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Abstract High-resolution seismic image is critically important for mining minerals. In this study, we collected seismic data from a local dense seismic array consisting of 154 stations around the Anyuan mining area and its adjacent region of Pingxiang City, Jiangxi Province in South China, and applied the ambient noise tomography (ANT) method to image the shear wave velocity structure in the study area. Shallow crustal velocities at depths less than 3.3 km were determined by direct inversion of Rayleigh wave group velocity dispersion curves at the period range of 0.5–5.0 s. Overall, the S-wave velocity structure has a tight correlation with surface geological and tectonic features in the study area. The shear wave velocity structure in the shallow crust of the Anyuan Mine and its adjacent areas displayed distinct low-velocity anomalies, which can be attributed to the depression of sedimentary structures and coal mining activities in the Pingxiang-Leping region. The zones surrounding the Anyuan fault (AYF) and Wangkeng fault (WKF) zones exhibited low-velocity anomalies from the ground surface to ~ 3.3 km underground. And the low-velocity anomalies at depths less than 1.2 km could be related to the sedimentary environment of coal mine and the coal mining activities, while the low-velocity anomalies at depths below 1.2 km are caused by the presence of fracture medium, oil and gas in the fault zone. The shear wave velocity changes sharply across the AYF, and the characteristics of the velocity change interface indicate that the AYF is inclined toward the northwest, with its extension reaching depths of approximately 3 km underground. Graphical Abstract

Statins are known to be anti-inflammatory, but the mechanism remains poorly understood. Here, we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the adenosine triphosphate (ATP) synthase in the inner mitochondrial membrane and changes the proton gradient in the mitochondria. This activates nuclear factor kappa-B (NF-κB) and Jmjd3 expression, which removes the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus lipopolysaccharide (M1), macrophages, either treated with statins in vitro or isolated from statin-fed mice, express lower levels proinflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL-4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

We analyzed the major chemical components, hydrogen (δD) and oxygen isotopes (δ18O), and tritium activity in groundwater from Jiujiang well number 2 (JJ2) as well as atmospheric precipitation and water from the Maweishui spring and Tianhuajing reservoir in the Mt. Lushan region, Eastern China. The results show that the water in JJ2 is of the HCO3-Ca·Mg type, with ionic components mainly arising from calcite and dolomite mineral dissolution. According to the δD and δ18O data, the groundwater of JJ2 mainly comes from atmospheric precipitation, and the recharge elevation is 554 m. Results for tritium activity indicate that JJ2 is fed by both an ancient water supply and a new water supply within a period of 10 years. These results demonstrate that JJ2 has characteristics of both shallow and deep circulating water, which implies that aquifers involving two different recharge sources rise to the well surface via different circulation paths. That is exactly why JJ2 is tectonically sensitive and could display a remarkable gas radon anomaly before the Ruichang-Yangxin ML 5.0 earthquake in 2011. Our results also indicate that ascertaining the hydrological characteristics and cycling process of groundwater are crucial for understanding the earthquake anomalies and judging whether a seismic groundwater monitoring well is reliable or not.

Based on the event waveform data and its observation report of the 2011 Ruichang-Yangxin MS4.6 earthquake sequence processed by the double-difference method, waveform cross-correlation and coda wave interferometry, two groups of repeating earthquakes (cc≥0.920, recorded by station Huangmei and station Jiujiang) can be obtained: D1 (2011-09-11 05:44 ML2.3 and 2011-10-24 08:06 ML2.2) and D2 (2011-09-18 07:06 ML2.8 and 2011-10-24 08:06 ML2.2). It could be found that the velocity of early S wave coda increased within 1.5 months (2011-09-11—10-24) in source region after the MS4.6 Ruichang-Yangxin earthquake.

First of all，based on the theoretical crustal model，the feasibility and reliability of using the radial and transverse receiver functions to jointly invert the crustal anisotropy program are analyzed. Then the program is applied to the actual analysis of the receiver functions of Yugan seismic station. The results show that the polarization direction and time delay of the fast wave calculated by different objective functions are different. The joint objective function shows that the fast wave direction of Yugan seismic station is about 79° and the time delay is about 0.19 s.

The plasma membrane in mammalian cells is rich in cholesterol, but how the cholesterol is partitioned between the two leaflets of the plasma membrane remains a matter of debate. Recently, Liu et al. used domain 4 (D4) of perfringolysin O as a cholesterol sensor to argue that cholesterol is mostly in the exofacial leaflet (Liu et al., 2017). This conclusion was made by interpreting D4 binding in live cells using in vitro calibrations with liposomes. However, liposomes may be unfaithful in mimicking the plasma membrane, as we demonstrate here. Also, D4 binding is highly sensitive to the presence of cytosolic proteins. In addition, we find that a D4 variant, which requires >35 mol% cholesterol to bind to liposomes in vitro, does in fact bind to the cytoplasmic leaflet of the plasma membrane in a cholesterol-dependent manner. Thus, we believe, based on the current evidence, that it is unlikely that there is a significantly higher proportion of cholesterol in the exofacial leaflet of the plasma membrane compared to the cytosolic leaflet.

ATP-binding cassette transporter A1 (ABCA1) is required for the lipidation of apolipoprotein A-I (apoA-I), although molecular mechanisms supporting this process remain poorly defined. In this study, we focused on the role of cytosolic Ca2+ and its signaling and found that cytosolic Ca2+ was required for cholesterol efflux to apoA-I. Removing extracellular Ca2+ or chelating cytosolic Ca2+ were equally inhibitory for apoA-I lipidation. We provide evidence that apoA-I induced Ca2+ influx from the medium. We further demonstrate that calcineurin activity, the downstream target of Ca2+ influx, was essential; inhibition of calcineurin activity by cyclosporine A or FK506 completely abolished apoA-I lipidation. Furthermore, calcineurin inhibition abolished apoA-I binding and diminished JAK2 phosphorylation, an established signaling event for cholesterol efflux to apoA-I. Finally, we demonstrate that neither Ca2+ manipulation nor calcineurin inhibition influenced ABCA1's capacity to release microparticles or to remodel the plasma membrane. We conclude that this Ca2+-dependent calcineurin/JAK2 pathway is specifically responsible for apoA-I lipidation without directly modifying ABCA1 activity.

ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I) and generates HDL. Here, we demonstrate that ABCA1 also directly mediates the production of apoA-I free microparticles. In baby hamster kidney (BHK) cells and RAW macrophages, ABCA1 expression led to lipid efflux in the absence of apoA-I and released large microparticles devoid of apoB and apoE. We provide evidence that these microparticles are an integral component of the classical cholesterol efflux pathway when apoA-I is present and accounted for approximately 30% of the total cholesterol released to the medium. Furthermore, microparticle release required similar ABCA1 activities as was required for HDL production. For instance, a nucleotide binding domain mutation in ABCA1 (A937V) that impaired HDL generation also abolished microparticle release. Similarly, inhibition of protein kinase A (PKA) prevented the release of both types of particles. Interestingly, physical modulation of membrane dynamics affected HDL and microparticle production, rigidifying the plasma membrane with wheat germ agglutinin inhibited HDL and microparticle release, whereas increasing the fluidity promoted the production of these particles. Given the established role of ABCA1 in expending nonraft or more fluid-like membrane domains, our results suggest that both HDL and microparticle release is favored by a more fluid plasma membrane. We speculate that ABCA1 enhances the dynamic movement of the plasma membrane, which is required for apoA-I lipidation and microparticle formation.

ATP-binding cassette transporter A1 (ABCA1) plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I), a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.

Abstract Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain largely unexplored. In this study, we conducted RNA sequencing on bleomycin-induced senescent lung tissues from mice and identified Clic3 as the most significantly upregulated CLIC member. Furthermore, our findings revealed that the knockdown of CLIC3 mitigated intracellular chloride ion lose, mitochondrial dysfunction, nuclear enlargement, DNA damage, CS progression, and expression of senescence-associated secretory phenotype (SASP) triggered by bleomycin. Mechanistically, CLIC3 controls CS by translocating to the membrane where it interacts with extracellular signal-regulated kinase 7 (ERK7). Overall, our work demonstrates that the chloride intracellular channel CLIC3 modulates CS by repressing ERK7 activity and provides novel insights into the role of chloride channels.

Abstract Background Internal migrants in China have long been at a disadvantage in terms of access to publicly financed services, as well as the utilization of public health services. The aim of the study was to examine inequities in the use of basic public health services between internal migrants and the local population and estimate the factors that contributed to inequity in use. Methods The data for this study was derived from the 2017 wave of the China Migrants Dynamic Survey. Basic public health services utilization was measured by the establishment of health records, health education and chronic disease management. We performed multivariable logistic regressions to examine inequities in the utilization of basic public health services between locals and internal migrants, and Oaxaca-Blinder decomposition was used to explore possible explanations for such inequities between the two groups. Results A total of 27,998 cases were included in the analysis. We found that the utilization rates for establishment of health records, health education and chronic disease management among internal migrants were 71.3%, 49.2% and 65.7% lower than their local counterparts, respectively. The decomposition results indicated that the inequities in the establishment of health records between locals and internal migrants were mainly explained by whether people had heard of the National Basic Public Health Services Program (NBPHSP) (17.67%) and by health insurance (5.99%). The contributors to the inequities in health education between locals and internal migrants were community involvement (14.71%) and whether people had heard of the NBPHSP (13.89%). The main factors contributing to the difference in utilization of chronic disease management between the two groups were whether people had heard of the NBPHSP (14.49%) and community involvement (8.43%). Conclusions To reduce inequities in the utilization of basic public health services between locals and internal migrants, measures need to be taken to improve knowledge about the basic public health services and to help migrants integrate into the local community.

Abstract Evidence suggest that dietary advanced glycation end products (AGEs) might exert harmful effects on female reproductive function. However, population-based studies exploring the associations between dietary AGEs intake and female infertility remain lacking. This studyaimed to determine the relationship between dietary AGEs intake and female infertility based on National Health and Nutrition Examination Survey (NHANES). A cross-sectional analysis of 2863 participants in the NHANES 2013–2018 were included. The dietary AGEs, i.e. Nε-(carboxymethyl)lysine(CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of ultra-performance LC-tandem MS dietary AGEs database and two 24-h dietary recall interviews. Multivariate Logistic regression analyses were adopted to explore the relationships between dietary AGEs intake and self-reported infertility risk. Compared to the lowest tertile, total dietary AGEs (P-trend = 0.089) and CML (P-trend = 0.032) in the upper tertile were positively correlated with female infertility, and the corresponding odds radios (ORs) (95% confidence interval (CI)) were 1.44 (1.01, 2.06) and 1.64 (1.10, 2.45) respectively. Subgroups analysis found that in participants with overweight and obese, each 1-SD increment in dietary AGEs, CML and MG-H1 level was associated with 18% (95% CI: 1-38%), 21% (95% CI: 1-46%), and 16% (95% CI: 0-36%) elevated risk of infertility. Elevated dietary AGEs intake was associated with the higher risk of infertility for female subjects, this positive association was more pronounced in women with excess body weight.

