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Abstract The deep‐sea ground contains a huge amount of energy and mineral resources, for example, oil, gas, and minerals. Various infrastructures such as floating structures, seabed structures, and foundations have been developed to exploit these resources. The seabed structures and foundations can be mainly classified into three types: subsea production structures, offshore pipelines, and anchors. This study reviewed the development, installation, and operation of these infrastructures, including their structures, design, installation, marine environment loads, and applications. On this basis, the research gaps and further research directions were explored through this literature review. First, different floating structures were briefly analyzed and reviewed to introduce the design requirements of the seabed structures and foundations. Second, the subsea production structures, including subsea manifolds and their foundations, were reviewed and discussed. Third, the basic characteristics and design methods of deep‐sea pipelines, including subsea pipelines and risers, were analyzed and reviewed. Finally, the installation and bearing capacity of deep‐sea subsea anchors and seabed trench influence on the anchor were reviewed. Through the review, it was found that marine environment conditions are the key inputs for any offshore structure design. The fabrication, installation, and operation of infrastructures should carefully consider the marine loads and geological conditions. Different structures have their own mechanical problems. The fatigue and stability of pipelines mainly depend on the soil‐structure interaction. Anchor selection should consider soil types and possible trench formation. These focuses and research gaps can provide a helpful guide on further research, installation, and operation of deep‐sea structures and foundations.

This paper carries out the transient behaviors of a thin rectangular plate considering different boundary conditions, Pasternak foundation, and thermal environment simultaneously. The governing differential equations of the system are derived by employing the Kirchhoff’s classical plate theory and Hamilton’s principle. This paper proposes a novel semi-analytical methodology, which integrates Laplace transform, the one-dimensional differential quadrature method, Fourier series expansion technique, and Laplace numerical inversion to analyze plates’ transient response. The proposed method can obtain dynamic response of the rectangular efficiently and accurately, which fills the gap of transient behaviors in semi-analytical method. A comparison between semi-analytical results and numerical solutions from the publication on this subject is presented to verify the method. Specifically, the results also agree well with the data generated by the Navier’s method. The convergence tests indicate that the semi-analytical algorithm is a quick convergence method. The effects of various variables, such as geometry, boundary conditions, temperature, and the coefficients of the Pasternak foundation, are further studied. The parametric studies show that geometry and temperature change are significant factors that affect the dynamic response of the plate.

In this paper, a 3D semi-analytical method is proposed by introducing the Durbin’s Laplace transform, as well as its numerical inversion method, state space approach and differential quadrature method to analyse the transient behaviour of functionally graded material cylindrical panels. Moreover, to investigate the effectiveness of the proposed semi-analytical solution, four boundary conditions are used to undertake the analyses. Comparing the proposed approach with other theoretical methods from the literatures, we see better agreements in the natural frequencies. Besides, the semi-analytical solution acquires nearly the same transient response as those obtained by ANSYS. Convergence studies indicate that the proposed method has a quick convergence rate with growing sample point numbers along the length direction, so do layer numbers increase along the radial direction. The effects of thickness/outer radius ratio, length/outer radius ratio and functionally graded indexes are also studied. When carbon nanotube is added to functionally graded material cylindrical panel, the composite structures have been reinforced greatly. The proposed 3D semi-analytical method has high accuracy for the analysis of composite structures. This study can serve as a foundation for solving more complicated environments such as fluid–structure interaction of flexible pipe or thermal effect analysis of functionally graded material in aerospace field.

Abstract Paclitaxel (PTX) is a first-line drug for ovarian cancer (OC) treatment. However, the regulatory mechanism of STUB1 on ferroptosis and PTX resistance in OC remains unclear. Genes and proteins levels were evaluated by RT-qPCR, western blot and IHC. Cell viability and proliferation were measured by CCK-8 and clone formation. The changes of mitochondrial morphology were observed under a transmission electron microscope (TEM). Reactive oxygen species (ROS), iron, malondialdehyde (MDA) and glutathione (GSH) were measured using suitable kits. The interactions among STUB1, HOXB3 and PARK7 were validated using Co-IP, and dual luciferase reporter assay. Our study found that STUB1 was decreased and PARK7 was increased in tumor tissue, especially from chemotherapy resistant ovarian cancer tissue and resistant OC cells. STUB1 overexpression or PARK7 silencing suppressed cell growth and promoted ferroptosis in PTX-resistant OC cells, which was reversed by HOXB3 overexpression. Mechanistically, STUB1 mediated ubiquitination of HOXB3 to inhibit HOXB3 expression, and HOXB3 promoted the transcription of PARK7 by binding to the promoter region of PARK7. Furthermore, STUB1 overexpression or PARK7 silencing suppressed tumor formation in nude mice. In short, STUB1 promoted ferroptosis through regulating HOXB3/PARK7 axis, thereby suppressing chemotherapy resistance in OC.

Abstract Under the condition of weak grid, the phase‐locked loop (PLL) is one of the main reasons for the sub‐synchronous oscillation of the grid‐connected inverter. Therefore, it is necessary to identify the PLL parameters of the grid‐connected inverter for the analysis of the inverter operating performance. This paper uses the sequence impedance model and measured impedance data of grid‐connected inverter to construct the identification function for parameter identification of PLL, and the function is calculated by particle swarm optimization algorithm to overcome the nonlinear problem of sequence impedance model. In addition, the identification frequency band is selected based on PLL parameter sensitivity to improve the parameter identification accuracy under the same impedance measurement error. At different frequencies, the positive correlation between the sensitivity of the PLL parameters and the identification accuracy is proven to determine the definite frequency band for PLL parameter identification of grid‐connected inverter. Finally, the feasibility and effectiveness of the above research are verified by simulation and semi‐physical experiments.

Abstract To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC.

