Effect of compound dietary fiber of soybean hulls on the gel properties of myofibrillar protein and its mechanism in recombinant meat products.

Response surface methodology was used to determine the optimum ratio of rice husk dietary fiber, soybean hull dietary fiber, and inulin as 1.40, 1.42, and 3.24%. The effects of compound and single dietary fiber on water holding capacity, gel strength, secondary structure, rheological properties, chemical action force, and microstructure of myofibrillar proteins (MP) gel were investigated. The application of composite dietary fiber significantly (P < 0.05) improved the gel strength, water holding capacity and storage modulus (G') of MP gel. Fourier transform infrared spectrum analysis shows that the addition of compound dietary fiber can make the gel structure more stable. The effect of dietary fiber complex on the chemical action of MP gel was further studied, and it was found that hydrophobic interaction and disulfide bond could promote the formation of compound gel. By comparing the microstructure of the MP gel with and without dietary fiber, the results showed that the MP gel with compound dietary fiber had smaller pores and stronger structure. Therefore, the rice hull dietary fiber, the soybean hull dietary fiber and the inulin are compounded and added into the low-fat recombinant meat product in a proper proportion, so that the quality characteristics and the nutritional value of the low-fat recombinant meat product can be effectively improved, the rice hull dietary fiber has the potential of being used as a fat substitute, and a theoretical basis is provided for the development of the functional meat product.

[Latest Findings on the Interaction Mechanism Between Depressive Disorder and Intestinal Permeability].

The intestinal barrier, a complex structure consisting of multiple layers of defense barriers, blocks the transfer of intestinal and foreign bacteria and their metabolites into the internal environment of the human body. Intestinal permeability can be used to evaluate the integrity of the intestinal barrier. Increased intestinal permeability has been observed in patients with depressive disorder. Some studies have reported an interaction between depressive disorder and intestinal barrier. Herein, we reviewed reported findings on the mechanisms of how systematic low-grade inflammation, vagal nerve dysfunction, and hypothalamic-pituitary-adrenal axis dysfunction cause changes in intestinal permeability in patients with depressive disorder and the pathogenic mechanism of how bacterial translocation caused by damaged intestinal barrier leads to depressive disorder. In addition, the potential mechanisms of how antidepressants improve intestinal permeability and how probiotics improve depressive disorder have been discussed.

Glucose supplementation improves intestinal amino acid transport and muscle amino acid pool in pigs during chronic cold exposure.

Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons. The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models (cold adaptation) and Yorkshire pig models (non-cold adaptation). Furthermore, this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs. Min pigs (Exp. 1) and Yorkshire pigs (Exp. 2) were divided into a control group (17 °C, n = 6) and chronic cold exposure group (7 °C, n = 6), respectively. Twelve Yorkshire pigs (Exp. 3) were divided into a cold control group and cold glucose supplementation group (8 °C). The results showed that chronic cold exposure inhibited peptide transporter protein 1 (PepT1) and excitatory amino acid transporter 3 (EAAT3) expression in ileal mucosa and cationic amino acid transporter-1 (CAT-1) in the jejunal mucosa of Yorkshire pigs (P < 0.05). In contrast, CAT-1, PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs (P < 0.05). Branched amino acids (BCAA) in the muscle of Yorkshire pigs were consumed by chronic cold exposure, accompanied by increased muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (atrogin-1) expression (P < 0.05). More importantly, reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs (P < 0.05). However, glycine concentration in the muscle of Min pigs was raised (P < 0.05). In the absence of interaction between chronic cold exposure and glucose supplementation, glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs (P < 0.05). It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle (P < 0.05). Moreover, dystrophin concentration was improved by glucose supplementation (P < 0.05). In summary, chronic cold exposure inhibits amino acid absorption in the small intestine, depletes BCAA and promotes protein degradation in muscle. Glucose supplementation ameliorates the negative effects of chronic cold exposure on amino acid transport and the amino acid pool in muscle.

Transcriptome analysis reveals the effect of grafting on gossypol biosynthesis and gland formation in cotton.

