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Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) signaling adaptor that is essential for the type I interferon response to DNA pathogens. Aberrant activation of STING is linked to the pathology of autoimmune and autoinflammatory diseases. The rate-limiting step for the activation of STING is its translocation from the ER to the ER-Golgi intermediate compartment. Here, we found that deficiency in the Ca 2+ sensor stromal interaction molecule 1 (STIM1) caused spontaneous activation of STING and enhanced expression of type I interferons under resting conditions in mice and a patient with combined immunodeficiency. Mechanistically, STIM1 associated with STING to retain it in the ER membrane, and coexpression of full-length STIM1 or a STING-interacting fragment of STIM1 suppressed the function of dominant STING mutants that cause autoinflammatory diseases. Furthermore, deficiency in STIM1 strongly enhanced the expression of type I interferons after viral infection and prevented the lethality of infection with a DNA virus in vivo. This work delineates a STIM1-STING circuit that maintains the resting state of the STING pathway. STIM1 is a calcium sensor that is essential for functional lymphocyte responses. Gwack and colleagues demonstrate a calcium-independent role for STIM1 in macrophages that regulates their production of type I interferons.

Background Icariin (ICA), an active ingredient extracted from Epimedium species, has shown promising results in the treatment of Alzheimer's disease (AD), although its potential therapeutic mechanism remains largely unknown. This study aimed to investigate the therapeutic effects and the underlying mechanisms of ICA on AD by an integrated analysis of gut microbiota, metabolomics, and network pharmacology (NP). Methods The cognitive impairment of mice was measured using the Morris Water Maze test and the pathological changes were assessed using hematoxylin and eosin staining. 16S rRNA sequencing and multi-metabolomics were performed to analyze the alterations in the gut microbiota and fecal/serum metabolism. Meanwhile, NP was used to determine the putative molecular regulation mechanism of ICA in AD treatment. Results Our results revealed that ICA intervention significantly improved cognitive dysfunction in APP/PS1 mice and typical AD pathologies in the hippocampus of the APP/PS1 mice. Moreover, the gut microbiota analysis showed that ICA administration reversed AD-induced gut microbiota dysbiosis in APP/PS1 mice by elevating the abundance of Akkermansia and reducing the abundance of Alistipe . Furthermore, the metabolomic analysis revealed that ICA reversed the AD-induced metabolic disorder via regulating the glycerophospholipid and sphingolipid metabolism, and correlation analysis revealed that glycerophospholipid and sphingolipid were closely related to Alistipe and Akkermansia . Moreover, NP indicated that ICA might regulate the sphingolipid signaling pathway via the PRKCA/TNF/TP53/AKT1/RELA/NFKB1 axis for the treatment of AD. Conclusion These findings indicated that ICA may serve as a promising therapeutic approach for AD and that the ICA-mediated protective effects were associated with the amelioration of microbiota disturbance and metabolic disorder. Graphical Abstract

Imbalanced M1/M2 macrophage phenotype activation is a key point in diabetic kidney disease (DKD). Macrophages mainly exhibit the M1 phenotype, which contributes to inflammation and fibrosis in DKD. Studies have indicated that autophagy plays an important role in M1/M2 activation. However, the mechanism by which autophagy regulates the macrophage M1/M2 phenotype in DKD is unknown. Thus, the aim of the present study was to explore whether high glucose-induced macrophages switch to the M1 phenotype via the downregulation of STAT-3-mediated autophagy. DKD model rats were established in vivo via the intraperitoneal injection of streptozocin (STZ). The rats were sacrificed at 18 weeks for histological and molecular analysis. RAW264.7 cells were cultured in vitro with 30 mM glucose in the presence or absence of a STAT-3 activator (colivelin) and an autophagy activator (rapamycin). Moreover, M1 and M2 macrophage activation models were established as a control group. Immunofluorescence and Western blot analyses were used to detect the expression of autophagy-related proteins (LC3 and Beclin-1), M1 markers (iNOS and CD11c) and M2 markers (MR and CD206). In DKD, macrophages exhibit an M1 phenotype. Under high-glucose conditions, RAW264.7 macrophages switched to the M1 phenotype. Autophagy was downregulated in high glucose-induced M1 macrophages. Both the STAT-3 activator and the autophagy activator promoted the transition of glucose-induced M1 macrophages to M2 macrophages. Moreover, STAT-3 activation increased the expression of autophagy markers (LC3 and Beclin-1). However, the autophagy activator had no effect on STAT-3 phosphorylation. High glucose promotes macrophage switching to the M1 phenotype via the downregulation of STAT-3-mediated autophagy.

