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Abstract Background Soybean seeds are rich in protein and oil. The selection of varieties that produce high-quality seeds has been one of the priorities of soybean breeding programs. However, the influence of improved seed quality on the rhizosphere microbiota and whether the microbiota is involved in determining seed quality are still unclear. Here, we analyzed the structures of the rhizospheric bacterial communities of 100 soybean varieties, including 53 landraces and 47 modern cultivars, and evaluated the interactions between seed quality traits and rhizospheric bacteria. Results We found that rhizospheric bacterial structures differed between landraces and cultivars and that this difference was directly related to their oil content. Seven bacterial families (Sphingomonadaceae, Gemmatimonadaceae, Nocardioidaceae, Xanthobacteraceae, Chitinophagaceae, Oxalobacteraceae, and Streptomycetaceae) were obviously enriched in the rhizospheres of the high-oil cultivars. Among them, Oxalobacteraceae (Massilia) was assembled specifically by the root exudates of high-oil cultivars and was associated with the phenolic acids and flavonoids in plant phenylpropanoid biosynthetic pathways. Furthermore, we showed that Massilia affected auxin signaling or interfered with active oxygen-related metabolism. In addition, Massilia activated glycolysis pathway, thereby promoting seed oil accumulation. Conclusions These results provide a solid theoretical basis for the breeding of revolutionary soybean cultivars with desired seed quality and optimal microbiomes and the development of new cultivation strategies for increasing the oil content of seeds. Video Abstract

Abstract We present a flow-based method for simulating and calculating nucleation rates of first-order phase transitions in scalar field theory on a lattice. Motivated by recent advancements in machine learning tools, particularly normalizing flows for lattice field theory, we propose the “partitioning flow-based Markov chain Monte Carlo (PFMCMC) sampling” method to address two challenges encountered in normalizing flow applications for lattice field theory: the “mode-collapse” and “rare-event sampling” problems. Using a (2+1)-dimensional real scalar model as an example, we demonstrate the effectiveness of our PFMCMC method in modeling highly hierarchical order parameter probability distributions and simulating critical bubble configurations. These simulations are then used to facilitate the calculation of nucleation rates. We anticipate the application of this method to (3+1)-dimensional theories for studying realistic cosmological phase transitions.

Abstract Morphology of right ventricular outflow tract (RVOT) is potentially related to cardiovascular outcomes. However, this relationship still remains to be verified with direct evidence. We retrospectively reviewed cases from the autopsy specimen library in the Center of Forensic Medicine in Sun Yat-sen University from 2017 to 2023. Six RVOT morphological characteristics were measured and their association with cardiovascular diseases (CVDs), sudden cardiac death (SCD) and age at death was evaluated. Relationship between myocardial fibrosis in RVOT and CVDs was investigated. RVOT characteristics were recruited by machine learning algorithms for diagnosing CVDs. A total of 2370 cases were finally recruited. Perimeter of sub-valve plane (pSBV) in RVOT was positively associated with risk of CVDs and SCD (OR: 1.21, 95%CI: 1.07–1.37, p = 0.003; OR: 1.33, 95%CI: 1.16–1.52, p

Abstract Background Currently, several randomized controlled trials (RCTs) have been conducted to investigate the efficacy of combining immune checkpoint inhibitors (ICIs) with chemotherapy as a first-line treatment for advanced or recurrent endometrial cancer; however, the optimal treatment strategy remains undetermined. Methods A comprehensive search of online databases was conducted to identify RCTs published until December 31, 2023. Network meta-analysis was performed to evaluate PFS, OS, TRAEs, irAEs, and the ranking of different treatment regimens. Results A total of 2702 patients from five RCTs (six reports) were included in the analysis. The combination therapy of ICIs significantly prolonged PFS (HR = 0.69, 95%CI 0.63–0.76, p

Abstract As a transdermal drug delivery method, microneedles offer minimal invasiveness, painlessness, and precise in-situ treatment. However, current microneedles rely on passive diffusion, leading to uncontrollable drug penetration. To overcome this, we developed a pneumatic microneedle patch that uses live Enterobacter aerogenes as microengines to actively control drug delivery. These microbes generate gas, driving drugs into deeper tissues, with adjustable glucose concentration allowing precise control over the process. Our results showed that this microorganism-powered system increases drug delivery depth by over 200%, reaching up to 1000 μm below the skin. In a psoriasis animal model, the technology effectively delivered calcitriol into subcutaneous tissues, offering rapid symptom relief. This innovation addresses the limitations of conventional microneedles, enhancing drug efficiency, transdermal permeability, and introducing a creative paradigm for on-demand controlled drug delivery.

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

An evaluation of low damage guar gum fracturing fluid system based on deep coalbed methane reservoir stimulation was carried out, its on-site application research was conducted. The results indicate that the gel breaking time decreases with increasing temperature. Low damage guar gum fracturing fluid has a significant breaking expression in a short period of time at temperature above 40 ℃, which is not obvious at 20 ℃ and 30 ℃. The permeability of coal core is sensitive to temperature, which leads to an increase in core damage rate, but the amplitude of change is relatively small. For low damage guar gum fracturing fluid, the increase rate of temperature sensitivity of coal core to damage rate is much lower than the decrease rate of guar gum fracturing fluid damage rate to coal core with the increasing temperature from 20 ℃ to 40 ℃. Overall, the damage rate of guar gum fracturing fluid to coal core significantly decreases with the increase of temperature. For active water, the damage rate of active water to coal core increases when the temperature rises from 20 ℃ to 40 ℃. The backflow fluid viscosity reaches 5 mPa·s of guar gum fracturing in 2 hours at temperatures above 40 ℃, meeting the needs of on-site construction. By comparing the fracturing results of low damage guar gum fracturing and active water in the same well and horizontal well at the same layer, low damage guar gum fracturing fluid can achieve a fracturing process with less injection volume, larger sand volume, higher sand ratio, and smoother pressure.

