ABSTRACT Mast cells (MCs), key innate immune sentinels at the host–environment interface, serve as primary responders to invading pathogens. However, their specific contribution to host defense against cutaneous Candida albicans (C. albicans) infection and their synergy with other immune and non‐immune cells remain poorly understood. Here, we show that MCs accumulate locally in skin lesions of patients with cutaneous candidiasis. In mouse models, MC‐deficient KitW‐sh/W‐sh mice developed more severe infection than wild‐type (WT) controls, and adoptive transfer of bone marrow‐derived mast cells (BMMCs) restored antifungal capacity, establishing a critical protective role for MCs in cutaneous C. albicans infection. Mechanistically, MCs secrete IL‐6 to drive antimicrobial peptide (AMP) production by keratinocytes (KCs). Reciprocally, KCs activate the non‐canonical NF‐κB (NF‐κB2) pathway and release CXCL2, which signals through CXCR2 on MCs to further promote IL‐6 secretion, establishing an NF‐κB2–CXCL2–IL‐6 amplification loop between the two cell types. Topical recombinant IL‐6 enhanced KC‐mediated antifungal activity and ameliorated cutaneous C. albicans infection in MC‐deficient mice, underscoring the essential, non‐redundant role of MC‐derived IL‐6 in this axis. Collectively, our findings reveal an MC‐KC amplification loop centered on the NF‐κB2–CXCL2–IL‐6 axis that orchestrates cutaneous antifungal defense and identify new therapeutic targets for cutaneous fungal infection.

Objective::It has been reported that dietary factors may be closely associated with psoriasis. However, their causal associations with psoriasis remain elusive. This study aimed to clarify the relationships between genetic determinants of dietary habits and psoriasis through the application of Mendelian randomization (MR) approaches.Methods::This two-sample MR study leveraged genome-wide association study data involving 4,510 cases and 212,242 controls (total n = 216,752) to evaluate 34 common dietary habits in relation to psoriasis risk. The primary methodological framework utilized the multiplicative random-effects inverse variance weighted approach, supported by the MR-Egger and weighted median approaches, to ascertain the causal relevance. External genome-wide association study summary statistics for psoriasis were used for replication analyses. For the dietary factors that were found to be associated with psoriasis in the discovery phase, secondary MR analyses were applied to clarify their causal roles on different subtypes of psoriasis. This MR study has been registered on the Open Science Framework (Registration doi: 10.17605/OSF.IO/28VPC) Results::The multiplicative random-effects inverse variance weighted analysis revealed that genetic predispositions for higher intakes of cereals (OR = 0.50, 95% CI: 0.27-0.92, P = 0.026) and dried fruits (OR = 0.40, 95% CI: 0.20-0.81, P = 0.011) had nominal correlations with reduced odds of psoriasis. These nominal inverse correlations were supported by the replication analyses. No evidence of heterogeneity or horizontal pleiotropy was observed in the sensitivity analyses (all P > 0.05). The secondary analyses revealed protective effects for the consumption of cereals and dried fruits on arthropathic psoriasis and psoriasis vulgaris, respectively. Conclusion::The present findings support increased intakes of cereals and dried fruits as potential protective factors against psoriasis.

Background Chronic intestinal inflammation is a hallmark of inflammatory bowel disease (IBD). Studies suggest that salivary bacteria associated with periodontitis may exacerbate colitis, but the specific contributory microbes and mechanisms remain unclear.Patients and methods We analyzed stool samples from 28 IBD patients and 21 controls. Bacterial DNA was extracted and quantified using qPCR targeting Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans). In a murine model, C57BL/6 mice received DSS followed by daily oral gavage with A. actinomycetemcomitans. Disease activity, histopathology and the gut microbiota were evaluated.Results Oral administration of A. actinomycetemcomitans exacerbated inflammatory symptoms in DSS-induced colitis. The bacterium was detectable in intestinal tissue transiently following high-dose oral administration during the inflammatory phase. Following high-dose gavage, bacterial DNA was transiently detectable in intestinal tissue during inflammation. This treatment was associated with reduced expression of the tight junction protein ZO-1 and mucin MUC-2, elevated inflammatory mediators, and altered gut microbial community structure, including an expansion of taxa associated with dysbiosis.Conclusion In a murine colitis model, A. actinomycetemcomitans exposure was associated with worsened disease severity, coinciding with impaired barrier integrity, heightened inflammation and gut microbiota alterations. These exploratory findings highlight the potential role for specific periodontal microbes in modulating intestinal inflammation and warrant further investigation.

