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Objective To screen the risk factors of hydrocephalus after decompressive craniectomy in patients with cerebral hernia after traumatic brain injury (TBI), and construct a Bayesian network model based on the risk factors. Methods A total of 77 patients with cerebral hernia after TBI who underwent decompressive craniotomy in Nanjing Tongren Hospital Affiliated to Southeast University from March 2020 to January 2022 were included. They were divided into hydrocephalus group (n = 25) and non - hydrocephalus group (n = 52) according to whether hydrocephalus was complicated after surgery. The risk factors of hydrocephalus after decompressive craniectomy in patients with cerebral hernia after TBI were analyzed by univariate and multivariate Logistic regression analyses. The Bayesian network model was constructed based on the risk factors, and the receiver operating characteristic (ROC) curve and calibration curve were drawn and Hosmer-Lemeshow goodness-of-fit test was conducted. Results In hydrocephalus group, the Glasgow Coma Scale (GCS) score at admission (t = 2.178, P = 0.032), the ratio of cerebrospinal fluid replacement after lumbar puncture (χ2 = 8.675, P = 0.003), and the level of β2 -microglobulin after operation (t = 11.146, P = 0.000) were lower than those in non-hydrocephalus group, while subarachnoid hemorrhage (χ2 = 5.901, P = 0.015), bilateral operation (χ2 = 6.441, P = 0.011), the ratio of dural unstitched during operation (χ2 = 9.759, P = 0.002), postoperative intraventricular hemorrhage (χ2 = 8.938, P = 0.003), postoperative midline displacement > 10 mm (χ2 = 7.589, P = 0.006), and intracranial infection (χ2 = 4.519, P = 0.034), as well as postoperative coma time (t = 2.709, P = 0.008) were higher than those in non - hydrocephalus group. Logistic regression analysis showed that subarachnoid hemorrhage (OR = 1.885, 95%CI: 1.432-2.240; P = 0.012), dural unstitched during operation (OR = 1.468, 95%CI: 1.215-1.930; P = 0.006), long postoperative coma time (OR = 1.574, 95%CI: 1.358-1.926; P = 0.007), postoperative intraventricular hemorrhage (OR = 1.550, 95%CI: 1.254-1.768; P = 0.010), the level of β2- microglobulin increased after operation (OR = 1.622, 95%CI: 1.165-1.840; P = 0.004) were risk factors for hydrocephalus after decompressive craniectomy in patients with cerebral hernia after TBI. Based on these 5 factors, the Bayesian network model was constructed, and the area under ROC curve was 0.886 (95%CI: 0.823-0.925, P = 0.000). The calibration curve showed that there was a good consistency between the predicted probability and the actual probability, while the Hosmer-Lemeshow goodness-of-fit test showed no significant difference (χ2 = 8.760, P = 0.232), which indicated that the model had good discrimination, calibration and accuracy. Conclusions Subarachnoid hemorrhage, dural unstitched during operation, long postoperative coma time, postoperative intra ventricular hemorrhage, and elevated β2 - microglobulin level are the risk factors for hydrocephalus after decompressive craniectomy in patients with cerebral hernia after TBI.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

IntroductionMonoclonal antibodies (mAbs) against cytokines and chemokines or their receptors promise to be a potential therapeutic option to address chronic obstructive pulmonary disease (COPD). We aim to provide a comprehensive literature review of the improvement in FEV1 and safety when comparing mAbs with conventional dichotomous agents.MethodsWe systematically searched 3 electronic databases (PubMed, EMBASE, and CENTRAL) up to August 1, 2023 to collect eligible randomized controlled trials (RCTs). A frequentist network meta-analysis using a random-effects model was deployed to calculate mean differences (MD) for FEV1, relative risk (RR) of treatment-emergent adverse events (TEAEs), and estimate the surface under cumulative rankings (SUCRA). A higher SUCRA indicates a better outcome.ResultsThis study included 23 RCTs involving a total of 20,853 patients. Overall, except for Dupilumab, mAbs did not significantly improve FEV1 compared to traditional conventional dichotomous agents. Among all the interventions included, Aclidinium bromide/Formoterol (AB/FF) (SUCRA 97.7%) ranked highest, followed by Umeclidinium/vilanterol (UMEC/VI) (SUCRA 93.5%), and Glycopyrrolate Formoterol Fumarate (GFF) (SUCRA 84.7%). Dupilumab (SUCRA 66.9%) ranked the fourth among all interventions but ranked the first among all the mAbs. Importantly, all mAbs demonstrated a good safety profile compared with placebo.ConclusionConsidering the improvement in FEV1 and its safety, the development of mAbs for COPD still holds significant clinical potential.Systematic review registrationPROSPERO, CRD42023452714.

Patients with type 2 diabetes mellitus (T2DM) are at higher risk for urinary tract infections (UTIs), which greatly impacts their quality of life. Developing a risk prediction model to identify high-risk patients for UTIs in those with T2DM and assisting clinical decision-making can help reduce the incidence of UTIs in T2DM patients. To construct the predictive model, potential relevant variables were first selected from the reference literature, and then data was extracted from the Hospital Information System (HIS) of the Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital for analysis. The data set was split into a training set and a test set in an 8:2 ratio. To handle the data and establish risk warning models, four imputation methods, four balancing methods, three feature screening methods, and eighteen machine learning algorithms were employed. A 10-fold cross-validation technique was applied to internally validate the training set, while the bootstrap method was used for external validation in the test set. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the performance of the models. The contributions of features were interpreted using the SHapley Additive ExPlanation (SHAP) approach. And a web-based prediction platform for UTIs in T2DM was constructed by Flask framework. Finally, 106 variables were identified for analysis from a total of 119 literature sources, and 1340 patients were included in the study. After comprehensive data preprocessing, a total of 48 datasets were generated, and 864 risk warning models were constructed based on various balancing methods, feature selection techniques, and a range of machine learning algorithms. The receiver operating characteristic (ROC) curves were used to assess the performances of these models, and the best model achieved an impressive AUC of 0.9789 upon external validation. Notably, the most critical factors contributing to UTIs in T2DM patients were found to be UTIs-related inflammatory markers, medication use, mainly SGLT2 inhibitors, severity of comorbidities, blood routine indicators, as well as other factors such as length of hospital stay and estimated glomerular filtration rate (eGFR). Furthermore, the SHAP method was utilized to interpret the contribution of each feature to the model. And based on the optimal predictive model a user-friendly prediction platform for UTIs in T2DM was built to assist clinicians in making clinical decisions. The machine learning model-based prediction system developed in this study exhibited favorable predictive ability and promising clinical utility. The web-based prediction platform, combined with the professional judgment of clinicians, can assist to make better clinical decisions.

