Inferior social hierarchy is vulnerable to anxiety-like behavior in chronic pain mice: Potential role of gut microbiota and metabolites.

Social dominance is a universal phenomenon among grouped animals that profoundly affects survival, health, and reproductive success by determining access to resources, and exerting a powerful influence on subsequent behavior. However, the understanding of pain and anxiety comorbidities in dominant or subordinate animals suffering from chronic pain is not well-defined. Here, we provide evidence that subordinate mice are more susceptible to pain-induced anxiety compared to dominant mice. We propose that the gut microbiota may play a mediating role in this mechanism. Our findings demonstrate that transplantation of fecal microbiota from subordinate mice with chronic inflammatory pain, but not dominant mice, into antibiotics-treated pseudo-germ-free mice significantly amplifies anxiety-like phenotypes, highlighting the critical involvement of gut microbiota in this behavioral response. Using chronic inflammatory pain model, we carried out 16S rRNA sequencing and untargeted metabolomic analyses to explore the relationship between microbiota and metabolites in a stable social hierarchy of mice. Interestingly, anxiety-like behaviors were directly associated with some microbial genera and metabolites, especially bile acid metabolism. Overall, we have demonstrated a close relationship between social status and anxiety susceptibility, highlighting the contributions of gut microbiota and the associated metabolites in the high-anxiety state of subordinate mice with chronic inflammatory pain.

Exploring the interplay of depression, sleep quality, and hearing in tinnitus-related handicap: insights from polysomnography and pure-tone audiometry.

BACKGROUND: Tinnitus affects approximately 740 million adults globally, involving hearing, emotion, and sleep systems. However, studies using polysomnography and pure-tone audiometry (PTA) are limited. We aimed to assess the correlation between tinnitus and hearing, sleep quality, characteristics, and depression using polysomnography and PTA. METHODS: In this cross-sectional study, we divided participants into tinnitus and non-tinnitus groups. We included 100 outpatients (65 with tinnitus, 35 without) from a medical center in Taiwan, who underwent polysomnography and completed rating scales including the Patient Health Questionnaire-9 (PHQ-9), Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM). We analyzed correlations, conducted group comparisons, assessed factors related to THI-CM scores, constructed ROC curves to predict depression in the tinnitus group, and performed multinomial and logistic regression to explore associations. RESULTS: Descriptive statistics identified a cohort with mean age 53.9 ± 12.80 years, 63% exhibited PHQ-9 scores ≥ 10, and 66% had Apnea-Hypopnea Index (AHI) > 5. The ratio of rapid eye movement and deep sleep to stage 1 + 2 sleep was relatively low and non-significant. Likewise, leg movements was higher in the tinnitus group but not statistically significant. In the tinnitus group, 63.08% had depression, and 81.54% had AHI > 5. Univariate logistic regression linked tinnitus to AHI > 5 (Odds ratio (OR) 2.67, p = 0.026) and male sex (OR 2.49, p = 0.034). A moderate positive correlation was found between the THI-CM score and PHQ-9 score (rs = 0.50, p < 0.001). Further adjustment for obstructive sleep apnea showed associations between PHQ-9 (total score) or depression and THI-CM Grade 3-5 (OR = 1.28; OR = 8.68). Single- and multifactor regression analyses highlighted significant associations of PSQI scores > 13 (OR 7.06, p = 0.018) and THI-CM scores > 47 (OR 7.43, p = 0.002) with depression. CONCLUSIONS: Our study recruited tinnitus participants with slight or mild hearing loss and mild tinnitus handicap. Depression was identified as a predominant factor in tinnitus-related handicap. The mild tinnitus handicap in tinnitus participants may explain the lack of significant differences in depression, sleep quality, and polysomnographic sleep characteristics between tinnitus and non-tinnitus groups. Further extensive and prospective studies are needed to elucidate the complex links among depression, sleep, and tinnitus.

A Bibliometric Analysis of Research on Perioperative Neurocognitive Disorder: A Systematic Review.