Ultraviolet B (UVB) radiation is a major environmental factor causing skin damage, yet the actual role of macrophages in UVB-induced inflammatory remains incompletely understood. This study aimed to investigate the function and metabolic regulation of macrophages in UVB-induced skin injury. Clinical specimens from sun-exposed and non-sun-exposed human skin, murine models of acute and chronic UVB-induced damage, ex vivo skin co-culture system, and in vitro keratinocyte-macrophage co-culture systems were employed in our study. We found that depletion of macrophages by clodronate liposome significantly alleviated UVB-induced mouse skin damage. Further analysis revealed that UVB radiation promoted M1 polarization and induced metabolic dysregulation of macrophages. Pharmacological inhibition of TNF signaling using R7050 suppressed M1 polarization and ameliorated skin damage, while also rescuing UVB-induced metabolic alterations in macrophages. Importantly, restoration of succinate dehydrogenase (SDH) in macrophages reversed M1 polarization. These results demonstrated that macrophages contributed to UVB-induced skin injury via metabolic alterations and M1 polarization, processes orchestrated by the TNF-SDH axis. Targeting this pathway may represent a promising therapeutic strategy for UVB-induced skin pathologies.

Psoriasis is a common, chronic inflammatory skin disorder with a high prevalence across all age groups, imposing a substantial burden on both individuals and society. It is characterized by epidermal hyperplasia and infiltration of immune cells into the dermis. Within the psoriatic microenvironment, epidermal keratinocytes contribute to a self-amplifying inflammatory response through the generation of “feed-forward” inflammation. Contrary to the earlier view of keratinocytes as passive “victims” in psoriasis pathogenesis, growing evidence supports their role as “active drivers” of disease progression. Programmed cell death (PCD) in keratinocytes interacts dynamically with immune cells, cytokines, damage-associated molecular patterns (DAMPs), and other factors, forming a complex regulatory network. Multiple PCD-related molecules in keratinocytes have been identified, many of which hold promise as biomarkers or therapeutic targets. These molecules may inform the development of new diagnostic and treatment strategies for psoriasis. This review outlines the major PCD pathways in keratinocytes—apoptosis, necroptosis, ferroptosis, and pyroptosis—and examines their roles in psoriasis. We also summarize recent therapeutic advances that modulate keratinocyte cell death and discuss how these pathways shape the cutaneous immune microenvironment.

Tendon injuries are often exacerbated by persistent inflammation, which hampers tissue regeneration. In this study, we developed a noninvasive, wirelessly controlled, and self-powered piezoelectric nanofilm fabricated by coaxial electrospinning of polycaprolactone (PCL) and tetragonal barium titanate nanoparticles (BTO), and investigated its roles in modulating inflammation and repairing Achilles tendon defects as well as the mechanism in a rat model. In vitro study and in vivo study upon subcutaneous implantation showed that the piezoelectric PCL/BTO nanofilms could inhibit M1 macrophage polarization and reduce the secretion of inflammatory factors. Moreover, when bridging an Achilles tendon defect, the nanofilms could promote tenogenic gene expression including collagen deposition, and collagen remodeling, facilitate functional tendon recovery and significantly reduce tissue inflammation by suppressing M1 macrophage polarization and promoting M2 polarization. Moreover, the piezoelectric stimulation could also enhance tendon regeneration by inhibiting angiogenesis, reducing lipid deposition, and decreasing ectopic ossification. Mechanistically, the piezoelectric nanofilms reduced tissue inflammation mainly via inhibiting the nuclear factor (NF)-κB signaling pathway that is mediated by interleukin (IL)-17A secreted from CD3+ T cells, and thus to reduce proinflammatory factors, such as IL-1β and IL-6, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and tumor necrosis factor-α. These findings indicate the potential of piezoelectric stimulation in immunomodulation, and in promoting tendon regeneration via IL-17A/NF-κB-mediated pathway.

