Integrated Analysis Identified TGFBI as a Biomarker of Disease Severity and Prognosis Correlated with Immune Infiltrates in Patients with Sepsis.

Background: Sepsis is a major contributor to morbidity and mortality among hospitalized patients. This study aims to identify markers associated with the severity and prognosis of sepsis, providing new approaches for its management and treatment. Methods: Data were mined from the Gene Expression Omnibus (GEO) databases and were analyzed by multiple statistical methods like the Spearman correlation coefficient, Kaplan-Meier analysis, Cox regression analysis, and functional enrichment analysis. Candidate indicator' associations with immune infiltration and roles in sepsis development were evaluated. Additionally, we employed techniques such as flow cytometry and neutral red staining to evaluate its impact on macrophage functions like polarization and phagocytosis. Results: Twenty-eight genes were identified as being closely linked to the severity of sepsis, among which transforming growth factor beta induced (TGFBI) emerged as a distinct marker for predicting clinical outcomes. Notably, reductions in TGFBI expression during sepsis correlate with poor prognosis and rapid disease progression. Elevated expression of TGFBI has been observed to mitigate abnormalities in sepsis-related immune cell infiltration that are critical to the pathogenesis and prognosis of the disease, including but not limited to type 17 T helper cells and activated CD8 T cells. Moreover, the protein-protein interaction network revealed the top ten genes that interact with TGFBI, showing significant involvement in the regulation of the actin cytoskeleton, extracellular matrix-receptor interactions, and phagosomes. These are pivotal elements in the formation of phagocytic cups by macrophages, squaring the findings of the Human Protein Atlas. Additionally, we discovered that TGFBI expression was significantly higher in M2-like macrophages, and its upregulation was found to inhibit lipopolysaccharide-induced polarization and phagocytosis in M1-like macrophages, thereby playing a role in preventing the onset of inflammation. Conclusion: TGFBI warrants additional exploration as a promising biomarker for assessing illness severity and prognosis in patients with sepsis, considering its significant association with immunological and inflammatory responses in this condition.

Enhancement of antitumor response of staphylococcal enterotoxin C2 mutant 2M-118 by promoting cell-mediated antitumor immunity.

BACKGROUND: Staphylococcal enterotoxin C2 (SEC2) is used as an immunotherapeutic drug in China. However, SEC2 are limited due to its immunosuppressive and toxic effects. A SEC2 2M-118 (H118A/T20L/G22E) mutant generated by site-directed mutagenesis was studied to elucidate the underlying antitumor mechanism. METHODS: The effects of 2M-118 on mouse fibrosarcoma (Meth-A) cells and cytokine responses were tested in vitro using a transwell assay and ELISA, respectively. 2M-118 effect on immune function in tumor-bearing mice was tested. Cytokine levels and antitumor responses were measured using ELISA and flow cytometry, respectively. TUNEL staining and immunohistochemistry were employed to detect the tumor apoptosis and CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in tumor tissue. RESULTS: 2M-118 demonstrated the growth inhibition on tumor cells, increase of cytokines production (IL-2, IFN-γ, and TNF-α) and splenocyte proliferation in vitro. 2M-118 effectively inhibited tumor development and increased lymphocytes and cytokines in a tumor-bearing mouse model. Additionally, 2M-118 regulated the tumormicroenvironment by reducing the number of myeloid-derived suppressor cells (MDSCs), increasing the number of TILs, and inducing tumorcell apoptosis. CONCLUSION: 2M-118 promotes immune function and enhances antitumor response. This indicates that 2M-118 could potentially be developed as a novel anti-tumor drug with-highefficiencyandlowtoxicity.

Erratum: Author correction to "Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles" [Acta Pharmaceutica Sinica B 12 (2022) 1523-1533].

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].

Food-water-land-ecosystem nexus in typical Chinese dryland under different future scenarios.