The study on the evolution characteristics of coal permeability is of great significance for rationally determining gas extraction parameters and increasing gas extraction efficiency. In order to study the effects of different coal stresses and gas pressures on coal permeability, the experiment on the deformation of stress-loaded coal and gas adsorption-diffusion was conducted, the segmented dynamic model of coal permeability was established, and the rationality of the established model was verified by the experimental results. The results shown that the gas adsorption amount and coal deformation both shown a Langmuir-type with the increasing gas pressure, and the dynamic diffusion coefficient of gas decreased exponentially with time. As the gas pressure decreased, the expansion deformation of the stress-loaded coal decreased, and the permeability increased gradually. The permeability and expansion deformation of stress-loaded coal gradually decreased with the increasing stress. The coal permeability shown a “V” shape with continuous stress loading, and it reached the smallest at the stress peak. The coupling between matrix and fracture deformation caused by gas adsorption, the dynamic diffusion of gas in matrix, and the mass exchange between matrix and fracture were all considered in the established permeability model of coal. The rationality of established segmented model of coal permeability was verified by the experimental results. The permeability model of coal based on elastic deformation can reflect the permeability evolution at the stage of elastic deformation. Within the experimental range, the absolute error between the experimental test and numerical simulation results of coal permeability was −0.135×10−15～0.296×10−15 m2, and the absolute error of volumetric strain of the coal due to gas seepage was −0.327×10−5～2.026×10−5. The permeability model considering plastic deformation can also reflect the permeability after stress peak. The error between experimental and numerical results was −0.435×10−15～0.997×10−15 m2.

Objective: To investigate the potential role of the regulator of G protein signaling 20 (RGS20) in radioresistance of non-small cell lung cancer (NSCLC). Methods: A total of 35 lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA), who underwent radiotherapy, were enrolled and divided into radiosensitive (n ​= ​16) and radioresistant (n ​= ​19) groups based on clinical prognosis. The expression and prognosis of RGS20 were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistant cell line (A549R) was constructed by irradiating A549 ​cells with 6 ​Gy X-rays for 10 fractions. Cell survival was measured by colony formation assay. The regulatory effect of RGS20 on pyroptosis were verified by LDH release and Western blot assay, and the underlying mechanism was investigated by transfecting RGS20 siRNA and applying a GSDMD inhibitor). Results: A total of 2,181 differentially expressed genes (DEGs) were identified by analyzing the data of radiosensitive and radioresistant individuals from the TCGA-LUAD dataset. These DEGs were enriched in G alpha (z) signalling events analyzed by Reactome database. RGS20 exhibited significant upregulation among the DEGs, and its higher expression predicted poor prognosis in LUAD patients. In vitro, the expression of RGS20 protein was increased by irradiation in A549 ​cells, whereas it remained at much high levels in A549R cells regardless of irradiation. After irradiation, the expressions of pyroptosis-related proteins were significantly increased in A549 cells (P ＜ 0.05), with no significant changes were observed in A549R cells. Treatment with LDC7559 significantly reduced LDH release (P ＜ 0.01) and improved the survival rate of irradiated A549 cells (P ＜ 0.01). Furthermore, knockdown of RGS20 gene in A549R cells significantly increased LDH release (P ＜ 0.001) and enhanced radiosensitivity (P ＜ 0.01), while LDC7559 administration reversed LDH release (P ＜0.01) and radiation-induced cell death increased by siRGS20 (P ＜0.05). Meantime, the increased expression level of GSDMD-NT was observed in A549 and A549R cells transfected with siRGS20 (P ＜ 0.05). Conclusion: RGS20 contributes to the radioresistance of NSCLC cells, which might be a potential target for NSCLC radiotherapy.

Abstract Background Grafting with dwarf rootstock is an efficient method to control plant height in fruit production. However, the molecular mechanism remains unclear. Our previous study showed that plants with Prunus mume (mume) rootstock exhibited a considerable reduction in plant height, internode length, and number of nodes compared with Prunus persica (peach) rootstock. The present study aimed to investigate the mechanism behind the regulation of plant height by mume rootstocks through transcriptomic and metabolomic analyses with two grafting combinations, ‘Longyan/Mume’ and ‘Longyan/Peach’. Results There was a significant decrease in brassinolide levels in plants that were grafted onto mume rootstocks. Plant hormone signal transduction and brassinolide production metabolism gene expression also changed significantly. Flavonoid levels, amino acid and fatty acid metabolites, and energy metabolism in dwarf plants decreased. There was a notable upregulation of PmLBD3 gene expression in plant specimens that were subjected to grafting onto mume rootstocks. Auxin signalling cues promoted PmARF3 transcription, which directly controlled this upregulation. Through its binding to PmBAS1 and PmSAUR36a gene promoters, PmLBD3 promoted endogenous brassinolide inactivation and inhibited cell proliferation. Conclusions Auxin signalling and brassinolide levels are linked by PmLBD3. Our findings showed that PmLBD3 is a key transcription factor that regulates the balance of hormones through the auxin and brassinolide signalling pathways and causes dwarf plants in stone fruits.

Metalenses with achromatic performance offer a new opportunity for high-quality imaging with an ultra-compact configuration; however, they suffer from complex fabrication processes and low focusing efficiency. In this study, we propose an efficient design method for achromatic microlenses on a wavelength scale using materials with low dispersion, an adequately designed convex surface, and a thickness profile distribution. By taking into account the absolute chromatic aberration, relative focal length shift (FLS), and numerical aperture (NA), microlens with a certain focal length can be realized through our realized map of geometric features. Accordingly, the designed achromatic microlenses with low-dispersion fused silica were fabricated using a focused ion beam, and precise surface profiles were obtained. The fabricated microlenses exhibited a high average focusing efficiency of 65% at visible wavelengths of 410–680 nm and excellent achromatic capability via white light imaging. Moreover, the design exhibited the advantages of being polarization-insensitive and near-diffraction-limited. These results demonstrate the effectiveness of our proposed achromatic microlens design approach, which expands the prospects of miniaturized optics such as virtual and augmented reality, ultracompact microscopes, and biological endoscopy.

Abstract In the last decade, laboratory-scale single-junction perovskite solar cells have achieved a remarkable power conversion efficiency exceeding 26.1%. However, the transition to industrial-scale production has unveiled a significant efficiency gap. The central challenge lies in the difficulty of achieving uniform, high-quality perovskite films on a large scale. To tackle this issue, various innovative strategies for manipulating crystallization have emerged in recent years. Based on an in-depth fundamental understanding of the nucleation and growth mechanisms in large-area perovskite films prepared through blade/slot-die coating methods, this review offers a critical examination of crystallization manipulation strategies for large-area perovskite solar modules. Lastly, we explore future avenues aimed at enhancing the efficiency and stability of large-area PSMs, thereby steering the field toward commercially viable applications.

