[Behavioral treatment of functional anejaculation and factors influencing the therapeutic effect].

OBJECTIVE: To study the effect of a modified behavioral treatment (MBT) on functional anejaculation and analyze the factors influencing the therapeutic efficacy. METHODS: We enrolled in this study 59 men aged 24－45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual intercourse but normally ejaculating during masturbation. Thirty-nine of the patients underwent conventional behavioral treatment (the CBT group) and the other 20 received MBT, namely, changing the masturbation method combined with audiovisual stimulation during sexual intercourse (the MBT group). We compared the therapeutic effects between the two groups of patients, and analyzed the correlation of the outcomes of MBT with age, abstinence duration, use of audiovisual stimulation, change of the sexual position, mean bilateral testis volume and sex hormone levels. RESULTS: After treatment, 22 (37.29%) of the patients achieved successful ejaculation at least once in sexual intercourse, 11 (55.00%) in the MBT group, and the other 11 (28.21) in the CBT group, with a significantly higher effectiveness rate in the former than in the latter (P<0.05). The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treatment (P<0.05). CONCLUSION: MBT has a certain effect on functional anejaculation, and targeting the previous events of the patient is the key to the therapeutic efficacy. Further exploration of more effective strategies of behavioral treatment will become the trend of development in the management of functional anejaculation.

OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation.

Leucine-rich glioma-inactivated protein 1 (LGI1), a secretory protein in the brain, plays a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding proteins through LGI1-3 × FLAG affinity chromatography with mouse brain lysates followed by mass spectrometry. An OL-specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional knockout (cKO) of OPALIN in the OL lineage caused hypomyelination and WMAs, phenocopying LGI1 deficiency in mice. Biochemical analysis revealed the downregulation of Sox10 and Olig2, transcription factors critical for OL differentiation, further confirming the impaired OL maturation in Opalin cKO mice. Moreover, virus-mediated re-expression of OPALIN successfully restored myelination in Opalin cKO mice. In contrast, re-expression of LGI1-unbound OPALIN_K23A/D26A failed to reverse the hypomyelination phenotype. In conclusion, our study demonstrated that OPALIN on the OL membrane serves as an LGI1 receptor, highlighting the importance of the LGI1/OPALIN complex in orchestrating OL differentiation and myelination.

Clinical, Laboratory, and Imaging Characteristics of Tropheryma Whipplei Detection in Bronchoalveolar Lavage Fluid Using Next-Generation Sequencing: A Case-Control Study.

Objective: The aim of this study was to assess the prevalence of Tropheryma whipplei (TW) infection in the population and to investigate the clinical symptoms, as well as the laboratory and imaging characteristics of patients testing positive for TW using next-generation sequencing (NGS). Methods: A retrospective review was conducted on 1346 bronchoalveolar lavage fluid (BALF) samples collected between January 2021 and September 2023. The case group comprised patients with TW detected using NGS while the control group included 65 randomly chosen Gram-positive bacterial infection patients without TW. Comparative analyses were carried out on the basic demographics, laboratory parameters, and imaging findings between the two groups. Additionally, the case group underwent an in-depth examination of underlying diseases, pathogens, final diagnoses, treatment strategies. Results: The case group comprised of 51 patients with TW, constituting 3.8% of the total. There was no significant difference in gender and age between the case and control groups (P = 0.84, P = 0.07). Symptoms such as coughing, expectoration, wheezing, fever, and hemoptysis are less commonly detected in the case group with a higher incidence of chest pain when compared to the control group (P >0.05). The case group exhibited decreased albumin levels and increased C-reactive protein and D-dimer levels compared to normal levels. Imaging findings in the case group commonly included nodules, patchy images, and interstitial changes, the most common underlying disease is cardiovascular disease, and the most frequently co-occurring pathogen is the human herpesvirus. Among the case group, 27 patients received a final diagnosis of pneumonia, and 3 patients clinically diagnosed with Whipple's disease demonstrated improvement in both symptoms and imaging after treatment. Conclusion: NGS revealed a relatively low overall detection rate of TW-positive patients using BALF. TW was more prevalent in middle-aged and elderly male patients characterized by symptoms such as cough, expectoration, shortness of breath, and fever. Chest imaging in these cases typically showed nodules and interstitial changes.

First Clarification of the Mechanism of Action of the Apple Glycosyltransferase MdUGT91AJ2 Involved in the Detoxification Metabolism of the Triketone Herbicide Sulcotrione.

