Predicting prostate cancer recurrence: Introducing PCRPS, an advanced online web server.

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. About 30% of PCa will develop a biochemical recurrence (BCR) following initial treatment, which significantly contributes to prostate cancer-related deaths. In clinical practice, accurate prediction of PCa recurrence is crucial for making informed treatment decisions. However, the development of reliable models and biomarkers for predicting PCa recurrence remains a challenge. In this study, the aim is to establish an effective and reliable tool for predicting the recurrence of PCa. Methods: We systematically screened and analyzed potential datasets to predict PCa recurrence. Through quality control analysis, low-quality datasets were removed. Using meta-analysis, differential expression analysis, and feature selection, we identified key genes associated with recurrence. We also evaluated 22 previously published signatures for PCa recurrence prediction. To assess prediction performance, we employed nine machine learning algorithms. We compared the predictive capabilities of models constructed using clinical variables, expression data, and their combinations. Subsequently, we implemented these machine learning models into a user-friendly web server freely accessible to all researchers. Results: Based on transcriptomic data derived from eight multicenter studies consisting of 733 PCa patients, we screened 23 highly influential genes for predicting prostate cancer recurrence. These genes were used to construct the Prostate Cancer Recurrence Prediction Signature (PCRPS). By comparing with 22 published signatures and four important clinicopathological features, the PCRPS exhibited a robust and significantly improved predictive capability. Among the tested algorithms, Random Forest demonstrated the highest AUC value of 0.72 in predicting PCa recurrence in the testing dataset. To facilitate access and usage of these machine learning models by all researchers and clinicians, we also developed an online web server (https://urology1926.shinyapps.io/PCRPS/) where the PCRPS model can be freely utilized. The tool can also be used to (1) predict the PCa recurrence by clinical information or expression data with high accuracy. (2) provide the possibility of PCa recurrence by nine machine learning algorithms. Furthermore, using the PCRPS scores, we predicted the sensitivity of 22 drugs from GDSC2 and 95 drugs from CTRP2 to the samples. These predictions provide valuable insights into potential drug sensitivities related to the PCRPS score groups. Conclusion: Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment for PCa.

Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway.

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk.

BACKGROUND: The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized. RESULTS: In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection. CONCLUSION: Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.

Identification and biological characteristics of Enterococcus casseliflavus TN-47 isolated from Monochamus alternatus.

With the widespread use of antibiotics, the incidence of antibiotic resistance in microorganisms has increased. Monochamus alternatus is a trunk borer of pine trees. This study aimed to investigate the in vitro antimicrobial and biological characteristics of Enterococcus casseliflavus TN-47 (PP411196), isolated from the gastrointestinal tract of M. alternatus in Jilin Province, PR China. Among 13 isolates obtained from the insects, five were preliminarily screened for antimicrobial activity. E. casseliflavus TN-47, which exhibited the strongest antimicrobial activity, was identified. E. casseliflavus TN-47 possessed antimicrobial activity against Staphylococcus aureus USA300 and Salmonella enterica serovar Pullorum ATCC 19945. Furthermore, E. casseliflavus TN-47 was sensitive to tetracyclines, penicillins (ampicillin, carbenicillin, and piperacillin), quinolones and nitrofuran antibiotics, and resistant to certain beta-lactam antibiotics (oxacillin, cefradine and cephalexin), macrolide antibiotics, sulfonamides and aminoglycosides. E. casseliflavus TN-47 could tolerate low pH and pepsin-rich conditions in the stomach and grow in the presence of bile acids. E. casseliflavus TN-47 retained its strong auto-aggregating ability and hydrophobicity. This strain did not exhibit any haemolytic activity. These results indicate that E. casseliflavus TN-47 has potential as a probiotic. This study provides a theoretical foundation for the future applications of E. casseliflavus TN-47 and its secondary metabolites in animal nutrition and feed.

The learning curve and experience of a novel multi-modal image fusion targeted transperineal prostate biopsy technique using electromagnetic needle tracking under local anesthesia.

