Assessing the global vulnerability of dryland birds to heatwaves.

As global average surface temperature increases, extreme climatic events such as heatwaves are becoming more frequent and intense, which can drive biodiversity responses such as rapid population declines and/or shifts in species distributions and even local extirpations. However, the impacts of extreme climatic events are largely ignored in conservation plans. Birds are known to be susceptible to heatwaves, especially in dryland ecosystems. Understanding which birds are most vulnerable to heatwaves, and where these birds occur, can offer a scientific basis for adaptive management and conservation. We assessed the relative vulnerability of 1196 dryland bird species to heatwaves using a trait-based approach. Among them, 888 bird species are estimated to be vulnerable to heatwaves (170 highly vulnerable, eight extremely vulnerable), of which ~91% are currently considered non-threatened by the IUCN, which suggests that many species will likely become newly threatened with intensifying climate change. We identified the top three hotspot areas of heatwave-vulnerable species in Australia (208 species), Southern Africa (125 species) and Eastern Africa (99 species). Populations of vulnerable species recorded in the Living Planet Database were found to be declining significantly faster than those of non-vulnerable species (p = .048) after heatwaves occurred. In contrast, no significant difference in population trends between vulnerable and non-vulnerable species was detected when no heatwave occurred (p = .34). This suggests that our vulnerability framework correctly identified vulnerable species and that heatwaves are already impacting the population trends of these species. Our findings will help prioritize heatwave-vulnerable birds in dryland ecosystems in risk mitigation and adaptation management as the frequency of heatwaves accelerates in the coming decades.

Predictive Impact of Prognostic Nutritional Index in Patients with Cancer Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

A few previous studies have investigated the prognostic value of the prognostic nutritional index (PNI) in patients treated with immune checkpoint inhibitors (ICIs); however, the results are inconsistent. Therefore, this study aimed to clarify the prognostic significance of PNI. The PubMed, Embase, and Cochrane Library databases were searched. A meta-analysis of the impact of PNI on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of adverse events (AEs) in patients treated with ICIs was performed. Twenty-three studies involving 2,386 patients were included. Low PNI was associated with significantly poor OS (hazard ratio [HR] = 2.26, 95% confidence interval [CI]: 1.81-2.82, P < .001) and short PFS (HR = 1.75, 95% CI: 1.54-1.99, P < .001). Patients with low PNI tended to have a low ORR (odds ratio [OR] = 0.47, 95% CI: 0.34-0.65, P < .001) and DCR (OR = 0.43, 95% CI: 0.34-0.56, P < .001). However, the subgroup analysis demonstrated no significant association between PNI and survival time in patients receiving a programmed death ligand-1 inhibitor. PNI was significantly associated with survival time and treatment efficacy in patients treated with ICIs.

Pretreatment Body Mass Index (BMI) as an Independent Prognostic Factor in Nasopharyngeal Carcinoma Survival: A Systematic Review and Meta-Analysis.

We performed a meta-analysis to investigate the association between pretreatment body mass index (BMI) and prognosis of nasopharyngeal carcinoma (NPC). Case-control and cohort studies were searched from PubMed, Web of Science, EMBASE, and CNKI databases. Pooled hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) or distant metastasis-free survival (DMSF) were used to estimate the prognostic value. Bias in the included studies was evaluated using funnel plots. The results showed that compared with normal weight patients, the estimated HR of OS was 1.54 (95% CI: 1.25-1.90; P < 0.05) for underweight, 0.63 (95% CI: 0.48-0.83; P < 0.05) for overweight, and 0.67 (95% CI: 0.41-1.08; P = 0.102) obese patients. We also found that compared with normal-weight patients, the estimated HR of DMFS was 1.63 (95% CI: 1.38-1.92; P < 0.05) for underweight, 0.83 (95% CI: 0.61-1.13; P = 0.244) for overweight, and 0.60 (95% CI: 0.39-0.92; P < 0.05) for patients with obesity. BMI is an independent prognostic factor for NPC survival. Being underweight before treatment was associated with poorer OS and DMFS in patients with NPC. Neither overweight nor obesity before treatment has an unfavorable effect on NPC survival.

Bromoacetic acid causes oxidative stress and uric acid metabolism dysfunction via disturbing mitochondrial function and Nrf2 pathway in chicken kidney.

