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Abstract Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes. We performed a retrospective analysis of adult asthma patients (aged ≥18 years) treated in the primary and specialist care settings in Singapore between 2015 to 2019. Medication adherence was measured using the medication possession ratio (MPR), and categorised into good adherence (MPR 0.75-1.2), poor adherence (MPR 0.75) or medication oversupply (MPR > 1.2). All statistical analyses were performed using R Studio. 8023 patients, mean age 57 years, were evaluated between 2015 and 2019. Most patients were receiving primary care (70.4%) and on GINA step 1–3 therapies (78.2%). ICS-long-acting beta-2 agonist (ICS-LABA) users increased over the years especially in the primary care, from 33% to 52%. Correspondingly, inpatient admission and ED visit rates decreased over the years. Between 2015 and 2019, the proportion of patients with poor adherence decreased from 12.8% to 10.5% (for ICS) and from 30.0% to 26.8% (for ICS-LABA) respectively. Factors associated with poor adherence included minority ethnic groups (Odds ratio of MPR 0.75–1.2: 0.73–0.93; compared to Chinese), presence of COPD (OR 0.75, 95% CI 0.59–0.96) and GINA step 4 treatment ladder (OR 0.71, 95% CI 0.61–0.85). Factors associated with good adherence were male gender (OR 1.14, 95% CI 1.01–1.28), single site of care (OR 1.22 for primary care and OR 1.76 for specialist care), GINA step 2 treatment ladder (OR 1.28, 95% CI 1.08–1.50). Good adherence was also associated with less frequent inpatient admission (OR 0.91, 95% CI 0.84–0.98), greater SABA overdispensing (OR 1.66, 95% CI 1.47–1.87) and oral corticosteroids use (OR 1.10, 95% CI 1.05–1.14). Inhaled corticosteroid (ICS) adherence has improved generally, however, poor adherence was observed for patients receiving asthma care in both primary and specialist care, and those from the minority ethnicities.

BackgroundIntegrating algorithm-based clinical decision support (CDS) systems poses significant challenges in evaluating their actual clinical value. Such CDS systems are traditionally assessed via controlled but resource-intensive clinical trials. ObjectiveThis paper presents a review protocol for preimplementation in silico evaluation methods to enable broadened impact analysis under simulated environments before clinical trials. MethodsWe propose a scoping review protocol that follows an enhanced Arksey and O’Malley framework and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to investigate the scope and research gaps in the in silico evaluation of algorithm-based CDS models—specifically CDS decision-making end points and objectives, evaluation metrics used, and simulation paradigms used to assess potential impacts. The databases searched are PubMed, Embase, CINAHL, PsycINFO, Cochrane, IEEEXplore, Web of Science, and arXiv. A 2-stage screening process identified pertinent articles. The information extracted from articles was iteratively refined. The review will use thematic, trend, and descriptive analyses to meet scoping aims. ResultsWe conducted an automated search of the databases above in May 2023, with most title and abstract screenings completed by November 2023 and full-text screening extended from December 2023 to May 2024. Concurrent charting and full-text analysis were carried out, with the final analysis and manuscript preparation set for completion in July 2024. Publication of the review results is targeted from July 2024 to February 2025. As of April 2024, a total of 21 articles have been selected following a 2-stage screening process; these will proceed to data extraction and analysis. ConclusionsWe refined our data extraction strategy through a collaborative, multidisciplinary approach, planning to analyze results using thematic analyses to identify approaches to in silico evaluation. Anticipated findings aim to contribute to developing a unified in silico evaluation framework adaptable to various clinical workflows, detailing clinical decision-making characteristics, impact measures, and reusability of methods. The study’s findings will be published and presented in forums combining artificial intelligence and machine learning, clinical decision-making, and health technology impact analysis. Ultimately, we aim to bridge the development-deployment gap through in silico evaluation-based potential impact assessments. International Registered Report Identifier (IRRID)DERR1-10.2196/63875

