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Acute rejection (AR) remains a major challenge in liver transplantation (LT) despite advances in immunosuppression. High-mobility group box 1 (HMGB1) has emerged as a critical driver of immune activation; however, its role in dendritic cell (DC)-mediated T helper 17 (Th17)/regulatory T cell (Treg) imbalance during AR is unclear. Orthotopic LT was performed in rats assigned to sham, isograft, and allograft groups. Liver injury, HMGB1 expression, and hepatic DC infiltration were assessed by histopathology, immunohistochemistry, and CD11c immunofluorescence staining (IF), respectively, while serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were measured to evaluate graft function. Th17/Treg populations were analyzed by flow cytometry to assess immune imbalance. RNA sequencing (RNA-seq) was conducted to explore transcriptional changes in bone marrow-derived DCs stimulated with HMGB1 or PBS. DC maturation, cytokine secretion (ELISA), antigen uptake, and metabolic activity (CCK-8 assay) were assessed. A DC-CD4 T cell coculture system was used to evaluate the ability of DCs to drive T cell proliferation and polarization. NF-κB signaling activation was examined by western blot (WB) and IF, and the NF-κB inhibitor helenalin was used to assess pathway relevance. Allograft recipients displayed elevated serum ALT/AST/TBIL, accompanied by aggravated liver injury, increased rejection activity index (RAI) scores, and upregulated HMGB1 expression. While CD11c IF demonstrated a pronounced increase in hepatic DC infiltration. Th17 cell frequencies and the Th17/Treg ratio were markedly increased, while Treg proportions were reduced. RNA-seq of DCs revealed HMGB1-induced transcriptional reprogramming with nominal enrichment of NF-κB signaling, which was further confirmed by WB and IF. HMGB1 stimulation promoted DC maturation, enhanced pro-inflammatory cytokine production, and impaired antigen uptake and metabolic function. These activated DCs further facilitated CD4 T cell proliferation and skewed differentiation toward the Th17 lineage while suppressing Treg induction. Notably, helenalin treatment effectively attenuated DC activation, restored their antigen uptake and metabolic activity, and reversed the Th17/Treg imbalance mediated by HMGB1-activated DCs. HMGB1 drives DC-mediated Th17/Treg imbalance during LT rejection through NF-κB activation. Targeting this pathway may offer a novel immunomodulatory strategy for managing AR.

Previous studies have examined the supply of housing support and the economic impact of job-housing separation. However, they have paid inadequate attention to the location selection of affordable housing with a job-housing balance and its effects on migrant workers’ job burnout. To examine the effects and mechanisms of the job-housing balance in affordable housing locations on job burnout, this study employs the latest 2018 China Labour Force Dynamic Survey data and in-depth interview data on housing support for migrant workers collected by our research team in 2023. Our findings indicate that the job-housing balance significantly reduces job burnout, with this effect being more pronounced in the manufacturing sector and other industries. Labour intensity masks the impact of job-housing balance on job burnout, whereas work quality fully mediates this relationship exclusively in dormitory-type arrangements. This study offers policy implications for optimizing the siting of housing support projects. It also enhances the living conditions of affordable housing and promotes integrated urban-rural development.

Picture fuzzy set (PFS) can intuitively express the answers of “yes”, “neutral”, “no” and “reject”, which have strong advantages in solving uncertain information. The similarity measure is an effective tool to determine the relationship between two picture fuzzy sets (PFSs). In this paper, we propose a hybrid picture fuzzy (PF) similarity measure which combines the Hamming distance and the transformed tetrahedral centroid distance and verifies that it satisfies the four properties of the similarity measure. The proposed and existing picture fuzzy similarity measures are compared and investigated through numerical examples and some applications of pattern recognition. The results show that the proposed similarity measure not only produces no unreasonable results, but also overcomes the shortcomings of the existing similarity measures. Furthermore, we investigate an improved VIKOR method based on the proposed similarity measure of PFS. Finally, through an example, several multi-attribute decision-making (MADM) methods are compared and analyzed to illustrate the effectiveness and practicability of the improved VIKOR method.

