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.

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.

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.

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.

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.

Safety and Efficacy Analysis of PD-1 Inhibitors in Combination with Gemcitabine Plus Nab-Paclitaxel for Advanced Pancreatic Cancer: A Real-World, Single-Center Study.

Background: Pancreatic cancer is a deadly disease with a low five years survival rate, and chemotherapy remains the standard treatment for advanced cases. However, the efficacy of chemotherapy alone is limited, and there is a need for new treatment options. Recently, immune checkpoint inhibitors (ICIs), particularly programmed death-1 (PD-1) inhibitors, have shown promising results in various cancers, including pancreatic cancer. In this study, we explore the safety and efficacy of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer. Materials and Methods: A retrospective analysis was conducted on clinical data from 27 patients with advanced pancreatic cancer who were administered a combination of anti-PD-1 antibody and gemcitabine plus nab-paclitaxel (GnP) regimen. The study evaluated the safety of the treatment as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: In this study, treatment with a combination of anti-PD-1 antibody and GnP regimen for pancreatic cancer resulted in partial response (PR) for 10 out of 27 (37.04%) patients, stable disease (SD) for 10 (37.04%) patients, and progressive disease (PD) for 7 (25.92%) patients. The study found that the median OS (mOS) for these patients was 16.4 months [standard error (SE) = 1.117, 95% confidence interval (CI) 14.211-18.589], while the median PFS (mPFS) was 6.4 months (SE = 1.217, 95% CI 3.981-8.752). Subgroup analysis revealed that pancreatic cancer patients' Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1) and treatment cycles (≤6 cycles vs >6 cycles) significantly affected OS and PFS. Patients experienced mostly grade 1-2 adverse events (AEs), which were relieved through clinical treatment. Conclusion: The combination of GnP with anti-PD-1 antibodies shows promise as a potential treatment option for advanced pancreatic cancer.

Genistein upregulates AHR to protect against environmental toxin-induced NASH by inhibiting NLRP3 inflammasome activation and reconstructing antioxidant defense mechanisms.

We have previously proven that the environmental toxin could accelerate the development and progression of nonalcoholic steatohepatitis (NASH). However, the underlying mechanism associated with such excessive inflammation hasn't been fully illustrated. Although Genistein has been well accepted for its capability in anti-inflammation and anti-oxidation, its effect in ameliorating contaminants-induced NASH still needs to be identified. In this study, using chickens and primary chicken hepatocytes as models, we found that NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome were over-activated in bromoacetic acid (BAA, one of the typical environmental toxins)-induced NASH, characterized by the infiltration of inflammatory cell, and the increase of NLRP3, Caspase-1 p20, and cytokines (IL-1ß, IL-18) expressions. Interestingly, genistein treatment could recover these changes, with the signs of restored activities of anti-oxidases, decreased expressions of NLRP3 inflammasome components, and increased levels of elements in phase I metabolic system. The detailed mechanism was that, via up-regulating aryl hydrocarbon receptor (AHR), genistein lifted mRNA levels of Cyp1-related genes to reconstruct cytochrome P450 (CYP450) systems, and the raised AHR negatively regulated NLRP3 inflammasome activity to relieve inflammation. More important, the interaction and co-localization between AHR and NLRP3 was first proved, and genistein could promote the levels of AHR that interacted with NLRP3, which thereafter blocked the activation of NLRP3 inflammasome. Conclusively, in this research, we confirmed the AHR-dependent protective role of genistein in environmental toxin-linked NASH, which shed light on the potential precautions for contaminants-induced NASH.

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.

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.

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.

Prognostic values of the prognostic nutritional index, geriatric nutritional risk index, and systemic inflammatory indexes in patients with stage IIB-III cervical cancer receiving radiotherapy.