With the progression of big data and cloud computing technologies, there has been an escalating trend in cross-institutional data sharing and interaction within the financial sector. However, the frequent occurrence of privacy breaches poses significant challenges to ensuring data security protection. This necessitates the elevation of requirements for identity authentication across data centers and other technologies related to data security management. The traditional centralized identity authentication schemes are inherently flawed in security and scalability, which hampers their ability to meet the demands of high-frequency cross-center data sharing applications. The blockchain technology has emerged as a potential solution, offering exceptional characteristics such as a distributed nature, tamper-proof properties, traceability, and the ability to achieve multi-party consensus. In practical application scenarios, it is essential to not only protect the privacy of user identities but also to effectively regulate anonymous identities. An anonymous and supervisable cross-data center identity authentication scheme based on blockchain was proposed. This scheme did not necessitate alterations to the original architecture of each data center. Instead, a distributed multi-center consortium blockchain was formed by leveraging more than one server from each data center to establish a data center union. Blockchain technology was utilized to ensure the transparency and reliability of the identity authentication process. Additionally, attribute signatures were employed to safeguard user identity privacy while simultaneously creating an identity mapping table that facilitated the tracking of real user identities. Consequently, the scheme was designed to protect user privacy during cross-data center identity authentication and to enable effective supervision over anonymous identities. A thorough security analysis and the results of experiments demonstrate that the proposed scheme possesses the following attributes: it does not require users to re-register, it exhibits characteristics of unforgeability and traceability, and it is capable of withstanding various network attacks, including replay attacks, denial of service attacks, tampering attacks, and man-in-the-middle attacks.

Streptococcus agalactiae (S. agalactiae) is a pathogen causing bovine mastitis that results in considerable economic losses in the livestock sector. To understand the distribution and drug resistance characteristics of S. agalactiae from dairy cow mastitis cases in China, multilocus sequence typing (MLST) was carried out and the serotypes and drug resistance characteristics of the bacteria in the region were analysed.

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming. Herein, we designed a “multiple vectors in one AAV” strategy for promoter construction in vivo. Through this strategy, we truncated a native promoter for Myo15 expression in hair cells (HCs) in the inner ear, from 1,611 bp down to 1,157 bp, and further down to 956 bp. Under the control of these 2 promoters, green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs. The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system. Driven by these 2 promoters, human otoferlin was selectively expressed in HCs, resulting in the restoration of hearing in treated Otof −/− mice for at least 52 weeks. In summary, we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.

Summary: Female receptivity in mating is crucial for successful copulation, but protocols for quantifying female behaviors reflecting receptivity are scarce compared to the analysis of male behaviors. Here, we present a protocol for assessing the sexual receptivity of female Drosophila that considers behaviors from both sexes. We describe steps for preparing and loading flies into a courtship chamber, video recording the behaviors of the pairs, and analyzing their behavioral displays. This protocol includes behavior recognition criteria suitable for typical laboratory settings.For complete details on the use and execution of this protocol, please refer to Yang et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objective: A Colon Cleanliness Rating Algorithm (CCRA) based on colonoscopy image analysis is proposed in this paper, in order to solve the problem that the results of Colon Cleanliness (or Bowel Preparation Quality) rating caused by manual inspection are inconsistent. Methods: Firstly, CCRA intercepts images from the colonoscopy video. Secondly, each colonoscopy image's stool area is segmented by U-Net to obtain the 2-classification segmentation results. Finally, the colon cleanliness is obtained by comparing the average area of the stool area with the standard proportion. Results: After testing, the pixel accuracy of the U-Net model is 97.02 %, IoU is 83.67 %, accuracy is 92.17 %, recall is 90.21 %, F1-Score is 90.95 %. The accuracy of CCRA is 92.45 %–99.275 % Conclusion: The experimental results show that the CCRA proposed in this paper can quickly and accurately output the colon cleanliness rating of patients without manpower.

Streptococcus agalactiae is an important zoonotic pathogen that affects milk production and quality and poses a threat to public health. Treatment of infections with this bacterium exploits antimicrobials, to which the resistance of S. agalactiae is a growing problem. Addressing the possibility of a correlation between this pathogen’s genetic factors for antimicrobial resistance and virulence, this study attempted to identify the relevant genes.

Background Functional dyspepsia (FD) after ischemic stroke belongs to the category of post-stroke gastrointestinal dysfunction, which is prevalent in middle-aged and elderly patients. Stroke patients may differ from the general population in the influencing factors of FD due to their own somatic and psychological changes. Objective To investigate the associated factors of the severity of functional dyspepsia after ischemic stroke. Methods A total of 180 middle and old aged patients with functional dyspepsia after ischemic stroke were selected from March 2017 to July 2018 in the Department of Acupuncture of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine. A self-designed dyspepsia symptom score scale was used to evaluate the severity of FD during hospitalization. The patients were divided into mild FD group (score≤7, n=115) and moderate-severe FD group (score>7, n=65) according to the dyspepsia symptom score. Patient data were collected through the medical record system, and multivariate Logistic regression were used to explore the influencing factors of functional dyspepsia severity after ischemic stroke. Results The FD symptom scores of 180 patients was in the range of 3-12 points, with an average of (7.2±1.7) points. Among them, 115 patients (63.9%) had symptom score≤7 points, and 65 patients (36.1%) had symptom score>7 points. The severity of functional dyspepsia patients with different ages and stroke duration (acute, convalescent, sequelae) was statistically different (P

