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Abstract The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Abstract In mammals, global passive demethylation contributes to epigenetic reprogramming during early embryonic development. At this stage, the majority of DNA-methyltransferase 1 (DNMT1) protein is excluded from nucleus, which is considered the primary cause. However, whether the remaining nuclear activity of DNMT1 is regulated by additional mechanisms is unclear. Here, we report that nuclear DNMT1 abundance is finetuned through proteasomal degradation in mouse zygotes. We identify a maternal factor, Pramel15, which targets DNMT1 for degradation via Cullin-RING E3 ligases. Loss of Pramel15 elevates DNMT1 levels in the zygote pronuclei, impairs zygotic DNA demethylation, and causes a stochastic gain of DNA methylation in early embryos. Thus, Pramel15 can modulate the residual level of DNMT1 in the nucleus during zygotic DNA replication, thereby ensuring efficient DNA methylation reprogramming in early embryos.

This study conducted fatigue tests on two 1:3 steel truss web-concrete external joints to investigate their fatigue performance. The fatigue failure mode of the external joints and the stress distribution of each component were investigated. In addition, a finite element analysis (FEA) model was established, and parametric analysis was carried out to discuss the influence of gusset plate thickness, stiffening plate layout, and gusset plate structural form on fatigue performance. The results show that the fatigue life of the external joints under the design load amplitude is 3.75 million times (187.5 years). Fatigue cracks appear in the junction area between the gusset plate and the end of the stiffening plate, which is a weak fatigue detail of the external joint. The fatigue cracks cause local stress redistribution of the gusset plate. The stress at the junction (GN3) between the gusset plate and the stiffening plate N3 can be reduced by up to 37%, 61%, and 21% by altering the above three factors. Furthermore, the fatigue life of the optimized joint is increased by 1.4 times, indicating that the fatigue performance can be significantly enhanced by improving the stiffening plate layout and the gusset plate structural form.

Abstract Precise forecasting of satellite clock bias is crucial for ensuring service quality and enhancing the efficiency of real-time precise point positioning (PPP).The grey model with many benefits is an excellent choice for predicting real-time clock bias. However, the absolute prediction error of a small number of satellites is very high in actual forecasting process. In order to address this issue, a non-homogeneous white exponential law grey model has been constructed specifically for predicting clock bias sequences with non-homogeneous class ratio approximating constants. Considering that any model is difficult to apply to different kinds of satellite clocks and clock bias signals, an adaptive selection strategy for forecast model is proposed to ensure more excellent prediction accuracy. Afterwards, a prediction scenario based on the observed products of the BeiDou satellite navigation system (BDS) is created to demonstrate the effectiveness of the approach described in this article. The outcomes of the method are then compared with those of a single grey model and the ultra-rapid predicted products. The outcomes demonstrate that this strategy’s prediction accuracy is less than 1 ns/day and that its prediction uncertainty is much decreased, which may improve data selection for real-time applications like real-time kinematics (RTK) and PPP.

Human adenovirus (HAdV) can cause severe respiratory infections in immunocompromised patients, but its clinical treatment is seriously limited by side effects of drugs such as poor efficacy, low bioavailability and severe nephrotoxicity. Trace element selenium (Se) has been found will affect the disease progression of pneumonia, but its antivirus efficacy could be improved by speciation optimization. Therefore, herein we performed anti-HAdV effects of different Se speciation and found that lentinan (LNT)-decorated selenium nanoparticles (SeNPs) exhibited low cytotoxicity and excellent anti-HAdV antiviral activity. Furthermore, SeNPs@LNT reduced the HAdV infection-induced mitochondrial damage and excessive production of reactive oxygen species (ROS). It was also involved in the repair of host cell DNA damage and inhibition of viral DNA replication. SeNPs@LNT inhibited HAdV-induced apoptosis mainly by modulating the p53/Bcl-2 apoptosis signaling pathway. In vivo, SeNPs@LNT replenished Se by targeting the infected site through the circulatory system and was involved in the synthesis of Glutathione peroxidase 1 (GPx1). More importantly, GPx1 played an antioxidant and immunomodulatory role in alleviating HAdV-induced inflammatory cytokine storm and alleviating adenovirus pneumonia in Se-deficient mice. Collectively, this study provides a Se speciation of SeNPs@LNT with anti-HAdV activity, and demonstrate that SeNPs@LNT is a promising pharmaceutical candidate for the treatment of HAdV.

Abstract The epithelial–mesenchymal transition (EMT) is a genetic reprogramming that tumor cells utilize for metastasis. Epsin-3 (EPN3) is an endocytic adapter protein involved in clathrin-mediated endocytosis and had been previously linked to EMT in breast cancer and glioma metastasis. In this study, identified the role of epsin-3 in lung adenocarcinoma and metastasis and epsin-3 levels identified using an expression profile analysis of patient data indicated the protein was abnormally overexpressed in lung adenocarcinoma patients and this was directly linked to disease severity. Gene knockdowns of EPN3 in human adenocarcinoma cell line A549 and the non-small cell lung carcinoma cell line H1299 decreased the levels of mesenchymal markers, including vimentin (VIM), N-cadherin (NCAD) and embryonic transcription factors like zinc finger E-box binding homeobox 1(ZEB1), snail, and the key molecules of Wnt pathway such as β-catenin and resulted in increased expression of the epithelial marker E-cadherin (ECAD). Our data links EPN3 to the EMT process in lung cancer and inhibition of its expression reduced the metastatic and invasive ability of lung adenocarcinoma cells by inhibiting the EMT process.

Abstract Phasing down fossil fuels is crucial for climate mitigation. Even though 80–90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China’s respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China’s emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

Abstract Background The objective of this study is to develop and validate a machine learning (ML) prediction model for the assessment of laparoscopic total mesorectal excision (LaTME) surgery difficulty, as well as to identify independent risk factors that influence surgical difficulty. Establishing a nomogram aims to assist clinical practitioners in formulating more effective surgical plans before the procedure. Methods This study included 186 patients with rectal cancer who underwent LaTME from January 2018 to December 2020. They were divided into a training cohort (n = 131) versus a validation cohort (n = 55). The difficulty of LaTME was defined based on Escal’s et al. scoring criteria with modifications. We utilized Lasso regression to screen the preoperative clinical characteristic variables and intraoperative information most relevant to surgical difficulty for the development and validation of four ML models: logistic regression (LR), support vector machine (SVM), random forest (RF), and decision tree (DT). The performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC), sensitivity, specificity, and accuracy. Logistic regression-based column-line plots were created to visualize the predictive model. Consistency statistics (C-statistic) and calibration curves were used to discriminate and calibrate the nomogram, respectively. Results In the validation cohort, all four ML models demonstrate good performance: SVM AUC = 0.987, RF AUC = 0.953, LR AUC = 0.950, and DT AUC = 0.904. To enhance visual evaluation, a logistic regression-based nomogram has been established. Predictive factors included in the nomogram are body mass index (BMI), distance between the tumor to the dentate line ≤ 10 cm, radiodensity of visceral adipose tissue (VAT), area of subcutaneous adipose tissue (SAT), tumor diameter >3 cm, and comorbid hypertension. Conclusion In this study, four ML models based on intraoperative and preoperative risk factors and a nomogram based on logistic regression may be of help to surgeons in evaluating the surgical difficulty before operation and adopting appropriate responses and surgical protocols.

