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Abstract Background Sperm capacitation is a prerequisite for natural or in vitro fertilization. After capacitation, sperm become hyperactivated and undergo an acrosome reaction, which helps them penetrate the oocyte. Cordycepin, a bioactive compound first isolated from Cordyceps militaris, is an adenosine analog with numerous physiological activities. However, its effects on sperm capacitation remain unclear. This study aims to elucidate the effects and mechanisms of cordycepin on human sperm capacitation. Methods During in vitro capacitation culture, healthy human sperm were treated with cordycepin (20, 100, 500 µM). Sperm motility and hyperactivation were detected using a computer-assisted sperm analyzer. Sperm acrosome reaction was measured using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin. Sperm protein kinase A (PKA) activity was analyzed using an ELISA kit. The levels of sperm protein tyrosine phosphorylation were detected by western blotting. Sperm DNA damage was detected by a sperm chromatin dispersion assay. Reactive oxygen species (ROS) were measured using the fluorescence probe 2′,7′-dichlorodihydrofluorescein diacetate. The expression and localization of adenosine receptors were analyzed by western blotting and immunofluorescence. The specific inhibitors of adenosine receptors were used to confirm their effects on cordycepin-induced sperm capacitation. Finally, molecular docking was performed to analyze the interaction between cordycepin and adenosine receptors. Results Cordycepin improved hyperactivated sperm motility, acrosome reaction, PKA activity, and protein tyrosine phosphorylation during capacitation while having no obvious effects on sperm ROS or DNA damage. Four adenosine receptor subtypes were expressed in human sperm, but their localizations differed. Inhibition of adenosine receptors significantly decreased cordycepin-induced sperm hyperactivation and the acrosome reaction. Molecular docking showed that cordycepin can bind to the four subtypes of adenosine receptors. Conclusion Cordycepin may promote human sperm capacitation through adenosine receptor-mediated signaling pathways. These findings may be useful for assisted reproductive technology and animal breeding.

Abstract The uncertainty regarding the correlation between sea spray aerosol (SSA) formation and sea surface temperature (SST) hinders the accurate estimation of SSA’s impact on global climate. Here, we developed a temperature-controlled plunging SSA simulation tank to investigate the impact of SST on SSA formation from two perspectives: SSA particle size distribution and organic enrichment. Our findings show that SSA particle size decreases with decreasing SST, as exhibited by an increase in SSA within Aitken mode and a decrease in SSA within accumulation and coarse modes. SST can significantly enhance organic enrichment in SSA particles, while the multiplicative increases vary from 2 to 10 times depending on the organic matter species and the SSA particle size. Based on our experimental results, it is predicted that SST reduction may lead to a significantly higher contribution of Aitken modal SSA-derived CCN in cold waters (0 °C) than in warm waters (30 °C). Additionally, we incorporate SST for the first time in estimating the global flux of dissolved organic carbon (DOC) emitted via SSA, yielding a value ranging from 23.45 to 55.78 Tg C yr−1. Compared to previous works, our study reveals the crucial role of SST in influencing both cloud formation and the atmospheric organic burden of SSA.

Abstract Recovering 3D human meshes from monocular images is an inherently ill‐posed and challenging task due to depth ambiguity, joint occlusion, and truncation. However, most existing approaches do not model such uncertainties, typically yielding a single reconstruction for one input. In contrast, the ambiguity of the reconstruction is embraced and the problem is considered as an inverse problem for which multiple feasible solutions exist. To address these issues, the authors propose a multi‐hypothesis approach, multi‐hypothesis human mesh recovery (MH‐HMR), to efficiently model the multi‐hypothesis representation and build strong relationships among the hypothetical features. Specifically, the task is decomposed into three stages: (1) generating a reasonable set of initial recovery results (i.e., multiple hypotheses) given a single colour image; (2) modelling intra‐hypothesis refinement to enhance every single‐hypothesis feature; and (3) establishing inter‐hypothesis communication and regressing the final human meshes. Meanwhile, the authors take further advantage of multiple hypotheses and the recovery process to achieve human mesh recovery from multiple uncalibrated views. Compared with state‐of‐the‐art methods, the MH‐HMR approach achieves superior performance and recovers more accurate human meshes on challenging benchmark datasets, such as Human3.6M and 3DPW, while demonstrating the effectiveness across a variety of settings. The code will be publicly available at https://cic.tju.edu.cn/faculty/likun/projects/MH‐HMR.

In the context of Industrial Internet of Things (IIoT) flexible production lines, accurately predicting production bottlenecks is crucial for optimizing efficiency and resource allocation. However, the dynamic and uncertain nature of these processes poses significant challenges. This study introduces a novel bottleneck prediction method by integrating the Drift Index (DI) with a Stacked Regression Model (SRM). This study marks the first application of stacked ensemble learning techniques in predicting bottlenecks within IIoT-enabled flexible production lines, leading to notable improvements in prediction accuracy and model robustness. The proposed method utilizes both real-time and historical data collected from IoT devices, encompassing three core steps: bottleneck data analysis, quantification of the drift index, and construction of the stacked regression model. By incorporating multiple production parameters such as equipment utilization and queue length, the method employs advanced time series analysis to forecast potential bottleneck drifts. Experimental results confirm that the DI-SRM model achieves high prediction accuracy and real-time responsiveness, effectively addressing the challenges of dynamic production environments. This approach provides reliable decision support for production scheduling and resource allocation, thereby optimizing production efficiency and enhancing market competitiveness.

Abstract Copper-induced cell death is regulated through protein lipoylation, which is critical for gene expression and phenotypic regulation. Neverless, the role of Cuproptosis-related genes in breast cancer (BC) remains unknown. This study aimed to construct a prognostic signature based on the expression of Cuproptosis-related genes in order to guide the diagnosis and treatment for BC. Cuproptosis-related genes prognostic signature has ata of 1250 BC tissues and 583 normal breast tissues were obtained from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and GEO GSE65212. The prognostic signature was established and evaluated with nineteen Cuproptosis-related genes. A series of in silico analyses based on SLC31A1, included expression analysis, independent prognostic analysis, correlation analysis, immune-related analysis and survival analysis. Finally, a series of cell experiments (including quantitative real-time polymerase chain reaction and western blot), and mice experiments were applied to evaluate the impact of SLC31A1 on BC. Cuproptosis-related genes prognostic signature has good predictive promising for survival in BC patients. We discovered that SLC31A1SLC31A1 was overexpressed in BC and was its independent prognostic factor. High expression of the SLC31A1 was correlated with poor prognosis and immune infiltrating of BC. SLC31A1 expression is associated with immune, chemotherapeutic and targeted therapy outcomes in BC. The proliferation, migration, and invasiveness of Her2 + enriched BC cells were decreased by SLC31A1 knockdown, also resulting in a decrease in tumor volume in mouse model. SLC31A1 is a candidate biomarker or therapeutic target in precision oncology, with diagnostic and prognostic significance in BC.