Abstract The objective of this research was to establish a rat model for cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation that is both practical and economical and simulates clinical cardiac surgery. Concurrently, the study aimed to evaluate the myocardial protective effects conferred by histidine–tryptophan–ketoglutarate (HTK) cardioplegia. Thirty rats were randomly assigned to three groups: the histidine–tryptophan–ketoglutarate (HTK), 4:1 blood cardioplegia (BC) and del Nido cardioplegia (DN) groups. The cardiopulmonary bypass (CPB) procedure was implemented and sustained for a duration of one hour. Subsequent to the cessation of CPB, the rats were subjected to monitoring and observation for an additional two hours. Following this observation period, the heart and blood samples were procured for subsequent analysis. During CPB, the average hematocrit level was significantly below the typical physiological range (P

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells. Mechanistically, Dem binds to the deubiquitinating enzyme USP22 and promotes its degradation, resulting in increased ubiquitination and degradation of PD-L1 through the proteasome pathway. In addition, Dem increased the activity of cytotoxic T cells and reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumor-infiltrating lymphocytes (TILs), thereby activating the tumor immune microenvironment and inhibiting the growth of subcutaneous MC38 tumors in C57BL/6 mice. Moreover, we also found that the combination of Dem and CTLA4 antibodies can further improve the efficacy of antitumor therapy. Our study reveals the mechanism by which Dem promotes PD-L1 degradation and suggests that the combination of Dem and CTLA4 antibodies may improve the efficacy of immunotherapy.

Ferroelectric phase transition has been identified as a promising avenue for designing high-performance electrocaloric materials for zero-emission and solid-state refrigeration. However, extensive research has been limited to developing ferroelectric materials with large electrocaloric effects near room temperature, preventing them from meeting diverse refrigeration requirements. In this study, by leveraging the room-temperature phase diagram of the (PbLa)(ZrTi)O3 solution, we prepared a series of Pb0.775La0.15ZrxTi1−xO3 bulk ceramics spanning the ferroelectric and relaxor ferroelectric phase regions. This enabled the attainment of various phase transition features and temperatures. Finally, large electrocaloric effects, coupled with adjustable operation temperatures ranging from 150 to −45 °C, are successfully achieved through manipulation of the Zr/Ti ratio. This comprehensive range of operation temperatures effectively addresses diverse refrigeration application requirements, ranging from industrial equipment to freezer cabinets. This work not only underscores the expansion of the electrocaloric refrigeration application domain but also proposes a material design strategy tailored to meet these evolving demands.

Abstract Internal combustion engine fueled by carbon-free hydrogen (H2-ICE) offers a promising alternative for sustainable transportation. Herein, we report a facile and universal strategy through the physical mixing of Pt catalyst with zeolites to significantly improve the catalytic performance in the selective catalytic reduction of nitrogen oxides (NO x ) with H2 (H2-SCR), a process aiming at NO x removal from H2-ICE. Via the physical mixing of Pt/TiO2 with Y zeolite (Pt/TiO2 + Y), a remarkable enhancement of NO x reduction activity and N2 selectivity was simultaneously achieved. The incorporation of Y zeolite effectively captured the in-situ generated water, fostering a water-rich environment surrounding the Pt active sites. This environment weakened the NO adsorption while concurrently promoting the H2 activation, leading to the strikingly elevated H2-SCR activity and N2 selectivity on Pt/TiO2 + Y catalyst. This study provides a unique, easy and sustainable physical mixing approach to achieve proficient heterogeneous catalysis for environmental applications.

Abstract Background This study aimed to investigate the relationship between childhood physical activity enjoyment and current kinesiophobia among individuals with chronic low back pain (CLBP), considering the mediating influence of adult physical activity. Methods We recruited 648 adults (474 males, 174 females) with CLBP through an online platform. Of these, 99.1% (n = 642) were aged 18–60 years, and 0.9% (n = 6) were older than 60 years. Childhood physical activity enjoyment was retrospectively assessed using a single-item question to gauge participants’ enjoyment during primary school. Kinesiophobia was measured with the 11-item Tampa Scale for Kinesiophobia (TSK-11), and physical activity was assessed focusing on walking, moderate, and vigorous physical activities. Age, sex, education, and income served as control variables in the analysis. Results A significant negative association was found between childhood physical activity enjoyment and adult kinesiophobia. Additionally, childhood physical activity enjoyment was positively associated with adult physical activity across the three types of physical activities. In the adjusted mediation model, walking was identified as the only statistically significant partial mediator. Conclusion The findings highlight the long-term protective role of childhood physical activity enjoyment against the development of kinesiophobia in adulthood. Walking, in particular, holds unique therapeutic potential, emphasizing the importance of fostering physical activity enjoyment early in life for sustained physical activity and reduced risk of kinesiophobia among CLBP patients.

Abstract The interplay between the insect immune system and entomopathogenic fungi during cuticle penetration is not yet fully understood. Here, we show that a secretory protein COA1 (coat of appressorium 1) from Metarhizium robertsii, an entomopathogenic fungus causing diseases in a wide range of insects, is required to avoid host immune recognition during cuticle penetration. COA1 is highly expressed on the cuticle and translocated to the cell surface, where it directly binds with and masks carbohydrates of the fungal cell wall to avoid provoking the host’s intense immune response. Deletion of Coa1 results in a robust immune response, leading to a reduction in bacterial load in both the gut and hemocoel and ultimately attenuating fungal virulence. Our work reveals a novel cell surface protein indispensable for fungal pathogenicity via masking cell wall carbohydrates to avert a hypersensitive response from the host.