Abstract Objectives To investigate the relationship between auditory pathway function and cochlear size in deaf children with a radiologically normal inner ear or Mondini malformation. Methods Thirty‐five deaf children without inner ear malformations (IEMs) and forty cases with Mondini malformation were included in this study. The electrically evoked auditory brainstem responses (EABRs) evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded during cochlear implantation (CI) surgery. The anatomical parameters of the cochlea were assessed by high‐resolution computed tomography and OTOPLAN 3‐D construction software. Correlations between EABRs and cochlear sizes were analyzed. Results The EABR thresholds and/or latencies were negatively correlated with the basal cochlear diameter, cochlear width and/or cochlear duct length in both patients without IEMs and those with Mondini malformation. Conclusion The physiological function of the peripheral auditory system depends on the anatomical structure of the cochlea to an extent. A larger cochlear size appears to be associated with better auditory conduction function. Our findings may be beneficial to selection of the proper electrode type and prediction of postoperative auditory rehabilitation. Level of Evidence Level 4.

Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.

BackgroundThe effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences.MethodsThis was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up.ResultsAmong the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP.ConclusionFemales have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.

Objective To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. Methods This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In‐hospital infection of clean limb incision, II, In‐hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non‐motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram‐positive bacteria (G+, mainly including Staphylococcus) and Gram‐negative bacteria (G‐, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two‐way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P 0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G‐ were resistant to the first‐ and the second‐generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third‐generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta‐lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. Conclusion In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out‐of‐hospital infection was lower than that of hospital infection.

Objective To investigate the efficacy and safety of combined anticoagulants with endovascular treatment for subacute and chronic cerebral venous sinus thrombosis (CVST) under the assistance of high resolution magnetic resonance black⁃blood thrombus imaging (MRBTI). Methods and Results A retrospective study was performed on the patients with CVST who were treated at Department of Neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2021. Preoperative high resolution MRBTI confirmed 15 patients with subacute and chronic CVST, and endovascular treatment was performed on the basis of systemic anticoagulant therapy. The results showed that 10 cases were in subacute stage and 5 cases were in chronic stage. After treatment, the venous sinus was completely recanalized in 4 cases and partially recanalized in 11 cases. Complications occurred in 2 cases (intracranial hematoma enlarged in one case, microguide wire penetrated straight sinus wall during surgery in one case), contact thrombolytic therapy was continued after the condition stabilized. The mean indwelling time of microcatheter in straight sinus was (6.27 ± 0.21) d and the mean length of hospital stay was (11.53 ± 1.30) d. The degree of impairment of consciousness [Glasgow Coma Scale (GCS) score] was improved at discharge [at discharge (13.67 ± 2.02) score vs. at admission (11.67 ± 2.13) score; t = 9.165, P = 0.000], the degree of neurological impairment [modified Rankin Scale (mRS) score] was improved 6 months after surgery [at 6 months after surgery 1 (0, 2) score vs. at admission 3 (2, 4) score; Z = ⁃ 3.624, P = 0.000]. Conclusions High resolution MRBTI is an effective technique to identify subacute and chronic CVST patients. For these patients, the combination of systemic anticoagulation and endovascular treatment can reduce venous sinus thrombosis load and improve symptoms in a short time, which is a safe, effective and preferred treatment.

There will be generated some adverse conditions in the process of acquculture farming with the continuous improvement of the intensive degree of modern aquaculture, such as crowding stress, hypoxia, and malnutrition, which will easily lead to oxidative stress. Se is an effective antioxidant, participating and playing an important role in the antioxidant defense system of fish. This paper reviews the physiological functions of selenoproteins in resisting oxidative stress in aquatic animals, the mechanisms of different forms of Se in anti-oxidative stress in aquatic animals and the harmful effects of lower and higher levels of Se in aquaculture. To summarize the application and research progress of Se in oxidative stress in aquatic animals and provide scientific references for its application in anti-oxidative stress in aquaculture.

To address the limitations of traditional aquaculture cages, such as poor performance in offshore environments, challenges in energy supply, and the inability to integrate modern farming facilities, a new semi-submersible aquaculture platform has been developed and put into operation. The hydrodynamic performance of the platform is analyzed using a fully coupled numerical model. The numerical model incorporates the main structure of the platform, the net system, and the mooring system, and is based on the linear potential flow theory and the Morison equation. The natural period of the platform is found to be far away from the common wave period. The mooring system for the platform in a specific sea area is proven to be safe. The net system significantly affects the hydrodynamic performance and alleviates the dynamic response of the platform. This study provides valuable insights for researchers and engineers in the design and optimization of this type of semi-submersible aquaculture platform in the future.

Objective. In this study, we aimed to explore the efficacy of the autologous platelet-rich plasma (PRP) interventional circulatory perfusion combined with radiofrequency ablation and thermocoagulation (RFAT) in the treatment of discogenic low back pain (DLBP). Methods. From January 2020 to November 2022, 158 patients of the Second Affiliated Hospital of Nanchang University were selected as the study subjects, and 24 patients met the exclusion criteria. The 134 patients who met the inclusion criteria were divided into 65 patients in the control group (3 patients lost to follow-up) and 69 patients in the observation group (5 patients lost to follow-up), so 126 patients were actually completed the study, including 62 patients in the control group and 64 patients in the observation group. The control group responsible disc received RFAT, and an interventional circulatory perfusion was performed; the observation group received RFAT, and an interventional circulatory perfusion was performed, and then autologous PRP 2 ml was injected. Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were performed before and 4 and 8 weeks after treatment, and the efficacy was evaluated at 4 and 8 weeks after treatment. The changes of lumbar disc MRI before and after treatment were observed. Results. The differences in the Visual Analog Scale (VAS) scores and the Oswestry Disability Index (ODI) between the observation group and the control group before the treatment were not statistically significant (P>0.05 in both). However, four weeks and eight weeks after the treatment, the VAS scores and the ODIs were significantly lower in both groups than those before the treatment (P

With the advantages of high energy density, long cycle life and high stability, lithium-ion batteries have been used in a large number of fields such as electric vehicles and grid scale energy storage. To ensure the safe and reliable operation of battery systems, it is important to make an accurate and rapid estimation of the state of health (SOH) of Li-ion cells. A Li-ion cell is a complex nonlinear dynamic system. The SOH of a Li-ion can not be measured directly in actual working conditions; it can only be estimated indirectly by external characteristic parameters that reflects the extent of cell aging. It is difficult to ensure the reliability of method based on a single aging feature or model. Therefore, this paper proposes a multi-feature SOH estimation method that combines data-driven XGBoost and a Kalman filter. Firstly, a principal component analysis algorithm to reconstruct multiple battery aging features based on data is used, and an XGBoost online estimation model incorporating multiple features based on the reconstructed feature data is constructed. Finally, the joint optimal estimation of SOH of Li-ion cells by introducing a time-domain Kalman filter based on the real-time correction of the XGBoost model is achieved in this method. The results show that the method improves the accuracy and robustness of the estimation model and achieves a high-precision joint estimation of SOH for Li-ion cells.