ObjectivesWe aim to investigate the prevalence of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) among pediatric patients with acute respiratory tract illness (ARTI) in southern China both pre- and post-COVID-19 pandemic, as well as identify associated risk factors for severe infections.MethodsThe study conducted a real-time PCR analysis on hospitalized children with ARTI from 2012 to 2023, specifically targeting RSV, hMPV, and other respiratory pathogens. Additionally, demographic data was collected during this analysis.ResultsThe prevalence of RSV occurs triennially, and likewise, the temporal pattern of hMPV outbreaks mirrors that of RSV. The peak infection rates of RSV and hMPV occurred during and following the implementation of COVID-19 epidemic prevention and control measures. The incidence of RSV infection exhibited bimodal peaks in 2022, while hMPV demonstrated seasonal peaks during the spring, fall, and winter periods post-COVID-19 pandemic. After the COVID-19 outbreak, there has been an upward trend in the proportion of female patients and patients aged one year and older presenting with ARTI, RSV infections, and hMPV infections. Infant (OR = 4.767, 95%CI: [3.888–5.846], p < 0.0001), presence of co-infection (OR = 0.540, 95%CI: [0.404–0.722], p < 0.0001), and existence of comorbidities (OR = 1.582, 95%CI: [1.285–1.949], p < 0.0001) was the risk ratio for the severity of RSV infection. Children infected with hMPV under the age of 1 year (OR = 0.322, 95%CI: [0.180 – 0.575], p < 0.0001), as well as those with comorbidities (OR = 8.809, 95%CI: [4.493 – 17.272], p < 0.0001), have a higher risk of developing severe illness.ConclusionThe changing epidemiological patterns have the potential to lead to widespread severe outbreaks among children, particularly those with underlying medical conditions who may experience more severe symptoms. Conducting surveillance for pneumoviridae viruses in children is an imperative measure to establish a robust foundation for future epidemic prevention and treatment strategies.

Abstract A stable and highly active core‐shell heterostructure electrocatalyst is essential for catalyzing oxygen evolution reaction (OER). Here, a dual‐trimetallic core‐shell heterostructure OER electrocatalyst that consists of a NiFeWS2 inner core and an amorphous NiFeW(OH)z outer shell is designed and synthesized using in situ electrochemical tuning. The electrochemical measurements of different as‐synthesized catalysts with a similar mass loading suggest that the core‐shell Ni0.66Fe0.17W0.17S2@amorphous NiFeW(OH)z nanosheets exhibit the highest overall performance compared with that of other bimetallic reference catalysts for the OER. Additionally, the nanosheet arrays were in situ grown on hydrophilic‐treated carbon paper to fabricate an integrated three‐dimensional electrode that affords a current density of 10 mA cm−2 at a small overpotential of 182 mV and a low Tafel slope of 35 mV decade−1 in basic media. The Faradaic efficiency of core‐shell Ni0.66Fe0.17W0.17S2@amorphous NiFeW(OH)z is as high as 99.5% for OER. The scanning electron microscope, transmission electron microscope, and X‐ray photoelectron spectroscopy analyses confirm that this electrode has excellent stability in morphology and elementary composition after long‐term electrochemical measurements. Importantly, density functional theory calculations further indicate that the core‐shell heterojunction increased the conductivity of the catalyst, optimized the adsorption energy of the OER intermediates, and improved the OER activity. This study provides a universal strategy for designing more active core‐shell structure electrocatalysts based on the rule of coordinated regulation between electronic transport and active sites.

Extensive research has made significant progress in exploring the potential application of extracellular vesicles (EV) in the diagnosis and treatment of osteoarthritis (OA). However, there is current a lack of study on bibliometrics. In this study, we completed a novel bibliometric analysis of EV research in OA over the past two decades. Specifically, we identified a total of 354 relevant publications obtained between January 1, 2003 and December 31, 2022. We also provided a description of the distribution information regarding the countries or regions of publication, institutions involved, journals, authors, citations, and keywords. The primary research focuses encompassed the role of extracellular vesicles in the diagnosis of OA, delivery of active ingredients, treatment strategies, and cartilage repair. These findings highlight the latest research frontiers and emerging areas, providing valuable insights for further investigations on the application of extracellular vesicles in the context of osteoarthritis.

As an important negative carbon technology to solve the carbon emission problem in the coal industry, the CO2 sequestration in the mine goaf has a wide application prospect in the secondary utilization of waste resources in the goaf and the capture and storage of CO2. In this study, the influence of different temperatures and pressures, formation water salinity and cationic solution type on the interfacial tension (IFT) of CO2-formation water system was investigated by using in-situ interfacial tension meter. The gas-liquid interface diffusion effect of CO2 injection into water-bearing coal rock mass was clarified. The equation of state (SAFT-LJ equation of state) based on statistical association theory combined with the Lanner-Jones potential energy model and density gradient theory (DGT) were combined to predict the theoretical value of IFT. Using a self-developed geological sequestration and geochemical reaction simulation experimental platform, various exploratory experiments were conducted to investigate the solubility of CO2 under the same conditions. The characteristics of CO2 solubility variation in the reservoir environment of the goaf were obtained, and the corresponding theoretical values of CO2 solubility were calculated using the D-S model. The experimental results show that when the ambient temperature is constant, the reservoir pressure in the goaf is linearly negatively correlated with the IFT value. As the reservoir temperature increases, the IFT value increases correspondingly, but the change range is small. Under constant temperature and pressure conditions, there is a positive correlation between salinity and IFT value. Within the scope of this experiment, low pressure, high temperature, and high salinity promote an increase in the IFT value. The IFT values between CO2-salt solutions show an increasing trend with the increasing valence of cations (K+ < Na+ < Ca2+ < Mg2+). The pressure of the depleted reservoir is positively correlated with the CO2 solubility. When the temperature is 25 °C and under conditions of pure water, as the pressure increases from 0.5 MPa to 2.5 MPa, the corresponding CO2 solubility increases from 0.1627 mol/kg to 0.7141 mol/kg. The CO2 solubility decreases with the increases of temperature and salinity. Under the same concentration, monovalent cation solutions (NaCl, KCl) can dissolve more CO2 than divalent cation solutions (CaCl2, MgCl2). The free phase CO2 injected into the goaf overcomes the interfacial tension and breaks the geochemical balance of the goaf strata through diffusion and dissolution mass transfer. By clarifying the influence of reservoir temperature and pressure conditions and goaf water environment on IFT value and CO2 solubility, the gas-liquid interface effect and dissolution mass transfer mechanism of CO2-formation water are clarified, so as to provide a theoretical basis for the safety and evaluation of CO2 sequestration in the closed mine goaf.

