Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

A High-Performance N2-Selective MXene Membrane with Double Selectivity Mechanism for N2/CH4 Separation.

Membrane-based separation process for unconventional natural gas purification (mainly N2/CH4 separation) has attracted more attention due to its considerable economic benefits. However, the majority of separation membranes at this stage, particularly N2-selective membranes, achieve the desired separation target by mainly relying on the diffusivity-selectivity mechanism. To overcome the limitation of a single mechanism, 2D lamellar MXene membranes with a double selectivity mechanism are prepared to enhance N2 permeance and N2/CH4 selectivity via introducing unsaturated metal sites into MXene, which can form specific interactions with N2 molecules and enhance N2 permeation. The resulting membranes exhibit an inspiring N2/CH4 separation performance with an N2 permeance of 344 GPU and N2/CH4 selectivity of 13.76. The collaboration of the double selectivity mechanism provides a new idea for the development of a novel N2-selective membrane for N2 removal and CH4 purification, which further broadens the application prospects of membrane separation technology in the field of unconventional natural gas purification.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Diastereomers of Steroidal Alkaloids with Cytotoxic Activities against Non-Small-Cell Lung Cancer from the Bulbs of Fritillaria sinica.

Eleven new steroidal alkaloids, along with nine known related compounds, were isolated from the bulbs of Fritillaria sinica. Seven pairs of diastereomers were identified, including six and four 20-deoxy cevanine-type steroidal alkaloid diastereomers with molecular weights of 413 and 415, respectively. Structures were elucidated based on spectroscopic data analysis, chemical derivatization, and single-crystal X-ray diffraction analysis. Compounds 5, 9, 11, 12, 16, and 20 exhibited significant in vitro cytotoxic activity against non-small-cell lung cancer with CC50 values from 6.8 ± 3.9 to 12 ± 5 µM.

TOPK promotes the development of psoriasis and worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity.

BACKGROUND: Psoriasis is an inflammatory skin disease. The pathogenesis of psoriasis has not been fully elucidated. T-lymphokine-activated killer cell-originated protein kinase (TOPK) activity increases in a proinflammatory environment, and inhibiting TOPK blocks inflammation. However, whether TOPK is involved in the pathogenesis of psoriasis remains to be identified. OBJECTIVES: We aimed to study the role of TOPK in psoriasis and attempted to find a drug targeting TOPK for the prevention and treatment of psoriasis. METHOD: Firstly, the expressions of TOPK in psoriatic patients, psoriatic cell and animal model were analysed by Gene Expression Omnibus database, immunohistochemistry (IHC) staining and western blot (WB). After inhibiting TOPK by chemical or gene knockout, the effect of TOPK on the development of psoriasis was verified in cell and animal model by WB, qRT-PCR, ELISA, haematoxylin-eosin (H&E) and IHC staining. Moreover, phosphoproteomic analysis was performed to explore the signalling pathways regulated by TOPK in the occurrence and development of psoriasis. Then, an in vitro kinase assay was performed to prove TOPK kinase activity was inhibited by worenine. Ultimately, WB, qRT-PCR, ELISA, H&E and IHC staining were used to verify the anti-psoriasis effect of worenine by inhibiting TOPK was in cell and animal model. RESULTS: In this study, we found that TOPK was highly expressed in psoriasis patients, psoriatic cell and animal model, which suggests that TOPK might be associated with psoriasis pathogenesis. Interestingly, chemical or genetic inhibition of TOPK alleviated M5- and imiquimod (IMQ)-induced psoriasis-like dermatitis, which further confirmed the role of TOPK in promoting the development of psoriasis. Moreover, we determined that worenine inhibited TOPK kinase activity. In addition, worenine relieved M5- and IMQ-induced psoriasiform dermatitis by inhibiting TOPK activity. CONCLUSIONS: T-lymphokine-activated killer cell-originated protein kinase promotes the development of psoriasis. Therefore, TOPK might be a promising drug target for the prevention and treatment of psoriasis. Worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity, providing new strategies for clinical intervention.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Identifying the function of the PI3K-AKT pathway during the pathogenic infection of Macrobrachium rosenbergii.

