central-North Asian countries are high; particularly, the proven reserves of natural gas account for 30% of the world. These countries also have high oil and gas self-sufficiency rates. These have laid a material foundation for China to strive for the sustained and stable import of oil and gas energy from Central-North Asian countries. At the same time, there are great imbalances in oil and gas reserves, production, consumption, available exports and their growth rates among Central-North Asian countries, which provide a basis for China and Central-North Asian countries to make strategic decisions on oil and gas energy differential cooperation. China imports 80 × 106 tons of oil and 490 × 108 cubic meters of gas from Central-North Asian countries every year and Chinese dependence on oil and gas imports in this region is 16% and 37%, respectively. The study believes that China has certain potential to increase the import of oil and gas from Central-North Asian countries and has good prospects for oil and gas cooperation. It is proposed that China should give priority to increasing oil and gas exploration and development cooperation with Central-North Asian countries with high oil and gas reserve–production ratios, and should strengthen oil and gas resource trade cooperation with Central-North Asian countries with high oil and gas self-sufficiency rates. At the same time, China should increase investment and cooperation in the midstream and downstream business of the oil industry in major Central-North Asian countries through various financing channels. China should uphold the principle of win–win cooperation to promote the in-depth and steady development of oil and gas energy cooperation between China and Central-North Asian countries.

The wall-associated kinase family contributes to plant cell elongation and pathogen recognition. Nine Cruciferous species were studied for identification and molecular evolution of the WAK gene family. Firstly, 178 WAK genes were identified. A phylogenetic tree was constructed of the Cruciferous WAK proteins into four categories, of which the Brassica rapa, Brassica oleracea and Brassica napus genes in the U’s triangle were more closely related. The WAK gene family was unevenly distributed in B. napus chromosomal imaging, with the largest number of BnWAK genes located on chromosome C08. In the expression analysis, the expression patterns of the WAK gene family varied under different stress treatments, and some members of BnWAKs were significantly different under stress treatments. This study lays a foundation for further revealing the functional mechanisms of the WAK gene family in Brassica napus.

Chronic alcohol consumption is associated with intestinal fungal dysbiosis, yet we understand little about how alterations of intestinal fungi (mycobiota) contribute to the pathogenesis of alcohol-associated liver disease. By reanalyzing internal transcribed spacer 2 amplicon sequencing of fecal samples from a cohort of 66 patients with alcohol use disorder for presence (as opposed to relative abundance) of fungal species, we observed that the presence of Malassezia restricta was associated with increased markers of liver injury. M. restricta exacerbates ethanol-induced liver injury both in acute binge and chronic ethanol-feeding models in mice. Using bone marrow chimeric mice, we found that the disease exacerbating effect by M. restricta was mediated by C-type lectin domain family 4, member N on bone marrow-derived cells. M. restricta induces inflammatory cytokines and chemokines in Kupffer cells through C-type lectin domain family 4, member N signaling. Targeting fungal pathobionts might be a therapeutic strategy for alcohol-associated liver disease.

Little is known about the effects of sedimentary environment and maturity on δD values of aromatic compounds deposited in geological bodies. Our simulation experiments showed that the δD value of pyrolytic polycyclic aromatic hydrocarbons (PAHs) was significantly different between the studied samples from high and low latitude regions. Comparative studies showed that the δD values of PAHs produced by pyrolysis were related to those of water in the two regions. With increasing maturity, the δD value of the PAHs becomes higher. Additionally, it was observed that some PAHs exhibited a propensity to increase the δD value upon demethylation. The thermodynamic fractionation of hydrogen isotopes between the PAHs produced by pyrolysis and both the n-alkanes and methane produced by pyrolysis indicated that the hydrogen isotopic value of the PAHs was higher than that of the n-alkanes or methane. The long-chain alkylbenzene produced by pyrolysis has a higher mean δD value compared with the n-alkanes produced by pyrolysis, but it is lower than that of the PAHs in the same sample. The lowest δD value among the aromatics was found in the ring A monoaromatic steroids produced by pyrolysis. The low δD values of these steroids should originate from isotopic fractionation during isoprenoid lipid biosynthesis.