BACKGROUND: Gossypol is a unique secondary metabolite and sesquiterpene in cotton, which is mainly synthesized in the root system of cotton and exhibits many biological activities. Previous research found that grafting affected the density of pigment glands and the gossypol content in cotton. RESULTS: This study performed a transcriptome analysis on cotton rootstocks and scions of four grafting methods. The gene expression of mutual grafting and self-grafting was compared to explore the potential genes involved in gossypol biosynthesis. A total of six differentially expressed enzymes were found in the main pathway of gossypol synthesis-sesquiterpene and triterpene biosynthesis (map00909): lupeol synthase (LUP1, EC:5.4.99.41), beta-amyrin synthase (LUP2, EC:5.4.99.39), squalene monooxygenase (SQLE, EC:1.14.14.17), squalene synthase (FDFT1, EC:2.5.1.21), (-)-germacrene D synthase (GERD, EC:4.2.3.75), ( +)-delta-cadinene synthase (CADS, EC:4.2.3.13). By comparing the results of the gossypol content and the density of the pigment gland, we speculated that these six enzymes might affect the biosynthesis of gossypol. It was verified by qRT-PCR analysis that grafting could influence gene expression of scion and stock. After suppressing the expression of the LUP1, FDFT1, and CAD genes by VIGS technology, the gossypol content in plants was significantly down-regulated. CONCLUSIONS: These results indicate the potential molecular mechanism of gossypol synthesis during the grafting process and provide a theoretical foundation for further research on gossypol biosynthesis.

STING agonism turns human T cells into interferon-producing cells but impedes their functionality.

The cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) axis is the predominant DNA sensing system in cells of the innate immune system. However, human T cells also express high levels of STING, while its role and physiological trigger remain largely unknown. Here, we show that the cGAS-STING pathway is indeed functional in human primary T cells. In the presence of a TCR-engaging signal, both cGAS and STING activation switches T cells into type I interferon-producing cells. However, T cell function is severely compromised following STING activation, as evidenced by increased cell death, decreased proliferation, and impaired metabolism. Interestingly, these different phenotypes bifurcate at the level of STING. While antiviral immunity and cell death require the transcription factor interferon regulatory factor 3 (IRF3), decreased proliferation is mediated by STING independently of IRF3. In summary, we demonstrate that human T cells possess a functional cGAS-STING signaling pathway that can contribute to antiviral immunity. However, regardless of its potential antiviral role, the activation of the cGAS-STING pathway negatively affects T cell function at multiple levels. Taken together, these results could help inform the future development of cGAS-STING-targeted immunotherapies.

Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC. DESIGN: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs. RESULTS: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells. CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.

Prevalence of depression and anxiety, and associated factors, among Chinese primary and high school students: A cross-sectional, epidemiological study.

INTRODUCTION: This study aimed to investigate the prevalence of depression and anxiety, and associated factors, among Chinese children and adolescents aged 8-18 years who attend primary or high school. METHODS: A total of 23 005 primary and high school students were recruited from February to December, 2019 for this cross-sectional study. The questionnaire included demographic information, questions assessing suicidality, resilience, depression (Center for Epidemiological Studies Depression Scale for Children), and anxiety (Screen for Child Anxiety Related Disorders). Binary logistic regression was used to analyze the independent correlates of depression and anxiety. RESULTS: Overall, 13.06% of participants experienced depressive symptoms, 22.34% experienced anxiety symptoms, 26.34% experienced transient suicidal ideation, 2.23% had serious suicidal ideation, and 1.46% had a history of suicide attempts. Anxiety (odds ratio [OR], 4.935; 95% confidence interval [CI][4.442-5.485]), suicidality (OR, 2.671; 95% CI[2.203-3.237]), skipping breakfast (OR, 1.920; 95% CI[1.348-2.736]), sleep duration (OR, 0.470; 95% CI[0.398-0.556]) and self-expectations (OR, 1.924; 95% CI[1.550-2.389]) were associated with depression (all p < .05). Depression (OR, 4.424; 95% CI[3.983-4.914]), female sex (OR, 1.903; 95% CI[1.759-2.060]), school-based traumatic experience(s) (OR, 1.905; 95% CI[1.747-2.077]), relationships with teachers (OR, 1.575; 95% CI[1.103-2.249]), and suicidality (OR, 1.467; 95% CI[1.218-1.766]) were associated with anxiety symptoms (all p < .05). DISCUSSION: Depression and anxiety are common among school-age children and adolescents in China. Childhood school- and family-based traumatic experience(s), female sex, and lifestyle factors (eating breakfast, sleep duration, exercising, and Internet use) are significantly associated with mental health among children and adolescents. Developing interventions targeting these factors to protect students from depression and anxiety are needed.

