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Abstract Background Asthma poses a significant global health challenge, characterized by high rates of morbidity and mortality. Despite available treatments, many severe asthma patients remain poorly managed, highlighting the need for novel therapeutic strategies. This study aims to identify potential drug targets for asthma by examining the influence of circulating plasma proteins on asthma risk. Methods This study employs summary-data-based Mendelian randomization (MR) and two-sample MR methods to investigate the association between 2940 plasma proteins from the UK Biobank study and asthma. The analysis includes discovery (FinnGen cohort) and replication (GERA cohort) phases, with Bayesian colocalization used to validate the relationships between proteins and asthma. Furthermore, protein–protein interaction and druggability assessments were conducted on high-evidence strength protein biomarkers, and candidate drug prediction and molecular docking were performed for proteins without targeted drugs. Given the complexity of asthma pathogenesis, the study also explores the relationships between plasma proteins and asthma-related endpoints (e.g., obesity-related asthma, infection-related asthma, childhood asthma) to identify potential therapeutic targets for different subtypes. Results In the discovery cohort, 75 plasma proteins were associated with asthma, including IL1RAP, IL1RL1, IL6, CXCL5, and CXCL8. Additionally, 6 proteins (IL4R, LTB, CASP8, MAX, PCDH12, and SCLY) were validated through co-localization analysis and validation cohort. The assessment of drug targetability revealed potential drug targets for IL4R, CASP8, and SCLY, while candidate drugs were predicted for LTB and MAX proteins. MAX exhibited strong binding affinity with multiple small molecules indicating a highly stable interaction and significant druggability potential. Analysis of the 75 proteins with 9 asthma-related endpoints highlighted promising targets such as DOK2, ITGAM, CA1, BTN2A1, and GZMB. Conclusion These findings elucidate the link between asthma, its related endpoints, and plasma proteins, advancing our understanding of molecular pathogenesis and treatment strategies. The discovery of potential therapeutic targets offers new insights into asthma drug target research.

Abstract Coal and gas outbursts, along with rock bursts, are common dynamic disasters in coal mining, threatening the safety and green production of coal mines. The distribution of coal seam stress is an external factor contributing to coal mine power disasters. The drainage of confined water in coal seam roof is the primary factor of coal seam stress changes. Using theoretical analysis and numerical simulations, the influence of roof confined water on coal seam stress by looking at the law of stress and stress conservation transfer in the drainage layer is investigated. Our results show that: (1) after drainage, there is an increase in the local stress within the coal seam, with a stress concentration factor of 1.35. The influence range of theoretically calculated stress is consistent with the measured results. (2) the maximum value of drainage boundary stress correlated positively with the angle of the water-rich abnormal area, with a linear fitting of R2 = 0.98. These findings hold significant theoretical and practical implications for preventing and controlling dynamic disasters during the mining of water-rich coal seams.

Abstract Background Lipid metabolism dysregulation is a key characteristic of hepatocellular carcinoma (HCC) onset and progression. Elevated expression of immunoglobulin (Ig), especially the Igκ free light chain with a unique Vκ4-1/Jκ3 rearrangement in cancer cells, is linked to increased malignancy and has been implicated in colon cancer tumorigenesis. However, the role of Igκ in HCC carcinogenesis remains unclear. The aim of this study was to elucidate the pivotal roles of hepatocyte-derived Igκ in HCC development. Methods The rearrangement sequence and expression level of hepatocyte-derived Igκ in HCC cells were determined via RT-PCR, Sanger sequencing, immunohistochemistry, and western blot analysis. The function of Igκ in HCC tumorigenesis was assessed by silencing Igκ using siRNA or gRNA in various HCC cell lines. To assess the role of Igκ in HCC pathogenesis in vivo, a mouse model with hepatocyte-specific Igκ knockout and diethylnitrosamine (DEN) and carbon tetrachloride (CCL4)-induced HCC was utilized. The molecular mechanism by which Igκ affects HCC tumorigenesis was investigated through multiomics analyses, quantitative real-time PCR, immunoprecipitation, mass spectrometry, immunofluorescence, and metabolite detection. Results We confirmed that Igκ, especially Vκ4-1/Jκ3-Igκ, is highly expressed in human HCC cells. Igκ depletion inhibited HCC cell proliferation and migration in vitro, and hepatocyte-specific Igκ deficiency ameliorated HCC progression in mice with DEN and CCL4-induced HCC in vivo. Mechanistically, Vκ4-1/Jκ3-Igκ interacts with electron transfer flavoprotein subunit α (ETFA), delaying its protein degradation. Loss of Igκ led to a decrease in the expression of mitochondrial respiratory chain complexes III and IV, resulting in aberrant fatty acid β-oxidation (FAO) and lipid accumulation, which in turn inhibited HCC cell proliferation and migration. Conclusion Our findings indicate that the Igκ/ETFA axis deregulates fatty acid β-oxidation, contributing to HCC progression, which suggests that targeting fatty acid metabolism may be an effective HCC treatment strategy. The results of this study suggest that hepatocyte-derived Vκ4-1/Jκ3-Igκ may serve as a promising therapeutic target for HCC.

Abstract Bladder cancer is the fourth most common malignancy in men with poor prognosis. Programmed cell death (PCD) exerts crucial functions in many biological processes and immunotherapy responses of cancers. Cell death signature (CDS) is novel gene signature comprehensively considering the characteristics of 15 patterns of programmed cell death, which could affect the prognosis and immunotherapy benefits of cancer patients. Integrative machine learning procedure including 10 algorithms was conducted to construct a prognostic CDS using TCGA, GSE13507, GSE31684, GSE32984 and GSE48276 datasets. Immunophenoscore, intratumor heterogeneity (ITH), tumor immune dysfunction and exclusion (TIDE) score and five immunotherapy cohorts were used to evaluate the predictive value of CDS in immunotherapy response. The prognostic CDS constructed by StepCox[backward] + Ridge algorithms was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting overall survival of bladder cancer patients with the AUCs at 3-year, 5-year, and 7-year ROC of 0.740, 0.763 and 0.820 in TCGA cohort. Moreover, CDS score acted as an independent risk factor for overall survival rate of bladder cancer patients. Low CDS score had a higher abundance of immuno-activated cells, higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score, lower immune escape score, lower ITH score, lower cancer-related hallmarks score in bladder cancer. The CDS score was higher in non-responders in pan-cancer patients receiving immunotherapy. Our study constructed a novel prognostic CDS, which could serve as an indicator for predicting the prognosis in postoperative bladder cancer cases and immunotherapy benefits in pan-cancer. Low CDS score indicated a better prognosis and immunotherapy benefits.

