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Neutrophil extrusion of neutrophil extracellular traps (NETs) in a process called NETosis provides immune defense against extracellular bacteria. It has been observed that bacteria are capable of activating neutrophils to release NETs that subsequently kill them or at least prevent their local spread within host tissue. However, existing studies have mainly focused on the isolated function of NETs, with less attention given to their anti-bacterial mechanisms through interactions with other immune cell populations. The net effect of these complex intercellular interactions, which may act additively, synergistically, or antagonistically, is a critical determinant in the outcomes of host-pathogen interactions. This review summarizes the mechanisms underlying classic NET formation and their crosstalk with the immune system, offering novel insights aimed at balancing the anti-microbial function with their potential inflammatory risks.

The desert ecosystem is an important part of the terrestrial ecosystem. Accurate estimations of the biomass and species richness of desert plants are of great value for maintaining ecosystem stability; however, current assessments remain a challenge due to the large spatial heterogeneity in biomass and species richness and difficulties posed by time-consuming field surveys, particularly in remote areas. In the present study, There were 527 sampling sites, and each sampling site contained approximately 9 quadrats. Approximately 4500 quadrats in total were taken from the Junggar Desert of northern Xinjiang, and the spatial distribution and factors driving the biomass and species richness of the desert ecosystem were quantitatively analyzed. The results showed that the average aboveground biomass, belowground biomass, litter, and the Patrick index of the Junggar Desert in northern Xinjiang were 115.42 gm−2, 924.77 gm−2, 13.06 gm−2, and 63, with values ranging from 2–708.12 gm−2, 120.25–3537.3 gm−2, 2–56.46 gm−2, and 0–377, respectively, The mean of the variation coefficient was 56.19%, 41.16%, 62.16% and 73.83%, suggesting moderate variation. The result is affected by the differences between the desert environment and climate. Climate factors had a relatively large impact on species richness, and the variation coefficient of species richness was large, indicating a large degree of dispersion of species richness. The direct influence of environmental and climatic factors on underground biomass (BGB) is relatively small, and its coefficient of variation is small. The spatial distribution of biomass and species richness in northern Xinjiang gradually decreased from west to east. Redundancy analysis showed that climate was the main factor driving desert biomass and species richness in northern Xinjiang, with an average independent explanatory power of 20.38% and 18.57%, respectively. Structural equation modeling indicated that climate factors, elevation, and community coverage had a direct positive effect on the aboveground biomass of the desert plants in northern Xinjiang and a direct negative effect on the belowground biomass. Moreover, climate factors and biological factors showed a direct positive effect on the species richness in northern Xinjiang.

Olfactory dysfunction (OD) is a key feature of chronic rhinosinusitis with nasal polyps (CRSwNP), resulting from both mechanical obstruction and sensorineural injury. Stapokibart is a humanized anti-IL-4 receptor alpha antibody, and this real-world study aimed to evaluate its efficacy in CRSwNP patients with moderate-to-severe OD, as well as the impact of baseline characteristics on olfactory recovery. A total of 40 CRSwNP patients with moderate-to-severe OD were enrolled. All patients received subcutaneous stapokibart at a dose of 300 mg every 2 weeks for 16 weeks. Subjective olfactory outcome (smell loss VAS) and objective olfactory outcome (SSIT-16) were assessed at Weeks 0, 2, 4, 8, and 16. Subgroup analyses were stratified by baseline inflammatory markers and prior surgery history. Stapokibart led to rapid and sustained olfactory improvement: smell loss VAS was significantly reduced by Week 2 (P<0.0001). At Week 16, 52.5% of patients achieved normosmia, with the mean objective olfactory score increasing from 3.05 ± 2.98 to 11.35 ± 3.73 (P<0.0001) and nasal polyp score decreasing from 4.03 ± 1.70 to 1.63 ± 1.61 (P<0.001). Olfactory recovery was consistent across subgroups, regardless of baseline IgE level, eosinophil count, or previous sinus surgery. Patients with higher baseline polyp burden showed faster early improvement but similar final outcomes. Stapokibart effectively and rapidly improves olfactory function in CRSwNP. Baseline nasal polyp burden affects the speed but not the magnitude of recovery, supporting the clinical utility of stapokibart in patients with moderate-to-severe OD.

Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous malignancy is often associated with unfavorable prognosis. Due to its unique anatomical position and the absence of effective early inspection methods, surgical intervention alone is frequently inadequate for achieving complete remission. Therefore, the identification of reliable biomarker is crucial to enhance the accuracy of screening and treatment strategies for HNSCC. To develop and identify a machine learning-derived prognostic model (MLDPM) for HNSCC, ten machine learning algorithms, namely CoxBoost, elastic network (Enet), generalized boosted regression modeling (GBM), Lasso, Ridge, partial least squares regression for Cox (plsRcox), random survival forest (RSF), stepwise Cox, supervised principal components (SuperPC), and survival support vector machine (survival-SVM), along with 81 algorithm combinations were utilized. Time-dependent receiver operating characteristics (ROC) curves and Kaplan-Meier analysis can effectively assess the model's predictive performance. Validation was performed through a nomogram, calibration curves, univariate and multivariate Cox analysis. Further analyses included immunological profiling and gene set enrichment analyses (GSEA). Additionally, the prediction of 50% inhibitory concentration (IC50) of potential drugs between groups was determined. From analyses in the HNSCC tissues and normal tissues, we found 536 differentially expressed genes (DEGs). Subsequent univariate-cox regression analysis narrowed this list to 18 genes. A robust risk model, outperforming other clinical signatures, was then constructed using machine learning techniques. The MLDPM indicated that high-risk scores showed a greater propensity for immune escape and reduced survival rates. Dasatinib and 7 medicine showed the superior sensitivity to the high-risk NHSCC, which had potential to the clinical. The construction of MLDPM effectively eliminated artificial bias by utilizing 101 algorithm combinations. This model demonstrated high accuracy in predicting HNSCC outcomes and has the potential to identify novel therapeutic targets for HNSCC patients, thus offering significant advancements in personalized treatment strategies.

Background/Aims: Heat stress could cause huge losses for Lentinula edodes in China and other Asian cultivation areas. Yet our understanding of mechanism how to defend to heat stress is incomplete. Methods: Using heat-tolerant and heat-sensitive strains of L. edodes, we reported a combined proteome and transcriptome analysis of L. edodes response to 40 °C heat stress for 24 h. Meanwhile, the effect of LeDnaJ on the thermotolerance and IAA (indoleacetic acid) biosynthesis in L. edodes was analyzed via the over-expression method. Results: The proteome results revealed that HSPs (heat shock proteins) such as Hsp40 (DnaJ), Hsp70, Hsp90 and key enzymes involved in tryptophan and IAA metabolism process LeTrpE, LeTrpD, LeTam-1, LeYUCCA were more highly expressed in S606 than in YS3357, demonstrating that HSPs and tryptophan as well as IAA metabolism pathway should play an important role in thermotolerance. Over-expression of LeDnaJ gene in S606 strains showed better tolerance to heat stress. It was also documented that intracellular IAA accumulation of S606 (8-fold up) was more than YS3357 (2-fold up), and exogenous IAA enhanced L. edodes tolerance to heat stress. Conclusion: Our data support the interest of LeTrpE, LeDnaJ, tryptophan and IAA could play a pivotal role in enhancing organism thermotolerance.

