The gut microbiota modulate locomotion via vagus-dependent glucagon-like peptide-1 signaling.

Locomotor activity is an innate behavior that can be triggered by gut-motivated conditions, such as appetite and metabolic condition. Various nutrient-sensing receptors distributed in the vagal terminal in the gut are crucial for signal transduction from the gut to the brain. The levels of gut hormones are closely associated with the colonization status of the gut microbiota, suggesting a complicated interaction among gut bacteria, gut hormones, and the brain. However, the detailed mechanism underlying gut microbiota-mediated endocrine signaling in the modulation of locomotion is still unclear. Herein, we show that broad-spectrum antibiotic cocktail (ABX)-treated mice displayed hypolocomotion and elevated levels of the gut hormone glucagon-like peptide-1 (GLP-1). Blockade of the GLP-1 receptor and subdiaphragmatic vagal transmission rescued the deficient locomotor phenotype in ABX-treated mice. Activation of the GLP-1 receptor and vagal projecting brain regions led to hypolocomotion. Finally, selective antibiotic treatment dramatically increased serum GLP-1 levels and decreased locomotion. Colonizing Lactobacillus reuteri and Bacteroides thetaiotaomicron in microbiota-deficient mice suppressed GLP-1 levels and restored the hypolocomotor phenotype. Our findings identify a mechanism by which specific gut microbes mediate host motor behavior via the enteroendocrine and vagal-dependent neural pathways.

Butterflies in the gut: the interplay between intestinal microbiota and stress.

Psychological stress is a global issue that affects at least one-third of the population worldwide and increases the risk of numerous psychiatric disorders. Accumulating evidence suggests that the gut and its inhabiting microbes may regulate stress and stress-associated behavioral abnormalities. Hence, the objective of this review is to explore the causal relationships between the gut microbiota, stress, and behavior. Dysbiosis of the microbiome after stress exposure indicated microbial adaption to stressors. Strikingly, the hyperactivated stress signaling found in microbiota-deficient rodents can be normalized by microbiota-based treatments, suggesting that gut microbiota can actively modify the stress response. Microbiota can regulate stress response via intestinal glucocorticoids or autonomic nervous system. Several studies suggest that gut bacteria are involved in the direct modulation of steroid synthesis and metabolism. This review provides recent discoveries on the pathways by which gut microbes affect stress signaling and brain circuits and ultimately impact the host's complex behavior.

Microbial metabolites regulate social novelty via CaMKII neurons in the BNST.

Social novelty is a cognitive process that is essential for animals to interact strategically with conspecifics based on their prior experiences. The commensal microbiome in the gut modulates social behavior through various routes, including microbe-derived metabolite signaling. Short-chain fatty acids (SCFAs), metabolites derived from bacterial fermentation in the gastrointestinal tract, have been previously shown to impact host behavior. Herein, we demonstrate that the delivery of SCFAs directly into the brain disrupts social novelty through distinct neuronal populations. We are the first to observe that infusion of SCFAs into the lateral ventricle disrupted social novelty in microbiome-depleted mice without affecting brain inflammatory responses. The deficit in social novelty can be recapitulated by activating calcium/calmodulin-dependent protein kinase II (CaMKII)-labeled neurons in the bed nucleus of the stria terminalis (BNST). Conversely, chemogenetic silencing of the CaMKII-labeled neurons and pharmacological inhibition of fatty acid oxidation in the BNST reversed the SCFAs-induced deficit in social novelty. Our findings suggest that microbial metabolites impact social novelty through a distinct neuron population in the BNST.

Experience and acceptability for HPV self-sampling among women in Jiangsu province, China: a cross-sectional survey.