Dietary full-fat rice bran prevents the risk of heart ferroptosis and imbalance of energy metabolism induced by prolonged cold stimulation.

The threat to human health from cold stimulation is increasing due to the frequent occurrence of temperature extremes. It is a challenge for people to resist the negative effects of prolonged cold stimulation on the heart. In this study, we created prolonged cold stimulation pig models to investigate the cardiac energy metabolism and injury during prolonged cold stimulation, and the molecular mechanisms by which dietary supplementation with full-fat rice bran reduces cardiac injury. The results showed that lesions in the morphological structure of the heart were detected under prolonged cold stimulation. At the same time, dystrophin was downregulated under the effect of prolonged cold stimulation. Cardiac fatty acid transport and utilization were promoted, and oxidative stress was increased under prolonged cold stimulation. It also increased MDA content and decreased T-AOC level in the heart, while promoting the mRNA expression of Nrf2 and NQO1, as well as the protein content of Nrf2 and HO-1. Prolonged cold stimulation induced mitochondrial lesions, mitochondrial fusion, and mitophagy in the heart. Prolonged cold stimulation promoted the mRNA expression of PTGS2, TLR4, MyD88, NLRP3, and IL-1ß; and protein expression of PTGS2, NLRP3, and mature-IL-1ß. GCH1 and FtH inhibited by prolonged cold stimulation caused the activation of heart ferroptosis. In addition, dietary supplementation with full-fat rice bran improved oxidative stress in the heart and inhibited mitophagy, ferroptosis, and pyroptosis. In conclusion, prolonged cold stimulation heightens the risk of cardiac ferroptosis and imbalance of energy metabolism, whereas dietary supplementation with full-fat rice bran mitigates the adverse effects of prolonged cold stimulation on the heart.

Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis.

Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.

Perinatal exposure to high concentration glyphosate-based herbicides induces intestinal apoptosis by activating endoplasmic reticulum stress in offspring.

Glyphosate-based herbicides (GBHs), the most widely used pesticide worldwide, have been reported to impair organ function in humans and animals. However, research on the effect of maternal GBHs exposure on the intestinal health of offspring has received little attention. Based on the glyphosate limits defined by Codex Alimentarius Commission and European Food Safety Authority, this study established pregnant sow exposure models to investigate the influence of low (L-GBHs, 20 mg/kg) and high concentration GBHs (H-GBHs, 100 mg/kg) on the intestinal health of offspring and proposed the protective mechanism mediated by betaine. The results showed that the intestinal morphology and barrier function of suckling piglets were damaged in the H-GBHs group. H-GBHs increased the activity of glutathione peroxidase (GPX) and levels of methane dicarboxylic aldehyde (MDA), hydrogen peroxide (H2O2) and inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10)) in suckling piglets and activated Nrf2-mediated antioxidant signaling pathway. Subsequently, we found that exposure to H-GBHs triggered endoplasmic reticulum stress (ERS) and further induced apoptosis by upregulating the expression of Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and Caspase12. Moreover, H-GBHs exposure perturbed mitochondrial membrane fusion and electron transport in mitochondrial respiratory chains by increasing the mRNA expression of mitofusin-2 (MFN2) and succinate dehydrogenase subunit A (SDHA), causing mitochondrial dysfunction. Dietary supplementation with betaine provided modest protection against GBHs-induced intestinal damage in suckling piglets. These findings reveal the mechanism of GBHs-induced intestinal damage in offspring, improving our understanding of the risk of GBHs exposure in pregnant women and suggesting the potential protective effects of betaine against GBHs poisoning.

Biomarkers of intestinal permeability and blood-brain barrier permeability in adolescents with major depressive disorder.

