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Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

In light of the challenges posed by the low density, diminished energy levels, and shrinkage holes in the loading arise of the current cast-cured explosive liquid vehicle, TNT, the investigation of low-melting eutectic materials as potential substitutes for TNT has emerged as a focal point of research. By employing the solvent-nonsolvent method, the lowest eutectic mixture of TNBA(2,4,6-trinitro-3-bromoanisole)/MTNP(1-methyl-3,4,5-trinitropyrazole) was synthesized, distinguished by a moderate melting point and markedly elevated energy levels as compared to TNT. Comprehensive SEM, EDS, IR, XRD, and XPS analyses were conducted on the lowest eutectic mixture, substantiating the absence of any chemical interaction between TNBA and MTNP and affirming their exceptional compatibility. Moreover, an exploration into the thermal decomposition behavior and mechanism of the lowest eutectic mixture was undertaken, its mechanical sensitivity was tested, and its detonation performance was evaluated by EXPLO-5 software. The thermal decomposition parameters of the lowest eutectic mixture closely paralleled those of the precursor materials, with the thermal decomposition kinetics model function being identified as the Jander function. The impact sensitivity of the lowest eutectic was 48.1 cm and the friction sensitivity was 12%. Furthermore, the density of the lowest eutectic mixture surpassed 1.8 g/cm3, and its detonation velocity approached 8000 m/s, markedly surpassing the explosive performance of TNT.

Investigating the causal relationship between insulin secretion and prostate cancer (PCa) development is challenging due to the multifactorial nature of PCa, which complicates the isolation of the specific impact of insulin-related factors. We conducted a Mendelian randomization (MR) study to investigate the associations between insulin secretion-related traits and PCa. We used 36, 60, 56, 23, 48, and 49 single nucleotide polymorphisms (SNPs) as instrumental variables for fasting insulin, insulin sensitivity, proinsulin, and proinsulin in nondiabetic individuals, individuals with diabetes, and individuals receiving exogenous insulin, respectively. These SNPs were selected from various genome-wide association studies. To clarify the causal relationship between insulin-related traits and PCa, we utilized a multivariable MR analysis to adjust for obesity and body fat percentage. Additionally, two-step Mendelian randomization was conducted to assess the role of insulin-like growth factor 1 (IGF-1) in the relationship between proinsulin and PCa. Two-sample MR analysis revealed strong associations between genetically predicted fasting insulin, insulin sensitivity, proinsulin, and proinsulin in nondiabetic individuals and the development of PCa. After adjustment for obesity and body fat percentage using multivariable MR analysis, proinsulin remained significantly associated with PCa, whereas other factors were not. Furthermore, two-step MR analysis demonstrated that proinsulin acts as a negative factor in prostate carcinogenesis, largely independent of IGF-1. This study provides evidence suggesting that proinsulin may act as a negative factor contributing to the development of PCa. Novel therapies targeting proinsulin may have potential benefits for PCa patients, potentially reducing the need for unnecessary surgical treatments.

AbstractContext Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear.Objective This study elucidates the possible mechanisms of QGSTW in treating AAMI.Materials and methods Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks.Results Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from −16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from −19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG.Discussion and conclusions This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.

Immunotherapy has been seriously retarded due to inadequate antigen presentation and a tumor cell-dominated immunosuppressive microenvironment (TME). Herein, biodegradable multifunctional mesoporous silica nanoparticles, with dispersed carbon nanodots incorporated into the frameworks, active TKD peptide modification on the surfaces and hydrophobic drug loading in the pores, were prepared for targeted chemotherapy synergized with trans-spatial immunotherapy. The nanoparticles were biodegradable due to nanodot-induced framework swelling, which would (1) kill the in situ tumor cells and promote antigen release by targeted chemotherapy and (2) trigger biodegraded debris involving TKD and CDs to largely adsorb the tumor antigens via π-π conjugation synergized hydrophobic interactions and then massively transport these antigens from the tumor cell-dominated TME to the immune cell-dominated spleen via TKD-mediated small size effects. Thereafter, these antigens can be processed into antigen peptides via TKD-mediated lysosome endocytosis and then activate T cells in the spleen via MHC complex construction and dendritic cell cytomembrane presentation. Therefore, improved immunotherapy with trans-spatial antigen presentation avoided TME immunosuppression, which when synergized with targeted chemotherapy, markedly enhanced the therapeutic outcomes of triple-negative breast cancer.

Abstract Background Alcohol drinking and gut microbiota are related to hepatocellular carcinoma (HCC), but the specific relationship between them remains unclear. Aims We aimed to establish the alcohol drinking-gut microbiota-liver axis and develop machine learning (ML) models in predicting the occurrence of early-stage HCC. Methods Two hundred sixty-nine patients with early-stage HCC and 278 controls were recruited. Alcohol drinking-gut microbiota-liver axis was established through the mediation/moderation effect analyses. Eight ML algorithms including Classification and Regression Tree (CART), Gradient Boosting Machine (GBM), K-Nearest Neighbor (KNN), Logistic Regression (LR), Neural Network (NN), Random Forest (RF), Support Vector Machine (SVM), and eXtreme Gradient Boosting (XGBoost) were applied. Results A total of 160 pairs of individuals were included for analyses. The mediation effects of Genus_Catenibacterium (P = 0.024), Genus_Tyzzerella_4 (P

Abstract Salicylic acid (SA) production in Brassicaceae plants is uniquely accelerated from isochorismate by EPS1, a newly identified enzyme in the BAHD acyltransferase family. We present crystal structures of EPS1 from Arabidopsis thaliana in both its apo and substrate-analog-bound forms. Integrating microsecond-scale molecular dynamics simulations with quantum mechanical cluster modeling, we propose a pericyclic rearrangement lyase mechanism for EPS1. We further reconstitute the isochorismate-derived SA biosynthesis pathway in Saccharomyces cerevisiae, establishing an in vivo platform to examine the impact of active-site residues on EPS1 functionality. Moreover, stable transgenic expression of EPS1 in soybean increases basal SA levels, highlighting the enzyme’s potential to enhance defense mechanisms in non-Brassicaceae plants lacking an EPS1 ortholog. Our findings illustrate the evolutionary adaptation of an ancestral enzyme’s active site to enable a novel catalytic mechanism that boosts SA production in Brassicaceae plants.