This aim of this study was to investigate women's knowledge about HPV along with their experience and acceptability of self-sampling in Jiangsu province, China. A total of 862 women aged 25-63 years old from Jiangsu province who purchased an HPV self-sampling test kit were invited to complete a questionnaire designed by the authors. Participants had high acceptability for HPV self-sampling with a mean score of 4.2 (95% [CI], 4.1-4.22) out of 5 points. 27% of participants preferred clinician-sampling, 33% preferred self-sampling, other 40% expressed no preference. Women with good knowledge about HPV and with a good experience with HPV self-sampling were more acceptable for self-sampling (P < 0.05). The biggest concern about HPV self-sampling of the participants includes 'specimens' spoilage', 'incorrect sampling', 'can't get results in time', and so on. HPV self-sampling can be used to improve cervical cancer screening coverage and participation rates in China.

Cancer screening and can be an alternative primary screening for cervical cancer.•What the results of this study add? This study adds new findings about Chinese women's experience and acceptability of HPV self-sampling. We found that most women had high acceptability for HPV self-sampling in Jiangsu province, China, and high knowledge about HPV as well as good•What is already known on this subject? HPV self-sampling testing was proven to be useful for improving the uptake rate of cervical experience of self-sampling can improve the acceptability for self-sampling in women.•What the implications are of these findings for clinical practice and/or further research? Further research should assess the acceptability of women with less education or who never screened.

Key Drivers of COVID-19 Vaccine Hesitancy: A Perspective of Collectivism.

Vaccination against the COVID-19 pandemic remains a major part of global immunization policy. The aim of this study was to explore young people's willingness to continue to receive vaccination against COVID-19 in a collectivist culture. In this study, an online questionnaire was used to measure willingness to continue vaccination, the tendency towards collectivism, the degree of disease anxiety, vaccine brand loyalty, and perceived infectability in 2022. The results showed that women were more willing to be vaccinated than men (70.1% vs. 29.9%). Young people who were willing to receive continuous vaccination had a relatively higher tendency towards collectivism (p < 0.001), a relatively higher degree of disease anxiety (p < 0.001), and lower vaccine brand loyalty (p = 0.034). The COVID-19 pandemic is still ongoing and, since young people are the most active in group activities, policy-makers should weigh the factors influencing vaccination among the young to create effective policy measures.

Management of Emerging Health Conditions to Improve Resilience and Mental Health.

Good health is when a person is in a complete, optimal physical, mental, and social condition [...].

Intracerebroventricular Delivery of Gut-derived Microbial Metabolites in Freely Moving Mice.

The impact of gut microbiota and their metabolites on host physiology and behavior has been extensively investigated in this decade. Numerous studies have revealed that gut microbiota-derived metabolites modulate brain-mediated physiological functions through intricate gut-brain pathways in the host. Short-chain fatty acids (SCFAs) are the major bacteria-derived metabolites produced during dietary fiber fermentation by the gut microbiome. Secreted SCFAs from the gut can act at multiple sites in the periphery, affecting the immune, endocrine, and neural responses due to the vast distribution of SCFAs receptors. Therefore, it is challenging to differentiate the central and peripheral effects of SCFAs through oral and intraperitoneal administration of SCFAs. This paper presents a video-based method to interrogate the functional role of SCFAs in the brain via a guide cannula in freely moving mice. The amount and type of SCFAs in the brain can be adjusted by controlling the infusion volume and rate. This method can provide scientists with a way to appreciate the role of gut-derived metabolites in the brain.

Oral short-chain fatty acids administration regulates innate anxiety in adult microbiome-depleted mice.

Anxiety is characterized by feelings of tension and worry even in the absence of threatening stimulus. Pathological condition of anxiety elicits defensive behavior and aversive reaction ultimately impacting individuals and society. The gut microbiota has been shown to contribute to the modulation of anxiety-like behavior in rodents through the gut-brain axis. Several studies observed that germ-free (GF) and the broad spectrum of antibiotic cocktail (ABX)-treated rodents display lowered anxiety-like behavior. We speculate that gut microbial short-chain fatty acids (SCFA) modulate the innate anxiety response. Herein, we administered SCFA in the drinking water in adult mice treated with ABX to deplete the microbiota and tested their anxiety-like behavior. To further augment the innate fear response, we enhanced the aversive stimulus of the anxiety-like behavior tests. Strikingly, we found that the anxiety-like behavior in ABX mice was not altered when enhanced aversive stimulus, while control and ABX mice supplemented with SCFA displayed increased anxiety-like behavior. Vagus nerve serves as a promising signaling pathway in the gut-brain axis. We determined the role of vagus nerve by subdiaphragmatic vagotomy (SDV) in ABX mice supplemented with SCFA. We found that the restored anxiety-like behavior in ABX mice by SCFA was unaffected by SDV. These findings suggest that gut microbiota can regulate anxiety-like behavior through their fermentation products SCFA.