Abstract The characterization of protein complex is vital for unraveling biological mechanisms in various life processes. Despite advancements in biophysical tools, the capture of non-covalent complexes and deciphering of their biochemical composition continue to present challenges for low-input samples. Here we introduce SNAP-MS, a Stationary-phase-dissolvable Native Affinity Purification and Mass Spectrometric characterization strategy. It allows for highly efficient purification and characterization from inputs at the pico-mole level. SNAP-MS replaces traditional elution with matrix dissolving during the recovery of captured targets, enabling the use of high-affinity bait-target pairs and eliminates interstitial voids. The purified intact protein complexes are compatible with native MS, which provides structural information including stoichiometry, topology, and distribution of proteoforms, size variants and interaction states. An algorithm utilizes the bait as a charge remover and mass corrector significantly enhances the accuracy of analyzing heterogeneously glycosylated complexes. With a sample-to-data time as brief as 2 hours, SNAP-MS demonstrates considerable versatility in characterizing native complexes from biological samples, including blood samples.

Abstract Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

Abstract We study the operator algebra of extended conformal defects in more than two spacetime dimensions. Such algebra structure encodes the combined effect of multiple impurities on physical observables at long distances as well as the interactions among the impurities. These features are formalized by a fusion product which we define for a pair of defects, after isolating divergences that capture the effective potential between the defects, which generalizes the usual Casimir energy. We discuss general properties of the corresponding fusion algebra and contrast with the more familiar cases that involve topological defects. We also describe the relation to a different defect setup in the shape of a wedge. We provide explicit examples to illustrate these properties using line defects and interfaces in the Wilson-Fisher CFT and the Gross-Neveu(-Yukawa) CFT and determine the defect fusion data thereof.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is one of the most lethal malignancies and highly heterogeneous. We thus aimed to identify and characterize iCCA cell subpopulations with severe malignant features. Methods Transcriptomic datasets from three independent iCCA cohorts (iCCA cohorts 1–3, n = 382) and formalin-fixed and paraffin-embedded tissues from iCCA cohort 4 (n = 31) were used. An unbiased global screening strategy was established, including the transcriptome analysis with the activated malignancy/stemness (MS) signature in iCCA cohorts 1–3 and the mass spectrometry analysis of the sorted stemness reporter-positive iCCA cells. A group of cellular assays and subcutaneous tumor xenograft assay were performed to investigate functional roles of the candidate. Immunohistochemistry was performed in iCCA cohort 4 to examine the expression and localization of the candidate. Molecular and biochemical assays were used to evaluate the membrane localization and functional protein domains of the candidate. Cell sorting was performed and the corresponding cellular molecular assays were utilized to examine cancer stem cell features of the sorted cells. Results The unbiased global screening identified RRM2 as the top candidate, with a significantly higher level in iCCA patients with the MS signature activation and in iCCA cells positive for the stemness reporter. Consistently, silencing RRM2 significantly suppressed iCCA malignancy phenotypes both in vitro and in vivo. Moreover, immunohistochemistry in tumor tissues of iCCA patients revealed an unreported cell membrane localization of RRM2, in contrast to its usual cytoplasmic localization. RRM2 cell membrane localization was then confirmed in iCCA cells via immunofluorescence with or without cell membrane permeabilization, cell fractionation assay and cell surface biotinylation assay. Meanwhile, an unclassical signal peptide and a transmembrane domain of RRM2 were revealed experimentally. They were essential for RRM2 trafficking to cell membrane via the conventional endoplasmic reticulum (ER)–Golgi secretory pathway. Furthermore, the membrane RRM2-positive iCCA cells were successfully sorted. These cells possessed significant cancer stem cell malignant features including cell differentiation ability, self-renewal ability, tumor initiation ability, and stemness/malignancy gene signatures. Patients with membrane RRM2-positive iCCA cells had poor prognosis. Conclusions RRM2 had an alternative cell membrane localization. The membrane RRM2-positive iCCA cells represented a malignant subpopulation with cancer stem cell features.

The Road of Tang Poetry in Eastern Zhejiang is a cultural route where nature and culture harmoniously intertwine. Mountain-type scenic areas play a vital role in providing core cultural ecosystem services (CES). To investigate the significance and distribution of landscape resources along the Poetry Road, a preliminary study was conducted in the densely concentrated areas of Shaoxing, Taizhou, and Ningbo. From these regions, six representative mountain-type scenic areas were selected for the research: Kuaiji Mountain, Qinwang Mountain, Wanwei Mountain, Tianmu Mountain, Tiantai Mountain, and Xuedou Mountain. Based on their designation status, these areas were categorized into national and non-national scenic areas. The research employed a combination of online and offline questionnaires, as well as semi-structured interviews. An importance-performance analysis (IPA) was introduced, and SPSS software was utilized to conduct U-tests on the statistical results. This analysis aimed to compare the differences in importance and performance of CES among the various mountain-type scenic areas. Furthermore, an overall evaluation of CES for the mountain-type scenic area was carried out using an optimization demand zoning approach, involving categories such as “Keeping up the good job”, “Concentrate here”, “Possible overkill”, and “Low priority”. Additionally, a comparative analysis was conducted between the two types of mountain-type scenic areas, considering aspects like aesthetic value, leisure tourism, cultural diversity, and nature education. The findings indicate that the overall importance of the core CES provided by mountain-type scenic areas significantly exceeds the performance score, implying that public expectations for these sites surpass the actual experience. Notably, the distinction between the two types of mountain-type scenic areas, national and non-national, lies primarily in their performance. Among the evaluation subcomponents, respondents’ perceptions are notably influenced by natural resource advantages, architectural style, recreation offerings, site iconicity, and historical heritage and preservation. The abundance of cultural activities emerges as a crucial factor contributing to the substantial performance disparity between the two types of scenic areas, underscoring the significant impact of cultural heritage on the development imbalance in mountain-type region. Furthermore, cultural heritage plays a pivotal role in promoting the establishment and enhancing the competitiveness and identity of mountain-type scenic areas. Consequently, prioritizing the protection and utilization of non-national mountain-type scenic areas cultural heritage can effectively elevate the level of CES supply and meet the demand in mountain-type scenic areas. The IPA has promoted the CES performance of mountain-type scenic areas to be closer to its importance, thereby fostering a more balanced CES of the Road of Tang Poetry in Eastern Zhejiang.

