Stabilizing High-Valence Copper(I) Sites with Cu-Ni Interfaces Enhances Electroreduction of CO2 to C2+ Products.

In this study, the copper-nickel (Cu-Ni) bimetallic electrocatalysts for electrochemical CO2 reduction reaction(CO2RR) are fabricated by taking the finely designed poly(ionic liquids) (PIL) containing abundant Salen and imidazolium chelating sites as the surficial layer, wherein Cu-Ni, PIL-Cu and PIL-Ni interaction can be readily regulated by different synthetic scheme. As a proof of concept, Cu@Salen-PIL@Ni(NO3)2 and Cu@Salen-PIL(Ni) hybrids differ significantly in the types and distribution of Ni species and Cu species at the surface, thereby delivering distinct Cu-Ni cooperation fashion for the CO2RR. Remarkably, Cu@Salen-PIL@Ni(NO3)2 provides a C2+ faradaic efficiency (FEC2+) of 80.9% with partial current density (jC 2+) of 262.9 mA cm-2 at -0.80 V (versus reversible hydrogen electrode, RHE) in 1 m KOH in a flow cell, while Cu@Salen-PIL(Ni) delivers the optimal FEC2+ of 63.8% at jC2+ of 146.7 mA cm-2 at -0.78 V. Mechanistic studies indicates that the presence of Cu-Ni interfaces in Cu@Salen-PIL@Ni(NO3)2 accounts for the preserve of high-valence Cu(I) species under CO2RR conditions. It results in a high activity of both CO2-to-CO conversion and C-C coupling while inhibition of the competitive HER.

Cytotoxic and viricidal effects of human semen on mumps virus-infected lymphocytes: In vitro studies.

Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of most viruses in semen remain largely unclear. The present study elucidated the inhibitory effects of human seminal plasma (SP) on Jurkat cell (JC)-mediated mumps virus (MuV) infection. We demonstrated that MuV efficiently infected JCs and that the JCs infected by MuV (JC-MuV) mediated MuV infection of HeLa cells. Remarkably, SP was highly cytotoxic to JCs and inhibited JC-MuV infection of HeLa cells. The cytotoxic factor possessed a molecular weight of less than 3 kDa, whereas that of the viricidal factor was over 100 kDa. The cooperation of cytotoxic and viricidal factors was required for the SP inhibition of JC-MuV infection, and prostatic fluid (PF) was responsible for both the cytotoxic and viricidal effects of SP. The cytotoxic effects we observed were resistant to the treatment of PF with boiling water, proteinase K, RNase A, and DNase I. Our results provide novel insights into the antiviral properties of SP, which may limit cell-mediated sexual viral transmission.

Balancing selection on an MYB transcription factor maintains the twig trichome color variation in Melastoma normale.

BACKGROUND: The factors that maintain phenotypic and genetic variation within a population have received long-term attention in evolutionary biology. Here the genetic basis and evolution of the geographically widespread variation in twig trichome color (from red to white) in a shrub Melastoma normale was investigated using Pool-seq and evolutionary analyses. RESULTS: The results show that the twig trichome coloration is under selection in different light environments and that a 6-kb region containing an R2R3 MYB transcription factor gene is the major region of divergence between the extreme red and white morphs. This gene has two highly divergent groups of alleles, one of which likely originated from introgression from another species in this genus and has risen to high frequency (> 0.6) within each of the three populations under investigation. In contrast, polymorphisms in other regions of the genome show no sign of differentiation between the two morphs, suggesting that genomic patterns of diversity have been shaped by homogenizing gene flow. Population genetics analysis reveals signals of balancing selection acting on this gene, and it is suggested that spatially varying selection is the most likely mechanism of balancing selection in this case. CONCLUSIONS: This study demonstrate that polymorphisms on a single transcription factor gene largely confer the twig trichome color variation in M. normale, while also explaining how adaptive divergence can occur and be maintained in the face of gene flow.

Biogenic Solution Map Based on the Definition of the Metabolic Correlation Distance between 4-Dimensional Fingerprints.

