Genetic analysis of feline parvovirus reveals predominance of feline parvovirus-G1 group among cats in China.

Feline parvovirus (FPV) or feline panleukopenia virus is a highly contagious, life-threatening infectious virus in cats. Although FPV vaccination is routinely practiced in China, clinical diseases continue to occur. The investigation of genotypes and viral evolution can contribute to the prevention, diagnosis, and treatment of FPV. Therefore, this study aimed to provide an up-to-date understanding of the epidemiological, genotypic, and phylogenetic characteristics of FPV. In total, 152 rectal swabs were collected from diseased cats. All swab samples were tested for FPV using molecular methods. Amplification of the complete viral protein 2 (VP2) gene was performed for further analysis and to infer the genotypic and evolutionary characteristics of FPV. Of the 152 samples, FPV DNA was detected in 17 (17/152, 11.18%). Cats with FPV showed variable clinical signs such as dehydration, anorexia, fever, vomiting, and blood-stained diarrhea. Furthermore, VP2 sequences were identified in 17 PCR-positive cats, confirming the presence of FPV. Phylogenetic and nucleotide pairwise identity analyses revealed high genetic similarity among FPV sequences (99.6-100%) and clustered them into the FPV-G1 group. Amino acid analysis indicated a novel mutation (Ala91Ser) in all VP2 gene sequences amplified in this study. Our study provides baseline epidemiological data for the better prevention of FPV with respect to vaccination strategies. Genotypic and phylogenetic analyses confirm that FPV-G1 was the predominant FPV group in infected cats in Kunshan. Therefore, a rigorous countrywide investigation of the genotypic and evolutionary characteristics of FPV is warranted.

Nanoparticle-Mediated Immunotherapy in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype with the worst prognosis and highest recurrence rates. The treatment choices are limited due to the scarcity of endocrine and HER2 targets, except for chemotherapy. However, the side effects of chemotherapy restrict its long-term usage. Immunotherapy shows potential as a promising therapeutic strategy, such as inducing immunogenic cell death, immune checkpoint therapy, and immune adjuvant therapy. Nanotechnology offers unique advantages in the field of immunotherapy, such as improved delivery and targeted release of immunotherapeutic agents and enhanced bioavailability of immunomodulators. As well as the potential for combination therapy synergistically enhanced by nanocarriers. Nanoparticles-based combined application of multiple immunotherapies is designed to take the tactics of enhancing immunogenicity and reversing immunosuppression. Moreover, the increasing abundance of biomedical materials holds more promise for the development of this field. This review summarizes the advances in the field of nanoparticle-mediated immunotherapy in terms of both immune strategies for treatment and the development of biomaterials and presents challenges and hopes for the future.

Orally available dextran-aspirin nanomedicine modulates gut inflammation and microbiota homeostasis for primary colorectal cancer therapy.

Reversing the aggravated immunosuppression hence overgrowth of colorectal cancer (CRC) caused by the gut inflammation and microbiota dysbiosis is pivotal for effective CRC therapy and metastasis inhibition. However, the low delivery efficiency and severe dose-limiting off-target toxicities caused by unsatisfied drug delivery systems remain the major obstacles in precisely modulating gut inflammation and microbiota in CRC therapy. Herein, a multifunctional oral dextran-aspirin nanomedicine (P3C-Asp) was utilized for oral treatment of primary CRC, as it could release salicylic acid (SA) while scavenging reactive oxygen species (ROS) and held great potential in modulating gut microbiota with prebiotic (dextran). Oral P3C-Asp retained in CRC tissues for over 12 h and significantly increased SA accumulation in CRC tissues over free aspirin (10.8-fold at 24 h). The enhanced SA accumulation and ROS scavenging of P3C-Asp cooperatively induced more potent inflammation relief over free aspirin, characterized as lower level of cyclooxygenase-2 and immunosuppressive cytokines. Remarkably, P3C-Asp promoted the microbiota homeostasis and notably increased the relative abundance of strengthening systemic anti-cancer immune response associated microbiota, especially lactobacillus and Akkermansia to 6.66- and 103- fold over the control group. Additionally, a demonstrable reduction in pathogens associated microbiota (among 96% to 79%) including Bacteroides could be detected. In line with our findings, inflammation relief along with enhanced abundance of lactobacillus was positively correlated with CRC inhibition. In primary CRC model, P3C-Asp achieved 2.1-fold tumor suppression rate over free aspirin, with an overall tumor suppression rate of 85%. Moreover, P3C-Asp cooperated with αPD-L1 further reduced the tumor weight of each mouse and extended the median survival of mice by 29 days over αPD-L1 alone. This study unravels the synergistic effect of gut inflammation and microbiota modulation in primary CRC treatment, and unlocks an unconventional route for immune regulation in TME with oral nanomedicine.