Abstract Background Sperm-associated antigen 5 (SPAG5) is a mitotic spindle protein crucial for coordinating the separation of sister chromatids into daughter cells. Increasing evidence suggests that SPAG5 is overexpressed in various malignancies, functioning as an oncogene. However, research specifically examining SPAG5 in esophageal cancer remains limited. Methods In this research, we leveraged bioinformatics techniques to evaluate the expression and prognostic significance of SPAG5 in a variety of cancer types. We conducted Gene Set Enrichment Analysis (GSEA) to elucidate the relationship between SPAG5 and cancer characteristics. Additionally, we investigated the correlation between SPAG5 expression and immune cell infiltration utilizing the TIMER2.0 platform. The TIDE platform was used to assess the impact of SPAG5 on the effectiveness of immunotherapy and to screen for potential therapeutic drugs. We employed qRT-PCR and immunohistochemistry staining to ascertain the expression of SPAG5 in esophageal cancer tissue. Through cellular functional experiments, we examined the influence of SPAG5 expression on the proliferation, apoptosis, invasion, and migration of esophageal cancer cells. The Pathscan Stress Signaling Antibody Array was utilized to probe the potential molecular mechanisms of SPAG5. Results SPAG5 exhibits high levels of expression in various cancers, encompassing esophageal cancer, and its presence indicates an unfavorable prognosis. SPAG5 is primarily enriched in pathways associated with cellular proliferation and demonstrates a correlation with immune gene expression as well as the infiltration of immune cells. Suppression of SPAG5 expression in esophageal cancer cells not only inhibits cell proliferation, but also attenuates cell invasion and migration while inducing cellular apoptosis. The depletion of SPAG5 results in a decline in the levels of critical signaling proteins. Conclusion SPAG5 plays a pivotal role in esophageal cancer cell proliferation, apoptosis, and metastasis within the tumor microenvironment, making it a promising therapeutic target.

Abstract Background Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have been proven to prevent decline in kidney function and failure. Whether SGLT2i affect the risk of contrast-associated acute kidney injury (CA-AKI) remains uncertain. Methods Use of SGLT2i was assessed in consecutive diabetics undergoing coronary angiography (CA) or percutaneous coronary intervention (PCI) from January 2020 to May 2023 at a tertiary hospital in Chongqing, China. Propensity-matched analysis was used to adjust for baseline variables. CA-AKI was defined by the Acute Kidney Injury Network (AKIN) as creatinine increase ≥ 0.3 mg/dl (26.4 μmol/l), or a percentage increase in the serum creatinine level of ≥ 50%. Results A total of 604 new users of SGLT2i, and 298 chronic users of SGLT2i were matched with non-users. New use of SGLT2i was not associated with an increased incidence of AKIN-defined CA-AKI (OR 1.60; 95% CI 0.97–2.63; p = 0.065), in-hospital new-onset dialysis (OR 0.50; 95% CI 0.09–2.73; p = 0.422), or death (OR 0.55; 95% CI 0.18–1.66; p = 0.289). However, it was associated with a minor (> 25%) creatinine elevation (OR 1.55; 95% CI 1.04–2.30; p = 0.030), a 0.3 mg/dl increase in creatinine (OR 1.66; 95% CI 1.01–2.75; p = 0.048), and CMSC-defined CA-AKI (OR 1.51; 95% CI 1.02–2.24; p = 0.039). By 90 days, there was no evidence creatinine elevation differed between the two groups (p = 0.590). Chronic use of SGLT2i was not associated with AKIN-defined CA-AKI (OR, 0.92; 95% CI 0.41–2.05; p = 0.838). Conclusions New use of SGLT2i during CA or PCI was not associated with an AKIN-defined CA-AKI, and it did not translate into new-onset dialysis or death during hospital stay. Chronic usage of SGLT2i did not affect creatinine. Further randomized clinical trials are warranted to confirm this finding.

Abstract Sustainable development is a hot topic of global concern and sustainable human settlements (HS) are crucial to people’s happiness. Thus, strengthening the construction of HS will help enrich human settlements geography with theories of HS interactions, clarify the existing problems of the Chengdu-Chongqing urban agglomeration (CC), promote the harmonization of the human-land relationship, and realize the SDGs. The results were as follows. (1) the quality of HS exhibited an upward trend with diminishing disparities in PLE functions. (2) A spatial layout featuring the high quality of HS in the east and west and low quality in the central areas was identified, with Chengdu and Chongqing serving as two high-value core areas. (3) The evolution of the quality of HS levels to achieve a leapfrog shift was challenging and the spatial spillover effect and phenomenon of “club convergence” were evident. (4) Living function was a primary obstacle at the criterion layer and indicators within production function became major obstacle factors at the element layer. These findings have enriched the research scope of human settlements geography from the scale of urban agglomerations, and provided scientific decisions for the SDGs.

Abstract Link prediction infers the likelihood of a connection between two nodes based on network structural information, aiming to foresee potential latent relationships within the network. In social networks, nodes typically represent users, and links denote the relationships between users. However, some user nodes in social networks are hidden due to unknown or incomplete link information. The prediction of implicit links between these nodes and other user nodes is hampered by incomplete network structures and partial node information, affecting the accuracy of link prediction. To address these issues, this paper introduces an implicit link prediction algorithm based on extended social graph (ILP-ESG). The algorithm completes user attribute information through a multi-task fusion attribute inference framework built on associative learning. Subsequently, an extended social graph is constructed based on user attribute relations, social relations, and discourse interaction relations, enriching user nodes with comprehensive representational information. A semi-supervised graph autoencoder is then employed to extract features from the three types of relationships in the extended social graph, obtaining feature vectors that effectively represent the multidimensional relationship information of users. This facilitates the inference of potential implicit links between nodes and the prediction of hidden user relationships with others. This algorithm is validated on real datasets, and the results show that under the Facebook dataset, the algorithm improves the AUC and Precision metrics by an average of 5.17 $$\%$$ % and 9.25 $$\%$$ % compared to the baseline method, and under the Instagram dataset, it improves by 7.71 $$\%$$ % and 16.16 $$\%$$ % , respectively. Good stability and robustness are exhibited, ensuring the accuracy of link prediction.