Abstract In this paper, an optimal distributed guidance law is proposed for cooperatively intercepting a manoeuvering target in three dimensional (3D) framework. Based on the 3D kinematic model of interceptors and the target, the kinematic engagement equations in line‐of‐sight (LOS) coordinate can be obtained. Along the LOS direction, a finite‐time consensus based on directed communication topology is applied to guarantee arrival‐time coordination of multiple interceptors, and sliding mode control is adopted to compensate target manoeuver. In the plane perpendicular to LOS, optimal control is used to design guidance law such that closed‐loop LOS angular rates converge to a tunable small neighbourhood of zero. The proposed cooperative guidance law is proved in theory, and its effectiveness is verified by simulations.

Abstract Transcriptional Co-Activator with PDZ-Binding Motif (TAZ, also known as WWTR1) is a downstream effector of the Hippo pathway, involved in the regulation of organ regeneration and cell differentiation in processes such as development and regeneration. TAZ has been shown to play a tumor-promoting role in various cancers. Currently, many studies focus on the role of TAZ in the process of mitophagy. However, the molecular mechanism and biological function of TAZ in renal clear cell carcinoma (KIRC) are still unclear. Therefore, we systematically analyzed the mRNA expression profile and clinical data of KIRC in The Cancer Genome Atlas (TCGA) dataset. We found that TAZ expression was significantly upregulated in KIRC compared with normal kidney tissue and was closely associated with poor prognosis of patients. Combined with the joint analysis of 36 mitophagy genes, it was found that TAZ was significantly negatively correlated with the positive regulators of mitophagy. Finally, our results confirmed that high expression of TAZ in KIRC inhibits mitophagy and promotes KIRC cell proliferation. In conclusion, our findings reveal the important role of TAZ in KIRC and have the potential to be a new target for KIRC therapy.

Abstract The cryptocurrency market is a complex and rapidly evolving financial landscape in which understanding the inter- and intra-asset dependencies among key financial variables, such as return and liquidity, is crucial. In this study, we analyze daily return and liquidity data for six major cryptocurrencies, namely Bitcoin, Ethereum, Ripple, Binance Coin, Litecoin, and Dogecoin, spanning the period from June 3, 2020, to November 30, 2022. Liquidity is estimated using three low-frequency proxies: the Amihud ratio and the Abdi and Ranaldo (AR) and Corwin and Schultz (CS) estimators. To account for autoregressive and persistent effects, we apply the autoregressive integrated moving average-generalized autoregressive conditional heteroscedasticity (ARIMA-GARCH) model and subsequently utilize the copula method to examine the interdependent relationships between the return on and liquidity of the six cryptocurrencies. Our analysis reveals strong cross-asset lower-tail dependence in return and significant cross-asset upper-tail dependence in illiquidity measures, with more pronounced dependence observed in specific cryptocurrency pairs, primarily involving Bitcoin, Ethereum, and Litecoin. We also observe that returns tend to be higher when liquidity is lower in the cryptocurrency market. Our findings have significant implications for portfolio diversification, asset allocation, risk management, and trading strategy development for investors and traders, as well as regulatory policy-making for regulators. This study contributes to a deeper understanding of the cryptocurrency marketplace and can help inform investment decision making and regulatory policies in this emerging financial domain.

The construction of China’s ecological civilization has entered a critical period in which carbon reduction is the key strategic direction since the “dual carbon” goal was proposed. Coal’s status as the least expensive energy source will be unchanged in the short term. CH4-CO2 coordinated emission reduction is the core of the convert from “dual control” of energy consumption to “dual control” of total carbon emissions and intensity. On the basis of accurately analyzing the challenges of CH4-CO2 dual carbon emission reduction in coal mines at the stage of carbon peak and carbon neutrality, the development of coal and gas co-mining technology in the dual carbon strategy has been clarified to be combined with the core principles of current demand-technical research-policy drive, the development path of coal and gas co-mining technology in the dual carbon strategy is formulated, and the key technical issues are discussed. At the peak stage of carbon emission, CH4 emission reduction is based on the perspective of emission source control. The core is the key technology for carbon emission reduction in the whole cycle of gas extraction and utilization, including the targeted and accurate extraction technology in gas-rich areas, the permeability-enhancement, replacement and flow-increasement extraction by injecting gas in low-permeability coal seams, the gas escape channel plugging and carbon reduction technology in closed mines, and the integrated technology of gas enrichment-concentration-utilization. The purpose is to greatly improve the efficiency of high-concentration gas extraction and utilization and to reduce the carbon emission from low-concentration and ventilated gas. CO2 emission reduction is centered on the “CCUS + ecological carbon sink” region-wide negative carbon emission technology to further absorb flue gas and pure CO2 emissions, including CO2 storage in coal seams, industrial solid waste goaf filling synergistic CO2 geological storage, soil-surface-atmosphere anomaly monitoring and ecological carbon sink technology in coal mine carbon storage areas, etc. The core task of the carbon neutralization stage is to achieve CH4-CO2 (near) zero carbon emission. CO2 emission reduction should be transformed from a technical research demonstration project to a large-scale application stage, and establishing an intelligent monitoring and dynamic control technology system for CH4-CO2 emission from coal mine in the whole life cycle to realize the in-deep matching between monitoring and control technology means and carbon emission links, and the in-deep docking between the monitoring-control cloud platform of carbon emission and the global monitoring-control system of coal mines. Finally, the insights and thoughts is put forward on the green and low-carbon development of the future coal and gas co-mining system. ① Continue to deepen the coal mine CH4 zero emission technology model of “efficient and accurate extraction + full-concentration cascade utilization”. ② Continue to tackle the CO2 zero emission technology system of “CO2 engineering storage + ecological carbon sinks”. ③ Actively exploring the comprehensive solution of “zero carbon wisdom park” in coal mines, and forming a policy support system for carbon emission reduction in coal mines that emphasizes both incentive and pushback.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein–protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14–CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Abstract Background Herpes simplex virus type 1 (HSV-1) infection is a common viral disease that mainly causes oral lesions, but can also cause genital lesions in some instances. Current treatments with nucleoside analogs are limited by the emergence of drug resistance. Therefore, novel anti-HSV-1 drugs are urgently needed. Methods In this study, we screened a library of 2080 compounds for anti-HSV-1 activity using a plaque formation assay. We selected 11 potential inhibitors of HSV-1 and further evaluated their antiviral effects by plaque reduction assay and real-time polymerase chain reaction (qPCR). Results Five compounds, namely ginsenoside Rd, brassinolide, rosamultin, 3’-hydroxy puerarin, and clinafloxacin HCl, showed potent anti-HSV-1 activity and completely suppressed plaque formation at a concentration of 10 µM. Among them, clinafloxacin HCl, a fluoroquinolone antibiotic, exhibited a high selectivity index for HSV-1. Conclusions Our findings suggest that these five compounds have potential antiviral properties against HSV-1 and may have different mechanisms of action. Further studies are warranted to elucidate the antiviral mechanisms of these compounds and to explore their therapeutic potential for HSV-1 infection.

