Pseudomonas aeruginosa outer membrane vesicle-packed sRNAs can enter host cells and regulate innate immune responses.

Bacterial outer membrane vesicles (OMVs) can package and deliver virulence factors into host cells, which is an important mechanism mediating host-pathogen interactions. It has been reported that small RNAs (sRNAs) can be packed into OMVs with varying relative abundance, which might affect the function and/or stability of host mRNAs. In this study, we used OptiPrep density gradient ultra-high-speed centrifugation to purify OMVs from Pseudomonas aeruginosa. Next, the sequences and abundance of sRNAs were detected by using Small RNA-Seq. In particular, sRNA4518698, sRNA2316613 and sRNA809738 were the three most abundant sRNAs in OMVs, which are all fragments of P. aeruginosa non-coding RNAs. sRNAs were shielded within the interior of OMVs and remained resistant to external RNase cleavage. The miRanda and RNAhybrid analysis demonstrated that those sRNAs could target a large number of host mRNAs, which were enriched in host immune responses by the functions of GO and KEGG enrichment. Experimentally, we demonstrated that the transfection of synthetic sRNA4518698, sRNA2316613, or sRNA809738 could reduce the expression of innate immune response genes in RAW264.7 cells. Together, we demonstrated that P. aeruginosa OMVs sRNAs can regulate innate immune responses. This study uncovered a mechanism in which the OMVs regulate host responses by transferring bacterial sRNAs.

Effects of season and slope orientation on stable isotopes of different water bodies in the subalpine shrub zone of the eastern Qilian Mountains in China.

The subalpine shrub zone of the Qilian Mountains is an important water-retaining area, and it is crucial to clarify the processes of its hydrological cycle. Therefore, based on the stable isotope values of different water bodies in the subalpine shrub zone of the eastern Qilian Mountains from May to October 2019, the characteristics of δD and δ18O of different water bodies and their hydraulic relationships with each other were studied. The results showed that the stable isotope values of precipitation exhibited the largest fluctuations, while they were the most stable for groundwater. Plant transpiration was stronger than the evaporation of other water bodies. The stable isotope of precipitation was enriched in high temperature and low humidity environments. Isotopic values of plant and soil water were higher and more stable on the semi-sunny slope than on the semi-shady slope. According to the stable isotopes, there was a strong hydraulic relationship between the different water bodies in the study area, and precipitation was the ultimate source of all of them. Precipitation replenished soil water through infiltration. Part of the soil water was absorbed by plants, while the rest continued to infiltrate to replenish groundwater. Groundwater and precipitation replenished the river water.

Colony composition and nutrient analysis of Polyrhachis dives ants, a natural prey of the Chinese pangolin (Manis pentadactyla).

The Chinese pangolin (Manis pentadactyla) is a critically endangered mammal with a highly specialized diet. To enhance nutritional knowledge of its diet, we analyzed the colony composition of a nest of Polyrhachis dives ants, which is the key natural prey in the Chinese pangolin's diet. In addition, we determined the nutrient composition of the total colony compared with adult ants. Nutrients quantified in this study included: crude protein, crude fat, carbohydrate, and amino acids, minerals, and vitamins, as well as formic acid and chitin, which have not been reported in previous diet studies. Our results showed that the colony consisted of adults (82%), pupae (10%), larvae (7%), and eggs (1%) (fresh mass). Both the total colony and adult ants, respectively, contained high concentrations of crude protein (62.97% and 64.68%), chitin (49.25% and 60.40%), crude fat (10.12% and 9.91%) (dry matter basis), and formic acid (2.06% and 3.07%) (fresh mass). This implies that Chinese pangolin might prefer prey with high protein, high chitin, low fat, and low formic acid content. Colony and adult ants differed in chemical composition in many aspects, thus it might be unsuitable to feed Chinese pangolin with only adult ants. Chitin and formic acid may play important roles in the diet and selectivity of Chinese pangolin. This study provides reference information that may be useful for developing better artificial diets with more comprehensive nutrient compositional data to meet the nutritional requirements of the Chinese pangolin under managed feeding programs.

Prevalence and associated risk factors of Helicobacter pylori infection in the Wuwei cohort of north-western China.