Abstract Deep understanding of sugar metabolite-protein interactions should provide implications on sugar metabolic reprogramming in human physiopathology. Although tremendous efforts have been made for determining individual event, global profiling of such interactome remains challenging. Here we describe thermal proteome profiling of glycolytic metabolite fructose-1,6-bisphosphate (FBP)-interacting proteins. Our results reveal a chemical signaling role of FBP which acts as a phosphate donor to activate phosphoglycerate mutase 1 (PGAM1) and contribute an intrapathway feedback for glycolysis and cell proliferation. At molecular level, FBP donates either C1-O-phosphate or C6-O-phosphate to the catalytic histidine of PGAM1 to form 3-phosphate histidine (3-pHis) modification. Importantly, structure-activity relationship studies facilitate the discovery of PGAM1 orthostatic inhibitors which can potentially restrain cancer cell proliferation. Collectively we have profiled a spectrum of FBP interactome, and discovered a unique covalent signaling function of FBP that supports Warburg effect via histidine phosphorylation which inspires the development of pharmacological tools targeting sugar metabolism.

Abstract There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop new systems for treating bone related diseases and even repurposing current drug therapies. In this review, we shall summarise the latest progress in this area and present a perspective for future development in the field. We will focus on calcium-based nanoparticle systems that modulate calcium metabolism and consequently, the bone microenvironment to inhibit disease progression (including cancer). We shall also review the bone affinity drug family, bisphosphonates, as both a nano-drug and nano-delivery system for bone targeted therapy. The ability to target and release the drug in a controlled manner at the disease site represents a promising safe therapy to treat bone diseases in the future.

Abstract Background Terniopsis yongtaiensis, a member of the Podostemaceae family, is an aquatic flowering plant displaying remarkable adaptive traits that enable survival in submerged, turbulent habitats. Despite the progressive expansion of chloroplast genomic information within this family, mitochondrial genome sequences have yet to be reported. Results In current study, the mitochondrial genome of the T. yongtaiensis was characterized by a circular genome of 426,928 bp encoding 31 protein-coding genes (PCGs), 18 tRNAs, and 3 rRNA genes. Our comprehensive analysis focused on gene content, repeat sequences, RNA editing processes, intracellular gene transfer, phylogeny, and codon usage bias. Numerous repeat sequences were identified, including 130 simple sequence repeats, 22 tandem repeats, and 220 dispersed repeats. Phylogenetic analysis positioned T. yongtaiensis (Podostemaceae) within the Malpighiales order, showing a close relationship with the Calophyllaceae family, which was consistent with the APG IV classification. A comparative analysis with nine other Malpighiales species revealed both variable and conserved regions, providing insights into the genomic evolution within this order. Notably, the GC content of T. yongtaiensis was distinctively lower compared to other Malpighilales, primarily due to variations in non-coding regions and specific protein-coding genes, particularly the nad genes. Remarkably, the number of RNA editing sites was low (276), distributed unevenly across 27 PCGs. The dN/dS analysis showed only the ccmB gene of T. yongtaiensis was positively selected, which plays a crucial role in cytochrome c biosynthesis. Additionally, there were 13 gene-containing homologous regions between the mitochondrial and chloroplast genomes of T. yongtaiensis, suggesting the gene transfer events between these organellar genomes. Conclusions This study assembled and annotated the first mitochondrial genome of the Podostemaceae family. The comparison results of mitochondrial gene composition, GC content, and RNA editing sites provided novel insights into the adaptive traits and genetic reprogramming of this aquatic eudicot group and offered a foundation for future research on the genomic evolution and adaptive mechanisms of Podostemaceae and related plant families in the Malpighiales order.

Abstract Background Alcohol-related liver disease (ALD) and cardiovascular diseases share some common risk factors. This study aims to investigate the associations between Life’s Essential 8 (LE8), a comprehensive measure of cardiovascular health (CVH), and outcomes of ALD. Methods Data were obtained from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Cox proportional hazards models were employed to assess the relationships between LE8 and all-cause and cardiovascular mortality in patients with ALD. Additionally, restricted cubic splines (RCS), piecewise regression, and subgroup analyses were conducted. Results A total of 5321 ALD patients were included in this study with a mean LE8 score of 67.38. During a median follow-up period of 63 months, 228 all-cause deaths were recorded. After adjusting for potential confounders, the risk of all-cause mortality in the high CVH group decreased by 53.7% compared to the low CVH group (HR = 0.463, 95%CI = 0.223–0.965). The result was robust in subgroup analyses. The RCS analysis indicated a non-linear relationship between LE8 and cardiovascular mortality, showing that the risk of cardiovascular mortality decreased with increasing LE8 scores for values below 71.12 (HR = 0.949, 95% CI = 0.915–0.984). Conclusions LE8 score is inversely and linearly linked to all-cause mortality in ALD patients. Promoting adherence to optimal cardiovascular health may unveil additional strategies for the effective management of ALD patients and contribute to reducing their long-term mortality.

Abstract Background Complicated crown-root fractures are a type of tooth fracture that involves the enamel, dentin, and cementum and accompanied by pulp exposure. The treatment of a complicated crown-root fracture is always challenging due to the difficulties in achieving a hermetic seal and a stable restoration with a fracture level close to the crestale bone level. This study aimed to evaluate and compare the efficacy of single-visit and multi-visit approaches for fragment reattachment in complicated crown-root fractures of anterior teeth. Methods Two cohort consist of 10 adolescent patients in each group at both genders, who suffered from permanent anterior tooth complicated crown-root fracture were included. Fragment reattachment with root canal treatment was performed with either single or multiple-visit approach. Single visit fragment attachement combined with root cannel therapy was conducted in single-visit approach group immediately after injury. Fragment attachment, root cananel therapy and post resoration were performed during three times ‘ clinical visit in multi-visit approach group. Results All the patients in both groups achieved satisfactory aesthetic results one year after fragment reattachment. Patients who underwent a multi-visit approach had a significantly shorter operative duration, less intra-operative pain and fatigue, slightly better periodontal health at an early stage, and a decreased incidence of temporomandibular joint disorders compared to those who underwent a single-visit approach. However, multiple visits approach may increase the risk of fragment detachment postoperatively. Conclusion Fragment reattachment a reliable but temporary technique for adolescent patients who have suffered from complicated crown-root fractures. Multi-visit approach showed similar effecacy to single-visit approach but with slightly less complications. The choose of these two merhos should depend on the specific patient situation and patient compliance. Trial registration This prospective cohort study was retrospectively registered in Chinese Clinical Trial Registry (ChiCTR2300076811) on 19/10/2023.