Healthy coupling of the food-water-land-ecosystem (FWLE) nexus is the basis for achieving sustainable development (SD), and FWLE in drylands is frontier scientific issues in the study of coupled human land systems. To comprehensively safeguard the future food, water, and ecological security of drylands, this study examined the implications for FWLE linkages in a typical Chinese dryland from the perspective of future land-use change. First, four different land-use scenarios were proposed using a land-use simulation model with a gray multi-objective algorithm, including an SD scenario. Then, the variation of three ecosystem services was explored: water yield, food production, and habitat quality. Finally, redundancy analysis was used to derive the future drivers of FWLE and explore their causes. The following results were obtained. In the future in Xinjiang, under the business as usual scenario, urbanization will continue, forest area will decrease, and water production will decline by 371 million m3. In contrast, in the SD scenario, this negative impact will be substantially offset, water scarcity will be alleviated, and food production will increase by 1.05 million tons. In terms of drivers, the anthropogenic drivers will moderate the future urbanization of Xinjiang to some extent, with natural drivers dominating the sustainable development scenario by 2030 and a potential 22 % increase in the drivers of precipitation. This study shows how spatial optimization can help protect the sustainability of the FWLE nexus in drylands and simultaneously provides clear policy recommendations for regional development.

Atmospheric dryness thresholds of grassland productivity decline in China.

Atmospheric dryness events are bound to have a broad and profound impact on the functions and structures of grassland ecosystems. Current research has confirmed that atmospheric dryness is a key moisture constraint that inhibits grassland productivity, yet the risk threshold for atmospheric dryness to initiate ecosystem productivity loss has not been explored. Based on this, we used four terrestrial ecosystem models to simulate gross primary productivity (GPP) data, analyzed the role of vapor pressure deficit (VPD) in regulating interannual variability in Chinese grasslands by focusing on the dependence structure of VPD and GPP, and then constructed a bivariate linkage function to calculate the conditional probability of ecosystem GPP loss under atmospheric dryness, and further analyzed the risk threshold of ecosystem GPP loss triggered by atmospheric dryness. The main results are as follows: we found that (1) the observed and modeled VPD of Chinese grasslands increases rapidly in both historical and future periods. VPD has a strongly negative regulation on ecosystem GPP, and atmospheric dryness is an important moisture constraint that causes deficit and even death to ecosystem GPP. (2) The probability of the enhanced atmospheric dryness that induced GPP decline in Chinese grasslands in the future period increases significantly. (3) When the VPD is higher than 40.07 and 27.65 percentile of the past and future time series, respectively, the risk threshold of slight ecosystem GPP loss can be easily initiated by atmospheric dryness. (4) When the VPD is higher than 82.57 and 65.09 percentile, respectively, the threshold of moderate ecosystem GPP loss can be exceeded by the benchmark probability. (5) The risk threshold of severe ecosystem GPP loss is not initiated by atmospheric dryness in the historical period, and the threshold of severe ecosystem GPP loss can be initiated when the future VPD is higher than 91.92 percentile. In total, a slight atmospheric dryness event is required to initiate a slight ecosystem GPP loss threshold, and a stronger atmospheric dryness event is required to initiate a severe ecosystem GPP loss. Our study enhances the understandings of past and future atmospheric dryness on grassland ecosystems, and strongly suggests that more attention be invested in improving next-generation models of vegetation dynamics processes with respect to the response of mechanisms of ecosystem to atmospheric dryness.

Spatiotemporal variability characteristics of extreme climate events in Xinjiang during 1960-2019.