OBJECTIVES: To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer. METHODS: Helicobacter pylori infection was analysed in 21 291 adults by 14 C-urea breath test, and H. pylori antibody were detected in 9183 serum samples by latex immunoturbidimetric method. The correlation of H. pylori infection with demographic-economic, lifestyle factors and medical history among the participants was determined by questionnaire. The antibodies against H. pylori urease, VacA and CagA in serum were determined by dot immunobinding assay. RESULTS: The infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P < 0.05). CONCLUSION: The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.

OBJECTIFS: Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée au 14 C, et des anticorps à H. pylori ont été détectés dans 9.183 échantillons de sérum par une méthode immuno-turbidimétrique au latex. La corrélation entre l'infection à H. pylori et les facteurs démographiques et économiques, le mode de vie et les antécédents médicaux des participants a été déterminée par un questionnaire. Les anticorps contre l'uréase de H. pylori, VacA et CagA dans le sérum ont été déterminés par un test dot par d'immuno-liaison. RÉSULTATS: Le taux d'infection à H. pylori était 53,0% et 90,1% des souches étaient du type I. Le taux d'infection à H. pylori est plus élevé chez les agriculteurs (OR = 1,34 ; IC95%: 1,19 à 1,50) et les personnes qui avaient un niveau d'instruction du premier cycle secondaire ou supérieur (OR = 1,10 ; IC95%: 01,06 à 01,15) et était plus faible chez les personnes âgées (OR = 0,86 ; IC95%: 0,83-0,90), les personnes à revenu élevé (OR = 0,93 ; IC95%: 0,90-0,95), les personnes ayant l'habitude de manger rapidement (OR = 0,93 ; IC9 %: 0,87-0,99) et les individus qui consommaient plus de fruits et de légumes (OR = 0,90 ; IC95%: 0,85-0,95). Les personnes ayant des antécédents de cholécystite/cholécystolithiase, d'hypertension et d'asthme avaient une corrélation négative avec l'infection à H. pylori (p <0,05 ). CONCLUSION: La prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

Prevalence and risk factors of Helicobacter pylori infection in Wuwei, a high-risk area for gastric cancer in northwest China: An all-ages population-based cross-sectional study.

OBJECTIVE: This study aimed to determine the prevalence and risk factors of Helicobacter pylori infection across all age groups in Wuwei City, a high-risk area for gastric cancer in Northwest China. METHODS: We conducted this study from 2016 to 2017 in an urban and a rural community in Wuwei City. Stool antigen tests targeted individuals aged 0 to 3 years old, and 13 C-urea breath tests targeted individuals aged above 3 years. We selected participants based on hierarchical cluster sampling. We assessed the association between variables and H. pylori infection based on logistic regression models. RESULTS: Ultimately, the results of 2,163 participants (age: 0 to 77 years old) were included (1,238 minors and 925 adults) in the analysis. The overall prevalence of H. pylori infection was 35.6%. It increased with age, reaching the peak in the 30 to 39 age group, and then began to decline. In multivariate analysis, age was positively associated with prevalence of H. pylori infection, and factors negatively associated with the prevalence were drinking running water, the frequency of yoghurt consumption, and an annual household income of Renminbi (¥) 30,000-100,000 or 100,000 above. In the subgroup analyses, however, the same variables associated differently in different age groups. Additionally, we interestingly noticed that boarding, eating at school cafeterias over six times per week, and frequently drinking untreated water were independent predictors of H. pylori infection in junior and senior high school students. CONCLUSION: The prevalence of H. pylori infection is moderate and closely associated with the socioeconomic conditions of Wuwei City, as well as the sanitary situations and dietary habits of the participants in the city. Boarding, eating at school, and drinking untreated water are the main factors explaining the rising infection rate in junior-senior high school students.

Reproductive behavior of the captive Sunda pangolin (Manis javanica Desmarest, 1822).