Discrimination of seismicity distributed in different areas is essential for reliable seismic risk assessment in mines. Although machine learning has been widely applied in seismic data processing, feasibility and reliability of applying this technique to classify spatially clustered seismic events in underground mines are yet to be investigated. In this research, two groups of seismic events with a minimum local magnitude (ML) of −3 were observed in an underground coal mine. They were respectively located around a dyke and the longwall face. Additionally, two types of undesired signals were also recorded. Four machine learning methods, i.e. random forest (RF), support vector machine (SVM), deep convolutional neural network (DCNN), and residual neural network (ResNN), were used for classifying these signals. The results obtained based on a primary dataset showed that these seismic events could be classified with at least 91% accuracy. The DCNN using seismogram images as the inputs reached the best performance with more than 94% accuracy. As mining is a dynamic progress which could change the characteristics of seismic signals, the temporal variance in the prediction performance of DCNN was also investigated to assess the reliability of this classifier during mining. A cascaded workflow consisting of database update, model training, signal prediction, and results review was established. By progressively calibrating the DCNN model, it achieved up to 99% prediction accuracy. The results demonstrated that machine learning is a reliable tool for the automatic discrimination of spatially clustered seismicity in underground mining.

CRIg is expressed on liver macrophages and binds Gram-positive bacteria to mediate phagocytosis, but it is not clear how its phagocytic functions contribute to liver homeostasis or disease. Here the authors report that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of alcoholic liver disease.

Abstract Objective COVID-19 prevention and control demand a reduction in crowd gathering, which has a significant impact on traditional teaching and offline case-based learning (CBL). In order to mitigate the impact of the COVID-19 outbreak on clinical teaching, we aimed to compare the effects of an online CBL with traditional teaching model on learning outcomes of anesthesia residents. Methods Residents rotated in the Department of Anesthesiology in Beijing Tsinghua Changgung Hospital from January 2020 to February 2021 were included in Group W (n = 19), which implemented the W-CBL teaching model. The performance of residents was evaluated with theory test and 2 survey questionnaires (A and B) were conducted after 1 month of rotating. All 20 residents rotating in the Department of Anesthesiology at our hospital from January 2018 to December 2019 were included in Group C, which implemented the traditional teaching model. Their examination results were acquired through the teaching files and survey questionnaire (A) were administered through WeChat. Results During the 1-month rotation, a total of 10 cases were discussed in Group W. The average score for theory test was higher in Group W than that in Group C (84.57 ± 4.87 vs. 79.35 ± 3.70, P = 0.001). The satisfaction rate was also in favor of Group W regarding to clinical thinking, communication skills, learning interest and self-learning ability (P

Colorectal diseases are threatening human health, especially inflammatory bowel disease (IBD) and colorectal cancer (CRC). IBD is a group of chronic, recurrent and incurable disease, which may affect the entire gastrointestinal tract, increasing the risk of CRC. Eukaryotic gene expression is a complicated process, which is mainly regulated at the level of gene transcription and mRNA translation. Protein translation in tissue is associated with a sequence of steps, including initiation, elongation, termination and recycling. Abnormal regulation of gene expression is the key to the pathogenesis of CRC. In the early stages of cancer, it is vital to identify new diagnostic and therapeutic targets and biomarkers. This review presented current knowledge on aberrant expression of eIFs, eEFs and eRFs in colorectal diseases. The current findings of protein synthesis on colorectal pathogenesis showed that eIFs, eEFs and eRFs may be potential targets for CRC treatment.

Abstract Background Acute pancreatitis (AP) lacks targeted prevention and treatment measures. Some key points in the pathogenesis of AP remain unclear, such as early activation of pancreatic enzymes. Several recent reports have shown the protective effect of hydrogen on several AP animal models, and the mechanism is related to antioxidant activity. Heat shock protein 60 (Hsp60) is known to accompany pancreatic enzymes synthesis and secretion pathway of in pancreatic acinar cells, while role of hsp60 in AP remains a topic. Aim of this study was to investigate effect of hydrogen pretreatment on AP and the mechanisms, focusing on pancreatic oxidative stress and Hsp60 expression. Methods 80 mice were randomly assigned into four groups: HAP group, AP group, HNS group, and NS group and each group were set 3 observation time point as 1 h, 3 h and 5 h (n = 6–8). Mouse AP model was induced by intraperitoneal injection of 50 μg/kg caerulein per hour for 6 injections both in AP and HAP groups, and mice in NS group and HNS group given normal saline (NS) injections at the same way as control respectively. Mice in HAP group and HNS group were treated with hydrogen-rich gases inhalation for 3 days before the first injection of caerulein or saline, while mice in AP group and NS group in normal air condition. Histopathology of pancreatic tissue, plasma amylase and lipase, plasma IL-1 and IL-6, pancreatic glutathione (GSH) and malondialdehyde (MDA), and Hsp60 mRNA and protein expression were investigated. Comparisons were made by one-way analysis of variance. Results The pancreatic pathological changes, plasma amylase and lipase activity, and the increase of plasma IL-1 and IL-6 levels in AP mice were significantly improved by the hydrogen-rich gases pretreatment, Meanwhile, the pancreatic GSH content increased and the pancreatic MDA content decreased. And, the hydrogen-rich gases pretreatment improved the Hsp60 protein expression in pancreatic tissues of AP mice at 1 h and 5 h. Conclusions Pre-inhalation of hydrogen-rich gases have a good protective effect on AP mice, and the possible mechanisms of reduced oxidative stress and the early increased pancreatic Hsp60 protein deserve attention.

The conversion of lignocellulose into valuable chemicals has been recognized as the key technology in green chemistry. However, selective degradation of hemicellulose and cellulose with the production of lignin is still a challenge. Therefore, a two-step process has been developed to degrade corncob into xylose and glucose under mild conditions. At first, the corncob was treated with the lower concentration of zinc chloride aqueous solution (30–55 w%) at 95 °C with a short reaction time (8–12 min) and 30.4 w% (selectivity = 89%) of xylose obtained with a solid residue of the composite of cellulose and lignin. Next, the solid residue was treated with a high concentration of zinc chloride aqueous solution (65–85 w%) at 95 °C for about 10 min, and 29.4 w% (selectivity = 92%) of glucose can be obtained. Combining the two steps, the total yield of xylose is 97%, while glucose is 95%. In addition, high pure lignin can be obtained simultaneously, which was confirmed using HSQC studies. Furthermore, for the solid residue of the first-step reaction, a ternary deep eutectic solvent (DES) (choline chloride/oxalic acid/1,4-butanediol, ChCl/OA/BD) has been used to separate the cellulose and lignin efficiently, and high-quality cellulose (Re-C) and lignin (Re-L) were obtained. Furthermore, it provides a simple method to disassemble the lignocellulose for monosaccharides, lignin, and cellulose.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor developing from the esophageal squamous epithelium, and is the most common histological subtype of esophageal cancer (EC). EC ranks 10th in morbidity and sixth in mortality worldwide. The morbidity and mortality rates in China are both higher than the world average. Current treatments of ESCC are surgical treatment, radiotherapy, and chemotherapy. Neoadjuvant chemoradiotherapy plus surgical resection is recommended for advanced patients. However, it does not work in the significant promotion of overall survival (OS) after such therapy. Research on targeted therapy in ESCC mainly focus on EGFR and PD-1, but neither of the targeted drugs can significantly improve the 3-year and 5-year survival rates of disease. Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is an important survival pathway in tumor cells, associated with its aggressive growth and malignant progression. Specifically, proliferation, apoptosis, autophagy, and so on. Related genetic alterations of this pathway have been investigated in ESCC, such as PI3K, AKT and mTOR-rpS6K. Therefore, the PI3K/AKT/mTOR pathway seems to have the capability to serve as research hotspot in the future. Currently, various inhibitors are being tested in cells, animals, and clinical trials, which targeting at different parts of this pathway. In this work, we reviewed the research progress on the PI3K/AKT/mTOR pathway how to influence biological behaviors in ESCC, and discussed the interaction between signals downstream of this pathway, especially eukaryotic translation initiation factors (eIFs) and the development and progression of ESCC, to provide reference for the identification of new therapeutic targets in ESCC.