Cell bionic culture requires the construction of cell growth microenvironments. In this paper, mechanical force and electrical stimulations are applied to the cells cultured on the surface of the piezoelectric laminated micro-beam driven by an excitation voltage. Based on the extended dielectric theory, the electromechanical microenvironment regulating model of the current piezoelectric laminated micro-beam is established. The variational principle is used to obtain the governing equations and boundary conditions. The differential quadrature method and the iterative method are used to solve two boundary value problems for cantilever beams and simply supported beams. In two cases, the mechanical force and electrical stimulations applied to the cells are analyzed in detail and the microscale effect is investigated. This study is meaningful for improving the quality of cell culture and promoting the cross-integration of mechanics and biomedicine.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious virus that poses a significant threat to the global pig farming industry, resulting in substantial economic losses. However, owing to the high variability of PRRSV and unclear mechanisms of infection, there are currently no effective vaccines or drugs available for its prevention and control. Our previous report revealed that highly pathogenic PRRSV (HP-PRRSV) requires the FAK-PI3K-AKT signaling pathway to facilitate its entry into cells. In this study, we further investigated whether the integrin subunit was involved in the entry process of NADC30-like PRRSV. First, the integrin subunits in Marc-145 cells were characterized by RT-PCR, and 11 of these subunits were identified, nearly all of which interacted with the integrin α V and β 1 subunits to form heterodimers. Western blot analysis revealed that the integrin α V subunit was highly expressed in Marc-145 cells, and blocking this subunit with a functional antibody or siRNA significantly attenuated NADC30-like PRRSV entry without affecting virus binding. Moreover, in Marc-145 cells, NADC30-like PRRSV could activate the FAK-PI3K-AKT signaling pathway through the integrin α V subunit. Blocking the α V subunit significantly inhibited signal transduction and virus entry, and treatment of cells with the PI3K activator greatly reversed this inhibitory effect. Furthermore, the α V subunit activator manganese could also enhance NADC30-like PRRSV entry and signal transduction. In conclusion, our results revealed that NADC30-like PRRSV could activate the integrin α V subunit and subsequently transduce signals to the FAK-PI3K-AKT signaling pathway to facilitate entry into Marc-145 cells.

Objectives Microvesicles (MVs) derived from human Wharton’s jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs. Methods MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism. Results MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR. Conclusion MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

Sinularin is a natural product extracted from soft coral and is shown to exhibit antitumor effects against multiple human cancers. We previously showed that Sinularin induces apoptotic cell death via stabilizing the FOXO3 protein in prostate cancer cells. In this study, we demonstrated that Sinularin triggers autophagy via two different mechanisms in prostate cancer cells. First, Sinularin reduced the S757 phosphorylation of ULK1 protein, which was mediated by mTOR, leading to ULK1 activation and autophagy initiation. Second, Sinularin enhanced the expression of autophagic protein ATG4A, which is the key regulator in the formation of autophagosome, through a FOXO3-dependent transcriptional mechanism. Next, we identified that ATG4A is a new target gene of the transcription factor FOXO3. Additionally, we also found that Sinularin-induced autophagy promoted survivin degradation and led to cell apoptosis. Taken together, these findings suggest that Sinularin induces prostate cancer cell autophagy by promoting autophagy initiation through activation of ULK1 and formation of autophagosome through the FOXO3-ATG4A pathway.

Long noncoding RNAs (lncRNAs) have been recognized as essential regulators in various human malignancies. Hundreds of lncRNAs were known to be abnormally expressed in renal cell carcinoma (RCC) through a lncRNA expression microarray, among which lncRNA OSTM1 antisense RNA 1(OSTM1-AS1) was revealed as one of the most abundant lncRNAs. However, the function of OSTM1-AS1 in RCC remains unknown. Here, we examined OSTM1-AS1 functional roles and mechanism in RCC development. OSTM1-AS1 expression was significantly highly expressed among RCC tissue specimens and cell lines. Functionally, OSTM1-AS1 knockdown significantly suppressed cell proliferation, migration along with metastasis of RCC cells. Mechanistically, miR-491-5p was targeted via OSTM1-AS1, and down-regulation of miR-491-5p reversed OSTM1-AS1 knockdown impact on RCC migration and invasion. MMP-9 was targeted via miR-491-5p, and MMP-9 overexpression reversed miR-491-5p or OSTM1-AS1 knockdown impact on cell migration and invasion. MMP-9 abundance was decreased by OSTM1-AS1 silence, that was reduced by miR-491-5p deficiency. Importantly, our investigation revealed that OSTM1-AS1 has the ability to interact with miR-491-5p, thereby increasing the MMP-9 expression. The in vivo trial demonstrated that OSTM1-AS1 suppression resulted in tumor growth inhibition among nude mice. In summary, our findings indicate, for the first time, at least to the best of our knowledge, that OSTM1-AS1 serves as an oncogene among RCC by promoting proliferation, invasion, and metastasis through its targeting of the miR-491-5p/MMP9 axis. Therefore, this axis could represent a promising alternative therapeutic target for RCC treatment.