Background: Growing evidence suggests that nutritional status and inflammation are associated with survival in various cancers. This study aimed to evaluate the prognostic value of the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and systemic inflammatory indexes (neutrophil/lymphocyte ratio [NLR], monocyte/lymphocyte ratio [MLR], and platelet/lymphocyte ratio [PLR]) in patients with stage IIB-III cervical cancer receiving radiotherapy. Results: The ideal cutoff values for the PNI, GNRI, NLR, MLR, and PLR were 48.3, 97.04, 2.8, 0.41, and 186.67, respectively. Low PNI and GNRI scores were associated with poor OS and PFS. High NLR, MLR, and PLR also predicted inferior 5-year OS and PFS rates in patients with stage IIB-III cervical cancer. Multivariate Cox regression analysis identified tumor size, histological type, stage, number of metastatic lymph nodes, PNI, GNRI, NLR, PLR, and MLR as significant prognostic factors for OS and PFS. Conclusions: The current findings suggest that the PNI, GNRI, NLR, PLR, and MLR are essential parameters for predicting prognosis in patients with stage IIB-III cervical cancer receiving radiotherapy.

Study on the Impact of Climate Change on China's Import Trade of Major Agricultural Products and Adaptation Strategies.

With global warming, China's agricultural products are facing severe production conditions and a complex international trade situation. In order to clarify the relationship between climate change and China's agricultural trade, this paper uses the GTAP model to explore the impact of climate change on China's agricultural trade from the perspectives of agricultural production and supply, energy substitution and trade policy. The results show that: (1) From the overall effect, the production supply risk and energy substitution risk caused by climate change have a positive impact on China's import trade, among which the energy substitution risk has brought about an import trade growth of 38.050%, the production supply risk has brought about an import trade growth of 12.635%, and the trade policy risk has a negative impact, bringing about an import trade decline of 12.589%. (2) Under the impact of production and supply risks caused by climate change, the import volume of different industrial sectors has increased by varying degrees, including livestock products (16.521%) > food crops (14.162%) > cash crops (7.220%). The increase in import trade mainly comes from the United States (10.731%), Canada (10.650%) and Australia (9.455%). (3) Under the impact of energy substitution risk caused by climate change, the increase in import trade was concentrated in food crops (48.144%) and livestock products (42.834%), mainly from the United States (57.098%), the European Union (55.014%) and Canada (53.508%). (4) Under the impact of trade policy risks caused by climate change, the import trade of different industrial sectors showed a downward trend, with cash crops (13.039%) > livestock products (12.588%) > cash crops (12.140%). The countries and regions with significant decline in import trade were ASEAN (-46.131%) and the United States (-28.028%). The trade deficit shifted to surplus, and the terms of trade were improved. Therefore, this paper suggests that we should deal with the impact of climate change on agricultural trade by developing "climate smart" agriculture, actively responding to low-carbon trade measures, and establishing an agricultural trade promotion mechanism to address the risk of climate change.

Estrogen receptor ß activation inhibits colitis by promoting NLRP6-mediated autophagy.

Estrogen receptor ß (ERß) and NOD-like receptor family pyrin domain containing 6 (NLRP6) are highly expressed in intestinal tissues. Loss of ERß and NLRP6 exacerbate colitis in mouse models; however, the underlying mechanisms are incompletely understood. Here, we report that ERß directly activates the NLRP6 gene expression via binding to estrogen responsive element of Nlrp6 gene promoter. ERß also physically interacts with the NLRP6 nucleotide-binding domain and promotes NLRP6 inflammasome assembly. The ERß-NLRP6 axis then interacts with multiple autophagy-related proteins, including ULK1, BECN1, ATG16L1, LC3B, and p62, and affects the autophagosome biogenesis and autophagic flux. Finally, NLRP6-mediated autophagy suppresses the inflammatory response by promoting the K48-linked polyubiquitination of ASC, Casp-1 p20, IL-1ß, TNF-α, and prohibitin-2. Thus, ERß-NLRP6 direct an anti-inflammatory response by promoting autophagy. Our work uncovers an ERß-NLRP6-autophagy pathway as a regulatory mechanism that maintains intestinal epithelial cell homeostasis and facilitates tissue repair in colitis.

Lactobacillus crispatus-derived exopolysaccharides with antibacterial activity limit Salmonella typhimurium invasion by inhibiting inflammasome-mediated pyroptosis.