Abstract Background Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions. Methods A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD. Results Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62–1.89), hypertensive diseases (1.49, 1.38–1.62), cardiac arrests (1.52, 1.30–1.77), arrhythmia (1.76, 1.44–2.15), cerebrovascular diseases (1.86, 1.65–2.10), stroke (1.77, 1.54–2.03), ischemic stroke (1.85, 1.61–2.12), atherosclerosis (1.77, 1.57–1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15–1.51), pneumonia (1.37, 1.16–1.61), inflammatory bowel diseases (1.34, 1.16–1.55), liver diseases (1.59, 1.43–1.77), type 2 diabetes (1.48, 1.26–1.73), lipoprotein metabolism disorders (2.20, 1.96–2.47), purine metabolism disorders (1.61, 1.38–1.88), anemia (1.29, 1.15–1.45), sleep disorders (1.54, 1.33–1.78), renal failure (1.44, 1.21–1.72), kidney stone (1.27, 1.13–1.43), osteoarthritis (2.18, 2.00–2.39), osteoporosis (1.36, 1.14–1.61). OM had max weights for joint effects of AP on many conditions. Conclusions Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Abstract Background Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study’s aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. Methods Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride–glucose (TyG) index, triglyceride–glucose/body mass index (TyG–BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. Results Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG–BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261–2.000; HR 1.428, 95% CI 1.067–1.910; HR 1.431, 95% CI 1.105–1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. Conclusion Significant associations were found between the TyG index, TyG–BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Abstract Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

Abstract Converting solar energy into fuels is pursued as an attractive route to reduce dependence on fossil fuel. In this context, photothermal catalysis is a very promising approach through converting photons into heat to drive catalytic reactions. There are mainly three key factors that govern the photothermal catalysis performance: maximized solar absorption, minimized thermal emission and excellent catalytic property of catalyst. However, the previous research has focused on improving solar absorption and catalytic performance of catalyst, largely neglected the optimization of thermal emission. Here, we demonstrate an optically selective catalyst based Ti3C2Tx Janus design, that enables minimized thermal emission, maximized solar absorption and good catalytic activity simultaneously, thereby achieving excellent photothermal catalytic performance. When applied to Sabatier reaction and reverse water-gas shift (RWGS) as demonstrations, we obtain an approximately 300% increase in catalytic yield through reducing the thermal emission of catalyst by ~70% under the same irradiation intensity. It is worth noting that the CO2 methanation yield reaches 3317.2 mmol gRu −1 h−1 at light power of 2 W cm−2, setting a performance record among catalysts without active supports. We expect that this design opens up a new pathway for the development of high-performance photothermal catalysts.

Cerium oxide nanoparticles (CeO2 NPs), as the oxides of the most abundant elements in rare earths, have been widely used in biomedical and industrial production and other fields that are closely related to human life. China is a large country in resources and production of rare earth, and the impact of CeO2 NPs on human health has been increasingly concerned. In response to the possible health risks of CeO2 NPs, researchers begin to focus on their toxic effects on living organisms, especially on the reproductive system. The male reproductive system is not only responsible for producing sperm and regulating the secretion of testosterone, but also plays a key role in maintaining male sexual characters and function. Any adverse effects on the male reproductive system may lead to reduced fertility and reproductive dysfunction. Some studies have shown that long-term exposure to CeO2 NPs may lead to gonadal damage, sex hormone disorders, and other problems in male animals. Therefore, an in-depth study of the potential effects of CeO2 NPs on the male reproductive system is of great scientific significance and practical value. In this study, we reviewed the male reproductive toxicity of CeO2 NPs in terms of spermatogenic cells, spermatozoa structure, blood-testis barrier, hypothalamic-pituitary-gonadal axis, and functional changes in epididymis, and analyzed the effects of the size and shape of physicochemical parameters of CeO2 NPs on the toxicity to male reproductive system. The findings will provide a theoretical basis and scientific evidence for the rational use of CeO2 NPs.

Abstract Background Intestinal obstruction represents a severe intestinal disease associated with higher mortality rates. However, the determinants of mortality in patients with intestinal obstruction remain inadequately understood. This study sought to elucidate the potential risk factors associated with mortality in the context of intestinal obstruction during the COVID-19 pandemic. Methods A retrospective analysis was performed on a cohort of 227 patients diagnosed with intestinal obstruction at the First Hospital of Hebei Medical University, spanning the period from September 7, 2022, to January 7, 2023. The primary endpoint of the study was mortality within four weeks following discharge. Univariate and multivariable logistic regression models were utilized to evaluate the risk factors associated with mortality outcomes. Results A cohort of 227 patients diagnosed with intestinal obstruction (median age, 59.02 years [IQR, 48.95–70.85 years]) was included in our study. Malignant bowel obstruction (MBO) and COVID-19 were identified as independent risk factors for mortality among these patients. Notably, the mortality rate increased significantly to 38.46% when MBO was concomitant with COVID-19. Furthermore, postoperative pulmonary complications (PPC) (OR, 54.21 [death]; 95% CI, 3.17-926.31), gastric cancer (OR, 9.71 [death]; 95% CI, 1.38–68.18), VTE (Caprini Score ≥ 5) (OR, 7.64 [death]; 95% CI, 1.37–42.51), and COVID-19 (OR, 5.72 [death]; 95% CI, 1.01–32.29) were all determined to be independent risk factors for postoperative mortality. Additionally, gastric cancer could have emerged as one of the most severe risk factors for mortality in individuals with intestinal obstruction within the cohort of cancer patients, of which gastric cancer exhibited higher mortality rates compared to individuals with other forms of cancer. Conclusion The study identifies MBO, gastric cancer, COVID-19, PPC, and VTE as potential risk factors for mortality in cases of intestinal obstruction. These findings highlight the necessity for continuous monitoring of indicators related to these mortality risk factors and their associated complications, thereby offering valuable insights for the management and treatment of intestinal obstruction.

Abstract Photosynthesis converting solar energy to chemical energy is one of the most important chemical reactions on earth. In cyanobacteria, light energy is captured by antenna system phycobilisomes (PBSs) and transferred to photosynthetic reaction centers of photosystem II (PSII) and photosystem I (PSI). While most of the protein complexes involved in photosynthesis have been characterized by in vitro structural analyses, how these protein complexes function together in vivo is not well understood. Here we implemented STAgSPA, an in situ structural analysis strategy, to solve the native structure of PBS–PSII supercomplex from the cyanobacteria Arthrospira sp. FACHB439 at resolution of ~3.5 Å. The structure reveals coupling details among adjacent PBSs and PSII dimers, and the collaborative energy transfer mechanism mediated by multiple super-PBS in cyanobacteria. Our results provide insights into the diversity of photosynthesis-related systems between prokaryotic cyanobacteria and eukaryotic red algae but are also a methodological demonstration for high-resolution structural analysis in cellular or tissue samples.