Abstract As one of the pioneering nations to heed the Food and Agriculture Organization (FOA) initiative, China has implemented a comprehensive evaluation and protection framework for China’s Nationally Important Agricultural Heritage Systems (CNIAHS). This research concentrated on 188 CNIAHS sites, utilizing methodologies including spatial information entropy, kernel density estimation and hotspot analysis to scrutinize the spatial configurations and evolutionary trajectories of CNIAHS throughout six historical epochs; combined with the history of agriculture in different periods, the laws of the formation of CNIAHS spatial distribution are discovered, and a foundation for the construction of CNIAHS protection system under the background of national spatial planning are provided. The results disclose: (1) CNIAHS manifests a clustered spatial distribution, predominantly situated in the southeastern sector of China’s Yangtze River Basin, with Jiangsu, Zhejiang, Fujian, and Jiangxi provinces emerging as significant hotspot areas; (2) concerning spatial pattern evolution, heritage sites experienced a phased transitional process, migrating from western frontier areas to the central Yellow River Basin, subsequently concentrating in the southeastern Yangtze River Basin, and then redistributing back to frontier regions. This progression has cumulatively formed a spatial pattern mainly concentrated in southeastern China; (3) pertaining to typological patterns, high-value crop and spice systems exhibit a clustered spatial distribution, whereas other types display uniform or dispersed configurations; and (4) the complexity of spatial patterns in various regions increased over different periods, with the number of heritage sites demonstrating cumulative characteristics. The spatial patterns indicated weakly correlated transitional shifts, signifying a non-linear progression in the spatial patterns of CNIAHS. (5) The subsequent excavation of CNIAHS should fan out from point to area to promote the exploration of various types of CNIAHS in northeast and southwest China; and the excavation of marine heritage in the southeast China. These insights provide substantial references for the future exploration and preservation of CNIAHS.

Abstract Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin promoted HCC progression by regulating the AKT signaling pathway. To investigate the upstream regulatory mechanism, the results from RNA Immunoprecipitation and RNA pull-down indicated that the specific region of circIPP2A2 interacted with Hornerin. Additionally, patients with circIPP2A2 upregulation exhibited a poorer survival outcome following surgery compared to the cases with downregulated circIPP2A2. After the structure verification of circIPP2A2, loss-of-function studies using a lentiviral vector revealed that circIPP2A2 downregulation significantly inhibited HCC tumorigenesis and progression both in vitro and in vivo. Mechanistically, the m7G-MeRIP results demonstrated significant enrichment of circIPP2A2. Subsequent studies validated that METTL1 influenced the stability of circIPP2A2 and its binding affinity with Hornerin. Immunoprecipitation and immunofluorescence indicated that circIPP2A2 served as a molecular scaffold to facilitate Hornerin to interact with PI3K. In conclusion, our findings reveal that circIPP2A2, regulated by N7-methylguanosine modification, promotes malignant behaviors in HCC by serving as a molecular scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis. Targeting circIPP2A2 may be a promising therapeutic strategy for patients with HCC.

Abstract Background The World Health Organization certified China malaria-free in 2021. Consequently, preventing the risk of malaria re-introduction caused by imported malaria has now become a major challenge. This study aims to characterize the dynamics and predict the risk of malaria importation in Jiangsu Province, where the number of imported malaria cases ranks among the highest in China. Methods The annual number of cases with imported malaria in Jiangsu Province, the annual number of travelers from sub-Saharan Africa (SSA) to Jiangsu Province (both Chinese and international travelers), and the annual number of Chinese migrant workers from Jiangsu Province who stayed abroad between 2013 and 2020 were assessed. The spatio-temporal dynamics of malaria importation was characterized with ArcGIS 10.8. A negative binomial model was applied to model malaria importation to Jiangsu Province, China. Results A total of 2,221 of imported malaria cases were reported from January 1, 2013, until December 31, 2020. Imported malaria cases into China were mainly from SSA (98%) and P. falciparum (78%), the most common species. A seasonal pattern was observed, with the most cases occurring from December to February. The negative binomial model, which incorporates the number of Chinese migrant workers from Jiangsu Province who stayed abroad as an independent variable, demonstrated better performance (AIC: 96.495, BIC: 94.230) compared to the model based solely on travelers from SSA to Jiangsu Province. The model indicated an estimated 139% increase in imported cases for a 10% increase in Chinese migrant workers from Jiangsu Province who stayed abroad. Conclusion In conclusion, our study underscores the importance of incorporating data on Chinese migrant workers who have stayed abroad when predicting malaria importation risks. By integrating both international travel patterns and migrant worker data, our findings offer a more robust framework for assessing and managing malaria risk in Jiangsu Province. This approach provides valuable insights for public health officials, enabling more effective resource allocation and targeted interventions to prevent the re-introduction of malaria and improve overall disease management.

Abstract Using 7.33 fb −1 of e + e − collision data samples collected with the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, we search for the radiative decay D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ for the first time. A hint of D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ is observed with a statistical significance of 2.5σ. The branching fraction of D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ is measured to be (2.2 ± 0.9stat. ± 0.2syst. ) × 10 −4, corresponding to an upper limit of 6.1 × 10 −4 at the 90% confidence level.

Abstract Background The Hengduan Mountains, one of the global biodiversity hotspots with exceptional species richness and high endemism, contains numerous arid valleys that create a distinctive geographical and ecological landscape. However, the adaptive evolutionary mechanisms of organism in the arid valley remain poorly understood. Minois aurata, an endemic butterfly species found exclusively in the arid valley of the upper Minjiang River, represents an attractive model system for studying adaptive evolutionary mechanisms to arid valley environments. Results Here, we present the first chromosome-level genome assembly for Minois aurata, with a total size of approximately 609.17 Mb, and a scaffold N50 size of 23.88 Mb. These scaffolds were further clustered and anchored onto 29 chromosomes based on Hi-C data. A total of 16,163 protein-coding genes were predicted, of which 91.83% were functionally annotated. The expansion of transposable elements (TEs) accounts for the relatively large genome size of M. aurata, potentially aiding its adaptation to environmental conditions. Phylogenomic analyses based on 3,785 single-copy genes revealed that M. aurata is most closely related to Hipparchia semele. Further mitochondrial genome analysis of four Minois species placed M. aurata in a basal position within the genus, supporting it as an independent species. A total of 185 rapidly evolving and 232 specific gene families were identified in M. aurata. Functional enrichment analysis indicated that these gene families were mainly associated with ultraviolet radiation, heat and hypoxia responses. We also identified 234 positive selected genes in M. aurata, some of which are related to compound eye photoreceptor development, osmotic stress, and light stimulus response. Demographic analysis indicated that the effective population size of M. aurata decreased around 0.4 and 0.04 million years ago, respectively, coinciding with the localized sub-glaciation. Conclusion The chromosome-level genome offers a comprehensive genomic basis for understanding the evolutionary and adaptive strategies of Minois aurata in the unique arid valley environment of the Hengduan Mountains, while also providing valuable insights into the broader mechanisms of organism adaptation to such habitats.