Understanding reproductive behavior is important for the conservation of endangered species, but research on the reproductive behavior of Sunda pangolins (Manis javanica Desmarest, 1822) is still very scarce. In this study, we used focal animal sampling and all-occurrence recording by an infrared monitor to observe the behaviors of two Sunda pangolins during a 5-day breeding period at the Pangolin Research Base for Artificial Rescue and Conservation Breeding of South China Normal University (PRB-SCNU). The behavioral characteristics and breeding strategies were analyzed, and the results were discussed together with information on other captive Sunda pangolin pairs at PRB-SCNU. The results found that there was no obvious estrus behavior in the captive female, while the male could exhibit sexual excitement and courtship behavior after a brief introduction period. Repeated copulation continued over many days after the female accepted the courtship. The average duration of copulatory behavior was 248.9 ± 148.7 s (n = 25), and all copulation occurred between 20:00 and 08:00 hr in the natural day-night photoperiod. The mating position of Sunda pangolins was lateral-ventral and was classified as the ninth or eleventh pattern under both Dewsbury's and Dixson's classification systems. This study can provide scientific guidance for the captive breeding and management of Sunda pangolins and other pangolin species, which is of great significance for ex situ conservation tactics.

CD64 Expression on Polymorph Nuclear Cells as a Sensitive and Specific Diagnostic Biomarker for Neonate Pneumonia.

BACKGROUND: Neonatal pneumonia (NP) is one of the major causes of neonatal death. Current NP diagnosis depends on a detailed history, physical examination, and radiographic and laboratory findings. There is no specific biomarker or diagnostic indicator of NP. METHODS: In this study, we tried to find a reliable biomarker for quick NP diagnosis by collecting peripheral blood from neonates with NP and transient tachypnea of the newborn (TTN), and subsequently tested the expression of CD64 on white blood cells using flow cytometry. The cellularity of each blood cell population was also quantified. Furthermore, procalcitonin (PCT) and C-reactive protein (CRP) levels were evaluated in the blood sera. RESULTS: We found that NP patients had moderately increased polymorphonuclear cells (PMNs), as well as elevated PCT and CRP levels in the blood sera. Importantly, the expression of CD64 on PMNs was profoundly increased in NP patients but not TTN patients. The receiver operating characteristic (ROC) curve of PMN CD64 index suggests that PMN CD64 index is sensitive and specific for NP diagnosis. CONCLUSIONS: Our study reveals that PMN CD64 could be a fast and reliable biomarker for NP diagnosis.

The Wnt/ß-catenin signaling pathway affects the distribution of cytoskeletal proteins in Aß treated PC12 cells.

Alzheimer's disease is pathologically characterized by the presence of senile plaques and neurofibrillary tangles in the central nervous system. Amyloid ß-protein is toxic to neurons and induces phosphorylation of Tau protein, which accumulates in paired helical filaments and leads to the formation of neurofibrillary tangles. This study is focused on the Wnt/ß-catenin pathway influence on Tau phosphorylation and the distribution of microtubules and neurofilaments in adrenal pheochromocytoma cells. It was found that neurofilament heavy polypeptide and microtubule-associated protein-2 aggregated after treatment with Aß1₋42. Treatment with Wnt5a reduced this aggregation, while Dickkopf-1 treatment promoted microtubule and neurofilament aggregation. Furthermore, Tau phosphorylation at Ser396, Ser422, and Ser199 was significantly reduced after Wnt5a treatment, whereas Dickkopf-1 increased the level of phosphorylation. These results suggest that the Wnt/ß-catenin pathway influences the distribution of microtubules and neurofilaments, possibly by modulating the phosphorylation of Tau protein in adrenal pheochromocytoma cells.