Abstract Underwater friction stir welding (UFSW) achieves reliable joining between dissimilar materials and meets the welding demand for function and properties in lightweight structures of modern engineering. A defect monitoring method based on Variational Mode Decomposition optimized by Beluga Whale Optimization and Hilbert–Huang Transform (BWO–VMD–HHT) is proposed to solve the unclear feature of AE signal in UFSW due to the aqueous medium. UFSW experiments on Al alloy and carbon fiber reinforced thermoplastic (CFRTP) are carried out with AE signals measured. The time–frequency domain features of AE signals are extracted by BWO–VMD–HHT. The experimental results show that the main frequency of the AE signal is 22.5 kHz, and surface crack defects, shallow hole defects, and deep hole defects are accompanied by the transfer phenomena of different frequency components. Then, the feature vectors are built by frequency components in the BWO–VMD–HHT spectrum and reduced by principal component analysis, including 22.5 kHz, 24 kHz, 20.6 kHz, 18.4 kHz, 17.3 kHz, and 15.6 kHz. The feature vectors are divided into the train and test sets, and the welding defect prediction model (ResNet18-attention) is built by ResNet18 and trained by feature vectors. In the test set, the ResNet18-attention is compared with the BP, SVM, and RBF. Test results show that the precision of models has improved by at least 10%, which are trained by BWO–VMD–HHT features vector. Also, ResNet18-attention has achieved an average precision of 0.906 and recognizes the category of weld defect accurately, and this method can be applied to the defect monitoring of UFSW.

Abstract Quantitative measurement of RNA expression levels through RNA-Seq is an ideal replacement for conventional cancer diagnosis via microscope examination. Currently, cancer-related RNA-Seq studies focus on two aspects: classifying the status and tissue of origin of a sample and discovering marker genes. Existing studies typically identify marker genes by statistically comparing healthy and cancer samples. However, this approach overlooks marker genes with low expression level differences and may be influenced by experimental results. This paper introduces “GENESO,” a novel framework for pan-cancer classification and marker gene discovery using the occlusion method in conjunction with deep learning. we first trained a baseline deep LSTM neural network capable of distinguishing the origins and statuses of samples utilizing RNA-Seq data. Then, we propose a novel marker gene discovery method called “Symmetrical Occlusion (SO)”. It collaborates with the baseline LSTM network, mimicking the “gain of function” and “loss of function” of genes to evaluate their importance in pan-cancer classification quantitatively. By identifying the genes of utmost importance, we then isolate them to train new neural networks, resulting in higher-performance LSTM models that utilize only a reduced set of highly relevant genes. The baseline neural network achieves an impressive validation accuracy of 96.59% in pan-cancer classification. With the help of SO, the accuracy of the second network reaches 98.30%, while using 67% fewer genes. Notably, our method excels in identifying marker genes that are not differentially expressed. Moreover, we assessed the feasibility of our method using single-cell RNA-Seq data, employing known marker genes as a validation test.

Abstract Background Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC. Methods We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024. Results Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively. Conclusion ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.

The mechanism of phenol degradation by micro-electrolytic systems can be fully understood by evaluating the oxidation of active substances from the two aspects of phenol bond-breaking and mineralization, and the direction of promoting the generation of active substances is pointed out. In this article, the effects of H2O2, O2-•, ·OH and 1O2 in the degradation of phenol were analyzed using phenol and chemical oxygen demand (COD) removal rates as judgment indicators, respectively. And the addition of C6O8H6 to the micro-electrolysis system was adopted to promote the generation of active substances. The experimental results showed that the active substances which played a dominant effect in the process of phenol bond-breaking and mineralization were changed. While 1O2 is dominant in the bond-breaking of phenol, •OH is dominant in the mineralization of phenol. After adding C6O8H6 (1 mmol/L), the removal rates of phenol and COD were increased by 7.35 and 4.85%, respectively. This was attributed to the autoxidation reaction of C6O8H6 and the continuous supply of H+ while reducing Fe3+ to Fe2+. Additionally, the C6O8H6 regulated the reaction pathway to improve the utilization of H2O2. This study provides a new perspective for the understanding of active substances in micro-electrolysis systems. HIGHLIGHTS The main active substances in the bond-breaking and mineralization are different.; is the main active substance in the phenol bond-breaking process.; •OH is the main active substance in the phenol mineralization process.; C6O8H6 can promote the formation of active substances in the system.; C6O8H6 can promote the Fe2+/Fe3+ cycle and improve the utilization of •OH.;

Abstract Background Promoting the work adaptation of nurses returning to work after childbirth is key to improving their physical and mental health and ensuring the quality of nursing care. Although postpartum nurses have reported high work stress and poor adaptation after returning to work, little is known regarding the experiences, problems and further needs. This study aimed to explore the adaptation experiences of postpartum nurses returning to work. Methods This was a qualitative study with descriptive phenomenological approach. Individual semi-structured interviews were conducted between March and May 2023 in four tertiary hospitals in Changsha, mainland China, which were selected using convenience sampling. A total of 16 postpartum nurses returning to work within one year were recruited using purposive sampling and maximum variation sampling. The interviews were analysed using the Colaizzi’s 7-step method. Results ‘Breakdown and healing’ is a strong thread in postpartum nurses’ work adaptation. It links 13 subthemes in the interview data, which can be grouped under three overarching themes: (a) changes and challenges of multiple roles; (b) self-coping and social support; and (c) further needs after returning to work. The phrase ‘breakdown and healing’ reflects the mutual relationship between stress and coping among postpartum nurses. The changes and challenges associated with being required to fulfil multiple roles of mothers, wives and nurses make the subjects feel on the verge of ‘breakdown’. When returning to work, most of them move slowly towards ‘healing’ through positive self-management and support from their partners, families, supervisors and colleagues. Moreover, their ongoing demands and unsolved problems – such as their desire for a workplace that is friendly and serves their needs – were generated by the constant process of ‘breakdown and healing’. Conclusions Understanding how postpartum nurses returning to work perceive adaptation experiences is essential for nursing managers, who can use the findings to implement targeted measures to shorten postpartum nurses’ maladaptation period after returning to work and promote their work adaptation. This study underscores the critical importance of personalized return-to-work training, flexible work arrangements, support from colleagues and managers, well-established maternal facilities and services, and targeted policy efforts in enhancing postpartum nurses’ work adaptation.