BACKGROUND: Perioperative neurocognitive disorder (PND) is a general term for cognitive impairment that negatively affects multiple domains, including memory, concentration, and physical functioning. Numerous articles have been published on PND; however, only a few quantitative analyses covering this disorder have been published. METHODS AND MATERIALS: To clarify PND's developmental history, research foci, and future directions, we conducted a bibliometric analysis using the bibliometric tools VOSviewer and CiteSpace. A total of 4704 publications were obtained from the Web of Science database, including annual publications and trends, keywords, institutions, journals, and collaboration between countries/regions and authors. RESULTS: In addition, we found that neuroinflammation is a hotspot in recent studies. CONCLUSIONS: This bibliometric analysis provides a broad overview of studies in the field of PND.

Investigation of Neuron Latency Modulated by Bilateral Inferior Collicular Interactions Using Whole-Cell Patch Clamp Recording in Brain Slices.

As the final level of the binaural integration center in the subcortical nucleus, the inferior colliculus (IC) plays an essential role in receiving binaural information input. Previous studies have focused on how interactions between the bilateral IC affect the firing rate of IC neurons. However, little is known concerning how the interactions within the bilateral IC affect neuron latency. In this study, we explored the synaptic mechanism of the effect of bilateral IC interactions on the latency of IC neurons. We used whole-cell patch clamp recordings to assess synaptic responses in isolated brain slices of Kunming mice. The results demonstrated that the excitation-inhibition projection was the main projection between the bilateral IC. Also, the bilateral IC interactions could change the reaction latency of most neurons to different degrees. The variation in latency was related to the type of synaptic input and the relative intensity of the excitation and inhibition. Furthermore, the latency variation also was caused by the duration change of the first subthreshold depolarization firing response of the neurons. The distribution characteristics of the different types of synaptic input also differed. Excitatory-inhibitory neurons were widely distributed in the IC dorsal and central nuclei, while excitatory neurons were relatively concentrated in these two nuclei. Inhibitory neurons did not exhibit any apparent distribution trend due to the small number of assessed neurons. These results provided an experimental reference to reveal the modulatory functions of bilateral IC projections.

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production.

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions.

Blood Cells and Venous Thromboembolism Risk: A Two-Sample Mendelian Randomization Study.

Background: Previous studies have shown that various cell indices are associated with a higher risk of venous thromboembolism (VTE), however, whether these findings reflect a causal relationship remains unclear. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to assess the causal association of various blood cells with VTE risk. Study Design and Methods: Summary statistics of genetic instruments representing cell indices for erythrocytes, leukocytes, and platelets were extracted from genome-wide association studies of European ancestry, by Two-Sample Mendelian Randomization. Inverse variance weighting (IVW) was used as the primary analytical method for MR. Sensitivity analyses were performed to detect horizontal pleiotropy and heterogeneity. Results: Genetically predicted red blood cell distribution width, mean reticulocyte volume, and mean red blood cell volume were positively associated with VTE, with odds ratio (OR) of 1.002 [CI 1.000-1.003, P = 0.022), 1.003 (CI 1.001-1.004, P = 0.001, respectively)] and 1.001 (CI 1.000-1.002, P = 0.005). Genetically predicted monocyte count was negatively correlated with VTE, with OR = 0.998 (CI 0.996-0.999, P = 0.041). Conclusion: Genetically liability to high- red blood cell distribution width, mean reticulocyte volume, mean red blood cell volume, and low monocyte count are associated with the higher risk of VTE. Targeting these factors might be a potential strategy to prevent VTE.

The impact of the COVID-19 pandemic on the care of pulmonary hypertension patients outside the Hubei province in China.