Bayesian Additive Regression Trees (BART) is a widely popular nonparametric regression model known for its accurate prediction capabilities. In certain situations, there is knowledge suggesting the existence of certain dominant variables. However, the BART model fails to fully utilize the knowledge. To tackle this problem, the paper introduces a modification to BART known as the Partially Fixed BART model. By fixing a portion of the trees' structure, this model enables more efficient utilization of prior knowledge, resulting in enhanced estimation accuracy. Moreover, the Partially Fixed BART model can offer more precise estimates and valuable insights for future analysis even when such prior knowledge is absent. Empirical results substantiate the enhancement of the proposed model in comparison to the original BART.

Objective(s): Neuroinflammation is considered an important step in the progression of secondary brain injury (SBI) induced by cerebral hemorrhage (ICH). The nucleotide-binding and oligomerization structural domain-like receptor family of pyridine structural domain-containing 3 (NLRP3) inflammasomes play an important role in the immune pathophysiology of SBI. Febuxostat (Feb) is a xanthine oxidase inhibitor that is approved for the treatment of gout and has been found to have potent anti-inflammatory effects. However, it has been less studied after ICH and we aimed to explore its protective role in ICH.Materials and Methods: We established an autologous blood-brain hemorrhage model in C57BL/6 mice. Functions of co-expressed genes were analyzed by trend analysis and bioinformatics analysis. Enzyme-linked immunosorbent assay were used to assess the inflammatory factor levels. Fluoro-Jade B histochemistry and TUNEL staining were used to detect neuronal apoptosis. Immunofluorescence staining and western blotting were used to detect the expression of NLRP3 inflammasomes.Results: Pretreatment with Feb reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders in vivo. Feb was found to modulate inflammation-related pathways by trend analysis and bioinformatics analysis. In addition, Feb inhibited microglia activation and elevated cytokine levels after ICH. Furthermore, double immunofluorescence staining showed that co-localization of NLRP3 with Iba1 positive cells was reduced after treatment with Feb. Finally, we found that Feb inhibited the activation of the NLRP3/ASC/caspase-1 pathway after ICH. Conclusion: By inhibiting the NLRP3 inflammasome, preconditioning Feb attenuates inflammatory injury after ICH. Our findings may provide new insights into the role of Feb in neuroprotection.

Abstract Background Aberrant Derlin-1 (DERL1) expression is associated with an overactivation of p-AKT, whose involvement in breast cancer (BRCA) development has been widely speculated. However, the precise mechanism that links DERL1 expression and AKT activation is less well-studied. Methods Bioinformatic analyses hold a promising approach by which to detect genes’ expression levels and their association with disease prognoses in patients. In the present work, a dual-luciferase assay was employed to investigate the relationship between DERL1 expression and the candidate miRNA by both in vitro and in vivo methods. Further in-depth studies involving immunoprecipitation-mass spectrum (IP-MS), co-immunoprecipitation (Co-IP), as well as Zdock prediction were performed. Results Overexpression of DERL1 was detected in all phenotypes of BRCA, and its knockdown showed an inhibitory effect on BRCA cells both in vitro and in vivo. The Cancer Genome Atlas (TCGA) database reported that DERL1 overexpression was correlated with poor overall survival in BRCA cases, and so the quantification of DERL1 expression could be a potential marker for the clinical diagnosis of BRCA. On the other hand, miR-181c-5p was downregulated in BRCA, suggesting that its overexpression could be a potent therapeutic route to improve the overall survival of BRCA cases. Prior bioinformatic analyses indicated a somewhat positive correlation between DERL1 and TRAF6 as well as between TRAF6 and AKT, but not between miR-181c-5p and DERL1. In retrospect, DERL1 overexpression promoted p-AKT activation through K63 ubiquitination. DERL1 was believed to directly interact with the E3 ligase TRAF6. As Tyr77Ala or Tyr77Ala/Gln81Ala/Arg85Ala/Val158Ala attempts to prevent the interaction between DERL1 and TRAF domain of TRAF6, resulted in a significant reduction in K63-ubiquitinated p-AKT production. However, mutations in Gln81Ala, Arg85Ala, or Val158Ala could possibly interrupt with these processes. Conclusions Our data confirm that mediation of the miR-181c-5p/DERL1 pathway by TRAF6-linked AKT K63 ubiquitination holds one of the clues to set our focus on toward meeting the therapeutic goals of BRCA.

Abstract Objective To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. Methods Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. Results Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. Conclusion It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

IntroductionThe surgery of clival chordoma remains one of the most formidable challenges for neurosurgeons because of its location at great depth in the cranium and proximity to critical neurovascular structures. Here, we describe the technique and feasibility of the purely endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) for resection of an intradural clival chordoma.Case descriptionA 68-year-old women presented with sudden ptosis on the left side for two weeks. Imaging examinations revealed an upper-middle clival lesion that transgressed dural confines towards the posterior fossa, which was separated from the sphenoid cavity by an intact thin layer of membrane structure in front. For surgery, the EF-SCITA approach via suboccipital craniotomy was attempted for protecting surrounding neurovascular tissue and the membrane barrier under direct vision. The patients were placed in a “head-up” lateral park-bench position. With the endoscopic holder, endoscopic procedures were performed using standard two-hand microsurgical techniques by one surgeon. Tentorium incision allowed a working corridor toward the clival bulge through the crural cistern, without brain traction seen in traditional retrosigmoid approach. Efficient tumor debulking facilitated the exposure of surrounding critical structures, including ipsilateral CN III and superior cerebellar artery above, the brainstem and basilar artery posteriorly, as well as ipsilateral CN VI displaced laterally, and subsequent tumor separation from them. Step-wise tumor resection was performed within dural and bone confines. After significant tumor removal, the pituitary stalk could be visualized anteriorly, together with contralateral internal carotid artery and CN III. Postoperative MRI depicted gross total excision of the lesion. The patient on follow-up at one year had complete recovery of cranial nerve functions, without signs of cerebrospinal fluid rhinorrhea.DiscussionThis technique combines advantages of the posterolateral approach and endoscopy, allowing access to the upper-middle clivus with seemingly low risks of postoperative morbidity. It would be a safe and effective alternative for resection of this rare entity.