The study focused on the utilization of heat-pressed and stuffy slag, processed into an ultrafine vertical grinding mill. This pressed-heat and stuffy slag powder replaced traditional anticorrosion fillers, such as epoxy resin, xylene, butanol, and polyamide, therefore forming a composite anticorrosion coating. Tests were conducted to assess the hardness, adhesion, abrasion resistance, and flexibility of these coatings according to various standards: GB/T 1730—2007 (paints and varnishes–pendulum damping test), GB/T 1720—2020 (circle-drawing test of coating films), GB/T 1768—2006 (paints and varnishes–determination of resistance to abrasion-rotating abrasive rubber wheel method), and GB/T 1731—2020 (determination of flexibility of coating and putty films), respectively. Additionally, the salt mist resistance was tested in conformance with GB/T 1771—2007 (paints and varnishes–determination of resistance to neutral salt spray) and water absorption was evaluated consistent with HG/T 3344—2012 (determination of water absorption of paint film) for coatings. The contact angle, impedance modulus, and corrosion potential of the coatings were also determined using a contact angle measuring instrument, a precision impedance tester, and an electrochemical workstation. Moreover, the micromorphology, chemical composition, mineral composition, and particle size distribution were evaluated using electron microscopy, X-ray spectroscopy, X-ray diffraction, and laser particle size analysis, respectively. The research analyzed the impact of pressed-heat and stuffy slag powder on the mechanical properties and anticorrosive properties of the epoxy composite anticorrosion coatings. It found that the pressed-heat and stuffy slag consisted of C3S, C2S, Ca(OH)2, C2F, RO phase, and f-CaO possessed properties similar to silicate, thereby improving durability. The processing method using an ultrafine vertical grinding mill facilitated the mineralization of f-CaO, reducing particle size and increasing specific surface area. The study concluded that the optimal performance of heat-pressed and stuffy slag powder/epoxy composite anticorrosion coatings was achieved when the particle size uniformity was 2.240 and the addition rate was 5%. At this rate, the performance of the composite anticorrosion coating is the best, the average swing rod hardness test result is 115.75 s, adhesion reached level 3, wear was minimized, flexibility measured 4 mm, impedance modulus was 106.1 Ω·cm−2, and corrosion potential (E) was 0.143 V. In summary, heat-pressed and stuffy slag, a type of rigid particle, can improve the hardness, friction resistance, and mechanical properties of the epoxy coating system. A uniform particle size can enhance the denseness and anticorrosive properties of these coatings. This opens up new possibilities for the high-value utilization of pressed-heat and stuffy slag outside of building materials and fulfilling the dual purpose of “increasing efficiency with waste” in the steel industry and “reducing cost with waste” in the paint industry.

Abstract We investigate finite-temperature observables in three-dimensional large N critical vector models taking into account the effects suppressed by 1 N $$ \frac{1}{N} $$ . Such subleading contributions are captured by the fluctuations of the Hubbard-Stratonovich auxiliary field which need to be handled with care due to a subtle divergence structure which we clarify. The examples we consider include the scalar O(N) model, the Gross-Neveu model, the Nambu-Jona-Lasinio model and the massless Chern-Simons Quantum Electrodynamics. We present explicit results for the free energy density to the subleading order in 1 N $$ \frac{1}{N} $$ , which captures the thermal one-point function of the stress-energy tensor to this order. We also include the dependence on a chemical potential. We determine the Wilson coefficient in the thermal effective action that is sensitive to global symmetry for the first time directly in interacting CFTs, which produces a symmetry-resolved asymptotic density of states. We further provide a formula from diagrammatics for the one-point functions of general single-trace higher-spin currents. We observe that in most cases considered, these subleading effects lift the apparent degeneracies between observables in different models at infinite N, while in special cases the discrepancies only start to appear at the next-to-subleading order.

Abstract This study deeply analyzes the ecocultural heritage of the Tiantai Mountain area in Eastern China, assesses its current status and explores effective mechanisms for its conservation and construction. Employing remote sensing technology, kernel density analysis and Minimum Cumulative Resistance Model, the study comprehensively evaluated the environmental characteristics of the region and its role in historical and modern conservation efforts. The results demonstrate the unique distribution patterns of ecocultural heritage in various conservation zones, such as restoration, controlled construction and core conservation zone. Furthermore, the study highlights the importance of religious beliefs and clan systems in the preservation of traditional knowledge and practices, with significant impacts of local community participation on conservation strategies. This research provides new theoretical and practical support for the implemention of ecocultural heritage conservation and development within religiously significant areas, highlights the need for conservation measures and synergistic strategies between ecological and cultural practices.

Freshwater crabs play essential roles in the well-functioning of the inland aquatic ecosystems. However, due to the lack of sufficient molecular resources, the study of freshwater crabs has been greatly hindered. In this study, the mitochondrial genome of Huananpotamon koatenense, a freshwater crab endemic to China, was sequenced for the first time. This mitogenome sequence is 15,528 bp long, and contains 13 protein-coding genes, 2 rRNA genes and 22 tRNA genes. Phylogenetic analyses based on 25 mitogenomes showed that H. koatenense was clustered with the known congeneric species of H. lichuanense.