Abstract Reports on the application of metagenomic next-generation sequencing (mNGS) in adult patients with severe pneumonia after cardiac surgery remain limited. This study aimed to evaluate the clinical outcomes of mNGS analysis of bronchoalveolar lavage fluid (BALF) in such patients.A retrospective cohort study was conducted on adult patients with severe pneumonia after cardiac surgery. Samples were collected from patients in the surgical intensive care unit (SICU) of Sichuan Provincial People’s Hospital between January 2019 and March 2024. Upon diagnosis of severe pneumonia, bronchoalveolar lavage fluid was obtained via bronchoscopy within 24 h. The mNGS group was composed of patients tested using mNGS and conventional microbiological tests. BALF was detected only by the conventional microbiological test (CMT) method in the CMT group, which involved examining bacterial and fungal smears and cultures at least. We reviewed a total of 4,064 cardiac surgeries, and based on the inclusion criteria, a total of 113 adult patients with severe pneumonia after cardiac surgery were included in this study. The overall positive rate detected by mNGS was significantly higher than that of the culture method (98% vs. 58%, P

Abstract This study aimed to assess the influence of ulinastatin (UTI) on lymphocyte apoptosis and autophagy in sepsis patients, as well as its effect on inflammatory factors and vital organ function, with the goal of providing insights for improved clinical management of sepsis. A total of 40 sepsis patients were randomly assigned to the UTI group or the control group. The UTI group received standard treatment plus intravenous UTI, while the control group received standard treatment alone. Peripheral blood samples were collected at multiple time points for analysis of lymphocyte apoptosis, autophagy, inflammatory markers, and organ function. Various experimental techniques including Hoechst staining, transmission electron microscopy, and Western blot analysis were utilized to assess lymphocyte apoptosis, autophagy, and related protein expression levels. The study revealed that UTI treatment significantly inhibited lymphocyte apoptosis and promoted autophagy in sepsis patients. The levels of autophagy-related proteins LC3-II and Beclin-1 were substantially elevated, while the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax was increased following UTI treatment. Furthermore, the levels of inflammatory markers IL-6, procalcitonin, and C-reactive protein were markedly reduced in the UTI group compared to the control group. Additionally, UTI treatment led to improved liver, kidney and cardiac function as evidenced by reduced levels of liver enzymes and creatinine, and cardiac enzymes. The findings of this study demonstrate that UTI exerts a protective effect on septic patients by inhibiting lymphocyte apoptosis, promoting autophagy, and attenuating systemic inflammation. Moreover, UTI treatment was associated with improved liver, kidney, and cardiac function in septic patients. These results contribute to a better understanding of the clinical management of sepsis and underscore the potential of UTI as a therapeutic intervention in septic patients.

Abstract The excavation of ivory and other artifacts from the Sanxingdui Ruins holds profound research significance in tracing of both the ancient Shu and Chinese civilizations. After being unearthed, a large quantity of ivory encountered issues such as dehydration, pulverization, and cracking, resulting from poor preservation conditions. To establish effective long-term conservation strategies for the excavated ivory, this paper takes the dentin of excavated ivory from the No.7 Sacrificial Pit (K7) at the Sanxingdui Ruins as the research object, focusing on the primary correlation between its microscopic porous structure and moisture states. The results show that the organic collagen protein component of the excavated ivory has already undergone basically diagenetic degradation. The remaining main mineral phases are hydroxyapatite and carbonated hydroxyapatite, exhibiting a mixed crystal structure with mainly needle-like and secondary lamellar. The porosity of the excavated ivory, as measured by dry and wet methods, is approximately 62 and 60%, respectively. The pore size distributions are primarily concentrated in the ranges of 5–100 nm for the dry method and 10–200 nm for the wet method. These diverse and heterogeneous pore structures store approximately 35–38% of water as free water and adsorbed water. Free water is primarily found in dentinal tubules, interlayer gaps and cracks, providing volume support and stabilizing equilibrium with the external environment. Adsorbed water is mainly present in the pores (d

Abstract Background Human epidermal growth factor receptor 2-targeted (HER2) therapy with antibody-drug conjugates has proven effective for patients with HER2-low breast cancer. However, intratumoral heterogeneity (ITH) poses a great challenge in identifying HER2-low tumors. ITH signatures were developed by quantifying ITH to differentiate HER2-positive, -low and -zero breast cancers. Methods This retrospective study included 614 patients from two institutions. The study was structured into two primary tasks: task 1 was to differentiate between HER2-positive and -negative tumors, followed by task 2 to differentiate HER2-low and -zero tumors. Whole-tumor radiomics features and habitat radiomics features were extracted from MRI to construct the radiomics and ITH signatures. Multivariable logistic regression analysis was used to determine significant independent predictors. A combined model integrating significant clinicopathologic variables, radiomics signature, and ITH signature was developed for task (1) Subsequently, the better-performing model was established using the same approach for task (2) The area under the receiver operating characteristic curve (AUC) was used to assess the performance of each model. Results Task 1 comprised 614 patients (training, n = 348; validation, n = 149; and test cohorts, n = 117). Task 2 encompassed 501 patients (training, n = 283; validation, n = 122; and test cohorts, n = 96). For task1, the ITH signature showed outstanding performance, achieving AUCs of 0.81, 0.81, and 0.81 in the training, validation and test cohorts, respectively. The combined model achieved improved performance, with AUCs of 0.83, 0.84 and 0.83 across the three cohorts, respectively. For task2, the ITH signature maintained superior performance, with AUCs of 0.94, 0.93 and 0.84 across the training, validation and test cohorts, respectively. Multivariable logistic regression analysis indicated that none of the clinicopathologic characteristics were retained as predictors associated with odds of HER2-low tumors. Conclusions Our study developed ITH signatures that quantified ITH using habitat-based MRI radiomics, achieving outstanding performance in differentiating HER2-postive and -negative tumors, and further differentiating HER2-low and -zero breast cancers.