Background: Prostate cancer is the most common malignant tumor of male genitourinary system, and the gold standard for its diagnosis is prostate biopsy. Focusing on the methods and skills of prostate biopsy, we explored the learning curve and experience of a novel magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) image fusion transperineal biopsy (TPB) technique using electromagnetic needle tracking under local anesthesia. Methods: The clinical and pathological data of 92 patients who underwent targeted TPB from January 2023 to July 2023 in our center were prospectively collected. The cumulative sum (CUSUM) analysis method and the best fitting curve were used to analyze the learning curve of this novel technique, and the clinical characteristics, perioperative data and tumor positive rate of prostate biopsy of patients at different stages of the learning curve were compared. Results: With the increase of the number of surgical cases, the overall operative time showed a downward trend. The best fitting curve of CUSUM reached its peak at the twelfth case, which is the minimum cumulative number of surgical cases needed to cross the learning curve of the operation. Taking this as the boundary, the learning curve is divided into two stages: learning improvement stage (group A, 12 cases) and proficiency stage (group B, 80 cases). The surgical time and visual analog scale score during prostate biopsy in group A were significantly higher than those in group B. The visual numerical scale score during prostate biopsy in group A was significantly lower than that in group B. There was no statistically significant difference between group A and group B in the detection rate of csPCa and the incidence of perioperative complications. Conclusion: The novel targeted TPB technique is divided into learning improvement stage and proficiency stage, and 12 cases may be the least cumulative number.

Assessment of carbon sequestration potential of mining areas under ecological restoration in China.

Mining activities aggravate the ecological degradation and emission of greenhouse gases throughout the world, thereby affecting the global climate and posing a serious threat to the ecological safety. Vegetation restoration is considered to be an effective and sustainable strategy to improve the post-mining soil quality and functions. However, we still have a limited knowledge of the impact of vegetation restoration on carbon sequestration potential in mining areas. In this pursuit, the present study was envisaged to integrate the findings from studies on soil organic carbon (SOC) sequestration in mining areas under vegetation restoration with field monitoring data. The carbon sequestration potential under vegetation restoration in China's mining areas was estimated by using a machine learning model. The results showed that (1) Vegetation restoration exhibited a consistently positive impact on the changes in the SOC reserves. The carbon sequestration potential was the highest in mixed forests, followed by broad-leaved forests, coniferous forests, grassland, shrubland, and farmland; (2) The number of years of vegetation restoration and mean annual precipitation were found to be the important moderating variables affecting the SOC reserves in reclaimed soils in mining areas; (3) There were significant differences in the SOC sequestration potential under different vegetation restoration scenarios in mining areas in China. The SOC sequestration potential reached up to 9.86 million t C a-1, when the soil was restored to the initial state. Based on the meta-analysis, the maximal attainable SOC sequestration potential was found to be 4.26 million t C a-1. The SOC sequestration potential reached the highest level of 12.86 million t C a-1, when the optimal vegetation type in a given climate was restored. The results indicated the importance of vegetation restoration for improving the soil sequestration potential in mining areas. The time lag in carbon sequestration potential for different vegetation types in mining areas was also revealed. Our findings can assist the development of ecological restoration regimens in mining areas to mitigate the global climate change.

Glutamine sustains energy metabolism and alleviates liver injury in burn sepsis by promoting the assembly of mitochondrial HSP60-HSP10 complex via SIRT4 dependent protein deacetylation.

Burns and burn sepsis, characterized by persistent and profound hypercatabolism, cause energy metabolism dysfunction that worsens organ injury and systemic disorders. Glutamine (Gln) is a key nutrient that remarkably replenishes energy metabolism in burn and sepsis patients, but its exact roles beyond substrate supply is unclear. In this study, we demonstrated that Gln alleviated liver injury by sustaining energy supply and restoring redox balance. Meanwhile, Gln also rescued the dysfunctional mitochondrial electron transport chain (ETC) complexes, improved ATP production, reduced oxidative stress, and protected hepatocytes from burn sepsis injury. Mechanistically, we revealed that Gln could activate SIRT4 by upregulating its protein synthesis and increasing the level of Nicotinamide adenine dinucleotide (NAD+), a co-enzyme that sustains the activity of SIRT4. This, in turn, reduced the acetylation of shock protein (HSP) 60 to facilitate the assembly of the HSP60-HSP10 complex, which maintains the activity of ETC complex II and III and thus sustain ATP generation and reduce reactive oxygen species release. Overall, our study uncovers a previously unknown pharmacological mechanism involving the regulation of HSP60-HSP10 assembly by which Gln recovers mitochondrial complex activity, sustains cellular energy metabolism and exerts a hepato-protective role in burn sepsis.

Trained immunity in recurrent Staphylococcus aureus infection promotes bacterial persistence.