Phishing email attacks have evolved into a significant threat, causing substantial economic and political harm. However, existing detection methods often neglect the data heterogeneity resulting from diverse email sources and are trained on balanced email datasets, which do not accurately reflect real-world scenarios. Meanwhile, with increasing privacy protection regulations, it is crucial to develop methods that enhance phishing email detection capabilities while preserving user privacy. To address these challenges, we propose PhFL, a framework based on heterogeneous federated learning, for detecting phishing emails. PhFL decouples clients’ models into representation learning models and classifiers. The representation learning models can be tailored to clients’ specific needs, and the classifiers are globally shared and re-trained on the server, leveraging the class feature means generated by the representation learning models. Our framework allows each client to leverage its private data locally without providing emails to other clients or the server. The collaboration of class feature means and re-training of classifiers effectively address the challenges of class imbalance and data heterogeneity, enabling improved model performance. Experimental results demonstrate that PhFL outperforms other federated learning methods, particularly when different clients have email datasets from diverse sources and face imbalanced class distributions.

The challenge in reusing high-impact recorders lies in developing an efficient and accurate failure prediction model under small-sample conditions. To address this issue, this study proposes an IPSO-SVM model. First, the particle swarms in the IPSO algorithm were grouped based on their exploration and exploitation functions, and dynamic inertia weight mechanisms were designed accordingly. The grouping ratio was dynamically adjusted during iterations to enhance optimization performance. Tests using benchmark functions verified that this approach improves convergence accuracy and stability compared to conventional PSO algorithms. Subsequently, the 5-fold cross-validation accuracy of the SVM model was used as the fitness value, and the IPSO algorithm was employed to optimize the penalty and kernel parameters of the SVM model. Trained on high-impact experimental data, the IPSO-SVM model achieved a prediction accuracy of 90.5%, outperforming the PSO-SVM model’s 85%. These results demonstrate the potential of the IPSO-SVM model in addressing failure prediction challenges under small-sample conditions.

This study aims to explain the role and related mechanisms of long non-coding RNA (lncRNA) X inactive specific transcript (XIST) in sepsis-induced acute lung injury (ALI). The in vivo septic models and in vitro septic model were established. In animal models, the lung injury of the rats was evaluated after XIST was overexpressed. In cell models, the effects of XIST and microRNA (miR)-16-5p on ALI was detected by MTT assay, Western blot and ELISA. The interaction between XIST and miR-16-5p was investigated by bioinformatics analysis, dual-luciferase reporter assay, RIP assay and RNA pull-down assay. We found that XIST expression was down-regulated in lung tissues of septic rats and lipopolysaccharide-stimulated cells, while the expression of miR-16-5p was up-regulated. Down-regulation of XIST significantly promoted pulmonary edema, increased the levels of TNF-α, IL-1β and malondialdehyde, inhibited the cell viability and decreased the level of superoxide dismutase. Mechanistically, it was confirmed that XIST could sponge miR-16-5p, and thus repress its expression, and the transfection of miR-16-5p mimics could reverse the effects of XIST over-expression in the cell model. Collectively, it is concluded that XIST reduces sepsis-induced ALI via regulating miR-16-5p.

Background Acute inflammation induced by reactive astrocytes after cerebral ischemia/reperfusion (I/R) injury is important for protecting the resultant lesion. Our previous study demonstrated that DJ-1 is abundantly expressed in reactive astrocytes after cerebral I/R injury. Here, we show that DJ-1 negatively regulates the inflammatory response by facilitating the interaction between SHP-1 and TRAF6, thereby inducing the dissociation of NLRX1 from TRAF6. Methods We used oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro in primary astrocyte cultures and transient middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo to mimic I/R insult. Results The inhibition of DJ-1 expression increased the expression of the inflammatory cytokines TNF-α, IL-1β, and IL-6. DJ-1 knockdown facilitated the interaction between NLRX1 and TRAF6. However, the loss of DJ-1 attenuated the interaction between SHP-1 and TRAF6. In subsequent experiments, a SHP-1 inhibitor altered the interaction between SHP-1 and TRAF6 and facilitated the interaction between NLRX1 and TRAF6 in DJ-1-overexpressing astrocytes. Conclusion These findings suggest that DJ-1 exerts an SHP-1-dependent anti-inflammatory effect and induces the dissociation of NLRX1 from TRAF6 during cerebral I/R injury. Thus, DJ-1 may be an efficacious therapeutic target for the treatment of I/R injury.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a severe complication following hematopoietic stem cell transplantation, with its pathogenesis not yet fully understood and a lack of highly effective treatment options currently available. This article reports a case of a female patient with acute myeloid leukemia (AML) who was diagnosed with TA-TMA three months after a second allogeneic hematopoietic stem cell transplantation (allo-HSCT). After promptly discontinuing cyclosporine (CSA), and following ineffective treatments with anti-infective therapy, glucocorticoids, and plasma exchange, a short-course combination regimen-defibrotide (10 days) and eculizumab (3 weeks)-was administered. The TA-TMA-related indicators rapidly improved and returned to normal. During follow-up, the patient's primary disease remained in remission, and she remained free of TA-TMA recurrence for five months. At eight months after the second allo-HSCT, TA-TMA recurred due to concurrent pneumonia and sepsis. The same short-course combination regimen-defibrotide (18 days) and eculizumab (3 weeks)-was administered, and the patient showed improvement in clinical and laboratory parameters again. This study is the first to report the use of a short-course combination therapy with defibrotide and eculizumab for TA-TMA. The combination regimen demonstrated good efficacy and tolerability, offering a potential treatment option for refractory TA-TMA, though its broader applicability requires further research and validation.