Construction and validation of an 18F-FDG-PET/CT-based prognostic model to predict progression-free survival in newly diagnosed multiple myeloma patients.

OBJECTIVE: To investigate the relationship between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma. METHODS: A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014-2021. All patients underwent PET/CT before treatment and were divided into a training cohort (n = 75) and a validation cohort (n = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve. RESULTS: Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility. CONCLUSION: The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.

Effectiveness of traditional Chinese exercise in patients with fibromyalgia syndrome: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND OBJECTIVE: Fibromyalgia syndrome (FMS) is a common disorder characterized by heterogeneous symptoms that leads to decreased functioning, work productivity, and quality of life. Exercise has been recommended for fibromyalgia treatment. Traditional Chinese exercise (TCE), including Taichi, Qigong, Badunjin, Wuqinxi, etc., as a kind of mind-body exercise, plays an important role in alleviating symptoms of FMS. The objective of this study is to summarize the available evidence, through meta-analysis, on the pain relief, quality of life, sleep improvement, and emotion regulation of FMS in TCE. METHODS: Databases of PubMed, EMBASE, Cochrane library, Google scholar, CNKI, WANFANG DATA, VIP, etc. were used to search eligible studies that were published from the time of their inception to February 11, 2022, in English and Chinese. The included studies were divided into two groups: TCE group (experimental group) and control group. The Cochrane collaboration's tool was used to assess the risk of bias, and Revman5.4.1 software was used to synthesize and analyze the data. RESULTS: A total of 12 literatures were included in this study, which contained 781 patients, and 448 of them were included in the treatment group, 333 of others in control group. TCE significantly alleviated pain [SMD = -0.83, 95% CI (-1.15, -0.51), p < .00001], improved quality of life [SMD = -0.53, 95% CI (-0.86, -0.19), p = .002] and improved qualities of sleep [SMD = -0.41, 95% CI (-0.57, -0.24), p < .00001] and relieved depression [SMD = -0.40, 95% CI (-0.69, -0.10), p < .008]. CONCLUSION: TCE may be a way to reduce pain, improve the quality of life and sleep, and relieve depression for FMS, and it could be part of the FMS treatment.

Deciphering the role of TNF­α­induced protein 8­like 2 in the pathogenesis of necrotizing enterocolitis in neonatal rats.

Neonatal necrotizing enterocolitis (NNEC) is a disease characterized by intestinal inflammation and ischemic necrosis. Despite progress having been made during decades of research, details regarding its pathophysiology remain to be elucidated. It is known that abnormal expressions of TNF-α-induced protein 8-like 2 (TIPE2) can be observed in several diseases. However, the expression of TIPE2 in necrotizing enterocolitis (NEC) rats has not been examined before. The present study aimed to describe the expression pattern of TIPE2 and its role in NNEC pathogenesis. An NEC rat model was generated and used in the present study. All rats were sacrificed when the phenotype developed and the intestine between the lower end of the duodenum and the ileocecal were collected for further study. Hematoxylin and eosin, and immunohistochemical staining, reverse transcription-quantitative PCR and western blotting analysis were used to examine the expression of TIPE2. The results showed that the average body weight was significantly decreased in the NEC group compared with the control group along with a significant decrease of TIPE2 expression. However, the expressions of phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase AKT were significantly increased in NEC rats. The correlation analysis showed that the expressions of TIPE2 and PI3K were negatively correlated with a correlation coefficient of -0.797. To further determine the association between TIPE2 and PI3K/AKT pathway, two groups of wild type Sprague Dawley rats were infected with recombinant adenovirus Ad-V and Ad-TIPE2 respectively. The results showed that the expression of TIPE2 was significantly increased among rats in the Ad-TIPE2-infected group (OE group) compared to the ones from the Ad-V-infected group (NC group). However, the mRNA and protein expressions of PI3K and AKT were significantly decreased in Ad-TIPE2-infected rates. The difference of each index between OE and NC groups was statistically significant. The present study showed that the expression of TIPE2 was downregulated in NEC rats. TIPE2 might be involved in the pathogenesis of NEC by activating the PI3K/Akt signaling pathway.

Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) Syndrome with Henoch-Schönlein Purpura: A Case Report.

Introduction: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare disease clinically characterized by a wide range of cutaneous and osteoarticular manifestations, involving multiple system impairments. Vasculitis is a rare comorbidity of SAPHO. Henoch-Schönlein purpura (HSP) is a vasculitis involving the capillaries and arterioles mediated by IgA immune complex. No case report of SAPHO syndrome with HSP was ever found. Case: Here we reported a case of SAPHO syndrome complicated with HSP and was successfully treated by methylprednisolone and tofacitinib. Discussion: Although the treat-to-target management of HSP and the first-line clinical medication have given some advices on the treatment. A precise treatment was still needed based on the pathogenesis of the comorbidity. The mechanism of the co-occurrence includes innate immunity and adapted immunity. Considering the active inflammatory reaction and the rapid disease progression, methylprednisolone and tofacitinib were prescribed. Conclusion: HSP is a new comorbidity of SAPHO. The spectrum of cutaneous small-vessel vasculitis in SAPHO syndrome was enriched. A new treatment approach for SAPHO with HSP was provided.

Integration of clinical features and sociodemographic factors: a simplified prognostic model for patients with multiple myeloma based on a double-center retrospective analysis.

This study aimed to develop and validate a prognostic nomogram that combines clinical and sociodemographic factors of patients with newly diagnosed multiple myeloma (MM). A total of 257 newly diagnosed patients with MM from two independent medical centers in China were included in this retrospective cohort study. Univariate and multivariate Cox regression models were used to identify independent risk factors and to construct the nomogram. The predictive ability of the nomogram was evaluated using the areas under the curve (AUCs) and calibration curves. K-fold cross-validation was employed for internal validation of the nomogram performance. Moreover, a stratification system to determine risk level was generated based on the nomogram. Hemoglobulin, creatinine, rurality, and marital status were significantly associated with overall survival (OS) and were incorporated into the nomogram for OS prediction. The prognostic nomogram showed good discrimination and accuracy, and its predictive capability was superior to the International Staging System. The AUC values predicting the 1-, 3-, and 5-year OS probabilities of the nomogram were 0.775, 0.755, and 0.754, respectively. Subsequently, patients were classified into high- and low-risk subgroups based on the median total points of the nomogram; this risk stratification clearly distinguished between high- and low-risk MM patients with significantly different clinical outcomes (median OS: 27 months vs. 84 months). We established a novel prognostic prediction model by comprehensively incorporating clinical and sociodemographic variables, which can effectively predict the survival outcomes in patients with MM.

Long non-coding RNA growth arrest-specific 5 inhibits liver fibrogenesis in biliary atresia by interacting with microRNA-222 and repressing IGF1/AKT signaling.