A gut-derived metabolite alters brain activity and anxiety behaviour in mice.

Integration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.

How Ethical Leadership Promotes Knowledge Sharing: A Social Identity Approach.

The aim of this study is to investigate the associations among ethical leadership, group identification, relational identification, organizational identification, and knowledge sharing. This study conducted a survey in Taiwan to collect the data. The administrative group members of schools were invited to participate in this study. The sample included 510 participants, and the hypotheses were tested by using the path analysis and bootstrapping methods in the Mplus program to examine how ethical leadership influences knowledge sharing, through various means of identification. The results of this study show that ethical leadership has both a direct and indirect effect on knowledge sharing. There are two mediating paths in the ethical leadership-knowledge sharing relationship. Firstly, group identification mediates the relationship between ethical leadership and knowledge sharing. Secondly, ethical leadership has an influence on knowledge sharing by means of increased relational and organizational identification. This is a pioneering article that explores the psychological mechanism between ethical leadership and knowledge sharing, using the social identity approach. This study has shown that the social identity theory (SIT) is a useful and promising perspective for future research studies on ethical leadership-knowledge sharing.

Microbiota regulate social behaviour via stress response neurons in the brain.

Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut-brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain.

Nomograms to Predict Overall and Cancer-Specific Survival in Gastric Signet-Ring Cell Carcinoma.

BACKGROUND: The objective of our study was to develop and validate nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with signet-ring cell carcinoma (SRCC) of the stomach. METHODS: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 1781 patients were randomly allocated to a training set (n = 1335) and a validation set (n = 446). Univariate and multivariate analyses were used to determine the prognostic effect of variables. Nomograms were developed to estimate OS and CSS and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC), and decision curve analyses (DCA). DCA was utilized to compare the nomograms and the Tumor-Node-Metastasis (TNM) staging system. RESULTS: Age, race, tumor size, T, N, M stage, and use of surgery and/or radiotherapy were included in the nomograms. C-indexes for OS and CSS were 0.74 and 0.75 in the training set, respectively. C-indexes for OS and CSS were 0.76 and 0.76 in the validation set. Calibration plots and receiver operating characteristic (ROC) curves showed good predictive accuracy. According to the decision curve analyses (DCA), the new model was more useful than the TNM staging system. CONCLUSIONS: We developed nomograms to predict OS and CSS in patients with SRCC of the stomach. Nomograms may be a valuable clinical supplement of the conventional TNM staging system.

How COVID-19 Triggers Our Herding Behavior? Risk Perception, State Anxiety, and Trust.

People have felt afraid during the outbreak of coronavirus disease 2019 (COVID-19), because a virus is an invisible enemy. During the pandemic outbreak, society has become worried about the spread of infections and the shortage of protective equipment. This common fear among the public subsequently deepens each person's fear, increasing their belief in the content reported by the media and thus actively compelling these individuals to engage in the behavior of panic buying. In this study, we explored the effects of the public's risk perception, state anxiety, and trust in social media on the herding effect among individuals. The study was based on an online questionnaire survey and convenience sampling. The results showed that the public's risk perception increased their state anxiety and then deepened their willingness to wait in line for a purchase. In addition, the more people that trust the message delivered by the media, the more actively they will join the queue to buy goods. This study also found that anxiety had a greater impact on the public's willingness to wait for a purchase than trust in social media. Therefore, the top priority for the government should be to reduce the public's state anxiety and then reduce the herding effect.

