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Abstract Background and aims Numerous research have focused on the relationship of metabolic markers and stroke risk, yet limited research has focused on the triglyceride glucose-waist circumference (TyG-WC) index. This study explored the possible association of TyG-WC and stroke among moderately aged and old Chinese adults over 45 years of age. Methods This observational cohort analysis involved 9054 participants from the Chinese Longitudinal Study of Health and Retirement and employed a standardized questionnaire administered via in-person interviews. Cox proportional hazard model, smoothed curve fitting, and threshold effect analysis were conducted for examining the potential nonlinear relationships among TyG-WC and stroke risk. Results Within an average follow-up period of six years, 463 new strokes occurred, representing 5.11% of the total number of patients. After adjusting for possible confounding factors, a nonlinear association between TyG-WC and stroke risk was identified, with a significant dose–response relationship (P = 0.023 for the log-likelihood ratio test). A turning point was identified at the TyG-WC level of 554.48, beyond that the likelihood of stroke increased markedly (HR = 1.323, 95% CI = 1.098–1.594, P = 0.003). Conclusion This study revealed a specific curvilinear association with the TyG-WC score and stroke risk, identifying a key threshold value. This study focused on Chinese middle-aged and senior adults over the age of 45, emphasizing that increased stroke risk is linked to higher TyG-WC levels.

ObjectiveTo assess the efficacy and safety of linear accelerator-based fractionated stereotactic radiotherapy (LINAC-FSRT) in patients with brain metastases (BM).MethodsWe retrospectively analyzed 214 patients treated with LINAC-FSRT, categorized based on biologically effective dose (BED10, α/β = 10) into two groups (≤55 Gy, >55 Gy). Stratified analyses were conducted based on targeted therapy to compare survival outcomes. To examine brain tissue dose-tolerance volume, patients were divided into two groups: the standard Hypofractionated Treatment Effects in the Clinic (HyTEC) protocol group and an adjusted HyTEC protocol group where dose-volume restrictions exclude the planning target volume (PTV).ResultsResults as of December 2023 showed median intracranial progression-free survival (iPFS) at 12.4 months, with median overall survival (OS) not reached and a one-year local control (LC) rate of 68.7%. Mild to moderate toxicity affected 17.3% of patients, while severe toxicity occurred in 2.8%. Multivariate Cox analysis indicated that uncontrolled extracranial disease significantly reduced iPFS (HR = 2.692, 95%CI:1.880–3.853, P < 0.001) and OS (HR = 3.063, 95%CI:1.987–4.722, P < 0.001). BED10 >55 Gy (HR = 0.656, 95%CI:0.431–0.998, P = 0.049) improved OS, showing statistical significance (P = 0.037) without affecting iPFS or CNS toxicity (P = 0.127, P = 0.091). Stratified analysis highlighted nearly significant OS improvements with high-dose FSRT and targeted therapy (P = 0.054), while concurrent therapy markedly enhanced iPFS (P = 0.027). No significant differences were observed in intracranial local failure (ILF—which represents progression in previously treated areas during follow-up), one-year LC rates, iPFS, or OS between dose-volume groups. Adjusting HyTEC volume restrictions did not significantly increase CNS adverse reactions (P = 0.889).ConclusionsLINAC-FSRT is safe and effective in BM. BED10>55 Gy notably enhances OS post-LINAC-FSRT and may benefit LC. High BED10 FSRT with targeted therapy likely boosts synergy, and concurrent targeted therapy significantly improves iPFS. Diminishing dose volume constraints at different fractions based on the HyTEC guidelines is feasible.

Abstract FAM20C, a member of the family with sequence similarity 20, is involved in many physiological functions. Obesity, characterized by excessive accumulation of adipose tissue, has attracted more and more attention as a worldwide health problem. Here we generated adipocyte‐specific FAM20C knockout mice to investigate the role of FAM20C in adipose tissue expansion and obesity. Our results demonstrate that knockout mice are protected against high fat diet‐induced obesity, adiposity, and fatty liver disease. Additionally, knockout mice exhibited improved metabolic phenotypes, including enhanced glucose tolerance and insulin sensitivity compared with control mice. Furthermore, we observed reduced inflammatory infiltration and collagen deposition in the adipose tissues of knockout mice. Taken together, our results indicate that targeting FAM20C in adipocytes may be a promising strategy for the treatment of obesity and associated metabolic disorders.

To achieve high thermal efficiency, today's nuclear reactor structures are exposed to higher temperatures and pressures, which requires the use of high-strength steels with specific properties, such as ODS steels. There is a need to clarify the evolution of the microstructure and properties of steels at elevated temperatures. This study systematically investigates the evolution of microstructure, texture, and mechanical property variations of 12Cr-ODS steels after hot-rolling and subsequent annealing at 1000 °C and 1200 °C. The investigation utilizes optical microscopy, electron backscatter diffraction technique, and mechanical property measurements. The microstructure of hot-rolled samples shows a layered alternating distribution, which is distinguished by a notable presence of the α-fiber texture. Following annealing at 1000 °C, the martensite grains are smaller with a reduced hardness, while maintaining a strong α-fiber texture. After annealing at 1200 °C, there is a rapid increase in the growth of martensite grains, a significant rise in hardness, a reduction in the α-fiber texture characteristics, and an improvement in the γ-fiber texture characteristics. Moreover, the maximum intensity of the α-fiber texture diminishes as the annealing temperature increases. The mechanical properties of the samples deteriorated after annealing at 1200 °C, which can be attributed to the coarse martensite grains and the texture components containing the {001} cleavage plane dominating the occurrence of brittle cleavage fracture. The 0.1Y sample after annealing at 1000 °C exhibits an excellent combination of strength (1458 MPa) and ductility (20.3%), which is owing to the unique heterogeneous grain structure and the evolution of favorable texture.

IntroductionThis study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV).MethodsA total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed.ResultsThe sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients.ConclusionBALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment.