This paper considers the time difference of arrival (TDOA) and frequency difference of arrival (FDOA) estimation problem for joint localization using unmanned aerial vehicles (UAVs), involving range migration (RM) and Doppler ambiguity within observation interval. A robust estimation method based on interpolation and resampling is proposed. Specifically, the interpolation artificially increases the pulse repetition frequency (PRF). After that, the resampling eliminates the coupling between range frequency and slow time. Finally, a coherent integration step based on inverse discrete Fourier transform (IDFT) is used to achieve parameter estimation and suppress the grating lobes caused by interpolation. The proposed method could be efficiently implemented by fast Fourier transform (FFT), inverse FFT (IFFT) and non-uniform FFT (NUFFT) without parameter searching procedures. Numerical experiments indicate that the proposed method has nearly optimal anti-noise performance but much lower computational complexity than the maximum likelihood estimator, which makes it more competitive in practical applications.

For a long time, wind speed profile measurement has been the primary task of weather forecasting. Therefore, the detection of atmospheric wind speed is extremely important for studying the changes in atmospheric motion. In order to solve the problems of insufficient data collection, low resolution, and low accuracy in atmospheric wind field detection, this paper introduces the relevant theories of wind speed detection, completes the optical design of the system according to the research objectives, and determines the selection of optical devices. At the same time, a Doppler wind lidar system based on a quadrichannel Mach–Zehnder interferometer is designed and built to carry out ground-based observation experiments, collect echo signal data, and inverse the atmospheric radial wind speed. Furthermore, the wind measurement error is analyzed. Firstly, the paper introduces the basic principle of the wind measurement system, i.e., using the Doppler effect of light, and then analyzes the frequency discrimination device of the system in detail, and obtains the theoretical calculation method of atmospheric wind speed inversion. At the same time, the relevant datasets of wind measurement system are analyzed, including backscattering ratio, aerosol, and molecular extinction coefficient, and the emission mechanism of the large pulse laser is also studied in detail, which provides a theoretical basis for the model construction of Doppler lidar and the research on the enhancement of pulsed laser emission energy. Secondly, according to the research index of wind measurement, a Doppler wind measurement lidar system based on a quadrichannel Mach–Zehnder interferometer is designed, including the design of ab external light path transceiver system, internal light path interferometer, software and hardware, and algorithm. The calibration of the quadrichannel Mach–Zehnder interferometer is completed, with its maximum interference contrast reaching 0.869. Through the self-developed optical transceiver system and data acquisition system, the echo signal of lidar is received and detected. Lastly, the data of echo signals collected by the interferometer are analyzed, the radial atmospheric wind speed profile is inversed, and the signal-to-noise ratio and wind speed measurement error of the system are evaluated. The experimental results show that the maximum signal-to-noise ratio (SNR) of the system can reach 1433 when the emission pulse energy of the large pulse laser is adjusted to 255 mJ, and the farthest wind speed detection distance is about 8 km. The high-precision wind speed detection range can reach 2 km, the actual wind measurement errors in this range are all within 1.593 m/s, and the minimum error is only 0.418 m/s. In addition, the backscattering coefficient and extinction coefficient of atmospheric molecules and aerosols in the range of 8 km and the atmospheric temperature in the range of 10 km are also measured. The measurement accuracy of the aerosol extinction coefficient is ±0.001 m−1, and the measurement error of atmospheric temperature within 10 km is within 2 K, achieving the expected goals.

Nutritional pancreatic atrophy (NPA) is a classical Se/vitamin E deficiency disease of chicks. To reveal molecular mechanisms of its pathogenesis, we fed day-old chicks a practical, low-Se diet (14 μg Se/kg), and replicated the typical symptoms of NPA including vesiculated mitochondria, cytoplasmic vacuoles, and hyaline bodies in acinar cells of chicks as early as day 18. Target pathway analyses illustrated a > 90% depletion (P

Tea powder has been reported to have some physiological functions. However, there is no report on whether there are differences in the active ingredients of tea powder with different qualities and whether there are different prebiotic mechanisms. This study was aimed to investigate the effects of different qualities of tea powder on preventing obesity from different aspects, namely antioxidation, inflammation, lipid-lowering, and intestinal flora, using an obesity mouse model. The results showed that all three types of tea powder with different qualities could reduce body weight and decrease serum TC, TG, and LDL-C. However, tea powder with different quality attributes exhibited diverse modulatory effects and mechanisms. Tender tea powder contained more tea polyphenols, and it had a better effect on improving oxidative stress. Tender tea powder significantly decreased the abundances of Blautia, Bilophila, and Oscillibacter, and increased the abundances of Alloprevotella, Lachnoclostridium, Romboutsia, and Ruminococcaceae_UCG-004. Coarse tea powder contained more dietary fiber, and had a better effect on reducing the food intake and improving lipid metabolism, which could reduce lipid synthesis and increase lipid β-oxidation. Coarse tea powder significantly decreased the abundance of Dubosiella and increased the abundances of the Lachnospiraceae_NK4A136 group and Coriobacteriaceae_UCG-002. Our findings provide a theoretical reference for the comprehensive utilization of tea powder.