Abstract To effectively enhance the ability to acquire information by making full use of the complementary features of infrared and visible images, the widely used image fusion algorithm is faced with challenges such as information loss and image blurring. In response to this issue, the authors propose a dual‐branch deep hierarchical fusion network (ADF‐Net) guided by an attention mechanism. Initially, the attention convolution module extracts the shallow features of the image. Subsequently, a dual‐branch deep decomposition feature extractor is introduced, where in the transformer encoder block (TEB) employs remote attention to process low‐frequency global features, while the CNN encoder block (CEB) extracts high‐frequency local information. Ultimately, the global fusion layer based on TEB and the local fusion layer based on CEB produce the fused image through the encoder. Multiple experiments demonstrate that ADF‐Net excels in various aspects by utilizing two‐stage training and an appropriate loss function for training and testing.

Based on the daily temperature data of 99 national meteorological stations in Beijing-Tianjin-Hebei region from March to May 1961 to 2020， the statistical methods such as Mann-Kendall trend test were used to analyze spatial and temporal distribution characteristics of late spring coldness from frequency， duration days and ratio of occurring stations to all stations， and the risk probability of different levels of late spring coldness was evaluated based on the information diffusion theory.The results indicated that： In the past 30 years， 2570 cases of late spring coldness occurred at 99 national meteorological stations， with the mildest and the least severe.In terms of frequency， the mild and moderate late spring coldness decreased from north to south， while severe late spring coldness decreased from northeast to southwest， the mild， moderate-severe and the total late spring coldness were most in April， the inter-annual occurrence frequency showed a downward trend， with a significant decrease from March to May and May.In terms of total duration days， mild and severe late spring coldness decreased from northeast to southwest， with moderate late spring coldness showing a pattern of high in north and south and low in middle.The average duration days of mild late spring coldness at each station was not significantly different， while the difference was significant in moderate and severe late spring coldness， the average duration days increased sharply with the increase of level.The annual mean duration days of late spring coldness was 6.9 d·a-1， showing a downward trend， with a decrease rate of 1.5 d·（10a）-1.The ratio of the stations showed an inter-annual downward trend in duration days was 88.9%， with 35 stations showing a significant decrease and the southern region experiencing a greater decrease than the northern region.The inter-annual downward trend in ratio of late spring coldness stations in March to May and May was significant， with the highest ratios of mild and moderate-severe late spring coldness in April， and the ratio of mild late spring coldness was much higher than that of moderate-severe late spring coldness in each month.The risk of late spring coldness decreased in a stepwise manner as the level increased， The stations with risk was mild and a return period of about 2 years or less was about 34.3% of all stations， mainly in Beijing， Shijiazhuang， Xingtai and Handan； The stations with risk was moderate and a return period of 5~10 years and 10 years or less was about 90% of all stations， and the former was concentrated at the north and south ends of Beijing-Tianjin-Hebei region， while the latter was mostly located in the central part of Beijing-Tianjin-Hebei region.The risk of severe late spring coldness in the research area was relatively low， with up to 97% of severe stations with a return period of about 25 years or less.

IntroductionThe US plays a crucial role in screening Asian women for breast disease. ABUS offers several advantages over traditional HHUS, including quicker examination, objectivity, and the ability to store and reconstruct images. This study marks the first large-scale opportunistic screening of ABUS in the population.MethodsBetween January 1, 2016, and December 31, 2019, 10,537 women aged 35–75 years from nine districts were randomly assigned to either HHUS or ABUS groups. Diagnostic methods were quantified, and comparisons were made using the Chi-square test.ResultsThe screening groups consisted of 5,445 participants for HHUS and 4,936 for ABUS. The HHUS and ABUS groups identified 90 carcinomas and 292 benign lesions or 71 carcinomas and 178 benign lesions, respectively. SE), SP, AC, PPV, and NPV for HHUS were 51.11%, 93.84%, 93.13%, 12.23%, and 99.13%, respectively, while for ABUS, they were 66.20%, 93.77%, 93.38%, 13.43%, and 98.98%. The area under the curve (AUC) values for HHUS and ABUS were 0.72 (95% CI: 0.67–0.78) and 0.86 (95% CI: 0.82–0.91), respectively, indicating superior diagnostic performance of ABUS over HHUS (Delong test p < 0.05).DiscussionABUS is user-friendly, requires minimal training, reduces reliance on examiner experience, and demonstrates potential for superior sensitivity compared to HHUS in breast cancer screening.

In this study, we evaluated the copy number variation in the genomes of two groups of Beichuan-white goat populations with large differences in litter size by FST method, and identified 1739 genes and 485 missense mutations in the genes subject to positive selection. Through functional enrichment, ITGAV, LRP4, CDH23, TPRN, RYR2 and CELSR1 genes, involved in embryonic morphogenesis, were essential for litter size trait, which received intensive attention. In addition, some mutation sites of these genes have been proposed (ITGAV: c.38C > T; TPRN: c.133A > T, c.1192A > G, c.1250A > C; CELSR1: c.7640T > C), whose allele frequencies were significantly changed in the high fecundity goat group. Besides, we found that new mutations at these sites altered the hydrophilicity and 3D structure of the protein. Candidate genes related to litter size in this study and their missense mutation sites were identified. These candidate genes are helpful to understand the genetic mechanism of fecundity in Beichuan white goat, and have important significance for future goat breeding.