Thermal environment deterioration has seriously threatened urban habitat quality and urban sustainable development. The evolution of the urban built environment (UBE) is an important cause for urban thermal environment variation. However, the dynamic effect of the UBE on the land surface temperature (LST) is rarely studied by combining the local climate zone (LCZ) theory and spatio-temporal heterogeneity. Based on a case study of Beilin District in Xi’an, China, this paper identified LCZ types of Beilin District in 2010, 2015, and 2020 using the GIS method. It also analyzed the spatial–temporal characteristics of the LST in summer based on the remote sensing retrieval method and explored the effects of the built environment on the LST by Geodetector and geographically weighted regression (GWR). The results showed the following: (1) The area share of dense building zones in Beilin District was greater than that of open building zones and natural surface zones, while the share of mid- and high-rise dense building zones continued to increase and the share of low-rise dense building zones continued to decrease during the study period. (2) The LST of different LCZ types in Beilin District was obviously different, and the LST of dense building zones was generally higher than that of open building zones and natural surface zones. Meanwhile, the LST of mid- and low-rise dense building zones increased gradually, and the LST of high-rise open building zones decreased gradually, but the overall warming area was obviously more than the cooling area. (3) The effects of the UBE factors on the LST varied greatly, with their interaction having an enhancement effect. The direct and interactive influence of the two-dimensional (2D) UBE indicators on the LST were greater than those of the three-dimensional (3D) indicators, but there was a gradual decrease in the force of the 2D indicators and a simultaneous diminution, enhancement, and invariance of the force of the 3D indicators. (4) Vegetation cover (VC) and floor area ratio (FAR) acted negatively, and the building height (BH) was changing from a positive to a negative role, with the average action intensity of VC changing from −0.27 to −0.15, FAR from −0.20 to −0.16, and BH from 0.05 to −0.04. The impervious surface area (ISA), building area (BA), and space congestion (SC) acted positively, with the average action intensity of the ISA changing from 0.12 to 0.20, BA from 0.12 to 0.19, and SC was stable at 0.04. The framework enables a deeper portrayal of LST changes in different LCZs, reflecting the direct and interactive effects of different UBE indicators on LST, as well as local variations in the impact effects and provides a basis for urban managers or planners to improve urban heat resilience.

The MerR-family proteins represent a unique family of bacteria transcription factors (TFs), which activate transcription in a manner distinct from canonical ones. Here, we report a cryo-EM structure of a B. subtilis transcription activation complex comprising B. subtilis six-subunit (2αββ‘ωε) RNA Polymerase (RNAP) core enzyme, σ A , a promoter DNA, and the ligand-bound B. subtilis BmrR, a prototype of MerR-family TFs. The structure reveals that RNAP and BmrR recognize the upstream promoter DNA from opposite faces and induce four significant kinks from the −35 element to the −10 element of the promoter DNA in a cooperative manner, which restores otherwise inactive promoter activity by shortening the length of promoter non-optimal −35/−10 spacer. Our structure supports a DNA-distortion and RNAP-non-contact paradigm of transcriptional activation by MerR TFs. BmrR is a member of the bacterial MerR transcription factor family that regulates the expression of the bacterial efflux pump Bmr. Here, the authors present the cryo-EM structure of a B. subtilis transcription activation complex (TAC) containing the RNA Polymerase (RNAP) core enzyme, σ A , promoter DNA and ligand-bound BmrR, which reveals that in contrast to most other transcription factors BmrR does not directly interact with RNAP and instead activates transcription by modulating the shape of the core promoter.