Under the global warming, it is particularly important to explore the response of extreme climate to global climate change over the arid regions. Based on daily temperature (maximum, minimum, and average) and precipitation data from meteorological stations in Xinjiang, China, we analyzed the spatiotemporal characteristics of extreme temperature and extreme precipitation events via combining thin plate smoothing spline function interpolation, Sen's slope, and Mann-Kendall test. Our results showed that during 1960-2019, the extreme low temperature index of frost days (FD), icing days (ID), cold days (TX10p), cold nights (TN10p), and cold speel duration index (CSDI) all showed the downward trend to varying degrees, and the extreme high temperature index of summer days (SD25), warm days (TX90p), warm night (TN90p), and warm speel duration index (WSDI) all showed an upward trend to varying degrees, and the extreme low temperature index of high altitude mountains decreases more than that of the basin and plains. In addition, all the extreme temperature indices are closely related to the annual average temperature in Xinjiang (R > 0.6). Among the extreme precipitation indices, except for the consecutive dry days (CDD), the other extreme precipitation indices showed increasing trends to different degrees, but the changes in extreme precipitation in Xinjiang were mainly manifested by the increase of heavy precipitation in a short period (the increase of heavy precipitation and extreme heavy precipitation was the largest, 44.8 mm/10a and 17.6 mm/10a, respectively) and spatially concentrated in the Ili River and Altai Mountains in northern Xinjiang. Meanwhile, annual precipitation was positively correlated with the extreme precipitation index (R > 0.4), except for the CDD. This study provides theoretical support for the prevention and control of natural disasters in the dry zone.

Satellite greenness and solar-induced chlorophyll fluorescence reveal reverse desertification in Gurbantunggut Desert.

The desertification reversal is a process of revegetation and natural restoration in fragile dryland areas due to human activities and climate change mediation. Understanding the impact of desertification reversion on terrestrial ecosystems, including vegetation greenness and photosynthetic capacity, is crucial for land policy-making and carbon-cycle model improvement. However, the phenomenon of desertification reversal is rarely mentioned in previous studies, which dramatically limits the understanding of vegetation dynamics in the arid area. Therefore, it is of great necessity to investigate the status of desertification reversal on the ecosystem in arid areas. In this study, we first reported the phenomenon of desertification reversion over the southern edge of the Gurbantunggut Desert through the Moderate-resolution Imaging Spectroradiometer classification map year by year. We discussed the consequences, ways, and causes of desertification reversion. Our results showed that the desertification reversal significantly increased vegetation greenness and photosynthetic capacity, which largely offset the negative impact of desertification on the ecosystem productivity; cropland expansion and grassland's natural restoration were the two main ways of desertification reversal; the improvement of soil-water condition was an essential environmental factor leading to the phenomenon of reverse desertification. This finding highlights the importance of desertification reversal in the carbon cycle of dryland ecosystems and prove that desertification reversal is an integral part of global and dryland vegetation greening.

The clinical application of flexible bronchoscopy in a neonatal intensive care unit.

Objective: Flexible bronchoscopy is widely used in infants and it plays a crucial role. The aim of this study was to investigate the value and clinical safety of flexible bronchoscopy in a neonatal intensive care unit. Methods: A retrospective analysis was performed on the clinical data of 116 neonates who underwent flexible bronchoscopy and the outcomes of 147 procedures. A correlation analysis was performed on the relationship between flexible bronchoscopy findings, microscopic indications, and clinical disease. Results: The 147 procedures performed were due to the following reasons: problems related to artificial airways, 58 cases (39.45%); upper respiratory problems, 60 cases (40.81%) (recurrent dyspnea, 23 cases; upper airway obstruction, 17 cases; recurrent stridor, 14 cases; and hoarseness, six cases), lower respiratory problems, 51 cases (34.69%) (persistent pneumonia, 21 cases; suspicious airway anatomical disease, 21 cases; recurrent atelectasis, eight cases; and pneumorrhagia, one case), feeding difficulty three cases (2.04%). The 147 endoscopic examinations were performed for the following reasons: pathological changes, 141 cases (95.92%); laryngomalacia, 78 cases (53.06%); mucosal inflammation/secretions, 64 cases (43.54%); vocal cord paralysis, 29 cases (19.72%); trachea/bronchus stenosis, 17 cases (11.56%) [five cases of congenital annular constriction of the trachea, seven cases of left main tracheal stenosis, one case of the right middle bronchial stenosis, two cases of tracheal compression, and two cases of congenital tracheal stenosis]; subglottic lesions, 15 cases (10.20%) [eight cases of subglottic granulation tissue, six cases of subglottic stenosis, one cases of subglottic hemangioma]; tracheomalacia, 14 cases (9.52%); laryngeal edema, five cases (3.40%); tracheoesophageal fistula, four cases (2.72%); rhinostenosis, three cases (2.04%); tracheal bronchus, three cases (2.04%); glossoptosis, two cases (1.36%); laryngeal cyst, two cases (1.36%); laryngeal cleft, two cases (1.36%); tongue base cysts, one case (0.68%); and pneumorrhagia, one case (0.68%). Complications were rare and mild. Conclusion: Flexible bronchoscopy is safe and effective for diagnosing and differentiating neonatal respiratory disorders in neonatal intensive care units.