In this study, a novel heteropolysaccharide (EPS 7-4) with a molecular weight of 53 387 Da was isolated from Lactobacillus crispatus, and it was mainly composed of mannose (36.9%) and glucose (30.8%). EPS 7-4 showed excellent inhibitory effects on the proliferation, biofilm formation, and virulence factor gene expression of Salmonella typhimurium (S. typhimurium) by disrupting the integrity of the bacterial wall. Furthermore, EPS 7-4 can effectively restrict bacterial translocation, upregulate the abundance of Lactobacillus spp. and Bifidobacterium spp., and alleviate the S. typhimurium induced severe inflammatory response in the intestinal tract of mice. Besides, we demonstrated that EPS 7-4 can protect mice by inhibiting S. typhimurium induced pyroptosis, with the mechanism that EPS 7-4 affects ASC oligomerization during inflammasome-mediated pyroptosis. Therefore, due to its excellent anti-bacterial and anti-inflammatory abilities, EPS 7-4 is a promising health regulator owing to its excellent antibacterial and anti-inflammatory abilities.

Bromoacetic acid induces neurogenic injury in the chicken brain by activating oxidative stress and NF-κB inflammatory pathway.

The bromoacetic acid (BAA) is one of the most teratogenic and neurotoxic disinfection byproducts. Birds take environmental water as their habitat and are inevitably affected by BAA in the environment. However, the neurotoxicity caused by BAA in birds has not been reported and the mechanism remains unclear. In this study, we chose chickens as the avian model to explore the effects of different concentrations of BAA on the brain tissues. Here, we selected the 3 µg/L dose of BAA detected in Tai Lake basin as a reference, and designed 1-, 100-, and 1000-fold of the environmental exposure dose as the experimental doses to explore the neurotoxicity of BAA in birds. Results showed that BAA increased the number of pyknotic nuclear neurons, deformed vascular sheaths, and glial cells in the brain. BAA inhibited the activity of antioxidant enzymes and the expression of antioxidant genes. With the increase of BAA concentration, the oxidative stress-responsive transcription factor NF-κB was activated. Furthermore, BAA remarkably changed the expression of lipid metabolism related genes (i.e., acc, gpat, hmgr, pparα, cpt1, and ampkα). Importantly, BAA decreased the mRNA and protein expression levels of autophagy-related genes (i.e., atg5, ulk1, beclin1, and lc3). Meantime, BAA increased the mRNA and protein levels of apoptotic and pro-apoptotic genes, such as p53, bax, cytochrome c, caspase-9, and caspase-3. Overall, our study provided new insights into the potential neurotoxic effects of BAA in birds, which was important for the clinical monitoring and prevention of BAA.

Spray drift evaluation with point clouds data of 3D LiDAR as a potential alternative to the sampling method.

Spray drift is an inescapable consequence of agricultural plant protection operation, which has always been one of the major concerns in the spray application industry. Spray drift evaluation is essential to provide a basis for the rational selection of spray technique and working surroundings. Nowadays, conventional sampling methods with passive collectors used in drift evaluation are complex, time-consuming, and labor-intensive. The aim of this paper is to present a method to evaluate spray drift based on 3D LiDAR sensor and to test the feasibility of alternatives to passive collectors. Firstly, a drift measurement algorithm was established based on point clouds data of 3D LiDAR. Wind tunnel tests included three types of agricultural nozzles, three pressure settings, and five wind speed settings were conducted. LiDAR sensor and passive collectors (polyethylene lines) were placed downwind from the nozzle to measure drift droplets in a vertical plane. Drift deposition volume on each line and the number of LiDAR droplet points in the corresponding height of the collecting line were calculated, and the influencing factors of this new method were analyzed. The results show that 3D LiDAR measurements provide a rich spatial information, such as the height and width of the drift droplet distribution, etc. High coefficients of determination (R 2 > 0.75) were observed for drift points measured by 3D LiDAR compared to the deposition volume captured by passive collectors, and the anti-drift IDK12002 nozzle at 0.2 MPa spray pressure has the largest R 2 value, which is 0.9583. Drift assessment with 3D LiDAR is sensitive to droplet density or drift mass in space and nozzle initial droplet spectrum; in general, larger droplet density or drift mass and smaller droplet size are not conducive to LiDAR detection, while the appropriate threshold range still needs further study. This study demonstrates that 3D LiDAR has the potential to be used as an alternative tool for rapid assessment of spray drift.