Abstract Background Dilated cardiomyopathy (DCM) is a major cause of heart failure and heart transplantation. Recently, some studies have reported that the autoimmune response in myocardial cells might be related to the pathogenesis of DCM. The CD247 gene has been previously found to be involved in autoimmune disease. Therefore, our study aimed to clarify the hypothesis that there is a certain linkage between polymorphisms of the CD247 gene and the triggering of DCM risk. Methods In the present study, two single nucleotide polymorphisms (SNPs) of the CD247 gene, rs12141731 and rs858543, were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) in 355 DCM patients and 404 age- and sex-matched controls. Results Pearson’s chi-squared test for the CD247 gene revealed that SNP rs858543 (p = 0.001, OR = 0.72, 95% CI = (0.588–0.882), but not SNP rs12141731, was associated with DCM in the Chinese Han population. Haplotype analysis revealed that the CC haplotype was associated with increased DCM susceptibility, while CT was a protective haplotype. Cox multivariate survival analysis indicated that the rs858543 TT genotype (HR: 0.608, 95% CI = 0.402–0.921, p = 0.019) was an independent multivariate predictor for longer overall survival in DCM patients. CD247 mRNA expression levels were significantly decreased in DCM patients (p = 0.02). Conclusions Our study suggested that a polymorphism in the CD247 gene may be a risk factor for DCM in the Chinese Han population. Trial registration ChiCTR2000029701.

Abstract Hepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy associated with high risks of recurrence and metastasis. Liver cancer stem cells (CSCs) are increasingly recognized as pivotal drivers of these processes. In our previous research, we demonstrated the involvement of TFCP2L1 in maintaining the pluripotency of embryonic stem cells. However, its relevance to liver CSCs remains unexplored. In this study, we report an inverse correlation between TFCP2L1 protein levels in HCC tissue and patient outcomes. The knockdown of TFCP2L1 significantly reduced HCC cell proliferation, invasion, metastasis, clonal formation, and sphere-forming capacity, while its overexpression enhanced these functions. In addition, experiments using a nude mouse model confirmed TFCP2L1’s essential role in liver CSCs’ function and tumorigenic potential. Mechanistically, we showed that TFCP2L1 promotes the stemness of CSCs by upregulating NANOG, which subsequently activates the JAK/STAT3 pathway, thereby contributing to HCC pathogenesis. Importantly, we identified a specific small molecule targeting TFCP2L1’s active domain, which, in combination with Sorafenib, sensitizes hepatoma cells to treatment. Together, these findings underscore TFCP2L1’s pathological significance in HCC progression, supporting its potential as a prognostic biomarker and therapeutic target in this disease.

Abstract Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a significant global health challenge, with limited therapeutic options for patients with KRAS-mutated tumors. Herein, a copper-based metal-organic framework (Cu-MOF) was applied as a novel cuproptosis-mediated nanoplatform for lung cancer therapy. Cu-MOF would disassemble and liberate copper ions under the acidic microenvironment of lysosomes of cancer cells, initiating a cascade of cellular events. The released copper ions catalyzes the Fenton reaction, generating hydroxyl radicals that induce oxidative damage, leading to cytoskeletal disruption and activation of caspase-3, ultimately triggering apoptosis. Simultaneously, with the mediation of the key regulatory factor FDX1, we found that the copper ions binding to the mitochondrial protein DLAT could result in the loss of iron-sulfur cluster proteins and aggregation of lipoylated proteins, which culminated in proteotoxic stress-induced cuproptosis. The pronounced anti-tumor effects of Cu-MOF with apoptosis and cuproptosis were confirmed both in vitro and in vivo experiments. Such dual induction of apoptosis and cuproptosis by Cu-MOF presents a promising therapeutic strategy for NSCLC, particularly for KRAS-mutated tumors, and expands potential applications of Cu-based nanomateirals for other cancers.

Laser powder bed fusion (L-PBF) of WE43 magnesium alloy has a promising application prospect in the fields of lightweight parts and biodegradable implants. Grain refinement in these components is expected for high strength and controlled biodegradation, however, grain structure of WE43 is sensitive to composition and processing. L-PBF WE43 exhibited significant diversity on the microstructure and properties with the fluctuation of powder composition, and the influencing mechanism remained unclear. In this study, L-PBF samples were fabricated with high formation quality using four different WE43 powders, in which the content of Nd and Zr were purposely adjusted. Their microstructure, tensile properties and corrosion resistance were characterized. L-PBF specimens composed of fine equiaxed grains were obtained from Mg-3.56Y-2.45Nd-1.14Gd-0.40Zr powder, achieving ultimate strength of 316 MPa and elongation of 15%. With the minor decrease of Nd and Zr content, which was still in the range of present standards of WE43, L-PBF specimens respectively exhibited abnormal grain growth and coarse columnar grains, leading to tremendous deterioration of mechanical properties and corrosion resistance. During the multiple layers of fusion and solidification, Zr promoted the columnar-to-equiaxed transition and generated finer grains, while Nd exerted pinning effect in the heat affected zone to keep the fine grains from abnormal grain growth. The results firstly demonstrate the significant influence of the minor change of alloying elements on the performance, and indicate that a stricter compositional standard of WE43 powder is necessary to achieve reliable properties for the L-PBF process.

Spinal Cord Independence Measure (SCIM) was an important functional outcome measure specifically designed for spinal cord injury (SCI) patients, with the self-reported version of SCIM (SCIM-SR) published in 2013. This study aims to translate the SCIM-SR into Chinese, and to investigate the validity of Chinese SCIM-SR among SCI patients. This Chinese version of SCIM-SR was translated into Chinese in a standardized approach, and then filled out by a sample of patients with SCI (n = 205) within 3 days after admission. Validity of Chinese SCIM-SR was then analyzed using Rasch analysis and principal component analysis. The subscale Selfcare and subscale Mobility showed good fit to the Rasch model, with no significance found in Chi-square test results for item-trait interaction, using Bonferroni adjustment for the significant level (χ2 =18.125, P = 0.111; χ2 =33.629, P = 0.006). Mean fit residual for items and persons of each subscale were within ± 2.5. The model fit of the subscale of Respiration and Sphincter Management was not satisfactory even after deleting one item and merging two items with local dependence. However, Kaiser-Meyer-Olkin test was > 0.50 in total score and all the subscales of Chinese SCIM-SR, and P

