Dual-ROS Sensitive Moieties Conjugate Inhibits Curcumin Oxidative Degradation for Colitis Precise Therapy.

Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti-oxidation and anti-inflammatory potential. However, curcumin exhibits low solubility (<1 µg mL-1), poor tissue-targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide-oxalate-curcumin) nanoparticle (SeOC-NP) with dual-reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one-step synthetic strategy. The results confirmed that dual-ROS sensitive chemical moieties endowed SeOC-NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high-efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4-fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC-NP significantly enhanced the antioxidant activity and anti-inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro-inflammatory cytokines. In mouse colitis models, orally administered SeOC-NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS-responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.

Learning curve of ultrasound-guided percutaneous nephrolithotripsy in the treatment of complex renal calculi.

OBJECTIVE: This study was performed to investigate the learning curve of ultrasound-guided percutaneous nephrolithotripsy (PCNL) for the treatment of complex renal calculi. METHODS: Seventy-two patients with complex renal stones who underwent ultrasound-guided PCNL by the same operator from November 2016 to September 2020 were retrospectively analyzed. The learning curve of PCNL for complex renal stones was analyzed using multifactorial cumulative sum (CUSUM) analysis and best-fit curves. RESULTS: The CUSUM best-fit curve peaked at Case 36, which represented the minimum number of cumulative cases required to cross the learning curve for this surgical procedure. Accordingly, the learning curve was divided into a learning improvement period (36 cases) and a proficiency phase (36 cases). Compared with the learning improvement period, the proficiency phase was characterized by a shorter puncture time and operation time, a smaller drop in the hemoglobin level, and a lower postoperative complication rate. CONCLUSION: The learning curve of PCNL for the treatment of complex renal calculi can be divided into a learning improvement period and a proficiency phase, and the minimum cumulative number of cases is 36.

La(OTf)3-Catalyzed [3+2] Cycloaddition Reactions for the Synthesis of Benzo[d]oxazoles/Benzofurans.

The La(OTf)3-catalyzed [3+2] cycloaddition reactions for the synthesis of benzo[d]oxazoles/benzofurans via quinones and 1,2-di-tert-butyl-3-(cyanimino)diaziridine (1,3-di-tert-butyl-2-cyanoguanidine)/vinyl azides have been explored. A series of 5-hydroxybenzofuran-4-carboxylic acid derivatives and 5-hydroxybenzo[d]oxazole-4-carboxylic acid derivatives were conveniently obtained with high yields and good stereoselectivities, which could be used for further transformations to valuable compounds.

The History and Prediction of Prebiotics and Postbiotics: A Patent Analysis.

Prebiotics and postbiotics have gained attention as functional food additives due to their substantial influence on the gut microbiome and potential implications for human health on a broader scale. In addition, the number of patents for these additives has also increased, yet their functional classification has been problematic. In this study, we classified 2215 patents granted from 2001 to 2020 by functionality to enable predictions of future development directions. These patents encompassed subjects as diverse as feed supplementation, regulation of intestinal homeostasis, prevention of gastrointestinal ailments, targeted drug administration and augmentation of drug potency. The progression of patents issued during this time frame could be divided into three phases: occasional accounts prior to 2001, a period from 2001 to 2013 during which an average of 42 patents were issued annually, followed by a surge exceeding 140 patents annually after 2013. The latter increase has indicated that pre- and post-biotics have been recognized as biologically relevant. Patent mining therefore can enable forecasts of the future trajectory of these biologics and provide insights to evaluate their advancement. Moreover, this research is the first attempt to generalize and predict the directions of prebiotics and postbiotics using patent information and offers a comprehensive perspective for the potential utilization of prebiotics and postbiotics across a wide variety of fields.

Deciphering the molecular symphony: Unraveling endothelial-to-mesenchymal transition in corneal endothelial cells.