Abstract Background Extranodal natural killer/T-cell lymphoma (ENKTL) with tonsil involvement is not common, especially in children. Case presentation A 13-year-old girl presented with an unexplained sore throat for more than 2 months, together with intermittent fever and suppurative tonsilitis. Nasopharyngoscopy revealed a pharyngeal mass. Enhanced computed tomography (CT) scan showed tonsillar hypertrophy and punctate calcification. Chronic pyogenic granulomatous inflammation with pseudoepithelial squamous epithelial hyperplasia was observed in left tonsil, and pyogenic granulomatous inflammation and a small number of T-lymphoid cells were detected in the right tonsil. The immunohistochemical results showed CD2+, CD3+, CD4+, CD5+, CD8+, granzyme B+, and TIA-1+. The Ki-67 proliferation index was 20%. The case showed T cell receptor gene rearrangement. Finally, the case was diagnosed as ENKTL of stage II with tonsil involvement. The patient received 6 cycles of chemotherapy with SMILE regimen, and showed complete response with no recurrence in the follow-up. Conclusion We presented a rare case of ENKTL with tonsil involvement in a child. The patient showed complete response to the SMILE chemotherapy with no recurrence.

Abstract Background The role of lifestyle factors and their relative contributions to the development and mortality of cardio-renal-metabolic multimorbidity (CRMM) remains unclear. Methods A study was conducted with 357,554 UK Biobank participants. CRMM was defined as the coexistence of two or three cardio-renal-metabolic diseases (CRMDs), including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD). The prospective study examined the associations of individual and combined lifestyle scores (diet, alcohol consumption, smoking, physical activity, sedentary behavior, sleep duration and social connection) with longitudinal progression from healthy to first cardio-renal-metabolic disease (FCRMD), then to CRMM, and ultimately to death, using a multistate model. Subsequently, quantile G-computation was employed to assess the relative contribution of each lifestyle factor. Results During a median follow-up of 13.62 years, lifestyle played crucial role in all transitions from healthy to FCRMD, then to CRMM, and ultimately to death. The hazard ratios (95% CIs) per score increase were 0.91 (0.90, 0.91) and 0.90 (0.89, 0.91) for healthy to FCRMD, and for FCRMD to CRMM, and 0.84 (0.83, 0.86), 0.87 (0.86, 0.89), and 0.90 (0.88, 0.93) for mortality risk from healthy, FCRMD, and CRMM, respectively. Among the seven factors, smoking status contributed to high proportions for the whole disease progression, accounting for 19.88–38.10%. High-risk diet contributed the largest proportion to the risk of transition from FCRMD to CRMM, with 22.53%. Less-frequent social connection contributed the largest proportion to the risk of transition from FCRMD to death, with 28.81%. When we further consider the disease-specific transitions, we find that lifestyle scores had slightly stronger associations with development to T2D than to CVD or CKD. Conclusions Our study indicates that a healthy lifestyle may have a protective effect throughout the longitudinal progression of CRMM, informing more effective management and treatment. Smoking status, diet, and social connection played pivotal roles in specific disease transitions.

Abstract Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the ‘hotspots’, which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where ‘hotspots’ are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10−14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.

Abstract Background The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. Methods This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. Results In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (β CMEC = 0.068, β UK−Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (β CMEC = 0.027, β UK−Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. Conclusions Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.

With the increasing importance of mine water prevention and control in coal mining, higher requirements have been put forward for precise seismic exploration methods. Conventional seismic exploration based on isotropy is increasingly unable to meet the high-precision exploration requirements for coal seams and their roof and floor under complex conditions. Based on the orthogonal anisotropy characteristics of coal bearing strata, the periodic thin interlayer anisotropy and fracture induced anisotropy are comprehensively considered. A wide-angle imaging method based on high-order motion correction is proposed to flatten the in-phase axis and improve the accuracy of far and near offset motion correction for the characteristics of the transverse isoropy medium with vertical symmetry axis(VTI). Applying the Offset Vector Tile(OVT) domain processing to eliminate anisotropy in different directions under structural fractures in coal bearing strata, in response to the characteristics of the transverse isoropy with horizontal axis ofs symmetry medium(HTI). Improve imaging accuracy and resolution during seismic data processing. Improve imaging accuracy and resolution during the seismic data processing phase. On the basis of wide azimuth and high fidelity imaging, lithology interpretation is based on the pseudo acoustic method of rock physical characteristics. By reconstructing the acoustic time difference logging curve and incorporating formation lithology information into the velocity curve, the spatial distribution characteristics of formation lithology can be analyzed through inversion iteration. Fracture interpretation is based on ellipse fitting of azimuth offset information contained in OVT gathers to obtain attenuation gradient of seismic wave in different azimuth, and fracture density and azimuth are fitted to obtain distribution characteristics of formation fracture density. To achieve precise exploration of the two key parameters affecting mine flooding, the coal seam roof aquifer and the water conducting fracture zone. On this basis, a comprehensive evaluation is conducted on the water production risk zone of the coal seam roof. The actual water content risk assessment of the data is in good agreement with the production well situation. The method was applied to the research area, and the actual data of water content risk assessment matched well with the production well situation. The results verified the feasibility and applicability of the proposed risk assessment method, providing useful reference for predicting mine flood risk areas in coal mining.