Since the outbreak of COVID-19, widespread utilization of disinfectants has led to a tremendous increase in the generation of disinfection byproducts worldwide. Bromoacetic acid (BAA), one of the common disinfection byproducts in the environment, has triggered public concern because of its adverse effects on urinary system in mammals. Nevertheless, the BAA-induced nephrotoxicity and potential mechanism in birds still remains obscure. According to the detected content in the Taihu Lake Basin, the model of BAA exposure in chicken was established at doses of 0, 3, 300, 3000 µg/L for 4 weeks. Our results indicated that BAA exposure caused kidney swelling and structural disarrangement. BAA led to disorder in renal function (CRE, BUN, UA) and increased apoptosis (Bax, Bcl-2, caspase3). BAA suppressed the expression of mitochondrial biogenesis genes (PGC-1α, Nrf1, TFAM) and OXPHOS complex I genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6). Subsequently, BAA destroyed the expression of Nrf2 antioxidant reaction genes (Nrf2, Keap1, HO-1, NQO1, GCLM, GCLC). Furthermore, renal oxidative damage led to disorder in uric acid metabolism genes (Mrp2, Mrp4, Bcrp, OAT1, OAT2, OAT3) and exacerbated destruction in renal function. Overall, our study provided insights into the potential mechanism of BAA-induced nephrotoxicity, which were important for the clinical monitoring and prevention of BAA.

iT4SE-EP: Accurate Identification of Bacterial Type IV Secreted Effectors by Exploring Evolutionary Features from Two PSI-BLAST Profiles.

Many gram-negative bacteria use type IV secretion systems to deliver effector molecules to a wide range of target cells. These substrate proteins, which are called type IV secreted effectors (T4SE), manipulate host cell processes during infection, often resulting in severe diseases or even death of the host. Therefore, identification of putative T4SEs has become a very active research topic in bioinformatics due to its vital roles in understanding host-pathogen interactions. PSI-BLAST profiles have been experimentally validated to provide important and discriminatory evolutionary information for various protein classification tasks. In the present study, an accurate computational predictor termed iT4SE-EP was developed for identifying T4SEs by extracting evolutionary features from the position-specific scoring matrix and the position-specific frequency matrix profiles. First, four types of encoding strategies were designed to transform protein sequences into fixed-length feature vectors based on the two profiles. Then, the feature selection technique based on the random forest algorithm was utilized to reduce redundant or irrelevant features without much loss of information. Finally, the optimal features were input into a support vector machine classifier to carry out the prediction of T4SEs. Our experimental results demonstrated that iT4SE-EP outperformed most of existing methods based on the independent dataset test.

Effects of bisphenol A at the safe reference dose on abdominal fat deposition in aged hens.

Bisphenol A (BPA) is an endocrine-disrupting chemical. Its influence on lipid homeostasis remains to be proven. In this study, the obese model of laying hens were induced using high-fat diet (HFD) to determine the lipid metabolism interference of BPA, especially its influence on estrogen receptors (ERs) and oxidative damage, at the dose of tolerable daily intake (TDI, 50 µg/kg body weight [BW]/day) and no observable adverse effect level (NOAEL, 5000 µg/kg BW/day). The results demonstrated that the TDI dose of BPA interacted with ERα more effectively than the NOAEL dose of BPA. The TDI dose of BPA increased the expression of ERα (esr1), which further changed the expression of lipid metabolism-related genes, such as cpt-1, lpl, creb1, and apov1. Furthermore, the abdominal fat rate, hematoxylin-eosin staining of adipocytes, and the average area of the hens were reduced. Therefore, the TDI dose of BPA played an estrogen-compensating role and weakened the effect of HFD on obesity in aged hens. By contrast, BPA at NOAEL dose exhibited great oxidative stress, which remarkably inhibited the activities of antioxidant-related enzymes (total superoxide dismutase and glutathione peroxidase) and promoted the excessive accumulation of lipid peroxidation products (malondialdehyde). Moreover, the increase in oxidative stress corresponded well with the increase in the expression of fat-forming genes (srebp-1, fas, acc, and ppar γ). That is, BPA at NOAEL may accelerate the process of fat formation.

Estrogen receptors participate in carcinogenesis signaling pathways by directly regulating NOD-like receptors.