Bacterial persister cells, a sub-population of dormant phenotypic variants highly tolerant to antibiotics, present a significant challenge for infection control. Investigating the mechanisms of antibiotic persistence is crucial for developing effective treatment strategies. Here, we found a significant association between tolerance frequency and previous infection history in bovine mastitis. Previous S. aureus infection led to S. aureus tolerance to killing by rifampicin in subsequent infection in vivo and in vitro. Actually, the activation of trained immunity contributed to rifampicin persistence of S. aureus in secondary infection, where it reduced the effectiveness of antibiotic treatment and increased disease severity. Mechanically, we found that S. aureus persistence was mediated by the accumulation of fumarate provoked by trained immunity. Combination therapy with metformin and rifampicin promoted eradication of persisters and improved the severity of recurrent S. aureus infection. These findings provide mechanistic insight into the relationship between trained immunity and S. aureus persistence, while providing proof of concept that trained immunity is a therapeutic target in recurrent bacterial infections involving persistent pathogens.

Enhanced thermophilic dark fermentation of hydrogen production from food waste by Fe-modified biochar.

The industrialization of hydrogen production through dark fermentation of food waste faces challenges, such as low yields and unpredictable fermentation processes. Biochar has emerged as a promising green additive to enhance hydrogen production in dark fermentation. Our study demonstrated that the introduction of Fe-modified biochar (Fe-L600) significantly boosted hydrogen production during thermophilic dark fermentation of food waste. The addition of Fe-L600 led to a remarkable 31.19% increase in hydrogen yield and shortened the time needed for achieving stabilization of hydrogen production from 18 h to 12 h. The metabolite analysis revealed an enhancement in the butyric acid pathway as the molar ratio of acetic acid to butyric acid decreased from 3.09 to 2.69 but hydrogen yield increased from 57.12 ± 1.48 to 76.78 ± 2.77 mL/g, indicating Fe-L600 improved hydrogen yield by regulating crucial metabolic pathways of hydrogen production. The addition of Fe-L600 also promoted the release of Fe2+ and Fe3+ and increased the concentrations of Fe2+ and Fe3+ in the fermentation system, which might promote the activity of hydrogenase and ferredoxin. Microbial community analysis indicated a substantial increase in the relative abundance of Thermoanaerobacterium after thermophilic dark fermentation. The relative abundances of microorganisms responsible for hydrolysis and acidogenesis were also observed to be improved in the system with Fe-L600 addition. This research provides a feasible strategy for improving hydrogen production of food waste and deepens the understanding of the mechanisms of biochar.

DNA methylation and histone post-translational modifications in atherosclerosis and a novel perspective for epigenetic therapy.

Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract.

FHIP1A-DT is a potential novel diagnostic, prognostic, and therapeutic biomarker of colorectal cancer: A pan-cancer analysis.

BACKGROUND: FHIP1A-DT is a long non-coding RNA (lncRNA) obtained by divergent transcription whose mechanism in pan-cancer and colorectal cancer (CRC) is unclear. We elucidated the molecular mechanism of FHIP1A-DT through bioinformatics analysis and in vitro experiments. METHODS: Pan-cancer and CRC data were downloaded from the University of California, Santa Cruz (UCSC) Genome Browser and the Cancer Genome Atlas (TCGA). We analyzed FHIP1A-DT expression and its relationship with clinical stage, diagnosis, prognosis, and immunity characteristics in pan-cancer. We also analyzed FHIP1A-DT expression in CRC and explored the relationship between FHIP1A-DT and CRC diagnosis and prognosis. Then, we analyzed the correlation between FHIP1A-DT and drug sensitivity, immune cell infiltration, and the biological processes involved in FHIP1A-DT. The competing endogenous RNA (ceRNA) regulatory network associated with FHIP1A-DT was explored. External validation was conducted using external data sets GSE17538 and GSE39582 and in vitro experiments. RESULTS: FHIP1A-DT expression was different in pan-cancer and had excellent diagnostic and prognostic capability for pan-cancer. FHIP1A-DT was also related to the pan-cancer tumor mutation burden (TMB), microsatellite instability (MSI), and immune cell content. FHIP1A-DT was downregulated in CRC, where patients with CRC with low FHIP1A-DT expression had a worse prognosis. A nomogram combined with FHIP1A-DT expression demonstrated excellent predictive ability for prognosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that FHIP1A-DT was associated with epigenetic modification and regulated many cancer-related pathways. The ceRNA network demonstrated the potential gene regulation of FHIP1A-DT. FHIP1A-DT was related to many chemotherapeutic drug sensitivities and immune cell infiltration such as CD4 memory resting T cells, monocytes, plasma cells, neutrophils, and M2 macrophages. The FHIP1A-DT expression and prognostic analysis of GSE17538 and GSE39582, and qPCR yielded similar external verification results. CONCLUSION: FHIP1A-DT was a novel CRC-related lncRNA related to CRC diagnosis, prognosis, and treatment sensitivity. It could be used as a significant CRC biomarker in the future.