Abstract PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame. BRCA1 splice isoforms △11 and △11q can contribute to PARPi resistance by splicing out the mutation-containing exon, producing truncated, partially functional proteins. However, the clinical impacts and underlying drivers of BRCA1 exon skipping are not fully understood. We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for exon skipping and therapy response, including a matched PDX pair derived from a patient pre- and post-chemotherapy/PARPi. BRCA1 exon 11 skipping was elevated in PARPi resistant PDX tumors. Two independent PDX models acquired secondary BRCA1 splice site mutations (SSMs) that drive exon skipping, confirmed using qRT-PCR, RNA sequencing, immunoblotting and minigene modelling. CRISPR/Cas9-mediated disruption of splicing functionally validated exon skipping as a mechanism of PARPi resistance. SSMs were also enriched in post-PARPi ovarian cancer patient cohorts from the ARIEL2 and ARIEL4 clinical trials. Few PARPi resistance mechanisms have been confirmed in the clinical setting. While secondary/reversion mutations typically restore a gene’s reading frame, we have identified secondary mutations in patient cohorts that hijack splice sites to enhance mutation-containing exon skipping, resulting in the overexpression of BRCA1 hypomorphs, which in turn promote PARPi resistance. Thus, BRCA1 SSMs can and should be clinically monitored, along with frame-restoring secondary mutations.

Metal–organic frameworks (MOFs) are highly promising porous materials known for their exceptional porosity, extensive surface area, and customizable pore structures, making them an ideal solution for hydrogen storage. However, most MOFs research remains confined to the laboratory, lacking practical applications. To address this, the author proposes a shift towards practical applications, the creation of a comprehensive MOFs database, alignment of synthesis with practical considerations, and diversification of MOFs applications. These steps are crucial for harnessing the full potential of MOFs in real-world energy challenges.

Long pressure short extraction ventilation and dust removal method is one of the effective methods for removing high mass concentration dust in the excavation area of coal mine comprehensive heading face. Especially, the local flow field generated by the combination of pressure and suction is conducive to the removal and reduction of respiratory dust. However, the dynamic changes in the location of dust production sources have an unclear impact on the dust removal performance of this method. By considering the movement paths and reciprocating times of the dust source location in both horizontal and vertical directions, four dust source movement paths were designed based on the long pressure short extraction test platform. Combined with the regulation of the parameters of the long pressure short extraction ventilation system, the impact of the dust source on the spatial dust mass concentration, particle size mass concentration, and particle size distribution under different movement conditions was tested and analyzed. The results show that under the same ventilation parameters, the dust mass concentration caused by the horizontal path on the respiratory belt positions of drivers and pedestrians is lower than that caused by the vertical path. In the horizontal path, when the pressure air duct is located on the side near the exhaust duct and the pressure air outlet is located in an area about 1 m in front of the driver, the particle size mass concentrations of PM1, PM2.5 and PM10 at the breathing zone between the driver and pedestrian are the lowest, and the ventilation and dust removal effect is the best. The diffusion of spatial dust is manifested as: particles with a particle size less than 2.5 µm are easily collected and removed by the exhaust flow field at the exhaust port, while the particles with a particle size greater than 10 µm will escape from the dust generation source and exhaust area to the driver and the area behind them, and mainly settle naturally. Based on the optimal dust source movement path and ventilation parameters obtained from preliminary experiments, on-site experiments were conducted on the 2304 fully mechanized heading face of a coal mine in northern Shaanxi. The results show that the total dust mass concentration at the driver's position and pedestrian breathing zone position under the lateral path decreased to 85.6 mg/m3 and 21.9 mg/m3, respectively, with the highest dust reduction rate reaching 76.9%. The mass concentration of respirable dust decreased to 15.3 mg/m3 and 10.5 mg/m3 respectively, with a maximum dust reduction rate of 85.2% and the dust removal performance was significantly improved.

The ecological quality of a region is significantly influenced by its geographical conditions, which can yield different effects on ecosystems. Nevertheless, the lack of adequate technology has impeded quantitative investigations into these differences. Consequently, there is an increasing demand for effective techniques to quantitatively measure differences in ecological quality resulting from variations in geographical conditions. This study applied the novel Remote Sensing-based Ecological Index (RSEI) concurrently to two distinct provincial-level regions in China, Fujian and Ningxia, to quantitatively detect their ecological differences. These two regions possess contrasting geographical conditions, with Fujian having high forest coverage and abundant rainfall, while Ningxia features low forest coverage and extensive loess plateau and desert terrain. By linking geographical factors with their corresponding ecological responses, we conducted a comprehensive analysis to determine whether the contrasting geographical conditions between the two regions had caused significant disparities in their ecological status. The results indicate that the contrasting geographical conditions have indeed led to marked ecological differences, with Fujian exhibiting excellent ecological status, while Ningxia lags behind due to unfavorable geographical conditions. In terms of RSEI scores, Fujian consistently achieved higher RSEI values (>0.8) in the study years, reaching an excellent ecological level, whereas Ningxia recorded scores lower than 0.45 during the comparable years, corresponding to a poor to moderate ecological level. Regarding the impact of geographical factors on ecological conditions, the positive contributions of greenness and wetness indicators to the ecology in Fujian were significantly greater than those in Ningxia (58% vs. 39%), whereas the contributions of negative indicators, dryness and hotness, were notably higher in Ningxia compared to Fujian (|–61|% vs. |–42|%). The successful concurrent application of RSEI to these two geographically distant regions also demonstrates the robustness of the RSEI technique.

Abstract Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher $${F}_{1}$$ F 1 scores (average $${F}_{1}$$ F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.

Abstract Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair. Graphical Abstract

Abstract We study generalized symmetries of quantum field theories in 1+1D generated by topological defect lines with no inverse. This paper follows our companion paper on gapped phases and anomalies associated with these symmetries. In the present work we focus on identifying fusion category symmetries, using both specialized 1+1D methods such as the modular bootstrap and (rational) conformal field theory (CFT), as well as general methods based on gauging finite symmetries, that extend to all dimensions. We apply these methods to c = 1 CFTs and uncover a rich structure. We find that even those c = 1 CFTs with only finite group-like symmetries can have continuous fusion category symmetries, and prove a Noether theorem that relates such symmetries in general to non-local conserved currents. We also use these symmetries to derive new constraints on RG flows between 1+1D CFTs.