BACKGROUND: The etiology in major depressive disorder (MDD) has not been fully understood. Accumulating evidence suggests an association between altered intestinal and blood-brain barrier (BBB) permeability and psychiatric disorders, while its changes in adolescent MDD populations have been received less attention. In this study, our aim was to explore the differences in plasma levels of intestinal and blood-brain barrier permeability markers in adolescents with MDD compared with healthy controls (HCs). METHODS: We enrolled MDD (n = 50), and HCs (n = 40) with the age of 13-18 years old. The plasma level of zonulin, I-FABP, LPS, and claudin-5 were quantified. The Hamilton Depression Scale 17 items (HAMD-17) and Hamilton Anxiety Scale 14 items (HAMA-14) were used for symptom assessments. RESULTS: The plasma levels of zonulin, I-FABP, LPS, and claudin-5 in the MDD group were significantly higher than those in the HCs. Plasma I-FABP levels in MDD with moderate to severe anxiety were significantly higher than those in MDD without moderate to severe anxiety and HCs. In addition, these four biomarkers (alone or combined) can be used as diagnostic markers for MDD in adolescents. LIMITATIONS: The key limitation of this study is the blood measurements at a single time point with a relatively small sample size. CONCLUSIONS: These findings advance our understanding of the pathophysiology of intestinal barrier injury, bacterial translocation, and blood-brain barrier injury involved in adolescents with MDD.

Cavity-enabled enhancement of ultrafast intramolecular vibrational redistribution over pseudorotation.

Vibrational strong coupling (VSC) between molecular vibrations and microcavity photons yields a few polaritons (light-matter modes) and many dark modes (with negligible photonic character). Although VSC is reported to alter thermally activated chemical reactions, its mechanisms remain opaque. To elucidate this problem, we followed ultrafast dynamics of a simple unimolecular vibrational energy exchange in iron pentacarbonyl [Fe(CO)₅] under VSC, which showed two competing channels: pseudorotation and intramolecular vibrational-energy redistribution (IVR). We found that under polariton excitation, energy exchange was overall accelerated, with IVR becoming faster and pseudorotation being slowed down. However, dark-mode excitation revealed unchanged dynamics compared with those outside of the cavity, with pseudorotation dominating. Thus, despite controversies around thermally activated VSC modified chemistry, our work shows that VSC can indeed alter chemistry through a nonequilibrium preparation of polaritons.

Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice.

Although neuronal Toll-like receptors (TLRs) (e.g., TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive. Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone-ether-water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA (mRNA) expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, TNF-α, and IFN-γ were inhibited in TLR2-/- mice, while CXCL2, IL-31, and IL-6 were inhibited in TLR7-/- mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, and TNF-α were inhibited in TLR2-/- mice, while CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, and TNF-α were inhibited in TLR7-/- mice. Incubation with Staphylococcus aureus (S. aureus) peptidoglycan (PGN-SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142-3p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C-X-C Motif Chemokine Receptor 1/2 and high mobility group box protein 1 dose-dependently attenuated acute and chronic itch in mice. Together, these results indicate that keratinocyte TLR2 and TLR7 signaling pathways are distinctly involved in the pathogenesis of chronic itch.

Mapping current research and identifying hotspots of ferroptosis in cardiovascular diseases.

Objective: Ferroptosis is a unique cell death depended on iron metabolism disorder which is different from previous apoptosis-regulated cell death. Early studies have proposed that ferroptosis is closely associated with multiple cardiovascular diseases (CVDs). However, the relationship of ferroptosis and CVDs has not been summarized by using bibliometric analysis. We intended to illustrate the development of ferroptosis in CVDs over the past years and provide relevant valuable information. Materials and methods: The authoritative database of Web of Science Core Collection was collected for retrieving ferroptosis studies in CVDs. In this work, statistical and visualization analysis were conducted using VOSviewer and Citespace. Results: A total of 263 studies were included in the final study. From the perspective of the overall literature, the study maintains an increased trend year by year and most manuscripts belonged to original article. China was the most productive country with the utmost scientific research output, as well as the institutions and authors, followed by Germany and the United States of America (USA). Jun Peng from China contributes to the most publications. Collaborative efforts between institutes and authors were limited and there was little widespread cooperation. In addition, burst keywords analysis discovered that ischemia-reperfusion (I/R) injury, heart failure (HF), and atherosclerosis were the top three research directions of ferroptosis in CVDs. The burst investigation and timeline views also indicated that endothelial injury and gut microbiota may also serve as new research topics in the future. Conclusion: This study provided comprehensive and specific information about the most influential articles on ferroptosis in CVDs. The relationship between ferroptosis and CVDs had attracted the scholar's concerns especially in China. Cooperations and communications between countries and institutions should be emphasized and future directions can be concentrated on endothelial disorder and gut microbiota.