Systematic analysis of prognostic and immunologic characteristics associated with coronavirus disease 2019 regulators in acute myeloid leukemia.

The coronavirus disease 2019 (COVID-19) pandemic has so far damaged the health of millions and has made the treatment of cancer patients more complicated, and so did acute myeloid leukemia (AML). The current problem is the lack of understanding of their interactions and suggestions of evidence-based guidelines or historical experience for the treatment of such patients. Here, we first identified the COVID-19-related differentially expressed genes (C-DEGs) in AML patients by analyzing RNA-seq from public databases and explored their enrichment pathways and candidate drugs. A total of 76 C-DEGs associated with the progress of AML and COVID-19 infection were ultimately identified, and the functional analysis suggested that there are some shared links between them. Their protein-protein interactions (PPIs) and protein-drug interactions were then recognized by multiple bioinformatics algorithms. Moreover, a COVID-19 gene-associated prognostic model (C-GPM) with riskScore was constructed, patients with a high riskScore had poor survival and apparently immune-activated phenotypes, such as stronger monocyte and neutrophil cell infiltrations and higher immunosuppressants targeting expressions, meaning which may be one of the common denominators between COVID-19 and AML and the reason what complicates the treatment of the latter. Among the study's drawbacks is that these results relied heavily on publicly available datasets rather than being clinically confirmed. Yet, these findings visualized those C-DEGs' enrichment pathways and inner associations, and the C-GPM based on them could accurately predict survival outcomes in AML patients, which will be helpful for further optimizing therapies for AML patients with COVID-19 infections.

Remodeling "cold" tumor immune microenvironment via epigenetic-based therapy using targeted liposomes with in situ formed albumin corona.

There is a close connection between epigenetic regulation, cancer metabolism, and immunology. The combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer management. As an epigenetic regulator of histone acetylation, panobinostat can induce histone acetylation and inhibit tumor cell proliferation, as well as regulate aerobic glycolysis and reprogram intratumoral immune cells. JQ1 is a BRD4 inhibitor that can suppress PD-L1 expression. Herein, we proposed a chemo-free, epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer. A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 receptor. It was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin corona. The lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells (e.g., tumor-associated macrophages). The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune normalization. Consequently, lactic acid production was reduced and angiogenesis inhibited; TAM switched to an anti-tumor phenotype, and the anti-tumor function of the effector CD8+ T cells was reinforced. The strategy provides a potential method for remodeling the tumor immune microenvironment (TIME).

Representation of Leaf-to-Canopy Radiative Transfer Processes Improves Simulation of Far-Red Solar-Induced Chlorophyll Fluorescence in the Community Land Model Version 5.