Abstract Background The clinical value and cost-effectiveness of invasive treatments for patients with coronary artery disease is unclear. Invasive treatments such as coronary artery bypass grafting and percutaneous coronary intervention are frequently used as a starting treatment, yet they are much more costly than optimal medical therapy. While patients may transition into other treatments over time, the choices of starting treatments are likely important determinants of costs and health outcomes. The aim is to predict by how much costs and health outcomes will change from a decision to use different starting treatments for patients with coronary artery disease in an Asian setting. Methods A cost-effectiveness study using a Markov model informed by data from Singapore General Hospital was done. All patients with initial presentations of stable coronary disease and no acute coronary syndromes who received medical treatments and interventional therapies were included. We compare existing practice, where the starting treatment can be medical therapy or stent percutaneous coronary interventions or coronary artery bypass grafting, with alternate starting treatment strategies. Results When compared to ‘existing practice’ a policy of starting 14% of patients with coronary artery bypass grafting and 86% with optimal medical therapy showed savings of $1,743 per patient and 0.23 additional quality adjusted life years. A change to policy nationwide would save $10 million and generate 1,380 quality adjusted life years. Conclusions Increasing coronary artery bypass grafting and use of medical therapy in the setting of coronary artery disease is likely to saves costs and improve health outcomes. A definitive study to address the question we investigate would be very difficult to undertake and so using existing data to model the expected outcomes is a useful tool. There are likely to be large and complex barriers to the implementation of any policy change based on the findings of this study.

Pituitary adenomas are benign tumors of the anterior pituitary gland for which surgery or pharmacological treatment is the primary treatment. When initial treatment fails, radiation therapy should be considered. There are several case reports demonstrating radiation-induced vascular injury. We report an adult patient who presented with headache and diplopia for 6 months and a sellar tumor with optic chiasm compression. The patient received transnasal surgery, and the tumor was partially removed, which demonstrated adenoma. Stereotactic radiosurgery (SRS) was arranged. However, owing to progressive tumor growth, the patient received further transnasal surgery and stereotactic radiosurgery (SRS). After 14 years, the patient reported the sudden onset of headache and diplopia, and a ruptured fusiform aneurysm from the left internal carotid artery with pituitary apoplexy was diagnosed. The patient received transarterial embolization of the aneurysm. There were no complications after embolization, and this patient was ambulatory on discharge with blindness in the left eye and cranial nerve palsies. Aneurysm formation may be a complication of SRS, and it may occur after several years. Further research is needed to investigate the pathogenesis of radiosurgery and the development of cerebral aneurysms.

Summary: The courtship ritual is a dynamic interplay between males and females. Courtship successfully leading to copulation is determined by the intention of both parties which is conveyed by complex action sequences. In Drosophila, the neural mechanisms controlling the female’s willingness to mate, or sexual receptivity, have only recently become the focus of investigations. Here, we report that pre-mating sexual receptivity in females requires activity within a subset of serotonergic projection neurons (SPNs), which positively regulate courtship success. Of interest, a male-derived sex peptide, SP, which was transferred to females during copulation acted to inhibit the activity of SPN and suppressed receptivity. Downstream of 5-HT, subsets of 5-HT7 receptor neurons played critical roles in SP-induced suppression of sexual receptivity. Together, our study reveals a complex serotonin signaling system in the central brain of Drosophila which manages the female’s desire to mate.