Abstract Objective This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

Abstract This study examines the impact of strong Madden-Julian Oscillation (MJO) phases (P1–P8) on diurnal rainfall patterns focusing on Afternoon Diurnal Convection (ADC) events in Sri Lanka during 2001–2020 spring and autumn. Daily mean rainfall increases (decreases) during the P2-to-P3 (P6-to-P7) MJO phases in both seasons, while the diurnal rainfall amplitude peaks during the P2-to-P3 (P8-to-P1) MJO phases in spring (autumn). ADC events also occur more frequently and intensely during MJO P2-to-P3 (P8-to-P1) in spring (autumn). The MJO’s modulation of diurnal rainfall amplitude and ADC events is more apparent in autumn than in spring. Active MJO phases enhance the westward propagation of diurnal rainfall associated with ADC events, sustained by moisture flux convergence and enhanced upward motion. The prevailing mid-to-upper level easterly wind, combined with deep convection over Sri Lanka, contributes to a more pronounced westward propagation during the P2-to-P3 (P8-to-P1) phases for ADC events in spring (autumn).

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. Methods Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. Results A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P

This mixed method study aims to address the lack of self-regulation in primary school students through providing self-regulation training with prompts and modeling in virtual flipped classroom (VFC). A four-week training was integrated into an extra-curricular program of Chinese speech with prompts or modeling embedded in pre-class videos. The study examines to what extent and how prompts and modeling affect students’ self-regulation and learning outcome. Forty-two primary school students from Grades 4 to 6 were randomly assigned into the prompt group and the modeling group. Both groups had not received self-regulation training before and did not show significant difference in the pre-test of self-regulation and the ability of speaking Chinese. The study collects multiple types of data including questionnaires, students’ notes, observations, interviews, and speaking tests. The study is innovative as it directly compares the effectiveness of modeling and prompts on enhancing students’ self-regulation. The results show that both prompts and modeling are effective in enhancing students’ self-regulation and learning outcome with modeling having an edge over prompts. The students and their parents expressed positive views towards self-regulation training in the program. This study provides several implications for practitioners on how to cultivate students’ self-regulation.

BackgroundAcanthamoeba castellanii infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce.Case presentationWe present a case of Acanthamoeba castellanii infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed Acanthamoeba castellanii infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient’s symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy.ConclusionImmunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for Acanthamoeba castellanii infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.

The corresponding author for this article [...]

Abstract Objective This study aimed to assess the feasibility of software-aided selection of monoenergetic level for acute necrotising pancreatitis (ANP) depiction compared to other automatic image series generated using dual-energy computed tomography (CT). Methods The contrast-enhanced dual-source dual-energy CT images in the portal venous phase of 48 patients with ANP were retrospectively analysed. Contrast-to-noise ratio (CNR) of pancreatic parenchyma-to-necrosis, signal-to-noise ratio (SNR) of the pancreas, image noise, and score of subjective diagnosis were measured, calculated, and compared among the CT images of 100 kV, Sn140 kV, weighted-average 120 kV, and optimal single-energy level for CNR. Results CNR of pancreatic parenchyma-to-necrosis in the images of 100 kV, Sn140 kV, weighted-average 120 kV, and the optimal single-energy level for CNR was 5.18 ± 2.39, 3.13 ± 1.35, 5.69 ± 2.35, and 9.99 ± 5.86, respectively; SNR of the pancreas in each group was 6.31 ± 2.77, 4.27 ± 1.56, 7.21 ± 2.69, and 11.83 ± 6.30, respectively; image noise in each group was 18.78 ± 5.20, 17.79 ± 4.63, 13.28 ± 3.13, and 9.31 ± 2.96, respectively; and score of subjective diagnosis in each group was 3.56 ± 0.50, 3.00 ± 0.55, 3.48 ± 0.55, and 3.88 ± 0.33, respectively. The four measurements of the optimal single-energy level for CNR images were significantly different from those of images in the other three groups (P

Abstract Background Biliary colic (BC) is a frequent hepatobiliary disorder encountered in emergency departments. Acupuncture may be effective as an alternative and complementary medicine for BC. Nonetheless, rigorous trials investigating its efficacy are lacking. Therefore, the aim of this study protocol is to determine whether acupuncture provides immediate relief of pain and associated symptoms in BC patients. Method Eighty-six participants who aged from 18 to 60 years with BC will be recruited in the First People's Hospital of Longquanyi District, Chengdu (West China Longquan Hospital Sichuan University). All participants will be allocated into two treatment groups including acupuncture group and sham acupuncture group using a 1:1 ratio. Each group will only receive a single 30-min needle treatment while waiting for their test results after completing the routine examination for BC. The primary outcome of the study is to assess the change in pain intensity after the 30-min acupuncture treatment. The secondary outcomes of the study include the change in pain intensity at various time points, the degree of gastrointestinal symptoms at different time points, the level of anxiety experienced during pain episodes at different time points, the score of Pain Anxiety Symptoms Scale-20 (PASS-20), the score of Fear of Pain Questionnaire-III (FPQ-III), and the score of Pain Catastrophizing Scale (PCS), among others. Discussion The results of this research will provide substantial evidence regarding the efficacy of acupuncture in alleviating symptoms associated with BC. Trial registration ClinicalTrials.gov, ChiCTR2300070661. Registered on 19 April 2023.