Background: Long non-coding RNA growth arrest-specific 5 (lncRNA GAS5) has been shown to inhibit liver fibrosis through serving as a competing endogenous RNA for microRNA-222 (miR-222). Progressive liver fibrosis is a typical characteristic of biliary atresia (BA). However, the role of GAS5/miR-222 and its underlying mechanisms remain largely unknown in BA. Methods: The expression of GAS5 was determined in the liver and primary hepatic stellate cells (HSCs) of BA patients. Then, the effects of GAS5 on the activation and proliferation of HSCs were evaluated. Furthermore, the interaction between GAS5 and miR-222 was investigated by a luciferase gene report assay. Next, the effects of IGF1/AKT signaling were determined to clarify the downstream mechanism of GAS5. Finally, GAS5 administration was performed to explore its role in an experimental BA mouse model. Results: GAS5 expression was decreased in liver tissues and HSCs of BA patients, and was inversely correlated with liver fibrosis in BA. Up-regulation of GAS5 in LX-2 cells significantly reduced smooth muscle α-actin (α-SMA) and collagen 1a1 (COL1A1) expression, inhibited cell proliferation and clone formation ability, induced S phase increase, and promoted cell apoptosis. Moreover, GAS5 was negatively regulated by miR-222, which promoted HSCs activation and proliferation, and was positively correlated with liver fibrosis in BA. Additionally, the expressions of IGF1, p-PI3K, and p-AKT were decreased when LX-2 cells over-expressed GAS5, whereas knockdown of IGF1 or AKT significantly decreased α-SMA and COL1A1 expression, suppressed cell proliferation, and enhanced cell apoptosis in LX-2 cells. Furthermore, GAS5 administration significantly increased apoptosis and reduced liver fibrosis, α-SMA and COL1A1 expressions in liver tissues of BA mice. Conclusions: GAS5 inhibited liver fibrosis in BA by interacting with miR-222 and regulating IGF1/AKT signaling, which may be a therapeutic target to alleviate liver fibrosis in BA.

Salt Tolerant Bacillus Strains Improve Plant Growth Traits and Regulation of Phytohormones in Wheat under Salinity Stress.

Soil salinity is a major constraint adversely affecting agricultural crops including wheat worldwide. The use of plant growth promoting rhizobacteria (PGPR) to alleviate salt stress in crops has attracted the focus of many researchers due to its safe and eco-friendly nature. The current study aimed to study the genetic potential of high halophilic Bacillus strains, isolated from the rhizosphere in the extreme environment of the Qinghai-Tibetan plateau region of China, to reduce salt stress in wheat plants. The genetic analysis of high halophilic strains, NMCN1, LLCG23, and moderate halophilic stain, FZB42, revealed their key genetic features that play an important role in salt stress, osmotic regulation, signal transduction and membrane transport. Consequently, the expression of predicted salt stress-related genes were upregulated in the halophilic strains upon NaCl treatments 10, 16 and 18%, as compared with control. The halophilic strains also induced a stress response in wheat plants through the regulation of lipid peroxidation, abscisic acid and proline in a very efficient manner. Furthermore, NMCN1 and LLCG23 significantly enhanced wheat growth parameters in terms of physiological traits, i.e., fresh weight 31.2% and 29.7%, dry weight 28.6% and 27.3%, shoot length 34.2% and 31.3% and root length 32.4% and 30.2%, respectively, as compared to control plants under high NaCl concentration (200 mmol). The Bacillus strains NMCN1 and LLCG23 efficiently modulated phytohormones, leading to the substantial enhancement of plant tolerance towards salt stress. Therefore, we concluded that NMCN1 and LLCG23 contain a plethora of genetic features enabling them to combat with salt stress, which could be widely used in different bio-formulations to obtain high crop production in saline conditions.

Outcomes of seromuscular bladder augmentation compared with standard bladder augmentation in the treatment of children with neurogenic bladder.

BACKGROUND: Intestinal seromuscular bladder augmentation (SMBA) surgery has produced no mucosal-related complications, but its outcomes need to be studied. AIM: To evaluate the safety and effectiveness of SMBA in the treatment of children with neurogenic bladder. METHODS: A retrospective analysis of the clinical data of children with SMBA was performed from March 2008 to February 2018, and the data were compared with those of children receiving standard cystoplasty (SC). RESULTS: In a cohort of 67 children who underwent bladder augmentation, the 46 children in the SC group had an average age of 10.6 years and a follow-up time of 36 mo, and the 21 children in the SMBA group had an average age of 7.6 years and a follow-up time of 29.7 mo. The preoperative and postoperative bladder volumes in the SMBA group were 151.7 mL and 200.4 mL, respectively, and those in the SC group were 173.9 mL and 387.0 mL, respectively. No significant difference in preoperative urinary dynamic parameters was found between the two groups, but the difference after operation was statistically significant. The main complications after SMBA were residual ureteral reflux and failed bladder augmentation, with incidences of 33.3% and 28.6%, respectively. In all 6 patients with failed augmentation in the SMBA group, ileum seromuscular patches were used for augmentation, and SC was chosen for reaugmentation. During reoperation, patch contracture and fibrosis were observed. CONCLUSION: The improvement of urinary dynamic parameters in the SMBA group was significantly lower than that in the SC group. Children with SMBA had a higher probability of patch contracture and reaugmentation, which might be related to impaired blood supply and urine stimulation, and the sigmoid colon patch should be the priority.

Bacillus halotolerans KKD1 induces physiological, metabolic and molecular reprogramming in wheat under saline condition.

Salt stress decreases plant growth and is a major threat to crop yields worldwide. The present study aimed to alleviate salt stress in plants by inoculation with halophilic plant growth-promoting rhizobacteria (PGPR) isolated from an extreme environment in the Qinghai-Tibetan Plateau. Wheat plants inoculated with Bacillus halotolerans KKD1 showed increased seedling morphological parameters and physiological indexes. The expression of wheat genes directly involved in plant growth was upregulated in the presence of KKD1, as shown by real-time quantitative PCR (RT-qPCR) analysis. The metabolism of phytohormones, such as 6-benzylaminopurine and gibberellic acid were also enhanced. Mining of the KKD1 genome corroborated its potential plant growth promotion (PGP) and biocontrol properties. Moreover, KKD1 was able to support plant growth under salt stress by inducing a stress response in wheat by modulating phytohormone levels, regulating lipid peroxidation, accumulating betaine, and excluding Na+. In addition, KKD1 positively affected the soil nitrogen content, soil phosphorus content and soil pH. Our findings indicated that KKD1 is a promising candidate for encouraging wheat plant growth under saline conditions.

Genome-wide analysis of HSP20 gene family and expression patterns under heat stress in cucumber (Cucumis sativus L.).

Cucumber is an important vegetable in China, and its yield and cultivation area are among the largest in the world. Excessive temperatures lead to high-temperature disorder in cucumber. Heat shock protein 20 (HSP20), an essential protein in the process of plant growth and development, is a universal protective protein with stress resistance. HSP20 plays crucial roles in plants under stress. In this study, we characterized the HSP20 gene family in cucumber by studying chromosome location, gene duplication, phylogenetic relationships, gene structure, conserved motifs, protein-protein interaction (PPI) network, and cis-regulatory elements. A total of 30 CsHSP20 genes were identified, distributed across 6 chromosomes, and classified into 11 distinct subgroups based on conserved motif composition, gene structure analyses, and phylogenetic relationships. According to the synteny analysis, cucumber had a closer relationship with Arabidopsis and soybean than with rice and maize. Collinearity analysis revealed that gene duplication, including tandem and segmental duplication, occurred as a result of positive selection and purifying selection. Promoter analysis showed that the putative promoters of CsHSP20 genes contained growth, stress, and hormone cis-elements, which were combined with protein-protein interaction networks to reveal their potential function mechanism. We further analyzed the gene expression of CsHSP20 genes under high stress and found that the majority of the CsHSP20 genes were upregulated, suggesting that these genes played a positive role in the heat stress-mediated pathway at the seedling stage. These results provide comprehensive information on the CsHSP20 gene family in cucumber and lay a solid foundation for elucidating the biological functions of CsHSP20. This study also provides valuable information on the regulation mechanism of the CsHSP20 gene family in the high-temperature resistance of cucumber.

The Role of Pyoluteorin from Pseudomonas protegens Pf-5 in Suppressing the Growth and Pathogenicity of Pantoea ananatis on Maize.

The rhizospheric bacterium Pseudomonas protegens Pf-5 can colonize the seed and root surfaces of plants, and can protect them from pathogen infection. Secondary metabolites, including lipopeptides and polyketides produced by Pf-5, are involved in its biocontrol activity. We isolated a crude extract from Pf-5. It exhibited significant surface activity and strong antibacterial activity against Pantoea ananatis DZ-12, which causes maize brown rot on leaves. HPLC analysis combined with activity tests showed that the polyketide pyoluteorin in the crude extract participated in the suppression of DZ-12 growth, and that the lipopeptide orfamide A was the major biosurfactant in the crude extract. Further studies indicated that the pyoluteorin in the crude extract significantly suppressed the biofilm formation of DZ-12, and it induced the accumulation of reactive oxygen species in DZ-12 cells. Scanning electron microscopy and transmission electron microscopy observation revealed that the crude extract severely damaged the pathogen cells and caused cytoplasmic extravasations and hollowing of the cells. The pathogenicity of DZ-12 on maize leaves was significantly reduced by the crude extract from Pf-5 in a dose-dependent manner. The polyketide pyoluteorin had strong antibacterial activity against DZ-12, and it has the potential for development as an antimicrobial agent.

DOK2 Has Prognostic and Immunologic Significance in Adults With Acute Myeloid Leukemia: A Novel Immune-Related Therapeutic Target.

Background: The role of downstream tyrosine kinase 2 (DOK2), a major member of the DOK family, remains poorly defined in acute myeloid leukemia (AML). Herein, we investigated the expression levels, clinical outcomes, and biological functions of DOK2 in patients with AML. Methods: Datasets were obtained from the Cancer Genome Atlas (TCGA) database for transcriptomic and clinical information. Nomogram construction and assessment were conducted using Cox regression analysis, receiver operating characteristic (ROC) curves, and calibration plots. Public databases, including the Gene Expression Omnibus, Cancer Cell Line Encyclopedia, LinkedOmics, GeneMANIA, TISIDB, and Gene Set Cancer Analysis, were employed for relevant bioinformatic studies. Moreover, we utilized the CIBERSORT algorithm to evaluate the level of infiltration of immune cells into the bone marrow microenvironment. Results: We observed that DOK2 transcription levels were markedly upregulated in AML samples (P < 0.001), and its high expression was associated with inferior overall survival (OS) (HR = 2.17, P < 0.001) and disease-free survival (DFS) (HR = 2.50, P < 0.001). ROC curve analysis also showed the reliable diagnostic efficiency of DOK2 in AML. For treatment regimens, patients with high DOK2 expression could significantly prolong OS by receiving hematopoietic stem cell transplantation (HSCT) (P < 0.001), whereas those with low DOK2 expression were more likely to improve DFS by chemotherapy alone rather than HSCT. Nomograms constructed for predicting OS and DFS exhibited satisfactory discrimination and accuracy. Functional enrichment analysis identified that DOK2 was involved in important pathways associated with immune-related activities. Furthermore, CIBERSORT scores reflected negative correlations of DOK2 with activated mast cells and resting CD4+ memory T cells, which indicated its adverse immunomodulatory potential. Conclusion: We suggest that elevated DOK2 expression could be an unfavorable prognostic indicator of survival in patients with AML. Our findings provide new insights into the role of DOK2 in AML, with promising clinical implications.

Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats.

Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague-Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF-ß1, Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also measured by reverse transcription-quantitative PCR, western blotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF-ß1, Collagen I, Collagen III and α-SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB.

Glucose-6-phosphate dehydrogenase and abscisic acid mediate programmed cell death induced by aluminum toxicity in soybean root tips.

Programmed cell death (PCD) induced by aluminum (Al) is considered an important reason of Al phytotoxicity. However, the underlying mechanism of how Al induces PCD remains largely unknown in plants. The roles of glucose-6-phosphate dehydrogenase (G6PDH) and abscisic acid (ABA) in regulating Al-induced PCD were investigated in soybean roots. Al treatment increased G6PDH activity, while inhibition of G6PDH activity alleviated PCD occurrence and reactive oxygen species (ROS) accumulation under Al stress. Overexpression of cytosolic G6PDH1 enhanced G6PDH activity, thus promoting ROS production and cell death under Al exposure. Inhibition of NADPH oxidase activity mitigated ROS generation and cell death under Al stress. Further investigation demonstrated that G6PDH positively regulated the activity of NADPH oxidase under Al treatment using pharmacological and transgenic approach. Furthermore, Al stress increased ABA production, while inhibition of ABA biosynthesis alleviated PCD occurrence and ROS accumulation under Al stress. Interestingly, ABA upregulated G6PDH1 expression and G6PDH activity under Al stress. These results suggest that G6PDH mediates Al-induced PCD occurrence through the activation of NADPH oxidase-dependent ROS production, and ABA acts upstream of G6PDH in this process. This study will provide novel clues for the improvement of Al phytotoxicity in acidic soils.

Genomic Features and Molecular Function of a Novel Stress-Tolerant Bacillus halotolerans Strain Isolated from an Extreme Environment.

Due to its topographical position and climatic conditions, the Qinghai-Tibet Plateau possesses abundant microorganism resources. The extremophilic strain KKD1 isolated from Hoh Xil possesses strong stress tolerance, enabling it to propagate under high salinity (13%) and alkalinity (pH 10.0) conditions. In addition, KKD1 exhibits promising biocontrol activity against plant pathogens. To further explore these traits at the genomic level, we performed whole-genome sequencing and analysis. The taxonomic identification according to the average nucleotide identity based on BLAST revealed that KKD1 belongs to Bacillus halotolerans. Genetic screening of KKD1 revealed that its stress resistance mechanism depends on osmotic equilibrium, membrane transportation, and the regulation of ion balance under salt and alkaline stress. The expression of genes involved in these pathways was analyzed using real-time quantitative PCR. The presence of different gene clusters encoding antimicrobial secondary metabolites indicated the various pathways by which KKD1 suppresses phytopathogenic growth. Moreover, the lipopeptides surfactin and fengycin were identified as being significant antifungal components of KKD1. Through comparative genomics analysis, we noticed that KKD1 harbored specific genes involved in stress resistance and biocontrol, thus providing a new perspective on the genomic features of the extremophilic Bacillus species.

Surgical outcomes of bladder augmentation: A comparison of three different augmentation procedures.

BACKGROUND: Augmentation cystoplasty is indispensable in many pediatric diseases, especially neurogenic bladder. Various methods and materials are used to augment the bladder, and these methods are associated with different shortcomings and complications. AIM: The present study reported the mid-term outcomes of patients undergoing various bladder augmentation procedures in a single institution, and assessed whether seromuscular cystoplasty lined with urothelium (SCLU) provided better urodynamic results than auto-augmentation (AA). METHODS: A retrospective review of 96 patients undergoing various augmentation methods between 2003 and 2018 was performed. The patients were divided into three groups according to the type of augmentation, and their outcomes were compared. All patients developed neurogenic bladder due to myelomeningocele or sacrococcygeal teratoma. The clinical data of all patients were collected. RESULTS: The mean ages at surgery in the three groups (standard cystoplasty [SC], SCLU, AA) were 10.8, 7.5, and 4.8 years, respectively, with mean follow-ups of 36, 61, and 36 mo, respectively. The mean preoperative and postoperative bladder capacities of the SC, SCLU, and AA groups were 174 ± 11.7 vs. 387 ± 13.7 (P < 0.0001), 165 ± 12.2 vs. 240 ± 14.7 (P = 0.0002), and 138 ± 16.7 vs. 181 ± 9.9 (P = 0.0360), respectively. Compared with the AA group, the SCLU procedure did not have better postoperative urodynamic parameters. Incontinence was reduced in most patients. The mean times of clean intermittent catheterization per day in the SC, SCLU, and AA groups were 5.6, 7.8, and 8.2, respectively. The main complications of the SC group were recurrent urinary tract infections (8%) and bladder calculi (6%). Re-augmentation was done in patients in the SCLU (8) and AA (3) groups. CONCLUSION: SC provided sufficient bladder capacity and improved compliance with acceptable complications. After AA and SCLU, the patients acquired limited increases in bladder capacity and compliance with a high rate of re-augmentation. Compared with AA, SCLU did not yield better postoperative urodynamic parameters.

Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial.

OBJECTIVE: To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. METHODS: In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18-35 years; body mass index <28 kg/m2; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. RESULTS: The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p<0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p<0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. CONCLUSION: Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinflammatory factors, which might confer adverse consequences for long-term health outcomes. TRIAL REGISTRATION NUMBER: NCT02355795; Results.