Increasing evidence indicates that the NOD-like receptors (NLRs) family may act as critical back-up defenses and provide synergistic responses when confronted with persistent danger. However, the precise regulatory mechanism of NLRs and the contribution of NLRs to cancer are still unknown. In our previous study, we found that estrogen receptors (ERs) have a close connection with NLRs in the inflammatory response. Here, ERs are first identified as NLRs transcription regulation factors, both regulate NLRs expression and promote inflammasome co-localization. Furthermore, we identified that NLRP3 was differentially expressed in colon normal and cancer cells, selective ERα antagonist could significantly decrease pro-inflammatory cytokines expression, suppress proliferation and promote apoptosis by inhibited NLRP3 expression and inflammasome activity. In short, the research demonstrates that ERs participate in the NLR-associated signaling pathway in cancer by directly regulating NLRs. Our results provide novel insight into ERs as therapeutic targets in NLR-related inflammation and cancer.

Zearalenone can relieve dextran sulfate sodium-induced inflammatory reaction.

In this study, we investigated the influence of zearalenone (ZEA) on the dextran sulfate sodium (DSS)-induced colitis model both in vitro and in vivo. Our results show that the mRNA levels of IL-1ß, IL-18, NLRP3, ASC, and caspase-1 in the DSS+ZEA-treated group are lower than those in either the DSS or ZEA group, and the protein expression trends are similar. Furthermore, colitis, which is characterized by body weight loss, stool consistency, and the presence of bloody feces, was significantly alleviated in the DSS+ZEA group when compared with that in the DSS group. In addition, histological analysis showed that inflammatory cell infiltration and tissue damage of the colon in the DSS+ZEA group were recovered compared with that in the DSS-treated group. These results suggest that, instead of aggravating DSS-induced colitis, ZEA relieves the inflammatory reaction in colon tissue, which may be related to its estrogenic activity.

A DEAD-box RNA helicase produces two forms of transcript that differentially respond to cold stress in a cryophyte (Chorispora bungeana).

MAIN CONCLUSION: This work demonstrated that a cold-induced DEAD-box RNA helicase, CbDRH, is also post-transcriptionally regulated upon cold stress, and it interacts with a cold-responsive, glycine-rich, RNA-binding protein, CbGRP. Chorispora bungeana (C. bungeana) is a representative alpine subnival plant species that shows strong tolerance to multiple abiotic stresses, especially cold stress. DEAD-box RNA helicases are implicated in almost all RNA metabolic processes and participate in multiple abiotic stress responses. Here, we characterized a cold-induced DEAD-box RNA helicase gene from C. bungeana. We cloned the full-length cDNA of the gene by RACE and called it C. bungeana DEAD-box RNA Helicase (CbDRH). Structurally, CbDRH possesses all nine conserved motifs characteristic of DEAD-box protein family members in its central region, and the N- and C- terminal extensions both harbor a glycine-rich region containing several RGG-box motifs. The CbDRH gene produces two forms of transcripts, CbDRH.2 and CbDRH.1, by alternative splicing. CbDRH.2 comes from the complete excision of all the nine introns, while CbDRH.1 results from the use of an alternative 5' splice site in the eighth intron, retaining part of the intron (the first 260 bp) with an early stop codon. Semi-quantitative RT-PCR analysis showed that CbDRH.2, but not CbDRH.1, is up-regulated by cold stress. However, the abundance of CbDRH.1 transcript can be elevated by cycloheximide (an inhibitor of nonsense-mediated decay) treatment, indicating that CbDRH.1 is targeted to nonsense-mediated decay (NMD). A subcellular localization analysis showed that CbDRH.2 protein is located in the nuclei. Further investigation suggested that CbDRH.2 can interact with a cold-responsive, glycine-rich, RNA-binding protein, CbGRP (Chorispora bungeana glycine-rich, RNA-binding protein). These data suggest that the cold-induced CbDRH is also post-transcriptionally regulated under cold stress and that CbDRH.2 may function together with the glycine-rich, RNA-binding protein, CbGRP, in the cold stress response.

miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma.

BACKGROUND AND AIM: MicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that miR-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of miR-224 in the migration and invasion in liver cancer cells. METHODS: A luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC). RESULTS: (i) The expression of miR-224 was strongly upregulated in MHHC97H and MHCC97L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of miR-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) miR-224 promoted expression of the tumor invasion-associated proteins p-PAK4 and MMP-9 by directly targeting HOXD10. CONCLUSION: Our findings suggest a previously undescribed regulatory pathway in which the miR-224/HOXD10/p-PAK4/MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment.

The roles of spatial pattern and size variation in shaping height inequality of plant population.