The Coronavirus disease 2019 (COVID-19) pandemic has severely affected the lives of people around the world, especially some patients with severe chronic diseases. This study aims to evaluate the impact of the COVID-19 outbreak from December 2019 to April 2020 on treating patients with PH. A questionnaire regarding the medical condition of PH patients during the COVID-19 pandemic was designed by PH diagnostic experts in The First Affiliated Hospital of Guangzhou Medical University, China Respiratory Center. One hundred and fifty-six subjects with PH from non-Hubei regions in China were invited to participate in this survey online. 63.4% (n = 99) of them had difficulty seeing a doctor, and the main reason was fear of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hospital. Medical treatment was affected in 25% (n = 39) of patients, and who lived in rural areas, and discontinued medical therapy for financial reasons were at a higher risk of medical treatment being affected. Patients who reduced nutrition, and had difficulty seeing a doctor were more likely to get deteriorated. During the epidemic, the hospitalization rate of PH patients was 33.33%. Patients with aggravated PH had a high risk of hospitalization (odds ratio [OR] = 2.844), while patients who visited a doctor during the epidemic reduced the risk of hospitalization (OR = 0.33). In conclusion, during the COVID-19 pandemic, PH patients had difficulty seeing a doctor, and their medical treatment was affected, even worsened, and increased the risk of hospitalization.

[Detection rate of thyroid nodules in routine health check-up and its influencing factors: a 10-year survey of 309 576 cases].

OBJECTIVE: To analyze the detection rate of thyroid nodules and its influencing factors among individuals undergoing routine health check-up in Guangdong Province. METHODS: We analyzed the results of thyroid ultrasonography of 309 576 individuals receiving routine health check-up in a general hospital in Guangdong Province over the past 10 years. The data were compared between the individuals with and without thyroid nodules using two independent samples t test, MannWhitney U test and Chi-square test. Binary logistic regression was used to analyze the relationship between different factors and thyroid nodules, and the odds ratio (OR) and 95% confidence interval (95% CI) were calculated. RESULTS: Based on the structured and standardized data, the total detection rate of thyroid nodules was 9.68% among the individuals, 7.71% in male and 13.51% in female subjects, showing a significant gender difference (χ2=2677.08, P < 0.001). In the overall population, the detection rates of thyroid nodules gradually increased with age, but in each age group, the detection rate remained significantly higher in female subjects than in male subjects (P < 0.001). The subjects with thyroid nodules showed a significant higher percentage of male gender, an older age, a greater BMI, and significantly higher SBP, DBP, FBG, TC, LDL-C, HDL-C, TG as well as higher detection rates of fatty liver, hyperlipidemia, hyperglycemia, and metabolic syndrome than those without thyroid nodules (all P < 0.001). Binary logistic regression analysis showed that thyroid nodules were significantly associated with gender (OR=0.455, 95%CI: 0.443-0.468), age (45-59 years: OR=1.660, 95%CI: 1.613-1.710; ≥ 60 years: OR=3.329, 95%CI: 3.202- 3.462), BMI (underweight: OR=0.808, 95%CI: 0.755-0.864; overweight: OR=1.074, 95%CI: 1.038-1.112; obesity: OR=1.281, 95%CI: 1.221-1.343), hyperlipidemia (OR=1.053, 95%CI:1.022-1.085), high blood glucose (OR=1.177, 95%CI: 1.105-1.252), and metabolic syndrome (OR=1.111, 95%CI: 1.071-1.152). CONCLUSIONS: The detection rate of thyroid nodule is much higher in female than in male individuals in Guangdong Province and is significantly associated with gender, age, BMI and metabolic related diseases. Male gender and underweight might be protective factors for thyroid nodules, while an advanced age, overweight/obesity, hyperlipidemia, high blood glucose and metabolic syndrome are associated with an increased risk of thyroid nodules. Thyroid ultrasound examination is recommended in routine health check-up for early detection and treatment of thyroid diseases.

Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk.