The -250G/A and -514C/T Polymorphisms in Hepatic Lipase Gene Promoter Confers an Increased Risk of Hepatocellular Carcinoma in a Chinese Population.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is a lethal malignancy, but the molecular mechanisms of hepatocarcinogenesis remain undefined. The present study aims to investigate the relationship between polymorphisms of the hepatic lipase (HL) gene promoters and risk of HCC. MATERIAL AND METHODS: Totally, 279 HCC patients and 200 healthy individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) was used to analyze the genotypes of HL gene. Logistic regression analysis was conducted to identify risk factors of HCC. RESULTS: There was significant difference in the distribution of smoking history, drinking history, and family history of subjects between the case and control groups (all p < 0.05). Difference in the -250G/A (p = 0.011; OR = 1.61; 95%CI: 1.11-2.34) and -514C/T (p = 0.007; OR = 1.65; 95%CI: 1.14-2.38) genotypes and allele frequencies between two groups was significant. A higher risk of HCC was identified in those with polymorphisms in the - 250G/A (p = 0.007; OR = 1.45; 95%CI: 1.11-1.89) and -514C/T (p = 0.003; OR = 1.51; 95%CI: 1.15-2.00). Polymorphisms at - 250G/A (GA + AA) (p = 0.025; OR = 1.55; 95%CI: 1.06-2.28), -514C/T (CT + TT) (p = 0.021; OR = 1.57; 95%CI: 1.07-2.29), smoking history (p = 0.017; OR = 1.70; 95%CI: 1.10-2.63) and drinking history (p = 0.003; OR = 2.04; 95%CI: 1.27-3.27) were significantly related to the risk of HCC (all p < 0.05). CONCLUSION: The results obtained from this study indicated that polymorphisms of -250G/A and -514C/T in HL gene promoters were associated with the risk of HCC.

Immune response- and viral control-related pathways in the progression of chronic hepatitis B.

BACKGROUND: Chronic hepatitis B (CHB) is a complicated and dynamic course, and is associated with advanced liver disease. Host immune response against viral infection plays a pivotal role in the progression of CHB. However, it is still uncharted that how the hepatic transcriptomes in patients with CHB are correlated with the clinical phases. OBJECTIVE: This study aimed to identify the specific sub-networks across various phases of CHB and infer potential pathways for phenotypic outcome prediction. METHODS: In this study, we performed the pairwise comparisons of the hepatic transcriptomes of CHB patients under different phases, and constructed the differential co-expression networks (DCNs). We firstly identified the critical genes from each DCN according to the adjacency matrix of the network. Then, the specific sub-networks were digged by iteratively affiliating genes that can increase the classification accuracy, using a snow-ball sampling strategy. Permutation test was implemented to determine the statistical significance of these sub-networks. Finally, each sub-network was given a most significant functional pathway. RESULTS: We constructed 3 DCNs by pairwise comparing the hepatic transcriptomes among three CHB phases, and systemically tracked 1, 1 and 2 specific sub-networks and pathways, respectively. Relative to immune tolerant phase, TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) pathway was significantly changed in the immune clearance phase, and nuclear receptor transcription pathway and adenylate cyclase activating pathway were altered in inactive carrier state. The host genes related to DNA strand elongation showed significant difference between the immune clearance phase and inactive carrier state. CONCLUSIONS: By pairwise comparing the hepatic transcriptomes of CHB patients under a network view, several immune- and viral control-related pathways were identified in this study. These results might serve as a foundation for characterizing the host transcriptomes responded to CHB infection, and hold clues for the development of potential targets for disease control.

Highly efficient one-step synthesis of carbon encapsulated nanocrystals by the oxidation of metal π-complexes.

Various carbon encapsulated nanocrystals, including MnS and MnO, Cr2O3, MoO2, Fe7S8 and Fe3O4, and ZrO2, are prepared in one step and in situ by a simple and highly efficient synthesis approach. The nanocrystals have an equiaxed morphology and a median size smaller than 30 nm. Tens and hundreds of these nanocrystals are entirely encapsulated by a wormlike amorphous carbon shell. The formation of a core-shell structure depends on the strongly exothermic reaction of metal π-complexes with ammonium persulfate in an autoclave at below 200 °C. During the oxidation process, the generated significant amounts of heat will destroy the molecular structure of the metal π-complex and cleave the ligands into small carbon fragments, which further transform into an amorphous carbon shell. The central metal atoms are oxidized to metal oxide/sulfide nanocrystals. The formation of a core-shell structure is independent of the numbers of ligands and carbon atoms as well as the metal types, implying that any metal π-complex can serve as a precursor and that various carbon encapsulated nanocrystals can be synthesized by this method.

Keeping and breeding the rescued Sunda pangolins (Manis javanica) in captivity.

