Search

ABSTRACT Phagocytosis of Mycobacterium tuberculosis (Mtb) followed by its integration into the matured lysosome is critical in the host defense against tuberculosis. How Mtb escapes this immune attack remains elusive. In this study, we unveiled a novel regulatory mechanism by which SIRT7 regulates cytoskeletal remodeling by modulating RAC1 activation. We discovered that SIRT7 expression was significantly reduced in CD14+ monocytes of TB patients. Mtb infection diminished SIRT7 expression by macrophages at both the mRNA and protein levels. SIRT7 deficiency impaired actin cytoskeleton-dependent macrophage phagocytosis, LC3II expression, and bactericidal activity. In a murine tuberculosis model, SIRT7 deficiency detrimentally impacted host resistance to Mtb, while Sirt7 overexpression significantly increased the host defense against Mtb, as determined by bacterial burden and inflammatory–histopathological damage in the lung. Mechanistically, we demonstrated that SIRT7 limits Mtb infection by directly interacting with and activating RAC1, through which cytoskeletal remodeling is modulated. Therefore, we concluded that SIRT7, in its role regulating cytoskeletal remodeling through RAC1, is critical for host responses during Mtb infection and proposes a potential target for tuberculosis treatment.IMPORTANCETuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health issue. Critical to macrophages’ defense against Mtb is phagocytosis, governed by the actin cytoskeleton. Previous research has revealed that Mtb manipulates and disrupts the host’s actin network, though the specific mechanisms have been elusive. Our study identifies a pivotal role for SIRT7 in this context: Mtb infection leads to reduced SIRT7 expression, which, in turn, diminishes RAC1 activation and consequently impairs actin-dependent phagocytosis. The significance of our research is that SIRT7 directly engages with and activates Rac Family Small GTPase 1 (RAC1), thus promoting effective phagocytosis and the elimination of Mtb. This insight into the dynamic between host and pathogen in TB not only broadens our understanding but also opens new avenues for therapeutic development.

Abstract Senescent cell clearance is emerging as a promising strategy for treating age-related diseases. Senolytics are small molecules that promote the clearance of senescent cells; however, senolytics are uncommon and their underlying mechanisms remain largely unknown. Here, we investigated whether genomic instability is a potential target for senolytic. We screened small-molecule kinase inhibitors involved in the DNA damage response (DDR) in Zmpste24 −/− mouse embryonic fibroblasts, a progeroid model characterized with impaired DDR and DNA repair. 4,5,6,7-tetrabromo-2-azabenzamidazole (TBB), which specifically inhibits casein kinase 2 (CK2), was selected and discovered to preferentially trigger apoptosis in Zmpste24 −/− cells. Mechanistically, inhibition of CK2 abolished the phosphorylation of heterochromatin protein 1α (HP1α), which retarded the dynamic HP1α dissociation from repressive histone mark H3K9me3 and its relocalization with γH2AX to DNA damage sites, suggesting that disrupting heterochromatin remodeling in the initiation of DDR accelerates apoptosis in senescent cells. Furthermore, feeding Zmpste24-deficient mice with TBB alleviated progeroid features and extended their lifespan. Our study identified TBB as a new class senolytic compound that can reduce age-related symptoms and prolong lifespan in progeroid mice.

Highlights Digital holography can realize the in situ observation of electrode/electrolyte interface and provide dynamic evolution information of the liquid phase of electrode, which is both efficient and effective in investing the interficial electrochemical mechanism and screening electrolyte additives. Thioacetamide electrolyte additive effectively enhances the electrochemical performance of Zn anode by regulating the interficial ion flux to induce dendrite-free Zn deposition and constructing adsorption molecule layers to inhibit side reactions.

Tailoring the morphologies and optical properties of the 2D and hierarchical nanostructures self-assembled by the π-conjugated molecules is both interesting and challenging. Herein, a series of 2D ribbon-like nanostructures with single or multiple H-aggregated perylene bisimides (PBI) monolayer and hierarchical nanostructures (including straw-like, dumbbell-shaped, and rod-like nanostructures) are fabricated by solution self-assembly of three chiral alanine-decorated PBI. The influence of the solvent’s dissolving capacity, the chirality of alanine, and the preparation methods on the morphologies and optical properties of the nanostructures were extensively studied. It was observed that the hierarchical nanostructures are formed by the reorganization of the 2D ribbon-like nanostructures. The size of the 2D ribbon-like nanostructures and the amount of the hierarchical nanostructures increase with the decrease in the solvent’s dissolving capacity. The small chiral alanine moiety is unable to induce chirality in the nanostructures, owing to its low steric hindrance and the dominant strong π-π stacking interaction of the PBI skeleton. A weaker π-π stacking interaction and better H-aggregated arrangement of the PBI skeleton could reduce the low-wavelength fluorescence intensity. The process of heating, cooling, and aging promotes the formation of H-aggregation in the PBI skeleton. The region of spectral overlap of the PBI solutions increases with the decrease in the dissolving capacity of the solvent and the steric hindrance of the chiral alanine. This study supplies a view to tailor the morphologies and optical properties of the nanostructures, which could be used as sensors and photocatalysts.

Summary: Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3′ UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3′ UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

Abstract Objective To evaluate RSF and Cox models for mortality prediction of hemorrhagic stroke (HS) patients in intensive care unit (ICU). Methods In the training set, the optimal models were selected using five-fold cross-validation and grid search method. In the test set, the bootstrap method was used to validate. The area under the curve(AUC) was used for discrimination, Brier Score (BS) was used for calibration, positive predictive value(PPV), negative predictive value(NPV), and F1 score were combined to compare. Results A total of 2,990 HS patients were included. For predicting the 7-day mortality, the mean AUCs for RSF and Cox regression were 0.875 and 0.761, while the mean BS were 0.083 and 0.108. For predicting the 28-day mortality, the mean AUCs for RSF and Cox regression were 0.794 and 0.649, while the mean BS were 0.129 and 0.174. The mean AUCs of RSF and Cox versus conventional scores for predicting patients’ 7-day mortality were 0.875 (RSF), 0.761 (COX), 0.736 (SAPS II), 0.723 (OASIS), 0.632 (SIRS), and 0.596 (SOFA), respectively. Conclusions RSF provided a better clinical reference than Cox. Creatine, temperature, anion gap and sodium were important variables in both models.