The non-coding RNAs (ncRNAs) comprise a large part of human genome that mainly do not code for proteins. Although ncRNAs were first believed to be non-functional, the more investigations highlighted tthe possibility of ncRNAs in controlling vital biological processes. The length of long non-coding RNAs (lncRNAs) exceeds 200 nucleotidesand can be present in nucleus and cytoplasm. LncRNAs do not translate to proteins and they have been implicated in the regulation of tumorigenesis. On the other hand, One way cells die is by a process called autophagy, which breaks down proteins and other components in the cytoplasm., while the aberrant activation of autophagy allegedly involved in the pathogenesis of diseases. The autophagy exerts anti-cancer activity in pre-cancerous lesions, while it has oncogenic function in advanced stages of cancers. The current overview focuses on the connection between lncRNAs and autophagy in urological cancers is discussed. Notably, one possible role for lncRNAs is as diagnostic and prognostic variablesin urological cancers. The proliferation, metastasis, apoptosis and therapy response in prostate, bladder and renal cancers are regulated by lncRNAs. The changes in autophagy levels can also influence the apoptosis, proliferation and therapy response in urological tumors. Since lncRNAs have modulatory functions, they can affect autophagy mechanism to determine progression of urological cancers.

BackgroundThe prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC.MethodThis study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis.ResultsAmong the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways.ConclusionsThis bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC.

BackgroundRecent research has found a new way of cell death: disulfidptosis. Under glucose starvation, abnormal accumulation of disulfide molecules such as Cystine in Solute Carrier Family 7 Member 11 (SLC7A11) overexpression cells induced disulfide stress to trigger cell death. The research on disulfidptosis is still in its early stages, and its role in the occurrence and development of colorectal malignancies is still unclear.MethodIn this study, we employed bioinformatics methods to analyze the expression and mutation characteristics of disulfidptosis-related genes (DRGs) in colorectal cancer. Consensus clustering analysis was used to identify molecular subtypes of Colorectal Adenocarcinoma (COAD) associated with disulfidptosis. The biological behaviors between subtypes were analyzed to explore the impact of disulfidptosis on the tumor microenvironment. Constructing and validating a prognostic risk model for COAD using diverse data. The influence of key genes on prognosis was evaluated through SHapley Additive exPlanations (SHAP) analysis, and the predictive capability of the model was assessed using Overall Survival analysis, Area Under Curve and risk curves. The immunological status of different patients and the prediction of drug treatment response were determined through immune cell infiltration, TMB, MSI status, and drug sensitivity analysis. Single-cell analysis was employed to explore the expression of genes at the cellular level, and finally validated the expression of key genes in clinical samples.ResultBy integrating the public data from two platforms, we identified 2 colorectal cancer subtypes related to DRGs. Ultimately, we established a prognosis risk model for COAD using 7 genes (FABA4+GIPC2+EGR3+HOXC6+CCL11+CXCL10+ITLN1). SHAP analysis can further explained the positive or negative impact of gene expression on prognosis. By dividing patients into high-risk and low-risk groups, we found that patients in the high-risk group had poorer prognosis, higher TMB, and a higher proportion of MSI-H and MSI-L statuses. We also predicted that drugs such as 5-Fluorouracil, Oxaliplatin, Gefitinib, and Sorafenib would be more effective in low-risk patients, while drugs like Luminesib and Staurosporine would be more effective in high-risk patients. Single-cell analysis revealed that these 7 genes not only differ at the level of immune cells but also in epithelial cells, fibroblasts, and myofibroblasts, among other cell types. Finally, the expression of these key genes was verified in clinical samples, with consistent results.ConclusionsOur research findings provide evidence for the role of disulfidptosis in COAD and offer new insights for personalized and precise treatment of COAD.

IntroductionOsteosarcoma is a common type of bone cancer characterized by a poor prognosis due to its metastatic nature. The tumor microenvironment (TME) plays a critical role in tumor metastasis and therapy response. Therefore, our study aims to explore the metastatic mechanism of osteosarcoma, potentially opening new avenues for cancer treatment.MethodsIn this study, we collected data from the GSE152048, GSE14359, and GSE49003 datasets. Differentially expressed genes (DEGs) were identified in osteosarcoma cases with primary and metastatic features using R software and the limma package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate metastasis-related genes. A protein–protein interaction (PPI) network was established using the STRING database to further analyze these metastasis-associated genes. The abundances of different cell types with a mixed cell population were estimated using the CIBERSORT approach. The scRNA-seq data were analyzed by the Seurat package in R software, and intercellular communications were elucidated using the CellChat R package.ResultsIn this study, 92 DEGs related to metastasis were identified, including 41 upregulated and 51 downregulated genes in both the GSE14359 and GSE49003 datasets. Metastasis-associated pathways were identified, including those involving the cyclin-dependent protein kinase holoenzyme complex, transferase complex, transferring phosphorus-containing groups, SCF ubiquitin ligase complex, and the serine/threonine protein kinase complex. KEGG and PPI network analyses revealed 15 hub genes, including Skp2, KIF20A, CCNF, TROAP, PHB, CKS1B, MCM3, CCNA2, TRIP13, CENPM, Hsp90AB1, JUN, CKS2, TK1, and KIF4A. Skp2 has been known as an E3 ubiquitin ligase involved in osteosarcoma progression. The proportion of CD8+ T cells was found to be higher in metastatic osteosarcoma tissues, and high expression of PHB was associated with a favorable prognosis in osteosarcoma patients. Additionally, 23 cell clusters were classified into eight cell types, including chondrocytes, MSC, T cells, monocytes, tissue stem cells, neurons, endothelial cells, and macrophages. The 15 hub genes were expressed across various cell types, and interactions between different cell types were observed.ConclusionOur study reveals the intricate communication between tumor microenvironment components and tumor metastasis in osteosarcoma.

