Does erectile dysfunction predict cardiovascular risk? A cross-sectional study of clinical characteristics in patients with erectile dysfunction combined with coronary heart disease.

Background: Erectile Dysfunction (ED) is a common sexual dysfunction in men who are unable to consistently obtain and maintain sufficient penile erection to accomplish a satisfactory sexual life. ED is currently considered to be a predictor of cardiovascular disease (CVD), but few studies have observed the association between ED and clinical features of coronary heart disease (CHD). An investigation of the association between ED and clinical characteristics of CHD was carried out using a cross-sectional study design. Methods: This cross-sectional single-center study was conducted in the Department of Cardiology and included 248 patients. Associations between patients' general information, underlying disease information, coronary heart disease information, and ED severity were statistically and analytically analyzed using SPSS 26.0 software. Patients with comparable clinical characteristics were grouped together using K-means clustering. Finally, ordered logistic regression analysis was performed for general and underlying disease information. Results: In the comparison of general data, age, education, and weekly exercise were associated with the distribution of ED severity. In the comparison of underlying disease information, the number of underlying diseases, hypertension, diabetes, hyperlipidemia, anxiety state, and depressive state were associated with the distribution of ED severity. In the comparison of CHD information, the degree of ED severity was associated with CHD subtypes, lesion sites, number of stenoses, degree of stenosis, and interventional interventions. The time from ED to CHD onset was associated with the subtypes of CHD and the number of stenoses. We clustered the main characteristics of low-risk and high-risk patients and ordered logistic regression analysis found that BMI, smoking, alcoholism, number of underlying diseases, diabetes, anxiety state, and depression state were all risk factors for CHD severity (P < 0.05); the higher the value of the above factors, the more severe the degree of CHD. Age was a protective factor for CHD severity; the younger the patient, the lower the likelihood of myocardial infarction. Conclusion: ED severity and the time from ED to CHD onset may be predictive of coronary heart disease severity. Reducing smoking and alcohol consumption, maintaining a healthy body weight, and regular physical activity are important in preventing CVD in ED patients.

Self-Powered and Self-Recoverable Multimodal Force Sensors Based on Trap State and Interfacial Electron Transfer.

Multi-dimensional force sensing that combines intensity, location, area and the like could gather a wealth of information from mechanical stimuli. Developing materials with force-induced optical and electrical dual responses would provide unique opportunities to multi-dimensional force sensing, with electrical signals quantifying the force amplitude and the luminescence output providing spatial distribution of force. However, the reliance on external power supply and high-energy excitation source brings significant challenges to the applicability of multi-dimensional force sensors. Here we reported the mechanical energy-driven and sunlight-activated materials with force-induced dual responses, and investigated the underlying mechanisms of self-sustainable force sensing. Theoretical analysis and experimental data unraveled that trap-controlled luminescence and interfacial electron transfer play a major role in force-induced optical and electrical output. These materials were manufactured into pressure sensor with renewable dual-mode output for quantifying and visualization of pressures by electrical and optical output, respectively, without power supply and high-energy irradiation. The quantification of tactile sensation and stimuli localization of mice highlighted the multi-dimensional sensing ability of the sensor. Overall, this self-powered pressure sensor with multimodal output provides more modalities of force sensing, poised to change the way that intelligent devices sense with the world.

UN peacekeeper health and risk factors --- a systematic scoping review.