Many studies have shown that crosstalk exists between apoptosis and autophagy, despite differences in mechanisms between these processes. Paeonol, a major phenolic compound isolated from Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), is widely used in traditional Chinese medicine as an antipyretic, analgesic and anti-inflammatory agent. In this study, we investigated the detailed molecular mechanisms of the crosstalk between apoptosis and autophagy underlying the cardioprotective effects of paeonol in rats subjected to myocardial ischemia/reperfusion (I/R) injury. Myocardial I/R injury was induced by occlusion of the left anterior descending coronary artery (LAD) for 1 h followed by 3 h of reperfusion. Paeonol was intravenously administered 15 min before LAD ligation. We found that paeonol significantly improved cardiac function after myocardial I/R injury and significantly decreased myocardial I/R-induced arrhythmia and mortality. Paeonol also significantly decreased myocardial infarction and plasma LDH activity and Troponin-I levels in carotid blood after I/R. Compared with vehicle treatment, paeonol significantly upregulated Bcl-2 protein expression and significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 and PARP protein expression in the I/R injured myocardium. Myocardial I/R-induced autophagy, including the increase of Beclin-1, p62, LC3-I, and LC3-II protein expression in the myocardium was significantly reversed by paeonol treatment. Paeonol also significantly increased the Bcl-2/Bax and Bcl-2/Beclin-1 ratios in the myocardium after I/R injury. The cardioprotective role of paeonol during I/R injury may be due to its mediation of crosstalk between apoptotic and autophagic signaling pathways, which inhibits apoptosis and autophagic cell death.

In Situ Monitoring of Chemical Reactions at a Solid-Water Interface by Femtosecond Acoustics.

Chemical reactions at a solid-liquid interface are of fundamental importance. Interfacial chemical reactions occur not only at the very interface but also in the subsurface area, while existing monitoring techniques either provide limited spatial resolution or are applicable only for the outmost atomic layer. Here, with the aid of the time-domain analysis with femtosecond acoustics, we demonstrate a subatomic-level-resolution technique to longitudinally monitor chemical reactions at solid-water interfaces, capable of in situ monitoring even the subsurface area under atmospheric conditions. Our work was proven by monitoring the already-known anode oxidation process occurring during photoelectrochemical water splitting. Furthermore, whenever the oxide layer thickness equals an integer  number of the effective atomic layer thickness, the measured acoustic echo will show higher signal-to-noise ratios with reduced speckle noise, indicating the quantum-like behavior of this coherent-phonon-based technique.

RNA interference against TRIM29 inhibits migration and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Tripartite motif-containing 29 (TRIM29) is a member of TRIM proteins family, which plays diverse physiological and pathological roles in humans. Recent studies found that TRIM29 expressed highly in CRC and promoted cell growth in vitro. However, its function in the metastasis of CRC has not been studied. In the present study, we confirmed the previous report that TRIM29 was upregulated in CRC tissues and high levels of TRIM29 expression were associated with poor overall survival of patients. Moreover, TRIM29 knockdown significantly reduced cancer cell proliferation via notably inducing cell cycle arrest and cell apoptosis. Silencing of TRIM29 significantly inhibited the migration and invasion ability of CRC cells. The protein levels of apoptosis­, migration­ and invasion­related proteins were also changed after TRIM29 knockdown. Furthermore, phosphorylation levels of JAK2 and STAT3 were clearly reduced in TRIM29 knockdown cells, indicating a possible mechanism underlying its effects on colorectal carcinogenesis. Collectively, TRIM29 may exert oncogenic effects in CRC cells via regulating JAK2/STAT3 signaling.

Overexpression and biological function of IQGAP3 in human pancreatic cancer.

IQGAP3 (IQ motif containing GTPase activating protein3) belongs to IQGAP family. Recent studies have investigated that IQGAP3 was overexpressed in several tumor tissues. This study was designed to explore the expression and role of IQGAP3 in pancreatic cancer, a highly lethal disease. IQGAP3 mRNA expression was significantly increased in pancreatic cancer tissues, compared with non-cancerous tissues. Moreover, its expression was strongly associated with tumor size, differentiation, lymph node metastasis and patients' overall survival. Gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) dataset showed that cell apoptosis, metastasis and Cdc42 pathways were strongly associated with IQGAP3 expression in pancreatic cancer patients. Knocking down of IQGAP3 in two pancreatic cancer cell lines with high level of IQGAP3 (BXPC-3 and SW1990) significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, silencing of IQGAP3 also affected the expression of cell apoptosis-, metastasis- and Cdc42 pathway-related proteins. Cdc42 knockdown had similar inhibitory effects on the cellular behavior of BXPC-3 cells. In conclusion, IQGAP3 may act as an oncogene in pancreatic cancer through regulating Cdc42 expression. Our data suggest IQGAP3 might be a novel diagnostic marker and therapeutic target for this cancer.