The Sunda pangolin (Manis javanica Desmarest, 1822) is a Critically Endangered species. Given that this species lacks effective policies for in situ conservation and prevention of poaching in the wild, ex situ conservation and a captive breeding program are urgently needed to save this species from extinction. However, techniques for the maintenance and captive breeding of pangolins have not been well developed. In June 2010, we established the Pangolin Research Base for Artificial Rescue and Conservation Breeding of South China Normal University (PRB-SCNU). To date, a total of 34 Sunda pangolin cubs have been born at PRB-SCNU, 26 of which were captive bred, indicating great progress in keeping and breeding the Sunda pangolin. The techniques for maintenance-including housing, transitioning to an artificial diet, husbandry, and captive breeding-are described in this paper. The purpose of this manuscript is to share our successful experiences and techniques in the maintenance, management, and captive breeding of Sunda pangolins, and to provide guidance and a reference for the captive care and management of Sunda pangolins and other pangolin species.

Association between the IL1B -31C > T polymorphism and Helicobacter pylori infection in Asian and Latin American population: A meta-analysis.

BACKGROUND: Host genetic factors that control the production of cytokines, including interleukin-1ß (IL-1ß), possibly affect susceptibility to many Helicobacter pylori-related diseases. There is a complex interplay between H. pylori infection, the subsequent production of certain cytokines, and H. pylori-related diseases. We conducted a meta-analysis to clarify the association between the IL1B -31C > T polymorphism and H. pylori infection, and possible subsequent pathogenic mechanisms. METHODS: Published literature contained within PubMed, Embase, and the Cochrane Library was used in our meta-analysis. Data were analyzed with the STATA 13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Egger's regression test, Begg's rank correlation test, and Begg's funnel plot were used to test publication bias. RESULTS: A total of 12 case-control studies comprising 5827 subjects (3335 cases and 2492 controls) were available for our meta-analysis. The IL1B -31C > T polymorphism was associated with an increased risk of H. pylori infection in Asian and Latin American population (TT + CT vs. CC, OR = 1.29, 95% CI = 1.14-1.46; TT vs. CT + CC, OR = 1.23, 95% CI = 1.09-1.39; TT vs. CC, OR = 1.43, 95% CI = 1.22-1.67; T allele vs. C allele, OR = 1.19, 95% CI = 1.10-1.29). A significant association was also found for all genetic models in various subgroups (cancer and no-cancer, hospital- and population-based). CONCLUSION: Our meta-analysis demonstrated that IL1B -31C > T polymorphism might increase H. pylori infection risk in Asian and Latin American population. Further studies with different ethnicities and larger sample size are required to validate this result.

Clinical Features of Surgical Resection for Liver Metastasis from Extremity Soft Tissue Sarcoma.

BACKGROUND/AIMS: The aim of the present study was to define the prognostic factors for survival after hepatic metastasectomy from extremity soft tissue sarcoma. METHODOLOGY: Between January 2000 and January 2009, 27 patients with hepatic metastases from extremity soft tissue sarcomas underwent liver resection with radical intent. Various clinicopathologic variables were investigated retrospectively to identify possible prognostic factors for survival after hepatic metastasectomy. RESULTS: Overall survival was 46% and 24% at 5 and 10 years after liver resection, respectively. Disease-free survival was 13% at 1 year after hepatic metastasectomy. On multivariate analysis, disease-free interval longer than 24 months (P = 0.010), no tumor recurrence before hepatic metastasectomy (P = 0.040) and negative margin resection (P = 0.002) provided a significantly favorable overall survival. Repeated hepatic metastasectomy for recurrent hepatic metastases (P = 0.007) also provided a favorable overall survival. CONCLUSION: Hepatic metastasectomy for extremity soft tissue sarcoma can be associated with prolonged survival. Complete resection, longer disease-free interval, no tumor recurrence before liver resection and repeated resection for recurrent liver metastases are the most predictive factors for prolonged survival.

Antifungal agents for secondary prophylaxis based on response to initial antifungal therapy in allogeneic hematopoietic stem cell transplant recipients with prior pulmonary aspergillosis.

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation.

Motion-Aware Video Frame Interpolation.