BACKGROUND: Conflicts, natural disasters, and complex emergencies present substantial health challenges to United Nations (UN) peacekeepers deployed in mission areas. This scoping review aims at summarizing previous research on the health of UN peacekeepers and identifies issues for further investigation. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews, we systematically searched Web of Science, PubMed, EMBASE, Scopus and China National Knowledge Infrastructure (CNKI) for English and Chinese literature published from April 1997 to November 2023. A data charting form was developed by two reviewers to extract relevant themes and provided narrative descriptions. RESULTS: We screened 1079 de-duplicated records and included 143 studies in this scoping review. There were 112 studies on the health status of UN peacekeepers, with more than half on mental health problems such as stress and anxiety. Many studies explored the health status of UN peacekeepers in African countries deployed from mainly U.S., Canada, U.K., China, Australia and Norway. There were 39 studies on the health risk factors of UN peacekeepers, including natural environmental, social environmental, psychological, behavioral lifestyle, biological factors and health service factors. There were 62 articles on the health protection of UN peacekeepers, mainly based on previous deployment experience, with a lack of theoretical guidance from global health perspectives. This scoping review found that health problems of UN peacekeepers are complicated, and whose impacts are cross-border. Social environmental factors were explored the most among health risk factors. Disease prevention measures, medical and health measures, and psychosocial measures were the main health protection for UN peacekeepers. CONCLUSIONS: This scoping review highlighted that health problems of UN peacekeepers were typical global health issues with complicated and cross-border health risk factors. Therefore, comprehensive strategies could be taken from global health perspectives, including multi-phases (before-deployment, during-deployment, and post-deployment), multi-disciplines (public health, medicine, politics, health diplomacy, and others), and multi-levels (the UN, host countries, troop-contributing countries, the UN peacekeeping team, and UN peacekeepers).

Prognostic factors and predictive models for patients with lung large cell neuroendocrine carcinoma: Based on SEER database.

BACKGROUND: Lung Large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive, high-grade neuroendocrine carcinoma with a poor prognosis, mainly seen in elderly men. To date, we have found no studies on predictive models for LCNEC. METHODS: We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database of confirmed LCNEC from 2010 to 2018. Univariate and multivariate Cox proportional risk regression analyses were used to identify independent risk factors, and then we constructed a novel nomogram and assessed the predictive effectiveness by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 2546 patients with LCNEC were included, excluding those diagnosed with autopsy or death certificate, tumor, lymph node, metastasis (TNM) stage, tumor grade deficiency, etc., and finally, a total of 743 cases were included in the study. After univariate and multivariate analyses, we concluded that the independent risk factors were N stage, intrapulmonary metastasis, bone metastasis, brain metastasis, and surgical intervention. The results of ROC curves, calibration curves, and DCA in the training and validation groups confirmed that the nomogram could accurately predict the prognosis. CONCLUSIONS: The nomogram obtained from our study is expected to be a useful tool for personalized prognostic prediction of LCNEC patients, which may help in clinical decision-making.

GPX4 degradation contributes to fluoride-induced neuronal ferroptosis and cognitive impairment via mtROS-chaperone-mediated autophagy.

Ferroptosis is a newly recognized type of programmed cell death that is implicated in the pathophysiological process of neurological disorders. Our previous studies have revealed that exposure to high concentrations of fluoride for long periods of time induces hippocampal neural injury and cognitive deficits. However, whether ferroptosis is involved in fluoride-induced neuronal death and the underlying mechanism remain unknown. In this study, the results indicated that exposure to high fluoride triggered ferroptosis in SH-SY5Y cells and in the hippocampus of mice. Fluoride exposure accelerated the lysosomal degradation of GPX4 and led to neuronal ferroptosis, while GPX4 overexpression protected SH-SY5Y cells against fluoride-induced neurotoxicity. Intriguingly, the enhanced chaperone-mediated autophagy (CMA) induced by fluoride stimulation was responsible for GPX4 degradation because the inhibition of CMA activity by LAMP2A knockdown effectively prevented fluoride-induced GPX4 loss. Furthermore, mitochondrial ROS (mtROS) accumulation caused by fluoride contributed to CMA activation-mediated GPX4 degradation and subsequent neuronal ferroptosis. Notably, the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or the ROS scavenger N-acetyl-L-cysteine (NAC) alleviated fluoride-evoked hippocampal neuronal death and synaptic injury as well as cognitive deficits in mice. The present studies indicates that ferroptosis is a novel mechanism of fluoride-induced neurotoxicity and that chronic fluoride exposure facilitates GPX4 degradation via mtROS chaperone-mediated autophagy, leading to neuronal ferroptosis and cognitive impairment.

Trueness evaluation of three intraoral scanners for the recording of maximal intercuspal position.