Invasive nontyphoidal Salmonella (iNTS) causes extraintestinal infections with ~15% case fatality in many countries. However, the mechanism by which iNTS emerged in China remains unaddressed. We conducted clinical investigations of iNTS infection with recurrent treatment failure, caused by underreported Salmonella enterica serovar Livingstone (SL). Genomic epidemiology demonstrated five clades in the SL population and suggested that the international animal feed trade was a likely vehicle for their introduction into China, as evidenced by multiple independent transmission incidents. Importantly, isolates from Clade‐5‐I‐a/b, predominant in China, showed an invasive nature in mice, chicken and zebrafish infection models. The antimicrobial susceptibility testing revealed most isolates (> 96%) in China are multidrug‐resistant (MDR). Overall, we offer exploiting genomics in uncovering international transmission led by the animal feed trade and highlight an emerging hypervirulent clade with increased resistance to frontline antibiotics. Synopsis The recent increase of human infections caused by invasive non‐typhoidal Salmonella , including Salmonella Livingstone, suggests their evolution towards niche adaptation to humans. This study reveals two novel subclades of S . Livingstone linked to human infections and mainly emerged in China. Genomic epidemiology showed imported animal feed was a major source of the early identified S . Livingstone in China, indicating international feed trading is a transmission route of this pathogen. Phylogeny of global Salmonella Livingstone isolates revealed five major clades of this pathogen, and clinical isolates from China largely belong to Clade‐5. Variabilities of stress responses were observed among isolates from distinct phylogenetic clades, with enhanced resistance to desiccation and diminished tolerance to oxidative stress for Clade‐5 isolates. Two novel subclades of Clade‐5 (i.e., C‐5‐I‐a/b) emerged in the last two decades and predominantly occurred in China accompanying the accumulation of antimicrobial resistance genes. The emerging clades showed significantly increased virulence in distinct animal models. i.e., chicken embryo, zebrafish embryo, and mice, indicating they have been undergoing evolution to adapt to humans. Graphical Abstract The recent increase of human infections caused by invasive non‐typhoidal Salmonella , including Salmonella Livingstone, suggests their evolution towards niche adaptation to humans. This study reveals two novel subclades of S . Livingstone linked to human infections and mainly emerged in China.

Skin cancer is affected by the uncommon evolution of skin cells and is a deadly type of cancer. In addition, skin lesion is affected by numerous factors, such as exposure to the sun, infections, allergies, etc. These skin illnesses have become a challenge in therapeutic diagnosis because of virtual resemblances, where image classification is vital to sufficiently diagnose dissimilar lesions. Therefore, early diagnosis is significant and can avert skin cancers like focal cell carcinoma and melanoma. A deep learning-based computer analyzing model can be an automatic solution in medical evaluations to overcome this issue. Hence, this paper suggests an improved chameleon swarm algorithm and convolutional neural networks (ICSA-CNN) for effective skin cancer identification and classification. The data are collected from the Kaggle dataset for classifying skin cancer. Chameleon swarm algorithm is a clustering technique utilized in data mining to the cluster dataset utilizing dynamic systems, and it can resolve constrained and global numerical optimization issues in skin cancer detection.

Despite the widespread use of COVID-19 vaccines, there is still a global need to find effective therapeutics to deal with the variants of SARS-CoV-2. Moslae herba (MH) is a herbal medicine credited with antiviral effects. This study aims to investigate the antiviral effects and the underlying mechanism of aqueous extract of Moslae herba (AEMH) for treating SARS-CoV-2. The in vitro anti-SARS-CoV-2 activity of AEMH was evaluated using cell viability and viral load. Component analysis was performed by HPLC-ESI-Q-TOF/MS. The connection between COVID-19 and AEMH was constructed by integrating network pharmacology and transcriptome profiles to seek the core targets. The components with antiviral activities were analyzed by molecular docking and in vitro pharmacological verification. AEMH exerted anti-SARS-CoV-2 effects by inhibiting viral replication and reducing cell death caused by infection (IC50 is 170 μg/mL for omicron strain). A total of 27 components were identified from AEMH. Through matching 119 intersection targets of ‘disease and drug’ with 1082 differentially expressed genes of COVID-19 patients, nine genes were screened. Of the nine, the PNP and TPI1 were identified as core targets as AEMH treatment significantly regulated the mRNA expression level of the two genes on infected cells. Three components, caffeic acid, luteolin, and rosmarinic acid, displayed antiviral activities in verification. Molecular docking also demonstrated they could form stable bonds with the core targets. This study explored the antiviral activity and possible mechanism of AEMH for treating SARS-CoV-2, which could provide basic data and reference for the clinical application of MH.

The continuous evolution of SARS-CoV-2 and its variants poses persistent challenges to global public health. As a sublineage of the XDV.1 variant, NB.1.8.1 has rapidly emerged as a dominant strain worldwide, triggering a new wave of infections. Representing a product of viral adaptation, this variant has acquired several critical amino acid mutations—including A435S and T478I—which enhance its transmissibility and immune evasion capabilities compared to the ancestral XDV.1 lineage. This review systematically summarizes the genomic characteristics, epidemiological features, and immune escape potential of NB.1.8.1. It emphasizes that sustained genomic surveillance and serological assessments are crucial for informing public health response strategies, guiding vaccine development, and optimizing containment measures.