Rock excavation is essentially an unloading behavior, and its mechanical properties are significantly different from those under loading conditions. In response to the current deficiencies in the peak strength prediction of rocks under unloading conditions, this study proposes a hybrid learning model for the intelligent prediction of the unloading strength of rocks using simple parameters in rock unloading tests. The XGBoost technique was used to construct a model, and the PSO-XGBoost hybrid model was developed by employing particle swarm optimization (PSO) to refine the XGBoost parameters for better prediction. In order to verify the validity and accuracy of the proposed hybrid model, 134 rock sample sets containing various common rock types in rock excavation were collected from international and Chinese publications for the purpose of modeling, and the rock unloading strength prediction results were compared with those obtained by the Random Forest (RF) model, the Support Vector Machine (SVM) model, the XGBoost (XGBoost) model, and the Grid Search Method-based XGBoost (GS-XGBoost) model. Meanwhile, five statistical indicators, including the coefficient of determination (R2), mean absolute error (MAE), mean absolute percentage error (MAPE), mean square error (MSE), and root mean square error (RMSE), were calculated to check the acceptability of these models from a quantitative perspective. A review of the comparison results revealed that the proposed PSO-XGBoost hybrid model provides a better performance than the others in predicting rock unloading strength. Finally, the importance of the effect of each input feature on the generalization performance of the hybrid model was assessed. The insights garnered from this research offer a substantial reference for tunnel excavation design and other representative projects.

Developing a flow rate model for the screw feeder and optimizing discharge performance are crucial for achieving automated intelligent precision feeding. This study constructs a mass flow rate model for screw conveyors, considering the coupled structural parameters of the hopper and screw conveyor. The model is developed using single-factor tests and central composite design (CCD) response surface tests and is validated through actual discharge tests. Results indicate that the discharge rate in the hopper–screw conveyor system is primarily influenced by the screw conveyor itself. Among the structural parameters, the hopper inclination angle and the hopper discharge opening length significantly affect the filling coefficient. Validation tests show an average error of 6.8% between the predicted and simulated mass flow rates and 5.0% with the actual mass flow rate, demonstrating the model’s high precision and accuracy.

Abstract Cutaneous wound healing, an integral part for protection of skin barrier, is a complex biological process and intimately associated with keratinocyte migration. However, mechanisms regulating keratinocyte migration in the process of cutaneous wound repair remain largely unknown. Here, we found that N-acetyltransferase 10 (NAT10) is essential for cutaneous wound repair in an in vivo skin wound healing model—a significant delay of wound repair in Nat10 haploinsufficient mice and a remarkable inhibition of keratinocyte migration by NAT10 knockdown in an in vitro keratinocyte migration model. We further demonstrate that loss of NAT10 expression attenuates the wound-induced IL-6/IL-8 expression through inhibiting NF-κB/p65 activity in keratinocytes. By deeply digging, silencing NAT10 compromises the level of nuclear p65 by facilitating its poly-ubiquitination, thus accelerates its degradation in the nucleus. Notably, we detected a strong positive correlation between the expression of NAT10 and relevant NF-kB/p65-IL6 signaling activity in mouse wound skin tissues. Overall, our study reveals an important role of NAT10 on cutaneous wound repair by potentiating NF-κB/p65-IL-6/8-STAT3 signaling. Targeting NAT10 might be a potential strategy for the treatment of skin wound dysfunctions and related diseases.

Abstract In the latest geophysical survey crossing the Ninety East Ridge of the Indian Ocean, a new method was employed to perform proportional double seismic source excitation and synchronously receive signals from the sea surface and the seabed. The two seismic sources used for excitation were two sets of gun arrays with different energies and dominant frequencies, a G gun array and a Bolt gun array. The G gun array consisted of 3 G.II guns with a total capacity of 450 in3 and a dominant frequency of 20–100 Hz. The Bolt gun array consisted of 4 Bolt 1500LL air guns with a total capacity of 6000 in3 and a dominant frequency of 10–40 Hz. The seismic receiving system comprised a 480-channel seismic streamer towed from the sea surface and 21 ocean bottom seismometers (OBS). During offshore operations, the integrated navigation system produced equidistant trigger signals at an interval of 50 m. The trigger signals were distributed to the G gun array and Bolt gun array at a ratio of 3:1 after passing through a pulse signal proportional distributor. The two sets of gun arrays fired alternatingly at a given ratio. The receiving equipment on the sea surface and seabed simultaneously received the seismic signals excited by the two sets of gun arrays. After targeted data processing, in addition to the seismic profile generated by the conventional G gun seismic source, the deep seismic profile generated by the Bolt gun seismic source and the survey profile of the active-source OBS were obtained simultaneously. The penetration depths of the three sets of profiles reach 2 km, 6 km, and 30 km, respectively, greatly improving the efficiency of offshore deep-sea seismic surveys.

Abstract Background Inferior vena cava tumor thrombus (IVCTT) invading the IVC wall majorly affects the surgical method choice and prognosis in renal tumors. Enhanced multiparameteric MRI plays an important role in preoperative evaluation. In this work, an MRI-based diagnostic model for IVCTT was established so as to guide the preoperative decisions. Methods Preoperative MR images of 165 cases of renal tumors with IVCTT were retrospectively analyzed, and imaging indicators were analyzed, including IVCTT morphology and Mayo grade, IVCTT diameter measurements, bland thrombosis, primary MRI-based diagnosis of renal tumor, and involvement of contralateral renal vein. The indicators were analyzed based on intraoperative performance and resection scope of the IVC wall. Multivariate logistic regression analysis was used to establish the diagnostic model. Results The morphological classification of the IVCTT, primary MRI-based diagnosis of renal tumors, maximum transverse diameter of IVCTT, and length of the bland thrombus were the main indexes predicting IVC wall invasion. The MRI-based diagnostic model established according to these indexes had good diagnostic efficiency. The prediction probability of 0.61 was set as the cutoff value. The area under the curve of the test set was 0.88, sensitivity was 0.79, specificity was 0.85, and prediction accuracy was 0.79 under the optimal cutoff value. Conclusion The preoperative MRI-based diagnostic model could reliably predict IVC wall invasion, which is helpful for better prediction of IVC-associated surgical operations.