Inflammatory processes play a central role in the development and complications of cardiovascular diseases (CVDs), profoundly affecting the severity and prognosis of these events. However, the current tools used to measure inflammation have some limitations. Blood biomarkers cannot pinpoint the location of inflammation and are vulnerable to various factors. Histological assessments ex vivo cannot accurately reflect the full dynamic picture of pathophysiology. The rapid development of positron emission tomography (PET) imaging not only enhances our understanding of biological processes in vivo but also contributes significantly to clinical management as a non-invasive biomarker. This review summarizes the PET imaging of key immune cell responses in CVDs, including immune cell metabolism, ligand/receptor interactions, and enzyme secretion, and discusses emerging opportunities and challenges in PET imaging-based inflammatory phenotyping and future perspectives.

Abstract Extracellular vesicles (EVs) composed of various biologically active constituents, such as proteins, nucleic acids, lipids, and metabolites, have emerged as a noteworthy mode of intercellular communication. There are several categories of EVs, including exosomes, microvesicles, and apoptotic bodies, which largely differ in their mechanisms of formation and secretion. The amount of evidence indicated that changes in the EV quantity and composition play a role in multiple aspects of cancer development, such as the transfer of oncogenic signals, angiogenesis, metabolism remodeling, and immunosuppressive effects. As EV isolation technology and characteristics recognition improve, EVs are becoming more commonly used in the early diagnosis and evaluation of treatment effectiveness for cancers. Actually, EVs have sparked clinical interest in their potential use as delivery vehicles or vaccines for innovative antitumor techniques. This review will focus on the function of biological molecules contained in EVs linked to cancer progression and their participation in the intricate interrelationship within the tumor microenvironment. Furthermore, the potential efficacy of an EV‐based liquid biopsy and delivery cargo for treatment will be explored. Finally, we explicitly delineate the limitations of EV‐based anticancer therapies and provide an overview of the clinical trials aimed at improving EV development.

Abstract Aiming at the optimal scheduling problem of virtual power plant (VPP) with multiple uncertainties on the source‐load side, this paper proposes a two‐stage stochastic robust optimal scheduling method considering the uncertainty of the source‐load side. This method combines the characteristics of robust optimization and stochastic optimization to model the source‐load uncertainty differentiation. The Wasserstein generative adversarial network with gradient penalty (WGAN‐GP) is used to generate electric and thermal load scenarios, and then K‐medoids clustering is used to obtain several typical scenarios. The min–max–min two‐stage stochastic robust optimization model is constructed, and the column constraint generation (C&CG) algorithm and dual theory are used to solve the problem, and the scheduling scheme with the lowest operating cost in the worst scenario is obtained.

Understanding the melting and sintering behavior of composite metal nanoparticles is of great significance to promote the synthesis and application of nanomaterials. In this work, molecular dynamics simulation method was employed to examine in detail the influence of sintering temperature, particle size and Fe content on the melting and sintering behavior of Cu-Fe mixed nanoparticles. The results show that the melting point of Cu-Fe mixed nanoparticles exhibits a strong size dependence and gradually increases with the increase in Fe content. High sintering temperatures significantly promotes the sintering process and the degree of atomic migration, and the diffusion behavior on the surface is enhanced, providing a significant driving force for sintering. Since smaller particle sizes have higher surface energy, the relationship between the neck parameters during the sintering process of different particle sizes is 4 nm > 6 nm > 8 nm, and the displacement of surface atoms is always greater than that of internal atoms. As the Fe content increases, the sintering of nanoparticles and the migration of atoms decrease, leading to a lower degree of sintering. This study further provides an atomic-scale theoretical basis for the melting and sintering behavior of Cu-Fe mixed nanoparticles.

To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. LISA for detection of anti-TP15, TP17, and TP47 antibodies were developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). Ninety serial serum samples from 6 syphilis rabbit models (3 treated, 3 untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as a reference. Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed a sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89–0.93) with TPPA were observed. In serial serum samples from rabbit models, significant differences in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31–51) and LISA-TP47 (day 41). In paired serum samples from syphilis patients, TRUST titres and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post-treatment (P

Backgrounds: The malfunction of peritoneal dialysis (PD) catheter is still an intractable problem. A modified open surgical revision technique with suturing fixation and without catheter removal for malfunctioning catheter was developed to evaluated the efficacy and safety between simultaneous catheter replacement technique.Methods: A total of 167 PD patients with malfunctioning catheter were retrospectively reviewed. For the salvage of PD catheters, patients underwent modified open surgical revision (group A) or simultaneous catheter replacement (group B). The baseline characteristics before operation, perioperative condition, complications and outcomes were compared between both groups.Results: Patients of group A showed significantly shorter operative time (67.4 ± 22.1 versus 82.8 ± 21.1 min, p = 0.009), less postoperative pain score within 24 h (median 0.0 versus 2.0, p

The direct preparation of large components by laser cladding (LC) is not economical, but if it is used as a means of trace element addition and combined with the high efficiency advantages of wire arc additive manufacturing (WAAM), efficient manufacturing and high degree of freedom design of components can be achieved. In this study, high toughness and high plasticity stainless steel components were successfully prepared by combining WAAM and LC. The microstructure in the hybrid deposited specimens evolved into a single austenite, and the proportion of cubic and {001} textures increased. The mechanical properties obtained were significantly greater than those recommended for use by ASTM A479. The toughness of the hybrid deposited specimens was significantly improved, with a maximum increase in yield strength of 32%, exceeding 350 MPa. The elongation increased by a maximum of 12.7%, reaching 89.2% in the horizontal direction.