Abstract Aim Tumor budding (TB) has excellent prognostic value in many solid tumors, but there is little research on it in hepatocellular carcinoma (HCC). This study assessed the prognostic value of TB in patients with HCC who received hepatectomy. Methods This retrospective study included 210 patients with HCC who received curative hepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University, between 2016 and 2018. TB was evaluated on hematoxylin‐ and eosin‐stained slides according to the criteria established by the 2016 International Tumor Budding Consensus Conference. t‐tests, Chi‐squared tests, and rank‐sum tests were used to correlate the extent of TB with clinicopathological parameters. Prognostic analysis was performed using Cox regression models and the Kaplan–Meier method. Results The positive detection rate of TB was 45.2% (95/210) in 210 patients with HCC. Patients positive for TB always exhibit lower tumor differentiation, higher hepatitis B virus DNA levels, and more severe liver fibrosis. Multivariate Cox analysis identified TB (hazard ratio [HR]: 2.232, 95% confidence interval [CI]: 1.479–3.368, p

Abstract Background Several core breeding and supporting lines of the Qingyuan partridge chicken, a representative local chicken breed in China, have been developed over 20 years. Consequently, its economic traits related to growth and reproduction have been significantly improved by breeding selection and commercial utilization, but some characteristic traits, such as partridge feathers, high meat quality and sufficient flavor, have always been retained. However, effective methods for genetic assessment and functional gene exploration of similar trait groups are lacking. The presence of identical haplotype fragments transmitted from parent to offspring results in runs of homozygosity (ROH), which offer an efficient solution. In this study, genomes of 134 Qingyuan partridge chickens representing two breeding populations and one preserved population were re-sequenced to evaluate the genetic diversity and explore functional genes by analyzing the diversity, distribution, and frequency of ROH. Results The results showed a low level of genomic linkage and degree of inbreeding within both the bred and preserved populations, suggesting abundant genetic diversity and an adequate genetic potential of the Qingyuan partridge chicken. Throughout the long-term selection process, 21 genes, including GLI3, ANO5, BLVRA, EFNB2, SLC5A12, and SVIP, associated with breed-specific characteristics were accumulated within three ROH islands, whereas another 21 genes associated with growth traits including IRX1, IRX2, EGFR, TPK1, NOVA1, BDNF and so on were accumulated within five ROH islands. Conclusions These findings provide new insights into the genetic assessment and identification of genes with breed-specific and selective characteristics, offering a solid genetic basis for breeding and protection of Qingyuan partridge chickens.

Abstract With the rapid proliferation of climate policies in both number and scope, there is an increasing demand for a global-level dataset that provides multi-indicator information on policy elements and their implementation contexts. To address this need, we developed the Global Climate Change Mitigation Policy Dataset (GCCMPD) using a semisupervised hybrid machine learning approach, drawing upon policy information from global, regional, and sector-specific sources. Differing from existing climate policy datasets, the GCCMPD covers a large range of policies, amounting to 73,625 policies of 216 entities. Through the integration of expert knowledge-based dictionary mapping, probability statistics methods, and advanced natural language processing technology, the GCCMPD offers detailed classification of multiple indicators and consistent information on sectoral policy instruments. This includes insights into objectives, target sectors, instruments, legal compulsion, administrative entities, etc. By aligning with the sector classification of the Intergovernmental Panel on Climate Change (IPCC) emission datasets, the GCCMPD serves to help policy-makers, researchers, and social organizations gain a deeper understanding of the similarities and distinctions among climate activities across countries, sectors, and entities.

Abstract Immune-related GTPase M (IRGM) induces autophagy and suppresses inflammation, but its putative role and signaling mechanism remain undefined in the pathogenesis of liver failure. This study aimed to address how IRGM attenuates inflammatory injury by regulating autophagy in liver failure. In this study, a total of 10 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and 10 healthy controls were prospectively enrolled. Intrahepatic expression of IRGM/Irgm1, NLRP3 inflammasome (NLRP3, ASC, and caspase-1), autophagy-related proteins (LC3II, P62), and inflammatory cytokines (IL-1β, TNF-α) were measured. Autophagy was activated by rapamycin (4 mg/kg) in an acute liver failure (ALF) mouse model, which was used to further study the expression of Irgm1, NLRP3 inflammasome, autophagy-related proteins, and inflammatory cytokines using both qRT-PCR and Western blot analyses. Irgm1 expression was knocked down using Irgm1 short hairpin RNA (shRNA) in lipopolysaccharide (LPS)-induced AML12 cells to investigate the effects of Irgm1 deletion on autophagy and inflammation. We found that the expression of IRGM and autophagy-related proteins was significantly downregulated while the NLRP3 inflammasome was significantly upregulated in the livers of HBV-ACLF patients and the ALF mouse model (all P

Abstract Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3–99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

Abstract In the realm of video salient object detection (VSOD), the majority of research has traditionally been centered on third‐person perspective videos. However, this focus overlooks the unique requirements of certain first‐person tasks, such as autonomous driving or robot vision. To bridge this gap, a novel dataset and a camera‐based VSOD model, CaMSD, specifically designed for egocentric videos, is introduced. First, the SalEgo dataset, comprising 17,400 fully annotated frames for video salient object detection, is presented. Second, a computational model that incorporates a camera movement module is proposed, designed to emulate the patterns observed when humans view videos. Additionally, to achieve precise segmentation of a single salient object during switches between salient objects, as opposed to simultaneously segmenting two objects, a saliency enhancement module based on the Squeeze and Excitation Block is incorporated. Experimental results show that the approach outperforms other state‐of‐the‐art methods in egocentric video salient object detection tasks. Dataset and codes can be found at https://github.com/hzhang1999/SalEgo.