OBJECTIVES: This clinical study aimed to assess the trueness of three intraoral scanners for the recor-ding of the maximal intercuspal position (MIP) to provide a reference for clinical practice. METHODS: Ten participants with good occlusal relationship and healthy temporomandibular joint were recruited. For the control group, facebow transferring procedures were performed, and bite registrations at the MIP were used to transfer maxillary and mandibular casts to a mechanical articulator, which were then scanned with a laboratory scanner to obtain digital cast data. For the experimental groups, three intraoral scanners (Trios 3, Carestream 3600, and Aoralscan 3) were used to obtain digital casts of the participants at the MIP following the scanning workflows endorsed by the corresponding manufacturers. Subsequently, measurement points were marked on the control group's digital casts at the central incisors, canines, and first molars, and corresponding distances between these points on the maxillary and mandibular casts were measured to calculate the sum of measured distances (DA). Distances between measurement points in the incisor (DI), canine (DC), and first molar (DM) regions were also calculated. The control group's maxillary and mandibular digital casts with the added measurement points were aligned with the experimental group's casts, and DA, DI, DC, and DM values of the aligned control casts were determined. Statistical analysis was performed on DA, DI, DC, and DM obtained from both the control and experimental groups to evaluate the trueness of the three intraoral scanners for the recording of MIP. RESULTS: In the control group, DA, DI, DC, and DM values were (39.58±6.40), (13.64±3.58), (14.91±2.85), and (11.03±1.56) mm. The Trios 3 group had values of (38.99±6.60), (13.42±3.66), (14.55±2.87), and (11.03±1.69) mm. The Carestream 3600 group showed values of (38.57±6.36), (13.56±3.68), (14.45±2.85), and (10.55±1.41) mm, while the Aoralscan 3 group had values of (38.16±5.69), (13.03±3.54), (14.23±2.59), and (10.90±1.54) mm. Analysis of variance revealed no statistically significant differences between the experimental and control groups for overall deviation DA (P=0.96), as well as local deviations DI (P=0.98), DC (P=0.96), and DM (P=0.89). CONCLUSIONS: With standardized scanning protocols, the three intraoral scanners demonstrated comparable trueness to traditional methods in recording MIP, fulfilling clinical requirements.

Adaptive under-sampling strategy for fast imaging in compressive sensing-based atomic force microscopy.

Compressive sensing (CS) can reconstruct the rest information almost without distortion by advanced computational algorithm, which significantly simplifies the process of atomic force microscope (AFM) scanning with high imaging quality. In common CS-AFM, the partial measurements randomly come from the whole region to be measured, which easily leads to detail loss and poor image quality in regions of interest (ROIs). Consequently, important microscopic phenomena are missed probably. In this paper, we developed an adaptive under-sampling strategy for CS-AFM to optimize the process of sampling. Under a certain under-sampling ratio, the weight coefficient of ROIs and regions of base (ROBs) were set to control the distribution of under-sampling points and corresponding measurement matrix. A series of simulations were completed to demonstrate the relationship between the weight coefficient of ROIs and image quality. After that, we verified the effectiveness of the method on our homemade AFM. Through a lot of simulations and experiments, we demonstrated how the proposed method optimized the sampling process of CS-AFM, which speeded up the process of AFM imaging with high quality.

Cadmium exposure induced neuronal ferroptosis and cognitive deficits via the mtROS-ferritinophagy pathway.

Exposure to environmental cadmium (Cd) is known to cause neuronal death and cognitive decline in humans. Ferroptosis, a novel iron-dependent type of regulated cell death, is involved in various neurological disorders. In the present study, Cd exposure triggered ferroptosis in the mouse hippocampus and in the HT22 murine hippocampal neuronal cell line, as indicated by significant increases in ferroptotic marker expression, intracellular iron levels, and lipid peroxidation. Interestingly, ferroptosis of hippocampal neurons in response to Cd exposure relied on the induction of autophagy since the suppression of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) substantially ameliorated Cd-induced ferroptosis. Furthermore, nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin was required for the Cd-induced ferroptosis of hippocampal neurons, demonstrating that NCOA4 knockdown decreased intracellular iron levels and lipid peroxidation and increased cell survival, following Cd exposure. Moreover, Cd-induced mitochondrial reactive oxygen species (mtROS) generation was essential for the ferritinophagy-mediated ferroptosis of hippocampal neurons. Importantly, pretreatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively attenuated Cd-induced hippocampal neuronal death and cognitive impairment in mice. Taken together, these findings indicate that ferroptosis is a novel mechanism underlying Cd-induced neurotoxicity and cognitive impairment and that the mtROS-ferritinophagy axis modulates Cd-induced neuronal ferroptosis.