In present study, the mitogenome of Rosa laevigata was assembled and characterized, with a total length of 281,693 bp and a GC content of 45.4%. The genome encompasses 53 genes, including 32 protein-coding genes, 3 rRNA genes and 18 tRNA genes. Furthermore, 19 MTPTs were identified, ranging from 48 to 1585 bp, covering 3.1% (8764 bp) of the mitogenome. Phylogenetic analysis of 34 Rosaceae species based on 21 common conserved protein-coding genes detected the monophyly of Rosa, with R. laevigata and R. chinensis forming a sister clade to R. rugosa. The mitogenome provides valuable genetic resources for R. laevigata utilization and for further phylogeny reconstruction of Rosa and Rosaceae.

Abstract Conventional methods for identifying voltage sag sources are difficult to categorize accurately due to the complexity of transmission lines and the influence of noise. In order to solve the problem of difficulty in recognizing voltage sag sources of transmission lines under different locations, this paper proposes a new method for transmission line fault diagnosis based on modified wavelet denoising and multi‐location information convolution transformer. The improved wavelet denoising method proposed in this paper solves the problems of discontinuity and bias of the traditional wavelet denoising method, and is able to better reconstruct the original voltage signal in a strong noise environment. In addition, multi‐location information convolution transformer adopts a new model combining multi‐location information convolution and multi‐scale convolution transformer, which realizes the combination of global information and local context information capturing ability under multi‐location faults. This paper validates the method through simulation experiments and practical situations, and the results show that the method can well classify and identify the type and location of voltage sag sources in transmission lines.

A novel genus, Paradingleyomyces was introduced to accommodate Pa. lepidopterorum sp. nov., based on a multigene phylogenetic analysis and its distinct morphological characteristics. Maximum likelihood (ML) and Bayesian inference analyses (BI) of ITS, SSU, LSU, tef-1α, rpb1, and rpb2 sequence data shown that Pa. lepidopterorum formed an independent lineage nested between Perennicordyceps and Dingleyomyces. Morphologically, Paradingleyomyces is distinguished from Perennicordyceps by the presence of a white subiculum on the stromata of Ophiocordyceps cf. cochlidiicola. Perithecia are produced sporadically from the base to the apex of the stromata, and the secondary ascospores exhibit a notable length-to-width ratio. These characteristics distinguish Paradingleyomyces from Perennicordyceps which exhibits tortuous, branched, clavate to cylindrical stromata with rhizomorphs, parasitism of coleopteran and hemipteran larvae, and colonizes a broader range of fungal hosts. Additionally, perithecia in Perennicordyceps typically arise from the middle to the upper regions of the stromata, with secondary ascospores displaying a comparatively lower length-to-width ratio. Paradingleyomyces is morphologically identical to Dingleyomyces in its direct production of superficial perithecia on the stromata of Ophiocordyceps species. However, the phylogenetic analysis indicates that Paradingleyomyces and Dingleyomyces are not congeneric. Moreover, this study introduces another novel species, Polycephalomyces tengchongensis, and a novel sexual morph of Pleurocordyceps yunnanensis. Dimorphic phialides and conidia of Pleurocordyceps parvicapitata were observed and described for the first time based on a fresh collection from Tengchong County, Yunnan Province, China.

Abstract The fundamental leucine zipper (bZIP) genes play a crucial role as transcriptional coactivators in plants. Pseudoroegneria libanotica served as the maternal contributor to several species within the tribe Triticeae (Poaceae), exhibiting commendable resilience to various stressors. Consequently, bZIP genes of Pseudoroegneria libanotica response to abiotic stresses was important for further understanding of stress tolerance studies in Triticeae. A total of 108 PsebZIPs were identified in this study, and they were divided into 10 subgroups. PsebZIPs were found to be extensively involved in the biological activities within P. libanotica. The RNA-seq results revealed differential responses of PsebZIPs to drought stress in both aerial and root tissues. PsebZIP44 and PsebZIP46 were regarded as potential genes capable of responding to abiotic stress, and their varying degrees of responsiveness to drought, salinity, heavy metals, heat, and oxidative stress have been demonstrated in yeast. Homologous proteins with intact bZIP gene structures of PsebZIP44 or PsebZIP46 have not been identified in wheat. The current investigation not only provides a fundamental basis for further probing into the biological functions of PsebZIPs within P. libanotica but also reveals previously undiscovered potential genes with the ability to respond to abiotic stress. They could contribute to improving the genetic constitution of Triticeae crops, including wheat.

Abstract Transthoracic echocardiography (TTE) is widely recognized as one of the principal modalities for diagnosing tricuspid regurgitation (TR). The diagnostic procedures associated with conventional methods are intricate and labor-intensive, with human errors leading to measurement variability, with outcomes critically dependent on the operators’ diagnostic expertise. In this study, we present an innovative assessment methodology for evaluating TR severity utilizing an end-to-end deep learning system. This deep learning system comprises a segmentation model of single cardiac cycle TR continuous wave (CW) Doppler spectra and a classification model of the spectra, trained on the TR CW Doppler spectra from a cohort of 11,654 patients. The efficacy of this intelligent assessment methodology was validated on 1500 internal cases and 573 external cases. The receiver operating characteristic (ROC) curves of the internal validation results indicate that the deep learning system achieved the areas under curve (AUCs) of 0.88, 0.84, and 0.89 for mild, moderate, and severe TR, respectively. The ROC curves of the external validation results demonstrate that the system attained the AUCs of 0.86, 0.79, and 0.87 for mild, moderate, and severe TR, respectively. Our study results confirm the feasibility and efficacy of this novel intelligent assessment method for TR severity.

Abstract Background Endometriosis (EMS) and chronic endometritis (CE) frequently coexist. This study aimed to examine the impact of CE on reproductive outcomes in patients with EMS. Methods We enrolled 685 patients with endometriosis-associated infertility from January 2018 to December 2020. The patients were divided into CE (318) and non-CE (367) groups. A subset of 123 clinically pregnant women from the CE group and 369 from the non-CE group was selected for detailed comparison. Pregnancy and delivery data were meticulously collected from hospital records and through telephone interviews. Results CE was diagnosed in 46.42% of EMS patients. Higher pregnancy rates were observed in patients with Endometriosis Fertility Index (EFI) scores of 7–10. EMS patients with CE had increased risks of placenta previa (13.01%), gestational hypertension (5.69%), and cesarean sections (59.34%). Conclusions CE, which is prevalent among EMS patients, is linked to increased risks of pregnancy complications, including placenta previa, gestational hypertension, and cesarean delivery. Although combined hysteroscopy and laparoscopy improve pregnancy rates, they demand careful management of these complications.