Abstract Background Abdominal ectopic fat deposition and excess visceral fat depots in obesity may be related to cardiovascular disease (CVD) as both are involved in the metabolic syndrome (MetS). The awareness of the link between abdominal adiposity and subclinical cardiac remodeling would help improve treatment and outcome. Besides, liver fibrosis has also shown a potential relationship with cardiac dysfunction. Thus, we aimed to investigate the associations of magnetic resonance (MR)-based abdominal adiposity and hepatic shear stiffness with subclinical left ventricular (LV) remodeling while taking account of MetS-related confounders in adults free of overt CVD. Methods This was an exploratory, prospective study of 88 adults (46 subjects with obesity, 42 healthy controls) who underwent 3 T cardiac and body MR exams. Measures of abdominal MR included hepatic and pancreatic proton density fat fraction (H-PDFF and P-PDFF), hepatic shear stiffness by MR elastography, and subcutaneous and visceral adipose tissue (SAT and VAT). Cardiac measures included epicardial adipose tissue (EAT) and parameters of LV geometry and function. Associations were assessed using Pearson correlation and multivariable linear regression analyses, in which age, sex, and MetS-related confounders were adjusted for. Results The LV ejection fractions of all participants were within the normal range. Higher H-PDFF, P-PDFF, SAT and VAT were independently associated with lower LV global myocardial strain parameters (radial, circumferential and longitudinal peak strain [PS], longitudinal peak systolic strain rate and diastolic strain rate) (β = − 0.001 to − 0.41, p < 0.05), and P-PDFF, SAT and VAT were independently and positively associated with LV end-diastolic volume and stroke volume (β = 0.09 to 3.08, p ≤ 0.02) in the over-all cohort. In the obesity subgroup, higher P-PDFF and VAT were independently associated with lower circumferential and longitudinal PS, respectively (β = − 0.29 to − 0.05, p ≤ 0.01). No independent correlation between hepatic shear stiffness and EAT or LV remodeling was found (all p ≥ 0.05). Conclusions Ectopic fat depositions in the liver and pancreas, and excess abdominal adipose tissue pose a risk of subclinical LV remodeling beyond MetS-related CVD risk factors in adults without overt CVD. VAT may play a more considerable role as a risk factor for subclinical LV dysfunction than does SAT in individuals with obesity. The underlying mechanisms of these associations and their longitudinal clinical implications need further investigation.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements, hardness distribution, and metallographic observations. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. Combined analysis of the Schmid factor (SF) and the strain compatibility factor (m’) was employed to study twin variant selection. Basal on SF ratio distribution, the Schmid factor criterion, can predict over 75% of observed twin variants in regions A and D (normal stress samples). In contrast, 64% of twin variant selection behavior in region C (shear stress sample) can be effectively explained using a pure shear model. Twin variants with high strain compatibility factors may prefer activation to reduce stress concentration. The strain compatibility factor is more appropriate than the Schmid factor for analyzing the effect of local strain on the selection behavior of twin variants.

Background and aimThe increased pancreatic enzymes have recently been reported in patients with severe fever with thrombocytopenia syndrome (SFTS). However, its significance has not been elucidated clearly. The aim of this study was to explore the prevalence, clinical characteristics of elevated pancreatic enzymes (amylase and lipase) and its association with AP in patients with SFTS.MethodsData of demographics, comorbid conditions, clinical symptoms, laboratory parameters and survival time of patients with SFTS were collected. Patients were assigned into the non-AP and AP groups according to the diagnostic criteria of AP. Patients in the non-AP group were divided into the normal (3×ULN) groups according to the serum amylase and lipase levels, and then their clinical data were compared.ResultsA total of 284 patients diagnosed with SFTS were retrospectively enrolled, including 248 patients in the non-AP group and 36 patients in the AP group. Patients in the non-AP group were composed of 48, 116 and 84 patients in the normal, EPE and HPE groups, respectively. Compared with patients in the normal and EPE groups, patients in the HPE group had higher serum levels of laboratory parameters referring to liver, kidney, heart and coagulation system injury, as well as higher viral load. The cumulative survival rate of patients in the HPE group was significantly lower than that of patients in the normal group. In addition, patients in the AP group also had higher serum levels of laboratory variables reflecting liver, heart, coagulation dysfunction and viral load than patients in the HPE group. The cumulative survival rate of patients in the AP group was significantly lower than that of patients in the HPE group.ConclusionThe increased pancreatic enzymes are very common in patients with SFTS, but they are not always associated with AP. Though AP accounts for the majority of deaths for patients with elevated pancreatic enzymes, patients with pancreatic enzymes >3×ULN except for AP also have a high in-hospital mortality rate.

Abstract To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X 2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods (X 2 = 54.206, P

High-strength and low-density materials are always needed in the aerospace, transportation, and other fields where lightweight is strictly required. The concept of the high-entropy alloy provides a new idea for designing the alloy with lightweight and high-strength. Mechanical properties and microstructure of the (TiZrV)100-xAlx (x = 10, 16, 25, at. %) medium-entropy alloys with different element Al content were investigated. With the increase of the element Al content in the (TiZrV)100-xAlx (x = 10, 16, 25, at. %) medium-entropy alloys, the densities of the specimens with the x = 10, 16, and 25 are 5.49, 5.37, and 5.15 g cm−3, respectively. The (TiZrV)90Al10 alloy and the (TiZrV)84Al16 alloy consist of the Ti(Zr,V) matrix phase and the ZrAl2 and Zr–V second phases, while the second phases in the (TiZrV)75Al25 alloy include the ZrAl2 and Zr–V and VAl2 phases. Also, more element Al is added, the coarser second phase grains tend to form in the alloys, resulting in decreasing of the room-temperature ductility and increasing of the high-temperature mechanical strength. Compressive ratio of the (TiZrV)100-xAlx (x = 10, 16, 25, at. %) medium-entropy alloys are larger than 30% at 1000 °C, and the (TiZrV)75Al25 alloy has a yield strength 184 MPa. The second phase grains are dispersed in the matrix, which can improve the deformation resistance of the alloy.

The high temperature compression is performed by isothermal compression tests using Gleeble 3500 thermo-mechanical simulator at a constant strain rate for the hot-pressed Nb-22.5Cr-2.5Mo alloy. The deformation temperature ranges from 800 to 1200 °C and the strain rate ranges from 0.001 to 0.1 s−1. The high temperature flow behavior and deformation mechanism of the alloy are investigated based on the compression test data and TEM observation of the deformed microstructure. The results show that the ductile–brittle transition temperature of the alloy is about 800 °C, and the flow stress is sensitive to the deformation temperature and strain rate, in which the plastic deformation ability increases obviously with the increase of deformation temperature and the decrease of strain rate. Besides, the hyperbolic sine Arrhenius model with stress exponent of 3.131 and apparent activation energy of 402 kJ/mol is established for the peak flow stress. The value of apparent activation energy is higher than that of Nb metal (246 kJ/mol), which implies the existence of Laves phase NbCr2 makes the deformation of the alloy more difficult. Moreover, it is found that the deformation mechanisms in the Nbss matrix are mainly DRV controlled by the glide and climb of the dislocations and DRX formed by bulging nucleation mechanism, while the deformation mechanisms in the Laves phase NbCr2 particles are mainly twinning and synchroshear of the Shockley partial dislocation.