Cross-resolution person re-identification is a challenging problem in the field of person re-identification. In order to solve the problem of resolution mismatch, many studies introduce super-resolution into person re-identification tasks. In this work, we propose a cross-resolution person re-identification method based on double transformer residual super-resolution network (DTRSR), which mainly includes super-resolution module and person re-identification module. In the super-resolution module, we propose the double transformer network as our attention module. First of all, we divide the features extracted by the residual network. Then calculate the similarity between each local feature and the global feature after average pooling and maximum pooling respectively, which makes our module quickly capture the hidden weight information in the spatial domain. In the person re-identification module, we propose an effective fusion method based on key point features (KPFF). The key point extraction model can not only solve the problem that local features can not be accurately aligned, but also remove the interference of background noise. In order to fully mine the relationship between the features of each key point, we calculate the two-way correlation between each key point feature and other features, and then superimpose the two-way correlation with the feature itself to get the superposition feature which contains global and local information. The effectiveness of this method is proved by extensive experiments. Compared with the most advanced methods, the test results in the three datasets show that our method improves rank-1 by 1.1%, 3.5% and 1.7%; and rank-5 by 1.3%, 1.7% and 0.3%; and rank-10 by 0.1%, 0.4% and 0.1%, respectively.

In the original publication [...]

Ehrlichia chaffeensis: TRP120 is a multifunctional effector that acts as a ligand mimic to activate evolutionary conserved eukaryotic signaling pathways Notch, Wnt, Hedgehog and Hippo. In addition, TRP120 is also a HECT E3 ubiquitin ligase known to ubiquitinate several host cell regulatory proteins (FBW7, PCGF5 and ENO-1) for degradation. We previously determined that TRP120 ubiquitinates the Notch negative regulator, FBW7, to maintain Notch signaling and promote infection. In this study, we investigated a potential mechanism used by Ehrlichia chaffeensis to maintain Hippo and Wnt signaling by ubiquitinating the tumor suppressor, adenomatous polyposis coli (APC), a negative regulator of Wnt and Hippo signaling. We determined that APC was rapidly degraded during E. chaffeensis infection despite increased APC transcription. Moreover, RNAi knockdown of APC significantly increased E. chaffeensis infection and coincided with increased active Yap and β-catenin in the nucleus. We observed strong nuclear colocalization between TRP120 and APC in E. chaffeensis-infected THP-1 cells and after ectopic expression of TRP120 in HeLa cells. Additionally, TRP120 interacted with both APC full length and truncated isoforms via co-immunoprecipitation. Further, TRP120 ubiquitination of APC was demonstrated in vitro and confirmed by ectopic expression of a TRP120 HECT Ub ligase catalytic site mutant. This study identifies APC as a TRP120 HECT E3 Ub ligase substrate and demonstrates that TRP120 ligase activity promotes ehrlichial infection by degrading tumor suppressor APC to positively regulate Hippo and Wnt signaling.

Abstract As a highly lethal adenocarcinoma of the hepatobiliary system, outcomes for cholangiocarcinoma (CCA) patients remain prominently poor with a 5-year survival of

Adenovirus (HAdV) can cause severe respiratory infections in children and immunocompromised patients. There is a lack of specific therapeutic drugs for HAdV infection, and the study of anti-adenoviral drugs has far-reaching clinical implications. Elemental selenium can play a specific role as an antioxidant in the human immune cycle by non-specifically binding to the amino acid methionine in body proteins. Methods: The antiviral mechanism of selenomethionine was explored by measuring cell membrane status, intracellular DNA status, cytokine secretion, mitochondrial membrane potential, and ROS production. Conclusions: Selenomethionine improved the regulation of ROS-mediated apoptosis by modulating the expression of Jak1/2, STAT3, and BCL-XL, which led to the inhibition of apoptosis. It is anticipated that selenomethionine will offer a new anti-adenoviral therapeutic alternative.

According to the Magnus principle, a rotating cylinder experiences a lateral force perpendicular to the incoming flow direction. This phenomenon can be harnessed to boost the lift of an airfoil by positioning a rotating cylinder at the leading edge. In this study, we simulate flapping-wing motion using the sliding mesh technique in a heaving coordinate system to investigate the energy harvesting capabilities of Magnus effect flapping wings (MEFWs) featuring a leading-edge rotating cylinder. Through analysis of the flow field vortex structure and pressure distribution, we explore how control parameters such as gap width, rotational speed ratio, and phase difference of the leading-edge rotating cylinder impact the energy harvesting characteristics of the flapping wing. The results demonstrate that MEFWs effectively mitigate the formation of leading-edge vortices during wing motion. Consequently, this enhances both lift generation and energy harvesting capability. MEFWs with smaller gap widths are less prone to induce the detachment of leading-edge vortices during motion, ensuring a higher peak lift force and an increase in the energy harvesting efficiency. Moreover, higher rotational speed ratios and phase differences, synchronized with wing motion, can prevent leading-edge vortex generation during wing motion. All three control parameters contribute to enhancing the energy harvesting capability of MEFWs within a certain range. At the examined Reynolds number, the optimal parameter values are determined to be a∗ = 0.0005, R = 3, and ϕ0 = 0°.