Understanding the molecular complexity of this phenomenon provides innovative targets for maintaining phenotypic integrity during in vitro expansion, thereby advancing corneal endothelial tissue engineering. In this study, we established an in vitro model to simulate endothelial-to-mesenchymal transition (EndMT) in corneal endothelial cells. Through RNA sequencing, we identified 452 upregulated and 163 downregulated genes, resulting in a total of 615 differentially expressed genes. Key pathways enriched by GO and KEGG analysis include extracellular matrix (ECM) regulation and the PI3K-Akt signaling pathway. Potential hub proteins such as THBS1, ITGA5, COL1A1, and SNAI1/2 were also identified, and their dynamic changes at different time points (0, 2, 12, 24 h) were monitored. Uncovering these key pathways and genes may deepen our understanding of the mechanisms underlying EndMT in corneal endothelial cells, providing valuable insights for optimizing in vitro cultivation strategies.

Self-assembly of H2S-responsive nanoprodrugs based on natural rhein and geraniol for targeted therapy against Salmonella Typhimurium.

Salmonellosis is a globally extensive food-borne disease, which threatens public health and results in huge economic losses in the world annually. The rising prevalence of antibiotic resistance in Salmonella poses a significant global concern, emphasizing an imperative to identify novel therapeutic agents or methodologies to effectively combat this predicament. In this study, self-assembly hydrogen sulfide (H2S)-responsive nanoprodrugs were fabricated with poly(α-lipoic acid)-polyethylene glycol grafted rhein and geraniol (PPRG), self-assembled into core-shell nanoparticles via electrostatic, hydrophilic and hydrophobic interactions, with hydrophilic exterior and hydrophobic interior. The rhein and geraniol are released from self-assembly nanoprodrugs PPRG in response to Salmonella infection, which is known to produce hydrogen sulfide (H2S). PPRG demonstrated stronger antibacterial activity against Salmonella compared with rhein or geraniol alone in vitro and in vivo. Additionally, PPRG was also able to suppress the inflammation and modulate gut microbiota homeostasis. In conclusion, the as-prepared self-assembly nanoprodrug sheds new light on the design of natural product active ingredients and provides new ideas for exploring targeted therapies for specific Enteropathogens. Graphical  illustration for construction of self-assembly nanoprodrugs PPRG and its antibacterial and anti-inflammatory activities on experimental Salmonella infection in mice.

TET-Yeasate: An engineered yeast whole-cell lysate-based approach for high performance tetracycline degradation.

The widespread of tetracycline (TC) residues in anthropogenic and natural environments pose an immediate threat to public health. Herein, we established the TET-Yeasate, an approach based on whole-cell lysate of engineered yeast, to mitigate the TC contamination in environment. The TET-Yeasate is defined as the biological matrix of whole cell lysate from engineered yeast that containing TC-degradative components (Tet(X), NADPH, Mg2+) and protective macromolecules. The TET-Yeasate was able to efficiently eliminate TC residues in tap water (98.8%), lake water (77.6%), livestock sewage (87.3%) and pharmaceutical wastewater (35.3%) without necessity for exogenous addition of expensive cofactors. The TET-Yeasate was further developed into lyophilized form for ease of storage and delivery. The TET-Yeasate in lyophilized form efficiently removed up to 74.6% TC residue within 0.25 h. In addition, the lyophilization confers promising resilience to TET-Yeasate against adverse temperatures and pH by maintaining degradation efficacy of 85.69%-97.83%. The stability test demonstrated that the biomacromolecules in lysate served as natural protectants that exerted extensive protection on TET-Yeasate during the 14-day storage at various conditions. In addition, 5 potential degradation pathways were elaborated based on the intermediate products. Finally, the analysis indicated that TET-Yeasate enjoyed desirable bio- and eco-safety without introduction of hazardous intermediates and spread of resistance genes. To summary, the TET-Yeasate based on whole cell lysate of engineered yeast provides a cost-effective and safe alternative to efficiently remove TC residues in environment, highlighting the great potential of such whole-cell based methods in environmental decontamination.