Ossification of the sacrotuberous ligament is a rare occurrence in soft tissue, with only 15 cases reported in the past few decades. We reported two cases of bilateral ossification in sacrotuberous ligaments and provided a concise review of the literature on this pathology. Clinical data, radiographic outcomes, and diagnostic and treatment details were obtained. This study aimed to summarize this disease's characteristics and investigate its pathogenesis through a review of literature from the last thirty years. This condition is often incidentally confirmed in elderly males via imagiological examination or gross anatomy and presents a low morbidity rate. Its pathogenesis may be related to stress concentration, excessive intake of element ions, injury repair, and improper operative technique. The majority of patients may not exhibit any clinical symptoms or signs and typically do not require medical interventions. It may be complicated with pudendal nerve entrapment syndrome. The long‐term effects of surgical resection and the most effective treatment approach remain areas for further research.

We evaluate the cytotoxicity, intracellular redox conditions, apoptosis, and methylation of DNMTs/TETs upon exposure to LiTFSI, a novel Per and Polyfluoroalkyl Substances (PFAS) commonly found in lithium-ion batteries, on human renal carcinoma cells (A498) and hepatoma cells (HepG2). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed both Perfluorooctane sulfonate (PFOS) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) had a dose-dependent effect on A498 and HepG2, with LiTFSI being less toxic. Intracellular redox conditions were assessed with a microplate reader and confocal, which showed a significant decrease in Reactive Oxygen Species (ROS) levels and an increase in Superoxide dismutase (SOD) content in both cells. Exposure to LiTFSI enhanced cell apoptosis, with HepG2 being more susceptible than A498. Quantitative analysis of mRNA expression levels of 19 genes associated with kidney injury, methylation, lipid metabolism and transportation was performed. LiTFSI exposure impacted kidney function by downregulating smooth muscle alpha-actin (Acta2) and upregulating transforming growth factor beta 1 (Tgfb1), B-cell lymphoma 2-like 1) Bcl2l1, hepatitis A virus cellular receptor 1 (Harvcr1), nuclear factor erythroid 2-like 2 (Nfe2l2), and hairy and enhancer of split 1 (Hes1) expression. LiTFSI exposure also affected the abundance of transcripts associated with DNA methylation by the expression of ten-eleven translocation (TET) and DNA methyltransferase (DNMT) genes. Furthermore, LiTFSI exposure induced an increase in lipid anabolism and alterations in lipid catabolism in HepG2. Our results provide new insight on the potential role of a new contaminant, LiTFSI in the regulation of oxidative stress, apoptosis and methylation in human renal carcinoma and hepatoma cells.

ABSTRACT Bombyx mori cypovirus (BmCPV), a member of the Reoviridae family, is a well-established research model for double-stranded RNA (dsRNA) viruses with segmented genomes. Despite its small genome size, the coding potential of BmCPV remains largely unexplored. In this study, we identified a novel small open reading frame within the S10 dsRNA genome, encoding a small viral peptide (VSP59) with 59 amino acid residues. Functional characterization revealed that VSP59 acts as a negative regulator of viral replication. VSP59 predominantly localizes to the cytoplasm, where it interacts with prohibitin 2 (PHB2), an inner membrane mitophagy receptor. This interaction targets mitochondria and triggers caspase 3-dependent apoptosis. Transient expression of vsp59 in BmN cells suppressed viral replication, an effect that was reversed by silencing PHB2 expression. Moreover, recombinant BmCPV with a mutated vsp59 exhibited reduced replication. Our findings demonstrate that VSP59 interacts with PHB2 on mitochondria, inducing apoptosis and thereby diminishing viral replication. This study expands our understanding of the genetic information encoded by the BmCPV genome and highlights the role of novel small peptides in host-virus interactions.IMPORTANCEA novel small open reading frame (sORF) from the viral genome was identified and characterized. The sORF could encode a small viral peptide (VSP59) that targeted mitochondria and induced prohibitin 2-related apoptosis, further attenuating Bombyx mori cypovirus replication.

Nanoparticles (NPs) have achieved extensive utilization across diverse domains, highlighting their unavoidable impact on health. The internalization of NPs carries the potential to trigger inflammation and instigate ailments by selectively targeting lysosomes, thereby posing significant public health concern. Lysosomes, essential organelles responsible for the degradation of biological macromolecules within cells, are crucial for cellular homeostasis and participate in key biological processes, including inter-organelle communication, signal transduction, plasma membrane repair, and immune responses. Consequently, a thorough understanding of lysosomal function is essential for elucidating the mechanisms underlying NPs-mediated toxicity. NPs-induced lysosomal dysfunction primarily involves disruptions in the acidic microenvironment of lysosomes, lysosomal membrane rupture, and membrane permeabilization. Additionally, potential molecular mechanisms contributing to the increased risk of lysosomal damage caused by NPs have been described, particularly concerning ion channel proteins such as V-ATPase, TRPM2, CLC-7, and LAMPs. This review aims to detail the alterations in lysosomal functionality induced by NPs and their associated mechanisms. By providing a theoretical framework, this review aims to support the potential application of NPs in biomedical fields.

ABSTRACT Nocardia farcinica can cause a rare, yet potentially fatal, central nervous system infection. NbtS protein may be a key virulence factor in N. farcinica infection of the brain. In this study, we investigated the function of the virulence-associated factor NbtS in microglial cells in vitro and in infected mice in vivo. We explored the interactions between NbtS and microglial cells (BV2 and human microglial clone 3), revealing that NbtS activates the toll-like receptor 4-dependent MyD88-IRAK4-IRAK1 and MAPK/nuclear factor kappa B (NF-κB) pathways, significantly enhancing pro-inflammatory responses as indicated by increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), as measured by ELISA and quantitative PCR. Apoptosis was elevated in these cells, as shown by increased expression of Bax and caspase-3 and decreased Bcl-2 levels. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay also confirmed the occurrence of apoptosis. In vivo, mice infected with an RS03155-deficient strain of N. farcinica exhibited higher survival rates and reduced brain inflammation, suggesting a pivotal role for the NbtS protein in the pathogenesis of Nocardia. Conservation of the RS03155 gene across Nocardia spp. was verified by PCR, and the immunogenic potential of NbtS was confirmed by Western blot analysis using sera from infected mice. These findings suggest that targeting NbtS may offer a novel therapeutic strategy against Nocardia infection.IMPORTANCEThe study presented in this article delves into the molecular underpinnings of Nocardia farcinica-induced neuroinflammation. By focusing on the salicylate synthase gene, RS03155, and its encoded protein, NbtS, we uncover a pivotal virulence factor that triggers a cascade of immunological responses leading to apoptosis in microglial cells. This research not only enhances our comprehension of the pathogenesis of Nocardia infections but also provides a potential therapeutic target. Given the rising importance of understanding host-microbe interactions within the context of the central nervous system, especially in immunocompromised individuals, the findings are of significant relevance to the field of microbiology and could inform future diagnostic and treatment modalities for Nocardia-associated neurological disorders. Our work emphasizes the need for continued research into the intricate mechanisms of microbial pathogenesis and the development of novel strategies to combat life-threatening infections.