Over a century ago, phenolic formaldehyde (PF) resin was developed and continues to increase in yield due to its diverse applications. However, PF resin is a thermosetting plastic lacking fluidity and moldability, which are nondegradable in natural environments, leading to severe threats to fossil resources as well as global environmental crises. As a result, recycling PF resin is extremely important. In this review, we provide the recent advances in the recycling of PF resin, which includes mechanical recycling, chemical recycling, and utilization of carbon-based materials. The advantages and disadvantages of each strategy are evaluated from a green chemistry perspective. This article aims to attract interest in PF resin design, synthesizing, application and recycling, offering useful suggestions.

The concept of the carbon cycle in the old goaf of a coal mine based on CO2 utilization and storage was put forward adhering to the principle of low-carbon development, utilization of space resources in old goafs, and associated gas resources development. Firstly, the evolution characteristics of overburden fissures in the goaf of the case was studied using a two-dimensional physical similarity simulation test, the sealing performance of the caprocks after stabilization was analyzed, and the fissures were counted and classified. Then, the process of gaseous CO2 injection in the connected fissure was simulated by Ansys Fluent software, and the migration law and distribution characteristics of CO2 under the condition of gaseous CO2 injection were analyzed. Finally, the estimation models of free CO2 storage capacity in the old goaf were constructed considering the proportion of connected fissure and the effectiveness of CO2 injection. The CO2 storage capacity in the old goaf of the case coal mine was estimated. The results showed that a caprock group of “hard-thickness low-permeability hard-thickness” was formed after the caprock-fissures system in the goaf of the case tended to be stable vertically. The connected fissure, occlude cracks, and micro-fractures in the goaf accounted for 85.5%, 8.5%, and 6% of the total fissures, respectively. Gaseous CO2 first migrated to the bottom of the connected fissure after CO2 was injected into the goaf, then spread horizontally along the bottom of the connected fissure after reaching the bottom, and finally spread longitudinally after filling the bottom of the entire connected fissure. The theoretical and effective storage capacities of free CO2 at normal temperature and pressure in the old goaf of the case were 9757 and 7477 t, respectively. The effective storage capacity of free CO2 at normal temperature and pressure in the old goaf after all minefield mined was 193404 t. The research can provide some reference for the coal mining industry to help the goal of “carbon peaking and carbon neutrality”.

Biochar modified by H3PO4 treatment can be used to purify malodorous gases during bio-drying of sludge, but the current understanding of multi-component adsorption of malodorous gases through biochar is limited. This study examined the adsorption mechanism of mixed malodorous gases including toluene and ammonia (NH3) on two kinds of biochar modified via H3PO4 pretreatment before and after pyrolysis. The biochar obtained by H3PO4 pretreatment of biomass before pyrolysis (C550) preferred to adsorb NH3 whether in the single or the dual system. In contrast, the biochar obtained by H3PO4 reprocessing after pyrolysis of biomass (C350-550) tended to adsorb toluene in the dual system but was more efficient in absorbing NH3 in the single system. The pseudo-second-order kinetic model indicated the synergistic adsorption between NH3 and toluene for all biochar samples. In-situ DRIFTS of C350-550 during adsorption demonstrated the formation of amino functional groups caused by NH3 chemical adsorption with -OH (or -COOH) in the dual system. These increases in basic groups on C350-550 could enhance the surface zero potential point of C350-550, thereby improving the non-polarity of C350-550 and benefit the adsorption of weak polar toluene.

Abstract Background To compare the clinical efficacy of two alimentary tract reconstruction methods—“P”-shape jejunal interposition (PJI) and Roux-en-Y anastomosis after total gastrectomy. Method The following search phrases were utilized to search PubMed, Cochrane Library, Embase, China Academic Journals Network Full-text Database (CNKI), and Wanfang Database as of April 2022: “gastrectomy,” “Roux-en-Y,” “interposition,” “total gastrectomy,” and “jejunal interposition.” Meta-analysis of the operation time, intraoperative blood loss, complication rate, and postoperative nutritional status of patients was performed using RevMan 5.4 software. Results A total of 24 studies and 1887 patients were included in the study. Among patients who received a total gastrectomy, the operation time in the PJI group was substantially longer than that in the Roux-en-Y group (WMD = 19.77, 95% CI: 5.84–33.70, P = 0.005). The incidence of postoperative reflux esophagitis in the PJI group was considerably reduced than that in the Roux-en-Y group (OR = 0.39, 95% CI: 0.28–0.56, P

Abstract The suspension-type monorail (STM) is a new type of rail transit, currently developing rapidly in China. Due to its short construction duration and high terrain adaptability, STM can save large land resources. In particular, by supplementing the traffic systems in large and medium-sized cities, STM can contribute to green tourism projects. However, no systematic study is devoted to the STM transit system in China, and there is still a lack of relevant knowledge and exploration, especially for the special combination system monorail bridge. In view of the real STM bridge, namely a long-span (55 + 100 + 55)-m cable-stayed bridge in this paper, and by applying wind-vehicle-bridge coupling vibration theory, ANSYS finite element method software, and Universal Mechanism multi-body dynamics software, finite element models are established for the bridge and multi-body vehicle, respectively. Furthermore, a co-simulation method is adopted to analyze vehicle-bridge coupling vibrations and ride comfort quality. According to the results, the dynamic responses of the monorail bridge and vehicle are greatly affected by the variation in wind speed, and it is necessary to take measures to decrease system vibrations, thereby ensuring ride comfort quality for vehicle passengers.