Efficacy and safety of ilioinguinal neurectomy in open tension-free inguinal hernia repair: A meta-analysis of randomized controlled trials.

BACKGROUND: There is still controversy surrounding routine ilioinguinal neurectomy in open tension-free inguinal hernia repair. METHOD: PubMed, Cochrane Library and EMBASE databases were searched for randomized controlled trials of ilioinguinal neurectomy in open tension-free inguinal hernia repair. Revman 5.3 software was used for meta-analysis. RESULT: Meta-analysis revealed that the incidence of severe pain on the first postoperative day was lower in the ilioinguinal neurectomy group (ING) than in the ilioinguinal nerve preservation group (INPG) [P < 0.0001]. The incidence of no pain in the first month postoperatively [P = 0.0004], the incidence of no pain in the sixth months postoperatively [P < 0.00001], and the numbness incidence in the first month postoperatively [P = 0.001] in the ING was higher than that in the INPG. There was no significant difference in the incidence of severe pain in the first month postoperatively [P = 0.20], the numbness incidence in the sixth postoperative month [P = 0.05], the hypoesthesia incidence in the first [P = 0.15] and sixth [P = 0.85] postoperative months between the two groups. CONCLUSION: Ilioinguinal neurectomy in open tension-free inguinal hernia repair can better prevent postoperative pain.

Exploring Key Biomarkers and Common Pathogenesis of Seven Digestive System Cancers and Their Correlation with COVID-19.

Digestive system cancer and COVID-19 significantly affect the digestive system, but the mechanism of interaction between COVID-19 and the digestive system cancers has not been fully elucidated. We downloaded the gene expression of COVID-19 and seven digestive system cancers (oral, esophageal, gastric, colorectal, hepatocellular, bile duct, pancreatic) from GEO and identified hub differentially expressed genes. Multiple verifications, diagnostic efficacy, prognostic analysis, functional enrichment and related transcription factors of hub genes were explored. We identified 23 common DEGs for subsequent analysis. CytoHubba identified nine hub genes (CCNA2, CCNB1, CDKN3, ECT2, KIF14, KIF20A, KIF4A, NEK2, TTK). TCGA and GEO data validated the expression and excellent diagnostic and prognostic ability of hub genes. Functional analysis revealed that the processes of cell division and the cell cycle were essential in COVID-19 and digestive system cancers. Furthermore, six related transcription factors (E2F1, E2F3, E2F4, MYC, TP53, YBX1) were involved in hub gene regulation. Via in vitro experiments, CCNA2, CCNB1, and MYC expression was verified in 25 colorectal cancer tissue pairs. Our study revealed the key biomarks and common pathogenesis of digestive system cancers and COVID-19. These may provide new ideas for further mechanistic research.

Modified pedicle screw fixation under guidance of stress analysis for cervicothoracic junction: Surgical technique and outcomes.

BACKGROUND: In cervicothoracic junction, the use of strong fixation device such as pedicle screw placement is often needed. OBJECTIVE: The current study aimed to evaluate the accuracy and safety of pedicle screw placement using stress conduction analysis in the clinical application. METHODS: We retrospectively collected patients who underwent pedicle screw internal fixation in cervicothoracic junction. Patients were divided into conventional nail placement (Group A) and modified pedicle screw implantation under guidance of stress analysis (Group B) according to the methods of pedicle screw placement. The accuracy of pedicle screw placement was assessed by computed tomography (CT) examination, and the success rate was calculated. RESULTS: A total of 80 patients who underwent pedicle screw internal fixation in cervicothoracic junction were included. There were no obvious differences in baseline characteristics between two groups. The success rate of total screw placement, cervical spine screw placement and upper thoracic spine screw placement in Group B was higher than those in Group A (P< 0.001, P= 0.005, P= 0.008). Additionally, Heary Grade I in the Group B was higher than Group A (P= 0.001). CONCLUSION: Stress analysis-guided technique can increase the accuracy of pedicle screw placement. Importantly, it meets the requirements of internal fixation of the cervicothoracic junction.

A large ectopic hepatocellular carcinoma with adrenal infiltration: a rare case report.