The complexity of depression presents a significant challenge to traditional treatment methods, such as medication and psychotherapy. Recent studies have shown that exercise can effectively reduce depressive symptoms, offering a new alternative for treating depression. However, some depressed patients are unable to engage in regular physical activity due to age, physical limitations, and other factors. Therefore, pharmacological agents that mimic the effects of exercise become a potential treatment option. A newly discovered myokine, irisin, which is produced during exercise via cleavage of its precursor protein fibronectin type III domain-containing protein 5 (FNDC5), plays a key role in regulating energy metabolism, promoting adipose tissue browning, and improving insulin resistance. Importantly, FNDC5 can promote neural stem cell differentiation, enhance neuroplasticity, and improve mood and cognitive function. This review systematically reviews the mechanisms of action of exercise in the treatment of depression, outlines the physiology of exercise-related irisin, explores possible mechanisms of irisin’s antidepressant effects. The aim of this review is to encourage future research and clinical applications of irisin in the prevention and treatment of depression.

Summary: This retrospective study demonstrated that patients with advanced non-small cell lung cancer who experienced any-grade or grade 1–2 immune-related adverse events (irAEs) with immune checkpoint inhibitor plus chemotherapy (ICI+Chemo) as first-line treatment regimen had significantly longer progression-free survival (PFS; p

IntroductionKawasaki disease (KD), a common cause of acquired heart disease in children in developed countries, is primarily treated with intravenous immunoglobulin (IVIG), but some children demonstrate IVIG resistance with increased coronary artery injury risk. T cells have been demonstrated to be involved in the pathogenesis of KD and its treatment with IVIG. However, the role and mechanism of dual TCR T lymphocytes in the occurrence of KD and IVIG therapy remain unclear.MethodsThis study, based on scRNA-seq combined with TCR-seq technology, clustered the peripheral blood mononuclear cells of 3 healthy controls and 6 KD patients before and after IVIG treatment. Comparative analysis was conducted to investigate the differences in the proportion of single/dual receptor T cells, the characteristics of CDR3 repertoires, cell types, and the expression of transcription factors among the three groups. The study aimed to explore the correlation between dual TCR T cells and KD as well as IVIG treatment.ResultsIn our experimental results, we observed the presence of dual TCR T cells in all three groups. However, compared to the healthy control group and the IVIG-treated group, the KD patients before IVIG treatment exhibited a lower proportion of dual TCR T cells, with variability between samples, ranging from 4% to 15%. Notably, after IVIG treatment, the proportion of dual TCR T cells significantly increased, stabilizing above 12%, and these T cells also exhibited clonal expansion and a preference for V gene usage. In addition we found differences in dual TCR T cell subsets among the three groups, for example, IVIG treatment increases the proportion of dual TCR Treg cells, but it still remains below that of healthy control groups, significantly higher proportions of both dual TCR CD8 central and effector memory T cells in IVIG-treated KD patients, and differences in the expression of transcription factors between single and dual TCR T cells. These results suggest dual TCR T cells correlate with KD and IVIG treatment.ConclusionDual TCR T lymphocytes, especially dual TCR CD8 T cells and Treg cells, play crucial roles in the pathogenesis of KD and during IVIG treatment, providing strong support for further elucidating KD pathogenesis and optimizing treatment strategies.

Reduction of the driving range under either cold temperature or real-world running condition has become the biggest challenge for battery electric vehicle (BEV). In this paper, a simulation platform that combines a kinematics model, a thermal management model, and extracted typical running conditions has been established to estimate the energy flows inside the electric vehicle under cold temperature and real-world running condition. Three vehicles have been selected to validate the accuracy of the simulation platform, giving an accuracy between 90.6% and 96.6% according to different running conditions. Under highway running condition, the driving range could be reduced by 54%. Under urban running condition, when the environment temperature drops down to −20°C, the driving range is only 49.1% of that under 20°C. In addition, there could be a 4.4% increase in driving range if the target cabin temperature could be decreased from 28°C to 20°C. According to simulation, the application of motor waste heat recovery, internal gas recirculation, and heat pump, could increase the driving range at −7°C under urban running condition by 3.5%, 2.9%, and 3.9%, indicating a 10.3% improvement in total. This has been validated via experimental test after implementing these three approaches onto the test vehicle.

This paper introduces a systematic method for segmenting the main trachea and bronchioles in lung computed tomography scans. It begins with a stack-based three-dimensional region growth algorithm to outline the main trachea, which is then refined using morphological techniques to improve accuracy. The segmentation of bronchioles is achieved through domain labeling, lung tissue segmentation, adaptive binarization, and inner product analysis. The main trachea and bronchioles are integrated using an operating room (OR) operation and a novel splicing algorithm to form a complete tracheal tree. The method’s accuracy is validated against manual labeling, showing a Dice coefficient of about 0.99, on average, in lung parenchyma segmentation and a segmentation overlap with expert results ranging from 79.89% to 93.31% in lung trachea tree segmentation. This robust methodology is thoroughly tested and validated.