Accurate discrimination and classification of unknown species are the basis to predict its characteristics or applications to make correct decisions. However, for biogenic solutions that are ubiquitous in nature and our daily lives, direct determination of their similarities and disparities by their molecular compositions remains a scientific challenge. Here, we explore a standard and visualizable ontology, termed "biogenic solution map", that organizes multifarious classes of biogenic solutions into a map of hierarchical structures. To build the map, a novel 4-dimensional (4D) fingerprinting method based on data-independent acquisition data sets of untargeted metabolomics is developed, enabling accurate characterization of complex biogenic solutions. A generic parameter of metabolic correlation distance, calculated based on averaged similarities between 4D fingerprints of sample groups, is able to define "species", "genus", and "family" of each solution in the map. With the help of the "biogenic solution map", species of unknown biogenic solutions can be explicitly defined. Simultaneously, intrinsic correlations and subtle variations among biogenic solutions in the map are accurately illustrated. Moreover, it is worth mentioning that samples of the same analyte but prepared by alternative protocols may have significantly different metabolic compositions and could be classified into different "genera".

Follow-up analysis of quality of life in elderly patients with bone trauma: a longitudinal observational study.

BACKGROUND: The quality of life (QoL) of elderly patients with bone trauma is significantly decreased and is affected by many complex factors. This study aims to conduct a half-year follow-up survey to clarify QoL and its influencing factors in elderly patients with bone trauma in order to provide targeted care measures for elderly patients with bone trauma. METHODS: This was a longitudinal observational study. We used the 36-Item Short Form Health Survey (SF-36) to investigate and evaluate the QoL of 100 patients with bone trauma at the time of hospital discharge and 1 month, 3 months, and 6 months after discharge. Our previous study confirmed that the SF-36 had higher reliability and validity for evaluating the QoL of elderly patients with bone trauma. At the same time, we also investigated the age, gender, location of bone trauma, and destination after discharge of those patients. Those factors that might affect the QoL of elderly patients with bone trauma were identified by univariate and multivariate analyses. RESULTS: The total physiological function, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health scores of elderly patients with bone trauma gradually increased from the time of discharge to 1 month, 3 months, and 6 months after discharge, and there were significant differences (p < 0.001). However, there was no significant difference in the general health score in the different periods (P = 0.095). The total QoL scores also significantly differed (F = 118.61, P < 0.001) at the time of discharge (335.252 ± 127.572) and 1 month (285.149 ± 112.827), 3 months (479.344 ± 153.663), and 6 months after discharge (544.396 ± 166.536). The univariate analysis results showed that the location of bone trauma (P < 0.005) and the destination after discharge (P < 0.001) were the main factors affecting QoL in different periods. The results of the multivariate analysis showed that the location of bone trauma was an important factor affecting QoL (P < 0.005 in different periods). Whether to undergo surgery was a factor affecting the patients' long-term QoL (P < 0.005 at 6 months after discharge). CONCLUSIONS: Although the QoL of elderly patients with bone trauma gradually improves after injury, their recovery time is long, and the influencing factors are complex. Follow-up services should continue for at least six months for these patients, and comprehensive treatment and long-term rehabilitation services should be provided.

Machine learning algorithms to estimate 10-Year survival in patients with bone metastases due to prostate cancer: toward a disease-specific survival estimation tool.