Workplace factors can predict the stress levels of healthcare workers during the COVID-19 pandemic: First interim results of a multicenter follow-up study.

Background: Research is lacking on the long-term influence of workplace factors on the mental health of health care workers during the COVID-19 pandemic. Methods: We distributed two online surveys to health care workers between May and October 2020 (T1) and between February and April 2021 (T2). Perceived stress, coronavirus-related risks, and workplace factors were measured via self-report questionnaires at both time points. We conducted hierarchical linear regression to investigate the predictive factors for high stress. Results: A total of 2,110 participants from seven countries and 4,240 participants from nine countries were enrolled at T1 and T2, respectively. Among them, 612 participated in both surveys. We called this cohort T1 + T2. High stress was reported in 53.8 and 61.6% of participants at T1 and T2, respectively. In cohort T1 + T2, compared with the baseline, the level of stress rose significantly (6.0 ± 2.9 vs. 6.4 ± 3.1), as did health/safety in the workplace (3.9 ± 0.8 vs. 4.2 ± 0.7). Unfortunately, we did not detect any significant difference concerning support in the workplace. Among all factors at baseline, being older than 35 [ß (95% CI) = -0.92 (-1.45, -0.40)], support [-0.80 (-1.29, -0.32)], and health/safety in the workplace [-0.33 (-0.65, -0.01)] were independent protective factors, while a positive history of mental disorders [0.81 (0.26, 1.37)] and rejection in private life [0.86 (0.48, 1.25)] were risk factors for high stress at T2. Conclusion: To relieve the high stress of health care workers, organizational-level approaches should be implemented, especially measures designed to enhance support, health/safety in the workplace, and to reduce the rejection of the public.

Perinatal exposure to glyphosate-based herbicides impairs progeny health and placental angiogenesis by disturbing mitochondrial function.

Glyphosate-based herbicides (GBHs) are the most widely used pesticide worldwide and can provoke placental injury. However, whether and how GBHs damage angiogenesis in the placenta is not yet known. This work evaluated the safety of glyphosate on pregnant sows based on the limit level by governments and investigated the effects and mechanism of Low-GBHs (20 mg/kg) and High-GBHs (100 mg/kg) exposure on placental angiogenesis. Results showed that gestational exposure to GBHs decreased placental vessel density and cell multiplication by interfering with the expression of VEGFA, PLGF, VEGFr2 and Hand2 (indicators of angiogenesis), which may be in relation to oxidative stress-induced disorders of mitochondrial fission and fusion as well as the impaired function of the mitochondrial respiratory chain. Additionally, GBHs destroyed barrier function and nutrient transport in the placenta, and was accompanied by jejunum oxidative stress in newborn piglets. However, GBHs exposure had no significant differences on sow reproductive performance. As a natural antioxidant, betaine treatment protected placenta and newborn piglets against GBHs-induced damage. In conclusion, GBHs impaired placental angiogenesis and function and further damaged the health of postnatal progeny, these effects may be linked to mitochondrial dysfunction. Betaine treatment following glyphosate exposure provided modest relief.

Motivation, self-efficacy, perception, curiosity, and barriers toward medical research among undergraduates in China.

Medical research is important to scientific progress and medical education. Institutions worldwide have sought to increase student involvement in research such as clinician-scientists training programs, while little is known about how medical undergraduates perceive research. A cross-sectional study was conducted in Chongqing Medical University, Chongqing, China, with first-fourth year undergraduates. An online, anonymous, and self-rating 5-point Likert questionnaire was conducted to investigate medical undergraduates' demographic characteristics and assess motivation, self-efficacy, perception, curiosity, and barriers regarding medical research. Content validity was checked with experts and face validity was checked for clarity and understanding of the questionnaire. The Cronbach's alpha coefficient of the questions ranged from 0.813 to 0.879. A total of 3273 medical undergraduates were surveyed, and 86.62% (2835) participants (male 962, female 1873) were identified as effective. Males scored higher than females on self-efficacy (p < 0.001), perception (p = 0.017), and curiosity (p < 0.001), and lower on barriers (p < 0.001). The second year students are at the peak of their perception (p = 0.006) and lowest barrier scores (p = 0.003). Students with scientific research experience scored higher in motivation (p = 0.002), self-efficacy (p < 0.001), perception (p < 0.001), and curiosity (p < 0.001). Lack of proper mentoring opportunity (86.2%) and knowledge (84.5%) were the main barriers in conducting research. Even though they have a positive perspective, only a few undergraduates enrolled in research. Medical universities should encourage faculties to supervise and guide undergraduates' projects, and provide feasible solutions for students to learn scientific knowledge and skills. It is vital to build a research-oriented environment and academic atmosphere.