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.

A six-miRNA signature as a novel biomarker for improving prediction of prognosis and patterns of immune infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death. MicroRNAs (miRNAs) belong to a subfamily of functional non-coding RNAs (ncRNAs) and are essential regulators of tumorigenesis. They affect tumor-related therapeutic response, tumor metastasis, and clinical outcomes of several human malignant tumors. However, the prognostic value of miRNAs and their role in the tumor immune microenvironment (TIME) of HCC have not been clarified. MATERIALS AND METHODS: Raw RNA-sequencing data (mRNA and miRNA) and clinicopathological characteristics of HCC samples were downloaded from the TCGA-GDC database. The Perl programming language, R software, Cytoscape software, and several online databases were used to clarify the clinical significance and biological functions of miRNAs and their target genes in HCC. RESULTS: A total of 424 mRNA-sequencing samples and 425 miRNA-sequencing samples were obtained from the TCGA database. There were 344 HCC cases with complete information in the TCGA dataset and they were randomly categorized into two subgroups. Six miRNAs were identified as independent prognostic biomarkers for HCC patients by univariate and multivariate Cox regression analysis. The constructed prognostic signature, which contains these six miRNAs, was significantly correlated with overall survival (OS). In addition, this prognostic signature is superior to single miRNA in predicting short-term prognosis of HCC patients. We also found that the prognostic signature was significantly associated with tumor-related immune cell infiltration, TIME, and immunotherapeutic response. Furthermore, a total of 4568 potential target genes of six miRNAs were identified. The miRNA-mRNA co-expression network, protein-protein interaction (PPI) network, and functional and pathway enrichment analysis demonstrated that these miRNA-related target genes have important biological effects during the initiation and progression of HCC. CONCLUSIONS: This study demonstrates that the miRNA signature can accurately predict the prognosis of HCC patients and provide a basis for novel immunotherapy treatments.

Pancancer Analyses Reveal Genomics and Clinical Characteristics of the SETDB1 in Human Tumors.

Background: Malignant tumor is one of the most common diseases that seriously affect human health. The prior literature has reported the biological function and potential therapeutic targets of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) as an oncogene. However, SETDB1 has rarely been analyzed from a pan-cancer perspective. Methods: Bioinformatics analysis tools and databases, including GeneCards, National Center for Biotechnology Information (NCBI), UniProt, Illustrator for Biological Sequences (IBS), Human Protein Atlas (HPA), GEPIA, TIMER2, Sangerbox 3.0, UALCAN, Kaplan-Meier (K-M) plotter, cBioPortal, Catalogue Of Somatic Mutations In Cancer (COSMIC), PhosphoSitePlus, TISIDB, STRING, and GeneMANIA, were utilized to clarify the biological functions and clinical significance of SETDB1 from a pan-cancer perspective. Results: In this study, the pan-cancer analysis demonstrated that SETDB1 showed significantly differential expression in most tumor tissues and paracancerous tissues, and SETDB1 expression was associated with clinicopathological features and clinical prognosis. We also found that SETDB1 mutations occurred in most tumors and were related to tumorigenesis. In addition, DNA methylation of SETDB1 primarily occurred at the cg10444928 site and was associated with prognosis in several human tumors. The predicted phosphorylation site of SETDB1 was Ser1006. We found that SETDB1 was significantly related to the specific tumor-infiltrating immune cell populations and expression of clinically targetable immune checkpoints and may be a promising immunotherapy target. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses also indicated that SETDB1 may function as crucial regulator in carcinogenesis of human cancers. Conclusions: SETDB1 is an important oncogene involved in tumorigenesis and tumor progression through different biological mechanisms. Furthermore, SETDB1 may be a potential therapeutic target for cancer treatment.