BACKGROUND: Prognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer. Such disease-specific models could be added to the PATHFx clinical-decision support tool, which is available worldwide, free of charge. Our secondary aim was to determine disease-specific factors that should be included in an international cancer registry. METHODS: We analyzed records of 438 men with metastatic prostate cancer who sustained SREs that required treatment with radiotherapy or surgery from 1989-2017. We developed and validated 6 models for 1-, 2-, 3-, 4-, 5-, and 10-year survival after treatment. Model performance was evaluated using calibration analysis, Brier scores, area under the receiver operator characteristic curve (AUC), and decision curve analysis to determine the models' clinical utility. We characterized the magnitude and direction of model features. RESULTS: The models exhibited acceptable calibration, accuracy (Brier scores < 0.20), and classification ability (AUCs > 0.73). Decision curve analysis determined that all 6 models were suitable for clinical use. The order of feature importance was distinct for each model. In all models, 3 factors were positively associated with survival duration: younger age at metastasis diagnosis, proximal prostate-specific antigen (PSA) < 10 ng/mL, and slow-rising alkaline phosphatase velocity (APV). CONCLUSIONS: We developed models that estimate survival duration in patients with metastatic bone disease due to prostate cancer. These models require external validation but should meanwhile be included in the PATHFx tool. PSA and APV data should be recorded in an international cancer registry.

Development of an SPR-based binding assay for characterization of anti-CD20 antibodies to CD20 expressed on extracellular vesicles.

Characterization of anti-CD20 antibody binding to CD20 is critical to development of anti-CD20 therapeutics. While SPR is widely used to characterize binding of therapeutics to their targets, its application to the characterization of anti-CD20 therapeutics has been limited by the challenges of obtaining recombinant or native full-length CD20 suitable for ligand binding assays. Extracellular vesicles (EVs) are nanoparticles naturally released from cells that provide a favorable microenvironment for membrane proteins such as CD20 to maintain proper conformation and activity. Here, we report a novel SPR-based assay that enables elucidation of binding kinetics and affinity measurements for anti-CD20 antibody binding to EV-expressed CD20. Our SPR assay is label-free, easy to perform, and demonstrates specific interaction of rituximab and obinutuzumab to CD20 expressed on EVs. The SPR assay revealed that rituximab and obinutuzumab have different binding kinetics and mechanisms to CD20 although both bind to CD20 with high affinity. Our results are consistent with existing literature and verified the validity of this method. The detailed binding kinetics information may also contribute to a better understanding of the interaction between these two antibodies and CD20. Moreover, our method provides a platform with which to characterize other therapeutic antibodies binding to EV-expressed membrane proteins.

Cohort Profile: The China Severe Trauma Cohort (CSTC).

PurposeTo establish a prospective hospital-based cohort, featured by detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in Chinese population.MethodsThe China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between 1st March 2020 and 8th July 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1-, 3-, 6-, 12-months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage.ResultsA total of 2,500 trauma patients were enrolled (response rate=87.1%) with an average age of 46.01 years, and most of the participants were males(62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. Upon 31st August 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-months follow-up, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance(39.4%), followed by depression(22.6%), anxiety(18.2%), and acute stress reaction(7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline.ConclusionsCSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.

[Application of high-throughput sequencing technology in prenatal thalassemia screening in Zhuhai region].

OBJECTIVE: To compare the performance of high-throughput sequencing technology in prenatal thalassemia screening in Zhuhai area through comparison with traditional methods. METHODS: A total of 1463 pregnant women were randomly selected. Following DNA extraction, high-throughput sequencing and conventional three-step thalassemia screening were carried out for each sample. Inconsistent results samples were validated by quantitative fluorescence PCR (QF-PCR) or Sanger sequencing. The results by the two methods were compared. RESULTS: Among the 1463 cases, 318 (21.74%) were detected by conventional method, which included 210 (14.35%) with α-thalassemia, 97 (6.63%) with ß-thalassemia, 11 (0.75%) with composite α- and ß-thalassemia. Meanwhile, 379 cases (25.91%) of thalassemia were detected by high-throughput sequencing, which included 260 (17.77%) with α-thalassemia, 107 (7.31%) with ß-thalassemia, 12 (0.82%) with composite α- and ß-thalassemia. Six one cases were missed by the conventional method, which yielded a missed diagnosis rate of 16.09%, including 50 cases of α- thalassemia,10 cases of ß-thalassemia, and 1 case of α-compound ß-thalassemia. No cases of thalassemia were missed by high-throughput sequencing, and 10 rare thalassemia genotypes were detected. CONCLUSION: High-throughput sequencing technology can improve the detection rate of thalassemia and reduce the missed diagnosis rate. It has a high application value in prenatal thalassemia screening in Zhuhai area and can more effectively prevent the birth of patients with severe thalassemia.