Abstract Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Abstract Background Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated. Results We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1. Conclusions The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs. Graphical Abstract

Abstract Personalized review generation is significant for e-commerce applications, such as providing explainable recommendation and assisting the composition of reviews. With the success of pre-trained language models (PLMs), prompt learning-based approaches have been employed to handle this task. However, the existing approach neglects the historical user-item interactions as well as the diverse semantics of the reviews (including semantically relevant reviews and semantically irrelevant reviews). In this paper, we propose GRAPA, a graph-enhanced prompt learning approach for personalized review generation. Specifically, GRAPA extracts topic-level information for each review to address the semantic diversity of reviews. Moreover, GRAPA employs a heterogeneous graph neural network (GNN) to explore the collaborative information hidden in historical user-item interactions. User and item representations generated by the GNN module as well as their ID embeddings are used as prompts and fed into a PLM to guide the generation process. To alleviate the interference of semantically irrelevant reviews, GRAPA further proposes a contrastive learning module to distinguish them. Experimental results on public datasets show that GRAPA outperforms existing methods by up to 4.3% in BLEU-4 and 5.4% in ROUGE2-F.

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn–Mg–Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Abstract Background Currently, industrial fermentation of Botrytis cinerea is a significant source of abscisic acid (ABA). The crucial role of ABA in plants and its wide range of applications in agricultural production have resulted in the constant discovery of new derivatives and analogues. While modifying the ABA synthesis pathway of existing strains to produce ABA derivatives is a viable option, it is hindered by the limited synthesis capacity of these strains, which hinders further development and application. Results In this study, we knocked out the bcaba4 gene of B. cinerea TB-31 to obtain the 1′,4′-trans-ABA-diol producing strain ZX2. We then studied the fermentation broth of the batch-fed fermentation of the ZX2 strain using metabolomic analysis. The results showed significant accumulation of 3-hydroxy-3-methylglutaric acid, mevalonic acid, and mevalonolactone during the fermentation process, indicating potential rate-limiting steps in the 1′,4′-trans-ABA-diol synthesis pathway. This may be hindering the flow of the synthetic pathway. Additionally, analysis of the transcript levels of terpene synthesis pathway genes in this strain revealed a correlation between the bchmgr, bcerg12, and bcaba1-3 genes and 1′,4′-trans-ABA-diol synthesis. To further increase the yield of 1′,4′-trans-ABA-diol, we constructed a pCBg418 plasmid suitable for the Agrobacterium tumefaciens-mediated transformation (ATMT) system and transformed it to obtain a single-gene overexpression strain. We found that overexpression of bchmgr, bcerg12, bcaba1, bcaba2, and bcaba3 genes increased the yield of 1′,4′-trans-ABA-diol. The highest yielding ZX2 A3 strain was eventually screened, which produced a 1′,4′-trans-ABA-diol concentration of 7.96 mg/g DCW (54.4 mg/L) in 144 h of shake flask fermentation. This represents a 2.1-fold increase compared to the ZX2 strain. Conclusions We utilized metabolic engineering techniques to alter the ABA-synthesizing strain B. cinerea, resulting in the creation of the mutant strain ZX2, which has the ability to produce 1′,4′-trans-ABA-diol. By overexpressing the crucial genes involved in the 1′,4′-trans-ABA-diol synthesis pathway in ZX2, we observed a substantial increase in the production of 1′,4′-trans-ABA-diol.

Abstract The exploration of eco‐friendly insulating gas to substitute the most potent greenhouse gas sulphur hexafluoride (SF6) has consistently garnered significant attention. Herein, the authors evaluated the feasibility of utilising perfluoromethyl vinyl ether (PMVE, C3F6O) as a new branch of eco‐friendly insulating gas for the first time. The primary dielectric and stability characteristics of PMVE regarding AC breakdown, partial discharge, dielectric recovery, and decomposition properties were revealed under various gas pressure and electrical field conditions. It was found that PMVE demonstrated superior dielectric strength, with the AC breakdown and PD inception voltage (PDIV) 1.10 and 1.14 times that of pure SF6. Furthermore, the dielectric strength of PMVE exhibits stability even after undergoing 100 cycles of AC breakdowns, and there is no observable formation of solid precipitation on the electrode surface. The discharge decomposition of PMVE mainly generates fluorocarbon (CF4, C2F6, C3F6, C3F8, etc.) and CO. Overall, the exceptional insulation stability and no absence of solid precipitation features endow PMVE to be utilised as a new eco‐friendly gas for SF6‐free gas‐insulated equipment.

Abstract China, the world’s largest carbon emitter, has one of the most stringent provincial emissions reduction programs, incorporated into its Five-Year National Plan to reduce carbon emissions. However, the widening energy intensity gap between provinces poses a great challenge for carbon reduction. In this study, we analyze the convergence of Energy intensity (EIC), i.e., the time-dependent decrease of differences among regional energy intensity over time focusing on a data set of 30 Chinese provinces from 2000 to 2015. Our goal is to identify the provinces that are responsible for the observed divergence in energy intensity and identify the factors causing that divergence in each individual case. The Theil index is used to capture inter-provincial energy inequality. We use the LMDI decomposition analysis to identify the drivers of energy inequality (energy consumption structure, energy efficiency, and industrial structure). The results suggest that reducing energy intensity in Inner Mongolia, Xinjiang, and Hebei is the key to solving China's increasing energy intensity “gap” dilemma. The factors causing the energy intensity divergence in Inner Mongolia and Xinjiang are related to lagging economic growth and low energy efficiency, which impedes carbon emission reductions significantly. The factors causing the divergence of energy intensity in Hebei are rooted in its heavy industrial structure. Our findings are directly applicable to crafting regional energy policy with more targeted and practical emission reduction programs.