Abstract Objectives This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). Materials and methods Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models’ performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. Results The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766–0.959), sensitivity of 88% (95% CI: 73.9–100), and specificity of 78.4% (95% CI: 63.6–90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. Conclusion A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. Critical relevance statement Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. Key Points After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer. Graphical Abstract

Abstract The locomotive action involves diverse coordination, necessitating the integration of multiple motor neural circuits. However, the precise circuitry mechanism governing emotion-driven accelerated locomotion remains predominantly elusive. Here we dissect projections from the tuberomammillary nucleus (TMN) to subiculum (SUB) which promote alert-driven accelerated locomotion. We find that TMN histaminergic neurons respond to high-speed locomotion in both natural and alert acceleration. The TMN-SUB circuit is sufficient but not essential for amplifying accelerated locomotion from low to high-speed movement in basal condition, but it is both sufficient and necessary in alert condition for modulating accelerated locomotion during high-speed escape behavior. TMN histaminergic neuron activates SUB glutamatergic “fast locomotor cell” that projects to retrosplenial granular cortex (RSG) mainly through histamine H2 receptor (H2R). This study reveals the critical role of the histamine-tuned SUB circuit in alert-driven accelerated locomotion in mice, providing a theoretical foundation for comprehending neural circuit mechanisms of instinctive behaviors under alert.

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules, alongside the rapid advancements in nucleic acid delivery systems. It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword. In the context of immunotherapy, extra supplementation of adjuvant is generally required for induction of robust immune responses. Conversely, in non-immunotherapeutic scenarios, immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins. Herein, mainly focused on the linear non-replicating mRNA, we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics. We also highlight the importance of focusing on the host-specific variations, including age, gender, pathological condition, and concurrent medication of individual patient, for maximized efficacy and safety upon mRNA administration. Furthermore, we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment, the current endeavors of improvement, as well as the application prospects for future advancements. Overall, this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.

Abstract Using e + e − collision data collected by the BESIII detector at BEPCII corresponding to an integrated luminosity of 30 fb −1, we measure Born cross sections and effective form factors for the process e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ at forty-five center-of-mass energies between 3.51 and 4.95 GeV. The dressed cross section is fitted, assuming a power-law function plus a charmonium(-like) state, i.e., ψ(3770), ψ(4040), ψ(4160), ψ(4230), ψ(4360), ψ(4415) or ψ(4660). No significant charmonium(-like) state decaying into Ξ 0 Ξ ¯ 0 $$ {\Xi}^0{\overline{\Xi}}^0 $$ is observed. Upper limits at the 90% confidence level on the product of the branching fraction and the electronic partial width are provided for each decay. In addition, ratios of the Born cross sections and the effective form factors for e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ and e + e − → Ξ − Ξ ¯ + $$ {e}^{+}{e}^{-}\to {\Xi}^{-}{\overline{\Xi}}^{+} $$ are also presented to test isospin symmetry and the vector meson dominance model.

Abstract Objectives Viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain a major global public health challenge, particularly in low- and middle-income countries. It is crucial to utilize a pointof-care (POC) testing platform that is sensitive, specific, rapid, and user-friendly for screening and diagnosis of the two infections. Here, a novel molecular diagnostic assay, integrating multiplex loop-mediated isothermal amplification with a gold nanoparticle-based lateral flow biosensor (mLAMP-AuNPs-LFB) was developed and applied for one-step, visual, rapid, sensitive, and specific identification of HBV and HCV. Methods The AuNPs-based LFB was devised and constructed for the simultaneous detection of HBV and HCV. The HBV-LAMP and HCV-LAMP primers were designed against the S and 5′-untranslated region (5′-UTR) genes from the major HBV genotypes (B, C, D, B/C recombinant, and C/D recombinant) and HCV subtypes (1b, 2a, 3a, 3b, and 6a) in China, respectively. Our assay conditions, both multiplex-LAMP amplification temperature and time were optimized. The sensitivity and specificity of our assay were tested, and the feasibility of our assay was verified through clinical samples. Results The AuNPs-based LFB used here was successfully manufactured according to our devise manual. The two unique independent primer pairs were successfully designed based on the S and 5′-UTR genes, respectively. The optimal mLAMP-AuNPs-LFB detection process, involving rapid nucleic acid isolation (10 min), mLAMP (63 °C for 35 min), and visual AuNPs-LFB interpretation (less than 2 min), could be completed within 50 min. The HBV&HCV-mLAMP-AuNPs-LFB assay can detect the target genes (HBV-S and HCV-5′-UTR) with as low as 20 copies of plasmid template per test, and the specificity was 100% for the experimental pathogens. Conclusions The preliminary results manifested that our mLAMP-AuNPs-LFB assay is a valuable tool and has tremendous potential as a POC testing approach for HBV and HCV identification, especially in undeveloped regions.

Abstract This study aimed to observe the characteristics of foot posture asymmetry and abnormal gait in patients with unilateral and bilateral knee osteoarthritis (KOA) and to explore the association between foot posture asymmetry, abnormal gait and the clinical symptoms and severity of KOA. Sixty patients with KOA were allocated as follows: unilateral group (UG; n = 30) and bilateral group (BG; n = 30). We accessed foot posture, foot posture asymmetry, gait and plantar pressure parameters and symmetry index, clinical symptom-related scores and disease severity, and investigated the relationship between these variables. The results showed that the overall percentage of asymmetry and severe asymmetry in foot posture were lower in BG than in UG. There was substantial asymmetry in many gait indicators within the two groups, but no significant differences were observed between the two groups. Moreover, foot posture asymmetry, multiple gait and plantar pressure parameters and symmetry indices were closely related to clinical symptoms and disease severity. In conclusion, both unilateral and bilateral KOA patients have foot posture asymmetry and gait asymmetry, but the foot posture asymmetry of the former is more severe than that of the latter. Intervention for this population should treat simultaneously both knee joints. The evaluation and monitoring of foot posture asymmetry, gait and plantar pressure parameters and symmetry indices can provide a more comprehensive and scientific basis for the prevention and treatment of KOA.