AbstractContext Jian Gan powder (JGP) is a Chinese medicine compound comprised ginseng, Radix Paeoniae Alba, Radix Astragali, Salvia miltiorrhiza, Yujin, Rhizoma Cyperi, Fructus aurantii, Sophora flavescens, Yinchen, Bupleurum and licorice.Objective This study explored the inhibitory effects, polarization and potential mechanisms associated with JGP in macrophages.Materials and methods RAW264.7 cells were randomly divided into six groups for 24 h: control, lipopolysaccharide (LPS), overexpression, 1% JGP, 2% JGP, 4% JGP, 8% JGP and 16% JGP. The effects of JGP on RAW264.7 cell proliferation were assessed using colony formation assays and cell counting kit-8 (CCK-8) assays. The Transwell assay was used to evaluate its impact on RAW264.7 cell migration. Moreover, we analysed the interleukin-6 (IL-6)/signal transducer and activator of the transcription 3 (IL-6/STAT3) signaling pathway using quantitative real-time PCR and Western blotting. Furthermore, we examined the M1/M2 polarization levels.Results Unlike LPS stimulation, JGP serum treatment markedly suppressed macrophage proliferation and migration capacity, while STAT3 overexpression enhanced RAW264.7 cell proliferation and migration. JGP inhibited the proliferation and migration of RAW264.7 cells by attenuating the IL-6/STAT3 signaling pathway. Furthermore, it inhibited macrophage M1 polarization, promoting M2 polarization.Discussion and conclusions JGP effectively suppressed the cellular function of RAW264.7 cells by down-regulating the IL-6/STAT3 signaling pathway and modulating macrophage M1/M2 polarization. These findings provide valuable theoretical and experimental basis for considering the potential clinical application of JGP in the treatment of immune-mediated liver injury in clinical practice.

We investigate the Sturm-Liouville (S-L) operator with boundary and transfer conditions dependent on the eigen-parameter. By utilizing interval partitioning and factorization techniques of characteristic function, it is proven that this problem has a finite number of eigenvalues when the coefficients of the equation meet certain conditions, and some conditions for determining the number of eigenvalues are provided. The results indicate that the number of eigenvalues in this problem varies when the transfer conditions depend on the eigen-parameter. Furthermore, the equivalence between this problem and matrix eigenvalue problems is studied, and an equivalent matrix representation of the S-L problem is presented.

Abstract While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.

Abstract Background Liver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated. Methods Mouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models. Results Our research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization. Conclusions The results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury.

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Background With the continuous improvement of diagnosis and treatment technology for cervical spine-related diseases in children at home and abroad, the demand for exploring the developmental anatomy and function of children's cervical spine of different ages is increasing. So the aim of this study was to investigate the changes of anatomical indicators in neurocentral synchondrosis (NCS) of C2–C7 with age and the developmental characteristics of different vertebrae in children aged 1–6 years old. Method A retrospective collection of 160 cases of normal cervical spine CT images of children aged 1–6 years old in provincial tertiary hospitals, according to the age group of 1-year-old into 6 groups. The original data of continuously scanned cervical spine tomography images were imported into Mimics16.0 software, under the two-dimensional image window, selected the measurement tool under the Measurements toolbar to measure and statistically analyzed the anatomical indicators such as cross diameter, sagittal diameter, height, perimeter and area of NCS in the C2–C7 segment of the cervical spine on the coronal plane and cross-section. Results There was no significant difference in the anatomical indexes of cervical spine NCS in children compared with the left and right sides of the same vertebrae (P > 0.05). The same cervical spine generally had differences between the age groups of 1–4 years old and 5–6 years old (P

Abstract With the increasing urban environmental problems, spontaneous vegetation has been gradually emphasized for high ecological value, whose distribution has been reported as strongly influenced by fine-scale environmental factors. As one of the major zones for urban spontaneous vegetation distribution, urban riparian corridors are well suited for research on the response of spontaneous plants to microhabitats. Taking the Wenyu River-North Canal in Beijing as the study site, we measured six microhabitat factors, including the level of maintenance and visitor activity, canopy density, litter thickness, and distance to water and road, to investigate their effects on spontaneous plant assemblages. The results showed that spontaneous plants respond significantly to fine-scale habitat variation, and were more responsive to human disturbance than other factors. Compared with diversity indicators, the functional trait compositions were more significantly correlated with microhabitat factors. Under lower maintenance of plants, the spontaneous communities had a higher invasion risk for plants. Thick litter can impede the occurrence of invasive species while favoring the growth of native ones. Our findings are important for furthering understanding of the spontaneous plant community establishment, and can serve as a good reference for the maintenance and management of spontaneous plants in urban riparian corridors.

Abstract Babesia spp. and Theileria spp. are tick-borne protozoan parasites with veterinary importance. In China, epidemiological and genetic investigations on many Babesia and Theileria species were still absent in many areas and many tick species. From Aug 2021 to May 2023, 645 ticks were collected from the body surface of domestic animals (camels, goats, sheep, and cattle) using tweezers in seven counties in three provinces including Xinjiang (Qitai, Mulei, Hutubi, and Shihezi counties), Chongqing (Youyang and Yunyang counties), and Qinghai (Huangzhong county). Three tick species were morphologically and molecularly identified (334 Hyalomma asiaticum from Xinjiang, 245 Rhipicephalus microplus from Chongqing, and 66 Haemaphysalis qinghaiensis from Qinghai). A total of three Babesia species and two Theileria species were detected targeting the 18S gene. The COI and cytb sequences were also recovered from Babesia strains for further identification. In R. microplus from Chongqing, Babesia bigemina, the agent of bovine babesiosis, was detected. Notably, in H. asiaticum ticks from Xinjiang, a putative novel genotype of Babesia caballi was identified (0.90%, 3/334), whose COI and cytb genes have as low as 85.82% and 90.64–90.91% nucleotide identities to currently available sequences. It is noteworthy whether the sequence differences of its cytb contribute to the drug resistance of this variant due to the involvement of cytb in the drug resistance of Babesia. In addition, Theileria orientalis and Theileria annulata were detected in R. microplus from Chongqing (12.20%, 31/245) and H. asiaticum from Xinjiang (1.50%, 5/334), respectively. These results suggest that these protozoan parasites may be circulating in domestic animals in these areas. The pathogenicity of the novel genotype of B. caballi also warrants further investigation.