Functional metagenomics reveals wildlife as natural reservoirs of novel ß-lactamases.

The antibiotic resistances in bacteria are believed to rapidly evolve over time in the anthropogenic environments which enriched with selection pressures. However, the knowledge regarding the development of antibiotic resistance in wildlife and their habitats is scarce. It is, therefore, of great interest and significance to unveil the yet-unknown antibiotic resistances in wildlife in accordance with One Health concept. To this end, we analyzed the samples taken from wildlife and surrounding environments using a functional metagenomics approach. By functional screening in combination with Illumina sequencing, a total of 32 candidate genes which encoding putative novel ß-lactamase were identified. These putative ß-lactamase were taxonomically assigned into bacteria of 23 genera from 7 phyla, where Proteobacteria, Actinobacteria and Firmicutes were dominant. The following functional assessment demonstrated that 4 novel ß-lactamases, namely blaSSA, blaSSB1, blaSSB2 and blaSSD, were functionally active to confer the phenotypical resistance to bacteria by increasing MICs up to 128-fold. Further analysis indicated that the novel ß-lactamases identified in the current study were able to hydrolyze a broad spectrum of ß-lactams including cephalosporins, and they were genetically unique comparing with known ß-lactamases. The plausible transmission of some novel ß-lactamase genes was supported by our results as the same gene was detected in different samples from different sites. This study shed the light on the active role of wildlife and associated environments as natural reservoirs of novel ß-lactamases, implying that the antibiotic resistances might evolve in absence of selection pressure and threaten public health once spread into clinically important pathogens.

Nomogram to predict risk and prognosis of synchronous lung metastasis in renal cell carcinoma: A large cohort analysis.

We aimed to construct and validate nomogram models that predict the incidence of lung metastasis (LM) in patients with renal cell carcinoma (RCC) and evaluate overall survival (OS) and cancer-specific survival (CSS) among RCC patients with LM. The Surveillance, Epidemiology, and End Results database was analyzed for RCC patients diagnosed between 2010 and 2015. The X-tile program was used to determine the best cutoff values for age at initial diagnosis and tumor size. Logistic regression analysis was performed to explore independent risk factors for LM, and COX regression analysis was used to identify prognostic indicators for OS and CSS in lung metastatic RCC patients. Subsequently, 3 nomograms were established, and receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were utilized to validate their accuracy. We randomly assigned 10,929 patients with RCC to 2 groups with 1:1 allocation. Multivariate logistic analyses revealed that pathology, tumor (T) stage, nodes (N) stage, race, grade, surgery, metastatic sites, and tumor size were independent risk factors for LM. Multivariate Cox analyses showed that pathology, T stage, N stage, age, surgery, metastatic sites, and residence were independent prognostic factors for OS and CSS in patients with LM. Then, nomograms were developed based on the multivariate logistic and Cox regression analyses results. The ROC and DCA curves confirmed that these nomograms achieved satisfactory discriminative power. Three effective nomograms were constructed and validated that can be used to assist clinicians in predicting the incidence of LM and evaluating the prognosis of lung metastatic RCC.

Construction and validation of a novel prognostic nomogram for patients with metastatic renal cell carcinoma: a SEER-based study.

OBJECTIVE: We aimed to establish and validate nomograms to evaluate overall survival (OS) and cancer-specific survival (CSS) in patients with metastatic renal cell carcinoma (MRCC). METHODS: Between 2010 and 2015, the clinical information of patients with MRCC was selected using the Surveillance, Epidemiology, and End Results database. Two nomograms were constructed based on Cox regression analysis, and their prediction accuracy was evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). RESULTS: After propensity score matching, there were 568 patients with MRCC in the training group and 568 in the validation group. Multivariate analyses revealed that age, residence, pathology, T stage, N stage, surgery, and metastatic sites were independent prognostic factors for the OS and CSS of MRCC. The C-index and ROC curves indicated that the two nomograms of OS and CSS showed satisfactory discriminative power. Furthermore, DCA displayed that the nomograms achieved more clinical net benefit than the American Joint Committee on Cancer staging system. CONCLUSION: We constructed and validated two effective prognostic nomograms for patients with MRCC that accurately predicted the probabilities of 1-, 2-, and 3-year OS and CSS.