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis caused by a novel bunyavirus. Until recently, the SFTS related acute kidney injury (AKI) was largely unexplored. This study aimed to investigate the clinical characteristics and outcomes of AKI in patients with SFTS.MethodsThe non-AKI and AKI groups were compared in terms of general characteristics, clinical features, laboratory parameters and cumulative survival rate. The independent risk factors for in-hospital mortality in patients with SFTS were analyzed by multivariate logistic regression to identify the population with poor prognosis.ResultsA total of 208 consecutive patients diagnosed with SFTS were enrolled, including 153 (73.6%) patients in the non-AKI group and 55 (26.4%) patients in the AKI group. Compared with patients without AKI, patients with AKI were older and had a higher frequency of diabetes. Among these laboratory parameters, platelet count, albumin and fibrinogen levels of patients with AKI were identified to be significantly lower than those of patients without AKI, while ALT, AST, ALP, triglyceride, LDH, BUN, uric acid, creatine, Cys-C, β2-MG, potassium, AMY, lipase, CK-MB, TnI, BNP, APTT, thrombin time, D-dimer, CRP, IL-6, PCT and ESR levels were significantly higher in patients with AKI. A higher SFTS viral load was also detected in the AKI patients than in the non-AKI patients. The cumulative survival rates of patients at AKI stage 2 or 3 were significantly lower than those of patients without AKI or at AKI stage 1. However, there was no significant difference in the cumulative survival rates between patients without AKI and those with stage 1 AKI. Univariate and multivariate binary logistic regression analyses demonstrated that stage 2 or 3 AKI was an independent risk factor for in-hospital mortality in patients with SFTS.ConclusionAKI is associated with poor outcomes in patients with SFTS, especially patients at AKI stage 2 or 3, who generally have high mortality. Our findings support the importance of early identification and timely treatment of AKI in patients with SFTS.

Selenium (Se) as an essential nutrient for human beings at trace concentrations, the allowable concentration for the human is only 40 μg/L. Iron sulfide (FeS) nanoparticles have been applied for excessive of selenium (Se) remediation in surface water and groundwater. In this study, FeS nanoparticles were anchored onto biochar (BC) to reduce agglomeration of FeS and prepared into the composite of FeS-BC by pyrolysis to economically and efficiently remove Se(IV) from simulated wastewater based on the excellent performance of FeS and the low cost of BC. Characterizations presented the uniform anchorage of FeS on the BC surface to prevent agglomeration. The results of batch experiments revealed that the removal of Se(IV) by FeS-BC nanomaterials significantly depended on the pH value, with the maximum removal of ∼174.96 mg/g at pH 3.0. A pseudo-second-order kinetic model well reflected the kinetic removal of Se(IV) in pure Se(IV) solution with different concentration, as well as the coexistence of K+, Ca2+, Cl-, and SO42- ions. The presence of K+ ions significantly inhibited the removal of Se(IV) with the increase of K+ ion concentration compared with the effect of the other three ions. SEM-EDS and XPS analyses indicated that the removal process was achieved through adsorption by surface complexation, and reductive precipitation of Se(IV) into Se0 with the electron donor of Fe(II) and S(-II) ions. The FeS-BC nanomaterial exhibited an excellent application prospect in the remediation of Se(IV).

Recently, wearable flexible sensors for intelligent sports monitoring have attracted much attention. In this work, we designed the polyvinyl alcohol (PVA)/polytrimethylene terephthalate (PTT)/LiCl hydrogel to act as the flexible conductive of triboelectric nanogenerator (PPL-TENG). Significantly, the PPL-TENG device has high transparency and stretchability, demonstrating excellent ability in complex mechanical energy harvesting. From the results, the PPL-TENG achieve the maximum power density of 159.6 µW cm−2. In addition, the PVA/PTT/LiCl hydrogel exhibits good mechanical properties, thus endowing PPL-TENG devices with excellent application value. Also, the electrical output of PPL-TENG exhibits good stability and excellent fast charging capability. In addition to mechanical energy harvesting, PPL-TENG also has excellent sensing performance and can be used as a self-powered sensor for basketball motion monitoring. After experimental testing, PPL-TENG can recognize the characteristics of body joints and gait in basketball, which will play an auxiliary role in basketball sports. This research will promote the development of intelligent wearable sports devices.

The record-setting winter of 2022–2023 came as an answer to both figurative and literal prayers for political leaders, policy makers, and water managers reliant on snowpacks in the Upper Colorado River Basin, a vital source of water for tens of millions of people across the Western United States. But this “drought-busting” winter was not well-predicted, in part because while interannual patterns of tropical ocean temperatures have a well-known relationship to precipitation patterns across much of the American West, the Upper Colorado is part of a liminal region where these connections tend to be comparatively weak. Using historical sea surface temperature and snowpack records, and leveraging a long-term cross-basin relationship to extend the timeline for evaluation, this analysis demonstrates that the 2022–2023 winter did not present in accordance with other high-snowpack winters in this region, and that the associative pattern of surface temperatures in the tropical Pacific, and snow water equivalent in the regions that stored and supplied most of the water to the Colorado River during the 2022–2023 winter, was not substantially different from a historically incoherent arrangement of long-term correlation. These findings suggest that stochastic variability plays an outsized role in influencing water availability in this region, even in extreme years, reinforcing the importance of other trends to inform water policy and management.

IntroductionThis article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI).MethodsThis longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student’s t-test and Mann–Whitney U test. Generalized linear mixed-effects model (GLMM) and value of p

Using the high-resolution numerical weather research and forecasting (WRF) model, study the squall line process that occurred on Hainan Island on 22 April 2020. The findings indicate that high terrain blocks the swift accumulation of water vapor carried by the sea breeze and aids in preserving the accumulated water vapor. According to the sensitivity experiment, terrain height has minimal impact on the macroscopic effects of mesoscale weather processes. However, it does influence where the sea breeze converges. During this process, the ocean-land thermal contrast not only takes the main responsibility for the sea breeze but also leads to uplift motion, which affects the formation, intensity, and duration of the squall line. Additionally, the unstable conditions suggest that a thermal and dynamic environment promote the scale of this squall line. Utilizing the Rotunno–Klemp–Weisman theory (RKW), this study analyzes the effects of the cold pool and vertical wind shear. The analysis reveals that significant vertical wind shear at lower levels and the ground-cold pool contribute to the sustenance and growth of the squall line system. This squall line process has had the greatest impact on the Haikou area due to the strong low-level vertical wind shear and prolonged interaction with the cold pool. When the interaction between the cold pool and the vertical wind shear weakens, the squall dissipates.