Abstract Background Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

The effects of aluminum (Al) additions (0.04, 0.4, and 0.8 wt%) on the microstructural evolution, tensile properties, and sheared-edge ductility of dual phase (DP) steels were investigated. The DP steels were processed with distinct coiling temperatures after finish rolling, cold rolled, and subjected to two continuous galvanizing line (CGL) simulations: standard galvanizing (GI) and supercooling process (SC). Al expanded both the ɑ-ferrite and (ɑ+γ) phase fields at the expense of the γ-austenite region. Continuous cooling transformation (CCT) diagrams showed that Al increased ferrite start temperatures, broadened the ferrite transformation zone, and reduced austenite stability. Austenite growth kinetics during intercritical annealing, quantified using a modified Johnson-Mehl-Avrami-Kolmogorov (JMAK) model, revealed Avrami exponents ranging from 0.72 to 0.81 and apparent activation energies increasing from 422.9 to 496.7 kJ mol−1 with Al additions. Microstructural characterization revealed larger ferrite grain sizes and higher ferrite volume fractions with higher Al levels. Ultimate tensile strength (UTS) was influenced by Al contents, coiling temperatures, and CGL simulation methods. Global ductility (total elongation, TE) was highest for the 0.8Al Steel with a high coiling temperature and GI annealing, while local ductility (hole expansion ratio, HER) was maximized for the 0.04 Al Steel with a low coiling temperature and SC annealing. The majority of the CGL simulated DP steels exhibited good strength-ductility combinations, with the 0.8Al Steels demonstrating superior properties compared to current automotive advanced high-strength steel (AHSS) grades.

Pulpitis, an inflammatory disease of dental pulp tissues, ultimately results in the loss of pulp defense properties. Existing clinical modalities cannot effectively promote inflamed pulp repair. Oxidative stress is a major obstacle inhibiting pulp repair. Due to their powerful antioxidative capacity, mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) exhibit potential for treating oxidative stress-related disorders. However, whether MSC-sEVs shield dental pulp tissues from oxidative damage is largely unknown. Here, we showed that dental follicle stem cell-derived sEVs (DFSC-sEVs) have antioxidative and prohealing effects on a rat LPS-induced pulpitis model by enhancing the survival, proliferation and odontogenesis of H2O2-injured dental pulp stem cells (DPSCs). Additionally, DFSC-sEVs restored the oxidative/antioxidative balance in DPSC mitochondria and had comparable effects on ameliorating mitochondrial dysfunction with the mitochondrion-targeted antioxidant Mito-Tempo. To improve the efficacy of DFSC-sEVs, we fabricated an intelligent and injectable hydrogel to release DFSC-sEVs by combining sodium alginate (SA) and the ROS sensor RhB-AC. The newly formed SA-RhB hydrogel efficiently encapsulates DFSC-sEVs and exhibits controlled release of DFSC-sEVs in a HClO/ClO− concentration-dependent manner, providing a synergistic antioxidant effect with DFSC-sEVs. These results suggest that DFSC-sEVs-loaded SA-RhB is a promising minimally invasive treatment for pulpitis by enhancing tissue repair in the pulp wound microenvironment.

Abstract Organic compounds released from wildfires and residential biomass burning play a crucial role in shaping the composition of the atmosphere. The solubility and subsequent reactions of these compounds in the aqueous phase of clouds and fog remain poorly understood. Nevertheless, these compounds have the potential to become an important source of secondary organic aerosol (SOA). In this study, we simulated the aqueous SOA (aqSOA) from residential wood burning emissions under atmospherically relevant conditions of gas-liquid phase partitioning, using a wetted-wall flow reactor (WFR). We analyzed and quantified the specific compounds present in these emissions at a molecular level and determined their solubility in clouds. Our findings reveal that while 1% of organic compounds are fully water-soluble, 19% exhibit moderate solubility and can partition into the aqueous phase in a thick cloud. Furthermore, it is found that the aqSOA generated in our laboratory experiments has a substantial fraction being attributed to the formation of oligomers in the aqueous phase. We also determined an aqSOA yield of 20% from residential wood combustion, which surpasses current estimates based on gas-phase oxidation. These results indicate that in-cloud chemistry of organic gases emitted from wood burning can serve as an efficient pathway to produce organic aerosols, thus potentially influencing climate and air quality.

Abstract The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2 −), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2 − production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Abstract To examine the influence of Body Mass Index (BMI) on laparoscopic gastrectomy (LG) short-term and long-term outcomes for gastric cancer. A retrospective analysis was conducted on gastric cancer patients undergoing LG at the Third Hospital of Nanchang City from January 2013 to January 2022. Based on WHO BMI standards, patients were categorized into normal weight, overweight, and obese groups. Factors such as operative time, intraoperative blood loss, postoperative complications, and overall survival were assessed. Across different BMI groups, it was found that an increase in BMI was associated with longer operative times (average times: 206.22 min for normal weight, 231.32 min for overweight, and 246.78 min for obese), with no significant differences noted in intraoperative blood loss, postoperative complications, or long-term survival among the groups. The impact of BMI on long-term survival following LG for gastric cancer was found to be insignificant, with no notable differences in survival outcome between different BMI groups. Although higher BMI is associated with increased operative time in LG for gastric cancer, it does not significantly affect intraoperative blood loss, postoperative complications, recovery, or long-term survival. LG is a feasible treatment choice for obese patients with gastric cancer.

Abstract Background This study aims to comprehensively explain of glycosylated Hemoglobin (HbA1c) control patterns and help determine the causal relationship between glycemic control patterns and atherosclerosis progression, thereby contributing to the effective management of diabetes complications. Method All participants registered at the National Metabolic Management Center (MMC) of Beijing Luhe Hospital. The HbA1c pattern was described by HbA1c variability and trajectory groups of HbA1c. Then we examined the associations between the HbA1c pattern and the changes of intima-media thickness (ΔIMT) using covariate-adjusted means (SE) of ΔIMT, which were calculated by multiple linear regression analyses adjusted for the covariates. Finally, a cross-lagged panel model (CLPM) was performed to further verify the bidirectional relationship between IMT and HbA1c. Results After data cleaning, a total of 1041 type 2 diabetes patients aged 20–80 years were included in this study. Except for average real variability (ARV), the other variation variables of HbA1c were associated with ΔIMT% (P

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.

Highlights A clear negative correlation between the size of water clusters and the concentration of dissolved oxygen was observed. This implied that smaller clusters water exhibits higher concentrations of dissolved oxygen. Oxygen molecules are primarily existed at the surfaces or interfaces of water clusters and can rapidly traverse the gas liquid interface. A semi empirical formula relating the average number of water molecules in a cluster to 17O NMR half peak width was derived, demonstrating an approximate lin ear relationship.