Improving efficiency and reducing emissions are essential to achieve carbon neutrality in transportation sector. The hydrogen-fueled argon power cycle (H2-APC) is a novel power system with high efficiency and zero emission by utilizing argon-oxygen mixture as working fluids. However, knock suppression is a problem within H2-APC engines. Direct water injection (DWI) is an effective method to inhibit detonation. Spray morphology greatly influences the effectiveness of DWI, the investigation of spray characteristics in oxygen/argon atmosphere is critical. This paper established a computational model based on experimental data to investigate DWI characteristics under different injection and ambient conditions within oxygen/argon atmosphere. The results reveal increased jet temperature leads to stronger superheated jet spray collapse, while Sauter mean diameter (SMD) decreases and atomization improves. Increasing jet pressure effectively reduces spray SMD and improves atomization effect and evaporation rate. Higher ambient temperature reduces ambient gas density, spray SMD and penetration are decreased and increased, respectively. Moreover, spray evaporation rate and evaporated mass are dropped with higher ambient pressure for both superheated and subcooled sprays. As ambient density rises, the capacity for jet perturbation and fragmentation is enhanced, and spray SMD decreases. The research results can provide an effective guide for the DWI strategy of H2-APC engines.

Fluoride exposure is widespread worldwide and poses a significant threat to organisms, particularly to their gastrointestinal tracts. However, due to limited knowledge of the mechanism of fluoride induced intestinal injury, it has been challenging to develop an effective treatment. To address this issue, we used a series of molecular biology in vitro and in vivo experiments. NaF triggered m6A mediated ferroptosis to cause intestinal damage. Mechanistically, NaF exposure increased the m6A level of SLC7A11 mRNA, promoted YTHDF2 binding to m6A-modified SLC7A11 mRNA, drove the degradation of SLC7A11 mRNA, and led to a decrease in its protein expression, which eventually triggers ferroptosis. Moreover, NaF aggravated ferroptosis of the colon after antibiotics destroyed the composition of gut microbiota. 16 S rRNA sequencing and SPEC-OCCU plots, Zi-Pi relationships, and Spearman correlation coefficients verified that Lactobacillus murinus (ASV54, ASV58, and ASV82) plays a key role in the response to NaF-induced ferroptosis. Collectively, NaF-induced gut microbiota alteration mediates severe intestinal cell injury by inducing m6A modification-mediated ferroptosis. Our results highlight a key mechanism of the gut in response to NaF exposure and suggest a valuable theoretical basis for its prevention and treatment.

Mounting evidence suggests that insect hormones associated with growth and development also participate in pathogen defense. We have discovered a previously undescribed midgut transcriptional control pathway that modulates the availability of 20-hydroxyecdysone (20E) in a worldwide insect pest (Plutella xylostella), allowing it to defeat the major virulence factor of an insect pathogen Bacillus thuringiensis (Bt). A reduction of the transcriptional inhibitor (PxDfd) increases the expression of a midgut microRNA (miR-8545), which in turn represses the expression of a newly identified ecdysteroid-degrading glucose dehydrogenase (PxGLD). Downregulation of PxGLD reduces 20E degradation to increase 20E titer and concurrently triggers a transcriptional negative feedback loop to mitigate 20E overproduction. The moderately elevated 20E titer in the midgut activates a MAPK signaling pathway to increase Bt tolerance/resistance. These findings deepen our understanding of the functions attributed to these classical insect hormones and help inform potential future strategies that can be employed to control insect pests.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear. We investigated the role of SOX9 in TGF-β1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast (RTF) cells. SOX9 overexpression adenovirus (Ad-SOX9) and siRNA were transfected into RTF cells. We found that SOX9 expression was up-regulated in RTF cells treated with TGF-β1. SOX9 overexpression activated fibroblasts and promoted ECM deposition. Silencing SOX9 inhibited cell proliferation, migration, and ECM deposition, induced G2 arrest, and increased apoptosis in RTF cells. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) assays identified MMP10, a matrix metalloproteinase involved in ECM deposition, as a direct target of SOX9, which promotes ECM degradation by increasing MMP10 expression through the Wnt/β-catenin signaling pathway. Furthermore, in vivo, SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis, as manifested by reduced tracheal stenosis. In conclusion, our findings indicate that SOX9 can drive fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/β-catenin signaling pathway. The SOX9–MMP10–ECM biosynthesis axis plays an important role in tracheal injury and repair. Targeting SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

Abstract Axion-like particles are predicted in many physics scenarios beyond the Standard Model (SM). Their interactions with SM particles may arise from the triangle anomaly of the associated global symmetry, along with other SM global and gauge symmetries, including anomalies with the global baryon number and electromagnetic gauge symmetries. We initiate the phenomenological study of the corresponding “electrobaryonic axion”—a particle that couples with both the baryon chemical potential and the electromagnetic field. Neutron stars, particularly magnetars, possessing high baryon density and strong magnetic fields, can naturally develop a thin axion hair around their surface. In this study, we calculate this phenomenon, considering the effects of neutron star rotation and general relativity. For axion particles lighter than the neutron star rotation frequency, the anomalous interaction can also induce the emission of axion particles from the neutron star. In the light axion regime, this emission can significantly contribute to the neutron star cooling rate.

Abstract Background Bacterial nanocellulose (BNC), a natural polymer material, gained significant popularity among researchers and industry. It has great potential in areas, such as textile manufacturing, fiber-based paper, and packaging products, food industry, biomedical materials, and advanced functional bionanocomposites. The main current fermentation methods for BNC involved static culture, as the agitated culture methods had lower raw material conversion rates and resulted in non-uniform product formation. Currently, studies have shown that the production of BNC can be enhanced by incorporating specific additives into the culture medium. These additives included organic acids or polysaccharides. γ-Polyglutamic acid (γ-PGA), known for its high polymerization, excellent biodegradability, and environmental friendliness, has found extensive application in various industries including daily chemicals, medicine, food, and agriculture. Results In this particular study, 0.15 g/L of γ-PGA was incorporated as a medium additive to cultivate BNC under agitated culture conditions of 120 rpm and 30 ℃. The BNC production increased remarkably by 209% in the medium with 0.15 g/L γ-PGA and initial pH of 5.0 compared to that in the standard medium, and BNC production increased by 7.3% in the medium with 0.06 g/L γ-PGA. The addition of γ-PGA as a medium additive resulted in significant improvements in BNC production. Similarly, at initial pH levels of 4.0 and 6.0, the BNC production also increased by 39.3% and 102.3%, respectively. To assess the characteristics of the BNC products, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis were used. The average diameter of BNC fibers, which was prepared from the medium adding 0.15 g/L γ-PGA, was twice thicker than that of BNC fibers prepared from the control culture medium. That might be because that polyglutamic acid relieved the BNC synthesis from the shear stress from the agitation. Conclusions This experiment held great significance as it explored the use of a novel medium additive, γ-PGA, to improve the production and the glucose conversion rate in BNC fermentation. And the BNC fibers became thicker, with better thermal stability, higher crystallinity, and higher degree of polymerization (DPv). These findings lay a solid foundation for future large-scale fermentation production of BNC using bioreactors.