Analysis of multidrug resistance in Streptococcus suis ATCC 700794 under tylosin stress.

Streptococcus suis is an important zoonotic pathogen. The massive use of tylosin and other antibiotics in swine production has led to the emergence of resistant phenotypes of S. suis. However, there are no adequate measures available to address the problem of bacterial resistance. This study involved the use of 1/4 MIC (0.125 µg/mL) of tylosin to investigate resistance-related proteins by S. suis ATCC 700794. Our results showed that 171 proteins were differentially expressed in S. suis tested with 1/4 MIC (0.125 µg/mL) of tylosin using iTRAQ-based quantitative proteomic methods. TCS, heat shock protein and elongation factors were differentially expressed at 1/4 MIC (0.125 µg/mL) of tylosin compared to non treated, control cells. Using quantitative RT-PCR analysis, we verified the relationship between the differentially expressed proteins in S. suis with different MIC values. The data showed that expression profile for elongation factor G (fusA), elongation factor Ts (tsf), elongation factor Tu (tuf), putative histidine kinase of the competence regulon, ComD (comD), putative competence-damage inducible protein (cinA) and protein GrpE (grpE), observed in tylosin-resistant S. suis, correlated with that of S. suis ATCC 700794 at 1/4 MIC (0.125 µg/mL). The MIC of tylosin-resistant showed high-level resistance in terramycin, chlortetracycline, ofloxacin and enrofloxacin. Our findings demonstrated the importance of elongation factors, TCS and heat shock protein during development of tylosin resistance in S. suis. Thus, our study will provide insight into new drug targets and help reduce bacterial multidrug resistance through development of corresponding inhibitors.

Endoscopic robot-assisted simple enucleation of renal tumours: Impact of learning curve and tumour complexity on trifecta outcomes.

BACKGROUND: In this article, we report the outcomes of endoscopic robot-assisted tumour enucleation (ERASE) using a trifecta system. METHODS: One hundred eighty-two patients were treated with ERASE by a single surgeon between October 2014 and February 2017 and were stratified by quartiles of distribution called ERASE eras 1 to 4 and preoperative aspects and dimensions used for an anatomical (PADUA) score risk group categories. The trifecta achievement rates in different ERASE eras and PADUA score risk group categories were analysed. RESULTS: The overall trifecta achievement rate was 76.4%; this rate progressively increased along the learning curve and reached 87.2% in ERASE era 4 (0.002). PADUA score risk group categories were inversely correlated with the trifecta achievement rate (P < .001). When both variables were simultaneously considered, a trend towards a higher trifecta achievement rate was observed in the recent series regardless of tumour anatomical complexity. CONCLUSIONS: The trifecta achievement rate increased with surgical experience and was inversely correlated with tumour complexity.

Primary urothelial carcinoma of the prostate: A rare case report.

RATIONALE: Prostatic urothelial carcinoma is a rare disease. Medical misdiagnosis rates remain high because there are no specific clinical symptoms or imaging features, which decreases patient survival. We report a case of prostatic urethral cancer confirmed by transrectal ultrasound-guided prostate biopsy because of an abnormal digital rectal exam. PATIENT CONCERNS: A 55-year-old man was referred to our hospital due to lower urinary tract symptoms that lasted for 5 years. DIAGNOSES AND INTERVENTIONS: On digital rectal examination, a hard and enlarged prostate was detected. Computed tomography, bone scintigraphy, and magnetic resonance imaging indicated benign prostatic hyperplasia. The patient underwent transrectal ultrasound-guided prostate biopsy. From the histopathological examination and immunohistochemical markers, a diagnosis of high-grade prostatic urothelial carcinoma was made. We excluded the possibility of urothelial cancer originating in the bladder lining after transurethral resection of the bladder. Radical cystoprostatectomy was performed, followed by 6 cycles of cisplatin and gemcitabine chemotherapy. Postoperative pathology showed primary urothelial carcinoma of the prostate. OUTCOMES: The patient recovered smoothly after surgery. After a 6-month follow-up, no evidence of local recurrence or metastatic disease was found. LESSONS: This case reminds clinicians that, for middle-aged men with suspicious digital rectal examinations, a diagnosis of prostatic urothelial carcinoma should be considered. Initial radical surgery followed by combination chemotherapy is suggested for therapeutic management.