This study introduces a pioneering design concept termed the “dual-feedback healing mechanism”, which investigates the relationship between oxidation products and protective coatings. Specifically, it focuses on channeling oxidation products generated at exposed cracks in the substrate to interact with the antioxidant coatings, enabling a self-repair mechanism for cracks. BNf/SiBN was chosen as the ceramic matrix, while the Si‒O‒Al system served as the antioxidant coating. The dynamic process of obtaining Si–O–Al (SOAC) coating involving the pyrolysis of organic precursors and the dual-feedback healing mechanism were systematically investigated. These findings indicate that when the temperature surpasses 1150 °C, the exposed BN fibers at the cracks are oxidized, transforming into B2O3(g). Subsequently, B2O3(g) reacts with SiO2, forming a SiBO mixture. The mixture effectively diminishes the viscosity of the coating, enabling it to flow and form a fresh protective layer that effectively blocks O2 infiltration. Consequently, after oxidation at 1500 °C, the coated samples experience a mere 3% weight loss. This technology emphasizes the interconnectivity during material transformation, utilizing matrix oxidation products as a driving force for self-healing of the coating. This approach achieves intelligent-like, targeted closure of oxygen pathways, thereby pioneering a novel concept and direction for the advancement of antioxidant coatings. Consequently, this approach not only enhances our understanding of the fundamental nature of “self-healing” but also holds significant potential in the development of reparable antioxidant coatings.

Abstract The branching fraction of D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ is measured for the first time using 7.93 fb −1 of e + e − annihilation data collected at the center-of-mass energy s $$ \sqrt{s} $$ = 3.773 GeV with the BESIII detector operating at the BEPCII collider, and is determined to be B D + → K S 0 π 0 e + ν e = 0.881 ± 0.017 stat . ± 0.016 syst . % $$ \mathcal{B}\left({D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e\right)=\left(0.881\pm {0.017}_{\textrm{stat}.}\pm {0.016}_{\textrm{syst}.}\right)\% $$ . Based on an analysis of the D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ decay dynamics, we observe the S-wave and P-wave components with fractions of f S-wave = (6.13 ± 0.27stat. ± 0.30syst. )% and f K ¯ ∗ 892 0 = 93.88 ± 0.27 stat . ± 0.29 syst . % $$ {f}_{{\overline{K}}^{\ast }{(892)}^0}=\left(93.88\pm {0.27}_{\textrm{stat}.}\pm {0.29}_{\textrm{syst}.}\right)\% $$ , respectively. From these results, we obtain the branching fractions B D + → K S 0 π 0 S − wave e + ν e = 5.41 ± 0.35 stat . ± 0.37 syst . × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\left({K}_S^0{\pi}^0\right)}_{S-\textrm{wave}}{e}^{+}{\nu}_e\right)=\left(5.41\pm {0.35}_{\textrm{stat}.}\pm {0.37}_{\textrm{syst}.}\right)\times {10}^{-4} $$ and B D + → K ¯ ∗ 892 0 e + ν e = 4.97 ± 0.11 stat . ± 0.12 syst . % $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e\right)=\left(4.97\pm {0.11}_{\textrm{stat}.}\pm {0.12}_{\textrm{syst}.}\right)\% $$ . In addition, the hadronic form-factor ratios of D + → K ¯ ∗ 892 0 e + ν e $$ {D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e $$ at q 2 = 0, assuming a single-pole dominance parameterization, are determined to be r V = V 0 A 1 0 = 1.43 ± 0.07 stat . ± 0.03 syst . $$ {r}_V=\frac{V(0)}{A_1(0)}=1.43\pm {0.07}_{\textrm{stat}.}\pm {0.03}_{\textrm{syst}.} $$ and r 2 = A 2 0 A 1 0 = 0.72 ± 0.06 stat . ± 0.02 syst . $$ {r}_2=\frac{A_2(0)}{A_1(0)}=0.72\pm {0.06}_{\textrm{stat}.}\pm {0.02}_{\textrm{syst}.} $$ .

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Abstract Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO2-MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO2-MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE−/− mouse model, Col@HMnO2-MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy.

Abstract In this study, nonaxisymmetric endwall contouring technology is employed as a passive control strategy to enhance the stable operating range of a centrifugal compressor with an asymmetric volute. The endwall contouring method is applied to the hub‐side wall of the vaned diffuser within a centrifugal compressor stage. Instead of utilizing a flat hub as the baseline diffuser, various diffuser configurations featuring hub‐side contoured endwalls are explored, with adjustments in the peak radial position and peak height of the convex and concave profiles. Numerical simulations are conducted to evaluate the performance of the centrifugal compressor stage with both the baseline and contoured vaned diffusers. The investigation explores the underlying flow control mechanisms and establishes the effective endwall contouring guidelines. The findings highlight the effectiveness of endwall contouring in enhancing the stable operating range of centrifugal compressors. Notably, a substantial enhancement of 15.1% in the stable operating range is achieved by employing the contoured diffuser with the peak radial position near the vane leading edge (LE) and the peak height at 20% of the vane height. The endwall contoured diffusers reduce the positive LE incidence angles to direct the fluid toward the suction side (SS), and increase the radial velocity near the SS to suppress the hub‐suction corner separations in the diffuser passages near the volute tongue. These improvements collectively contribute to the enhancement of diffuser flow characteristics. Finally, a set of effective endwall contouring guidelines is proposed to guide the endwall contouring design for enhancing the stable operating range of centrifugal compressors.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with limited treatment options and efficacy. Evidence suggests that IPF arises from genetic, environmental, and aging-related factors. The pathogenic mechanisms of IPF primarily involve dysregulated repeated microinjuries to epithelial cells, abnormal fibroblast/myofibroblast activation, and extracellular matrix (ECM) deposition, but thus far, the exact etiology remains unclear. Noncoding RNAs (ncRNAs) play regulatory roles in various biological processes and have been implicated in the pathophysiology of multiple fibrotic diseases, including IPF. This review summarizes the roles of ncRNAs in the pathogenesis of IPF and their potential as diagnostic and therapeutic targets.

Abstract Background Fusarium head blight (FHB), a devastating disease of wheat production, is predominantly elicited by Fusarium graminearum (Fg). The tetraploid Thinopyrum elongatum is a tertiary gene resource of common wheat that possesses high affinity and displays high resistance traits against multiple biotic and abiotic stress. We aim to employ and utilize the novel FHB resistance resources from the wild germplasm of common wheat for breeding. Results Durum wheat-tetraploid Th. elongatum amphiploid 8801 was hybridized with common wheat cultivars SM482 and SM51, and the F5 generation was generated. We conducted cytogenetically in situ hybridization (ISH) technologies to select and confirm a genetically stable 7E(7D) substitution line K17-1069-5, which showed FHB expansion resistance in both field and greenhouse infection experiments and displayed no significant disadvantage in agronomic traits compared to their common wheat parents in the field. The F2 segregation populations (K17-1069-5 × SM830) showed that the 7E chromosome conferred dominant FHB resistance with dosage effect. We developed 19 SSR molecular markers specific to chromosome 7E, which could be conducted for genetic mapping and large breeding populations marker-assisted selection (MAS) during selection procedures in the future. We isolated a novel Fhb7 allele from the tetraploid Th. elongatum chromosome 7E (Chr7E) using homology-based cloning, which was designated as TTE7E-Fhb7. Conclusions In summary, our study developed a novel wheat-tetraploid Thinopyrum elongatum 7E(7D) K17-1069-5 substitution line which contains stable FHB resistance.

Abstract Expiratory CO2 concentrations can directly reflect human physiological conditions, and their detection is highly important in the treatment and rehabilitation of critically ill patients. Existing respiratory gas analyzers suffer from large sizes and high power consumption due to the limitations of the internal CO2 sensors, which prevent them from being wearable to track active people. The internal and external interference and sensitivity limitations must be overcome to realize wearable respiratory monitoring applications for CO2 sensors. In this work, an ultra-compact CO2 sensor was developed by integrating a microelectromechanical system emitter and thermopile detectors with an optical gas chamber; the power consumption of the light source and ambient temperature of the thermally sensitive devices were reduced by heat transfer control; the time to reach stabilization of the sensor was shortened; the humidity resistance of the sensor was improved by a dual-channel design; the light loss of the sensor was compensated by improving the optical coupling efficiency, which was combined with the amplitude trimming network to equivalently improve the sensitivity of the sensor. The minimum size of the developed sensor was 12 mm × 6 mm × 4 mm, and the reading error was

The direct one-step separation of polymer-grade C2H4 from complex light hydrocarbon mixtures has high industrial significance but is very challenging. Herein, an ethylene-adsorption-weakening strategy is applied for precise regulation of the pore geometry of four tailor-made metal–organic frameworks (MOFs) with pillar-layered structures, dubbed TYUT-10/11/12/13. Based on its pore geometry design and functional group regulation, TYUT-12 exhibits exceptional selective adsorption selectivity toward C3H8, C3H6, C2H6, C2H2, and CO2 over C2H4; its C2H6/C2H4 adsorption selectivity reaches 4.56, surpassing the record value of 4.4 by Fe2(O2)(dobdc) (dobdc4− = 2,5-dioxido-1,4-benzenedicarboxylate). The weak π–π stacking binding affinity toward C2H4 in TYUT-12 is clearly demonstrated through a combination of neutron powder diffraction measurements and theoretical calculations. Breakthrough experiments demonstrate that C2H4 can be directly obtained from binary, ternary, quaternary, and six-component light hydrocarbon mixtures with over 99.95% purity.

Abstract Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Abstract The ubiquitous smart meters are expected to be a central feature of future smart grids because they enable the collection of massive amounts of fine-grained consumption data to support demand-side flexibility. However, current smart meters are not smart enough. They can only perform basic data collection and communication functions and cannot carry out on-device intelligent data analytics due to hardware constraints in terms of memory, computation, and communication capacity. Moreover, privacy concerns have hindered the utilization of data from distributed smart meters. Here, we present an end-edge-cloud federated split learning framework to enable collaborative model training on resource-constrained smart meters with the assistance of edge and cloud servers in a resource-efficient and privacy-enhancing manner. The proposed method is validated on a hardware platform to conduct building and household load forecasting on smart meters that only have 192 KB of static random-access memory (SRAM). We show that the proposed method can reduce the memory footprint by 95.5%, the training time by 94.8%, and the communication burden by 50% under the distributed learning framework and can achieve comparable or superior forecasting accuracy to that of conventional methods trained on high-capacity servers.

Abstract The Riemerella anatipestifer bacterium is known to cause infectious serositis in ducklings. Moreover, its adherence to the host’s respiratory mucosa is a critical step in pathogenesis. Membrane cofactor protein (MCP; CD46) is a complement regulatory factor on the surface of eukaryotic cell membranes. Bacteria have been found to bind to this protein on host cells. Outer membrane proteins (OMPs) are necessary for adhesion, colonisation, and pathogenicity of Gram-negative bacteria; however, the mechanism by which R. anatipestifer adheres to duck cells remains unclear. In this study, pull-down assays and LC–MS/MS identified eleven OMPs interacting with duck CD46 (dCD46), with OMP71 exhibiting the strongest binding. The ability of an omp71 gene deletion strain to bind dCD46 is weaker than that of the wild-type strain, suggesting that this interaction is important. Further evidence of this interaction was obtained by synthesising OMP71 using an Escherichia coli recombinant protein expression system. Adhesion and invasion assays and protein and antibody blocking assays confirmed that OMP71 promoted the R. anatipestifer YM strain (RA-YM) adhesion to duck embryo fibroblasts (DEFs) by binding to CD46. Tests of the pathogenicity of a Δomp71 mutant strain of RA-YM on ducks compared to the wild-type parent supported the hypothesis that OMP71 was a key virulence factor of RA-YM. In summary, the finding that R. anatipestifer exploits CD46 to bind to host cells via OMP71 increases our understanding of the molecular mechanism of R. anatipestifer invasion. The finding suggests potential targets for preventing and treating diseases related to R. anatipestifer infection.