Abstract Background This study aimed to investigate the alterations in structural integrity of superior longitudinal fasciculus subcomponents with increasing white matter hyperintensity severity as well as the relationship to cognitive performance in cerebral small vessel disease. Methods 110 cerebral small vessel disease study participants with white matter hyperintensities were recruited. According to Fazekas grade scale, white matter hyperintensities of each subject were graded. All subjects were divided into two groups. The probabilistic fiber tracking method was used for analyzing microstructure characteristics of superior longitudinal fasciculus subcomponents. Results Probabilistic fiber tracking results showed that mean diffusion, radial diffusion, and axial diffusion values of the left arcuate fasciculus as well as the mean diffusion value of the right arcuate fasciculus and left superior longitudinal fasciculus III in high white matter hyperintensities rating group were significantly higher than those in low white matter hyperintensities rating group (p

Abstract We analyze correlation functions of SU(k) × SU(2) F flavor currents in a family of three-dimensional N $$ \mathcal{N} $$ = 4 superconformal field theories, combining analytic bootstrap methods with input from supersymmetric localization. Via holographic duality, we extract gluon and graviton scattering amplitudes of M-theory on AdS4 × S 7/ℤ k which contains a ℂ2/ℤ k orbifold singularity. From these results, we derive aspects of the effective description of M-theory on the orbifold singularity beyond its leading low energy limit. We also determine a threshold correction to the holographic correlator from the combined contribution of two-loop gluon and tree-level bulk graviton exchange.

Abstract Background Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is an effective therapeutic target for diseases such as cancer, diabetes, aging, and neurodegeneration. However, an efficient tool for monitoring mTORC1 inhibition in living cells or tissues is lacking. Results We developed a genetically encoded mTORC1 sensor called TORSEL. This sensor changes its fluorescence pattern from diffuse to punctate when 4EBP1 dephosphorylation occurs and interacts with eIF4E. TORSEL can specifically sense the physiological, pharmacological, and genetic inhibition of mTORC1 signaling in living cells and tissues. Importantly, TORSEL is a valuable tool for imaging-based visual screening of mTORC1 inhibitors. Using TORSEL, we identified histone deacetylase inhibitors that selectively block nutrient-sensing signaling to inhibit mTORC1. Conclusions TORSEL is a unique living cell sensor that efficiently detects the inhibition of mTORC1 activity, and histone deacetylase inhibitors such as panobinostat target mTORC1 signaling through amino acid sensing.

Cardiovascular disease has emerged as the leading cause of death worldwide. Since coronary arteries, carotid arteries, and other blood vessels are prone to narrowing, small‐diameter artificial blood channels offer a crucial solution for restoring blood flow. Ideal grafts must emulate the structure of natural blood vessels, possess adequate mechanical strength, ensure long‐term patency, and incorporate functional cells with minimal immunogenicity. Enhanced cell sources and engineering methods are vital for the creation of functional small‐diameter blood vessels (SDBVs). Among potential cell sources, stem cells stand out due to their ability to differentiate into multiple cell types, self‐renew, and exhibit low immunogenicity. Additionally, three‐dimensionally (3D) printed vascular stents have attracted widespread attention for their precision and controllable bioink application. The need for tissue‐engineered blood vessels is currently rising, and innovative design concepts integrating stem cells and 3D printing present promising solutions. Herein, the construction requirements of vascular grafts are reviewed, current status of using stem cells as a cell source and 3D printing as an engineering strategy is described, and prospects and challenges for the development of SDBVs in the medical field are discussed.

Abstract Angiogenesis is crucial for successful bone defect repair. Co‐transplanting Bone Marrow Stromal Cells (BMSCs) and Endothelial Cells (ECs) has shown promise for vascular augmentation, but it face challenges in hostile tissue microenvironments, including poor cell survival and limited efficacy. In this study, the mitochondria of human BMSCs are isolated and transplanted to BMSCs from the same batch and passage number (BMSCsmito). The transplanted mitochondria significantly boosted the ability of BMSCsmito‐ECs to promote angiogenesis, as assessed by in vitro tube formation and spheroid sprouting assays, as well as in vivo transplantation experiments in balb/c mouse and SD rat models. The Dll4‐Notch1 signaling pathway is found to play a key role in BMSCsmito‐induced endothelial tube formation. Co‐transplanting BMSCsmito with ECs in a rat cranial bone defect significantly improves functional vascular network formation, and improve bone repair outcomes. These findings thus highlight that mitochondrial transplantation, by acting through the DLL4‐Notch1 signaling pathway, represents a promising therapeutic strategy for enhancing angiogenesis and improving bone repair. Hence, mitochondrial transplantation to BMSCS as a therapeutic approach for promoting angiogenesis offers valuable insights and holds much promise for innovative regenerative medicine therapies.

Many soils face dual challenges of cadmium (Cd) contamination and salinization. However, the response of crops, especially wheat, to combined Cd and salinity stress is not understood. Here, wheat was grown in a hydroponic model for 14 days under single and combined Cd and NaCl stresses. Growth parameters, tissue Cd2+ and Na+ contents, and leaf chlorophyll (Chl), O2•−, and MDA levels were determined. Comparative transcriptomic and metabolomic analyses of the leaves were performed. The results showed that combined stress had a greater inhibitory effect on Chl contents and generated more O2•− and MDA, resulting in more severe wheat growth retardation than those under Cd or NaCl stress. Stress-induced decrease in Chl levels may be attributed to the inhibition of Chl biosynthesis, activation of Chl degradation, or a decline in glutamate content. Cd addition weakened the promotional effect of NaCl on SOS1 gene expression, thereby increasing the Na+ content. Contrastingly, NaCl supplementation downregulated the Nramp and ZIP gene expressions related to Cd uptake and transport, thereby impeding Cd2+ accumulation. All stresses enhanced tryptophan content via promoting tryptophan biosynthesis. Meanwhile, Cd and NaCl stresses activated phenylpropanoid biosynthesis and purine metabolism, respectively, thereby increasing the levels of caffeic acid, fumaric acid, and uric acid. Activating the TCA cycle was important in the wheat’s response to combined stress. Additionally, NaCl and combined stresses affected starch and sucrose metabolism, resulting in sucrose and trehalose accumulation. Our findings provide a comprehensive understanding of the response of wheat to the combined Cd and salinity stress.