[Ectopic seminal tract opening in enlarged prostatic utricle: A report of 22 cases].

OBJECTIVE: To explore the diagnosis, classification and treatment of ectopic seminal tract opening in enlarged prostatic utricle (EPU). METHODS: We retrospectively analyzed the clinical data on 22 cases of ectopic seminal tract opening in EPU confirmed by spermography, EPU open cannula angiography or intraoperative puncture of the vas deferens and treated by transurethral incision of EPU, cold-knife incision or electric incision of EPU, full drainage of the anteriorwal, and open or laparoscopic surgery from October 1985 to October 2017. RESULTS: Five of the patients were diagnosed with ectopic opening of the vas deferens and the other 17 with ectopic opening of the ejaculatory duct in EPU. During the 3－48 months of postoperative follow-up, symptoms disappeared in all the cases, semen quality was improved in those with infertility, and 2 of the infertile patients achieved pregnancy via ICSI. CONCLUSIONS: Ectopic seminal tract opening in EPU is rare clinically. Spermography is a reliable method for the diagnosis of the disease, and its treatment should be aimed at restoring the smooth flow of semen based on proper classification and typing of the disease.

How Spiritual Leadership Boosts Nurses' Work Engagement: The Mediating Roles of Calling and Psychological Capital.

Work engagement is an important topic in the field of nursing management. Meanwhile, spiritual leadership has been demonstrated to have a positive impact on healthcare workers. However, the relationship between spiritual leadership and work engagement is unclear. The main purpose of this study was to investigate the influence of spiritual leadership on work engagement through increased spiritual well-being and psychological capital. This study used a cross-sectional survey to collect data in Taiwan. The sample included 164 nurses, with empirical testing carried out by PROCESS Macro for SPSS. The results show that spiritual leadership has a positive influence on work engagement and that spiritual well-being (i.e., calling) and psychological capital mediate the effect of spiritual leadership on work engagement. According to the results of this study, nursing leaders must be aware of the role of spiritual leadership in promoting work engagement.

Do Work Engagement and Transformational Leadership Facilitate Knowledge Sharing? A Perspective of Conservation of Resources Theory.

Based on the perspective of conservation of resources (COR) theory, this study adopts a multilevel approach to examine the influences of employees' personal resources (i.e., work engagement and intrinsic motivation) and external resources (i.e., transformational leadership) on knowledge sharing. This study conducts a survey to explore the interrelationships among transformational leadership, work engagement, intrinsic motivation, and knowledge sharing. The sample includes 33 healthcare work groups consisting of 214 group members. The results show that an individual's personal and external resources are positive and benefit the promotion of knowledge sharing. As for personal resources, work engagement has a positive impact on knowledge sharing by increasing intrinsic motivation. Regarding external resources, transformational leadership acts as a facilitator for knowledge sharing. Specifically, the conditional indirect effects of work engagement on knowledge sharing through intrinsic motivation are more positive under high levels of transformational leadership, rather than low levels of transformational leadership. Based on the COR theory, this is the first study to argue that knowledge sharing could be considered as an active activity and that individuals could be eager to perform knowledge sharing when they possess significant personal and external resources. The results of this study provide new insights into knowledge sharing.

Shared Decision Making and Choice for Bariatric Surgery.

: The number of people undergoing bariatric surgery is increasing every year, and their expectations for surgery often differ greatly. The purpose of this study was to develop a patient-centered decision-making aid to help people define their weight loss goals and assist them in discussing their surgical treatment with surgeons. Before the operation, the patients were asked to read the shared decision-making text and conduct a self-assessment. After the operation, we evaluated the program using survey questionnaires. A total of 103 patients were formally included in this study. The results show that patients were very satisfied with the use of patient decision aids (PDAs), with a score of 4.3 points (±0.6), and the postoperative decision-making satisfaction was also very high, at 4.4 points (±0.5), while the postoperative regret score was low, at 1.6 points (±0.6). Their satisfaction with surgical decision making and decision regret were statistically significantly negatively correlated (r = -0.711, p < 0.001). The experience of using PDAs was statistically significantly negatively correlated with decision regret (r = -0.451, p < 0.001); the experience of PDA use was statistically positively correlated with decision satisfaction (r = 0.522, p < 0.001). Patient decision aids are a means of helping patients make informed choices before they seek to undergo bariatric surgery.