Video frame interpolation methodologies endeavor to create novel frames betwixt extant ones, with the intent of augmenting the video's frame frequency. However, current methods are prone to image blurring and spurious artifacts in challenging scenarios involving occlusions and discontinuous motion. Moreover, they typically rely on optical flow estimation, which adds complexity to modeling and computational costs. To address these issues, we introduce a Motion-Aware Video Frame Interpolation (MA-VFI) network, which directly estimates intermediate optical flow from consecutive frames by introducing a novel hierarchical pyramid module. It not only extracts global semantic relationships and spatial details from input frames with different receptive fields, enabling the model to capture intricate motion patterns, but also effectively reduces the required computational cost and complexity. Subsequently, a cross-scale motion structure is presented to estimate and refine intermediate flow maps by the extracted features. This approach facilitates the interplay between input frame features and flow maps during the frame interpolation process and markedly heightens the precision of the intervening flow delineations. Finally, a discerningly fashioned loss centered around an intermediate flow is meticulously contrived, serving as a deft rudder to skillfully guide the prognostication of said intermediate flow, thereby substantially refining the precision of the intervening flow mappings. Experiments illustrate that MA-VFI surpasses several representative VFI methods across various datasets, and can enhance efficiency while maintaining commendable efficacy.

The competitive relationship of scrub plants for water use in the subalpine zone of the Qilian Mountains in China.

Samples of scrub plants and soil were collected from May to October 2019 in the subalpine scrub zone of the Qilian Mountains. Based on measured oxygen isotope values (δ18O) in plant xylem water and soil water, the multivariate linear mixed model (IsoSource) and the proportional similarity index (PS index) were used to analyze the using proportion for each potential water source and the competition relationship for water use of scrub plants in different growing periods and habitats. The results showed that the soil water content gradually decreased with increasing depth of the soil layer, with the maximum value in the soil layer of 0-10 cm. Most of the scrub plants mainly used soil water in the soil layer of 0-30 cm during the different periods of growing season, but Salix sclerophylla Anderss. and Salix oritrepha Schneid. on the semi-sunny slope habitat mainly used soil water in the soil layer of 40-80 cm during the middle period of growing season (July-August), with the proportion of 59.5% and 52.1%, respectively; and Potentilla fruticosa Linn. and Salix cupularis Rehd. on the semi-shady slope habitat mainly used soil water in the soil layer of 30-60 cm during the early period of growing season (May-June), with the proportion of 61.1% and 49.7%, respectively. The competition relationships of scrub plants for water use varied during different periods of growing season (P < 0.05). On the semi-sunny slope habitat, they were fiercest for Salix cupularis Rehd. and Rhododendron thymifolium Maxim., Potentilla fruticosa Linn., and Salix sclerophylla Anderss. during the early period of growing season; Salix cupularis Rehd. and Rhododendron thymifolium Maxim. during the middle period of growing season, and Salix sclerophylla Anderss. and Salix oritrepha Schneid. during the end period of growing season (September-October). On the semi-shady slope habitat, they were fiercest for Salix oritrepha Schneid. and Caragana jubata (Pall.) Poir. during the early period of growing season; Rhododendron przewalskii Maxim. and Rhododendron thymifolium Maxim. during the middle period of growing season; and Salix cupularis Rehd. and Salix oritrepha Schneid. during the end period of growing season. This study reveals the competitive relationship of scrub plants for water use in the subalpine zone and their response to environmental changes, so as to provide theoretical references for the ecological conservation in the ecologically fragile areas of the Qilian Mountains.

Salmonella T3SS-elicited inflammatory innate immune response inhibits type I IFN response in macrophages.

As a gram-negative intracellular bacterial pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium) invades different cell types including macrophages. Its infection in macrophages induces robust innate immune responses that are featured by proinflammatory and type I interferon (IFN) responses. The type III secretion systems (T3SSs) of S. Typhimurium play a crucial role in activating host inflammasome pathways. It has been recognized that the inflammasome pathways inhibit the type I IFN cascade. However, the potential role of T3SS in regulating the type I IFN response and the underlying mechanisms are largely unknown. In this study, we showed that S. Typhimurium infection activated strong proinflammatory, type I IFN and IFN-stimulated genes (ISGs) expression in macrophages. Furthermore, we showed that T3SS-defective S. Typhimurium mutant ΔinvC elicited attenuated inflammatory response but enhanced type I IFN and ISGs expression. Additionally, the inhibition of caspase-1 by a specific inhibitor VX-765 resulted in increased type I IFN response. Moreover, cell-permeable pan-caspase inhibitor Z-VAD-FMK also enhanced the type I IFN response upon S. Typhimurium infection. Intriguingly, compared with exponential phase S. Typhimurium infection, stationary phase bacteria triggered higher levels of type I IFN responses. Finally, the inhibition of caspase-1 by VX-765 substantially increased the intracellular S. Typhimurium burden. In conclusion, we demonstrated that the proinflammatory response induced by S. Typhimurium T3SS can inhibit the type I IFN response, which provides insight into the role of T3SS in orchestrating innate immunity during S. Typhimurium infection.

Irisin delays the onset of type 1 diabetes in NOD mice by enhancing intestinal barrier.

Type 1 diabetes (T1D), a complex autoimmune disease, is intricately linked to the gut's epithelial barrier function. Emerging evidence emphasizes the role of irisin, an exercise-related hormone, in preserving intestinal integrity. This study investigates whether irisin could delay T1D onset by enhancing the colon intestinal barrier. Impaired colon intestinal barriers were observed in newly diagnosed T1D patients and non-obese diabetic (NOD) mice, worsening with age and accompanied by islet inflammation. Using an LPS-induced colonic inflammation model, a dose-dependent impact of LPS on colon cells irisin expression, secretion, and barrier function was revealed. Exogenous irisin demonstrated remarkable effects, mitigating islet insulitis, enhancing energy expenditure, and alleviating autoimmune symptoms by reducing colon intestinal permeability. Single-cell RNA sequencing (scRNA-seq) highlighted irisin's positive impact on colon epithelial cell clusters, effectively restoring the intestinal barrier. Irisin also selectively modulated bacterial composition, averting potential bacterial translocation. Mechanistically, irisin enhanced colon intestinal barrier tight junction proteins through the AMPK/PI3K/AKT pathway, with FAM120A playing a crucial role. Irisin upregulated MUC3 expression, a protector against damage and inflammation. Harnessing irisin's exercise-mimicking properties suggests therapeutic potential in clinical settings for preventing T1D progression, offering valuable insights into fortifying the colon's intestinal barrier and managing autoimmune conditions associated with T1DM.

Molecular monitoring and stepwise preemptive therapy for Epstein-Barr virus viremia after allogeneic stem cell transplantation.

The optimal preemptive therapy for Epstein-Barr virus (EBV)-associated diseases remains under discussion. We developed a stepwise preemptive therapy (antiviral agents and reduction of immunosuppressants [RI] followed by rituximab) for EBV viremia, based on duration of EBV viremia and changes of viral loads. The blood EBV-DNA loads were regularly monitored by quantitative real-time polymerase chain reaction in 251 recipients undergoing allogeneic stem cell transplantation. The 3-year cumulative incidence of EBV viremia and EBV-associated diseases were 31.1% ± 3.1% and 15.6% ± 2.5%, which rose steeply with greater numbers of major risk factors. Of the 64 patients undergoing first-step preemption, 24 achieved complete response (CR) and 40 showed no response, including 25 progressing to EBV-associated diseases. The effective rates of antiviral agents and RI plus antiviral agents were 2/16 and 22/48 (P = 0.017). Fourteen achieved CR and one progressed to lymphoproliferative disease in the 15 patients undergoing rituximab preemption. Of the 26 patients progressing to EBV-associated diseases during preemptive therapy, 20 obtained CR in the 23 cases with rituximab-based treatments. The preemptive efficacy of RI plus antiviral agents was correlated with the numbers of major risk factors (rs = -0.298; P = 0.04). B-cell reconstitution was significantly delayed for at least 6 months in patients with rituximab preemption. The risk of herpesvirus infection was similar in patients who showed effective progress to first-step and rituximab preemption (P = 0.094). RI plus antiviral agents could be given priority to low-risk patients, whereas more frequent monitoring of blood EBV-DNA and earlier preemptive rituximab should be advocated in high-risk patients.