Sulcotrione is a member of triketone herbicides, a class of HPPD (4-hydroxyphenylpyruvate dioxygenase) inhibitors with broad-spectrum herbicidal activity. Modifications of glycosylation mediated by glycosyltransferases (GT) are involved in plant detoxification. In this study, we analyzed chip data published online and found that eight glycosyltransferases from group A of the apple glycosyltransferase family 1 may be involved in the metabolic mechanism of detoxification of triketone herbicides. To verify this prediction, we induced apple seedlings with six types of triketone herbicides, and then detected the expression levels of eight glycosyltransferase genes through real-time PCR. We found that triketone herbicides induced up-regulation of eight glycosyltransferase genes to varying degrees, with MdUGT91AJ2 being the most significantly up-regulated by sulcotrione-induced glycosyltransferase gene expression. Then, through in vitro enzymatic reactions and HPLC identification of glycoside substrates, it was found that the glycosyltransferase MdUGT91AJ2 had the highest specific enzyme activity against the triketone herbicide sulcotrione. Furthermore, the in vivo mechanism of the glycosyltransferase MdUGT91AJ2 in the detoxification metabolism of sulcotrione was further validated by overexpressing the strain in the plant. HPLC analysis showed that the content of sulcotrione glycosides in the overexpressing strain of MdUGT91AJ2 was significantly higher than that in the wild type. This result indicated that the apple glycosyltransferase MdUGT91AJ2 can still glycosylate and modify sulfotrione in plants, and participate in its detoxification metabolism. In summary, this study identified for the first time a novel apple glycosyltransferase MdUGT91AJ2 and elucidated its mechanism of action in the detoxification and metabolism of the triketone herbicide sulfotriene.

NTCE-KD: Non-Target-Class-Enhanced Knowledge Distillation.

Most logit-based knowledge distillation methods transfer soft labels from the teacher model to the student model via Kullback-Leibler divergence based on softmax, an exponential normalization function. However, this exponential nature of softmax tends to prioritize the largest class (target class) while neglecting smaller ones (non-target classes), leading to an oversight of the non-target classes's significance. To address this issue, we propose Non-Target-Class-Enhanced Knowledge Distillation (NTCE-KD) to amplify the role of non-target classes both in terms of magnitude and diversity. Specifically, we present a magnitude-enhanced Kullback-Leibler (MKL) divergence multi-shrinking the target class to enhance the impact of non-target classes in terms of magnitude. Additionally, to enrich the diversity of non-target classes, we introduce a diversity-based data augmentation strategy (DDA), further enhancing overall performance. Extensive experimental results on the CIFAR-100 and ImageNet-1k datasets demonstrate that non-target classes are of great significance and that our method achieves state-of-the-art performance across a wide range of teacher-student pairs.

STAT3-induced lncRNA GNAS-AS1 accelerates keloid formation by mediating the miR-196a-5p/CXCL12/STAT3 axis in a feedback loop.

Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS-AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS-AS1 and miR-196a-5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS-AS1, miR-196a-5p and C-X-C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS-AS1 and CXCL12 expression were upregulated and miR-196a-5p expression was downregulated in clinical tissues from patients with keloids. GNAS-AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR-196a-5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS-AS1 transcription through GNAS-AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS-AS1 expression. GNAS-AS1 positively regulated CXCL12 by sponging miR-196-5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS-AS1/miR-196a-5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.

First Clarification of the Involvement of Glycosyltransferase MdUGT73CG22 in the Detoxification Metabolism of Nicosulfuron in Apple.

Nicosulfuron, an acetolactate synthase (ALS) inhibitor herbicide, is a broad-spectrum and highly effective post-emergence herbicide. Glycosyltransferases (GTs) are widely found in organisms and transfer sugar molecules from donors to acceptors to form glycosides or sugar esters, thereby altering the physicochemical properties of the acceptor molecule, such as participating in detoxification. In this study, nine glycosyltransferases in group D of the apple glycosyltransferase family I were predicted to possibly be involved in the detoxification metabolism of ALS-inhibiting herbicides based on gene chip data published online. In order to confirm this, we analysed whether the expression of the nine glycosyltransferase genes in group D was induced by the previously reported ALS-inhibiting herbicides by real-time PCR (polymerase chain reaction). It was found that the ALS-inhibiting herbicide nicosulfuron significantly increased the expression of the MdUGT73CG22 gene in group D. Further investigation of the mechanism of action revealed that the apple glycosyltransferase MdUGT73CG22 glycosylated and modified nicosulfuron both in vivo and ex vivo to form nicosulfuron glycosides, which were involved in detoxification metabolism. In conclusion, a new glycosyltransferase, MdUGT73CG22, was identified for the first time in this study, which can glycosylate modifications of the ALS-inhibiting herbicide nicosulfuron and may be involved in the detoxification process in plants, which can help to further improve the knowledge of the non-targeted mechanism of herbicides.

Impact of treatment interval between neoadjuvant immunochemotherapy and surgery in lung squamous cell carcinoma.

OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

A survival nomogram model for patients with resectable non-small cell lung cancer and lymph node metastasis (N1 or N2) based on the Surveillance, Epidemiology, and End Results Database and single-center data.

Background: The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. Methods: The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. Results: ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. Conclusions: The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

Drug-induced hypersensitivity syndrome related to piperacillin-tazobactam: a case report and review of the literature.

Allergic reactions to drugs caused by piperacillin-tazobactam are common in clinical practice. However, we also found a few cases of drug-induced hypersensitivity syndrome (DiHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by piperacillin-tazobactam in our clinical work. We report a case of a 60-year-old female patient who was treated with piperacillin-tazobactam anti-infective therapy after the diagnosis of hematogenous lung abscess, developed fever, rash, and blood abnormalities after 26 days of application, and was later diagnosed as DIHS, which was improved after the administration of glucocorticoid and anti-allergic drugs. In addition, we also retrospectively analyzed 17 cases of DiHS caused by piperacillin-tazobactam from the PubMed databases between March 1980 and September 2023. The majority of the patients had an incubation period of more than 14 days, and the common clinical features included elevated eosinophil count/percentage, fever, rash, liver damage, and lymph node enlargement. After treatment with topical or systemic glucocorticoids, 16 of the 17 patients improved and one died because of the underlying condition. The clinical features of DiHS were diverse and included a long incubation period, skin rash, elevated eosinophils, and impaired organ function. Since some patients have atypical clinical features, clinicians should raise awareness of the disease, recognize these features early, and treat them promptly.

A Pathologically Friendly Strategy for Determining the Organ-specific Spatial Tumor Microenvironment Topology in Lung Adenocarcinoma Through the Integration of snRandom-seq and Imaging Mass Cytometry.

Heterogeneous organ-specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single-cell profiling using formalin-fixed paraffin-embedded (FFPE) materials. In this study, single-cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ-specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single-cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ-specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ-specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM-3. This study originally deciphers the single-cell landscape of the organ-specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ-specific treatment approaches.

Acute pneumonia due to Tropheryma whipplei diagnosed by metagenomic next-generation sequencing and pathology: A case report.

Tropheryma whipplei (TW) is a rod-shaped, gram-positive bacterium that, when chronically infects humans, can lead to multi-system pathologies, including joint pain, abdominal pain with diarrhea and weight loss, myocarditis, pericarditis, and neurologic inflammation. Moreover, acute infections can lead to bronchopulmonary infections, bacteraemia, and acute diarrhea. However, fewer cases of acute pneumonia due to TW have been reported, and this diagnosis is not well founded. Herein, we report a case of acute pneumonia caused by a TW infection. The patient, a middle-aged man, underwent bronchoscopic alveolar lavage, and the metagenomic next-generation sequencing of the lavage fluid suggested TW infection. A lung puncture biopsy tissue specimen was also positive based on periodic acid-Schiff staining. After confirming the diagnosis, the patient was administered ceftriaxone for anti-infection treatment, improving clinical symptoms and lung imaging results. Therefore, in cases where conventional anti-infective treatment is ineffective for patients with acute pneumonia, we should consider the possibility of TW infection, conduct prompt pathogenetic examination, and provide timely treatment after diagnosis to improve overall patient prognosis.

Effects of Exercise Habits and Gender on Sports e-Learning Behavior: Evidence from an Eye-Tracking Study.

Background/Objective: In the post-epidemic era, an increasing number of individuals were accustomed to learning sports and physical activity knowledge online for fitness and health demands. However, most previous studies have examined the influence of e-learning materials and resources on learners and have neglected intrinsic factors such as experience and physiological characteristics. Therefore, we conducted a study to investigate the effect of exercise habits and gender on sports e-learning behavior via eye-tracking technology. Methods: We recruited a sample of 60 undergraduate students (mean age = 19.6) from a university in Nanjing, China. They were randomly assigned into 4 groups based on 2 genders × 2 exercise habits. Their gaze behavior was collected by an eye-tracking device during the experiment. The cognitive Load Test and Learning Effect Test were conducted at the end of the individual experiment. Results: (1) Compared to the non-exercise habit group, the exercise habit group had a higher fixation count (P<0.05), a shorter average fixation duration (P<0.05), a smaller average pupil diameter (P<0.05), and a lower subjective cognitive load (P<0.05) and better learning outcome (P<0.05). (2) Male participants showed a greater tendency to process information from the video area of interest (AOIs), and had lower subjective cognitive load (P < 0.05) and better learning outcomes (P < 0.05). (3) There was no interaction effect between exercise habits and gender for any of the indicators (P > 0.05). Conclusion: Our results indicate that exercise habits effectively enhance sports e-learning outcomes and reduce cognitive load. The exercise habits group showed significant improvements in fixation counts, average fixation duration, and average pupil diameter. Furthermore, male subjects exhibited superior learning outcomes, experienced lower cognitive load, and demonstrated greater attentiveness to dynamic visual information. These conclusions are expected to improve sports e-learning success and address educational inequality.