Downregulation of the circadian Period family genes is positively correlated with poor head and neck squamous cell carcinoma prognosis.

We investigated the relationship between head and neck squamous cell carcinoma (HNSCC) and the mRNA and protein expression levels of the circadian genes of the Period (Per) family, Per1, Per2 and Per3. Tissue sections of HNSCC and normal head and neck tissues from two patient cohorts from two different hospitals were collected to assess the mRNA and protein expressions of the three Per family genes using real-time quantitative PCR (RT-PCR) and immunohistochemistry (IHC). The clinicopathological features and disease prognosis for the latter cohort were analyzed through IHC and statistical methods. Protein positive expression levels of the three Per family genes in HNSCC tissues was found to be approximately two times lower than that in normal tissues (p < .01). Moreover, patients with locally advanced HNSCC showed significantly greater downregulation of Per1, Per2 and Per3 mRNA expression levels as compared to patients with early-stage cancer (p < .05). Immunohistochemical examination of HNSCC patient tissues revealed a positive correlation between the Per family protein expression and the clinical tumor staging (p < .05). In addition, the Per protein-positive expression group showed higher 3-year survival rates [overall survival (OS) and progression-free survival (PFS)] as assessed by Kaplan-Meier plots and statistical analysis (p < .05). Our findings confirm the positive correlation between Per family gene expression and survival outcomes and support their role as prognostic markers for HNSCC.

Metabolic reprogramming and its clinical application in thyroid cancer.

Warburg found that tumor cells exhibit high-level glycolysis, even under aerobic condition, which is known as the 'Warburg effect'. As systemic changes in the entire metabolic network are gradually revealed, it is recognized that metabolic reprogramming has gone far beyond the imagination of Warburg. Metabolic reprogramming involves an active change in cancer cells to adapt to their biological characteristics. Thyroid cancer is a common endocrine malignant tumor whose metabolic characteristics have been studied in recent years. Some drugs targeting tumor metabolism are under clinical trial. This article reviews the metabolic changes and mechanisms in thyroid cancer, aiming to find metabolic-related molecules that could be potential markers to predict prognosis and metabolic pathways, or could serve as therapeutic targets. Our review indicates that knowledge in metabolic alteration has potential contributions in the diagnosis, treatment and prognostic evaluation of thyroid cancer, but further studies are needed for verification as well.

The Effect of ASIC3 Knockout on Corticostriatal Circuit and Mouse Self-grooming Behavior.

Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. Herein, we investigate in depth whether and how ASIC3 is involved in the regulation of self-grooming behavior. First, we observed that Asic3 null mutant mice exhibited increased self-grooming in social interaction during juvenile stage. Similarly, they displayed increased self-grooming behavior in a novel cage in the absence of cagemate. To further understand the mechanism by which ASIC3 affects grooming behavior, we analyzed neurochemical, neuropathological and electrophysiological features in the dorsal striatum of Asic3 null mutant mice. Knockout of Asic3 increased dopamine (DA) activity and phospho-ERK immunoreactivities in the dorsal striatum. Furthermore, we detected a lower paired-pulse ratio (PPR) and impaired long-term potentiation (LTP) in corticostriatal circuits in Asic3 null mutant mice as compared with wild-type (WT) littermates. Moreover, knockout of Asic3 altered the medial spiny neurons in the striatum with defects in presynaptic function and decrease of dendritic spines. Lastly, genetic ablation of Asic3 specifically in parvalbumin-positive (PV+) cells resulted in the increase of self-grooming behavior in mice. These findings suggest knockout of Asic3 in the PV+ neurons alters grooming behavior by co-opting corticostriatal circuits.