The June 2013 extreme precipitation event in Alberta resulted in devastating flash floods that caused significant economic losses and societal disruption. In this study, two high-resolution experiments were conducted using the Weather Research and Forecasting (WRF) model to study the change of the 2013 Alberta extreme precipitation event in a warmer climate. The control experiment was forced with 6-hourly ERA-Interim reanalysis data, while the sensitivity experiment was forced with perturbed ERA-Interim reanalysis data with climate change signals derived from ten global climate models under the Representative Concentration Pathway 8.5 emission scenario. The results indicate that the 2013 Alberta extreme precipitation event is projected to exhibit two significant characteristics in a warming climate. First, precipitation is expected to increase over the Canadian Rocky Mountain region and eastern British Columbia. Second, the precipitation is expected to decrease over the Alberta and Saskatchewan Prairies. Future changes in the extreme precipitation event are associated with changes in the cyclone evolution, moisture transport, and atmospheric stability change caused by climate change. We also found that the increase in atmospheric stability due to the decrease of relative humidity in the lower atmosphere cause less precipitation to form over the plains and later enhance the orographic precipitation in the Canadian Rockies. In addition to the general increase of precipitable water under global warming, this mechanism causes the storm's precipitation to be more concentrated near the Canadian Rockies. The findings from this study could be beneficial for understanding future changes in extreme precipitation events that share similar characteristics.

There is a great deal of interest in improving the efficiency of arc-directed energy deposition (Arc-DED) of aluminium matrix composites and the uniform introduction of reinforcing particles. In this work, ceramic/aluminum-titanium gradient composites were manufactured by hybrid additive manufacturing with arc and laser cladding eutectic pools. The results show that the laser cladding powder feed method can have a higher powder capture rate compared to bypass feeding. Coupling the laser and powder changed the pulsed base-arc characteristics and increased the peak arc length. After the addition of the powder mixture, the aluminium matrix formed an Al3Ti reinforced phase, which evolved from needles to rods as the amount of powder increased. As the content of ceramic particles and the Al3Ti phase increased, the average hardness of the AMC components increased from 55.5–126 HV0.1 and the wear rate decreased from 6.16 × 10−3–1.25 × 10.−3 mm3·N−1·m−1.

ABSTRACT: Rising temperatures and intensified agricultural practices have heightened heat stress (HS)-related challenges in poultry farming, notably heat-induced sudden death in chickens. Wenchang chickens, recognized for their heat resistance, have emerged as the potential candidates for improving the economic efficiency of poultry farming. The adrenal gland plays a crucial role in preventing HS-induced heart failure sudden death by secreting hormones. However, little is known about the damage to and resilience of Wenchang chicken adrenal glands during HS. In this study, 34 healthy Wenchang chickens with similar weights were selected for formal experimentation, with 10 as the control group (Con). Following a single exposure to acute HS of 42 ± 1°C and 65% relative humidity for 5 h, 15 deceased individuals formed the HS death (HSD) group, and 9 survived comprised the HS survival (HSS) group. ELISA revealed significant higher (P < 0.05) levels of COR and NE in the HSS and the lowest levels of CORT and EPI in the HSD. Histopathological analysis indicated major degeneration in HSS cortical and chromaffin cells and extensive cell necrosis (nuclear pyknosis) in HSD. Proteomic analysis identified 572 DEPs in HSD vs. Con and 191 DEPs in HSS vs. Con. Bioinformatics highlighted ER protein processing, especially ERAD as a key pathway for heat stress resistance (HSR) in the adrenal gland, with HSPH1, DNAJA1, HSP90AA1, HSPA8 and HERPUD1 identified as regulating key molecules. Western blotting validated significantly higher (P < 0.01) protein levels in both HSS and HSD compared to the Con. Immunohistochemical staining showed increased cytoplasmic HSPH1-positive signal intensity under HS and enhanced HSP90AA1 nuclear signals, strongest in HSS. In summary, HS induces pathological damage in Wenchang chicken adrenal glands, affecting hormone secretion, and various heat shock proteins play crucial roles in cellular resistance. These results elucidate the biological basis of HSR in Wenchang chickens from the perspective of the adrenal gland and provide necessary research foundations for enhancing economic performance of various broilers in high-heat environments and screening drugs for HS treatment.

Abstract Objective This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. Methods Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. Results CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. Conclusion CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.

Abstract Background Osteonecrosis of the femoral head (ONFH) often leads to the collapse of the femoral head, ultimately resulting in patients undergoing premature total hip arthroplasty (THA). The surgical hip dislocation (SHD) technique is a type of hip-preserving surgery aimed at delaying or avoiding THA. This study aims to evaluate the clinical efficacy of SHD techniques through femoral head fovea fenestration and impaction bone grafting for the treatment of non-traumatic ONFH. Methods A retrospective analysis was conducted on the clinical data of 39 patients (39 hips) with non-traumatic ONFH who underwent SHD for treatment from 2016 to 2017. The Harris hip score (HHS) and the minimum clinically important difference (MCID) are used to evaluate clinical outcomes, while radiographic evaluations are conducted using X-rays. Kaplan-Meier survival analysis defined clinical failure as further THA, and conducted univariate survival analysis and Cox regression analysis. Any complications were recorded. Results All patients were followed up for 24–72 months, with an average of (60 ± 13.0) months. At the last follow-up, based on the HHS, 25 patients (64.1%) reported excellent and good clinical outcomes. 29 patients (74.3%) achieved MCID. Imaging evaluation of the postoperative femoral head status showed that 6 cases improved, 20 cases remained stable, and 13 cases showed progressed. Out of 39 hips, 12 hips had postoperative clinical failure, resulting in a clinical success rate of 69.2%. Association Research Circulation Osseous (ARCO) stage, China-Japan Friendship Hospital (CJFH) classification, and postoperative crutch-bearing time are risk factors for clinical failure. Postoperative crutch-bearing time of less than 3 months is an independent risk factor for clinical failure. After surgery, there was one case of sciatic nerve injury and one case of heterotopic ossification. There were no infections or non-union of the greater trochanter osteotomy. Conclusion The SHD technique through the femoral head fovea fenestration and impaction bone grafting provides a safe and effective method for treating non-traumatic ONFH, with good mid-term clinical outcomes. ARCO staging, CJFH classification, and postoperative crutch-bearing time are risk factors that affect clinical outcomes after surgery and lead to further THA. Insufficient postoperative crutch-bearing time is an independent risk factor for clinical failure.