Melasma is a recurrent and treatment-resistant hyperpigmentation disorder characterized by a complex and multifactorial pathogenesis. However, the lack of a stable and reliable animal model has hindered systematic investigations into its onset and progression. In this study, we established a melasma-like model in C57BL/6J mice by combining broadband UVB irradiation, intramuscular progesterone administration, and induced emotional stress. The affected skin areas exhibited irregular, brown hyperpigmented patches. Histopathological analysis revealed an accumulation of melanin granules in the epidermis and superficial dermis, elevated levels of tyrosinase (TYR) in both skin and plasma, systemic oxidative stress imbalance, and reduced autophagic activity in the lesional skin. Furthermore, this model displayed distinct differences from a UV-induced post-inflammatory hyperpigmentation (PIH) model. Notably, the melasma-like mice responded to tranexamic acid treatment in a manner that closely resembled clinical outcomes observed in human patients. Collectively, these findings establish a stable, reproducible, and clinically relevant mouse model of melasma, providing a valuable platform for future research into its pathogenesis and treatment.

>Precise risk stratification is crucial for selecting the optimal risk-adapted treatment for newly diagnosed multiple myeloma (NDMM) patients. Various prognostic factors and staging systems have been developed to predict NDMM patient outcomes. The Durie-Salmon (D-S) staging system reflects tumor burden and clinical progression staging with prognostic value.

BACKGROUND:Melasma is a common disease that is difficult to treat, with no recognized animal model for mechanism research or drug screening. OBJECTIVES:To develop a novel, standardized mouse model of melasma. MATERIALS AND METHODS:Three different strains of mice (C57BL/6J, BALB/c, and KM) were used to create a melasma-like model across various body regions. The skin of the mice was removed on Day 28 and subjected to staining to examine histopathological changes. Data were analyzed using SPSS19.0 software. RESULTS:Compared with KM and BALB/c mice, C57BL/6J mice were identified as the ideal strain for demonstrating hyperpigmentation more sensitively. The head and ear were identified as more appropriate irradiation sites. Furthermore, a lower irradiation dose was determined to be appropriate for modeling. CONCLUSION:The C57BL/6J mouse model more accurately simulates the clinical phenotype of melasma.

Objective::Metformin is a well-known anti-diabetic drug that has also been reported to alleviate various inflammatory diseases. However, whether metformin can mitigate contact dermatitis and the underlying mechanisms remain unknown. Therefore, we conducted these in vitro and in vivo experiments to investigate the therapeutic effects of metformin on 2,4-dinitrochlorobenzene (DNCB)–induced contact dermatitis. Methods::The animal model used in the experiment was DNCB-induced contact dermatitis model, and HaCaT cells were used for in vitro experiments. Animal experiments were conducted in randomized groups. Patch tests were conducted to evaluate the irritation caused by different concentrations of metformin on mouse skin, and determined the optimal metformin concentration for following experiments. Propidium iodide staining was used to label dead cells, and western blotting was performed to assess changes in protein levels following metformin treatment. Immunofluorescence experiments were used to compare phosphorylated mixed lineage kinase domain-like protein levels before and after topical metformin administration in a DNCB-induced contact hypersensitivity mouse model. Data from the 2 groups were analyzed using the t test, and for comparisons involving 3 or more groups, a one-way analysis of variance was used. Results::In a DNCB-induced contact hypersensitivity mouse model, topical application of 4.0% metformin significantly alleviated skin inflammation (the dermatitis score reduced from 9.83 ± 0.29 to 5.17 ± 0.76, P < 0.05), and reduced the proportion of dead cells from 46.83% ± 9.25% to 9.77% ± 9.54% ( P < 0.05), and reduced phosphorylation levels of mixed lineage kinase domain-like protein in keratinocytes. In vitro experiments further demonstrated that metformin inhibited necroptosis in HaCaT cells under a contact dermatitis–like environment simulated by tumor necrosis factor-α and interferon-γ. Conclusions::These findings suggest that metformin inhibits keratinocyte necroptosis, thereby alleviating inflammation in contact dermatitis. The topical application of metformin may represent a potential therapeutic approach for contact dermatitis, which needs further in vitro and in vivo experiments for investigation.

Allogeneic hematopoietic stem cell transplantation is one of the most effective treatment strategies for leukemia, lymphoma, and other hematologic malignancies. However, graft-versus-host disease (GVHD) can significantly reduce the survival rate and quality of life of patients after transplantation, and is therefore the greatest obstacle to transplantation. The recent development of new technologies, including high-throughput sequencing, metabolomics, and others, has facilitated great progress in understanding the complex interactions between gut microbiota, microbiota-derived metabolites, and the host. Of these interactions, the relationship between gut microbiota, microbial-associated metabolites, and GVHD has been most intensively researched. Studies have shown that GVHD patients often suffer from gut microbiota dysbiosis, which mainly manifests as decreased microbial diversity and changes in microbial composition and microbiota-derived metabolites, both of which are significant predictors of poor prognosis in GVHD patients. Therefore, the purpose of this review is to summarize what is known regarding changes in gut microbiota and microbiota-derived metabolites in GVHD, their relationship to GVHD prognosis, and corresponding clinical strategies designed to prevent microbial dysregulation and facilitate treatment of GVHD.