Investigation of the Quality of Recovery of Surgical Patients Based on the Chinese Version of the Quality of Recovery-15 Survey, a Cross-Sectional Study.

PURPOSE: The quality of recovery (QoR) is an important indicator of a patient's health status in the early postoperative period. Despite its importance, the QoR from the patient's perspective is often neglected in clinical practice. This study was performed to survey and determine the QoR of surgical patients from their own subjective perspective and to provide a reference for the targeted postoperative care of surgical patients in the future. DESIGN: A descriptive and cross-sectional study. METHODS: The Chinese version of the Quality of Recovery-15 (QoR-15) scale was used to survey the QoR of 503 surgical patients in 20 surgical wards from 17 surgical departments of a large tertiary hospital in Sichuan Province, China. A questionnaire survey was administered to each patient before and after the operation, and the scores were compared. FINDINGS: There were no significant differences in "feeling worried or anxious" and "feeling sad or depressed" between the preoperative and postoperative periods (P > 0.05). The postoperative scores for the other items were significantly lower than the preoperative scores. The total postoperative QoR-15 score was significantly lower than the total preoperative score (P < 0.001). CONCLUSIONS: The QoR-15 scores of surgical patients were lower after the surgery than before, and patients still needed care after discharge. Therefore, due to the gradual shortening of the length of stay (LOS) of surgical patients, it is necessary for hospitals to construct a complete surgical patient transitional care process to meet the needs of patients after discharge and promote patient rehabilitation.

Pattern recognition receptor-initiated innate immune responses in mouse prostatic epithelial cells‡.

Three major pathogenic states of the prostate, including benign prostatic hyperplasia, prostate cancer, and prostatitis, are related to the local inflammation. However, the mechanisms underlying the initiation of prostate inflammation remain largely unknown. Given that the innate immune responses of the tissue-specific cells to microbial infection or autoantigens contribute to local inflammation, this study focused on pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs). Primary mouse PECs abundantly expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5), and IFN-inducible protein 16 (p204 in mouse). These PRRs can be activated by their respective ligands: lipopolysaccharide (LPS) and flagellin of Gram-negative bacteria for TLR4 and TLR5, polyinosinic-polycytidylic acid (poly(I:C)) for TLR3 and MDA5, and herpes simplex virus DNA analog (HSV60) for p204. LPS and flagellin predominantly induced the expression of inflammatory cytokines, including tumor necrosis factor alpha (TNFA), interleukin 6 (IL6), chemokines monocyte chemoattractant protein-1 (MCP1), and C-X-C motif chemokine 10 (CXCL10). Poly(I:C) and HSV60 predominantly induced the expression of type 1 interferons (IFNA and IFNB) and antiviral proteins: Mx GTPase 1, 2',5'-oligoadenylate synthetase 1, and IFN-stimulated gene 15. The replication of mumps virus in PECs was inhibited by type 1 IFN signaling. These findings provide insights into the mechanisms underlying innate immune response in the prostate.

A Urine Exosome Gene Expression Panel Distinguishes between Indolent and Aggressive Prostate Cancers at Biopsy.