The sudden onset of the coronavirus disease 2019 (COVID-19) in January 2020 has affected essential global health services. Cancer-screening services that can reduce cancer mortality are strongly affected. However, the specific role of COVID-19 in cancer screening is not fully understood. This study aimed to assess the efficiency of global cancer screening programs before and during the COVID-19 pandemic and to promote potential cancer-screening strategies for the next pandemic. Electronic searches in PubMed, Embase, and Web of Science, and manual searches were performed between January 1, 2020 and March 1, 2023. Cohort studies that reported the number of participants who underwent cancer screening before and during the COVID-19 pandemic were included. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Differences in cancer-screening rates were estimated using the incidence rate ratio (IRR). Fifty-five cohort studies were included in this meta-analysis. The screening rates of colorectal cancer using invasive screening methods (Pooled IRR = 0.52, 95% CI: 0.42 to 0.65, p < 0.01), cervical cancer (Pooled IRR = 0.56, 95% CI: 0.47 to 0.67, p < 0.01), breast cancer (Pooled IRR = 0.57, 95% CI: 0.49 to 0.66, p < 0.01) and prostate cancer (Pooled IRR = 0.71, 95% CI: 0.56 to 0.90, p < 0.01) during the COVID-19 pandemic were significantly lower than those before the COVID-19 pandemic. The screening rates of lung cancer (Pooled IRR = 0.77, 95% CI: 0.58 to 1.03, p = 0.08) and colorectal cancer using noninvasive screening methods (Pooled IRR = 0.74, 95% CI: 0.50 to 1.09, p = 0.13) were reduced with no statistical differences. The subgroup analyses revealed that the reduction in cancer-screening rates varied across economies. Our results suggest that the COVID-19 pandemic has had a noteworthy impact on colorectal, cervical, breast, and prostate cancer screening. Developing innovative cancer-screening technologies is important to promote the efficiency of cancer-screening services in the post-COVID-19 era and prepare for the next pandemic.

Background: The complexity of the neurophysiological mechanisms underlying human consciousness is widely acknowledged, with information processing and flow originating in cortex conceived as a core mechanism of consciousness emergence. Combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is considered as a promising technique to understand the effective information flow associated with consciousness. Objectives: To investigate information flow with TMS-EEG and its relationship to different consciousness states. Methods: We applied an effective information flow analysis by combining time-varying multivariate adaptive autoregressive model and adaptive directed transfer function on TMS-EEG data of frontal, motor and parietal cortex in patients with disorder of consciousness (DOC), including 14 vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients, 21 minimally conscious state (MCS) patients, and 22 healthy subjects. Results: TMS in DOC patients, particularly VS/UWS, induced a significantly weaker effective information flow compared to healthy subjects. The bidirectional directed information flow was lost in DOC patients with TMS of frontal, motor and parietal cortex. The interactive ROI rate of the information flow network induced by TMS of frontal and parietal cortex was significantly lower in VS/UWS than in MCS. The interactive ROI rate correlated with DOC clinical scales. Conclusions: TMS-EEG revealed a physiologically relevant correlation between TMS-induced information flow and levels of consciousness. This suggests that breakdown of effective cortical information flow serves as a viable marker of human consciousness. Significance: Findings offer a unique perspective on the relevance of information flow in DOC, thus providing a novel way of understanding the physiological basis of human consciousness.

Zero-inflated count outcomes are common in many studies, such as counting claim frequency in the insurance industry in which identifying and understanding excessive zeros are of interest. Moreover, with the progress of data collecting and storage techniques, the amount of data is too massive to be stored or processed by a single node or branch. Hence, to develop distributed data analysis is blossoming. In this paper, several communication-efficient distributed zero-inflated Poisson regression algorithms are developed to analyse such kind of large-scale zero-inflated data. Both asymptotic properties of the proposed estimators and algorithm complexities are well studied and conducted. Various simulation studies demonstrate that our proposed method and algorithm work well and efficiently. Finally, in the case study, we apply our proposed algorithms to car insurance data from Kaggle.

Abstract Background and objectives Aging poses a significant challenge worldwide, with China’s aging status becoming particularly severe. What is the impact of Internet use on the health of the elderly? Existing studies have drawn conflicting conclusions that Internet use improves or harms health. The purpose of this study was to explore how Internet use affects the health of older adults, and the mechanisms and heterogeneity of these effects. Research design and methods Based on Grossman’s theory, this paper constructs a health production function model. Using the data of China Family Panel Studies (CFPS) from 2014 to 2020, we investigated the impact of Internet use on the health of older adults using fixed effect model and instrumental variable method. We also examined the mediating role of health information acquisition, lifestyle, and social interaction in these associations. Results Internet use is positively associated with self-rated health and negatively associated with psychological sub-health level. Internet use promotes the health of older adults by facilitating access to health information, healthy lifestyles, and enhancing social interaction. And the impacts are heterogeneous at the individual and regional levels. Discussion and implications We should progressively enhance the level of internet accessibility for older adults, while concurrently addressing and narrowing the ‘digital divide’. By generating an abundance of superior health-related information, we can significantly improve health education tailored for the elderly. Additionally, it is crucial to offer extensive training opportunities designed to equip older adults with the necessary skills to proficiently navigate the internet.

As an important negative carbon technology to solve the carbon emission problem in the coal industry, the CO2 sequestration in the mine goaf has a wide application prospect in the secondary utilization of waste resources in the goaf and the capture and storage of CO2. In this study, the influence of different temperatures and pressures, formation water salinity and cationic solution type on the interfacial tension (IFT) of CO2-formation water system was investigated by using in-situ interfacial tension meter. The gas-liquid interface diffusion effect of CO2 injection into water-bearing coal rock mass was clarified. The equation of state (SAFT-LJ equation of state) based on statistical association theory combined with the Lanner-Jones potential energy model and density gradient theory (DGT) were combined to predict the theoretical value of IFT. Using a self-developed geological sequestration and geochemical reaction simulation experimental platform, various exploratory experiments were conducted to investigate the solubility of CO2 under the same conditions. The characteristics of CO2 solubility variation in the reservoir environment of the goaf were obtained, and the corresponding theoretical values of CO2 solubility were calculated using the D-S model. The experimental results show that when the ambient temperature is constant, the reservoir pressure in the goaf is linearly negatively correlated with the IFT value. As the reservoir temperature increases, the IFT value increases correspondingly, but the change range is small. Under constant temperature and pressure conditions, there is a positive correlation between salinity and IFT value. Within the scope of this experiment, low pressure, high temperature, and high salinity promote an increase in the IFT value. The IFT values between CO2-salt solutions show an increasing trend with the increasing valence of cations (K+ < Na+ < Ca2+ < Mg2+). The pressure of the depleted reservoir is positively correlated with the CO2 solubility. When the temperature is 25 °C and under conditions of pure water, as the pressure increases from 0.5 MPa to 2.5 MPa, the corresponding CO2 solubility increases from 0.1627 mol/kg to 0.7141 mol/kg. The CO2 solubility decreases with the increases of temperature and salinity. Under the same concentration, monovalent cation solutions (NaCl, KCl) can dissolve more CO2 than divalent cation solutions (CaCl2, MgCl2). The free phase CO2 injected into the goaf overcomes the interfacial tension and breaks the geochemical balance of the goaf strata through diffusion and dissolution mass transfer. By clarifying the influence of reservoir temperature and pressure conditions and goaf water environment on IFT value and CO2 solubility, the gas-liquid interface effect and dissolution mass transfer mechanism of CO2-formation water are clarified, so as to provide a theoretical basis for the safety and evaluation of CO2 sequestration in the closed mine goaf.

Abstract This study investigates the Tip Clearance Cavitation (TCC) characteristics of three different Tip Clearances (TC) (0.4, 0.6, 0.8) and five inlet negative pressure conditions Pj = (− 20–60)kPa to improve the reliability of the aerospace high-speed centrifugal pump during in-orbit operation, based on the premise of good agreement between the TC 0.6 test curve and the simulation performance curve. Under negative pressure and high-speed conditions, the variation gradient of cavitation characteristics with various inlet negative pressures is non-linear and has a sudden change, but the trend becomes stable after the inlet negative pressure drops to a certain stage. The tip clearance cavitation characteristics vary from the blade surface cavitation characteristics due to the difference in forces on both sides. This study is a proper starting point for the design of aerospace power pumps.

Objective: To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma (OSCC) cells. Methods: The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma (HNSC) patients was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistance cell line (CAL-27R) was constructed by irradiating CAL-27 ​cells with fractional doses. Cell survival was measured by colony formation assay. Cell migration and invasion were detected by transwell assay. The formation of γH2AX foci was detected by immunofluorescence assay. The protein expressions were detected by Western blot assay. In some experiments, CAL-27R cells were effectively transferred with siRNA YWHAZ (siYWHAZ). Results: GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues, and the HNSC patients with higher level of YWHAZ had a shorter survival. In vitro experiments demonstrated that the expression of YWHAZ protein in CAL-27 ​cells was lower than HSC-3 ​cells (t ​= ​18.89, P ​

Abstract Background Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. Methods The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC–MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. Results The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. Conclusion We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Abstract Mutations in the Contactin-associated protein-like 2 (CNTNAP2) gene are associated with autism spectrum disorder (ASD), and ectodomain shedding of the CNTNAP2 protein plays a role in its function. However, key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown, and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive. In this report we showed that CNTNAP2 undergoes sequential cleavages by furin, ADAM10/17-dependent α-secretase and presenilin-dependent γ-secretase. We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96, and the main α-cleavage product C79 by ADAM10 is required for the subsequent γ-secretase cleavage to generate CNTNAP2 intracellular domain (CICD). ASD-associated CNTNAP2 mutations impair the α-cleavage to generate C79, and the inhibition leads to ASD-like repetitive and social behavior abnormalities in the Cntnap2 -I1254T knock-in mice. Finally, exogenous expression of C79 improves autism-like phenotypes in the Cntnap2 -I1254T knock-in and Cntnap2 −/− knockout mice. This data demonstrates that the α-secretase is essential for CNTNAP2 processing and its function. Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis, and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

Objectives: Infection by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious clinical problem worldwide. However, the molecular epidemiology of the clinical isolates varies depending on the region. This study was conducted to analyse the resistance phenotype and clarify the genetic and epidemiological properties of CRPA clinical isolates from southeast Shanxi, China. Methods: Fifty-seven isolates of CRPA were collected from a hospital in this region. These isolates were reidentified by MALDI-TOF and subjected to whole-genome sequencing by next-generation sequencing. Phylogenetic trees were constructed based on single nucleotide polymorphisms (SNPs), after which multilocus sequence typing (MLST) was performed and antimicrobial resistance genes were identified. Results: All the 57 CRPA isolates carried at least one kind of gene encoding carbapenemase, such as blaIMP-1, blaIMP-10, blaOXA-10, blaOXA-395, blaOXA-396, blaOXA-485, blaOXA-486, blaOXA-488, blaOXA-494, and blaOXA-50. The isolates harboured AIM-1, CMY-51, mecD, and NmcR genes and carried one kind of Pseudomonas-derived cephalosporinase (PDC) β-lactamase-encoding gene, such as blaPCD-1 to blaPCD-3, blaPCD-5, or blaPCD-7 to blaPCD-10. Two isolates were found to harbour the aminoglycoside-modifying enzyme genes aadA1 and aadA7; however, no isolates were found to harbour genes encoding 16S rRNA methylase or quinolone resistance-related genes. These CRPA isolates belonged to various sequence types (STs), two of which, namely, ST235 and ST277, were high-risk types. Conclusions: Our findings indicate that CRPA isolates carrying resistance genes with unique regional characteristics are spreading in this region, with a high diversity of STs, especially in high-risk clones. These findings highlight the necessity for further measures to prevent CRPA spread in Shanxi.