The phosphoinositide-3-kinase/protein kinase b (PI3K-Akt) pathway is a signalling pathway based on protein phosphorylation and can be activated by a wide range of factors. To investigate the function of the PI3K-AKT signalling pathway in antibacterial immunity, we analysed the gene expression level of three key factors (PI3K, AKT and FoxO) and innate immune factors in immune tissues at different time points after Vibrio parahaemolyticus and Staphylococcus aureus infection. Tissues analysis showed that PI3K, AKT, and FoxO were expressed at high levels in the intestinal, hemocytes and hepatopancreas. Moreover, the expression levels of PI3K, AKT and FoxO can be regulated postinfection by different pathogens. In hemocytes and the intestine, V. parahaemolyticus infection was found to regulate the levels of PI3K, AKT, and FoxO more rapidly; however, an S. aureus infection regulated the levels of these factors more rapidly in the hepatopancreas and gills. Analysis showed that V. parahaemolyticus and S. aureus infection caused changes in the gene expression level of crustin, caspase 3 and NF-κB. Therefore, PI3K-AKT regulates the downstream immune pathway differentially in different immune tissues and participates in the regulation of cell apoptosis and the inflammatory response by activating caspase and NF-κB, respectively, following infection with V. parahaemolyticus and S. aureus.

Maternal exposure to dibutyl phthalate (DBP) impairs angiogenesis and AR signalling pathway through suppression of TGFB1I1 in hypospadias offspring.

Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.

Effects of glutaraldehyde and povidone-iodine on apoptosis of grass carp liver and hepatocytes.

Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.

Epigallocatechin-3-gallate mitigates cadmium-induced intestinal damage through modulation of the microbiota-tryptophan-aryl hydrocarbon receptor pathway.

Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5 mg kg-1) for four weeks. Through 16 S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20 mg kg-1) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1 µg/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG.

Chemical constituents from the leaves and branches of Wikstroemia chamaedaphne with their activation of latent HIV activities.

A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7-9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 µM and compounds 1, 9-11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.

Dual Functional Ultrasensitive Point-of-Care Clinical Diagnosis Using Metal-Organic Frameworks-Based Immunobeads.

Sepsis is an acute systemic infectious syndrome with high fatality. Fast and accurate diagnosis, monitoring, and medication of sepsis are essential. We exploited the fluorescent metal-AIEgen frameworks (MAFs) and demonstrated the dual functions of protein detection and bacteria identification: (i) ultrasensitive point-of-care (POC) detection of sepsis biomarkers (100 times enhanced sensitivity); (ii) rapid POC identification of Gram-negative/positive bacteria (selective aggregation within 20 min). Fluorescent lateral flow immunoassays (LFAs) are convenient and inexpensive for POC tests. MAFs possess a large surface area, excellent photostability, high quantum yield (∼80%), and multiple active sites serving as protein binding domains for ultrasensitive detection of sepsis biomarkers (IL-6/PCT) on LFAs. The limit of detection (LOD) for IL-6/PCT is 0.252/0.333 pg/mL. Rapid appraisal of infectious bacteria is vital to guide the use of medicines. The dual-functional fluorescent MAFs have great potential in POC tests for the clinical diagnosis of bacterial infections.

Aldehyde Dehydrogenase 2 (ALDH2) rs671 Polymorphism is a Predictor of Pulmonary Hypertension Due to Left Heart Disease.

AIM: Pulmonary hypertension due to left heart disease (PH-LHD) is commonly seen in patients with heart failure (HF), but there are limited treatment options. Recent studies have shown an association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and pulmonary hypertension (PH). Therefore, this study aimed to investigate the occurrence of ALDH2 rs671 polymorphisms, and the association between ALDH2 and risk of PH-LHD in patients with HF. It also investigated different ALDH2 genotypes and examined their association with cardiac structure and function in HF patients with PH-LHD. METHODS: A total of 178 HF patients were consecutively enrolled in this study: 102 without PH-LHD and 76 with PH-LHD. Clinical data, parameters of echocardiography, and relevant biochemical indexes were recorded in both groups. Differences in data obtained between groups were compared, and the risk of variant ALDH2 polymorphisms with PH-LHD in HF patients was analysed using univariate and multivariate logistic regression. RESULTS: The prevalence of ALDH2 rs671 GA/AA polymorphisms (variant ALDH2) was 24 of 102 patients (23.53%) in the HF without PH-LHD group, and 32 of 76 patients (42.10%) in the HF with PH-LHD group, with a statistically significant difference. Univariate and multivariate logistical regression showed that variant ALDH2 is an independent risk factor for HF combined with PH-LHD. A higher proportion of patients with variant ALDH2 in the HF with PH-LHD group had a tricuspid regurgitation velocity >2.8 m/s, and they had higher values of peak early diastolic velocity of the mitral orifice/peak velocity of the early diastolic wave of the mitral orifice, maximum frequency shift of pulmonary valve flow, and pulmonary artery stiffness. CONCLUSIONS: Variant ALDH2 may be an independent risk factor for HF combined with PH-LHD. Variant ALDH2 may also be involved in pulmonary artery remodelling and is a potential new target for clinical treatment of PH-LHD.