Backgrounds In advanced pancreatic ductal adenocarcinoma (PDAC), immune therapy, including immune checkpoint inhibitors, has limited efficacy, encouraging the study of combination therapy.Methods Tumor necrosis factor receptor 2 (TNFR2) was analyzed via immunohistochemistry, immunofluorescence, western blotting, and ELISAs. The in vitro mechanism that TNFR2 regulates programmed cell death 1 ligand 1 (PD-L1) was investigated using immunofluorescence, immunohistochemistry, flow cytometry, western blotting, and chromatin immunoprecipitation (ChIP). In vivo efficacy and mechanistic studies, using C57BL/6 mice and nude mice with KPC cell-derived subcutaneous and orthotopic tumors, employed antibodies against TNFR2 and PD-L1. Survival curves were constructed for the orthotopic model and a genetically engineered PDAC model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre). Mass cytometry, immunohistochemistry, and flow cytometry analyzed local and systemic alterations in the immunophenotype.Results TNFR2 showed high expression and is a prognostic factor in CD8+ T cell-enriched pancreatic cancer. TNFR2 promotes tumorigenesis and progression of pancreatic cancer via dual effect: suppressing cancer immunogenicity and partially accelerating tumor growth. TNFR2 positivity correlated with PD-L1, and in vitro and in vivo, it could regulate the expression of PDL1 at the transcription level via the p65 NF-κB pathway. Combining anti-TNFR2 and PD-L1 antibodies eradicated tumors, prolonged overall survival in pancreatic cancer, and induced strong antitumor immune memory and secondary prevention by reducing the infiltration of Tregs and tumor-associated macrophages and inducing CD8+ T cell activation in the PDAC microenvironment. Finally, the antitumor immune response derived from combination therapy is mainly dependent on CD8+ T cells, partially dependent on CD4+ T cells, and independent of natural killer cells.Conclusions Anti-TNFR2 and anti-PD-L1 combination therapy eradicated tumors by inhibiting their growth, relieving tumor immunosuppression, and generating robust memory recall.

Alcohol‐related liver disease is a major public health burden, and the gut microbiota is an important contributor to disease pathogenesis. The aim of the present study is to characterize functional alterations of the gut microbiota and test their performance for short‐term mortality prediction in patients with alcoholic hepatitis. We integrated shotgun metagenomics with untargeted metabolomics to investigate functional alterations of the gut microbiota and host co‐metabolism in a multicenter cohort of patients with alcoholic hepatitis. Profound changes were found in the gut microbial composition, functional metagenome, serum, and fecal metabolomes in patients with alcoholic hepatitis compared with nonalcoholic controls. We demonstrate that in comparison with single omics alone, the performance to predict 30‐day mortality was improved when combining microbial pathways with respective serum metabolites in patients with alcoholic hepatitis. The area under the receiver operating curve was higher than 0.85 for the tryptophan, isoleucine, and methionine pathways as predictors for 30‐day mortality, but achieved 0.989 for using the urea cycle pathway in combination with serum urea, with a bias‐corrected prediction error of 0.083 when using leave‐one‐out cross validation. Conclusion: Our study reveals changes in key microbial metabolic pathways associated with disease severity that predict short‐term mortality in our cohort of patients with alcoholic hepatitis.

Abstract Background The Vesical Imaging-Reporting and Data System (VI-RADS) was created in 2018, and a 5-point VI-RADS scoring system was proposed to determine whether the muscularis of the bladder has been infiltrated by tumor tissues. Purpose To verify the accuracy of the VI-RADS scoring system in predicting muscle-invasive bladder cancer and to explore its value in clinical application. Materials and methods A total of 220 patients with bladder cancer who underwent multiparameter magnetic resonance imaging from January 2017 to June 2019 were selected. Then, two radiologists with equivalent qualifications gave their diagnoses of bladder tumors on T2-weighted imaging, diffusion-weighted imaging and dynamic contrast enhanced imaging. Meanwhile, the bladder tumor was also scored on the basis of the VI-RADS system; for multifocal tumors, the highest tumor load was selected for scoring. Furthermore, the final pathological results of the patients were unknown during the imaging diagnosis and scoring. Next, the VI-RADS score was compared with the pathological results after surgery, and the ability of the VI-RADS score to assess the degree of muscularis infiltration was finally analyzed. Results A total of 220 patients were included in our study, including 194 males and 26 females. Among them, the pathological results were 113 cases of muscle-invasive bladder cancer and 107 cases of non-muscle-invasive bladder cancer. The results showed that there was a positive correlation between the pathological results and VI-RADS score (r = 0.821, P

BackgroundAlcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein.MethodsWe studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples.ResultsPatients with AUD had significantly increased abundance of the genera Candida, Debaryomyces, Pichia, Kluyveromyces, and Issatchenkia, and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida, Malassezia, Pichia, Kluyveromyces, Issatchenkia, and the species C. albicans and C. zeylanoides. This was mirrored by significantly higher specific anti-C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease.ConclusionIn conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia, and lower serum anti-C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.

Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients. Keywords: breast cancer, circBMPR2, tumor suppressor, tamoxifen resistance, miR-553, USP4

Background and Aims Alcoholic hepatitis is the most severe form of alcohol-related liver disease. While the gut microbiome is known to play a role in disease development and progression, less is known about specific compositional changes of the gut bacterial microbiome associated with disease severity. Therefore, the aim of our study was to correlate gut microbiota features with disease severity in alcoholic hepatitis patients. Methods We used 16S rRNA gene sequencing on fecal samples from 74 alcoholic hepatitis patients, which were enrolled at 9 centers in Europe, the United States, and Mexico in a multi-center observational study. The relative abundance of gut bacterial taxa on genus level, as well as the microbiome diversity, was correlated to various clinical, laboratory, and histologic parameters. Results We observed a negative correlation between the model for end-stage liver disease score and Shannon diversity, independent of potentially confounding factors (Padjust = 0.046). Alcoholic hepatitis patients with more severe disease had significantly decreased relative abundances of Akkermansia while the relative abundance of Veillonella was increased. We observed a reduction in the Bacteroides abundance (Padjust = 0.048) and Shannon diversity (Padjust = 0.018) in antibiotic-treated patients and patients receiving steroids had an increase in Veillonella abundance (Padjust = 0.005), which was both independent of potentially confounding factors. Conclusion We observed distinct changes in the gut bacterial microbiome of alcoholic hepatitis patients with more severe disease. The gut bacterial microbiome might be an attractive target to prevent and treat this deadly disease.

Excessive alcohol consumption is associated with hepatic steatosis and dysregulation of the gut microbiota in patients with alcohol use disorder (AUD). However, how gut microbiota responds when patients stop drinking has not been well studied. In this study, we use shotgun metagenomic sequencing to elucidate the alterations in the functional capacity of gut microbiota in patients with AUD when they stop drinking for 2-weeks. Sensitive microbial pathways to alcohol abstinence were identified in AUD patients. Further, we found the functional microbial responses to alcohol abstinence were different in AUD patients with different degree of hepatic steatosis. Our results provide insights into the link between functional alterations of the gut microbiota and steatosis associated with alcohol consumption.

Cytolysin-positive Enterococcus faecalis (E. faecalis) cause more severe alcohol-associated hepatitis, and phages might be used to specifically target these bacteria in a clinical trial. Using a humanized mouse model of ethanol-induced liver disease, the effect of cytolytic E. faecalis phage treatment on the intestinal and liver immune response was evaluated. The observed immune response was predominantly anti-inflammatory and tissue-restoring. Besides, live phages could be readily recovered from the serum, spleen, and liver following oral gavage in ethanol-fed mice. We also isolated 20 new phages from the sewage water; six of them exhibited a relatively broad host range. Taken together, the oral administration of cytolytic E. faecalis phages leads to the translocation of phages to the systemic circulation and appears to be safe, following chronic-binge ethanol administration. A cocktail of three phages covers the majority of tested cytolysin-positive E. faecalis strains and could be tested in a clinical trial.