Abstract Background Alexithymia is common and causes serious harm to people living with HIV/AIDS. Therefore, this study aimed to examine its prevalence and associated factors among people living with HIV/AIDS in China. Methods A cross-sectional study was conducted in two designated AIDS medical institutions in Harbin, China between January and December 2019. In total, 767 participants completed the 20-item Toronto Alexithymia Scale, the University of California Los Angeles Loneliness short-form, the Patient Health Questionnaire-9, the HIV Treatment Regimen Fatigue Scale, and the Alcohol Use Disorders Identification Test‐Consumption. The participants responded to several questions regarding their demographic characteristics, life satisfaction, disease-related economic burden, and their antiretroviral therapy (ART) side effects. Multivariate logistic regression assessed the relationship between alexithymia and associated factors. Odds ratios (OR) and 95% confidence intervals (CI) for OR were calculated. Results Approximately 36.1% of the participants were classified as having alexithymia. After adjusted age and education, the logistic regression model indicated that disease-related economic burden (OR = 1.477, 95% CI = 1.155–1.888), ART side effects (OR = 1.249, 95% CI = 1.001–1.559), loneliness (OR = 1.166, 95% CI = 1.101–1.236), and HIV treatment regimen fatigue (OR = 1.028, 95% CI = 1.017–1.039) were positively associated with alexithymia. Conclusions The mental health problems of people living with HIV/AIDS are essential to understand and deserve attention. Disease-related economic burdens are major associated factors. Multiple actors should provide better services and guarantees for patients.

One popular method of obtaining the acoustic parameters of seabed sediments is by measuring the sound velocity of sediment samples in a laboratory. However, the effects of environmental variation and physical perturbation on acoustic properties are typically neglected in the application of such measured acoustic parameters. In this study, sediment samples were collected from the Huanghai and Bohai seas to measure sound velocity both on the deck and in the laboratory using a digital sonic measuring system. Additionally, sediment compositions, physical and mechanical properties and microstructures were determined. Sound velocity comparisons between on-deck and laboratory measurements indicate that laboratory-measured velocities are generally higher than those measured on the deck, with differences ranging from 1.45 m/s to 130.05 m/s, due to the water loss and densification of sedimentary particles in laboratory settings. The discrepancy of sound velocities measured in the laboratory and on the deck also differ based on the types of sediments sampled. Overall, the discrepancy increases with measurement frequency, increasing average grain diameter and sand content, as well as with decreasing clay content.

Based on data on the shear wave speed and physical properties of the shallow sediment samples collected in the northwest South China Sea, the hyperparameter selection and contribution of the characteristic factors of the machine learning model for predicting the shear wave speed of seafloor sediments were studied using the eXtreme Gradient Boosting (XGBoost) algorithm. An XGBoost model for predicting the shear wave speed of seafloor sediments was established based on four physical parameters of the sediments: porosity (n), water content (w), density (ρ), and average grain size (MZ). The result reveals that: (1) The shear wave speed has a good correlation with n, w, ρ, and MZ, and their Pearson correlation coefficients are all above 0.75, indicating that they can be used as the suitable characteristic parameters for predicting the shear wave speed based on the XGBoost model; (2) When the number of weak learners (n_estimators) is 115 and the maximum depth of the tree (max_depth) is 6, the XGBoost model has a very high goodness of fit (R2) of the validation data of 0.914, the very low mean absolute error (MAE) and mean absolute percentage error (MAPE) of the predicted shear wave speed are 3.366 m/s and 9.90%, respectively; (3) Compared with grain-shearing (GS) model and single- and dual-parameter regression equation prediction models, the XGBoost model for the shear wave speed of seafloor sediments has higher fitting goodness and lower prediction error.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.

Abstract Cerebral ischemic stroke is a leading cause of morbidity and mortality globally. However, the mechanisms underlying ischemic stroke injury remain poorly understood. Here, it is found that deficiency of the ubiquitin‐specific protease USP25 significantly aggravate ischemic stroke injury in mice. USP25 has no impact on neuronal death under hypoxic conditions, but reduced ischemic stroke‐induced neuronal loss and neurological deficits by inhibiting microglia‐mediated neuroinflammation. Mechanistically, USP25 restricts the activation of NF‐κB and MAPK signaling by regulating TAB2. As a deubiquitinating enzyme, USP25 removeds K63‐specific polyubiquitin chains from TAB2. AAV9‐mediated TAB2 knockdown ameliorates ischemic stroke injury and abolishes the effect of USP25 deletion. In both mouse and human brains, USP25 is markedly upregulated in microglia in the ischemic penumbra, implying a clinical relevance of USP25 in ischemic stroke. Collectively, USP25 is identified as a critical inhibitor of ischemic stroke injury and this data suggest USP25 may serve as a therapeutic target for ischemic stroke.

Abstract Background Inflammation plays an important role in the development of acute kidney injury (AKI). However, there are few studies exploring the prognostic influence of C-reactive protein to albumin ratio (CAR) among AKI patients. In this study, we investigated whether CAR could be a useful marker to predict the mortality of AKI. Methods A total of 358 AKI patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. C-reactive protein (CRP) and albumin were measured at ICU admission. The clinical outcome was 365-day mortality. Cox proportional hazards model and Kaplan-Meier survival analysis were conducted to evaluate the association between CAR and outcome. Results Compared with patients in the survival group, nonsurvivors had higher CAR levels. The area under the receiver operating characteristic (ROC) curve of CAR was higher than that of CRP and albumin for mortality (0.64 vs. 0.63, 0.59, respectively). The cut-off point of CAR for mortality was 7.23. In Cox proportional-hazard regression analysis, CAR (hazards ratio (HR) =2.04, 95% confidence interval (CI) =1.47-2.85, p

Abstract Background Patients with normal preoperative serum albumin still suffer from a significant reduction in serum albumin after major abdominal surgery. The current study aims to explore the predictive value of ∆ALB for AL in patients with normal serum albumin and examine whether there is a gender difference in the prediction of AL. Methods Medical reports of consecutive patients undergoing elective sphincter-preserving rectal surgery between July 2010 and June 2016 were reviewed. Receiver operating characteristic (ROC) analysis was adopted to examine the predictive ability of ∆ALB and determine the cut-off value according to the Youden index. The logistic regression model was performed identify independent risk factors for AL. Results Out of the 499 eligible patients, 40 experienced AL. Results of the ROC analyses showed that ΔALB displayed a significant predictive value for females, and the AUC value was 0.675 (P = 0.024), with a sensitivity of 93%. In male patients, the AUC was 0.575 (P = 0.22), but did not reach a significant level. In the multivariate analysis, ∆ALB ≥ 27.2% and low tumor location prove to be independent risk factors for AL in female patients. Conclusions The current study suggested that there may be a gender difference in the prediction of AL and ∆ ALB can serve as a potential predictive biomarker for AL in females. A cut-off value of the relative decline in serum albumin can help predict AL in female patients as early as postoperative day 2. Although our study needs further external validation, our findings may provide an earlier, easier and cheaper biomarker for the detection of AL.

Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1 +/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

A truncating variant of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), a lipid droplet -associated protein, associates with lower risk of chronic liver disease. Here the authors identify a phosphorylation site in 17β-HSD13 which promotes lipolysis, and report that a knock-in mouse with a 17β-HSD13 mutant defective for phosphorylation is more susceptible to nonalcoholic steatohepatitis.

Abstract Background CCN6 is a matricellular protein that critically regulates the tumourigenesis and progression of breast cancer. Although the tumour‐suppressive function of CCN6 has been extensively studied, molecular mechanisms regulating protein levels of CCN6 remain largely unclear. This study aims to investigate the regulation of CCN6 by ubiquitination and deubiquitinating enzymes (DUBs) in breast cancer. Methods A screening assay was performed to identify OTUB1 as the DUB for CCN6. Various biochemical methods were applied to elucidate the molecular mechanism of OTUB1 in the regulation of CCN6. The role of OTUB1–CCN6 interaction in breast cancer was studied with cell experiments and the allograft model. The correlation of OTUB1 and CCN6 in human breast cancer was determined by immunohistochemistry and Western blot. Results We found that CCN6 protein levels were controlled by the ubiquitin–proteasome system. The K48 ubiquitination and degradation of CCN6 was inhibited by OTUB1, which directly interacted with CCN6 through its linker domain. Furthermore, OTUB1 inhibited the ubiquitination of CCN6 in a non‐canonical manner. Deletion of OTUB1, concomitant with reduced CCN6 abundance, increased the migration, proliferation and viability of breast cancer cells. Supplementation of CCN6 abolished the effect of OTUB1 deletion on breast cancer. Importantly, OTUB1 expression was downregulated in human breast cancer and positively correlated with CCN6 levels. Conclusion This study identified OTUB1 as a novel regulator of CCN6 in breast cancer.

ObjectiveDuring the past decade, the concept of complete mesocolic excision (CME) has been developed in an attempt to minimize recurrence for right-sided colon cancer. This study aims to compare outcomes of robotic versus laparoscopic right hemicolectomy with CME for right-sided colon cancer.MethodsWe performed a retrospective multicenter propensity score matching study. From July 2016 to July 2021, 382 consecutive patients from different Chinese surgical departments were available for inclusion out of an initial cohort of 412, who underwent robotic or laparoscopic right hemicolectomy with CME. Data of all patients were retrospectively collected and reviewed. Of these, 149 cases were performed by a robotic approach, while the other 233 cases were done by laparoscopy. Propensity score matching was applied at a ratio of 1:1 to compare perioperative, pathologic, and oncologic outcomes between the robotic and the laparoscopic groups (n = 142).ResultsBefore propensity score matching, there were no statistical differences regarding the sex, history of abdominal surgery, body mass index (BMI), American Joint Committee on Cancer (AJCC) staging system, tumor location, and center between groups (p > 0.05), while a significant difference was observed regarding age (p = 0.029). After matching, two comparable groups of 142 cases were obtained with equivalent patient characteristics (p > 0.05). Blood loss, time to oral intake, return of bowel function, length of stay, and complications were not different between groups (p > 0.05). The robotic group showed a significantly lower conversion rate (0% vs. 4.2%, p = 0.03), but a longer operative time (200.9 min vs. 182.3 min, p < 0.001) and a higher total hospital cost (85,016 RMB vs. 58,266 RMB, p < 0.001) compared with the laparoscopic group. The number of harvested lymph nodes was comparable (20.4 vs. 20.5, p = 0.861). Incidence of complications, mortality, and pathologic outcomes were similar between groups (p > 0.05). The 2-year disease-free survival rates were 84.9% and 87.1% (p = 0.679), and the overall survival rates between groups were 83.8% and 80.7% (p = 0.943).ConclusionDespite the limitations of a retrospective analysis, the outcomes of robotic right hemicolectomy with CME were comparable to the laparoscopic procedures with fewer conversions to open surgery. More clinical advantages of the robotic surgery system need to be further confirmed by well-conducted randomized clinical trials with large cohorts of patients.

Graphene and its derivatives have been confirmed to be among the best fillers for rubber due to their excellent properties, such as high mechanical strength, improved interface interaction, and strain-induced crystallization capabilities. Graphene rubber materials can be widely used in tires, shoes, high-barrier conductive seals, electromagnetic shielding seals, shock absorbers, etc. In order to reduce the graphene loading and endow more desirable functions to rubber materials, graphene-based hybrid fillers are extensively employed, which can effectively enhance the performance of rubber composites. This review briefly summarizes the recent research on rubber composites with graphene-based hybrid fillers consisting of carbon black, silica, carbon nanotubes, metal oxide, and one-dimensional nanowires. The preparation methods, performance improvements, and applications of different graphene-based hybrid fillers/rubber composites have been investigated. This study also focuses on methods that can ensure the effectiveness of graphene hybrid fillers in reinforcing rubber composites. Furthermore, the enhanced mechanism of graphene- and graphene derivative-based hybrid fillers in rubber composites is investigated to provide a foundation for future studies.

This study focuses on the inversion of sub-bottom profile (SBP) data in the northern South China Sea using an empirical relationship derived from sediment acoustic data. The sub-bottom profile is primarily utilized for various marine applications, such as geological mapping and resource exploration. In this research, we present a study conducted in the northern slope canyon of the South China Sea. Firstly, we obtained the seabed reflection coefficient from sub-bottom profiles obtained by the autonomous underwater vehicle (AUV) detection system. Secondly, we utilized the acoustic empirical relationship in the northern South China Sea to establish relationship equations between the seabed reflection coefficient and the porosity, density, and average particle size of the sediment at a main frequency of 4 kHz (the AUV shallow profile main frequency). Then, using these equations, we were able to invert the physical parameters such as porosity, density, and average particle size of the seabed surface sediments. Finally, the inverted results are compared and analyzed by using the sediment samples test data. The overall deviation rate of the inverted physical parameters is within the range of ±10% when compared. The inverted results closely match the measured values, accurately reflecting the dynamic changes in the physical properties of seabed surface sediments. Notably, the average grain size is a direct indicator of the sediment particles size with smaller particles found in deeper water. The variation characteristics of sediment physical parameters align well with the variation of sediment types in the canyon, which is consistent with changes in the water depth, topography, and hydrodynamic conditions of the area. This further demonstrates the reliability of the inversion results.