The feasibility and safety of modified robot-assisted enucleation for highly complex renal tumors: research on a surgical technique.

BACKGROUND: To report the technical feasibility and oncological safety of modified robot-assisted enucleation for highly complex renal tumors using the combined retroperitoneoscopic and transperitoneoscopic accesses. METHODS: The present research is a retrospective analysis of 166 cases of highly complex renal tumors that underwent a partial nephrectomy at a tertiary academic institution between September 2014 and August 2017. Consecutive consented patients were grouped into two cohorts. Seventy-two cases underwent conventional robot-assisted partial nephrectomy (C-RAPN), and 94 cases were treated with modified robot-assisted tumor enucleation (MRATE). The perioperative and oncological outcomes of both groups were reported. Furthermore, pathological examinations of 225 cases of highly complex renal tumors treated with radical nephrectomy were analyzed. RESULTS: Although preoperative clinical data were similar between the two groups, the perioperative outcomes were distinctly different. Total renal function at postoperative day 1 was better (P<0.001), and the surgical margin width was narrower (P<0.001) in the MRATE group. In addition, the MRATE group presented less blood loss (143.29 and 90.76 mL; P<0.001) and lower 30-d complication rates (4.2% and 16.7%, respectively; P=0.033). Mean ischemia time and operative time was 3 and 14 minutes shorter in the MRATE group, respectively. Finally, histopathological analysis of 225 cases of renal tumors with high surgical complexity provided objective evidence for the feasibility of MRATE. CONCLUSIONS: MRATE technique may offer an efficient and safe method to treat anatomically complex renal masses in referral centers. The long-term outcome of MRATE technique merits further investigation.

Effects of adult male circumcision on premature ejaculation: results from a prospective study in China.

The purpose of this study is to investigate the effects of adult male circumcision on premature ejaculation (PE). Therefore, between December 2009 and March 2014, a total of 575 circumcised men and 623 uncircumcised men (control group) were evaluated. Detailed evaluations (including circumcision and control groups) on PE were conducted before circumcision and at the 3-, 6-, 9-, and 12-month follow-up visits after circumcision. Self-estimated intravaginal ejaculatory latency time (IELT), Patient-Reported Outcome measures, and 5-item version of the International Index of Erectile Function were used to measure the ejaculatory and erectile function for all subjects. The results showed that, during the one-year follow-up, men after circumcision experienced higher IELT and better scores of control over ejaculation, satisfaction with sexual intercourse, and severity of PE than men before circumcision (P < 0.001 for all). Similarly, when compared with the control group, the circumcised men reported significantly improved IELT, control over ejaculation, and satisfaction with sexual intercourse (P < 0.001 for all). These findings suggested that circumcision might have positive effects on IELT, ejaculatory control, sexual satisfaction, and PE severity. In addition, circumcision was significantly associated with the development of PE.

Relationships between intravaginal ejaculatory latency time and national institutes of health-chronic prostatitis symptom index in the four types of premature ejaculation syndromes: a large observational study in China.