The electrodeposition process confronts significant challenges arising from mass transfer limitation and residual stress. To address these issues, an innovative method, combining megasonic agitation with coaxial jet electrodeposition, is introduced. This approach aims to enhance mass transfer and mitigate residual stress. First, an electrodeposition nozzle device was designed, and the liquid-phase mass transfer during electrodeposition was analyzed through finite element simulation. Simulation results indicate that the mass transfer coefficient increases with rising megasonic power density. Notably, when the megasonic power density reached 20 W/cm2, the mass transfer coefficient increased from 0.45 × 10−7 m/s to 18.63 × 10−7 m/s, compared to electrodeposition without megasonic agitation. Secondly, electrodeposition experiments were conducted both with and without megasonic assistance. X-ray diffraction (XRD) was employed to measure the residual stress values of the electrodeposited layers. The results reveal that samples processed with megasonic assistance exhibit lower residual stress values compared to those without. Specifically, at a megasonic power density of 10 W/cm2, the residual stress was 94.3 MPa, representing a 37.7 % reduction compared to the residual stress of 151.5 MPa observed in samples without megasonic agitation. Overall, the findings demonstrate that coaxial megasonic agitation can effectively enhance the liquid-phase mass transfer capability during electrodeposition and reduce the residual stress of the electroplated layer. This innovative method presents a promising avenue for improving electrodeposition processes and achieving superior material properties.

The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-β/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of high-quality studies, significant progress will be made in the treatment of fibrosis.

ObjectivesThe objective of this study was to investigate the effect of different harvest times and processing methods on the B vitamins and α-tocopherol contents of Leymus chinensis (Trin.).MethodsL. chinensis was harvested on 11 July (T1 group), 16 July (T2 group), 21 July (T3 group), 26 July (T4 group), and 31 July (T5 group) in 2022 and processed using natural drying and silage fermentation to evaluate fermentation quality, chemical composition, in vitro digestibility and vitamin content.ResultsThe fermentation quality of L. chinensis silage prepared at all five times of harvest was better. The silage fermentation group showed a significant increase (p

ObjectiveAlzheimer’s Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver Disease (MASLD). This study aimed to assess the relative risk of AD in individuals with MASLD.MethodsIn this retrospective cohort study, we analyzed data from individuals aged over 65 who underwent health check-ups between January 2018 and June 2023. MASLD was diagnosed based on ultrasound findings and cardiometabolic criteria. AD incidence was identified using ICD-10 codes and self-reports. Poisson regression models estimated the relative risk of AD in relation to MASLD, adjusting for age, BMI, sex, SBP, HbA1c, HDL-c, triglycerides, hs-CRP, GGT, and estimated GFR.ResultsThe study included 4,582 MASLD patients and 6,318 controls. MASLD patients showed a higher incidence of AD (127 cases) compared to controls (61 cases). The fully adjusted Poisson regression model indicated an increased AD risk in MASLD patients [RR: 2.80 (95% CI: 1.79-4.38)].ConclusionOur findings suggested MASLD as an independent risk factor for AD, underlining the role of metabolic dysfunctions in AD pathogenesis. The study emphasized the need for comprehensive metabolic health management in AD prevention strategies, particularly among high-risk groups.

Abstract In the field of deep learning, the attention mechanism, as a technology that mimics human perception and attention processes, has made remarkable achievements. The current methods combine a channel attention mechanism and a spatial attention mechanism in a parallel or cascaded manner to enhance the model representational competence, but they do not fully consider the interaction between spatial and channel information. This paper proposes a method in which a space embedded channel module and a channel embedded space module are cascaded to enhance the model’s representational competence. First, in the space embedded channel module, to enhance the representational competence of the region of interest in different spatial dimensions, the input tensor is split into horizontal and vertical branches according to spatial dimensions to alleviate the loss of position information when performing 2D pooling. To smoothly process the features and highlight the local features, four branches are obtained through global maximum and average pooling, and the features are aggregated by different pooling methods to obtain two feature tensors with different pooling methods. To enable the output horizontal and vertical feature tensors to focus on different pooling features simultaneously, the two feature tensors are segmented and dimensionally transposed according to spatial dimensions, and the features are later aggregated along the spatial direction. Then, in the channel embedded space module, for the problem of no cross-channel connection between groups in grouped convolution and for which the parameters are large, this paper uses adaptive grouped banded matrices. Based on the banded matrices utilizing the mapping relationship that exists between the number of channels and the size of the convolution kernels, the convolution kernel size is adaptively computed to achieve adaptive cross-channel interaction, enhancing the correlation between the channel dimensions while ensuring that the spatial dimensions remain unchanged. Finally, the output horizontal and vertical weights are used as attention weights. In the experiment, the attention mechanism module proposed in this paper is embedded into the MobileNetV2 and ResNet networks at different depths, and extensive experiments are conducted on the CIFAR-10, CIFAR-100 and STL-10 datasets. The results show that the method in this paper captures and utilizes the features of the input data more effectively than the other methods, significantly improving the classification accuracy. Despite the introduction of an additional computational burden (0.5 M), however, the overall performance of the model still achieves the best results when the computational overhead is comprehensively considered.

Abstract Backgrounds Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. Methods We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. Results Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p

Abstract Background Mitochondrial diseases (MDs) can be caused by single nucleotide variants (SNVs) and structural variants (SVs) in the mitochondrial genome (mtDNA). Presently, identifying deletions in small to medium-sized fragments and accurately detecting low-percentage variants remains challenging due to the limitations of next-generation sequencing (NGS). Methods In this study, we integrated targeted long-range polymerase chain reaction (LR-PCR) and PacBio HiFi sequencing to analyze 34 participants, including 28 patients and 6 controls. Of these, 17 samples were subjected to both targeted LR-PCR and NGS to compare the mtDNA variant detection efficacy. Results Among the 28 patients tested by long-read sequencing (LRS), 2 patients were found positive for the m.3243 A > G hotspot variant, and 20 patients exhibited single or multiple deletion variants with a proportion exceeding 4%. Comparison between the results of LRS and NGS revealed that both methods exhibited similar efficacy in detecting SNVs exceeding 5%. However, LRS outperformed NGS in detecting SNVs with a ratio below 5%. As for SVs, LRS identified single or multiple deletions in 13 out of 17 cases, whereas NGS only detected single deletions in 8 cases. Furthermore, deletions identified by LRS were validated by Sanger sequencing and quantified in single muscle fibers using real-time PCR. Notably, LRS also effectively and accurately identified secondary mtDNA deletions in idiopathic inflammatory myopathies (IIMs). Conclusions LRS outperforms NGS in detecting various types of SNVs and SVs in mtDNA, including those with low frequencies. Our research is a significant advancement in medical comprehension and will provide profound insights into genetics.