Based on the data of the acoustic and physical properties of seafloor sediments obtained on the continental shelf area of the East China Sea (ECS), prediction equations of the sediment sound speed based on single and dual parameters were established, and the correlation of the sound speed with physical parameters was discussed. The results show that the sediment sound speed (c) is strongly correlated with water content (w), density (ρ), void ratio (e), mean grain size (Mz) and median grain size (Md), and the coefficient of determination R2 of the empirical regression equation is generally greater than 0.80, while the empirical regression equation coefficient of determination R2 of the compression coefficient (a) and compression modulus (E) are slightly lower, with 0.79 and 0.73, respectively. The coefficients of determination of the dual parameter regression equations between sediment sound speed with physical property parameters are generally higher than those of the single parameter equations, which are all higher than 0.90 indicating better prediction performance. The sensitivity of the physical parameters to the sound speed was analyzed, and the result shows that the sequence of sensitivity from high to low influence on sediment sound speed is void ratio, density, compressibility coefficient, median grain size and mean grain size. The prediction equations established in this study are a good extension and supplement to marine geoacoustic models and is of great significance for obtaining the acoustic properties of the seafloor sediments on the shelf of the East China Sea.

Abstract. Background:. Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy. Methods:. Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020. Results:. A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t = 4.694, P

We examine the impact of institutional investor cross holding (IICH) on the cost of equity. The findings suggest that IICH firms have a lower cost of equity than non-IICH firms. We find that it is mainly IICH firms in the same industry that successfully reduce their cost of equity. Additional results indicate that IICH investors are more successful at reducing idiosyncratic risk and informational risk and can improve firm performance and governance when they cross hold firms in the same industry. We also find that IICHs with longer tenure, higher competition, and greater analyst following are more successful at reducing the cost of equity.

Preserving Tibet’s unique history and cultural heritage relies on the sustainability of the Tibetan croplands, which are characterized by highland barley, the only cereal crop cultivated over 4000 m above sea level. Yet it is unknown how these croplands will respond to climate change. Here, using yield statistics from 1985 to 2015, we found that the impact of temperature anomalies on the Tibetan crop yield shifted from nonsignificant (P > 0.10) in the 1980s and 1990s to significantly negative (P

Introduction: Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21.Methods: In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo. Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1, 37 and 86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich Enzyme-linked immunosorbent assay. Blood samples were collected on day 0, 30, 65, and 87 for blood and blood biochemical tests. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days).Results: The average AUC(0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 μg h/L, and the average AUC(0–24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 μg h/L, respectively. Analysis of the blood and blood biochemical indexes showed that prothrombin time and AST content in the high-dose FGF-21 group increased. However, no significant changes in other blood and blood biochemical indexes were observed. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys.Discussion: Our results have guiding significance for the preclinical research and clinical use of FGF-21.

Seafloor sediment acoustics is a burgeoning field of marine scientific research. In situ measurement technique is a key technique for investigating sediment acoustic properties. Establishing a correlation between in situ acoustic parameters and physical parameters is of great scientific significance for advancing the theory of seafloor acoustics. This study employed an in situ sediment acoustic measurement system to measure the sound speed and attenuation of various types of sediment, such as sand, silty sand, silty clay, and clayey silt. The results showed that in situ sound speed and attenuation were strongly curvilinear correlated with physical properties, such as wet bulk density, porosity, and mean grain size. Empirical regression relationships between in situ acoustic properties and physical properties were derived. These findings supplement the in situ measurement data of acoustic properties of seafloor sediments, compensate for the lack of an empirical relationship of in situ attenuation in previous studies, and broaden the predicting theory and method of the acoustic properties of seafloor sediments.

Background & Aims: CREB-H is a key liver-enriched transcription factor governing lipid metabolism. Additional targets of CREB-H remain to be identified and characterized. Here, we identified a novel fasting- and CREB-H–induced (FACI) protein that inhibits intestinal lipid absorption and alleviates diet-induced obesity in mice. Methods: FACI was identified by reanalysis of existing transcriptomic data. Faci-/- mice were generated by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated genome engineering. RNA sequencing was performed to identify differentially expressed genes in Faci-/- mice. Lipid accumulation in the villi was assessed by triglyceride measurement and Oil red O staining. In vitro fatty acid uptake assay was performed to verify in vivo findings. Results: FACI expression was enriched in liver and intestine. FACI is a phospholipid-binding protein that localizes to plasma membrane and recycling endosomes. Hepatic transcription of Faci was regulated by not only CREB-H, but also nutrient-responsive transcription factors sterol regulatory element-binding protein 1 (SREBP1), hepatocyte nuclear factor 4α (HNF4α), peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), and CREB, as well as fasting-related cyclic adenosine monophosphate (cAMP) signaling. Genetic knockout of Faci in mice showed an increase in intestinal fat absorption. In accordance with this, Faci deficiency aggravated high-fat diet–induced obesity, hyperlipidemia, steatosis, and other obesity-related metabolic dysfunction in mice. Conclusions: FACI is a novel CREB-H–induced protein. Genetic disruption of Faci in mice showed its inhibitory effect on fat absorption and obesity. Our findings shed light on a new target of CREB-H implicated in lipid homeostasis.

Tang et al. propose the use of a small molecule compound D6 to treat EGFRTKI resistant tumors. The authors demonstrate potent and selective inhibition of NSCLC with T790M-mediated EGFR-TKI resistance through inhibiting HSP90-mediated protein–protein interaction.