Abstract Preoperative prediction of tumor recurrence after radiofrequency ablation (RFA) in patients with early hepatocellular carcinoma (HCC) is helpful for clinical decision-making before treatment. A total of 162 patients with HCC of 3 cm or less who were completely ablated by percutaneous RFA were divided into a derivation cohort (n = 108) and a validation cohort (n = 54). Based on X-Tiles software, Kaplan–Meier curve analysis and COX multivariate analysis to obtain valuable predictive indicators, a clinical scoring system for predicting tumor recurrence was established. In the verall cohort, derivation cohort and validation cohort, we found circulating tumor cells (CTC) > 2/3.2 mL, alpha-fetoprotein (AFP) > 20 ng/mL, and des-γ-carboxyprothrombin (DCP) > 40 mAU/mL, maximum tumor diameter > 20 mm, and the number of multiple tumors (≥ 2) are independent risk factors affecting tumor recurrence. Each independent risk factor was assigned a score of 1 to construct a predictive clinical scoring system, and X-Tiles software was used to divide the clinical score into a low-risk group (0 score–1 score), a medium-risk group (2 scores–3 scores), and a high-risk group (4 scores–5 scores). The cumulative tumor recurrence rates of patients in the low-risk group, middle-risk group, and high-risk group in 1 year, 2 years, and 3 years were 19.4%/27.5%/30.9%, 37.0%/63.2%/79.9% and 68.2%/100%/100%, respectively (Low-risk group vs medium-risk group: P

Fiber-reinforced resin-based plastics are widely used in structural composites for aerospace and automotive applications, and they often face extreme load conditions in actual working environments. It is challenging to monitor the damage of the structure during the vibration process. This study was aimed at using buckypaper (BP) sensors to monitor the structural health status of composite structures under ambient vibrations. First, the feasibility of flexible printed circuit instead of wire is verified by the tensile experiment. Then the vibration monitoring experiment of the composite cantilever beam is carried out by using BP sensors systematically. The sweep frequency experiment determines the excitation frequency of the cantilever beam. Low-period vibration fatigue cycle and high-period vibration fatigue cycle experiments are designed to verify the vibration monitoring method using BP sensors. Besides, the signal response of BP sensors in the vibration experiment is analyzed, and the relationship between ΔR/R0 and vibration acceleration is obtained. Finally, through the change law of ΔR/R0 of the sensor, the cumulative damage caused by vibration fatigue is visualized. It is demonstrated that the monitoring method based on BP sensors can be applied to study the damage behavior of composite structure under the vibration environment. Abbreviations: FRP, fiber-reinforced resin-based plastics; SHM, structural health monitoring; SEM, scanning electron microscopic; FPC, flexible printed circuit; FBG, Fiber Bragg Grating; AE, acoustic emission.

Despite recent advances in therapies, cardiovascular diseases ( CVDs ) are still the leading cause of mortality worldwide. Previous studies have shown that metabolic perturbations in cardiac energy metabolism are closely associated with the progression of CVDs. As expected, metabolic interventions can be applied to alleviate metabolic impairments and, therefore, can be used to develop therapeutic strategies for CVDs. β-hydroxybutyrate (β-HB) was once known to be a harmful and toxic metabolite leading to ketoacidosis in diabetes. However, the minor metabolite is increasingly recognized as a multifunctional molecular marker in CVDs. Although the protective role of β-HB in cardiovascular disease is controversial, increasing evidence from experimental and clinical research has shown that β-HB can be a “super fuel” and a signaling metabolite with beneficial effects on vascular and cardiac dysfunction. The tremendous potential of β-HB in the treatment of CVDs has attracted many interests of researchers. This study reviews the research progress of β-HB in CVDs and aims to provide a theoretical basis for exploiting the potential of β-HB in cardiovascular therapies.

Staphylococcus aureus infections pose a potential threat to livestock production and public health. A novel strategy is needed to control S. aureus infections due to its adaptive evolution to antibiotics. Autophagy plays a key role in degrading bacteria for innate immune cells. In order to promote S. aureus clearance via Toll-like receptor (TLR)-induced autophagy pathway, the domain fusion TLR2-4 with the extracellular domain of TLR2, specific recognizing S. aureus, and transmembrane and intracellular domains of TLR4 is assembled, then the goat expressing TLR2-4 is generated. TLR2-4 substantially augments the removal of S. aureus within macrophages by elevating autophagy level. Phosphorylated JNK and ERK1/2 promote LC3-puncta in TLR2-4 macrophages during S. aureus-induced autophagy via MyD88 mediated the TAK1 signaling cascade. Meantime, the TRIF-dependent TBK1-TFEB-OPTN signaling is involved in TLR2-4-triggered autophagy after S. aureus challenge. Moreover, the transcript of ATG5 and ATG12 is significantly increased via cAMP-PKA-NF-κB signaling, which facilitates S. aureus-induced autophagy in TLR2-4 macrophages. Overall, the novel receptor TLR2-4 enhances the autophagy-dependent clearance of S. aureus in macrophages via TAK1/TBK1-JNK/ERK, TBK1-TFEB-OPTN, and cAMP-PKA-NF-κB-ATGs signaling pathways, which provide an alternative approach for resistant against S. aureus infection.