Abstract Parental or ancestral environments can induce heritable phenotypic changes, but whether such environment-induced heritable changes are a common phenomenon remains unexplored. Here, we subject 14 genotypes of Arabidopsis thaliana to 10 different environmental treatments and observe phenotypic and genome-wide gene expression changes over four successive generations. We find that all treatments caused heritable phenotypic and gene expression changes, with a substantial proportion stably transmitted over all observed generations. Intriguingly, the susceptibility of a genotype to environmental inductions could be predicted based on the transposon abundance in the genome. Our study thus challenges the classic view that the environment only participates in the selection of heritable variation and suggests that the environment can play a significant role in generating of heritable variations.

Managers generally possess complex social networks and occupy central positions within their networks. We investigate the influence of managers’ social network relationships on capital market pricing efficiency by specifically analysing the relationship between top management team network centrality and stock price synchronicity. Using stock price synchronicity as a proxy for information efficiency, we examine data from Chinese A-share listed companies over a period of ten years (2013–2022). Based on the social network perspective, we empirically test the relationship between top management team network centrality and stock price synchronicity. Our results reveal that top management team network centrality promotes stock price synchronicity, which is more significant for non-state-owned enterprises. Mechanism testing indicates that analyst attention plays a partial mediating role between top management team network centrality and stock price synchronicity based on herd behaviour and social network theory. Additionally, institutional investors’ shareholding ratios weaken the impact of top management team network centrality, whereas analyst herding strengthens the promotion of stock price synchronicity. After excluding the endogenous effects these main findings remain robust. Overall, the results support the idea that executive networks promote stock price synchronicity.

Material and structure made by additive manufacturing (AM) have received much attention lately due to their flexibility and ability to customize complex structures. This study first implements multiple objective topology optimization simulations based on a projectile perforation model, and a new topologic projectile is obtained. Then two types of 316L stainless steel projectiles (the solid and the topology) are printed in a selective laser melt (SLM) machine to evaluate the penetration performance of the projectiles by the ballistic test. The experiment results show that the dimensionless specific kinetic energy value of topologic projectiles is higher than that of solid projectiles, indicating the better penetration ability of the topologic projectiles. Finally, microscopic studies (scanning electron microscope and X-ray micro-CT) are performed on the remaining projectiles to investigate the failure mechanism of the internal structure of the topologic projectiles. An explicit dynamics simulation was also performed, and the failure locations of the residual topologic projectiles were in good agreement with the experimental results, which can better guide the design of new projectiles combining AM and topology optimization in the future.

Abstract With the popularity of smart terminals, wearable electronic devices have shown great market prospects, especially high-sensitivity pressure sensors, which can monitor micro-stimuli and high-precision dynamic external stimuli, and will have an important impact on future functional development. Compressible flexible sensors have attracted wide attention due to their simple sensing mechanism and the advantages of light weight and convenience. Sensors with high sensitivity are very sensitive to pressure and can detect resistance/current changes under pressure, which has been widely studied. On this basis, this review focuses on analyzing the performance impact of device structure design strategies on high sensitivity pressure sensors. The design of structures can be divided into interface microstructures and three-dimensional framework structures. The preparation methods of various structures are introduced in detail, and the current research status and future development challenges are summarized.

Abstract Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.

Abstract We study generalized discrete symmetries of quantum field theories in 1+1D generated by topological defect lines with no inverse. In particular, we describe ’t Hooft anomalies and classify gapped phases stabilized by these symmetries, including new 1+1D topological phases. The algebra of these operators is not a group but rather is described by their fusion ring and crossing relations, captured algebraically as a fusion category. Such data defines a Turaev-Viro/Levin-Wen model in 2+1D, while a 1+1D system with this fusion category acting as a global symmetry defines a boundary condition. This is akin to gauging a discrete global symmetry at the boundary of Dijkgraaf-Witten theory. We describe how to “ungauge” the fusion category symmetry in these boundary conditions and separate the symmetry-preserving phases from the symmetry-breaking ones. For Tambara-Yamagami categories and their generalizations, which are associated with Kramers-Wannier-like self-dualities under orbifolding, we develop gauge theoretic techniques which simplify the analysis. We include some examples of CFTs with fusion category symmetry derived from Kramers-Wannier-like dualities as an appetizer for the Part II companion paper.

Abstract Background Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. Methods We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. Results The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. Conclusions The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

This work aimed to explore the difference of quality among commercial ready-to-eat sea cucumber products. The sensory, texture, chemical composition, nutritional quality and digestibility of four common commercial sea cucumber from Dalian (sea cucumber with high moisture content (HW-DLS), seasoned sea cucumber with low moisture content (FLW-DLS), sea cucumber with low moisture content (LW-DLS)) or Fujian (sea cucumber with high moisture content (HW-FJS)) were determined. Furthermore, principal component analysis (PCA) was applied to evaluate comprehensive quality of products. The results from sensory analysis revealed that the colour appearance of all sample were good. FLW-DLS had the most acceptable taste characteristics. There was a difference of texture characteristics in samples. The ash, total carbohydrate, and salt contents of FLW-DLS were significantly higher than those of other sea cucumbers (P

Abstract Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-HL patients in China. Nineteen cases of HIV-HL were diagnosed and treated at three center and including the sixth people’s hospital of Zhengzhou, Peking union medical college hospital, and Chongqing university cancer hospital, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed. The median age at diagnosis was 43(22–74) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man having sex with man (MSM) and nine cases transmitted through heterosexual transmission. Seven patients were diagnosed with lymphoma and found to be infected with HIV. Four cases were in stage III, and fifteen cases were in stage IV. After a median follow up of 46.8(4.0-112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with combination antiretroviral therapy (cART). The 5-year progression-free survival (PFS) and overall survival (OS) rate were 83.9% and 89.5%,respectively. HIV-HL exhibits an invasive process in clinical practice, and cART combined with ABVD regimen chemotherapy can achieve long-term survival for patients.