Abstract Framed by social learning theory, the study examines a set of personal and social factors determining off-task social media multitasking inside university classrooms. We aim to clarify the relationships between social media multitasking and self-efficacy, intrinsic motivation, multitasking preference as well as peer distraction, and to elucidate the interactive relationships between these factors. Questionnaire data from 203 university students in China show that academic self-efficacy fully mediates the association between intrinsic motivation and off-task multitasking. Moreover, multitasking preference partially mediates the association between peer distraction and off-task multitasking during class time. The findings of the study contribute to a deeper understanding of why students multitask during class, which can inform the development of strategies for combating social media distraction and enhancing students’ learning engagement.

Abstract Background Phosphatidylinositol 4-phosphate 5-kinase type I c (PIP5K1c) catalyses the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphorylating phosphatidylinositol 4 phosphate, which plays multiple roles in regulating focal adhesion formation, invasion, and cell migration signal transduction cascades. Here, a new physiological mechanism of PIP5K1c in adipocytes and systemic metabolism is reported. Methods Adipose-specific conditional knockout mice were generated to delete the PIP5K1c gene in adipocytes. In addition, in vitro research investigated the effect of PIP5K1c deletion on adipogenesis. Results Deletion of PIP5K1c in adipocytes significantly alleviated high fat diet (HFD)-induced obesity, hyperlipidaemia, hepatic steatosis, and insulin resistance. PIP5K1c deficiency in adipocytes also decreased adipocyte volume in HFD-induced obese mice, whereas no significant differences were observed in body weight and adipose tissue weight under normal chow diet conditions. PIP5K1c knockout in adipocytes significantly enhanced energy expenditure, which protected mice from HFD-induced weight gain. In addition, adipogenesis was markedly impaired in mouse stromal vascular fraction (SVF) from PIP5K1c-deleted mice. Conclusion Under HFD conditions, PIP5K1c regulates adipogenesis and adipose tissue homeostasis. Together, these data indicate that PIP5K1c could be a novel potential target for regulating fat accumulation, which could provide novel insight into the treatment of obesity.

Numerous studies have demonstrated that soybean meal (SBM) contains high levels of anti-nutritional factors, which interrupt gastrointestinal homeostasis or metabolism normally of the weaned piglets. Here, the mixed probiotics, including Bacillus licheniformis (B. licheniformis, CGMCC 8147), Saccharomyces cerevisiae H11 (S. cerevisiae H11) and Lactobacillus casei (L. casei, CGMCC 8149) were applied to the three-stage fermentation of functional feed. Our research investigated the optimum ratio of inoculation, optimal time of inoculation, combination of substrates, and nutritional value of the fermented feed. The optimal microbial combination was B. licheniformis: S. cerevisiae: L. casei = 2:2:1, inoculating at 0, 12 and 24 h, respectively. The results revealed that crude protein and acid-soluble protein were remarkably improved and had lower pH. Trypsin inhibitor, glycinin and β-conglycinin were reduced by 79.86, 77.18, and 69.29%, respectively. Moreover, animal trials further evaluated the growth-promoting effects of the fermented feed. It was noted that the average daily gain of weaned piglets was significantly higher, and the ratio of feed with weight, diarrhea incidence and mortality were lower significantly. The concentrations of serum immunoglobulin G(IgG), IgA, IgM, Complement C3 and interferon-γ (IFN-γ), and lysozyme activity were all increased. The relative abundance of fecal microbiota improved, especially lactobacillus, which increased the abundance of fecal dominant probiotics. Overall, the fermented feed may be conducive to the growth and health of weaned piglets by improving nutritional value, immunity properties, relative abundance of fecal microflora, and decreasing anti-nutritional factors of feed, thereby making them viable and usable feedstuffs for potential use in livestock industries.

Abstract Comorbidities are important for the disease outcome of COVID‐19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID‐19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID‐19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID‐19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan‐Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS‐CoV‐2 virus clearance, however, the use of Angiotensin‐Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID‐19 patients.

Abstract Background Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. Study design This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. Results We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337–0.989; P = 0.045). Conclusions Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

Long-term satellite precipitation products (SPPs) provide insight into how precipitation has changed in the past. As the changes observed from various SPPs may differ, research is needed to clarify related uncertainties using multiple SPPs. This study aims to explore long-term changes in the summer (June to August) diurnal precipitation over Luzon and its adjacent seas using multiple SPPs from 2000 − 2019, and to determine the possible atmospheric thermodynamic causes of such changes using the latest atmospheric reanalysis data. The four SPPs include the TRMM 3B42, the IMERG Final Run, the PERSIANN-CDR, and the PERSIANN-CCS-CDR. Our results show that all four SPPs depicted a common diurnal precipitation signal formed over the coastal region of western Luzon propagating westward to the adjacent South China Sea (SCS). This feature had been enhanced from 2000–2009 (Period1) to 2010–2019 (Period2). By contrast, there was uncertainty for central to eastern Luzon, where most SPPs with the exception of PERSIANN-CCS-CDR, captured a decline in diurnal precipitation from Period1 to Period2. These long-term changes in diurnal precipitation, which were suggested by the majority of SPPs, were further attributed to a strengthening (weakening) of local diurnal heating and related wind convergence over the SCS (Luzon), coupled with an intensification of regional prevailing winds. These findings highlight how the formation of precipitation over Luzon and SCS has changed under a changing climate.