Introduction: Microvascular invasion (MVI) of is generally considered to be an important prognostic factor for hepatocellular carcinoma (HCC) after operation, An accurate prediction of MVI before operation is helpful for clinical decision-making before operation. Material and methods: A retrospective analysis of 227 cases of hepatocellular carcinoma patients after hepatectomy has been confirmed the pathological result whether there was MVI, and has been determined the independent risk factors of MVI. Based on these independent risk factors, we constructed a clinical scoring risk model for predicting MVI. Results: Among the 227 patients with HCC, 74 (34.6%) were MVI positive. Using receiver operating characteristic (ROC) curve and logistic regression model, we found that alpha-fetoprotein(AFP)≥158 ng/mL(odds ratio[OR] = 4.152,95% confidence interval [95%CI]:1.602∼10.760,p = 0.003), Des-γ-carboxy prothrombin (DCP)≥178mAU/mL(OR = 9.730,95%CI:3.392∼27.910,p

Background The role of cardiac arrest centers (CACs) in out‐of‐hospital cardiac arrest care systems is continuously evolving. Interpretation of existing literature is limited by heterogeneity in CAC characteristics and types of patients transported to CACs. This study assesses the impact of CACs on survival in out‐of‐hospital cardiac arrest according to varying definitions of CAC and prespecified subgroups. Methods and Results Electronic databases were searched from inception to March 9, 2021 for relevant studies. Centers were considered CACs if self‐declared by study authors and capable of relevant interventions. Main outcomes were survival and neurologically favorable survival at hospital discharge or 30 days. Meta‐analyses were performed for adjusted odds ratio (aOR) and crude odds ratios. Thirty‐six studies were analyzed. Survival with favorable neurological outcome significantly improved with treatment at CACs (aOR, 1.85 [95% CI, 1.52–2.26]), even when including high‐volume centers (aOR, 1.50 [95% CI, 1.18–1.91]) or including improved‐care centers (aOR, 2.13 [95% CI, 1.75–2.59]) as CACs. Survival significantly increased with treatment at CACs (aOR, 1.92 [95% CI, 1.59–2.32]), even when including high‐volume centers (aOR, 1.74 [95% CI, 1.38–2.18]) or when including improved‐care centers (aOR, 1.97 [95% CI, 1.71–2.26]) as CACs. The treatment effect was more pronounced among patients with shockable rhythm (P=0.006) and without prehospital return of spontaneous circulation (P=0.005). Conclusions were robust to sensitivity analyses, with no publication bias detected. Conclusions Care at CACs was associated with improved survival and neurological outcomes for patients with nontraumatic out‐of‐hospital cardiac arrest regardless of varying CAC definitions. Patients with shockable rhythms and those without prehospital return of spontaneous circulation benefited more from CACs. Evidence for bypassing hospitals or interhospital transfer remains inconclusive.

Tumor is a metabolic disease. The effect of oncogene expression on the metabolism of cancer cells is one of the hotspots in cancer research. In this study, 1H NMR-based metabonomics analysis was used to explore the metabolic characteristics of glioma cell lines with low expression of SIRT7, and to identify the characteristic metabolites and metabolic pathways related to the expression of SIRT7. The results showed that there were significant differences in metabolic profiles between the SIRT7 low expression group and the control group, and 22 aqueous metabolites were found to vary significantly. Compared with the control group, the concentration of 12 metabolites including lactate, glycine, and glutamate, and so on, increased in SIRT7 low expression glioma cell lines, while the concentration of 10 metabolites such as valine, leucine, lysine, et al. decreased. Pathway enrichment analysis indicated that the metabolic pathways of aminoacyl-tRNA biosynthesis, tyrosine metabolism, and so on, were closely related to the low expression of SIRT7. The results provide a theoretical basis for further mechanism elucidation of SIRT7 regulating glioma cell metabolism.