Rapid Detection of Bacterial Pathogens Causing Lower Respiratory Tract Infections via Microfluidic-Chip-Based Loop-Mediated Isothermal Amplification.

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.

Spread of antibiotic resistance genes in drinking water reservoirs: Insights from a deep metagenomic study using a curated database.

The exploration of antibiotic resistance genes (ARGs) in drinking water reservoirs is an emerging field. Using a curated database, we enhanced the ARG detection and conducted a comprehensive analysis using 2.2 Tb of deep metagenomic sequencing data to determine the distribution of ARGs across 16 drinking water reservoirs and associated environments. Our findings reveal a greater diversity of ARGs in sediments than in water, underscoring the importance of extensive background surveys. Crucial ARG carriers-specifically Acinetobacter, Pseudomonas, and Mycobacterium were identified in drinking water reservoirs. Extensive analysis of the data uncovered a considerable concern for drinking water safety, particularly in regions reliant on river sources. Mobile genetic elements have been found to contribute markedly to the propagation of ARGs. The results of this research suggest that the establishment of drinking water reservoirs for supplying raw water may be an effective strategy for alleviating the spread of water-mediated ARGs.

Digital cross-mounting of intraoral scan casts from a virtual articulator to a mechanical articulator by using a custom transfer plate: A dental technique.

With the development of digital dental technologies, a complete digital workflow without using physical casts has become possible. However, for certain clinical and dental laboratory procedures, especially in complex rehabilitation treatments, physically mounted casts in an ideal location in a mechanical articulator are still necessary for treatment planning and restoration fabrication. This technique report describes a digital approach to fabricating a custom transfer plate to cross mount intraoral scan casts from a virtual articulator to the corresponding mechanical articulator. This technique eliminates the need for conventional physical facebow transfer processes and offers a straightforward approach to integrating virtual procedures with analog workflows.

Orchestrated codelivery of peptide antigen and adjuvant to antigen-presenting cells by using an engineered chimeric peptide enhances antitumor T-cell immunity.

The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. Here, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of antigens and CpG to modulate vaccine efficacy via translating an engineered chimeric peptide, eTAT, as an intramolecular adjuvant. Linking antigens to eTAT enhanced cytosolic delivery of the antigens. This, in turn, led to improved activation and lymph node-trafficking of antigen-presenting cells and antigen cross-presentation, thus promoting antigen-specific T-cell immune responses. Simple mixing of eTAT-linked antigens and CpG significantly enhanced codelivery of antigens and CpG to the antigen-presenting cells, and this substantially augmented the adjuvant effect of CpG, maximized vaccine immunogenicity and elicited robust and durable CD8+ T-cell responses. Vaccination with this formulation altered the tumor microenvironment and exhibited potent antitumor effects, with generally further enhanced therapeutic efficacy when used in combination with anti-PD1. Altogether, the engineered chimeric peptide-based orchestrated codelivery of antigen and adjuvant may serve as a promising but simple strategy to improve the efficacy of peptide-based cancer vaccines.

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain.

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

Rapid discrimination of four Salmonella enterica serovars: A performance comparison between benchtop and handheld Raman spectrometers.

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.

Differentiation of closely-related species within Acinetobacter baumannii-calcoaceticus complex via Raman spectroscopy: a comparative machine learning analysis.

Bacterial species within the Acinetobacter baumannii-calcoaceticus (Acb) complex are very similar and are difficult to discriminate. Misidentification of these species in human infection may lead to severe consequences in clinical settings. Therefore, it is important to accurately discriminate these pathogens within the Acb complex. Raman spectroscopy is a simple method that has been widely studied for bacterial identification with high similarities. In this study, we combined surfaced-enhanced Raman spectroscopy (SERS) with a set of machine learning algorithms for identifying species within the Acb complex. According to the results, the support vector machine (SVM) model achieved the best prediction accuracy at 98.33% with a fivefold cross-validation rate of 96.73%. Taken together, this study confirms that the SERS-SVM method provides a convenient way to discriminate between A. baumannii, Acinetobacter pittii, and Acinetobacter nosocomialis in the Acb complex, which shows an application potential for species identification of Acinetobacter baumannii-calcoaceticus complex in clinical settings in near future.