Alcoholic hepatitis is a major health care burden in the United States due to significant morbidity and mortality. Early identification of patients with alcoholic hepatitis at greatest risk of death is extremely important for proper treatments and interventions to be instituted. In this study, we used gradient boosting, random forest, support vector machine and logistic regression analysis of laboratory parameters, fecal bacterial microbiota, fecal mycobiota, fecal virome, serum metabolome and serum lipidome to predict mortality in patients with alcoholic hepatitis. Gradient boosting achieved the highest AUC of 0.87 for both 30-day mortality prediction using the bacteria and metabolic pathways dataset and 90-day mortality prediction using the fungi dataset, which showed better performance than the currently used model for end-stage liver disease (MELD) score.

In order to understand the influence of diagenetic water medium on hydrogen isotope of thermogenic coalbed gas, the hydrous and anhydrous pyrolytic simulation experiments have been carried out on herbaceous peat. We studied hydrogen isotope composition and its difference and evolution pattern of the pyrolysis hydrocarbon gases It was observed that diagenetic water medium exerts a significant influence on hydrogen isotopic composition of the pyrolysis hydrocarbon gases. The experiment added water with heavier hydrogen isotopic composition than peat-formed environmental water generated hydrocarbon gases with heavier hydrogen isotopic compositions. When peat was subject to continuous pyrolysis until 5.5%Ro, average δD values of the generated methane, ethane and propane were increased by 74‰, 42‰ and 66‰, respectively. It was considered that the reason for hydrous simulation experiment to increase hydrogen isotopic value of pyrolytic hydrocarbon gases is due to isotopic exchange between water-derived hydrogen and organic hydrogen. Mathematical models between the δD values of the hydrocarbon gases generated under the participation of freshwater with higher δD values and Ro values as well as between δD values of the generated hydrocarbon gases were established. These research results provide a scientific basis for the genetic study of thermogenic coalbed methane pyrolyzated by coal-forming materials formed in herbaceous marsh under the participation of diagenetic water media. Keywords: Simulation experiment, Gas product, Hydrogen isotope, Diagenetic water medium, Influencing factor

Alcohol-related liver disease is associated with intestinal dysbiosis. Functional changes in the microbiota affect bile acid metabolism and result in elevated serum bile acids in patients with alcohol-related liver disease. The aim of this study was to identify the potential role of the bile acid sequestrant colesevelam in a humanized mouse model of ethanol-induced liver disease. We colonized germ-free (GF) C57BL/6 mice with feces from patients with alcoholic hepatitis and subjected humanized mice to the chronic–binge ethanol feeding model. Ethanol-fed gnotobiotic mice treated with colesevelam showed reduced hepatic levels of triglycerides and cholesterol, but liver injury and inflammation were not decreased as compared with non-treated mice. Colesevelam reduced hepatic cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1) protein expression, although serum bile acids were not lowered. In conclusion, our findings indicate that colesevelam treatment mitigates ethanol-induced liver steatosis in mice.

This paper describes a recent study on using fly ash for backfilling abandoned room and pillar mines. Detailed investigations on fly ash properties such as the strength and stiffness of settled fly ash, flowability of fly ash grout, as well as chemistry and environmental aspects of fly ash backfill have been undertaken in the laboratory. Numerical modelling was also conducted to quantify the effects of fly ash backfill on the stability of underground pillars. The laboratory tests showed that with a solid concentration of approximate 50%, fly ash grout has an excellent flowability and very low viscosity. It is capable of penetrating and filling almost any voids underground if designed properly and settling as a reasonably stiff solid to provide support to the pillars. Several different types of strength tests proved that a consolidated fly ash should exhibit a friction angle above 42°. 3D numerical modelling on interaction between fly ash backfill and underground pillars has shown that fly ash backfill to 90% roadway height can raise the factor of safety (FoS) of a marginally stable area to above 1.6, which is the number often used in rock engineering design for long term stability. Chemistry and leachate analysis of representative fly ash samples from a local power station showed that the elemental concentrations in the fly ash solid sample are lower than the allowed contaminant threshold and specific contaminant concentration levels. Geotechnical monitoring in the high risk areas of an abandoned mine has been carried out as part of the risk management and control for potential subsidence. The monitoring has been very helpful in understanding the ground behaviour around the abandoned mine which can provide timely information to the parties concerned in order to make correct decisions to control the subsidence risk. Keywords: Abandoned mine, Backfill, Fly ash, Laboratory tests, Monitoring, Modelling