Game-theoretic models predict that there is an ESS height for the plant population to which all individual plants should converge. To attain this conclusion, the neighborhood factors were assumed to be equal for all the individual plants, and the spatial pattern and size variation of population were left without consideration, which is clearly not right for the scenario of plant competition. We constructed a spatially-explicit, individual-based model to explore the impacts of spatial structure and size variation on individual plant's height and population's height hierarchies under the light competition. The monomorphic equilibrium of height that all the individual plants will converge to only exists for a population growing in a strictly uniform spatial pattern with no size variation. When the spatial pattern of the population is non-uniform or there's size variation among individual plants, the critical heights that individual plants will finally reach are different from each other, and the height inequality at the end of population growth will increase when the population's spatial pattern's degree of deviation from uniform and population's size variation increase. Our results argue strongly for the importance of spatial pattern and neighborhood effects in generating the diversity of population's height growth pattern.

Investigating the causal association between obesity and risk of hepatocellular carcinoma and underlying mechanisms.

Obesity is a global health concern and independent risk factor for cancers including hepatocellular carcinoma (HCC). However, evidence on the causal links between obesity and HCC is limited and inconclusive. This study aimed to investigate the causal relationship between obesity-related traits and HCC risk and explore underlying mechanisms using bioinformatics approaches. Two-sample Mendelian randomization analysis was conducted leveraging publicly available genome-wide association study summary data on obesity traits (body mass index, body fat percentage, waist circumference, waist-to-hip ratio, visceral adipose tissue volume) and HCC. Associations of obesity with primary mechanisms (insulin resistance, adipokines, inflammation) and their effects on HCC were examined. Differentially expressed genes in obesity and HCC were identified and functional enrichment analyses were performed. Correlations with tumor microenvironment (TME) and immunotherapy markers were analyzed. Genetically predicted higher body mass index and body fat percentage showed significant causal relationships with increased HCC risk. Overall obesity also demonstrated causal links with insulin resistance, circulating leptin levels, C-reactive protein levels and risk of severe insulin resistant type 2 diabetes. Four differentially expressed genes (ESR1, GCDH, FAHD2A, DCXR) were common in obesity and HCC. Enrichment analyses indicated their roles in processes like RNA capping, viral transcription, IL-17 signaling and endocrine resistance. They exhibited negative correlations with immune cell infiltration and immunotherapy markers in HCC. Overall obesity likely has a causal effect on HCC risk in Europeans, possibly via influencing primary mechanisms. The identified differentially expressed genes may be implicated in obesity-induced hepatocarcinogenesis through regulating cell cycle, inflammation and immune evasion. Further research on precise mechanisms is warranted.

Pan-cancer analysis revealing the multidimensional expression and prognostic and immunologic roles of TGFB1 in cancer.

OBJECTIVE: This study aimed to perform an integrated pan-cancer analysis to characterize the expression patterns, prognostic value, genetic alterations, and immunologic roles of transforming growth factor beta 1 (TGFB1) across diverse human cancer types. METHODS: Bioinformatics analyses were conducted using multiple public databases including The Cancer Genome Atlas, Genotype-Tissue Expression, Clinical Proteomic Tumor Analysis Consortium, TIMER2, GEPIA2, cBioPortal, StringDB, and others. Differential expression, survival, immune correlation, and protein interaction network analyses were performed. RESULTS: TGFB1 was overexpressed in several tumor types compared with that in normal tissues. High TGFB1 expression was associated with an advanced stage and poorer prognosis in certain cancers. TGFB1 mutations occurred in 1.3% of 10,967 cases surveyed. TGFB1 expression correlated with tumor-infiltrating immune cells and immunotherapy-related genes. CONCLUSIONS: This comprehensive multi-omics analysis revealed the complex expression and prognostic landscape of TGFB1 across cancers. TGFB1 is emerging as a potential immunotherapeutic target in certain contexts. Further research should elucidate its multifaceted tumor-promoting and tumor-suppressive mechanisms. Our pan-cancer analysis provides new insights into TGFB1 as a prognostic biomarker and immunotherapeutic target in human cancers, and our findings may guide future preclinical and clinical investigations of TGFB1-directed therapies.

Microencapsulate Probiotics (MP) Promote Growth Performance and Inhibit Inflammatory Response in Broilers Challenged with Salmonella typhimurium.