BackgroundIn-hospital mortality, prolonged length of stay (LOS), and 30-day readmission are common outcomes in the intensive care unit (ICU). Traditional scoring systems and machine learning models for predicting these outcomes usually ignore the characteristics of ICU data, which are time-series forms. We aimed to use time-series deep learning models with the selective combination of three widely used scoring systems to predict these outcomes.Materials and methodsA retrospective cohort study was conducted on 40,083 patients in ICU from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Three deep learning models, namely, recurrent neural network (RNN), gated recurrent unit (GRU), and long short-term memory (LSTM) with attention mechanisms, were trained for the prediction of in-hospital mortality, prolonged LOS, and 30-day readmission with variables collected during the initial 24 h after ICU admission or the last 24 h before discharge. The inclusion of variables was based on three widely used scoring systems, namely, APACHE II, SOFA, and SAPS II, and the predictors consisted of time-series vital signs, laboratory tests, medication, and procedures. The patients were randomly divided into a training set (80%) and a test set (20%), which were used for model development and model evaluation, respectively. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and Brier scores were used to evaluate model performance. Variable significance was identified through attention mechanisms.ResultsA total of 33 variables for 40,083 patients were enrolled for mortality and prolonged LOS prediction and 36,180 for readmission prediction. The rates of occurrence of the three outcomes were 9.74%, 27.54%, and 11.79%, respectively. In each of the three outcomes, the performance of RNN, GRU, and LSTM did not differ greatly. Mortality prediction models, prolonged LOS prediction models, and readmission prediction models achieved AUCs of 0.870 ± 0.001, 0.765 ± 0.003, and 0.635 ± 0.018, respectively. The top significant variables co-selected by the three deep learning models were Glasgow Coma Scale (GCS), age, blood urea nitrogen, and norepinephrine for mortality; GCS, invasive ventilation, and blood urea nitrogen for prolonged LOS; and blood urea nitrogen, GCS, and ethnicity for readmission.ConclusionThe prognostic prediction models established in our study achieved good performance in predicting common outcomes of patients in ICU, especially in mortality prediction. In addition, GCS and blood urea nitrogen were identified as the most important factors strongly associated with adverse ICU events.

The classification of marine sediment based on acoustic data is crucial for various applications such as marine resource exploitation, marine engineering construction, and marine ecological environment maintenance. It serves as a valuable alternative to limited geological sampling. However, the accuracy of sediment classification is limited due to constraints in acoustic data detection methods, data quality, and classification techniques. To address this issue, this study proposes an automatic classification method for marine sediment using an improved U-convolutional neural network and K-means clustering algorithm. In the coding part, a spatial pyramid pool layer is introduced to fuse low-dimensional feature data of different scales with the features of each level of the corresponding coding layer. This fusion method enhances the accuracy of the constructed relationship between the physical property parameters of the seabed bottom. The K-means clustering algorithm is optimized through selecting the point at the density center as the initial clustering center during the initial clustering center selection stage. This approach solves the sensitivity problem of the initial clustering center of K-means, improves the edge extraction effect of sediment types, and enhances the classification accuracy of sediment types. To validate the proposed method, an application test is conducted in the Northern Slope area of the South China Sea. The mean grain size of sediments in the study area is predicted using the improved U-Net neural network and the seafloor reflection intensity of the sub-bottom profile. Compared to the standard U-Net network results, the mean grain size prediction results show an increase of 4.9% and 2.8%, respectively. The sediment with the predicted mean grain size is then classified using the K-means clustering algorithm, resulting in the division of five sediment types: gravelly sand, sand, silty sand, sandy silt, and clayey silt. These classifications align well with the South China Sea sediment type map. The findings of this study not only provide an important supplement to existing marine sediment classification methods but also contribute significantly to understanding the sedimentary environment and processes in the Northern Slope of the South China Sea.

The inversion method based on the reflection loss-grazing angle curve is an effective tool to obtain local underwater acoustic parameters. Because geoacoustic parameters vary in sensitivity to grazing angle, it is difficult to get accurate results in geoacoustic parameter inversion based on small-grazing-angle data in shallow water. In addition, the normal-mode model commonly used in geoacoustic parameter inversion fails to meet the needs of accurate local sound field simulation as the influence of the secant integral is ignored. To solve these problems, an acoustic data acquisition scheme was rationally designed based on a sparker source, a fixed vertical array, and ship drifting with the swell, which could balance the trade-off among signal transmission efficiency and signal stability, and the actual local acoustic data at low-to-mid frequencies were acquired at wide grazing angles in the South Yellow Sea area. Furthermore, the bottom reflection coefficients (bottom reflection losses) corresponding to different grazing angles were calculated based on the wavenumber integration method. The local seafloor sediment parameters were then estimated using the genetic algorithm and the bottom reflection loss curve with wide grazing angles, obtaining more accurate local acoustic information. The seafloor acoustic velocity inverted is cp=1659 m/s and the sound attenuation is αp=0.656 dB/λ in the South Yellow Sea. Relevant experimental results indicate that the method described in this study is feasible for local inversion of geoacoustic parameters for seafloor sediments. Compared with conventional large-scale inversion methods, in areas where there are significant changes in the seabed sediment level, this method can obtain more accurate local acoustic features within small-scale areas.

The combination of intermittent fasting and chemotherapy can improve the response to treatment. Here, the authors show that SIRT7 activation is required to inactivate Akt during intermittent fasting and that the combination of intermittent fasting and inhibitors that block the Erk pathway can improve efficacy of treatment.

AbstractSince the safety and stability of the original tunnel structure are easily affected by the adjacent foundation pit excavation, it is strongly necessary to study the deformation evolution of tunnels during the adjacent foundation pit excavation. With regard to the two cases that tunnel is adjacently located at the right and bottom of foundation pit, the influence of different supporting methods, including pile support, bolt support, pile-bolt support, and shotcrete-bolt support, on the tunnel stability was investigated on the basis of the whole excavation process numerical simulation of deep foundation pit for determining the best foundation pit supporting beneficial to the stability of adjacent tunnel. The results indicate that both one-step excavation and multistep excavation have great influences on the displacement of adjacent tunnels, wherein the influences on the tunnel located at the right of foundation pit are greater than those at the bottom of foundation pit. Multistep excavation is recommended for the foundation pit adjacent to shallow tunnel. In the case of the tunnel located on the bottom of the foundation pit, the maximum stress generated around the tunnel is small, the maximum stress area is limited, and the displacement of tunnel monitoring points is also small. For the tunnel located at the right of the foundation pit, the pile-bolt supporting can effectively limit the displacement of soil between the tunnel and the foundation pit, reduce the maximum stress and the maximum stress distribution area, and effectively control the tunnel displacement.