Abstract Background Dental caries prevalence reaches the first peak around 6 years old. It is necessary to take effective measures to prevent and treat caries at this stage. This study investigated the prevalence and associated factors of dental caries among schoolchildren aged 6–8 years in Hangzhou City, China. Methods A cross-sectional survey was conducted in Hangzhou from October 2017 to May 2018. Oral health status of schoolchildren in 1st and 2nd grades of primary schools aged 6–8 years was examined by well-trained examiners according to the WHO criteria. Questionnaires about potential caries-related factors were distributed to their parents. ANOVA test and logistic regression were conducted for the statistical analyses (α = 0.05). Results A total of 7959 pairs of schoolchildren and their parents were invited to participate, and 5595 were included in this study according to the eligible criteria (response rate: 70.3%). The overall prevalence and mean dmft/DMFT of dental caries in the investigated schoolchildren were 52.78% and 2.11. The prevalence and mean dmft/DMFT were 39.05% and 1.63 in the deciduous teeth, while these were 21.45% and 0.48 in the permanent teeth, respectively. For the first permanent molars (FPMs), the rate of fully eruption and pit and fissure sealing (PFS) were 79.09% and 6.60%, respectively. Multiple logistic regression showed that girl (OR = 1.12, 95% CI 1.01–1.25, p

Abstract Influenza viruses cause a severe threat to global health, which can lead to annual epidemics and cause pandemics occasionally. However, the number of anti‐influenza therapeutic agents is very limited. Polysaccharides, extracted from Picochlorum sp. (PPE), seaweed Polysaccharides, have exhibited antiviral activity and were expected to be used for influenza treatment. In our research, the capability of PPE to inhibit H1N1 infection was proved in MDCK cells. PPE could make MDCK cells avoid being infected with H1N1 and inhibited nuclear fragmentation and condensation of chromatin. PPE evidently inhibited the generation of reactive oxygen species in MDCK cells. Mechanism study revealed that PPE prevented MDCK cells from H1N1 infection through induction of apoptosis by stimulating AKT signaling pathway and suppressing p‐p53 signaling pathway. In conclusion, PPE turns out to act as a prospective antiviral drug for H1N1 influenza.

Existing image super-resolution algorithms still suffer from the problems of not extracting rich image features and losing realistic high-frequency details. In order to solve these problems, this paper proposes an improved generative adversarial network algorithm for super-resolution reconstruction of remote sensing images by multi-scale residual blocks. The original generative adversarial network (GAN) structure is improved and multi-scale residual blocks are introduced in the generator to fuse features at different scales. After extracting the parallel information of multi-scale features, information is exchanged between multi-resolution information streams to obtain contextual information through spatial and channel attention mechanisms, and multi-scale features are fused according to the attention mechanism. In the discriminator, the concept of relative average GAN (RaGAN) is introduced, and the loss function of the network is redesigned so that the discriminator can predict relative probabilities instead of absolute probabilities thus enabling clear learning of edge and texture details. Experimental results show that the proposed method in this paper significantly outperforms state-of-the-art (SOTA) methods in terms of both subjective and objective metrics.In three test datasets, compared with SOTA methods, the Peak Signal to Noise Ratio(PSNR) is improved by a maximum of 1.18 dB, 0.84 dB and 1.29 dB respectively, and the Structural Similarity Index (SSIM) is improved by 0.0264, 0.0077 and 0.0109 respectively in scale of 2, 3 and 4 times images super-resolution.The model proposed in this paper effectively improved the super-resolution re-construction results of remote sensing images.

Abstract Xinjiang is an important power production base in China, and its electric energy production needs not only meet the demand of Xinjiang's electricity consumption, but also make up for the shortage of electricity in at least 19 provinces or cities in China. Therefore, it is of great significance to know ahead of time the electric energy production of Xinjiang in the future. In such terms, accurate electric energy production forecasts are imperative for decision makers to develop an optimal strategy that includes not only risk reduction, but also the betterment of the economy and society as a whole. According to the characteristics of the historical data of monthly electricity generation in Xinjiang from January 2001 to August 2020 , the suitable and widely used SARIMA (Seasonal autoregressive integrated moving mean model) method and Holt-winter method were used to construct the monthly electric energy production in Xinjiang for the first time. The results of our analysis showed that the established SARIMA((1,2,3,4,6,7,11),2,1)(1,0,1)12 model had higher prediction accuracy than that of the established Holt-Winters' multiplicative model. We predicted the monthly electric energy production from August 2021 to August 2022 by the SARIMA((1,2,3,4,6,7,11),2,1)(1,0,1)12 model, and errors are very small compared to the actual values, indicating that our model has a very good prediction performance. Therefore, based on our study, we provided a simple and easy scientific tool for the future power output prediction in Xinjiang. Our research methods and research ideas can also provide scientific reference for the prediction of electric energy production elsewhere.

Abstract Background Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests sequential Aβ and tau brain pathology with age-dependent onset. Variants in the microglial immune receptor TREM2 are associated with enhanced risk of onset in sporadic Alzheimer’s disease (AD). While recent studies suggest TREM2 dysfunction can aggravate tau pathology, mechanisms underlying TREM2-dependent modulation of tau pathology remains elusive. Methods Here, we characterized differences in progressive tau spreading from the medial entorhinal cortex (MEC) to the hippocampus in wildtype (WT) and Trem2 knockout (KO) mice by injection of AAV-P301L tau into the MEC, and correlated changes in hippocampal tau histopathology with spatial and fear memory. We also compared effects of intraneuronal dispersion between cultured microglia and neurons using a microfluidic dispersion assay, analyzed differences in microglial tau trafficking following uptake, and quantified exosomal tau secretion and pathogenicity from purified WT and Trem2 KO exosomes. Results Trem2 deletion in mice (Trem2 KO) can enhance tau spreading from the medial entorhinal cortex (MEC) to the hippocampus, which coincides with impaired synaptic function and memory behavior. Trem2 deletion in microglia enhances intraneuronal dispersion of tau in vitro between neuronal layers cultured in a microfluidic chamber, and the presence of exosome inhibitors can significantly reduce tau in exosomes and extracellular media from tau-loaded microglia. Although microglial Trem2 deletion has no effect on tau uptake, Trem2 deletion enhances distribution to endosomal and cellular pre-exosomal compartments following internalization. Trem2 deletion has little effect on exosome size, however, proteomic analysis indicates that Trem2 deletion can modulate changes in the microglial proteomic landscape with tau and LPS/ATP treatment conditions associated with exosome induction. Furthermore, exosomes from Trem2 KO microglia show elevated tau levels, and feature enhanced tau-seeding capacity in a tau FRET reporter line compared to exosomes from WT microglia. Conclusion Together, our results reveal a role for Trem2 in suppressing exosomal tau pathogenicity, and demonstrates that Trem2 deletion can enhance tau trafficking, distribution and seeding through microglial exosomes. Graphical abstract