Recurrent Tuberous Sclerosis Complex/Mammalian Target of Rapamycin Mutations Define Primary Renal Hemangioblastoma as a Unique Entity Distinct From Its Central Nervous System Counterpart.

ABSTRACT: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 ( TSC1 , 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification.

JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis.

BACKGROUND/AIMS: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. METHODS: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. RESULTS: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. CONCLUSION: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

Comparison of Superhydrophilic, Liquid-Like, Liquid-Infused, and Superhydrophobic Surfaces in Preventing Catheter-Associated Urinary Tract Infection and Encrustation.

Over the past decade, superhydrophilic zwitterionic surfaces, slippery liquid-infused porous surfaces, covalently attached liquid-like surfaces, and superhydrophobic surfaces have emerged as the most promising strategies to prevent biofouling on biomedical devices. Despite working through different mechanisms, they have demonstrated superior efficacy in preventing the adhesion of biomolecules (e.g., proteins and bacteria) compared with conventional material surfaces. However, their potential in combating catheter-associated urinary tract infection (CAUTI) remains uncertain. In this research, we present the fabrication of these four coatings for urinary catheters and conduct a comparative assessment of their antifouling properties through a stepwise approach. Notably, the superhydrophilic zwitterionic coating demonstrated the highest antifouling activity, reducing 72.3% of fibrinogen deposition and over 75% of bacterial adhesion (Escherichia coli and Staphylococcus aureus) when compared with an uncoated polyvinyl chloride (PVC) surface. The zwitterionic coating also exhibited robust repellence against blood and improved surface lubricity, decreasing the dynamic coefficient of friction from 0.63 to 0.35 as compared with the PVC surface. Despite the fact that the superhydrophilic zwitterionic and hydrophobic liquid-like surfaces showed great promise in retarding crystalline biofilm formation in the presence of Proteus mirabilis, it is worth noting that their long-term antifouling efficacy may be compromised by the proliferation and migration of colonized bacteria as they are unable to kill them or inhibit their swarming. These findings underscore both the potential and limitations of these ultralow fouling materials as urinary catheter coatings for preventing CAUTI.

Early cumulus cell removal increases cumulative live birth rate while having no negative effect on the malformation rate in in vitro fertilization: a propensity score-matched cohort study.

PURPOSE: The aim of this study was to investigate the efficacy and safety of early cumulus cell removal (ECCR) during human in vitro fertilization (IVF). METHODS: A retrospective analysis was performed between January 2011 and December 2019. The study enrolled 1131 couples who underwent IVF treatment with ECCR. After propensity score matching at a 1:1 ratio, 1131 couples who underwent overnight coincubation of gametes were selected. The main outcome measure was the cumulative live birth rate. Secondary outcome measures included the cumulative pregnancy rate, polyspermy rate, available embryo rate, miscarriage rate, malformation rate, time to live birth, and oocyte-to-baby rate. RESULTS: There were no significant differences found between the two groups in the polyspermy rate, available embryo rate, miscarriage rate, time to live birth, oocyte-to-baby rate, and neonatal congenital anomalies rate. The results of the study showed that ECCR was associated with a significantly higher cumulative live birth rate and cumulative pregnancy rate, along with a significantly lower fertilization rate. CONCLUSIONS: ECCR tended to confer increased cumulative live birth rate and had no negative effect on the neonatal malformation rate.

Circ_0002395 promotes aerobic glycolysis and proliferation in pancreatic adenocarcinoma cells via miR-548c-3p/PDK1 axis.

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.

FOXP1 and KLF2 reciprocally regulate checkpoints of stem-like to effector transition in CAR T cells.

In cancer and infections, self-renewing stem-like CD8+ T cells mediate the response of immunotherapies and replenish terminally exhausted T cells and effector-like T cells. However, the programs governing the lineage choice in chimeric antigen receptor (CAR) T cells are unclear. Here, by simultaneously profiling single-cell chromatin accessibility and transcriptome in the same CAR T cells, we identified heterogeneous chromatin states within CD8+ T cell subsets that foreshadowed transcriptional changes and were primed for regulation by distinct transcription factors. Transcription factors that controlled each CD8+ T cell subset were regulated by high numbers of enhancers and positioned as hubs of gene networks. FOXP1, a hub in the stem-like network, promoted expansion and stemness of CAR T cells and limited excessive effector differentiation. In the effector network, KLF2 enhanced effector CD8+ T cell differentiation and prevented terminal exhaustion. Thus, we identified gene networks and hub transcription factors that controlled the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.