It was to compare the differences in efficacy and safety for the treatment of hyperpigmentation disorders by Q-switched alexandrite (Q-SA) laser and Neodymium-doped Yttrium Aluminium Garnet (Nd:YAG) laser. The clinical data of 86 patients with hyperpigmentation disorders were collected and grouped: in the Q-SA laser and Nd:YAG laser groups according to the treatment methods, with 43 cases in each group. The clinical efficacy, skin barrier function (transdermal water loss (TEWL), stratum corneum water content, pH value, proteoglycan content), degree of pigmentation, serum inflammatory factors (high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)), and adverse reaction rate were compared after treatment. Compared with the Q-SA laser group, Nd:YAG laser group had decreased scab formation, healing, and scab shedding time, TEWL, pH value, and proteoglycan content, the increased water content of stratum corneum, decreased pigmentation score and area, and decreased serum levels of hs-CRP, TNF-α, and IL-6 (P<0.05). The total effective rates were 76.74% and 95.35%, and the adverse reaction rates were 30.23% and 6.98%, respectively in the Q-SA laser and Nd:YAG laser groups. Compared with the Q-SA laser group, Nd:YAG laser group had a higher total effective rate and lower incidence rate of adverse reactions (P<0.05). Nd:YAG laser plus rhEGF gel in the treatment of hyperpigmentation disorders can effectively protect the skin barrier function, reduce skin pigmentation, reduce the inflammatory response, and improve the therapeutic effect, with high safety.

Dermal fibroblasts are the main resident cells of the dermis. They have several significant functions related to wound healing, extracellular matrix production and hair cycling. Dermal fibroblasts can also act as sentinels in defence against infection. They express pattern recognition receptors such as toll‐like receptors to sense pathogen components, followed by the synthesis of pro‐inflammatory cytokines (including IL‐6, IFN‐β and TNF‐α), chemokines (such as IL‐8 and CXCL1) and antimicrobial peptides. Dermal fibroblasts also secrete other molecules‐like growth factors and matrix metalloproteinases to benefit tissue repair from infection. Crosstalk between dermal fibroblasts and immune cells may amplify the immune response against infection. Moreover, the transition of a certain adipogenic fibroblasts to adipocytes protects skin from bacterial infection. Together, we discuss the role of dermal fibroblasts in the war against pathogens in this review. Dermal fibroblasts have important immune functions in anti‐infection immunity, which should not be overlooked.

Gasdermin D (GSDMD)-mediated pyroptosis has a significant pro-inflammation characteristic due to dramatic secretion of pro-inflammatory substances. However, its role remains unclear in psoriasis as one chronic inflammatory skin disorder with high prevalence. We found that N-terminal GSDMD (N-GSDMD) was aberrantly expressed in epidermis of skin lesion in psoriasis patients and imiquimod-induced psoriasis-like dermatitis (IIPLD) mice. In epidermis of IIPLD mice and M5 (simulating psoriatic inflammatory challenge)-treated keratinocytes cultured in vitro, cleavage products of caspase-1, GSDMD and IL-1β were increased. M5-stimulated keratinocyte presented typical pyroptosis morphology accompanied with PI-staining. Gsdmd −/− keratinocytes could not present pyroptosis morphology while stimulated with M5. Electroporation of recombinant N-GSDMD could make the pyroptosis morphology reappear. In Gsdmd −/− mice or keratinocyte-specific Gsdmd conditional knockout mice, we observed the alleviation of psoriatic inflammation and epidermal aberrant expression of Ki-67 and differentiation markers (loricrin and keratin 5) after imiquimod stimulation. Transplanting skin tissue from control mice to Gsdmd −/− mice can evoke the response to imiquimod stimulation in the background of Gsdmd −/− mice (not limited in transplanting area). In M5-stimulated keratinocytes, disulfiram or GSDMD siRNA transfection can inhibit pyroptosis and eliminate disproportionate increases of Ki-67 and PI. We further validated that topically application of disulfiram (pyroptosis inhibitor) also alleviated IIPLD in mice. These findings indicate a novel mechanism that GSDMD-mediated keratinocyte pyroptosis facilitates hyperproliferation and aberrant differentiation induced by immune microenvironment in psoriatic skin inflammation, which contributes to pathogenesis of psoriasis. Our study provides an innovative insight that targeting pyroptosis can be considered as a therapeutic strategy against psoriasis.