Activation of Inflammatory Networks in the Lungs Caused by Chronic Cold Stress Is Moderately Attenuated by Glucose Supplementation.

Mammals that live in cold climates endure months of exposure to low temperature in the winter. The incidence of respiratory diseases has increased. The goal of this study was to investigate the effects of chronic cold stress on lung inflammatory networks, apoptosis, and mitochondrial function via Yorkshire pig models, as well as the ameliorative effect of glucose as energy supplements. Here, two trials were conducted (chronic cold stress and glucose supplementation). The results showed that chronic cold stress induced obvious inflammatory cell infiltration in the lungs and damaged the lung tissue structure. Compared with the Y-Con group, the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), high mobility group box 1 (HMGB1), nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3), IL-1ß, IL-2, IL-6, and IFN-γ in the lungs of the Y-CS group was enhanced by chronic cold stress (p < 0.05). Moreover, chronic cold stress promoted the expression of the Bax and Mfn2 in lungs of Y-CS group (p < 0.05). Interestingly, dietary glucose supplementation significantly reduced inflammatory cell infiltration in the lungs. Moreover, glucose supplementation inhibited the expression of TLR4, MyD88, HMGB1, NLRP3, IL-1ß, IL-2, IL-6, IFN-γ, and Bax during chronic cold stress. In conclusion, chronic cold stress promoted inflammatory networks, apoptosis, and mitochondrial fusion in the lungs. Dietary glucose supplementation inhibited the inflammatory network during chronic cold stress.

[Mechanism of Panlongqi Tablets intervening in vertebral artery type of cervical spondylosis in rats through PI3K/AKT signaling pathway based on network pharmacology and experimental verification].

This study aimed to further explore the relevant mechanism of action by network pharmacology integrated with animal experimental verification based on previous proven effective treatment of vertebral artery type of cervical spondylosis(CSA) by Panlongqi Tablets. Bionetwork analysis was performed to establish drug-disease interaction network, and it was found that the key candidate targets of Panlongqi Tablets were enriched in multiple signaling pathways related to CSA pathological links, among which phosphatidylinositol 3-kinase(PI3 K)/serine-threonine kinase(AKT/PKB) signaling pathway was the most significant. Further, mixed modeling method was used to build the CSA rat model, and the rats were divided into normal, model, Panlongqi Tablets low-, medium-and high-dose(0.16, 0.32, 0.64 g·kg~(-1)) and Jingfukang Granules(positive drug, 1.35 g·kg~(-1)) groups. After successful modeling, the rats were administered for 8 consecutive weeks. Pathological changes of rat cervical muscle tissues were detected by hematoxylin-eosin(HE) staining, and the content of interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), vascular endothelial cell growth factor(VEGF) and chemokine(C-C motif) ligand 2(CCL2) in rat serum and/or cervical tissues was determined by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to detect the protein expression levels of chemokine(C-C motif) receptor 2(CCR2), PI3 K, AKT, phosphorylated AKT(p-AKT), I-kappa-B-kinase beta(IKK-beta/IKKß), nuclear factor kappa B(NF-κB P65) and phosphorylated nuclear factor kappa B(NF-κB p-P65) in rat cervical tissues, and positive expression of p-NF-κB P65 in rat cervical muscle tissues was detected by immunofluorescence. The results showed that Panlongqi Tablets at different doses improved the degree of muscle fibrosis and inflammation in cervical muscle tissues of CSA rats, and reduced the content of inflammatory factors IL-1ß, TNF-α, VEGF, CCL2 and CCR2 in serum and/or cervical tissues. The protein expression levels of PI3 K, p-AKT, IKKß and p-NF-κB P65 as well as the nuclear entry of p-NF-κB P65 in cervical tissues were down-regulated. These findings suggest that Panlongqi Tablets can significantly inhibit the inflammatory response of CSA rats, and the mechanism of action may be related to the down-regulation of the activation of PI3 K/AKT signaling pathway.