PURPOSE: Prostate cancer is predominantly indolent at diagnosis with a small fraction (15% to 25%) representing aggressive subtype (Gleason score 7-10), which is prone to metastatic progression. It is critical to explore noninvasive assays for the early detection of this aggressive subtype, when it still can be treated effectively. Additionally, there is an emerging need to develop markers that perform equally well across races, as racial differences in the prevalence and mortality of prostate cancer has become evident. MATERIALS AND METHODS: First catch, nondigital rectal examination urine specimens were collected from patients undergoing diagnostic biopsy. Total RNA was extracted from urinary exosomes and a quantitative expression assay protocol using droplet digital polymerase chain reaction was developed for detection of candidate genes in exosomal mRNAs from urine. Clinical performance for the gene expression assay was evaluated to predict high grade cancer (Gleason score 7-10) from low grade cancer (Gleason score 6) and cancer negative cases at biopsy. Assay performance was examined in combination with standard of care to determine improvement in model prediction. RESULTS: In a racially diverse patient cohort a 2-gene panel (PCA3, PCGEM1), in combination with standard of care variables, significantly improved the prediction of high grade cancer at diagnosis compared to standard of care variables alone (AUC 0.88 vs 0.80, respectively, p=0.016). Decision curve analysis showed that there is a benefit of adopting the gene panel for detection of high grade cancer compared to standard of care alone. CONCLUSIONS: This study highlights the potential for developing broadly applicable prostate cancer diagnostic biomarker panels for aggressive prostate cancer using our novel gene expression assay platform.

Timing of Androgen Deprivation Treatment for Men with Biochemical Recurrent Prostate Cancer in the Context of Novel Therapies.

PURPOSE: There were 3 recent U.S. Food and Drug Administration approvals for drugs to be used in nonmetastatic castration resistant prostate cancer, a state that arises from the unproven start of continuous androgen deprivation therapy (ADT) for biochemical recurrent prostate cancer (BCR), before metastatic disease is evident. This report examines the outcome of men with BCR who defer ADT until time of metastasis. MATERIALS AND METHODS: Retrospective review of men diagnosed with clinically localized prostate cancer who underwent radical prostatectomy at Johns Hopkins Hospital and Walter Reed National Military Medical Center and developed BCR with a prostate specific antigen doubling time of not more than 10 months (806 patients). The primary end points were metastasis-free survival and overall survival from time of local treatment among men who delayed ADT until time of metastasis. RESULTS: The median metastasis-free survival of men with BCR and a prostate specific antigen doubling time <6 months and 10 months who delay ADT until metastasis is 144 months (95% CI 48-not reached) and 192 months (95% CI 72-not reached), respectively, with a median overall survival of 168 months (95% CI 96-276 months) and 204 months (95% CI 120-276), respectively. CONCLUSIONS: Metastasis-free survival and overall survival of men with BCR who delay hormone therapy is long. This underscores the need to reevaluate when to start primary ADT in this patient population.

Real-world characteristics and outcomes of advanced non-small-cell lung cancer patients with EGFR exon 19 deletions or exon 21 mutations.

Aim: To estimate real-world (rw) outcomes for first-line therapy in patients with advanced EGF receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), focusing on specific mutation types. Patients & methods: Retrospective observational study (n = 244 patients). Results: Univariate/multivariate analyses showed longer rw progression-free survival (rwPFS) and rwPFS2 in patients with ex19del versus Leu858Arg mutations. Median overall survival was 12.3 months longer with ex19del versus Leu858Arg mutations (HR: 1.47 [95% CI: 0.96-2.25]; p = 0.074). With EGFR-tyrosine kinase inhibitor monotherapy, unadjusted rwPFS for ex19del mutations was longer than for Leu858Arg mutations (HR: 1.62 [95% CI: 1.03-2.56]; p = 0.036). Conclusion: In this rw cohort of patients with advanced EGFR+ NSCLC, ex19del mutations conferred a prognostic advantage over Leu858Arg mutations, with significantly better rwPFS and rwPFS2.

Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung.