Evaluation of the accuracy of a fully digital method of measuring sagittal condylar inclination.

OBJECTIVES: This clinical study aimed to evaluate the accuracy of a fully digital technique for measuring sagittal condylar inclination (SCI), as well as validating whether differences existed between the left and right SCI values of the same participant, to provide a reference for clinical practice. METHODS: Ten participants with good occlusal relationship and normal temporomandibular joint were recruited. Three methods were used to measure the SCI values of the participants, namely, A (mechanical facebow transferring and mechanical articulator-based measuring method with physical protrusive interocclusal registration), B (face scan-based virtual facebow and virtual articulator-based measuring method with digital protrusive interocclusal registration), and C (jaw motion tracking system-based measuring method). With the group subjected to methods A and C as the control, the SCI values obtained by the three methods were statistically analyzed. The left and right SCI values of the same participant were also compared. RESULTS: The left and right SCI values measured by method A were 41.70°±7.09° and 42.80°±8.62°, those by method B were 35.09°±12.49° and 37.63°±12.10°, and those by method C were 39.43°±8.72° and 38.45°±6.91°. No significant difference existed among the SCI values measured by the three methods (P>0.05). Meanwhile, no statistical difference existed between the SCI values on the left and right sides of the same participant (P>0.05). CONCLUSIONS: The accuracy of the virtual facebow and digital protrusive occlusal registration based SCI measuring method was the same as that of mechanical facebow based and jaw motion tracking system-based methods. The SCI values on the left and right sides of the same participant were similar. Clinically, an appropriate SCI measurement and setting strategy can be selected based on the actual situations.

Rapid discrimination and ratio quantification of mixed antibiotics in aqueous solution through integrative analysis of SERS spectra via CNN combined with NN-EN model.

INTRODUCTION: Abusing antibiotic residues in the natural environment has become a severe public health and ecological environmental problem. The side effects of its biochemical and physiological consequences are severe. To avoid antibiotic contamination in water, implementing universal and rapid antibiotic residue detection technology is critical to maintaining antibiotic safety in aquatic environments. Surface-enhanced Raman spectroscopy (SERS) provides a powerful tool for identifying small molecular components with high sensitivity and selectivity. However, it remains a challenge to identify pure antibiotics from SERS spectra due to coexisting components in the mixture. OBJECTIVES: In this study, an intelligent analysis model for the SERS spectrum based on a deep learning algorithm was proposed for rapid identification of the antibiotic components in the mixture and quantitative determination of the ratios of these components. METHODS: We established a water environment system containing three antibiotic residues of ciprofloxacin, doxycycline, and levofloxacin. To facilitate qualitative and quantitative analysis of the SERS spectra antibiotic mixture datasets, we developed a computational framework integrating a convolutional neural network (CNN) and a non-negative elastic network (NN-EN) method. RESULTS: The experimental results demonstrate that the CNN model has a recognition accuracy of 98.68%, and the interpretation analysis of Shapley Additive exPlanations (SHAP) shows that our model can specifically focus on the characteristic peak distribution. In contrast, the NN-EN model can accurately quantify each component's ratio in the mixture. CONCLUSION: Integrating the SERS technique assisted by the CNN combined with the NN-EN model exhibits great potential for rapid identification and high-precision quantification of antibiotic residues in aquatic environments.

Swine pseudorabies virus attenuated vaccine reprograms the kidney cancer tumor microenvironment and synergizes with PD-1 blockade.

The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti-neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV-LAV) against KC. The findings clearly demonstrate that PRV-LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV-LAV was confirmed in both a subcutaneous tumor-bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA-seq analysis and flow cytometry revealed that PRV-LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV-LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV-LAV with anti-PD-1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV-LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.

NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.