Typhoid fever, caused by Salmonella Typhi ( S . Typhi), is a life-threatening disease, usually food-borne and commonly associated with international travel. The disease transmission remains endemic in many low- and middle-income countries, representing further hotspots for seeding new global outbreaks. China has historically been affected by typhoid fever, but the respective roles of local transmission and importation remain unknown. Here, we generated a nationwide map of the typhoid burden in China and investigated the associations between typhoid disease, climate and various socioeconomic parameters. To assess transmission dynamics, we sub-sampled S . Typhi isolated within China over five decades and sequenced their genomes. The resulting 705 new genomes, placed in context with 5,190 global isolates from 87 countries on six continents, led to the discovery of several predominant inland Chinese clones belonging to the clades 2.1/2.3/3.2/4.3. These clones were associated with multiple introductions from overseas, followed by local expansion. Notably, 4.3.1 isolates from eastern China were not genetically close to those from northwestern China but to the international isolates, indicating their association with international travel. Additional in vitro assays showed that 4.3.1 elaborated better intracellular survival, acid tolerance, and desiccation tolerance than other lineages, partially explaining its success. For the first time, we have probed typhoid transmission in China, finding local transmission and importation, which could guide the policy for typhoid control. Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network.

Mpox clade Ib is significant as it is associated with human cases and plays a key role in understanding the transmission and public health implications of mpox outbreaks. Here we present a case report of the first confirmed human infection of clade Ib in China, which occurred in December 2024 in Zhejiang Province. The case was a 28-year-old woman from South Africa who had sexual contact with an asymptomatic man from the Democratic Republic of the Congo. She presented with disseminated vesicular lesions on the extremities, face, buttocks, trunk, palms, and dorsum of the hands, but lesions were absent from the oral cavity, perineum, and anus. By the 18th day post-onset (DPO), only vesicles remained on the dorsum of the right foot and in the finger web spaces, with complete resolution by the 24th DPO. Among 59 consecutive samples collected, 55 tested positive for mpox virus. Oropharyngeal swabs turned negative by the 16th DPO, while skin lesion samples, urine samples, and scab specimens remained positive through the 20th DPO. Consecutive scab samples consistently exhibited high viral loads. In total, 211 contacts of the symptomatic patient were identified, and no secondary cases occurred. This study underscores the importance of multisite sampling for diagnostic sensitivity, highlights the transmission risk associated with asymptomatic sexual contact, and emphasizes the need for refined contact definitions and management strategies. Further research is needed to explore infection risks across different types of exposure. The first outbreaks of mpox outside Africa in 2022 were caused by clade II but cases of a new clade Ib have been increasing in the Democratic Republic of Congo and neighbouring countries since 2024. Here, the authors describe a case report and public health investigation of the first detected case of mpox clade Ib in China.

The body of research on tumor-infiltrating lymphocytes (TILs) is expanding rapidly; yet, a comprehensive analysis of related publications has been notably absent. This study utilizes bibliometric methodologies to identify emerging research hotspots and to map the distribution of tumor-infiltrating lymphocyte research. Literature from the Web of Science database was analyzed and visualized using VOSviewer, CiteSpace, Scimago Graphica, R-bibliometrix, and R packages. Research on tumor-infiltrating lymphocytes began in 1975 and has experienced significant growth, particularly after 2015. Leading contributors include the United States, the National Cancer Institute, the journal Cancer Immunology Immunotherapy, and researcher Steven A. Rosenberg. Other prominent contributors include China, the National Institutes of Health, researcher Roberto Salgado, and the Journal of Immunology. Prominent institutions in the USA and Europe occupy central roles within collaborative networks. Financial support plays a pivotal role in driving research advancements. Keyword clustering analysis reveals four primary knowledge domains: adoptive cell therapy; the prognostic value of TILs; PD-1/PD-L1 and TILs; and prognostic studies of TILs across various cancers. Keyword and reference analyses further indicate that \"adoptive cell therapy,\" \"the prognostic value of TILs,\" and \"immune checkpoint inhibitors and TILs\" are central themes in current and future research. Combination therapies; tumor neoantigens; gene editing; dominant population selection of TILs therapy; TILs in Tumor microenvironment; emerging predictive biomarkers; TILs in predicting the efficacy of neoadjuvant chemotherapy and immunotherapy; the relationship between TILs and PD-L1; TIL-based patient stratification; tertiary lymphoid structures; and TIL evaluation through digital pathology and artificial intelligence are identified as key areas of interest. This analysis highlights the increasing academic focus on tumor-infiltrating lymphocyte research and identifies key recent themes in the field such as prognostic value of TILs, personalized treatments, and combination therapies.