Recent advances in satellite observations of solar-induced chlorophyll fluorescence (SIF) provide a new opportunity to constrain the simulation of terrestrial gross primary productivity (GPP). Accurate representation of the processes driving SIF emission and its radiative transfer to remote sensing sensors is an essential prerequisite for data assimilation. Recently, SIF simulations have been incorporated into several land surface models, but the scaling of SIF from leaf-level to canopy-level is usually not well-represented. Here, we incorporate the simulation of far-red SIF observed at nadir into the Community Land Model version 5 (CLM5). Leaf-level fluorescence yield was simulated by a parametric simplification of the Soil Canopy-Observation of Photosynthesis and Energy fluxes model (SCOPE). And an efficient and accurate method based on escape probability is developed to scale SIF from leaf-level to top-of-canopy while taking clumping and the radiative transfer processes into account. SIF simulated by CLM5 and SCOPE agreed well at sites except one in needleleaf forest (R 2 > 0.91, root-mean-square error <0.19 W⋅m-2⋅sr-1⋅µm-1), and captured the day-to-day variation of tower-measured SIF at temperate forest sites (R 2 > 0.68). At the global scale, simulated SIF generally captured the spatial and seasonal patterns of satellite-observed SIF. Factors including the fluorescence emission model, clumping, bidirectional effect, and leaf optical properties had considerable impacts on SIF simulation, and the discrepancies between simulate d and observed SIF varied with plant functional type. By improving the representation of radiative transfer for SIF simulation, our model allows better comparisons between simulated and observed SIF toward constraining GPP simulations.

Amazonian terrestrial water balance inferred from satellite-observed water vapor isotopes.

Atmospheric humidity and soil moisture in the Amazon forest are tightly coupled to the region's water balance, or the difference between two moisture fluxes, evapotranspiration minus precipitation (ET-P). However, large and poorly characterized uncertainties in both fluxes, and in their difference, make it challenging to evaluate spatiotemporal variations of water balance and its dependence on ET or P. Here, we show that satellite observations of the HDO/H2O ratio of water vapor are sensitive to spatiotemporal variations of ET-P over the Amazon. When calibrated by basin-scale and mass-balance estimates of ET-P derived from terrestrial water storage and river discharge measurements, the isotopic data demonstrate that rainfall controls wet Amazon water balance variability, but ET becomes important in regulating water balance and its variability in the dry Amazon. Changes in the drivers of ET, such as above ground biomass, could therefore have a larger impact on soil moisture and humidity in the dry (southern and eastern) Amazon relative to the wet Amazon.

Lipid Metabolism Regulation Based on Nanotechnology for Enhancement of Tumor Immunity.

The hallmarks of cancer include dysregulated metabolism and immune evasion. As a basic way of metabolism, lipid metabolism is reprogrammed for the rapid energy and nutrient supply in the occurrence and development of tumors. Lipid metabolism alterations that occur in the tumor microenvironment (TME) affect the antitumor responses of immune cells and cause immune evasion. Therefore, targeting lipid metabolism in the TME for enhancing the antitumor effect of immune cells is a promising direction for cancer treatment. Cancer nanomedicine has great potential in regulating tumor metabolism and tumor immunity. This review summarizes the nanotechnology-based strategies for lipid metabolism regulation in the TME for enhanced anticancer immune responses.

Inhaled heparin polysaccharide nanodecoy against SARS-CoV-2 and variants.

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.

Quantifying Northern High Latitude Gross Primary Productivity (GPP) Using Carbonyl Sulfide (OCS).