In the task scheduling problem of phased array radar, the objective function is usually based on the time shifting rate (TSR). However, the TSR cannot achieve expected scheduling performance in non-linear filtering systems. To further improve the scheduling performance, a novel index named shifting improve rate (SIR) is proposed by analysing the influence of time shifting and its formula in Kalman filtering and expand Kalman filtering is derived. Based on SIR, a new objective function for scheduling of phased array radar tasks was designed and used the genetic algorithm to solve it. Simulated experiments are done to validate the proposed index and the new objective function. The results demonstrate that the SIR achieves better scheduling performance and tracking accuracy than TSR in non-linear filtering systems while keeping similar performance in linear filtering systems.

BackgroundIncreasing evidence indicated a close relationship between aberrant splicing variants and carcinoma, whereas comprehensive analysis of prognostic alternative splicing (AS) profiling in breast cancer (BRCA) is lacking and largely unknown.MethodsRNA-seq data and corresponding clinical information of BRCA patients were obtained and integrated from The Cancer Genome Atlas (TCGA). Then SpliceSeq software was used to assess seven AS types and calculate the Percent Spliced In (PSI) value. Univariate followed by stepwise multivariate Cox regression analyses identified survival associated AS events and constructed the AS signature, which were further sent for enrichment analysis, respectively. Besides, the splicing correlation network was constructed. Additionally, nomogram incorporating AS signature and clinicopathological characteristics was developed and its efficacy was evaluated with respect to discrimination, calibration and clinical utility.ResultsA total of 45,421 AS events were detected, among which 3071 events were found associated with overall survival (OS) after strict filtering. Parent genes of these prognostic events were involved in BRCA-related processes including NF-kappaB and HIF-1 signaling pathway. Besides, the final prognostic signature built with 20 AS events performed well with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.957 for 5 years. And gene set enrichment analysis (GSEA) also confirmed the candidate 20 AS events contributed to progression of BRCA. Moreover, the nomogram that incorporated 20-AS-event-based classifier, age, pathological stage and Her-2 status showed good calibration and moderate discrimination, with C-index of 0.883 (95% CI, 0.844–0.921). Decision curve analysis (DCA) confirmed more benefit was added to survival prediction with our nomogram, especially in 5 or 8 years with threshold probability up to 80%. Finally, splicing correlation network revealed an obvious regulatory pattern of prognostic splicing factors (SF) in BRCA.ConclusionThis study provided a systematic portrait of survival-associated AS events involved in BRCA and further presented a AS-clinicopathological nomogram, which could be conveniently used to assist the individualized prediction of long-term survival probability for BRCA patients. And a series of bioinformatic analysis provided a promising perspective for further uncovering the underlying mechanisms of AS events and validating therapeutic targets for BRCA.

BACKGROUND:The present study aims to investigate the gene expression changes in papillary renal cell carcinoma(pRCC) and screen several genes and associated pathways of papillary renal cell carcinoma progression. METHODS:The papillary renal cell carcinoma RNA sequencing (RNA-seq) data set was downloaded from TCGA (The Cancer Genome Atlas). We identified the differentially expressed mRNAs between cancer and normal tissues and performed annotation of differentially expressed mRNAs to figure out the functions and pathways they were enriched in. Then, we constructed a risk score that relied on the 5-mRNA. The optimal value for the patients'classification risk level was identified by ROC analysis. The relationship between mRNA expression and prognosis of papillary renal cell carcinoma was evaluated by univariate Cox regression model. The 5-mRNA based risk score was validated in both complete set and testing set. RESULT:In general, the 5-mRNA (CCNB2, IGF2BP3, KIF18A, PTTG1, and BUB1) were identified and validated, which can predict papillary renal cell carcinoma patient survival. This study revealed the 5-mRNA expression profile and the potential function of a single mRNA as a prognostic target for papillary renal cell carcinoma. CONCLUSION:In addition, these findings may have significant implications for potential treatments options and prognosis for patients with papillary renal cell carcinoma.