The health system has encountered great challenges since the COVID-19 outbreak, volunteers are urgently needed in every situation during this crisis. The current study aimed to explore the relationship between empathy and COVID-19 volunteer behavior, along with the moderating role of COVID-19 risk perception in the above relationship. The cross-sectional survey was conducted online using Wenjuanxing from February 12th to March 16th, 2021, in Jiangsu, China. A total of 1,486 participants completed the Toronto Empathy COVID-19 volunteer behavior and COVID-19 risk perception questionnaires. The SPSS PROCESS macro was yielded to examine the moderating effect. Simple slopes analysis was conducted to detect the associations between empathy and COVID-19 volunteer behavior at three levels of the COVID-19 risk perception. The Johnson-Neyman (J-N) technique was used to calculate where the moderating effect is significance. Results showed that empathy was positively related with COVID-19 volunteer behavior (β= 0.080, p < 0.001). COVID-19 risk perception played a moderation effect on association between empathy and COVID-19 volunteer behavior (β = −0.005, p < 0.001), the greater the levels of COVID-19 risk perception, the weaker the associations between empathy and COVID-19 volunteer behavior. The J-N test showed the association between empathy and COVID-19 volunteer behavior was no longer significant when values of COVID-19 risk perception was >10.71. Current findings could enlighten researchers and policy makers, that fostering volunteerism among public during crisis situation through arousing more empathy and reducing unnecessary risk perception of the public.

Abstract Based on the seafloor reflection coefficient obtained from autonomous underwater vehicle (AUV) sub-bottom profile survey data of the northern slope of the South China Sea, combined with the sample test data of seafloor surface sediments, we use the Biot–Stoll model to establish the equations relating the seafloor reflection coefficient to the porosity, density, and mean grain size of the sediments at the dominant frequency of 5 kHz (the dominant frequency of the AUV sub-bottom profiler). The physical property parameters such as the porosity, density, and mean grain size of seafloor surface sediments are further inverted. Comparison of inversion results with measured results shows that the overall deviation ratios of the inverted mean grain size, porosity, and density of the surface sediments are in the ranges of − 13.56 to 14.44%, − 6.15 to 8.06%, and − 10.85 to 0.46%, respectively. Among them, the mean grain size directly reflects the size of seafloor sediment particles, and the particles are finer in deeper water. Overall, the inversion results are basically consistent with the measured values and thus can well reflect the variation characteristics of the physical properties of seafloor surface sediments.

Cellular senescence is the occurrence of irreversible cell cycle arrest resulting from accumulated DNA damage and the loss of proteostasis over time. Senescent cells contribute to age-related diseases and aging itself. Therefore, the targeted elimination of senescent cells may be beneficial for long-term human health in general. In this review, we summarize three key areas of recent research into the clearance of senescent cells, including senolysis via senolytic drugs, immune-based senescent cell clearance, and neutralization of the senescence-associated secretory phenotype (SASP). Therapeutic strategies for the targeted clearance of senescent cells are being developed at a rapid pace, with some already undergoing clinical trials in humans. In the future, advances in the targeted clearance of senescent cells will undoubtedly yield further beneficial ways to improve human health during aging and increase human longevity.

Abstract Background The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here, we identified hyperactivated mitophagy is essential for sorafenib resistance, and the mitophagy core regulator gene ATAD3A (ATPase family AAA domain containing 3A) was down regulated in hypoxia induced resistant HCC cells. Blocking mitophagy may restore the sorafenib sensitivity of these cells and provide a new treatment strategy for HCC patients. Methods Hypoxia induced sorafenib resistant cancer cells were established by culturing under 1% O2 with increasing drug treatment. RNA sequencing was conducted in transfecting LM3 cells with sh-ATAD3A lentivirus. Subsequent mechanistic studies were performed in HCC cell lines by manipulating ATAD3A expression isogenically where we evaluated drug sensitivity, molecular signaling events. In vivo study, we investigated the combined treatment effect of sorafenib and miR-210-5P antagomir. Results We found a hyperactivated mitophagy regulating by ATAD3A-PINK1/PARKIN axis in hypoxia induced sorafenib resistant HCC cells. Gain- and loss- of ATAD3A were related to hypoxia-induced mitophagy and sorafenib resistance. In addition, ATAD3A is a functional target of miR-210-5p and its oncogenic functions are likely mediated by increased miR-210-5P expression. miR-210-5P was upregulated under hypoxia and participated in regulating sorafenib resistance. In vivo xenograft assay showed that miR-210-5P antagomir combined with sorafenib abrogated the tumorigenic effect of ATAD3A down-regulation in mice. Conclusions Loss of ATAD3A hyperactivates mitophagy which is a core event in hypoxia induced sorafenib resistance in HCC cells. Targeting miR-210-5P-ATAD3A axis is a novel therapeutic target for sorafenib-resistant HCC.

Abstract Background Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa. Results In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes. Conclusions Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in non-regenerative organisms via small RNA mimics based therapies.

BackgroundThe Chinese health system has long been committed to eliminating inequalities in health services utilization. However, few studies have analyzed or measured these inequalities in economically underdeveloped regions in China.MethodsA total of 6,627 respondents from 3,000 households in Heilongjiang Province were extracted from the Sixth National Health Services Survey. We measured horizontal inequity in both 2-week outpatient rate and annual inpatient rate, and then identified the factors contributing to inequality.ResultsThe horizontal inequity indices of the 2-week outpatient and annual impatient rates in Heilongjiang Province were 0.0586 and 0.1276, respectively. Household income, health status, place of residence, basic medical insurance, and commercial health insurance were found to be the main factors affecting inequality in health services utilization. The contributions of household income to these two indices were 184.03 and 253.47%, respectively. Health status factors, including suffering from chronic disease, limitations in daily activities, and poor self-rated health, played positive roles in reducing inequality in these two indices. The contributions of place of residence to these two indices were 27.21 and −28.45%, respectively. Urban Employee Basic Medical Insurance made a pro-rich contribution to these two indices: 56.25 and 81.48%, respectively. Urban and Rural Resident Basic Medical Insurance, Urban Resident Basic Medical Insurance, New Rural Cooperative Medical Scheme, and other basic medical insurance made a pro-poor contribution to these two indices: −73.51 and −54.87%, respectively. Commercial health insurance made a pro-rich contribution to these two indices: 20.79 and 7.40%, respectively. Meanwhile, critical illness insurance made a slightly pro-poor contribution to these two indices: −4.60 and −0.90%, respectively.ConclusionsThe findings showed that the “equal treatment in equal need” principle was not met in the health services utilization context in Heilongjiang Province. To address this issue, the government could make policy changes to protect low-income populations from underused health services, and work to improve basic medical insurance, critical illness insurance, and social security systems.

Previous work suggested that histone demethylase JMJD3 is detrimental to somatic cell reprogramming. Here, the authors show that while JMJD3 has a context-independent detrimental effect on early stages of reprogramming, during late stages it activates epithelial and pluripotency genes together with Klf4.