Antibiotic-resistant bacteria are prevalent in husbandry around the world due to the abuse of antibiotic growth promoters (AGPs); therefore, it is necessary to find alternatives to AGPs in animal feed. Among all the candidates, probiotics are promising alternatives to AGPs against Salmonella infection. The anti-Salmonella effects of three probiotic strains, namely, Lactobacillus crispatus 7-4, Lactobacillus johnsonii 3-1, and Pediococcus acidilactici 20-1, have been demonstrated in our previous study. In this study, we further obtained the alginate beads containing compound probiotics, namely, microencapsulate probiotics (MP), and evaluated its regulatory effect on the health of broilers. We incubated free and microencapsulate probiotics in simulated gastric and intestinal juice for 2 h, and the results showed that compared to free probiotics, encapsulation increased tolerance of compound probiotics in the simulated gastrointestinal condition. We observed that the application of probiotics, especially MP, conferred protective effects against Salmonella typhimurium (S.Tm) infection in broilers. Compared to the S.Tm group, the MP could promote the growth performance (p < 0.05) and reduce the S.Tm load in intestine and liver (p < 0.05). In detail, MP pretreatment could modulate the cecal microflora and upregulate the relative abundance of Lactobacillus and Enterobacteriaceae. Besides, MP could reduce the inflammation injury of the intestine and liver, reduce the pro-inflammatory cytokines (IL-6, TNF-α, IL-1ß) expression, and induce of anti-inflammatory cytokine (IL-10) expression. Furthermore, MP could inhibit NLRP3 pathway in ileum, thereby attenuating S.Tm-induced inflammation. In conclusion, MP could be a new feeding supplementation strategy to substitute AGPs in poultry feeding.

Lactobacillus crispatus 7-4 Mitigates Salmonella typhimurium-Induced Enteritis via the γ­Glutamylcysteine-Mediated Nrf2 Pathway.

Salmonella typhimurium (S. typhimurium) constitutes a major public health concern. We have previously proven that Lactobacillus crispatus 7-4 (L. crispatus 7-4) can inhibit the growth of S. typhimurium and thus can be used as a biocontrol strategy to suppress foodborne S. typhimurium infections. However, the inhibitory effect and in-depth mechanism of L. crispatus 7-4 remain to be elucidated. In this study, we found that L. crispatus 7-4 can protect against S. typhimurium-induced ileum injury by promoting intestinal barrier integrity, maintaining intestinal mucosal barrier homeostasis, and reducing intestinal inflammatory response. Furthermore, we demonstrated that this probiotic strain can increase the abundance of Lactobacillus spp. to maintain microbial homeostasis and simultaneously increase the amount of γ­glutamylcysteine (γ-GC) by activating the glutathione metabolic pathway. The increased γ-GC promoted the transcription of Nrf2 target genes, thereby improving the host antioxidant level, reducing reactive oxygen species (ROS) accumulation, and removing pro-inflammatory cytokines. In other words, L. crispatus 7-4 could activate the enterocyte Nrf2 pathway by improving γ-GC to protect against S. typhimurium-induced intestinal inflammation and oxidative damage.

Toward a remote sensing method based on commercial LiDAR sensors for the measurement of spray drift and potential drift reduction.

Spray drift is inevitable in chemical applications, drawing global attention because of its potential environmental pollution and the risk of exposing bystanders to pesticides. This issue has become more pronounced with a growing consensus on the need for enhanced environmental safeguards in agricultural practices. Traditionally, spray drift measurements, crucial for refining spray techniques, relied on intricate, time-consuming, and labor-intensive sampling methods utilizing passive collectors. In this study, we investigated the feasibility of using close-range remote sensing technology based on Light Detection and Ranging (LiDAR) point clouds to implement drift measurements and drift reduction classification. The results show that LiDAR-based point clouds vividly depict the spatial dispersion and movement of droplets within the vertical plane. The capability of LiDAR to accurately determine drift deposition was demonstrated, evident from the high R2 values of 0.847, 0.748 and 0.860 achieved for indoor, wind tunnel and field environments, respectively. Droplets smaller than 100 µm and with a density below 50 deposits·cm-2·s-1 posed challenges for LiDAR detection. To address these challenges, the use of multichannel LiDAR with higher wavelengths presents a potential solution, warranting further exploration. Furthermore, we found a satisfactory consistency when comparing the drift reduction classification calculated from LiDAR measurements with those obtained though passive collectors, both in indoor tests and the unmanned air-assisted sprayer (UAAS) field test. However, in environments with less dense clouds of larger droplets, a contradiction emerged between higher drift deposition and lower scanned droplet counts, potentially leading to deviations in the calculated drift potential reduction percentage (DPRP). This was exemplified in a field test using an unmanned aerial vehicle sprayer (UAVS). Our findings provide valuable insights into the monitoring and quantification of pesticide drift at close range using LiDAR technology, paving the way for more precise and efficient drift assessment methodologies.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