Although desert plants often establish multiple simultaneous symbiotic associations with various endophytic fungi in their roots, most studies focus on single fungus inoculation. Therefore, combined inoculation of multiple fungi should be applied to simulate natural habitats with the presence of a local microbiome. Here, a pot experiment was conducted to test the synergistic effects between three extremely arid habitat-adapted root endophytes (Alternaria chlamydospora, Sarocladium kiliense, and Monosporascus sp.). For that, we compared the effects of single fungus vs. combined fungi inoculation, on plant morphology and rhizospheric soil microhabitat of desert plant Astragalus adsurgens grown under drought and non-sterile soil conditions. The results indicated that fungal inoculation mainly influenced root biomass of A. adsurgens, but did not affect the shoot biomass. Both single fungus and combined inoculation decreased plant height (7–17%), but increased stem branching numbers (13–34%). However, fungal inoculation influenced the root length and surface area depending on their species and combinations, with the greatest benefits occurring on S. kiliense inoculation alone and its co-inoculation with Monosporascus sp. (109% and 61%; 54% and 42%). Although A. chlamydospora and co-inoculations with S. kiliense and Monosporascus sp. also appeared to promote root growth, these inoculations resulted in obvious soil acidification. Despite no observed root growth promotion, Monosporascus sp. associated with its combined inoculations maximally facilitated soil organic carbon accumulation. However, noticeably, combined inoculation of the three species had no significant effects on root length, surface area, and biomass, but promoted rhizospheric fungal diversity and abundance most, with Sordariomycetes being the dominant fungal group. This indicates the response of plant growth to fungal inoculation may be different from that of the rhizospheric fungal community. Structural equation modeling also demonstrated that fungal inoculation significantly influenced the interactions among the growth of A. adsurgens, soil factors, and rhizospheric fungal groups. Our findings suggest that, based on species-specific and combinatorial effects, endophytic fungi enhanced the plant root growth, altered soil nutrients, and facilitated rhizospheric fungal community, possibly contributing to desert plant performance and ecological adaptability. These results will provide the basis for evaluating the potential application of fungal inoculants for developing sustainable management for desert ecosystems.

Abstract Background Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear. Methods RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser (SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10 (METTL14exon10) and Cyclin L2exon6.3 skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10 and Cyclin L2exon6.3 skipping were surveyed. Results CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10 skipping while promoted Cyclin L2exon6.3 skipping. In addition, aberrant METTL14exon 10 skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3 promoted proliferation of PDAC cells. Conclusions The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.

The intracranial blood blister⁃like aneurysms (BBA) arising from the supraclinoid segment of internal carotid artery are very rary, and grow aggressively with high reruptured rate and mortality. Currently, the treatment methods of BBA are various but achieve no consensus, although including microsurgery and interventional therapy. The article collects the recent research and makes a review of the therapeutic progress of BBA, in order to provide clinical basis for the treatment of BBA and improve its therapeutic effect. doi：10.3969/j.issn.1672⁃6731.2021.04.016

Stroke is the second leading cause of death worldwide and the leading cause of long-term disability that seriously endangers health and quality of human life. Tissue-type fibrinogen activator is currently the only drug approved by FDA for the treatment of ischemic stroke. Neuroprotection is theoretically a common strategy for the treatment of both ischemic and hemorrhagic stroke; therefore, the development of neuroprotective agent has been the focus of research. However, no ideal neuroprotective drug is clinically available. Phosphoglycerate kinase-1 (PGK1) activator has the effect of inhibiting apoptosis and protecting tissue damage, and therefore could be a potential neuroprotective agent. To obtain effective PGK1 activators, we virtually screened a large chemical database and their evaluated the efficacy by the Drosophila oxidative stress model, PGK1 enzymatic activity assay, and oxygen-glucose stripping reperfusion (OGD/R) model. The results showed that compounds 7979989, Z112553128 and AK-693/21087020 are potential PGK1 activators with protective effects against PQ-induced oxidative stress in the Drosophila model and could effectively ameliorate apoptosis induced by OGD/R-induced neuronal cell injury. Additionally, compounds 7979989 and Z112553128 are effective in alleviating LPS-induced cellular inflammation. This study indicated that these compounds are promising lead compounds that provide theoretical and material basis to the neuroprotective drug discovery.

Abstract Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70–85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. Methods The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). Conclusions The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.

Cellular mesenchymal–epithelial transition factor (c-Met), an oncogenic transmembrane receptor tyrosine kinase (RTK), plays an essential role in cell proliferation during embryo development and liver regeneration. Thioredoxin reductase (TrxR) is overexpressed and constitutively active in most tumors closely related to cancer recurrence. Multi-target-directed ligands (MTDLs) strategy provides a logical approach to drug combinations and would adequately address the pathological complexity of cancer. In this work, we designed and synthesized a series of selenium-containing tepotinib derivatives by means of selenium-based bioisosteric modifications and evaluated their antiproliferative activity. Most of these selenium-containing hybrids exhibited potent dual inhibitory activity toward c-Met and TrxR. Among them, compound 8b was the most active, with an IC50 value of 10 nM against MHCC97H cells. Studies on the mechanism of action revealed that compound 8b triggered cell cycle arrest at the G1 phase and caused ROS accumulations by targeting TrxR, and these effects eventually led to cell apoptosis. These findings strongly suggest that compound 8b serves as a dual inhibitor of c-Met and TrxR, warranting further exploitation for cancer therapy.

Obolodiplosis robiniae was discovered in Eurasia at the beginning of the 21st century. In this study, we explore the present and future (in the years 2050 and 2070) trends in the potential distribution of O. robiniae in Eurasia under diverse climate change scenarios based on a maximum entropy model. Our findings indicated that the current potential distribution area of O. robiniae is within the range of 21°34′ and 65°39′ N in the Eurasian continent. The primary factor controlling the distribution of O. robiniae is temperature. The highly and moderately suitable areas are mainly distributed in the semi-humid and semi-arid regions, which also happen to be the locations where the host black locust (Robinia pseudoacacia L.) grows at its fastest rate. The forecast of the potential distribution area of O. robiniae revealed that the species would benefit from global warming. The region suitable for the habitat of O. robiniae is characterized by a large-scale northward expansion trend and an increase in temperature. This information would help the forestry quarantine departments of Asian and European countries provide early warnings on the probable distribution areas of O. robiniae and provide a scientific basis for the prevention and control of O. robiniae spread and outbreaks.