BackgroundType 2 diabetes mellitus (T2DM) and its related complications represent a growing economic burden for many countries and health systems. Diabetes complications can be prevented through better disease control, but there is a large gap between the recommended treatment and the treatment that patients actually receive. The treatment of T2DM can be challenging because of different comprehensive therapeutic targets and individual variability of the patients, leading to the need for precise, personalized treatment. ObjectiveThe aim of this study was to develop treatment recommendation models for T2DM based on deep reinforcement learning. A retrospective analysis was then performed to evaluate the reliability and effectiveness of the models. MethodsThe data used in our study were collected from the Singapore Health Services Diabetes Registry, encompassing 189,520 patients with T2DM, including 6,407,958 outpatient visits from 2013 to 2018. The treatment recommendation model was built based on 80% of the dataset and its effectiveness was evaluated with the remaining 20% of data. Three treatment recommendation models were developed for antiglycemic, antihypertensive, and lipid-lowering treatments by combining a knowledge-driven model and a data-driven model. The knowledge-driven model, based on clinical guidelines and expert experiences, was first applied to select the candidate medications. The data-driven model, based on deep reinforcement learning, was used to rank the candidates according to the expected clinical outcomes. To evaluate the models, short-term outcomes were compared between the model-concordant treatments and the model-nonconcordant treatments with confounder adjustment by stratification, propensity score weighting, and multivariate regression. For long-term outcomes, model-concordant rates were included as independent variables to evaluate if the combined antiglycemic, antihypertensive, and lipid-lowering treatments had a positive impact on reduction of long-term complication occurrence or death at the patient level via multivariate logistic regression. ResultsThe test data consisted of 36,993 patients for evaluating the effectiveness of the three treatment recommendation models. In 43.3% of patient visits, the antiglycemic medications recommended by the model were concordant with the actual prescriptions of the physicians. The concordant rates for antihypertensive medications and lipid-lowering medications were 51.3% and 58.9%, respectively. The evaluation results also showed that model-concordant treatments were associated with better glycemic control (odds ratio [OR] 1.73, 95% CI 1.69-1.76), blood pressure control (OR 1.26, 95% CI, 1.23-1.29), and blood lipids control (OR 1.28, 95% CI 1.22-1.35). We also found that patients with more model-concordant treatments were associated with a lower risk of diabetes complications (including 3 macrovascular and 2 microvascular complications) and death, suggesting that the models have the potential of achieving better outcomes in the long term. ConclusionsComprehensive management by combining knowledge-driven and data-driven models has good potential to help physicians improve the clinical outcomes of patients with T2DM; achieving good control on blood glucose, blood pressure, and blood lipids; and reducing the risk of diabetes complications in the long term.

Summary: Traumatic experiences generate stressful neurological effects in the exposed persons and animals. Previous studies have demonstrated that in many species, including Drosophila, the defeated animal has a higher probability of losing subsequent fights. However, the neural basis of this “loser effect” is largely unknown. We herein report that elevated serotonin (5-HT) signaling helps a loser to overcome suppressive neurological states. Coerced activation of 5-HT neurons increases aggression in males and promotes losers to both vigorously re-engage in fights and even defeat the previous winners and regain mating motivation. P1 neurons act upstream and 5-HT1B neurons in the ellipsoid body act downstream of 5-HT neurons to arouse losers. Our results demonstrate an ancient neural mechanism of regulating depressive behavioral states after distressing events.

With a broad range of hosts, Salmonella enterica serovar Typhimurium (S. Typhimurium) is the major cause of gastroenteritis in human beings and systemic disease in susceptible mice strains. However, different S. Typhimurium strains differ in regard to virulence and host adaptation. Here, C57BL/6 mice were infected, respectively, with different S. Typhimurium strains SL1344 (calf), CVCC541 (chicken) and CMCC50115 (mutton) to determine their virulence and host immune responses. It was found that mice were less susceptible to infection by S. Typhimurium CVCC541 and CMCC50115 strains, with lower lethality and decreased bacterial burden in liver and spleen. Besides, S. Typhimurium strains CVCC541 and CMCC50115 enhanced host innate immune responses by increased frequencies of macrophages and neutrophils 3 days after infection. But SL1344 strain evaded immune response by inducing apoptosis of macrophages. Moreover, CVCC541 could elicit adaptive immune responses of host 11 days after infection upon examination of the proliferation and activation of CD4+ T cells. In addition, 125 and 138 unique mutant coding genes, respectively, in S. Typhimurium strains CVCC541 and CMCC50115 and 78 shared mutant coding genes were annotated by genomic alignment to SL1344 genome and the signal pathways involving these genes were further analyzed. The acquired results indicate that different original S. Typhimurium strains show differential virulence and may induce diverse immune responses in the same host infected.