Emerging and existing viruses from various human and animal samples have been studied and analyzed using viral metagenomics, which has proven to be an effective technique. Foxes, as a kind of significant economic animal, are widely raised in China. Viruses carried by foxes may potentially infect humans or other animals. There are currently very few studies of faecal virome in farmed foxes. Using viral metagenomics, we evaluated the faecal virome of twenty-four foxes collected from the same farm in Jilin Province, China. Some sequences more closely related to the families Parvoviridae, Picornaviridae, Smacoviridae, Anelloviridae, and Herpesviridae were detected in the faecal sample. The main animal viruses that infect farmed red foxes were parvovirus and picornavirus. Five smacovirus strains were found and provided evidence for genetic diversity in the genus Smacoviridae. In addition, some viruses infecting avian species or rats were detected in this study. The study helped us better understand faecal virome in farmed red foxes and assisted in the surveillance and prevention of viral diseases in these animals.

目的探讨白念珠菌对小鼠骨髓来源巨噬细胞(BMDM)焦亡的影响。方法通过活细胞工作站实时观察白念珠菌[感染复数(MOI)= 50, 下同]体外诱导BMDM后是否发生焦亡;将BMDM分为对照组、白念珠菌组, 分别用磷酸盐缓冲液和白念珠菌酵母诱导BMDM 6 h, 实时荧光定量PCR检测NOD样受体热蛋白结构域相关蛋白3(NLRP3)、白细胞介素1β(IL-1β)、IL-18 mRNA表达水平, Western印迹法检测NLRP3、胱天蛋白酶1(Caspase-1)、Gasdermin D(GSDMD)的表达及剪切水平。用白念珠菌诱导BMDM不同时间(0、10、15、20及25 h)后, 酶联免疫吸附试验检测IL-1β、IL-18分泌水平。白念珠菌体外诱导野生型(WT)BMDM及GSDMD敲除(KO)BMDM 15 min, 采用流式细胞仪比较WT、GSDMD KO BMDM对白念珠菌的吞噬率;诱导6 h后, 采用流式细胞仪及乳酸脱氢酶(LDH)释放法分别检测WT、GSDMD KO BMDM的死亡率。分别设置空白对照组、对照组、样品最大酶活性对照孔组、IL-1β组、白念珠菌组、IL-1β +白念珠菌组, 用IL-1β和/或白念珠菌酵母诱导BMDM后用LDH释放法分析WT及GSDMD KO BMDM死亡率。采用非配对t检验、Kruskal-Wallis检验、方差分析等统计学方法进行统计分析。结果白念珠菌体外诱导BMDM后细胞可出现气球样变及出泡现象, 证实焦亡发生;与对照组相比, 白念珠菌组诱导BMDM 6 h后NLRP3、IL-1β的mRNA表达水平明显升高(t = 13.02、17.51, P =或<0.001), 而IL-18 mRNA表达水平无明显变化(P = 0.486), 且白念珠菌诱导可引起炎症小体NLRP3表达增多及Caspase-1、GSDMD剪切。白念珠菌诱导BMDM不同时间(0、10、15、20及25 h)后IL-1β的分泌水平随时间逐渐升高(H = 12.90, P = 0.012), 而IL-18的分泌水平无明显变化(F = 0.48, P = 0.753), 且GSDMD KO组BMDM的IL-1β分泌水平低于WT BMDM组(F = 24.22, P = 0.008)。白念珠菌体外诱导15 min后, GSDMD KO BMDM[(50.3 ± 1.10)%]对白念珠菌的吞噬率低于WT BMDM[(58.53 ± 1.19)%, t = 5.09, P = 0.007];白念珠菌体外诱导6 h后, 流式细胞仪检测显示GSDMD KO组BMDM的死亡率(38.40% ± 0.50%)高于WT组BMDM(34.37% ± 0.52%), t = 4.72, P = 0.009;LDH检测同样显示GSDMD KO BMDM的死亡率(22.52% ± 0.18%)高于WT BMDM(12.48% ± 0.15%), t = 42.36, P<0.001;IL-1β预处理后予白念珠菌体外诱导的WT BMDM及GSDMD KO BMDM的细胞死亡率均较单纯白念珠菌诱导组降低(均P<0.001)。结论白念珠菌可诱导BMDM发生焦亡, 焦亡的发生可促进IL-1β释放, 并通过提高巨噬细胞的免疫活性, 降低巨噬细胞死亡率。