Purpose. This study aimed to determine whether and how stress-induced thyroid hormone changes occur during the COVID-19 pandemic in the northern area of Tianjin. Methods. This study comprised two groups of study subjects in Tianjin: before (2019) and during (2020) the COVID-19 outbreak. Subjects were included if they had FT3, FT4, and TSH concentrations and thyroid TPOAb or TgAb information available. People who were pregnant, were lactating, or had mental illness were excluded. We used propensity score matching to form a cohort in which patients had similar baseline characteristics, and their anxiety level was measured by the Hamilton Anxiety Rating Scale (HAMA). Results. Among the 1395 eligible people, 224 in Group A and 224 in Group B had similar propensity scores and were included in the analyses. The detection rate of abnormal thyroid function was decreased in pandemic Group B (69.2% vs. 93.3%, χ2 = 42.725, p

Abstract Background The number of patients receiving anaesthesia is increasing, but the impact of general anaesthesia on the patient's immune system remains unclear. The aim of the present study is to investigate dynamics of systemic immune cell responses to anaesthesia during perioperative period at a single‐cell solution. Methods The peripheral blood mononuclear cells (PBMCs) and clinical phenomes were harvested and recorded 1 day before anaesthesia and operation, just after anaesthesia (0 h), and 24 and 48 h after anaesthesia. Single‐cell sequencing of PBMCs was performed with 10× genomics. Subsequently, data analysis was performed with R packages: Seurat, clusterProfiler and CellPhoneDB. Results We found that the cluster of CD56+ NK cells changed at 0 h and the cluster of monocytes increased at 24 and 48 h after anaesthesia. The characteristic genes of CD56+ NK cells were mainly enriched in the Jak‐STAT signalling pathway and in cell adhesion molecules (24 h) and carbon metabolism (48 h). The communication between CD14+ monocytes and other cells decreased substantially 0 and 48 h after operation. The number of plasma cells enriched in protein export in men was substantially higher than that in women, although the total number in patients decreased 24 h after operation. CD14+ monocytes dominated that cell‐cell communications appeared in females, while CD8+ NKT cells dominated that cell‐cell communications appeared in male. The number of plasma cells increased substantially in patients with major surgical trauma, with enrichments of pentose phosphate pathway. The communications between plasma cells with other cells varied between surgical severities and anaesthetic forms. The intravenous anaesthesia caused major alterations of cell types, including CD14+ monocytes, plasmas cells and MAIT cells, as compared with inhalation anaesthesia. Conclusion We initially reported the roles of perioperative anaesthesia/surgery in temporal phenomes of circulating immune cells at a single‐cell solution. Thus, the protection against immune cell changes would benefit the recovery from anaesthesia/surgery.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear.Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance.Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children.Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

There have been several genome-wide association study (GWAS) reported for carcass, growth, and meat traits in chickens. Most of these studies have been based on single SNPs GWAS. In contrast, haplotype-based GWAS reports have been limited. In the present study, 2 Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) and genotyped with the chicken 60K SNP chip were used to perform a haplotype-based GWAS. The lean and fat chicken lines were selected for abdominal fat content for 11 yr. Abdominal fat weight was significantly different between the 2 lines; however, there was no difference for body weight between the lean and fat lines. A total of 132 haplotype windows were significantly associated with abdominal fat weight. These significantly associated haplotype windows were primarily located on chromosomes 2, 4, 8, 10, and 26. Seven candidate genes, including SHH, LMBR1, FGF7, IL16, PLIN1, IGF1R, and SLC16A1, were located within these associated regions. These genes may play important roles in the control of abdominal fat content. Two regions on chromosomes 3 and 10 were significantly associated with testis weight. These 2 regions were previously detected by the single SNP GWAS using this same resource population. TCF21 on chromosome 3 was identified as a potentially important candidate gene for testis growth and development based on gene expression analysis and the reported function of this gene. TCF12, which was previously detected in our SNP by SNP interaction analysis, was located in a region on chromosome 10 that was significantly associated with testis weight. Six candidate genes, including TNFRSF1B, PLOD1, NPPC, MTHFR, EPHB2, and SLC35A3, on chromosome 21 may play important roles in bone development based on the known function of these genes. In addition, several regions were significantly associated with other carcass and growth traits, but no candidate genes were identified. The results of the present study may be helpful in understanding the genetic mechanisms of carcass and growth traits in chickens.

ABSTRACT: Coal measure gas (also known as coal-bearing unconventional gas) is the key field and development direction of unconventional natural gas in recent years. The exploration and evaluation of coal measure gas (coalbed methane, coal shale gas and coal measure tight sandstone gas) from single coalbed methane has greatly expanded the field and space of resource evaluation, which is of positive significance for realizing the comprehensive utilization of coal resources, maximizing the benefits and promoting the innovation of oil and gas geological theory and technological advances in exploration and development. For the first time, in Yangmeishu Syncline of Western Guizhou Province, the public welfare coalbed methane geological survey project of China Geological Survey has been carried out a systematic geological survey of coal measure gas for the Upper Permian Longtan Formation, identified the geological conditions of coal measure gas and found high quality resources. The total geological resource quantity of coalbed methane and coal shale gas is 51.423×109 m3 and the geological resource abundance is up to 566×109 m3/km2. In this area, the coal measures are characterized by many layers of minable coal seams, large total thickness, thin to the medium thickness of the single layer, good gas-bearing property of coal seams and coal measure mudstone and sandstone, good reservoir physical property and high-pressure coefficient. According to the principle of combination of high quality and similarity of key parameters of the coal reservoir, the most favorable intervals are No.5−2, No.7 and No.13−2 coal seam in Well YMC1. And the pilot tests are carried out on coal seams and roof silty mudstone, such as staged perforation, increasing hydraulic fracturing scale and “three gas” production. The high and stable industrial gas flow with a daily gas output of more than 4000 m3 has been obtained, which has realized the breakthrough in the geological survey of coal measure gas in Southwest China. Based on the above investigation results, the geological characteristics of coal measure gas in the multi-thin-coal-seam-developed area and the co-exploration and co-production methods, such as the optimization method of favorable intervals, the high-efficiency fracturing and reservoir reconstruction method of coal measures, and the “three gas” drainage and production system, are systematically summarized in this paper. It will provide a reference for efficient exploration and development of coal measure gas in similar geological conditions in China.