The northern high latitude (NHL, 40°N to 90°N) is where the second peak region of gross primary productivity (GPP) other than the tropics. The summer NHL GPP is about 80% of the tropical peak, but both regions are still highly uncertain (Norton et al. 2019, https://doi.org/10.5194/bg-16-3069-2019). Carbonyl sulfide (OCS) provides an important proxy for photosynthetic carbon uptake. Here we optimize the OCS plant uptake fluxes across the NHL by fitting atmospheric concentration simulation with the GEOS-CHEM global transport model to the aircraft profiles acquired over Alaska during NASA's Carbon in Arctic Reservoirs Vulnerability Experiment (2012-2015). We use the empirical biome-specific linear relationship between OCS plant uptake flux and GPP to derive the six plant uptake OCS fluxes from different GPP data. Such GPP-based fluxes are used to drive the concentration simulations. We evaluate the simulations against the independent observations at two ground sites of Alaska. The optimized OCS fluxes suggest the NHL plant uptake OCS flux of -247 Gg S year-1, about 25% stronger than the ensemble mean of the six GPP-based OCS fluxes. GPP-based OCS fluxes systematically underestimate the peak growing season across the NHL, while a subset of models predict early start of season in Alaska, consistent with previous studies of net ecosystem exchange. The OCS optimized GPP of 34 PgC yr-1 for NHL is also about 25% more than the ensembles mean from six GPP data. Further work is needed to fully understand the environmental and biotic drivers and quantify their rate of photosynthetic carbon uptake in Arctic ecosystems.

Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles.

The spread of coronavirus disease 2019 (COVID-19) throughout the world has resulted in stressful healthcare burdens and global health crises. Developing an effective measure to protect people from infection is an urgent need. The blockage of interaction between angiotensin-converting enzyme 2 (ACE2) and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs. A full-length ACE2 protein could be a potential drug to block early entry of SARS-CoV-2 into host cells. In this study, a therapeutic strategy was developed by using extracellular vesicles (EVs) with decoy receptor ACE2 for neutralization of SARS-CoV-2. The EVs embedded with engineered ACE2 (EVs-ACE2) were prepared; the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression. The potential effect of the EVs-ACE2 on anti-SARS-CoV-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein (S-pseudovirus). EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells, and importantly, the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium. Therefore, the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-CoV-2 infection. This EVs-based strategy offers a potential route to COVID-19 drug development.

Association between the RETN -420C/G polymorphism and type 2 diabetes mellitus susceptibility: A meta-analysis of 23 studies.

Background: The published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research. Methods: PubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0. Results: A total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87-1.10, pheterogeneity <.001; I 2 = 84.6%; for the dominant model: OR = 0.96, 95% CI = 0.80-1.15, pheterogeneity <.001; I 2 = 87.1%; and for the recessive model: OR = 0.96, 95% CI = 0.82-1.12, pheterogeneity <.001; I 2 = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; pheterogeneity <.001; I 2 = 80.9%)] and decreased risk in older people [for dominant: OR = 3.14 (95% CI, 2.35-4.19; pheterogeneity = .98; I 2 = 0.0%)]. Conclusions: Current results found no evidence that the RETN -420C/G variant was linked to T2DM susceptibility, but the patient's age appears to be a potential factor that contributed to high heterogeneity across studies. Additional high-quality and well-designed investigations are required to confirm these results.

Diversity of RNA viruses of three dominant tick species in North China.

Background: A wide range of bacterial pathogens have been identified in ticks, yet the diversity of viruses in ticks is largely unexplored. Methods: Here, we used metagenomic sequencing to characterize the diverse viromes in three principal tick species associated with pathogens, Haemaphysalis concinna, Dermacentor silvarum, and Ixodes persulcatus, in North China. Results: A total of 28 RNA viruses were identified and belonged to more than 12 viral families, including single-stranded positive-sense RNA viruses (Flaviviridae, Picornaviridae, Luteoviridae, Solemoviridae, and Tetraviridae), negative-sense RNA viruses (Mononegavirales, Bunyavirales, and others) and double-stranded RNA viruses (Totiviridae and Partitiviridae). Of these, Dermacentor pestivirus-likevirus, Chimay-like rhabdovirus, taiga tick nigecruvirus, and Mukawa virus are presented as novel viral species, while Nuomin virus, Scapularis ixovirus, Sara tick-borne phlebovirus, Tacheng uukuvirus, and Beiji orthonairovirus had been established as human pathogens with undetermined natural circulation and pathogenicity. Other viruses include Norway mononegavirus 1, Jilin partitivirus, tick-borne tetravirus, Pico-like virus, Luteo-like virus 2, Luteo-likevirus 3, Vovk virus, Levivirus, Toti-like virus, and Solemo-like virus as well as others with unknown pathogenicity to humans and wild animals. Conclusion: In conclusion, extensive virus diversity frequently occurs in Mononegavirales and Bunyavirales among the three tick species. Comparatively, I. persulcatus ticks had been demonstrated as such a kind of host with a significantly higher diversity of viral species than those of H. concinna and D. silvarum ticks. Our analysis supported that ticks are reservoirs for a wide range of viruses and suggested that the discovery and characterization of tick-borne viruses would have implications for viral taxonomy and provide insights into tick-transmitted viral zoonotic diseases.