Abstract Backgrounds MIR31 host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association of MIR31HG polymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation between MIR31HG polymorphisms and SONFH susceptibility in the Chinese Han population. Methods A total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model. Results According to the results of genetic model, rs10965059 in MIR31HG was significantly correlated with the susceptibility to SONFH (OR = 0.56, p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30, p

Abstract Background Myocardial infarction (MI) is characterized by coronary artery occlusion, ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Therefore, it is urgent to explore the potential mechanism of myocardial injury during the MI process to develop effective therapies for myocardial cell rescue. Methods We downloaded the GSE71906 dataset from GEO DataSets, and the R software was used to identify the differentially expressed genes (DEGs) in mouse heart tissues of MI and sham controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to understand the significantly activated signaling pathways in MI. Protein–protein interaction (PPI) network was constructed to highlight the hub genes in DEGs. The Western Blot, qRT-PCR and TUNEL staining were used to explore the function of hub gene in hypoxia-induced cardiomyocytes in vitro. Results A total of 235 DEGs were identified in GSE71906 dataset. Functional enrichment analysis revealed that the upregulated genes were primarily associated with the inflammatory response and apoptosis. 20 hub genes were identified in PPI network, and the early growth response 2 (EGR2) was highlighted. In vitro. We confirmed the EGR2 was upregulated induced by hypoxia and revealed the upregulated EGR2 aggravates pro-inflammation and pro-apoptotic genes expression. In addition, EGR2 knockout mitigates hypoxia-induced inflammation and apoptosis in cardiomyocytes. Conclusion The present study identified the EGR2 was a hub gene in myocardial damage during MI process, the excessive EGR2 aggravates hypoxia-induced myocardial damage by accelerating inflammation and apoptosis in vitro. Therefore, targeting EGR2 offers a potential pharmacological strategy for myocardial cell rescue in MI.

Abstract BLDCMs are widely used in automotive, industrial and intelligent equipment fields due to their high power density, simple control, and good dynamic performance. However, its non‐sinusoidal characteristics have brought problems such as turn‐off phase freewheeling to the research and application of BLDCM DTC. This paper proposes the definition, particular characteristic analysis, selection scheme and realization method of the voltage vector, especially the novel zero‐voltage vector. Based on the novel zero‐voltage and twelve‐sector vector selection switch table, an improved PWM modulation strategy in a single cycle is proposed to cooperate with them to achieve the reduction of torque ripple. Finally, the correctness and feasibility of the proposed voltage vector and control strategy theory are verified by a series of experiments.

Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer.Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher’s precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes.Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ2 = 6.632, p = 0.010; OS: χ2 = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram’s predictive clinical utility for clinical decision was better than IOSS.Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.

Severe adenovirus pneumonia is becoming more common in children infected with human mastadenovirus (HAdV)-3 and HAdV-7 than in those infected with other types of adenoviruses. Recently, there has been a trend toward an increasing prevalence of pneumonia caused by HAdV-7, an important viral pathogen in Pediatric Intensive Care Unit infections. Children infected with HAdV-7 have more serious symptoms of acute respiratory infections and other complications than those infected with HAdV-3. No specific anti-adenovirus drugs or vaccines are available for treatment or prevention. Therefore, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAbs) against HAdV-3 and HAdV-7 in healthy children in Guangdong Province. We found that the seropositivity rates and antibody titers for HAdV-3 NAb were higher than those for HAdV-7 NAb. In children between 6 and 12 months of age, the seropositivity rates and titers were significantly low against HAdV-3 and HAdV-7. The HAdV-7-positive rate was significantly higher in the HAdV-3-positive samples than in the HAdV-3-negative samples. The HAdV-7 NAbs carried by the 0–6-month age group were dominated by low titers. These results reveal a low level of herd immunity against HAdV-3 and HAdV-7 in children, clarifying the importance of monitoring these two highly virulent adenoviruses, developing prophylactic vaccines, and predicting potential outbreaks.

Prostate cancer is a common disease that seriously endangers the health of middle-aged and elderly men. MRI images are the gold standard for assessing the health status of the prostate region. Segmentation of the prostate region is of great significance for the diagnosis of prostate cancer. In the past, some methods have been used to segment the prostate region, but segmentation accuracy still has room for improvement. This study has proposed a new image segmentation model based on Attention UNet. The model improves Attention UNet by using GN instead of BN, adding dropout to prevent overfitting, introducing the ASPP module, adding channel attention to the attention gate module, and using different channels to output segmentation results of different prostate regions. Finally, we conducted comparative experiments using five existing UNet-based models, and used the dice coefficient as the metric to evaluate the segmentation result. The proposed model achieves dice scores of 0.807 and 0.907 in the transition region and the peripheral region, respectively. The experimental results show that the proposed model is better than other UNet-based models.

In the marine environments, NiCrAlY coatings with high content of Cr would suffer much severer corrosion due to the effect of NaCl. Thus, NiSiAlY coatings with different Si content were proposed and deposited on Ni-based superalloys by multi-arc ion plating. The as-deposited coating was mainly composed of γ’-Ni3Al phase with a small amount of β-NiAl phase. NaCl-induced hot corrosion tests were performed on the coatings at 500°C, 600°C, and 700°C, respectively. Compared with Ni-based alloy substrates, the NiSiAlY coatings exhibited a good corrosion resistance to NaCl at elevated temperatures. However, with an excessive amount of Si, the NiSiAlY coating showed a degradation in the hot corrosion resistance. In this work, the corrosion mechanisms of the tested coatings were discussed. Moreover, the role of Si was also investigated.

Summary: Pancreatic progenitor cell differentiation and proliferation factor (PPDPF) has been reported to play a role in tumorigenesis. However, its function in hepatocellular carcinoma (HCC) remains poorly understood. In this study, we report that PPDPF is significantly downregulated in HCC and the decreased PPDPF expression indicates poor prognosis. In the dimethylnitrosamine (DEN)-induced HCC mouse model, hepatocyte-specific depletion of Ppdpf promotes hepatocarcinogenesis, and reintroduction of PPDPF into liver-specific Ppdpf knockout (LKO) mice inhibits the accelerated HCC development. Mechanistic study shows that PPDPF regulates nuclear factor κB (NF-κB) signaling through modulation of RIPK1 ubiquitination. PPDPF interacts with RIPK1 and facilitates K63-linked ubiquitination of RIPK1 via recruiting the E3 ligase TRIM21, which catalyzes K63-linked ubiquitination of RIPK1 at K140. In addition, liver-specific overexpression of PPDPF activates NF-κB signaling and attenuates apoptosis and compensatory proliferation in mice, which significantly suppresses HCC development. This work identifies PPDPF as a regulator of NF-κB signaling and provides a potential therapeutic candidate for HCC.