Abstract Background This study aimed to investigate the clinical relevance of the immune microenvironment in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC‐ICC). Patients and Methods The density of tumor‐infiltrating CD3+, CD8+, CD163+, and Foxp3+ immune cells, as well as Programmed cell death 1, Programmed cell death‐ligand 1, and Tumor necrosis factor receptor superfamily member 4, was measured in the peritumor liver, tumor invasive margin, and intratumor subregions of 56 cHCC‐ICC by immunohistochemistry. The immune index was established to stratify patients. Prognostic significance of immune cell subsets and immune indices was evaluated. Results The distribution of immune cells was highly heterogeneous among different subregions of cHCC‐ICC. As compared with the hepatocellular carcinoma (HCC) component, the lower density of CD8+ T cells and higher intensity of Foxp3+ Tregs and immune checkpoints in the intrahepatic cholangiocarcinoma (ICC) component may indicate a stronger immune evasive ability of ICC. Based on clustering classification or a combination of random forest and lasso‐cox, two models of immune indices were established and both were identified as independent prognostic factors for cHCC‐ICC patients. The selected immune variables in the immune prognostic models derived from both HCC and ICC subregions, indicating that the prognosis of cHCC‐ICC patients was a complex interaction of both components. Conclusions The immune contexture was heterogeneous among different subregions of cHCC‐ICC patients and contributed differently to patient prognosis. Immune score based on the densities of immune cells might serve as a promising prognostic predictor for cHCC‐ICC patients.

The long short-term memory (LSTM) model trained on the universal language modeling task overcomes the bottleneck of vanishing gradients in the traditional recurrent neural network (RNN) and shows excellent performance in processing multiple tasks generated by natural language processing. Although LSTM effectively alleviates the vanishing gradient problem in the RNN, the information will be greatly lost in the long distance transmission, and there are still some limitations in its practical use. In this paper, we propose a new model called NEWLSTM, which improves the LSTM model, and alleviates the defects of too many parameters in LSTM and the vanishing gradient. The NEWLSTM model directly correlates the cell state information with current information. The traditional LSTM's input gate and forget gate are integrated, some components are deleted, the problems of too many LSTM parameters and complicated calculations are solved, and the iteration time is effectively reduced. In this paper, a neural network model is used to identify the relationship between input information sequences to predict the language sequence. The experimental results show that the improved new model is simpler than traditional LSTM models and LSTM variants on multiple test sets. NEWLSTM has better overall stability and can better solve the sparse words problem.

Strain C was isolated from chicken manure, and its phenotypic characteristics were gram-stain negative, yellow-pigmented, aerobic bacterium, heterotrophic, non-motile, chemoorganotrophic, non-gliding as well as non-spore-forming. A 16S rRNA gene sequence analysis showed that strain C occupied a distinct lineage within the family of the genus Chryseobacterium, and it shared highest sequence similarity with Chryseobacterium solincola strain 1YB-R12 (80%). The new isolate has been studied for removing ammonium-nitrogen (NH4-N) and the optimization of suitable conditions. The strain C was able to degrade over 42.8% of NH4-N during its active growth cycle. Experimental study of the effect of temperature and pH on NH4-N removal showed that the temperature and pH optima for NH4-N removal were 30–35℃ and 4–8, respectively. The results indicated that strain C shows a potential application for wastewater treatment.

Selenoprotein V (SELENOV) is a new and the least conserved member of the selenoprotein family. Herein we generated Selenov knockout (KO) mice to determine its in vivo function. The KO led to 16–19% increases (P

Liver necroptosis of chicks is induced by selenium (Se)/vitamin E (VE) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms of liver necrosis, a pool of the corn–soy basal diet (10 μg Se/kg; no VE added), a basal diet plus all-rac-α-tocopheryl acetate (50 mg/kg), Se (sodium selenite at 0.3 mg/kg), or both of these nutrients were provided to day-old broiler chicks (n = 40/group) for 6 weeks. High incidences of liver necrosis (30%) of chicks were induced by –SE–VE, starting at day 16. The Se concentration in liver and glutathione peroxidase (GPX) activity were decreased (P < 0.05) by dietary Se deficiency. Meanwhile, Se deficiency elevated malondialdehyde content and decreased superoxide dismutase (SOD) activity in the liver at weeks 2 and 4. Chicks fed with the two Se-deficient diets showed lower (P < 0.05) hepatic mRNA expression of Gpx1, Gpx3, Gpx4, Selenof, Selenoh, Selenok, Selenom, Selenon, Selenoo, Selenop, Selenot, Selenou, Selenow, and Dio1 than those fed with the two Se-supplemented diets. Dietary Se deficiency had elevated (P < 0.05) the expression of SELENOP, but decreased the downregulation (P < 0.05) of GPX1, GPX4, SELENON, and SELENOW in the liver of chicks at two time points. Meanwhile, dietary Se deficiency upregulated (P < 0.05) the abundance of hepatic proteins of p38 mitogen-activated protein kinase, phospho-p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, phospho-c-Jun N-terminal kinase, extracellular signal-regulated kinase, phospho-mitogen-activated protein kinase, receptor-interacting serine-threonine kinase 1 (RIPK1), receptor-interacting serine-threonine kinase 3 (RIPK3), and mixed lineage kinase domain-like (MLKL) at two time points. In conclusion, our data confirmed the differential regulation of dietary Se deficiency on several key selenoproteins, the RIPK1/RIPK3/MLKL, and mitogen-activated protein kinase signaling pathway in chicks and identified new molecular clues for understanding the etiology of nutritional liver necrosis.

Objective: Inflammatory cytokines are increased during one-lung ventilation in patients undergoing lung resection, and this increase can be fatal. Propofol and sevoflurane are the main anesthetics used for these patients. Unfortunately, there is no consensus on the best choice of an anesthetic agent concerning an inflammatory response in patients undergoing lung resection. This meta-analysis aimed to compare the effects of propofol and sevoflurane on the inflammatory response in patients undergoing lung resection.Methods: We searched electronic databases to identify randomized controlled trials comparing the effects of different anesthetics (sevoflurane vs. propofol) on the inflammatory response. The primary outcome concerned the concentration of systemic inflammatory cytokines. The secondary outcomes concerned the concentrations of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid from the dependent and independent lung. Random effects analysis of the meta-analyses were performed to synthesize the evidence and to assess the concentrations of inflammatory factors in the sevoflurane and propofol groups.Results: Eight trials involving 488 participants undergoing lung resection with one-lung ventilation were included. There was no significant difference in the concentrations of systemic interleukin (IL)-6, IL-10, or tumor necrosis factor α between the sevoflurane and propofol groups. Compared with the propofol group, BAL levels of IL-6 in the dependent ventilated lung were decreased in the sevoflurane group (three trials, 256 participants; standardized mean difference [SMD], −0.51; 95% confidence interval [CI], −0.90 to −0.11; p = 0.01; I2 = 46%). The BAL levels of IL-6 in the independent ventilated lung were also decreased by sevoflurane (four trials, 362 participants; SMD, −0.70; 95% [CI], −0.93 to −0.47; p < 0.00001; I2 = 0%).Conclusions: There was no difference in the systemic inflammatory response between the sevoflurane and propofol groups. However, compared with propofol, sevoflurane can reduce the local alveolar inflammatory response. Additional research is necessary to confirm whether the inflammatory response is direct or indirect.