Abstract Introduction Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. Methods Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. Results A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. Conclusions These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.

Abstract Numerous policies have been implemented to advance the growth of renewable energy. Nonetheless, certain policies have not yielded the anticipated impact on the progression of renewable energy development. In order to maximize the promotion effect of renewable energy policies, this study proposes a capacity allocation optimization method of wind power generation, solar power and energy storage in power grid planning under different policy objectives. First, based on the policy quantification, grey relation analysis (GRA) is used to calculate the correlation degree of the policy indicators on the planning capacity of renewable energy. Further, a multi‐objective capacity estimation model for wind, solar and energy storage is comprehensively presented. Some highly correlated policy indicators are transformed into the special constraints. And the economy and the stability of the power grid are integrated as the objective function. Meanwhile, the carbon trading and punishment for wind power and solar power abandonment are considered. Finally, the proposed model is solved by NSGA‐II‐PSO (particle swarm optimization) algorithm. The novelty of the algorithm is that the crossover operation of NSGA‐II is replaced by the position updating of particle swarm. The calculation result of the case study can effectively evaluate the optimal planning capacity of renewable energy under different policies, while ensuring the economic and the stability of the power system. The study can provide the reasonable basis and the valid analytical method for the policy formulation and the renewable energy development.

Soybean (Glycine max) is a short-day crop whose flowering time is regulated by photoperiod. The long-juvenile trait extends its vegetative phase and increases yield under short-day conditions. Natural variation in J, the major locus controlling this trait, modulates flowering time. We report that the three J-family genes influence soybean flowering time, with the triple mutant Guangzhou Mammoth-2 flowering late under short days by inhibiting transcription of E1-family genes. J-family genes offer promising allelic combinations for breeding.

Abstract Broad‐spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage‐displayed peptide onto a broad‐spectrum antimicrobial peptide and explored its structure–function relationship through one‐factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage‐derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

Abstract Background Inherited retinal dystrophies (IRDs) are a group of debilitating visual disorders characterized by the progressive degeneration of photoreceptors, which ultimately lead to blindness. Among the causes of this condition, mutations in the PCYT1A gene, which encodes the rate-limiting enzyme responsible for phosphatidylcholine (PC) de novo synthesis via the Kennedy pathway, have been identified. However, the precise mechanisms underlying the association between PCYT1A mutations and IRDs remain unclear. To address this knowledge gap, we focused on elucidating the functions of PCYT1A in the retina. Results We found that PCYT1A is highly expressed in Müller glial (MG) cells in the inner nuclear layer (INL) of the retina. Subsequently, we generated a retina-specific knockout mouse model in which the Pcyt1a gene was targeted (Pcyt1a-RKO or RKO mice) to investigate the molecular mechanisms underlying IRDs caused by PCYT1A mutations. Our findings revealed that the deletion of Pcyt1a resulted in retinal degenerative phenotypes, including reduced scotopic electroretinogram (ERG) responses and progressive degeneration of photoreceptor cells, accompanied by loss of cells in the INL. Furthermore, through proteomic and bioinformatic analyses, we identified dysregulated retinal fatty acid metabolism and activation of the ferroptosis signalling pathway in RKO mice. Importantly, we found that PCYT1A deficiency did not lead to an overall reduction in PC synthesis within the retina. Instead, this deficiency appeared to disrupt free fatty acid metabolism and ultimately trigger ferroptosis. Conclusions This study reveals a novel mechanism by which mutations in PCYT1A contribute to the development of IRDs, shedding light on the interplay between fatty acid metabolism and retinal degenerative diseases, and provides new insights into the treatment of IRDs.

Abstract Background Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. Methods Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan–Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. Results The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17–609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. Conclusions We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

High-entropy alloys (HEA) are a unique class of engineering alloys with excellent properties, and the study of their weldability is one of the key steps in applying them in the engineering field. AC/DC mixed gas tungsten arc welding (MIX-GTAW) can achieve high-quality welding of metal components, but there are few reports on the use of MIX-GTAW for HEA welding. This study focused on the (FeCoNi)96Al4 HEA and investigated the weld formation, microstructure, and mechanical properties of the (FeCoNi)96Al4 HEA MIX-GTAW to explore the possibility of using MIX-GTAW for high-entropy alloys. The results showed that the MIX-GTAW weld seam produced fish scale patterns, and compared to those of the DC-GTAW weld seam, the surface oxidation phenomenon was improved. The microstructure of the MIX mode weld seam with 40% AC (MIX-2) is significantly improved, resulting in a smaller average grain size. The weld structure index J of MIX-2 (40% AC) is 3.27, and the maximum strength in the PF diagram decreases to 6.90. The minimum ultimate tensile strength after welding can reach 435 MPa, with an elongation after fracture of 61%, maintaining a tensile strength of 94.26% of the base material and an elongation of approximately 90%. The average hardness of the (FeCoNi)96Al4 HEA welded sample fluctuates between 167 and 180 HV, and the hardness of the center of the weld seam is higher than that of the base metal.