ABSTRACTThe widespread prevalence of Helicobacter pylori infection, particularly in China, contributes to the development of gastrointestinal diseases. Antibiotics have limitations, including adverse reactions and increased antibiotic resistance. Therefore, identification of novel gastrogenic probiotics capable of surviving the acidic gastric environment and effectively combating H. pylori infection has potential in restoring gastric microbiota homeostasis. Five novel strains of human gastrogenic Weizmannia coagulans (BCF-01–05) were isolated from healthy gastric mucosa and characterized using 16S rDNA identification. Acid resistance, H. pylori inhibition, and adherence to gastric epithelial cells were evaluated in in-vitro experiments and the molecular mechanism explored in in-vivo experiments. Among the gastric-derived W. coagulans strains, BCF-01 exhibited the strongest adhesion and H. pylori inhibition, warranting further in-vivo safety evaluation. Through 16S rRNA sequencing of a mouse model, BCF-01 was determined to significantly restore H. pylori-associated gastric dysbiosis and increase the abundance of potential probiotic bacteria. Furthermore, BCF-01 enhanced mucosal tight junction protein expression and inhibited the TLR4-NFκB-pyroptosis signaling pathway in macrophages, as demonstrated by qRT-PCR and western blotting.These findings highlight the potential of BCF-01 in the prevention and control of H. pylori infection. Specifically, treatment with BCF-01 effectively restored gastric microecology and improved H. pylori-mediated mucosal barrier destruction while reducing inflammation through inhibition of the TLR4-NFκB-pyroptosis signaling pathway in macrophages. BCF-01 is a promising alternative to traditional triple therapy for H. pylori infections, offering minimal side effects with high suitability for high-risk individuals.

Distant metastasis is the major cause of death in patients with breast cancer. Epithelial–mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulates metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and MIR539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

The key challenge created by global climate change is to implement effective carbon–neutral programs. The carbon sequestration service (CSS) establishes spatial and temporal connections between carbon sequestration supply and demand, so accurate scientific quantification of the CSS supply–demand balance is essential. However, a standard assessment framework for quantifying CSS supply–demand is currently lacking. In this study, we developed a spatio-temporal assessment framework for quantifying CSS supply–demand balance under land use change, based on the SPANs model. We followed the flow of CSS from supply to demand areas through spatial visualization based on the main wind direction and defined the transport path and quantity of CSS flow, taking Lancang Mekong River Basin (LMRB) as a case. The results showed that: (1) The total supply of CSS decreased by 1.14 million tons from 2000 to 2020, and total demand for CSS increased by 8.1 million tons. (2) CSS surplus areas were mainly concentrated in forested regions, with a maximum surplus of 4.31 t/ha. Deficit areas were dominated by cultivated land and artificial surfaces, with a maximum deficit of −1101.21 t/ha. There was spatial heterogeneity in CSS distribution and a clear imbalance between supply and demand. (3) Three out of six countries in the basin showed significant changes in CSS flow, with a decrease in demand area observed in Thailand and an increase in demand area observed in Cambodia and Vietnam. (4) CSS flow was mainly from north to south, with higher CSS in Thailand and lower flow in China. Thus the analysis revealed supply–demand imbalances in CSS and provided an objective understanding of the spatial flow of CSS. This scientific and intuitive theoretical basis and data support can be used for regional carbon management in LMRB and global carbon balance control.

This study explores the impact of government subsidies on the production dynamics within the medical product supply chain, particularly focusing on the remanufacturing of medical goods. Amidst the backdrop of the COVID-19 pandemic, which has underscored the critical shortages in medical supplies, our research delves into the adoption of remanufacturing practices by medical product manufacturers as a strategic response to these shortages and environmental concerns. We investigate how government subsidies influence the production volumes of original manufacturers and remanufacturers and examine the competitive interplay between newly manufactured and remanufactured medical products. Through the development of three production game models—Scenario B (manufacturers produce both new and refurbished products), Scenario N (separate production of new and refurbished products by manufacturers and remanufacturers, respectively), and Scenario C (similar to Scenario N but includes a certification fee paid by remanufacturers to original manufacturers)—we analyze the strategies that could mitigate supply deficiencies during medical crises. Our findings indicate that the certification strategy (Scenario C) not only yields the highest total production of medical products but also offers a viable solution to enhance the sustainability of the entire medical production system by alleviating supply chain disruptions. Furthermore, we discuss the managerial implications of our results, emphasizing the potential of a joint remanufacturing strategy to stabilize the supply chain and foster environmental conservation. Lastly, we highlight our study's limitations and suggest future research directions, particularly concerning the variability in product quality and the reliance on government subsidies. This research contributes to a nuanced understanding of green remanufacturing within the pharmaceutical supply chain, offering insights for manufacturers, remanufacturers, and policymakers aiming for sustainable industry practices.

Rapid transit is important for the green development of China’s tourism industry because it profoundly affects the optimal structural layout and rational allocation of elements that impact regional tourism. Based on provincial panel data from 2009 to 2020, the entropy weight method, tourism carbon emission measurement model, Super efficiency slacks-based measure model and threshold regression model were used to determine the impact of the rapid transit system on tourism eco-efficiency in China. The findings showed that rapid transit system has increased steadily, while tourism eco-efficiency has fluctuated significantly, and the relative development characteristics of rapid transit system and tourism eco-efficiency gradually changed from “lagging rapid transit system” to “lagging tourism eco-efficiency.” In addition, the rapid transit system and the highway and civil aviation have a nonlinear relationship with tourism eco-efficiency, while the high-speed railway has not passed the threshold effect test, and at the regional level, the impacts of rapid transit system have heterogeneous characteristics. As the deepening construction of rapid transit system, its threshold effect on tourism eco-efficiency will change from positive “V” to positive “U” type, promoting the more efficient development of environmentally friendly tourism.

Unreinforced masonry (URM) structure consisting of bricks and mortar suffers severe damage under impact loading, owing to its poor ductility and brittle failure modes. However, natural nacre with a similar structure to that of masonry exhibits superior mechanical properties through the well-designed assembly process. Therefore, a nacre-inspired design method, which hierarchically assembled bricks and engineered cementitious composites (ECC) into novel masonry walls at the macro-scale, was proposed in present study. The variations of the bionic measurements were experimentally explored. Test results demonstrated that the ductility and toughness of the novel masonry structure were dramatically improved by replacing mortar with ECC as horizontal joint and setting artificial local separations. The energy absorption of masonry wall and masonry beam were improved 5.66 times and 8.05 times, respectively. A theoretical frame model for hierarchically-assembled masonry was established, which considered the randomness of masonry and simulated the crack propagation. Finally, a numerical verification was conducted based on the frame model. This study lays the groundwork for applying the nacre-inspired design method in masonry structure to improve its shear properties in terms of ductility and toughness.