Prevailing dogma holds that cell-cell communication through Notch ligands and receptors determines binary cell fate decisions during progenitor cell divisions, with differentiated lineages remaining fixed. Mucociliary clearance in mammalian respiratory airways depends on secretory cells (club and goblet) and ciliated cells to produce and transport mucus. During development or repair, the closely related Jagged ligands (JAG1 and JAG2) induce Notch signalling to determine the fate of these lineages as they descend from a common proliferating progenitor. In contrast to such situations in which cell fate decisions are made in rapidly dividing populations, cells of the homeostatic adult airway epithelium are long-lived, and little is known about the role of active Notch signalling under such conditions. To disrupt Jagged signalling acutely in adult mammals, here we generate antibody antagonists that selectively target each Jagged paralogue, and determine a crystal structure that explains selectivity. We show that acute Jagged blockade induces a rapid and near-complete loss of club cells, with a concomitant gain in ciliated cells, under homeostatic conditions without increased cell death or division. Fate analyses demonstrate a direct conversion of club cells to ciliated cells without proliferation, meeting a conservative definition of direct transdifferentiation. Jagged inhibition also reversed goblet cell metaplasia in a preclinical asthma model, providing a therapeutic foundation. Our discovery that Jagged antagonism relieves a blockade of cell-to-cell conversion unveils unexpected plasticity, and establishes a model for Notch regulation of transdifferentiation.

Multi-omic serum biomarkers for prognosis of disease progression in prostate cancer.

BACKGROUND: Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients 'sera using a multi-omics discovery platform. METHODS: Pre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined. Linear Regression and Bayesian computational approaches integrated with multi-omics, were used to select markers to predict biochemical recurrence (BCR). BCR-free survival was modeled using unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis, adjusted for key pathologic variables. Receiver operating characteristic (ROC) curve statistics were used to examine the predictive value of markers in discriminating BCR events from non-events. The findings were further validated by creating a training set (N = 267) and testing set (N = 115) from the cohort. RESULTS: Among 382 patients, 72 (19%) experienced a BCR event in a median follow-up time of 6.9 years. Two proteins-Tenascin C (TNC) and Apolipoprotein A1V (Apo-AIV), one metabolite-1-Methyladenosine (1-MA) and one phospholipid molecular species phosphatidic acid (PA) 18:0-22:0 showed a cumulative predictive performance of AUC = 0.78 [OR (95% CI) = 6.56 (2.98-14.40), P < 0.05], in differentiating patients with and without BCR event. In the validation set all four metabolites consistently reproduced an equivalent performance with high negative predictive value (NPV; > 80%) for BCR. The combination of pTstage and Gleason score with the analytes, further increased the sensitivity [AUC = 0.89, 95% (CI) = 4.45-32.05, P < 0.05], with an increased NPV (0.96) and OR (12.4) for BCR. The panel of markers combined with the pathological parameters demonstrated a more accurate prediction of BCR than the pathological parameters alone in prostate cancer. CONCLUSIONS: In this study, a panel of serum analytes were identified that complemented pathologic patient features in predicting prostate cancer progression. This panel offers a new opportunity to complement current prognostic markers and to monitor the potential impact of primary treatment versus surveillance on patient oncological outcome.

Lipopolysaccharide-induced testicular dysfunction and epididymitis in mice: a critical role of tumor necrosis factor alpha†.

Systemic inflammation may impair male fertility, and its underlying mechanisms remain poorly understood. The present study investigates the effect of lipopolysaccharide (LPS)-induced systemic inflammation on the testis and epididymis in mice. Intraperitoneal injection of LPS significantly impaired testicular functions, including testosterone production, spermatogenesis, and blood-testis barrier permeability. The epididymitis characterized by leukocyte infiltration and fibrosis was observed in the cauda epididymis after LPS injection. LPS-induced testicular dysfunction and epididymitis were abolished in tumor necrosis factor alpha (Tnfa) knockout mice. Pomalidomide, a TNFA inhibitor, blocked the detrimental effects of LPS on the testis and epididymis. The results indicate that LPS-induced systemic inflammation impairs male fertility through TNFA production, suggesting that the intervention on TNFA production would be considered for the prevention and treatment of inflammatory impairment of male fertility.

Pattern recognition receptor-mediated innate immune responses in seminal vesicle epithelial cell and their impacts on cellular function†.