Construction and validation of a metabolic gene-associated prognostic model for cervical carcinoma and the role on tumor microenvironment and immunity.

Metabolic reprogramming is a common feature of tumor cells and is associated with tumorigenesis and progression. In this study, a metabolic gene-associated prognostic model (MGPM) was constructed using multiple bioinformatics analysis methods in cervical carcinoma (CC) tissues from The Cancer Genome Atlas (TCGA) database, which comprised fifteen differentially expressed metabolic genes (DEMGs). Patients were divided into a high-risk group with shorter overall survival (OS) and a low-risk group with better survival. Receiver operating characteristic (ROC) curve analysis showed that the MGPM precisely predicted the 1-, 3- and 5-year survival of CC patients. As expected, MGPM exhibited a favorable prognostic significance in the training and testing datasets of TCGA. And the clinicopathological parameters including stage, tumor (T) and metastasis (M) classifications had significant differences in low- and high-risk groups, which further demonstrated the MGPM had a favorite prognostic prediction ability. Additionally, patients with low-ESTMATEScore had a shorter OS and when those combined with high-risk scores presented a worse prognosis. Through "CIBERSORT" package and Wilcoxon rank-sum test, patients in the high-risk group with a poor prognosis showed lower levels of infiltration of T cell CD8 (P < 0.001), T cells memory activated (P = 0.010) and mast cells resting (P < 0.001), and higher levels of mast cells activated (P < 0.001), and we also found these patients had a worse response for immunosuppressive therapy. These findings demonstrate that MGPM accurately predicts survival outcomes in CC patients, which will be helpful for further optimizing immunotherapies for cancer by reprogramming its cell metabolism.

Bisphenol F promotes the secretion of pro-inflammatory cytokines in macrophages by enhanced glycolysis through PI3K-AKT signaling pathway.

Bisphenol F (BPF) is a member of endocrine disrupting chemicals (EDCs). As a substitute of bisphenol A (BPA), BPF is widely used in various consumer products, leading to an increased risk of people's exposure. However, there are few studies on the immunotoxicity and mechanism of BPF. This study aimed to investigate the effect of BPF on the secretion of pro-inflammatory cytokines by macrophages and explore its mechanism. In our study, RAW264.7 macrophages were treated with different concentrations of BPF (0, 5, 10 and 20 µM) for 24 h. The results showed that the secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1ß) and the production of lactate were increased in a dose-dependent manner. BPFalso led to the activation of the PI3K-AKT signaling pathway. After pretreatment with glycolysis inhibitor (2-DG) and exposure to BPF (20 µM), the secretion of pro-inflammatory cytokines induced by BPF was inhibited. PI3K inhibitor (LY294002) and estrogen receptor (ER) antagonist (ICI 182,780) could also inhibit the above effects induced by BPF (20 µM). In conclusion, our results suggested that BPF can enhance glycolysis through ER mediated PI3K-AKT signaling pathway, and the enhanced glycolysis further promoted the secretion of pro-inflammatory cytokines. Our research provides basic data for future studies on bisphenol exposure and immunotoxicity.