Ectopic hepatocellular carcinoma (EHCC) originates from the ectopic liver, which refers to a liver organ or tissue unrelated to surrounding tissues. EHCC is a rare disease that lacks specific clinical signs, and preoperative diagnosis is often difficult. In a 61-year-old male patient with positive hepatitis B virus antibody, abdominal contrast-enhanced computed tomography scan showed a large heterogenously enhancing mass both on arterial and portal venous phase imaging arising from the right adrenal gland. Similar enhancement features were seen on magnetic resonance imaging. Serum potassium, aldosterone, cortisol, and plasma metanephrines were normal. The tumor markers of serum alpha-fetoprotein and alpha-fetoprotein-L3% were increased to 23.69 ng/mL and 82.1%, respectively. Exploratory laparotomy was performed and operative findings showed that the retroperitoneal tumor was disconnected from the right kidney and the liver, but invaded the right adrenal gland. Immunohistochemical examination showed that Arginase-1 was positive expression, and the retroperitoneal tumor was finally diagnosed as EHCC. We report a rare EHCC with adrenal infiltration that is difficult to diagnose preoperatively and mimics a retroperitoneal tumor or adrenal tumor, and we present a review of the literature on EHCC case reports.

Precise diagnosis and treatment of non-muscle invasive bladder cancer - A clinical perspective.

According to the guidelines, transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains the standard strategy for the management of non-muscle invasive bladder cancer (NMIBC). However, even if patients receive standard strategy, the risk of postoperative recurrence and progression is high. From the clinical perspective, the standard strategy needs to be optimized and improved. Compared to conventional TURBT, the technique of en bloc resection of bladder tumor (ERBT) removes the tumor tissue in one piece, thus following the principles of cancer surgery. Meanwhile, the integrity and spatial orientation of tumor tissue is protected during the operation, which is helpful for pathologists to make accurate histopathological analysis. Then, urologists can make a postoperative individualized treatment plan based on the patient's clinical characteristics and histopathological results. To date, there is no strong evidence that NMIBC patients treated with ERBT achieve better oncological prognosis, which indicates that ERBT alone does not yet improve patient outcomes. With the development of enhanced imaging technology and proteogenomics technology, en bloc resection combined with these technologies will make it possible to achieve precise diagnosis and treatment of bladder cancer. In this review, the authors analyze the current existing shortcomings of en bloc resection and points out its future direction, in order to promote continuous optimization of the management strategy of bladder cancer.

Erratum: Mixed lineage kinase-like protein protects against Clostridium perfringens infection by enhancing NLRP3 inflammasome-extracellular traps axis.

[This corrects the article DOI: 10.1016/j.isci.2022.105121.].

Culturing the Chicken Intestinal Microbiota and Potential Application as Probiotics Development.

Pure cultures of chicken intestinal microbial species may still be crucial and imperative to expound on the function of gut microbiota, and also contribute to the development of potential probiotics and novel bioactive metabolites from gut microbiota. In this study, we isolated and identified 507 chicken intestinal bacterial isolates, including 89 previously uncultured isolates. Among these, a total of 63 Lactobacillus strains, belonging to L. vaginalis, L. crispatus, L. gallinarum, L. reuteri, L. salivarius, and L. saerimneri, exhibited antibacterial activity against S. Pullorum. Acid tolerance tests showed Limosilactobacillus reuteri strain YPG14 (L. reuteri strain YPG14) has a particularly strong tolerance to acid. We further characterized other probiotic properties of L. reuteri strain YPG14. In simulated intestinal fluid, the growth of L. reuteri strain YPG14 remained stable after incubation for 4 h. The auto-aggregation test showed the auto-aggregation percentage of L. reuteri strain YPG14 was recorded as 15.0 ± 0.38%, 48.3 ± 2.51%, and 75.1 ± 4.44% at 3, 12, and 24 h, respectively. In addition, the mucin binding assay showed L. reuteri strain YPG14 exhibited 12.07 ± 0.02% adhesion to mucin. Antibiotic sensitivity testing showed that L. reuteri strain YPG14 was sensitive to the majority of the tested antibiotics. The anti-Salmonella Pullorum (S. Pullorum) infection effect in vivo revealed that the consumption of L. reuteri strain YPG14 could significantly improve body weight loss and survival rate of chicks infected by S. Pullorum; reduce the loads of S. Pullorum in the jejunum, liver, spleen, and feces; and alleviate the jejunum villi morphological structure damage, crypt loss, and inflammatory cell infiltration caused by S. Pullorum. Overall, this study may help us to understand the diversity of chicken intestinal microflora and provide some insights for potential probiotic development from gut microbiota and may find application in the poultry industry.