Self-Assembling Sulfated Lactobacillus Exopolysaccharide Nanoparticles as Adjuvants for SARS-CoV-2 Subunit Vaccine Elicit Potent Humoral and Cellular Immune Responses.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic since its onset in 2019, and the development of effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce potent and long-lasting immunity remains a priority. Herein, we prepared two Lactobacillus exopolysaccharide (EPS) nanoparticle adjuvants (NPs 7-4 and NPs 8-2) that were constructed by using sulfation-modified EPS and quaternization-modified chitosan. These two NPs displayed a spherical morphology with sizes of 39 and 47 nm. Furthermore, the zeta potentials of NPs 7-4 and NPs 8-2 were 50.40 and 44.40 mV, respectively. In vitro assays demonstrated that NPs could effectively adsorb antigenic proteins and exhibited a sustained release effect. Mouse immunization tests showed that the NPs induced the expression of cytokines and chemokines at the injection site and promoted the uptake of antigenic proteins by macrophages. Mechanically, the NPs upregulated the expression of pattern recognition receptors (toll-like receptors and nod-like receptors) and activated the immune response of T cells and the production of neutralizing antibodies. In addition, the NP adjuvants had favorable immune-enhancing effects in cats, which are of great significance for controlling the trans-host transmission and re-endemicity of SARS-CoV-2. Overall, we demonstrated that NP-adjuvanted SARS-CoV-2 receptor binding domain proteins could induce robust specific humoral and cellular immunity.

The Evolutions of Microstructure, Texture and Hardness of A1050 Deformed by HPT at the Transition Area.

High-pressure torsion (HPT) is an effective severe plastic deformation method to produce ultrafine-grained (UFG) and nanocrystalline (NC) materials. In the past, most studies have focused on the evolutions in the microstructure, texture and mechanical properties of HPT-deformed materials at peripheral regions. The corresponding evolutions at a special area were observed in this study to reveal the potential plastic deformation mechanism for face-centred cubic (FCC) material with high stacking fault energy. A decreasing trend was found in grain size, and the final grain size was less than 1 µm. However, close observation revealed that the general trend could be divided into different sub-stages, in which grain elongation and grain fragmentation were dominant, respectively. Additionally, microhardness demonstrated a non-linear increase with the development of plastic deformation. Finally, the microhardness reached a high level of ~64 HV. At the early stages of HPT, the C component was transformed into a cube component, suggesting the material flows around the shear plane normal (SPN) axis at these stages. However, finally they will be replaced by ideal simple shear orientations.

Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends.

Background: Hepatocellular carcinoma (HCC) is a primary malignant tumor responsible for approximately 90% of all liver cancers in humans, making it one of the leading public health problems worldwide. The gut microbiota is a complex microbial ecosystem that can influence tumor formation, metastasis, and resistance to treatment. Therefore, understanding the potential mechanisms of gut microbiota pathogenesis is critical for the prevention and treatment of HCC. Materials and methods: A search was conducted in the Web of Science Core Collection (WoSCC) database for English literature studies on the relationship between gut microbiota and HCC from 2011 to 2022. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were used to analyze global trends and research hotspots in this field. Results: A total of 739 eligible publications, comprising of 383 articles and 356 reviews, were analyzed. Over the past 11 years, there has been a rapid increase in the annual number of publications and average citation levels, especially in the last five years. The majority of published articles on this topic originated from China (n=257, 34.78%), followed by the United States of America (n=203, 27.47%), and Italy (n=85, 11.50%). American scholars demonstrated high productivity, prominence, and academic environment influence in the research of this subject. Furthermore, the University of California, San Diego published the most papers (n=24) and had the highest average citation value (value=152.17) in the study of the relationship between gut microbiota and HCC. Schnabl B from the USA and Ohtani N from Japan were the authors with the highest number of publications and average citation value, respectively. Conclusion: In recent years, research on the gut microbiota's role in HCC has made rapid progress. Through a review of published literature, it has been found that the gut microbiota is crucial in the pathogenesis of HCC and in oncotherapy.