The seminal vesicles can be infected by microorganisms, thereby resulting in vesiculitis and impairment in male fertility. Innate immune responses in seminal vesicles cells to microbial infections, which facilitate vesiculitis, have yet to be investigated. The present study aims to elucidate pattern recognition receptor-mediated innate immune responses in seminal vesicles epithelial cells. Various pattern recognition receptors, including Toll-like receptor 3, Toll-like receptor 4, cytosolic ribonucleic acid, and deoxyribonucleic acid sensors, are abundantly expressed in seminal vesicles epithelial cells. These pattern recognition receptors can recognize their respective ligands, thus activating nuclear factor kappa B and interferon regulatory factor 3. The pattern recognition receptor signaling induces expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (Tnfa) and interleukin 6 (Il6), chemokines monocyte chemoattractant protein-1 (Mcp1) and C-X-C motif chemokine 10 (Cxcl10), and type 1 interferons Ifna and Ifnb. Moreover, pattern recognition receptor-mediated innate immune responses up-regulated the expression of microsomal prostaglandin E synthase and cyclooxygenase 2, but they down-regulated semenogelin-1 expression. These results provide novel insights into the mechanism underlying vesiculitis and its impact on the functions of the seminal vesicles.

Environmental enrichment reduces adolescent anxiety- and depression-like behaviors of rats subjected to infant nerve injury.

BACKGROUND: Infant nerve injury causes delayed adolescent neuropathic pain, but whether it also leads to psychiatric illness is unknown. Environmental enrichment (EE) increases social communication and activity. Thus, our goal was to test anxiety- and depression-like behaviors after infant peripheral nerve injury and evaluate the effect of environmental enrichment on these models of affective disorders. METHODS: Open field, elevated plus maze, sucrose preference, and pain behaviors (paw withdrawal threshold, spontaneous guarding score, and cold response to acetone) were measured in rats that received infant spared nerve injury (SNI). Enzyme-linked immune absorbent assay of cytokines was performed to evaluate the inflammatory response in the brain. Then, the ability of intracerebroventricular (ICV) injection of a microglia inhibitor, minocycline (MIN), and EE (a free-running wheel, a staircase, a plastic tunnel, a raised platform, and various colored balls) to reverse the infant SNI effects on behaviors and cytokines was examined. RESULTS: Infant nerve injury resulted in adolescent anxiety- and depression-like behaviors. The medial prefrontal cortex, basolateral amygdala, and ventral hippocampus were skewed to a pro-inflammatory profile. ICV injection of MIN reduced anxiety- and depression-like behaviors without affecting pain behaviors. In addition, ICV MIN skewed the brain towards an anti-inflammatory profile. Finally, environmental enrichment improved anxiety- and depression-like behaviors, as well as pain behaviors. EE increased brain IL-10 and decreased IL-1ß and TNF-α. CONCLUSIONS: Infant nerve injury induces adolescent anxiety- and depression-like behaviors and central nervous inflammation. Environmental enrichment reduces these behaviors by normalizing the inflammation balance in the brain.

Neisseria flavescens: A Urease-Expressing Potential Pathogen Isolated from Gastritis Patients.

Parasitic pathogens, such as H. pylori (Helicobacter pylori), are considered as primary elements for causing stomach infection and leading to chronic gastritis or ulcers. Here, an unreported urease- and oxidase-producing Neisseria flavescens-like bacteria was isolated from the gastroscopic biopsies of 14C-UBT-positive gastritis patients. The isolate expressed the activity of urease, which is a pathogenic factor and considered as a reliable marker for diagnosis of H. pylori infection. However, the isolate didn't express the key functional genes of H. pylori including vacA and hpaA, and also the morphological feature of isolate was significantly different with H. pylori. Eventually, the 16S rDNA of isolate was sequenced and its sequence shared about 99.8% similarity with the N. flavescens standard strains, but about 20.8% similarity with the H. pylori. Further study of antibiotics-resistance revealed the N. flavescens isolate is high resistant to metronidazole, but highly sensitive to ampicillin sodium. To summarize, a urease-expressing N. flavescens strain was isolated and identified from Chinese gastritis patients; the encouraging results provides an important reference for the further study of its pathogenicity and the reasonable diagnosis and use of antibiotics clinically.