The bromodomain containing protein BRD9 has been reported to regulate chromatin remodeling and transcription. Here the authors reveal a role for BRD9 in homologous recombination by facilitating RAD51–RAD54 interaction.

Abstract Background China’s fragmentation of social health insurance schemes has become a key obstacle that hampers equal access to health care and financial protection. This study aims to explores if the policy intervention Urban and Rural Residents Basic Medical Insurance (URRBMI) scheme, which integrates Urban Resident Basic Medical Insurance (URBMI) and New Rural Cooperative Medical Scheme (NCMS), can curb the persistent inequity of catastrophic health expenditure (CHE) and further analyses the determinants causing inequity. Methods Data were derived from the Fifth National Health Service Survey (NHSS). A total of 11,104 households covered by URRBMI and 20,590 households covered by URBMI or NCMS were selected to analyze CHE and the impoverishment rate from medical expenses. Moreover, the decomposition method based on a probit model was employed to analyse factors contributing CHE inequity. Results The overall incidence of CHE under integrated insurance scheme was 15.53%, about 1.10% higher than the non-integrated scheme; however, the intensity of CHE and impoverishment among the poorest was improved. Although CHE was still concentrated among the poor under URRBMI (CI = -0.53), it showed 28.38% lower in the degree of inequity. For URRBMI households, due to the promotion of integration reform to the utilization of rural residents’ better health services, the factor of residence (24.41%) turns out to be a major factor in increasing inequity, the factor of households with hospitalized members (− 84.53%) played a positive role in reducing inequity and factors related to social economic status also contributed significantly in increasing inequity. Conclusion The progress made in the integrated URRBMI on CHE equity deserves recognition, even though it did not reduce the overall CHE or the impoverishment rate effectively. Therefore, for enhanced equity, more targeted solutions should be considered, such as promoting more precise insurance intervention for the most vulnerable population and including costly diseases suitable for outpatient treatment into benefit packages. Additionally, comprehensive strategies such as favourable targeted benefit packages or job creation are required for the disadvantaged.

The influence of foundation pit excavation on deformation and stability of the supporting structure of underlying adjacent existing tunnel is a comprehensive geotechnical engineering problem, including unloading effect of foundation pit excavation and the coupling effect of deformation of the tunnel surrounding rock and supporting structure. Using numerical calculation methods, this paper changes the different excavation depths and widths of foundation pit and discusses the evolution law about force and deformation of tunnel supporting structure, and the changing relationship of the axial force of tunnel anchor with the distance between foundation pit and tunnel is obtained and compares the influence of different excavation way of foundation pit on the axial force of anchor rod near the existing tunnel. It is found that with the increase of distance between foundation pit and tunnel, the axial force of anchor rod at the top of tunnel under the foundation pit entirely symbolizes a trend of increases first and then decreases, the axial force of the leftmost anchor rod changes from pressure to tension, then decreases gradually. When the foundation pit depth increases, the axial force of the anchor rod at the top of the tunnel increases, the axial force of the leftmost anchor rod decreases, and the width of foundation pit absolutely has little effect on the axial force of the leftmost and the top tunnel.

Vascular calcification (VC) is regarded as an important pathological change lacking effective treatment and associated with high mortality. Sirtuin 6 (SIRT6) is a member of the Sirtuin family, a class III histone deacetylase and a key epigenetic regulator. SIRT6 has a protective role in patients with chronic kidney disease (CKD). However, the exact role and molecular mechanism of SIRT6 in VC in patients with CKD remain unclear. Here, we demonstrated that SIRT6 was markedly downregulated in peripheral blood mononuclear cells (PBMCs) and in the radial artery tissue of patients with CKD with VC. SIRT6-transgenic (SIRT6-Tg) mice showed alleviated VC, while vascular smooth muscle cell–specific (VSMC-specific) SIRT6 knocked-down mice showed severe VC in CKD. SIRT6 suppressed the osteogenic transdifferentiation of VSMCs via regulation of runt-related transcription factor 2 (Runx2). Coimmunoprecipitation (co-IP) and immunoprecipitation (IP) assays confirmed that SIRT6 bound to Runx2. Moreover, Runx2 was deacetylated by SIRT6 and further promoted nuclear export via exportin 1 (XPO1), which in turn caused degradation of Runx2 through the ubiquitin-proteasome system. These results demonstrated that SIRT6 prevented VC by suppressing the osteogenic transdifferentiation of VSMCs, and as such targeting SIRT6 may be an appealing therapeutic target for VC in CKD.

BackgroundAlthough academic stress is a well-known risk factor for students' depression, little is known about the possible psychological mechanisms underlying this association. In this study, we investigated the prevalence of depression and sleep disturbance among Chinese students, examined the relationship between perceived academic stress and depression, considered if mobile phone addiction and sleep quality is a mediator of this relationship, and tested if mobile phone addiction and sleep quality together play a serial mediating role in the influence of perceived academic stress on depression.MethodA cross-sectional survey was conducted among students from September to December 2018 in Heilongjiang Province, China. The final analysis included 5,109 students. Mobile phone addiction, sleep quality, and depressive symptoms were assessed using the Mobile Phone Addiction Index, Pittsburgh Sleep Quality Index, and Center for Epidemiologic Studies-Depression scales, respectively. The serial mediation model was used to analyse the relationship between perceived academic stress, mobile phone addiction, sleep quality, and depression.ResultsAmong all participants, the prevalence of depressive symptoms and sleep disturbance was 28.69 and 27.95%, respectively. High school students showed the highest scores of perceived academic stress (2.68 ± 1.06), and the highest prevalence of depressive symptoms (33.14%) and sleep disturbance (36.47%). The serial mediation model indicated that perceived academic stress was a significant predictor of depression (B = 0.10, SE = 0.02, 95% CI = 0.06 – 0.13). Additionally, mobile phone addiction (B = 0.08, 95% boot CI = 0.06–0.11) and sleep quality (B = 0.27, 95% boot CI = 0.22–0.33) played a mediating role between perceived academic stress and depression. Mobile phone addiction and sleep quality together played a serial mediating role in the influence of perceived academic stress on depression (B = 0.11, 95% boot CI = 0.08–0.14). Furthermore, the indirect effect (i.e., the mediating effect of mobile phone addiction and sleep quality) was significant and accounted for 64.01% of the total effect.ConclusionsOur research results underscore the need for stakeholders—including family members, educators, and policy makers—to take preventative intervention measures to address depression among Chinese students, especially high school students.