Human adenovirus type 7 (HAdV7) infection causes severe pneumonia, yet there are still no breakthroughs in treatment options for adenovirus, and the road to antiviral drug development faces major challenges. We attempted to find new drugs and we stumbled upon one: selenadiazole. Selenadiazole has been shown to have significant anti-tumor effects due to its unique chemical structure and drug activity. However, its effectiveness against viruses has not been evaluated yet. In our study, selenadiazole also showed superior antiviral activity. In vitro experiments, selenadiazole was able to inhibit adenovirus-mediated mitochondrial-oxidative-damage-related apoptosis, and in in vivo experiments, selenadiazole was able to inhibit apoptosis by modulating the apoptotic signaling pathway Bcl-2/Stat3/NF-κB, etc., and was able to largely attenuate adenovirus-infection-induced pneumonia and lung injury in mice. This study aims to describe a new antiviral treatment option from the perspective of anti-adenovirus-mediated oxidative stress and its associated apoptosis and to provide theoretical guidance for the treatment of clinical adenovirus infection to a certain extent.

Abstract Background Fat mass and obesity-related (FTO) mRNA was downregulated in osteonecrosis patients. The study aimed to evaluate the correlation between FTO polymorphisms and the susceptibility of osteonecrosis of the femoral head (ONFH). Methods Six polymorphisms in FTO were genotyped via the Agena MassARRAY in 498 ONFH patients and 498 healthy controls. Multiple genetic models were used to assess the correlation between FTO polymorphisms and ONFH risk by SNPStats. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a logistic regression model adjusted by age, gender, smoking and drinking. Results The risk-increasing association of rs62033406 A>G with ONFH was found (OR = 1.25, 95% CI 1.05–1.50, p = 0.014). Specially, FTO rs62033406 A>G was related to the risk of ONFH in the subgroup at age > 51 years (OR = 1.25, p = 4.00 × 10–4), females (OR = 1.74, p = 1.00 × 10–4), smokers (OR = 1.82, p = 0.005) and drinkers (OR = 1.89, p = 0.002), respectively. The best multi–loci model was the five–loci model, a combination of rs9930333 T>G, rs1558902 T>A, rs56094641 A>G, rs3751812 G>T, and rs62033406 A>G (testing accuracy, 0.5351; p = 0.0004; cross–validation consistency, 10/10). Conclusion Our study first revealed that FTO rs62033406 A>G was a risk factor for ONFH among the Chinese Han population, which might provide the new candidate gene for elucidating the pathogenesis of ONFH.

Abstract Background Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer globally, with average age of cancer patients becoming younger gradually. It is of significance to gain a comprehensive understanding of molecular mechanism underlying NSCLC. Methods Quantitative polymerase chain reaction (qPCR) and western blot were applied to measure RNA and protein levels separately. Functional assays and western blot were performed to determine the effects of miR-489-3p and USP48 on cell growth, migration and epithelial-mesenchymal transition (EMT) in NSCLC. TOP/FOP flash luciferase reporter assay was carried out to detect the activity of Wnt pathway. Besides, qPCR, RNA pulldown and luciferase reporter assays were conducted to probe into the target gene of miR-489-3p. Immunoprecipitation-western blot (IP-western blot) analysis was implemented to assess the effect of USP48 on the ubiquitination of β-catenin. Results miR-489-3p hampers NSCLC cell proliferation, migration and EMT in vitro and NSCLC tumorigenesis and metastasis in vivo. Additionally, miR-489-3p inactivates Wnt/β-catenin signaling pathway and regulates USP48 to inhibit the ubiquitination of β-catenin. Moreover, USP48 propels the development of NSCLC cells. Conclusions The current study demonstrated that miR-489-3p promotes the malignant progression of NSCLC cells via targeting USP48, which might offer a new perspective into NSCLC treatment. Graphical abstract

The Paris Agreement has set the goal of carbon neutrality to cope with global climate change. China has pledged to achieve carbon neutrality by 2060, which will strategically change everything in our society. As the main source of carbon emissions, the consumption of fossil energy is the most profoundly affected by carbon neutrality. This work presents an analysis of how China can achieve its goal of carbon neutrality based on its status of fossil energy utilization. The significance of transforming fossils from energy to resource utilization in the future is addressed, while the development direction and key technologies are discussed.

Abstract Background This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

Background & Aims: Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor with high morbidity and mortality. AT-rich interaction domain 1A (ARID1A) accounts for up to 10% of mutations in liver cancer, however, its role in HCC remains controversial, and no targeted therapy has been established. Methods: The expression of ARID1A in clinical samples was examined by Western blot and immunohistochemical staining. ARID1A was knocked out by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) in HCC cell lines, and the effects of glucose deprivation on cell viability, proliferation, and apoptosis were measured. Mass spectrometry analysis was used to find ARID1A-interacting proteins, and the result was verified by co-immunoprecipitation and Glutathione S Transferase (GST) pull-down. The regulation of ARID1A target gene USP9X was investigated by chromatin immunoprecipitation, Glutathione S Transferase (GST) pull-down, luciferase reporter assay, and so forth. Finally, drug treatments were performed to explore the therapeutic potential of the agents targeting ARID1A-deficient HCC in vitro and in vivo. Results: Our study has shown that ARID1A loss protected cells from glucose deprivation–induced cell death. A mechanism study disclosed that AIRD1A recruited histone deacetylase 1 via its C-terminal region DUF3518 to the promoter of USP9X, resulting in down-regulation of USP9X and its target protein kinase AMP-activated catalytic subunit α2 (PRKAA2). ARID1A knockout and a 1989∗ truncation mutant in HCC abolished this effect, increased the levels of H3K9 and H3K27 acetylation at the USP9X promoter, and up-regulated the expression of USP9X and protein kinase AMP-activated catalytic subunit α2 (PRKAA2), which mediated the adaptation of tumor cells to glucose starvation. Compound C dramatically inhibited the growth of ARID1A-deficient tumors and prolongs the survival of tumor-bearing mice. Conclusions: HCC patients with ARID1A mutation may benefit from synthetic lethal therapy targeting the ubiquitin-specific peptidase 9 X-linked (USP9X)–adenosine 5‘-monophosphate–activated protein kinase (AMPK) axis.