Osteoarthritis (OA) is a degenerative disease that ultimately leads to joint deformity. The pathogenesis of OA is believed to involve abnormal chondrocyte death, with ferroptosis serving a key role in chondrocyte damage. The present study investigated whether acetyl zingerone (AZ), a newly identified antioxidant derived from curcumin, can alleviate the progression of OA. To investigate this, the present study performed various experiments, including crystal violet staining, flow cytometry, immunofluorescence and western blot analysis. In addition, dual validation was performed using in vivo and in vitro experiments; a mouse OA model was constructed for the in vivo experiments, and chondrocytes were used for the in vitro experiments. Destabilization of the medial meniscus (DMM) surgery was performed to establish an OA model in mice and IL-1 beta was used to induce an OA model in vitro. The results indicated that AZ may promote chondrocyte viability and the expression of extracellular matrix components. Furthermore, AZ reduced the occurrence of ferroptosis by promoting the expression of glutathione peroxidase 4, inhibiting cartilage destruction and osteophyte formation, and alleviating damage to articular cartilage caused by DMM surgery. Mechanistically, the activation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 may be responsible for the anti-ferroptosis effects of AZ on chondrocytes. These findings indicated that AZ may be considered a promising candidate for OA therapy.

Accurate early detection of the human papillomavirus (HPV) status in head and neck cancer (HNC) is crucial to identify at-risk populations, stratify patients, personalized treatment options, and predict prognosis. Artificial intelligence (AI) is an emerging tool to dissect imaging features. This systematic review and meta-analysis aimed to evaluate the performance of AI to predict the HPV positivity through the HPV-associated diseased images in HNC patients. A systematic literature search was conducted in databases including Ovid-MEDLINE, Embase, and Web of Science Core Collection for studies continuously published from inception up to October 30, 2022. Search strategies included keywords such as "artificial intelligence," "head and neck cancer," "HPV," and "sensitivity & specificity." Duplicates, articles without HPV predictions, letters, scientific reports, conference abstracts, or reviews were excluded. Binary diagnostic data were then extracted to generate contingency tables and then used to calculate the pooled sensitivity (SE), specificity (SP), area under the curve (AUC), and their 95% confidence interval (CI). A random-effects model was used for meta-analysis, four subgroup analyses were further explored. Totally, 22 original studies were included in the systematic review, 15 of which were eligible to generate 33 contingency tables for meta-analysis. The pooled SE and SP for all studies were 79% (95% CI: 75-82%) and 74% (95% CI: 69-78%) respectively, with an AUC of 0.83 (95% CI: 0.79-0.86). When only selecting one contingency table with the highest accuracy from each study, our analysis revealed a pooled SE of 79% (95% CI: 75-83%), SP of 75% (95% CI: 69-79%), and an AUC of 0.84 (95% CI: 0.81-0.87). The respective heterogeneities were moderate (I2 for SE and SP were 51.70% and 51.01%) and only low (35.99% and 21.44%). This evidence-based study showed an acceptable and promising performance for AI algorithms to predict HPV status in HNC but was not comparable to the routine p16 immunohistochemistry. The exploitation and optimization of AI algorithms warrant further research. Compared with previous studies, future studies anticipate to make progress in the selection of databases, improvement of international reporting guidelines, and application of high-quality deep learning algorithms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.

Growing evidence suggests that highly intestinal microbiota diversity modulates host inflammation and promotes immune tolerance. Several studies have reported that patients undergoing allo-HSCT have experienced microbiota disruption that is characterized by expansion of potentially pathogenic bacteria and loss of microbiota diversity. Thus, the primary aim of this meta-analysis was to determine the association of intestinal microbiota diversity and outcomes after allo-HSCT, and the secondary aim was to analyze the associations of some specific microbiota abundances with the outcomes of allo-HSCT. Electronic databases of Pubmed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2023, and 17 studies were found eligible. The pooled estimate suggested that higher intestinal microbiota diversity was significantly associated with overall survival (OS) benefit (HR = 0.66, 95