Nuclear factor (NF)-κB–ty -50mediated neuroinflammation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). As an important negative feedback regulator of NF-κB, A20 is essential for inflammatory homeostasis. Herein, we tested the hypothesis that A20 attenuates EBI by establishing NF-κB–associated negative feedback after experimental SAH. In vivo and in vitro models of SAH were established. TPCA-1 and lentivirus were used for NF-κB inhibition and A20 silencing/overexpression, respectively. Cellular localization of A20 in the brain was determined via immunofluorescence. Western blotting and enzyme-linked immunosorbent assays were applied to observe the expression of members of the A20/tumor necrosis factor receptor-associated factor 6 (TRAF6)/NF-κB pathway and inflammatory cytokines (IL-6, IL-1β, TNF-α). Evans blue staining, TUNEL staining, Nissl staining, brain water content, and modified Garcia score were performed to evaluate the neuroprotective effect of A20. A20 expression by astrocytes, microglia, and neurons was increased at 24 h after SAH. A20 and inflammatory cytokine levels were decreased while TRAF6 expression was elevated after NF-κB inhibition. TRAF6, NF-κB, and inflammatory cytokine levels were increased after A20 silencing but suppressed with A20 overexpression. Also, Bcl-2, Bax, MMP-9, ZO-1 protein levels; Evans blue, TUNEL, and Nissl staining; brain water content; and modified Garcia score showed that A20 exerted a neuroprotective effect after SAH. A20 expression was regulated by NF-κB. In turn, increased A20 expression inhibited TRAF6 and NF-κB to reduce the subsequent inflammatory response. Our data also suggest that negative feedback regulation mechanism of the A20/TRAF6/NF-κB pathway and the neuroprotective role of A20 to attenuate EBI after SAH.

Magnetic skyrmion in chiral magnet exhibits a variety of unique topological properties associated with its innate topological structure. This inspires a number of ongoing searching for new topological magnetic textures. In this work, we used micromagnetic simulations and Monte Carlo simulations to investigate an exotic Néel-type magnetic kinks in square-shaped nanostructures of chiral magnets, which performs rather stably in the absence of magnetic field. The individual magnetic kink can reside in one of the four possible corners, and carry possibly upward or downward core polarity, constituting eight degenerate states. In addition, these kinks also exhibit unique behaviors of generation, stability and dynamics, as revealed by micromagnetic simulations. It was found that such kinks can be created, annihilated, displaced, and polarity-reversed on demand by applying a spin-polarized current pulse, and are easily switchable among the eight degenerate states. In particularly, the kinks can be switched toward the ferromagnetic-like states and backward reversibly by applying two successive current pulses, indicating the capability of writing and deleting the kink structures. These findings predict the existence of Néel-type magnetic kinks in the square-shaped nanostructures, as well as provide us a promising approach to tailor the kinks by utilizing the corners of the nanostructures, and control these states by spin-polarized currents. The present work also suggests a theoretical guide to explore other chiral magnetic textures in nanostructures of polygon geometries.

Background: Osteoarthritis (OA) is imposing substantial burdens on individuals and society with the aging population. Cortex Daphnes patch is widely used for symptomatic knee OA in China with a satisfying clinical efficacy; however, there is scant clinical evidence supporting its use. To evaluate its efficacy, we conducted a multicenter, non-inferiority, randomized, parallel-group study comparing Cortex Daphnes patch with topical nonsteroidal anti-inflammatory drugs in patients with knee OA (NCT02770950).Methods: A total of 264 symptomatic knee OA patients were treated with Cortex Daphnes or indomethacin cataplasms applied to affected sites once daily for 2 weeks. The primary outcome was improvement in knee pain on walking as assessed using a visual analog scale (VAS). The non-inferiority margin based on the full analysis population was set as –5 mm on the pain VAS. The secondary outcomes were changes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, WOMAC scores for pain, function and stiffness, the 36-item Short Form Health Survey (SF-36), and global assessment of knees by the patients. Responder rates for pain VAS, WOMAC total score, and WOMAC pain were also included in the secondary outcomes.Results: The Cortex Daphnes patch was non-inferior to indomethacin cataplasms for the primary outcome with a group difference (Cortex Daphnes patch–indomethacin cataplasm) of 2.1 mm (95% confidence interval: 2.1–6.4); similar results were found in the per-protocol population. For all other outcomes, no significant differences were found in the full analysis set or in the per-protocol analysis set, except the responder rates for WOMAC pain was higher in the Cortex Daphnes patch group than in the indomethacin cataplasm group (78.4 vs. 64.7%, p = 0.022) in the per-protocol analysis set. Overall, 28.8% patients in the Cortex Daphnes patch group and 9.8% in the indomethacin cataplasm group reported treatment-related adverse events, the vast majority of which were mild-to-moderate skin irritation, resulting in only 3.8 and 0.8% of patients dropping out, respectively.Conclusion: The Cortex Daphnes patch, which provides satisfactory analgesic efficacy and enhances the physical function of the knee, as well as improving quality of life, may be a promising alternative to knee OA.

Chronic myelogenous leukemia (CML) typically results from a reciprocal translocation between chromosomes 9 and 22 to produce the bcr-abl oncogene that when translated, yields the p210 BCR-ABL protein in more than 90% of all CML patients. This protein has constitutive tyrosine kinase activity that activates numerous downstream pathways that ultimately produces uncontrolled myeloid proliferation. Although the use of the BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib have increased the overall survival of CML patients, their use is limited by drug resistance and severe adverse effects. Therefore, there is the need to develop novel compounds that can overcome these problems that limit the use of these drugs. Therefore, in this study, we sought to find novel compounds using Hypogen and Hiphip pharmacophore models based on the structures of clinically approved BCR-ABL TKIs. We also used optimal pharmacophore models such as three-dimensional queries to screen the ZINC database to search for potential BCR-ABL inhibitors. The hit compounds were further screened using Lipinski’s rule of five, ADMET and molecular docking, and the efficacy of the hit compounds was evaluated. Our in vitro results indicated that compound ZINC21710815 significantly inhibited the proliferation of K562, BaF3/WT, and BaF3/T315I leukemia cells by inducing cell cycle arrest. The compound ZINC21710815 decreased the expression of p-BCR-ABL, STAT5, and Crkl and produced apoptosis and autophagy. Our results suggest that ZINC21710815 may be a potential BCR-ABL inhibitor that should undergo in vivo evaluation.

Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.

Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) directly interact with intracellular interleukin receptor associated kinase (IRAK) family members to initialize innate immune and inflammatory responses following activation by pathogen-associated or host-derived elements. Although four IRAK family members [IRAK1, 2, 3 (i.e., IRAK-M), and 4] are involved in TLR and IL-1R signaling pathways, IL-1R > IRAK1 signaling appears to be the most studied pathway, with sufficient evidence to support its central role linking the innate immune response to the pathogenesis of various diseases, including cancers, metabolic disorders, and non-infectious immune disorders. However, IRAK1’s involvement in cardiovascular diseases was only recently revealed and the detailed mechanism underling the pathogenesis of cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure (all non-infectious disorders), remains largely unknown with very limited publications to date. This review aims to summarize the overall roles of the IRAK family, especially IRAK1, in mediating the development of cardiovascular diseases.

Tendinopathy is a complex multifaceted tendinopathy often associated with overuse and with its high prevalence resulting in significant health care costs. At present, the pathogenesis and effective treatment of tendinopathy are still not sufficiently elucidated. The purpose of this research is to intensely explore the genes, functional pathways, and immune infiltration characteristics of the occurrence and development of tendinopathy. The gene expression profile of GSE106292, GSE26051 and GSE167226 are downloaded from GEO (NCBI comprehensive gene expression database) and analyzed by WGCNA software bag using R software, GSE26051, GSE167226 data set is combined to screen the differential gene analysis. We subsequently performed gene enrichment analysis of Gene Ontology (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG), and immune cell infiltration analysis. By constructing the LASSO regression model, Support vector machine (SVM-REF) and Gaussian mixture model (GMMs) algorithms are used to screen, to identify early diagnostic genes. We have obtained a total of 171 DEGs through WGCNA analysis and differentially expressed genes (DEGs) screening. By GO and KEGG enrichment analysis, it is found that these dysregulated genes were related to mTOR, HIF-1, MAPK, NF-κB and VEGF signaling pathways. Immune infiltration analysis showed that M1 macrophages, activated mast cells and activated NK cells had infiltration significance. After analysis of THE LASSO SVM-REF and GMMs algorithms, we found that the gene MACROD1 may be a gene for early diagnosis. We identified the potential of tendon disease early diagnosis way and immune gene regulation MACROD1 key infiltration characteristics based on comprehensive bioinformatics analysis. These hub genes and functional pathways may as early biomarkers of tendon injuries and molecular therapy level target is used to guide drug and basic research.

Tendinopathy is a complex multifaceted tendinopathy often associated with overuse and with its high prevalence resulting in significant health care costs. At present, the pathogenesis and effective treatment of tendinopathy are still not sufficiently elucidated. The purpose of this research is to intensely explore the genes, functional pathways, and immune infiltration characteristics of the occurrence and development of tendinopathy. The gene expression profile of GSE106292, GSE26051 and GSE167226 are downloaded from GEO (NCBI comprehensive gene expression database) and analyzed by WGCNA software bag using R software, GSE26051, GSE167226 data set is combined to screen the differential gene analysis. We subsequently performed gene enrichment analysis of Gene Ontology (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG), and immune cell infiltration analysis. By constructing the LASSO regression model, Support vector machine (SVM-REF) and Gaussian mixture model (GMMs) algorithms are used to screen, to identify early diagnostic genes. We have obtained a total of 171 DEGs through WGCNA analysis and differentially expressed genes (DEGs) screening. By GO and KEGG enrichment analysis, it is found that these dysregulated genes were related to mTOR, HIF-1, MAPK, NF-κB and VEGF signaling pathways. Immune infiltration analysis showed that M1 macrophages, activated mast cells and activated NK cells had infiltration significance. After analysis of THE LASSO SVM-REF and GMMs algorithms, we found that the gene MACROD1 may be a gene for early diagnosis. We identified the potential of tendon disease early diagnosis way and immune gene regulation MACROD1 key infiltration characteristics based on comprehensive bioinformatics analysis. These hub genes and functional pathways may as early biomarkers of tendon injuries and molecular therapy level target is used to guide drug and basic research.

Monitoring the mutation and evolution of the virus is important for tracing its ongoing transmission and facilitating effective vaccine development. A total of 342 complete genomic sequences of SARS-CoV-2 were analyzed in this study. Compared to the reference genome reported in December 2019, 465 mutations were found, among which, 347 occurred in only 1 sequence, while 26 occurred in more than 5 sequences. For these 26 further identified as SNPs, 14 were closely linked and were grouped into 5 profiles. Phylogenetic analysis revealed the sequences formed 2 major groups. Most of the sequences in late period (March and April) constituted the Cluster II, while the sequences before March in this study and the reported S/L and A/B/C types in previous studies were all in Cluster I. The distributions of some mutations were specific geographically or temporally, the potential effect of which on the transmission and pathogenicity of SARS-CoV-2 deserves further evaluation and monitoring. Two mutations were found in the receptor-binding domain (RBD) but outside the receptor-binding motif (RBM), indicating that mutations may only have marginal biological effects but merit further attention. The observed novel sequence divergence is of great significance to the study of the transmission, pathogenicity, and development of an effective vaccine for SARS-CoV-2.

The imbalance of reactive oxygen species is the main cause in aging, accompanied by oxidative stress. As the most abundant in human milk oligosaccharides (HMOs), 2′-Fucosyllactose (2′-FL) has been confirmed to have great properties in immunity regulation and anti-inflammatory. The research on 2′-FL is focused on infants currently, while there is no related report of 2′-FL for the elderly. A d-galactose-induced accelerated aging model was established to explore the protective effect of 2′-FL on the intestines and brain in mice. In this study, 2′-FL significantly reduced oxidative stress damage and inflammation in the intestines of aging mice, potentially by regulating the sirtuin1 (SIRT1)-related and nuclear factor E2-related factor 2 (Nrf2) pathways. In addition, 2′-FL significantly improved the gut mucosal barrier function and increased the content of short-chain fatty acids (SCFAs) in the intestine. The gut microbiota analysis indicated that 2′-FL mainly increased the abundance of probiotics like Akkermansia in aging mice. Moreover, 2′-FL significantly inhibited apoptosis in the brains of aging mice, also increasing the expression of SIRT1. These findings provided a basis for learning the benefits of 2′-FL in the aging process.