Abstract Background AIDS-related KS generally involves cutaneous lesions, that slowly progress over months to years. Neither rapidly progressing of KS nor KS complicated with hemophagocytic syndrome (HPS) has rarely been reported. Case presentation We report a rare case of rapid progression of Kaposi’s sarcoma complicated with hemophagocytic syndrome in a severely immunosuppressed patient with HIV-infection. The symptoms of this patient were atypical, showing only persistent high fever and rapid progressed to hemophagocytic syndrome. This patient was successfully treated with antiretroviral therapy combined with liposomal doxorubicin. Conclusions The condition of the KS patient could deteriorate rapidly over a period of days and even developeded into HPS, which was life-threatening. However, chemotherapy initiated in a timely manner might improve prognosis.

Abstract Background Lung cancer is the most common malignant tumor in the world. The Whole-proteome microarray showed that ubiquitin ligase chromatin assembly factor 1 subunit B (CHAF1B) expression in A549/DDP cells is higher than in A549 cells. Our study explored the molecular mechanism of CHAF1B affecting cisplatin resistance in lung adenocarcinoma (LUAD). Methods Proteome microarray quantify the differentially expressed proteins between LUAD cell line A549 and its cisplatin-resistant strain A549/DDP. Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB) confirmed the CHAF1B expression. Public databases analyzed the prognosis of LUAD patients with varied LUAD expression followed by the substrates prediction of CHAF1B. Public databases showed that nuclear receptor corepressor 2 (NCOR2) may be substrates of CHAF1B. WB detected that CHAF1B expression affected the expression of NCOR2. Cell and animal experiments and clinical data detected function and integrating mechanism of CHAF1B compounds. Results Proteome chips results indicated that CHAF1B, PPP1R13L, and CDC20 was higher than A549 in A549/DDP. Public databases showed that high expression of CHAF1B, PPP1R13L, and CDC20 was negatively correlated with prognosis in LUAD patients. PCR and WB results indicated higher CHAF1B expression in A549/DDP cells than that in A549 cells. NCOR2 and PPP5C were confirmed to be substrates of CHAF1B. CHAF1B knockdown significantly increased the sensitivity of cisplatin in A549/DDP cells and the upregulated NCOR2 expression. CHAF1B and NCOR2 are interacting proteins and the position of interaction between CHAF1B and NCOR2 was mainly in the nucleus. CHAF1B promotes ubiquitination degradation of NCOR2. Cells and animal experiments showed that under the action of cisplatin, after knockdown of CHAF1B and NCOR2 in A549/DDP group compared with CHAF1B knockdown alone, the cell proliferation and migratory ability increased and apoptotic rate decreased, and the growth rate and size of transplanted tumor increased significantly. Immunohistochemistry suggested that Ki-67 increased, while apoptosis-related indicators caspase-3 decreased significantly. Clinical data showed that patients with high expression of CHAF1B are more susceptible to cisplatin resistance. Conclusion Ubiquitin ligase CAHF1B can induce cisplatin resistance in LUAD by promoting the ubiquitination degradation of NCOR2.

ABSTRACTQuantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27–55%), 100% (95% CI: 54–100%), 100%, 16% (95% CI: 13–19%), 0.6 (95% CI: 0.48–0.75) and 47% (95% CI: 33–60%) for RT-PCR to 94% (95% CI: 83–99%), 100% (95% CI: 48–100%), 100%, 63% (95% CI: 36–83%), 0.06 (95% CI: 0.02–0.18), and 95% (95% CI: 84–99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5–12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, driven by the BCR-ABL1 fusion oncoprotein. The discovery of orthosteric BCR-ABL1 tyrosine kinase inhibitors (TKIs) targeting its active ATP-binding pocket, such as first-generation Imatinib and second-generation Nilotinib (NIL), has profoundly revolutionized the therapeutic landscape of CML. However, currently targeted therapeutics still face considerable challenges with the inevitable emergence of drug-resistant mutations within BCR-ABL1. One of the most common resistant mutations in BCR-ABL1 is the T315I gatekeeper mutation, which confers resistance to most current TKIs in use. To resolve such conundrum, co-administration of orthosteric TKIs and allosteric drugs offers a novel paradigm to tackle drug resistance. Remarkably, previous studies have confirmed that the dual targeting BCR-ABL1 utilizing orthosteric TKI NIL and allosteric inhibitor ABL001 resulted in eradication of the CML xenograft tumors, exhibiting promising therapeutic potential. Previous studies have demonstrated the cooperated mechanism of two drugs. However, the conformational landscapes of synergistic effects remain unclear, hampering future efforts in optimizations and improvements. Hence, extensive large-scale molecular dynamics (MD) simulations of wide type (WT), WT-NIL, T315I, T315I-NIL, T315I-ABL001 and T315I-ABL001-NIL systems were carried out in an attempt to address such question. Simulation data revealed that the dynamic landscape of NIL-bound BCR-ABL1 was significantly reshaped upon ABL001 binding, as it shifted from an active conformation towards an inactive conformation. The community network of allosteric signaling was analyzed to elucidate the atomistic overview of allosteric regulation within BCR-ABL1. Moreover, binding free energy analysis unveiled that the affinity of NIL to BCR-ABL1 increased by the induction of ABL001, which led to its favorable binding and the release of drug resistance. The findings uncovered the in-depth structural mechanisms underpinning dual-targeting towards T315I BCR-ABL1 to overcome its drug resistance and will offer guidance for the rational design of next generations of BCR-ABL1 modulators and future combinatory therapeutic regimens.

Water vapor transport plays a significant role in maintaining the water cycle over the Tibetan Plateau (TP). This study investigates the characteristics of water vapor transport across the TP southern boundaries and its impacts on TP precipitation during the Indian summer monsoon (ISM) season from 2000 to 2019. The southern boundary is subdivided into four sub-boundaries from the east to the west: boundaries 7 (100°–95° E), 8 (95°–89° E), 9 (89°–80° E), and 10 (80°–70° E) (B7, B8, B9, and B10). ISM can affect the water vapor transports of B7, B8, and B9, while mid-latitude westerlies dominate the water vapor transport of B10. An area with concentrated spatial precipitation in both strong and weak ISM months is regarded as a precipitation concentration region (PCR). The results show that the PCR precipitation is smaller in the weak ISM month than in the normal month for most of the day, while it is larger in the strong ISM month than in the normal month. The PCR precipitation difference from afternoon to evening in strong and weak ISM months between normal months shows a dependency on the water vapor transport of B8 and B10. Water vapor transported across B9 also contributes to the increased PCR precipitation in the afternoon. The PCR precipitation shows a more dependable relationship to the water vapor from the BoB and the Arabian Sea in strong ISM months than in weak ISM months. Conversely, the water vapor transport efficiency is low in strong ISM months due to a cyclonic circulation over northern India, preventing water vapor transport from reaching the TP directly.

More attention has been paid in recent times to the application of Broussonetia papyrifera (BP) silage in ruminants, owing to its nutritional value. This study aimed to characterize the functionality of fermented BP and preliminarily explore its dietary effects on the gut health of laying hens. In this study, we characterized the antioxidant and antibacterial activities, bioactive compound profile, and bacterial community in Lactobacillus plantarum-fermented BP (FBP), as well as its dietary effects on intestinal morphology, microbiota and gene expression of laying hens. Improved contents of protein, total polyphenol and flavonoids as well as antioxidant and antibacterial activities were found after fermentation of BP. Untargeted metabolomics displayed more abundant apigenin, luteolin, diosmetin, and quercetin within the FBP, which may contribute to its functionality. Microbiome demonstrated increased abundance of Firmicutes at the expense of Cyanobacteria phylum, accompanied with raised levels of Lactobacillus genus. The results of a feeding trial showed dietary FBP supplementation increased the serum superoxide dismutase, but down-regulated gene expression of aryl hydrocarbon receptor (AhR), mucin2, and ZO-2, without obviously affecting the intestinal morphology and colonic microbiota. These findings suggest that FBP warrants further investigation as it may serve as a functional dietary supplement in laying hen feed.

Abstract Background Data that indicate vitamin A status in critically ill children with sepsis are sparse. The association between serum vitamin A levels and the clinical outcomes of sepsis has not been well assessed. The aim of this study was to assess the prevalence of vitamin A deficiency in critically ill children with sepsis and its association with clinical outcomes. Methods Critically ill children with sepsis admitted to the pediatric intensive care unit were engaged in this prospective study. Sex- and age-matched approximate-health children from the Department of Pediatric Surgery were enrolled as the control group. Blood samples were collected from all patients in the first 24 h of admission for the measurement of serum vitamin A status. We compared vitamin A status between the sepsis group and the control group. In addition, we compared the clinical characteristics of the two subgroups of septic patients with vitamin A deficiency and those without vitamin A deficiency. Univariate and multivariable methods were used to evaluate the association between vitamin A deficiency and septic shock. Results One hundred sixty septic children and 49 approximate-health children were enrolled in this study. Vitamin A deficiency was found in 94 (58.8%) subjects in the study group and 6 (12.2%) subjects in the control group (P 0.05). However, vitamin A levels were inversely associated with higher PRISM scores in septic children with VAD (r = − 0.260, P = 0.012). Vitamin A deficiency was associated with septic shock with an unadjusted odds ratio (OR) of 3.297 (95% confidence interval (CI), 1.169 to 9.300; P = 0.024). In a logistic model, vitamin A deficiency (OR, 4.630; 95% CI, 1.027–20.866; P = 0.046), procalcitonin (OR, 1.029; 95% CI, 1.009–1.048; P = 0.003), and the Pediatric Risk of Mortality scores (OR, 1.132; 95% CI, 1.009–1.228; P = 0.003) were independently associated with septic shock. Conclusion The prevalence of vitamin A deficiency was high in children with sepsis. Vitamin A deficiency may be a marker of mortality in critically ill children with sepsis. Trial registration Clinicaltrials.gov, NCT03598127

DGCR8 is a component of the canonical microprocessor complex for microRNA biogenesis. Here the authors implicate DGCR8 in heterochromatin maintenance and aging attenuation independent of its miRNA-processing activity through Lamin B1, KAP1 and HP1 interaction. DGCR8 overexpression can alleviate aging and senescence

PurposeLong non-coding RNAs (lncRNAs) play an important role in the occurrence and development of bladder cancer, but the underlying molecular mechanisms remain largely unknown. In this study, we found that LINC00467 was significantly highly expressed in bladder cancer through bioinformatic analysis. The present study aimed to explore the role of LINC00467 in bladder cancer and its possible underlying molecular mechanisms.MethodsThe expression of LINC00467 was obtained from GEO (GSE31189), the TCGA database, and qRT-PCR. The role of LINC00467 in bladder cancer was assessed both in vitro and in vivo. RIP, RNA pulldown, and CO-IP were used to demonstrate the potential mechanism by which LINC00467 regulates the progression of bladder cancer.ResultsThrough the analysis of GEO (GSE133624) and the TCGA database, it was found that LINC00467 was highly expressed in bladder cancer tissues and that the expression of LINC00467 was significantly negatively correlated with patient prognosis. Cell and animal experiments suggest that LINC00467 promotes the proliferation and invasion of bladder cancer cells. On the one hand, LINC00467 can directly bind to NF-kb-p65 mRNA to stabilize its expression. On the other hand, LINC00467 can directly bind to NF-kb-p65 to promote its translocation into the nucleus to activate the NF-κB signaling pathway, which promotes the progression of bladder cancer.ConclusionsLINC00467 is highly expressed in bladder cancer and can promote the progression of bladder cancer by regulating the NF-κB signaling pathway. Therefore, targeting LINC00467 is very likely to provide a new strategy for the treatment of bladder cancer and for improving patient prognosis.

Background: Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis and progression. TMPO antisense RNA 1 (TMPO-AS1) has been found to be involved in several cancers by acting as a competing endogenous RNA. However, the potential roles of TMPO-AS1 in bladder cancer (BC) and the potential interactions with proteins remain poorly understood.Methods: The expression of the lncRNA TMPO-AS1 was evaluated via bioinformatic analysis and further validated by quantitative real-time PCR (qRT-PCR). Loss- and gain-of-function assays were performed to determine the biological functions of TMPO-AS1 in BC cell proliferation, migration, and invasion. Moreover, chromatin immunoprecipitation, Western blotting, and fluorescence in situ hybridization, as well as RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays, were conducted to explore the upstream and downstream molecules interacting with TMPO-AS1.Results: TMPO-AS1 is upregulated in BC. Functional experiments demonstrated that TMPO-AS1 promotes cell proliferation, migration, and invasion in BC and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization; therefore, TMPO-AS1 promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner.Conclusions: Our study is the first to uncover the novel TMPO-AS1/E2F1 positive regulatory loop important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.