INTRODUCTION: Besides lifelong premature ejaculation (LPE) and acquired premature ejaculation (APE), Waldinger and Schweitzer proposed two addition PE syndromes (variable PE [VPE] and subjective PE [SPE]). AIM: We assessed the associations between intravaginal ejaculatory latency time (IELT) and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) in men with different PE syndromes. METHODS: From September 2011 to September 2012, a total of 4,000 men were enrolled from the Anhui province of China. Subjects were required to complete a verbal questionnaire, including demographic information, medical and sexual history (e.g., IELT), and self-estimated scales (e.g., NIH-CPSI). MAIN OUTCOME MEASURES: IELT; NIH-CPSI; the new classification of PE syndromes. RESULTS: Of 3,016 of the men evaluated, 25.80% complained of PE. Distribution of the four PE syndromes among men with complaints of PE was as follows: LPE, 12.34%; APE, 18.77%; VPE, 44.09%; and SPE, 24.81%. Men with complaints of PE reported worse NIH-CPSI scores and lower IELT than men without complaints of PE (P < 0.001 for all). Moreover, total and subdomain scores of NIH-CPSI were higher in men with APE, and IELT was higher in men with SPE. IELT was negatively associated with NIH-CPSI scores in men with complaints of PE. Negative relationships between total and subdomain scores of NIH-CPSI and IELT were stronger in men with APE (total scores: adjusted r = -0.68, P < 0.001; pain symptoms: adjusted r = -0.70, P < 0.001; urinary symptoms: adjusted r = -0.67, P < 0.001; quality of life impact: adjusted r = -0.64, P < 0.001). CONCLUSION: Men with complaints of PE reported worse NIH-CPSI scores than men without complaints of PE. Relationships between IELT and NIH-CPSI scores were strongest in men with APE.

The impact of intravaginal ejaculatory latency time and erectile function on anxiety and depression in the four types of premature ejaculation: a large cross-sectional study in a Chinese population.

INTRODUCTION: A new classification of premature ejaculation (PE) has been proposed, including the categories of lifelong PE (LPE), acquired PE (APE), natural variable PE (NVPE), and premature-like ejaculatory dysfunction (PLED). AIM: The aim of this study was to evaluate the impact of intravaginal ejaculation latency time (IELT) and erectile function on anxiety and depression among patients with PE in general and according to the four types of PE. METHODS: Between September 2011 and September 2012, we conducted a cross-sectional study in the Anhui province of China. We enrolled 4,000 men aged over 18 years, each of whom had been in a stable, monogamous, heterosexual relationship with the same partner for at least 6 months. MAIN OUTCOME MEASUREMENTS: Self-estimated IELT, the International Index of Erectile Function-5 (IIEF-5) and the Zung Self-Rating Anxiety and Depression Scales (SAS/SDS) were used to measure PE, erectile dysfunction (ED), anxiety, and depression, respectively, among the entire study population. RESULTS: Of the 3,016 men evaluated, 25.80% complained of PE. Distribution of the four types of PE among men with PE was as follows: LPE, 12.34%; APE, 18.77%; NVPE, 44.09%; PLED, 24.81%. Men with PE presented lower IIEF-5 scores and higher SAS and SDS scores vs. men without PE (P < 0.001 for all). Similar findings were observed in men with APE when compared with other PE syndromes. After adjustment for age in men with PE, IELT was negatively associated with SAS and SDS scores (SAS, adjusted r = -0.42, P < 0.001; SDS, adjusted r = -0.45, P < 0.001). IIEF-5 score was negatively associated with SAS and SDS scores (SAS, adjusted r = -0.54, P < 0.001; SDS, adjusted r = -0.50, P < 0.001). These negative relationships were strongest in men with PLED (IELT vs. SAS: adjusted r = -0.63, P < 0.001; IELT vs. SDS, adjusted r = -0.60, P < 0.001; IIEF-5 vs. SAS: adjusted r = -0.57, P < 0.001; IELT vs. SDS, adjusted r = -0.55, P < 0.001). CONCLUSIONS: APE patients reported higher rates of ED, anxiety, and depression than men with other types of PE. The negative relationships between IELT/IIEF-5 and SAS/SDS were strongest in men with PLED.