Non-methane hydrocarbons (NMHCs) are a common type of volatile organic compounds (VOCs) pollutant in the petrochemical industry and have attracted widespread attention because of their adverse health effects and environmental impacts. In this paper, we report a new porous slurry formed with zeolitic imidazolate framework-8 (ZIF-8) and iso-hexadecane to capture the low-concentration and multi-component NMHCs (mainly ethane (C2H6), propane (C3H8), and n-butane (n-C4H10)) from the oil field exhaust. The sorption capacity of C2H6 in the slurry is significantly higher than that of nitrogen (N2) and methane (CH4). Moreover, the slurry demonstrated a clear advantage for C2H6 over N2 and CH4 in competitive adsorption through the pressure-drop curves. In the NMHCs capture experiments, the C3H8 and n-C4H10 concentrations after purification can be reduced to below 100 ppm, while the C2H6 concentration can reach approximately 180 ppm. More encouragingly, in the breakthrough tests, the slurry exhibits a perfect kinetic separation selectivity for multi-component NMHCs. Furthermore, to avoid structural collapse of ZIF-8 material during long-term use in acidic and wet environments, a certain amount of 2-methylimidazole was retained in the slurry as a protective agent in the material synthesis process. In this way, the ZIF-8 materials in the slurry can retain the stable characteristic structure in an aqueous and acidic environment and keep the capture capacity for NMHCs without degradation. We believe the porous ZIF-8/iso-hexadecane slurry is a promising capture agent for low-concentration and multi-component NMHCs with strong purification capacity and stability.

Non-structural protein 2 (NSP2) of PRRSV is highly variable and plays crucial roles in the virus's life cycle. To elucidate the function of NSP2 during PRRSV infection, we identified SH3KBP1 as an NSP2-interacting host protein using mass spectrometry. Exogenous SH3KBP1 expression significantly inhibited PRRSV replication by enhancing IFN-I and related ISGs production. Conversely, SH3KBP1 knockdown promoted viral replication by downregulating IFN-I and ISGs levels. In vivo experiments revealed that Sh3kbp1-/- mice were more susceptible to VSV infection, exhibiting reduced serum IFN-β levels. Further investigation showed that SH3KBP1 enhances RIG-I signal transduction by increasing K63-linked polyubiquitination through interaction with the E3 ubiquitin ligase TRIM25. We also found that PRRSV infection and NSP2 overexpression induce the autophagic degradation of SH3KBP1, counteracting the host's innate immune response. A critical interaction site was identified within the third polyproline-arginine motif in NSP2 (453PVPAPR458). Recombinant PRRSV lacking this motif displayed reduced virulence and decreased SH3KBP1 degradation. This study advances our understanding of how PRRSV interferes with the host immune response and offers valuable insights for developing novel attenuated vaccines against PRRSV.

Plant factories are efficient systems for vegetable production under a clean and controlled environment. To improve the sterilization efficiency of nutrient solutions (NS) in plant factories, this study examined the changes in the number and composition of colonies from in-use and post-use stored NS. The sterilization effect under ultraviolet (UV) light-emitting diode light was also investigated. The results indicated that the total plate count of bacteria (TPC) of newly prepared NS was 3.99 lg CFU/mL (9870 CFU/mL); within 7 days of cultivation, this number sharply increased ∼7.8 times to 4.88 lg CFU/mL (76,000 CFU/mL), then remained stable. After dark sealed storage (DSS) of post-use NS, TPC dramatically decreased by 82.8% and reached its lowest point at 4.29 lg CFU/mL (19,566 CFU/mL) on day 3, equivalent to a log survival ratio of −0.76, then rapidly rebounded by 235.6% to 4.82 lg CFU/mL (65,666 CFU/mL) on day 4. During storage, bacterial community composition was also remarkably changed, and the relative abundance of heterotrophic bacteria such as Variovorax paradoxus and Pararhizobium giardinii and photosynthetic bacteria such as Pseudo-Nitzschia multiseries were greatly decreased. The log survival ratio for in-use and post-use stored NS under UV sterilization were −1.29 and −1.30, respectively, and was not significantly different. Coupled with the dramatic decrease in TPC during DSS, the overall log survival ratio of post-use NS UV sterilization was −2.06 and was the most effectively form of sterilization in our study. In short, TPC of in-use NS remained high for a long period, and DSS may serve as a low-cost NS sterilization method in plant factories.

Background: Tumor genomic profiling has a significant impact on the selection of targeted therapy. Circulating tumor DNA (ctDNA) has emerged as a noninvasive, and reproducible assay compared with tissue biopsy. We aimed to evaluate its utility in identifying mutations and guiding targeted therapy for lung cancer. Methods: A total of 173 lung cancer patients underwent next-generation sequencing (NGS) using a targeted enrichment panel covering 20 lung cancer-related genes. The performance of the ctDNA NGS assay in identifying genetic mutations or alterations was compared with tissue biopsy and droplet digital PCR (ddPCR). The treatment response to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapies based on the ctDNA assay results was also assessed. Results: The ctDNA was detected in 61.85% of patients. Tissue mutations were detected in paired ctDNA in 38.57% of cases, while ctDNA mutations were detected in paired tissues in 89.1% of cases. The ctDNA increased the number of advanced non-small cell lung cancer (NSCLC) patients who received NCCN-recommended genetic testing by 12%. The concordance between ddPCR and ctDNA was relatively high reaching 99.43%. EGFR T790M/C797S c.G2390C and EGFR T790M/C797S c.T2389A were detected in tissue and ctDNA, respectively, in patient 01015. Moreover, ctDNA assay identified the EGFR T790M mutation, which was missed by tissue biopsy in patient 01149, who developed drug resistance after 1 year of EGFR-TKI therapy. Of the 17 patients who received EGFR-TKI targeted therapies based on the ctDNA NGS results, 12 patients achieved a partial response and two patients had stable disease. Conclusions: The results demonstrated that the ctDNA assay could partially overcome tumor heterogeneity in detecting mutations and provide complementary information on tumor genomic profiles. Moreover, the presence of EGFR mutations in ctDNA could offer valuable guidance for selecting appropriate EGFR-TKI treatment for advanced lung cancer patients. However, it is important to note that the ctDNA NGS assay has certain limitations in fully identifying all genomic alterations present in the tumor.

Fine classification and phenological information of rice paddy are of great significance for precision agricultural management. General compact polarimetric (CP) synthetic aperture radar (SAR) offers the advantage of providing rich polarimetric information, making it an important means of monitoring rice growth. Therefore, in response to the current challenges of difficulty in rice type classification and the small differences in phenological polarimetric characteristics, a novel strategy for fine classification and phenological analysis of rice paddy is proposed. This strategy thoroughly explores the polarimetric information of general CP SAR data and the target scattering characterization capabilities under different imaging modes. Firstly, the general CP SAR data is formalized using the standard CP descriptors, followed by the extraction of general CP features through the ΔαB/αB target decomposition method. optimal CP features are generated to achieve fine classification of rice paddy. Finally, 6 phenological stages of rice are analyzed based on the general CP features. The experiment results of rice classification show that the classification accuracy based on this strategy exceeds 90%, with a Kappa coefficient above 0.88. The highest classification accuracies were observed for transplanting hybrid rice paddy (T-H) and direct-sown japonica rice paddy (D-J), at 80.9% and 89.9%, respectively. The phenological evolution rule of the two rice types indicate that from early June (seedling stage) to late July (elongation stage), the CP feature variation trends of T-H and D-J are generally consistent. However, from October (mature stage) to November (harvest stage), the variation trends of the CP features for T-H and D-J are significantly different. The study found that from the booting-heading stage to the harvest stage, the linear π/4 mode outperforms circular and elliptical polarimetric modes in distinguishing different types of rice. Throughout the entire phenological period of rice growth, CP SAR of linear π/4 mode is surpasses that of other linear modes in discriminating different type of rice. The proposed strategy enables high-precision fine classification rice paddy, and the extracted general CP αB parameter effectively reflects the phenological change trends in rice growth.

Diet is an important component to influence microbiota, there are less data available about the microbiome of Suffolk cross with Tibetan (SCT) animals with different fodders. The current study was conducted for comparing the fungi microbiota in SCT sheep fed with different forages. Sequencing of ileum samples from sheep groups of AH (alfalfa and oat grass), BH (mixture of grass and concentrated feeds), CH (concentrated feed I), DH (concentrated feed II) and EH (concentrated feed III) achieved 3,171,271 raw and 2,719,649 filtered sequences. Concentrated feeds changed fungi microbiota in SCT sheep with three phyla and 47 genera significantly different among the groups. Genera include positive genus of Scytalidium and negative fungi of Sarocladium, Kazachstania, Gibberella, Scytalidium, Candida, Wickerhamomyces. The findings of our study will contribute to efficient feeding of SCT sheep at cold plateau areas.

Objective: TPMS porous structures have adjustable stiffness, a smooth surface, and highly connected pores, which help avoid stress concentration within the dot-matrix structure and promote cell adhesion and proliferation. A cervical interbody cage based on this type of porous structure was designed and fabricated, and its mechanical properties and biocompatibility were evaluated. Methods: TPMS porous structures have adjustable stiffness, a smooth surface, and highly connected pores, which help avoid stress concentration within the dot-matrix structure and promote cell adhesion and proliferation. A cervical interbody cage based on this type of porous structure was designed and fabricated, and its mechanical properties and biocompatibility were evaluated. Results: The volume fraction of the 3D-printed TC4-based Tubular-G structure was linearly related to compressive strength. Adjusting the volume fraction resulted in a Tubular-G structure with a modulus and yield strength similar to human bone, without stress concentration within the structure. The designed and fabricated TC4-based Tubular-G porous cervical interbody cage demonstrated excellent anti-sagging properties and biocompatibility. Conclusions: The volume fraction of the 3D-printed TC4-based Tubular-G structure was linearly related to compressive strength. Adjusting the volume fraction resulted in a Tubular-G structure with a modulus and yield strength similar to human bone, without stress concentration within the structure. The designed and fabricated TC4-based Tubular-G porous cervical interbody cage demonstrated excellent anti-sagging properties and biocompatibility.

Extracellular vesicles (EVs) are nanometer-sized lipid bilayer vesicles released by cells, playing a crucial role in mediating cellular communication. This review evaluates the effect of EVs on early embryonic development in vitro by systematically searching the literature across three databases, Embase, PubMed, and Scopus, from inception (Embase, 1947; PubMed, 1996; and Scopus, 2004) to 30 June 2024. A total of 28 studies were considered relevant and included in this review. The EVs included in these investigations have been recovered from a range of sources, including oviduct fluid, follicular fluid, uterine fluid, seminal plasma, embryos, oviduct epithelial cells, endometrial epithelial cells, amniotic cells, and endometrial-derived mesenchymal stem cells collected primarily from mice, rabbits, cattle and pigs. This diversity in EV sources highlights the broad interest and potential applications of EVs in embryo culture systems. These studies have demonstrated that supplementation with EVs derived from physiologically normal biofluids and cells to the embryo culture medium system has positive effects on embryonic development. Conversely, EVs derived from cells under pathological conditions have shown a negative impact. This finding underscores the importance of the source and condition of EVs used in culture media. Further, the addition of EVs as a culture medium supplement holds significant therapeutic potential for optimizing in vitro embryo culture systems. In conclusion, this evaluation offers a thorough assessment of the available data on the role of EVs in embryo culture media and highlights the potential and challenges of using EVs in vitro embryo production.

Schizophrenia is a chronic, severe, and disabling mental disorder that significantly impacts individuals’ lives. Long-term treatment with antipsychotic drugs, coupled with the complications of the disease itself, increases the risk of dysphagia in patients. These disorders further heighten the likelihood of choking and asphyxia death among this population. This project aims to comprehensively review the pathological mechanisms behind dysphagia in schizophrenia, alongside proposing early screening and evaluation methods. It also suggests treatment recommendations to mitigate the risks and complications associated with dysphagia in these patients.

Understanding how the bacteriomes in tuberculous lesions can be influenced by the susceptibility of Mycobacterium tuberculosis (MTB) can provide valuable information for preventing and treating drug resistant tuberculosis (DR-TB). High-throughput 16S rRNA sequencing was employed to analyze the bacteriome in pulmonary TB lesions from 14 patients with DR-TB and 47 patients with drug sensitive tuberculosis (DS-TB), along with 18 normal lung tissues (NT) from 18 lung cancer patients serving as the bacterial baseline. The phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) algorithm was utilized to predict bacterial metabolic functions. The major phyla of pulmonary bacteriomes included Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Fusobacteria. Alpha diversity indices, including ACE, Chao1, Shannon and OTU observed, all demonstrated different bacterial communities of DS-TB samples from that of NT samples; while only Shannon indicated difference between DR-TB and NT samples. The analysis of similarity (ANOSIM) showed significantly different bacterial communities within TB lesions compared to NT samples (R = 0.418, p = 0.001). However, difference was not observed between DR-TB and DS-TB samples (ANOSIM, R = 0.069, p = 0.173). The bacterial profiles within each DR-TB individual appeared unique, with no obvious clusters corresponding to drug-resistant phenotypes. Nevertheless, indicator genera identified in DR-TB and DS-TB lesions demonstrated distinctive micro-ecological environments. Most COG functions were enriched in TB lesions, and the most significant one was [J] translation, ribosomal structure and biogenesis. The distinct enrichment patterns of bacterial enzymes in DR-TB and DS-TB lesions suggest that pulmonary bacterial activities can be modulated by the susceptibility of MTB bacilli. This study provides fresh perspectives and strategies for the precise diagnosis and assessment of drug resistance tuberculosis.

Adult-onset immunodeficiency (AOID) mediated by anti-interferon-γ autoantibodies (AIGA) is a rare condition, particularly prevalent in Southeast Asia and southern China. We present a case study of a 62-year-old female with AOID who developed a severe pulmonary infection caused by Talaromyces marneffei (TM), leading to acute respiratory failure, generalized rash, multiple lymphadenopathies, bone destruction, and a mediastinal mass. Treatment included mechanical ventilation, antifungal medication, and corticosteroids, resulting in complete recovery and discharge. This case underscores the challenges of managing complex infections in AOID patients and highlights the importance of early diagnosis through metagenomic next-generation sequencing (mNGS) and appropriate intervention to improve clinical outcomes.

Summary: Probiotics typically refer to microorganisms that have been identified for their health benefits, and they are added to foods or supplements to promote the health of the host. A growing number of probiotic strains have been identified lately and developed into valuable regulatory pharmaceuticals for nutritional and medical applications. Gene editing technologies play a crucial role in addressing the need for safe and therapeutic probiotics in disease treatment. These technologies offer valuable assistance in comprehending the underlying mechanisms of probiotic bioactivity and in the development of advanced probiotics. This review aims to offer a comprehensive overview of gene editing technologies applied in the engineering of both traditional and next-generation probiotics. It further explores the potential for on-demand production of customized products derived from enhanced probiotics, with a particular emphasis on the future of gene editing in the development of live biotherapeutics.

We proposed and fabricated a miniaturized multi-core fiber grating vibration sensor. The size of the miniaturized vibration sensor is 10mm × 10mm × 10 mm with a mass of only 0.25g. Finite element analysis and experimental tests were carried out to validate the performance of the vibration sensor. The experiment results indicate that the sensor has a sensitivity of 68.72 pm/g in the X direction and 64.52 pm/g in the Y direction within the operating frequency range of 20–240Hz. The cross-interference between the two directions of vibration measurement falls within 4 %. The sensor is suitable for measuring mechanical vibrations in the mid-low frequency range, especially in cases where size, quality, and distributed measurement are of particular concern.

Hepatic diseases pose a significant threat to community health, impacting the quality of life and longevity of millions worldwide. Despite revolutionary advancements in treatment, liver diseases remain a pressing issue, necessitating the development of more effective therapeutic approaches. Here, we conducted a comprehensive multi-omics analysis to investigate the underlying mechanism of Swertiamarin in alleviating hepatic injuries induced by CCl4 in mice. We divided 100 Kunming mice into five groups: RC (control), RM (CCl4), RD (15 mg/Kg Swertiamarin), RZ (30 mg/Kg Swertiamarin), and RG (60 mg/Kg Swertiamarin). Animals in groups RD, RZ, and RG received daily Swertiamarin via gavage, while those in groups RM, RD, RZ, and RG were treated with CCl4 solution intraperitoneally every four days, nine times in total. Our findings revealed that mice in the RM group exhibited slightly lower average weights compared to other groups, along with significantly higher liver weight (p

A novel method for the preparation of highly functionalized 4-oxo-3-(1H-pyrrol-3-yl)-4H-chromenes (OPCMs) from 3-formylchromones and α-isocyanoacetates via an unprecedented three-component [1 ​+ ​1 ​+ ​3] cycloaddition reaction in one pot was developed. The three-component cascade reaction was enabled by refluxing a mixture of the substrates in 1,4-dioxane in the presence of Ag2CO3 as a Lewis acid promoter. As a result, a series of functionalized pyrroles (OPCMs, 3), was prepared regioselectively and in high yields (80%–88%) through the formation of three bonds. This protocol can be used in the synthesis of OPCMs rather than through conventional, multi-step reactions and is suitable for both combinatorial and parallel syntheses of pyrroles.

Abstract While the forests on Mount Taishan are predominantly man-made, there is a notable vertical variation in vegetation. This study employs the method of cloud model, quantifying uncertainty (fuzziness and randomness) of things. Utilizing digital elevation model (DEM) and vegetation distribution data, we constructed elevation cloud models for Mount Taishan’s deciduous broad-leaved, temperate coniferous, and mixed coniferous-broadleaved forests. Using three numerical features of the cloud model—Expectation (EX), Entropy (EN), and Hyper-entropy (HE)—we quantitatively analyzed the macro regularity and local heterogeneity of Mount Taishan’s forests vertical distribution from the perspective of uncertainty theory. The results indicate: (1) The EX of the core zone elevation of deciduous broad-leaved forest is 716.65 m, temperate coniferous forest is 1053.51 m, and mixed coniferous-broadleaved forest is 1384.09 m. The variation range of the core zone distribution height is smaller in the mixed coniferous-broadleaved forest (EN: 53.74 m) compared to deciduous broad-leaved forest (EN: 99.63 m) and temperate coniferous forest (EN: 121.70 m). (2) The fuzziness and randomness of the distribution height of the lower extension zones of deciduous broad-leaved forest and temperate coniferous forest (EN: 75.15 m, 184.56 m; HE: 24.09 m, 63.54 m) are greater than those of the upper extension zones (EN: 44.75 m, 42.49 m; HE: 14.48 m, 13.23 m). (3) The distribution fuzziness and randomness within temperate coniferous forests exceed those of deciduous broad-leaved forests. Within the core zones, the uncertainty regarding the vertical distribution of vegetation across different aspects remains consistent, which retains the characteristic of man-made forests. However, in transition areas, there is significant disparity, reflecting the adaptive relationship between vegetation and its environment to some extent. In the upper and lower extension zones of deciduous broad-leaved forests, the EX values for the vertical distribution height of mixed coniferous and broad-leaved forests differ significantly from those of deciduous broad-leaved forests (the difference is 22.82–39.15 m), yet closely resemble those of temperate coniferous forests (the difference is 4.79–7.94 m). This suggests a trend wherein deciduous broad-leaved tree species exhibit a proclivity to encroach upon coniferous forest habitats. The elevation cloud model of vertical vegetation zones provides a novel perspective and method for the detailed analysis of Mount Taishan’s vegetation vertical differentiation.

Abstract A catalytic diastereoselective Prins reaction for hydroxymethylation and hydroxylation of 1,3-diarylpropene was successfully utilized to prepare various 1,3-dioxanes 7 in 14–88% yields. Take advantage of the synthetic intermediate 7h, the key B/C rings in brazilin core could be constructed by the sequential of Friedel–Crafts/Ullmann-Ma rather than Ullmann-Ma/Friedel–Crafts reactions. Graphical Abstract

In this work, preeminent bendability at room temperature is achieved by simultaneously introducing the gradient microstructure and texture along the normal direction (ND) of Mg-4.05Gd-0.57Zr alloy sheets prepared by turned bearing extrusion (TBE). The grain size of the VK-TBE sheet at the top, middle and bottom layers are 4.54 μm, 8.48 μm and 7.84 μm respectively. In addition, the fine-grained layer presents the highest texture deviation angle witch provides this layer with the highest Schmid factor (SF) for basal slip. When this layer is placed at the outer side, the bending angle is promoted by about 99.8% compared with the conventionally extruded sheet. The sample with a thickness of 3 mm is bent to 60° without cracking, revealing an excellent promotion in the bendability. During bending, the combination of high SF for basal slip and fine grains contributes to the elevated plasticity of the outer layer. Furthermore, at the inner region, a lot of twin bands appear in the relatively coarse grains with high SF for tensile twinning, which significantly regulates the strain distribution along the ND. Consequently, the VK-TBE-FG sample exhibits preeminent bendability owing to the cooperative effects of enhanced plasticity of the outer layer and regulated strain distribution.

Abstract Background Immunological liver injury (ILI) is a common liver disease associated with the microbiota-gut-liver axis. Jian Gan powder (JGP) exhibits both protective and therapeutic effects on hepatitis virus-induced ILI in the clinic. However, the underlying mechanisms remain elusive. The aim of this study is to investigate the hepatoprotective effects and associated mechanisms of JGP in the context of gut microbiota, utilizing a mouse model of ILI. Methods The mouse model was established employing Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS). Following treatment with JGP (7.5, 15, or 30 g/kg), serum, liver, and fresh fecal samples were analyzed. 16S rRNA gene sequencing and untargeted metabolomics profiling were performed to assess the role of JGP on the gut microbiota and its metabolites. Results JGP treatment markedly reduced serum IFN-γ, IL-6, IL-22, and hepatic p-STAT3 (phosphorylated transducer and activator of transcription-3) expression. In contrast, JGP increased the percentage of proliferating cell nuclear antigen-positive liver cells in treated mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the levels of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, metabolomics analysis of fecal samples showed that JGP restored the levels of allylestrenol, eplerenone, phosphatidylethanolamine (PE) (P-20:0/0:0), sphingomyelin (SM) d27:1, soyasapogenol C, chrysin, and soyasaponin I. Conclusions JGP intervention improves ILI by restoring gut microbiota and modifying its metabolic profiles. These results provide a novel insight into the mechanism of JGP in treating ILI and the scientific basis to support its clinical application.

Abstract Background Myopericytoma is a rare spindle cell tumor of mesenchymal origin, typically benign, characterized by concentric proliferation of tumor cells around blood vessels within subcutaneous tissue. It primarily occurs in middle-aged adults and is often located in distal extremities, although cases have been reported in proximal extremities and head-neck regions. However, occurrences within the oral cavity are exceedingly rare. To date, literature reviews have identified only two cases in children under 10 years old and reported only five cases of myopericytoma occurring in the lip region. We provide a comprehensive review and analysis of all documented cases to better understand this condition. Case presentation A 7-year-old girl presented to oral and maxillofacial surgery with the discovery of a painless mass on the inner aspect of the upper lip. The diagnosis of myopericytoma was confirmed by histological examination (HE staining), alcian blue staining, and immunohistochemistry. Conclusions Following surgical excision, there were no signs of recurrence at a 3-month follow-up. The pathological diagnosis of myopericytoma is quite challenging, and immunohistochemical testing is necessary.

Abstract Background Hyalomma ticks are widely distributed in semi-arid zones in Northwest China. They have been reported to harbor a large number of zoonotic pathogens. Methods In this study, a total of 334 Hyalomma asiaticum ticks infesting domestic animals were collected from four locations in Xinjiang, Northwest China, and the bacterial agents in them were investigated. Results A putative novel Borrelia species was identified in ticks from all four locations, with an overall positive rate of 6.59%. Rickettsia sibirica subsp. mongolitimonae, a human pathogen frequently reported in Europe, was detected for the second time in China. Two Ehrlichia species (Ehrlichia minasensis and Ehrlichia sp.) were identified. Furthermore, two Anaplasma species were characterized in this study: Candidatus Anaplasma camelii and Anaplasma sp. closely related to Candidatus Anaplasma boleense. It is the first report of Candidatus Anaplasma camelii in China. Conclusions Six bacterial agents were reported in this study, many of which are possible or validated pathogens for humans and animals. The presence of these bacterial agents may suggest a potential risk for One Health in this area. Graphical Abstract

The extraction and decolorization conditions for Spirulina platensis polysaccharides using hot alkali and hydrogen peroxide were investigated, and the process was optimized. Based on the results of a single-factor test, the yield and decolorization rate of polysaccharides were taken as indices to optimize the technological conditions for extracting polysaccharides from Spirulina platensis using the hot alkali method and decolorizing them with hydrogen peroxide using the response surface methodology. The optimal conditions for hot alkali extraction of polysaccharides from Spirulina platensis were determined as follows: NaOH concentration of 1.5%, extraction temperature of 90 ℃, extraction time of 4 hours, and material-to-liquid ratio of 1:20 g/mL. Under these conditions, the yield of polysaccharides from Spirulina platensis was 5.18%±0.23%. The optimal conditions for decolorization using hydrogen peroxide were found to be: 17% hydrogen peroxide solution, decolorization time of 55 minutes, and decolorization temperature of 50 ℃. Under these conditions, the actual decolorization rate was 82.54%±0.03%, and the retention rate of polysaccharides was 83.45%±0.13%. The findings of this study provide valuable insights for the development and utilization of Spirulina platensis polysaccharides.

Abstract Background The data of the prognostic role of V‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early‐stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. Methods We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan–Meier method and compared by log‐rank test. Cox proportional hazard models, propensity‐score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence‐free survival (RFS). Results The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E‐mutant patients were detected to have concurrent EGFR mutations, one for 19‐del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild‐type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). Conclusions In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.