Abstract Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Abstract Background The prevalence of chronic conditions increases rapidly among older population. However, it is unclear how different chronic conditions progression contributes to the health care utilization, and whether intergenerational support modified this relationship. This study aimed to explore the longitudinal link between chronic condition progression and health care utilization, and examine whether intergenerational financial support is a moderator in this relationship among Chinese rural older people. Methods Data was derived from the Shandong Rural Elderly Health Cohort (SREHC), which was conducted from 2019 to 2020. A total of 2,785 participants were included in this study. Kruskal-Wallis rank tests and generalized estimating equation (GEE) models were employed to analyze the association between chronic condition progression and health care utilization. Moderating effect analysis was performed using GEE model and margins plot. Results Older people with progressive chronic conditions used more outpatient (no chronic condition to emerging multimorbidity: OR = 1.83; p = 0.028; one chronic condition to emerging multimorbidity: OR = 2.17; p

Abstract Background Among heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox. Methods The study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints. Results In MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p

Abstract Background Wheat is one of major sources of human cadmium (Cd) intake. Reducing the grain Cd concentrations in wheat is urgently required to ensure food security and human health. In this study, we performed a field experiment at Wenjiang experimental field of Sichuan Agricultural University (Chengdu, China) to reveal the effects of FeCl3 and Fe2(SO4)3 on reducing grain Cd concentrations in dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB). Results Soil application of FeCl3 and Fe2(SO4)3 (0.04 M Fe3+/m2) significantly reduced grain Cd concentration in DPW at maturity by 19.04% and 33.33%, respectively. They did not reduce Cd uptake or root-to-shoot Cd translocation, but increased Cd distribution in lower leaves, lower internodes, and glumes. Meanwhile, application of FeCl3 and Fe2(SO4)3 up-regulated the expression of TpNRAMP5, TpNRAMP2 and TpYSL15 in roots, and TpYSL15 and TpZIP3 in shoots; they also downregulated the expression of TpZIP1 and TpZIP3 in roots, and TpIRT1 and TpNRAMP5 in shoots. Conclusions The reduction in grain Cd concentration caused by application of FeCl3 and Fe2(SO4)3 was resulted from changes in shoot Cd distribution via regulating the expression of some metal transporter genes. Overall, this study reports the physiological pathways of soil applied Fe fertilizer on grain Cd concentration in wheat, suggests a strategy for reducing grain Cd concentration by altering shoot Cd distribution.

Abstract Background Observational studies have demonstrated the alterations of gut microbiota composition in diabetic nephropathy (DN), however, the correlation between gut microbiota and DN remains unclear. Methods A two-sample Mendelian randomization (MR) analysis was designed to estimate the association between gut microbiota and DN. The summary statistics of gut microbiota from phylum level to genus level were obtained from a large-scale, genome-wide association study involving 18,340 individuals, and the data at the species level was derived from the study of TwinsUK Registry, including 1126 twin pairs. The summary statistics of DN were originated from the latest release data of FinnGen (R7, 299623 participants). The MR estimation was calculated using inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was assessed using Cochrane’s Q test. Results Inverse variance weighted results indicated that the order Bacteroidetes and its corresponding class and phylum [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.15–2.17], the family Verrucomicrobiaceae and its corresponding class and order (OR, 1.46; 95% CI, 1.14–1.87), the genera Akkermansia (OR, 1.46; 95% CI, 1.14–1.87) and Catenibacterium (OR, 1.33; 95% CI, 1.07–1.66) might be associated with a higher risk of DN; whereas the genera Coprococcus2 (OR, 0.68; 95% CI, 0.51–0.91) and Eubacterium_coprostanoligenes_group (OR, 0.69; 95% CI, 0.52–0.92) might play protective roles in DN. Conclusions This MR study suggested that several gut bacteria were potentially associated with DN, further studies are required to validate these findings.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disorder for which effective treatments remain limited. Recent investigations revealed a potential link between altered glucose metabolism and the activation of fibroblasts, the key cells responsible for generating and depositing extracellular matrix proteins within the lung interstitium during IPF development. Method In this study, we aimed to investigate the potential therapeutic impact of albendazole on fibroblast to myofibroblast transition in IPF. We assess albendazole’s effectiveness in attenuating the activation of fibroblasts. We focused on elucidating the mechanism underlying albendazole's impact on TGF-β1-induced aerobic glycolysis in both lung tissues and fibroblasts obtained from patients with IPF and other lung fibrosis types. Furthermore, the antifibrotic effects of oral administration of albendazole were investigated in mouse models of pulmonary fibrosis induced by BLM or SiO2. Human precision-cut lung slices were employed to evaluate the impact of albendazole following TGF-β1 stimulation. Result In this work, we demonstrated that albendazole, a first-line broad-spectrum anthelmintic drug, effectively attenuated fibroblast to myofibroblast transition through alleviating TGF-β1-induced aerobic glycolysis dependent on the LRRN3/PFKFB3 signaling pathway. Additionally, LRRN3 expression was downregulated in both lung tissues and fibroblasts from patients with IPF and other types of lung fibrosis. Importantly, the levels of LRRN3 correlated with the progression of the disease. Notably, oral administration of albendazole exerted potent antifibrotic effects in mouse models of pulmonary fibrosis induced by BLM or SiO2, and in human precision-cut lung slices after TGF-β1 stimulation, as evidenced by improvements in lung morphology, reduced myofibroblast formation, and downregulation of α-SMA, collagen type 1 and Fibronectin expression in the lungs. Conclusion Our study implies that albendazole can act as a potent agonist of LRRN3 during fibroblast to myofibroblast differentiation and its oral administration shows potential as a viable therapeutic approach for managing IPF.

Objective: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations. Methods: Patients with ROHHAD syndrome reported before and after 2019 were divided into groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups. Results: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among groups 1–3, the rates of cardiovascular manifestations were NA vs 12.8% vs 81.2%; gastrointestinal disturbances were 11.4% vs 8.5% vs 62.5%; strabismus was 25.7% vs 12.8% vs 62.5%; sleep disturbance was NA vs 6.4% vs 50.0%; and abnormal pain threshold was NA vs 10.6% vs 25.0% (all P < 0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (P < 0.01). Conclusion: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

Abstract Background In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. Methods This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. Results After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P

Abstract Cutaneous squamous cell carcinoma (CSCC) is common among the elderly, typically treated with surgery. However, for surgery-ineligible patients or those with non-healing wounds progressing to malignant ulcers, non-surgical local treatments are viable. This case details an 80-year-old with recurrent back CSCC and intractable malignant ulcers post-radiotherapy and chemotherapy. Treatment involved Hematoporphyrin Derivative (HpD) Photodynamic Therapy (PDT) with low-dose cindilimab immunotherapy (intravenous and intralesional). Two cycles achieved lesion remission, altering peripheral immune cell counts. HpD-PDT combined with immunotherapy is promising for treating CSCC, particularly with malignant ulcers.