BackgroundAt present, the relationship between thyrotropin (TSH) and free thyroxine (FT4) in relation to postmenstrual age (PMA) in preterm infants is still unclear, and there is no reliable standard thyroid hormone reference ranges, resulting in different diagnostic criteria for congenital hypothyroidism been used by different newborn screening programs and different countries.ObjectivesTo investigate the relationship between TSH/FT4 and PMA in very preterm infants (VPIs) born with gestational age (GA)

ABSTRACT: This article combines influencing factors of farmers’ participation in the Rural Living Environment Renovation Project (RLERP) and conceptualizes a model that depicts the relationships between the demographic characteristics of farmers and their perceptions and behavioral response to RLERP. Using a questionnaire survey to collect empirical data, we found (1) A total of 92% of farmers have fully realized the importance of rural living environment, but most people have adopted a wait-and-see attitude and a lack of motivation to participate. (2) A total of 65% of farmers participate in the collection and classification of domestic waste, 22% of the farmers participate in captivity livestock behavior, and 19% of farmers participate in the response behavior of domestic sewage treatment. (3) A significant positive correlation occurs between income level and farmers’ cognition and behavior response. (4) The education standards of the public are not correlated with the farmers’ cognition but is significantly correlated with farmers’ behavioral response. (5) The cognitive and behavioral response of females to RLERP is significantly higher than that of men. 6) In the process from cognition to the action response, farmers’ cognition is positively correlated with action response. On this basis, some measures and suggestions to improve the response of farmers to rural living environment renovation are put forward.

Abstract Long noncoding RNAs (lncRNAs) play a crucial role in progression of bladder urothelial carcinoma (BUC). However, the molecular mechanisms behind this role have not been elucidated yet. Here, we found that the lncRNA MAFG‐AS1, which is highly expressed in BUC, is correlated with aggressive characteristics and poor prognosis of BUC. We demonstrate that MAFG‐AS1 can promote BUC proliferation, invasion, metastasis, and epithelial‐mesenchymal transition in vitro and in vivo. Mechanistically, MAFG‐AS1 direct binding to Hu antigen R (HuR) could recruit ubiquitin‐specific proteinase 5 (USP5) to prevent HuR from degrading by ubiquitination. We further demonstrate that overexpression of MAFG‐AS1 can upregulate the expression of polypyrimidine tract‐binding protein 1 (PTBP1) through promoting its stability mediated by bound HuR. In conclusion, these findings indicate that MAFG‐AS1 promotes the progression of BUC via regulation of the HUR/PTBP1 axis. Targeting MAFG‐AS1 may provide a novel strategy for individualized therapy and a potential biomarker for prognosis of BUC.

Summary: The outbreak of SARS-CoV-2 in China, attracted a large number of medical staff to help in the city's hospitals and this put them at a high risk of infection. We describe twenty medical staff who were diagnosed with COVID-19 within one week in the department of surgery in a Wuhan hospital. Epidemiological investigation of these cases identified misdiagnosed patients (source of infection), an inappropriate clinical meeting and working without wearing face masks to be the causes of the outbreaks. This report emphasizes the importance of wearing a facemask and applying other standard infection control precautions to protect medical personnel from infection with the virus.

Ubiquitin ligases have been shown to regulate drug sensitivity. This study aimed to explore the role of the ubiquitin ligase WD repeat and HMG-box DNA binding protein 1 (WDHD1) in regulating cisplatin sensitivity in lung adenocarcinoma (LUAD). A quantitative analysis of the global proteome identified differential protein expression between LUAD A549 cells and the cisplatin-resistant strain A549/DDP. Public databases revealed the relationship between ubiquitin ligase expression and the prognosis of patients with LUAD. Quantitative real-time polymerase chain reaction and Western blotting were used to estimate the WDHD1 expression levels. Analysis of public databases predicted the substrate of WDHD1. Western blotting detected the effect of WDHD1 on microtubule-associated protein RP/EB family member 2 (MAPRE2) and DSTN. Functional analysis of MAPRE2 verified the interaction between WDHD1 and MAPRE2, as well as the interacting sites by methyl-thiazolyl-tetrazolium assay and flow cytometry, immunoprecipitation, protein stability, and immunofluorescence. Cell and animal experiments confirmed the effect of WDHD1 and MAPRE2 on cisplatin sensitivity in LUAD. Clinical data evaluated the impact of WDHD1 expression level on cisplatin sensitivity. Quantitative analysis of the global proteome revealed ubiquitin-dependent protein catabolism to be more active in A549/DDP cells than in A549 cells. WDHD1 expression was higher in A549/DDP cells than in A549 cells, and knocking out WDHD1 increased the sensitivity of A549/DDP cells to cisplatin. WDHD1 overexpression negatively correlated with the overall survival of LUAD patients. We observed that MAPRE2 was upregulated when WDHD1 was knocked out. A MAPRE2 knockout in A549 cells resulted in increased cell viability while decreasing apoptosis when the A549 cells exposed to cisplatin. WDHD1 and MAPRE2 were found to interact in the nucleus, and WDHD1 promoted the ubiquitination of MAPRE2. Following cisplatin exposure, the WDHD1 and MAPRE2 knockout groups facilitated cell proliferation and migration, inhibited apoptosis in A549/DDP cells, decreased apoptosis, and increased tumor size and growth rate in animal experiments. Immunohistochemistry showed that Ki67 levels increased, and levels of apoptotic indicators significantly decreased in the WDHD1 and MAPRE2 knockout groups. Clinical data confirmed that WDHD1 overexpression negatively correlated with cisplatin sensitivity. Thus, the ubiquitin ligase WDHD1 induces cisplatin resistance in LUAD by promoting MAPRE2 ubiquitination.

Abstract Background CSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited. Methods Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR). Results Cryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death. Conclusion CNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.