Robotic Gastrectomy Versus Laparoscopic Gastrectomy for Gastric Cancer: A Multicenter Cohort Study of 5402 Patients in China.

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching. The primary outcome was postoperative complications. RESULTS: After propensity score matching, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001).The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.

Transcriptome analysis of Macrobrachium rosenbergii hemocytes in response to Staphylococcus aureus infection.

The aquaculture industry has suffered significant financial losses as a result of disease outbreaks. In particular, disease outbreaks have become a major problem that can seriously affect the sustainable development of the Macrobrachium rosenbergii aquaculture industry. It is crucial to determine the defense mechanism of the host after pathogenic invasion in order to provide effective defense measures after disease outbreaks. Shrimp, like other invertebrates, primarily depend on their innate immune systems to defend against pathogens, and recognize and resist pathogens through humoral and cellular immune responses. In this investigation, we used RNA-seq technology to investigate the transcriptome of hemocytes from M. rosenbergii induced by Staphylococcus aureus. Our main targets were immune pathways and genes related to innate immunity. RNA-seq identified 209,069 and 204,775 unigenes in the control and experimental groups, respectively. In addition, we identified 547 and 1734 differentially expressed genes (DEGs) following S. aureus challenge after 6 and 12 h (h), respectively. GO and KEGG enrichment analysis revealed that the DEGs were significantly enriched in several biological signalling pathways, including NOD-like receptor, PI3K-Akt, Toll and Imd, IL-17, TGF-beta, RIG-I-like receptor, cAMP, apoptosis, and C-type lectin receptor. Sixteen DEGs were chosen at random for qPCR verification; these results concurred with those from sequencing. Our findings revealed that immune-related genes play an important role in antibacterial activities and have specific functions for gram-positive bacteria. These results provide more data for the prevention of M. rosenbergii diseases and offer a basis for the better prevention of diseases.

Transcriptome analysis of Macrobrachium rosenbergii hemocytes reveals in-depth insights into the immune response to Vibrio parahaemolyticus infection.

Macrobrachium rosenbergii as one of the common freshwater prawn species in Southeast Asia, which breeding industry is seriously threatened by vibriosis and causes high mortality. In this study, the RNA-seq was employed for assessing the M. rosenbergii hemocytes transcriptomes following Vibrio parahaemolyticus challenge. After challenge for 6 h (h), there were overall 1849 DEGs or differentially expressed genes, including 1542 up-regulated and 307 down-regulated genes, and there was a total of 1048 DEGs, including 510 up-regulated genes and 538 down-regulated genes, after challenge for 12 h. Mitogen-activated protein kinase (MAPK) immune-related pathways, Toll, immune deficiency (IMD), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) were among the immune pathways where a lot of the DEGs were connected. The expression patterns of 18 chosen immune-related genes were examined utilizing qRT-PCR or quantitative real-time polymerase chain reaction, which revealed that the V. parahaemolyticus infection activated the M. rosenbergii's immune response. Permutational multivariate analysis of variance (PERMANOVA) showed that V. parahaemolyticus infection modulated immune regulation and apoptosis pathways. The gathered information provided new insight into M. rosenbergii's immunity and suggested a novel approach to fight against bacterial infection.

Characterization analysis of TLR5a and TLR5b immune response after different bacterial infection in grass carp (Ctenopharyngodon idella).

Toll-like receptor (TLR) is an important pattern recognition receptor, which specifically recognizes microbial components, and TLR5 recognizes bacterial flagellin in vertebrates and invertebrates. In this study, two forms of TLR5 (TLR5a and TLR5b) were identified in grass carp (Ctenopharyngodon idella). Aeromonas hydrophila and Staphylococcus aureus were used to investigate the role of grass carp TLR5a and TLR5b against bacteria (flagellate and non-flagellate) in innate immunity, and the expression of TLR5a and TLR5b genes and proteins were detected in immune-related tissues. Quantitative real-time polymerase chain reaction results showed that TLR5a and TLR5b genes of grass carp were highly expressed in the liver, spleen, and head kidney, and their expression patterns were similar in tissues. Meanwhile, the TLR5b gene expression was higher than TLR5a in most tissues. Following exposure to A. hydrophila and S. aureus, the expression levels of TLR5a and TLR5b genes in the liver, spleen, and head kidney were up-regulated significantly. Moreover, the downstream gene, NF-κB, was up-regulated significantly. After A. hydrophila infection, the expression of TLR5a gene was up-regulated in the liver and spleen at 24 h, while TLR5b was up-regulated at 6 h. In the head kidney, TLR5a was up-regulated at 6 h, while TLR5b was up-regulated at 6 h and 12 h. After S. aureus infection, TLR5a and TLR5b were up-regulated at 6 h in the liver and 12 h in the spleen. However, in the head kidney, TLR5a was down-regulated, while TLR5b was up-regulated. Compared with TLR5a, TLR5b had a higher expression level and stronger response to pathogen stimulation. The immunofluorescence results showed that TLR5a and TLR5b proteins in the liver of grass carp infected with A. hydrophila and S. aureus were similar but different in the spleen and head kidney. The results indicated that TLR5a and TLR5b play a critical role in resisting bacterial infection, and TLR5a and TLR5b had obvious tissue and pathogen specificity. TLR5b may play a major role in immune tissues, while TLR5a may play an auxiliary regulatory role in early infection. In addition, TLR5a and TLR5b have an irreplaceable regulatory role in response to flagellate and non-flagellate bacteria. This lays a foundation to explore further the role of TLR5 in resisting flagellate and non-flagellate infections in fish and provides a reference for the innate immunity research of grass carp.

The Keap1-Nrf2 signaling pathway regulates antioxidant defenses of Ctenopharyngodon idella induced by bacterial infection.

Respiratory burst is a process involving rapid production of reactive oxygen species (ROS) for eliminating invading pathogens. However, excessive ROS production can be fatal to the host organism. The Keap1-Nrf2-ARE (Kelch-like ECH-associated protein 1 [Keap1]; Nuclear factor erythroid-derived 2-like 2 [Nrf2]; Antioxidant responsive element [ARE]) signaling pathway plays an important role in alleviating oxidative stress and preserving cellular homeostasis. However, the role of Keap1 during bacterial infection in fish remains unclear. In this study, we cloned and characterized the Keap1 gene of grass carp (CiKeap1) for the first time. CiKeap1 encodes a 593-amino acid protein of the Keap1b type. The tissue distribution analysis data revealed that the brain contains the highest transcription level of Keap1, followed by the heart and liver. The infection of Aeromonas hydrophila and Staphylococcus aureus obviously modulated the gene transcription and protein expression levels of Keap1, which suggested that the CiKeap1 participates in antibacterial immune responses. Furthermore, in vitro overexpression assays clarified the defensive and regular roles of CiKeap1 in maintaining host redox homeostasis in response to bacterial infection through the Keap1-Nrf2-ARE signaling pathway. In conclusion, the present results provide an expanded perspective on the role of Keap1 in teleost immunology that can guide healthy farming cultivation of grass carp.

A rare case of severe leptospirosis infection presenting as septic shock in a non-endemic area: a case report and literature review.

BACKGROUND: Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and myalgia, to severe forms. Leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis when clinical similarities exist. CASE PRESENTATION: A 63-year-old man presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage. Peripheral blood Metagenomic Next-generation Sequencing (mNGS) reported Leptospira interrogans. The patient was treated with piperacillin-tazobactam (TZP) plus doxycycline and improved dramatically after 7 days. CONCLUSION: We conclude that leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis. Correctly evaluation of thrombocytopenia in acute febrile illnesses facilitates the differential diagnosis of leptospirosis. mNGS can accurately detect Leptospira DNA during the early stage of the infection.

Upregulation of FGF7 Induced Intravesical Prostatic Protrusion of Benign Prostatic Hyperplasia via the ERK1/2 Signaling Pathway.

INTRODUCTION: Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. METHODS: Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. RESULTS: First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. CONCLUSIONS: Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression.