Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

The amino acid pattern and dynamics of body protein, body fat deposition in male and female broilers under different temperatures.

The present study was conducted 1) to investigate the effects of gender and temperature on growth performance in broiler chickens and 2) to establish body protein and fat deposition curves and amino acid patterns for broilers of both genders at different ambient temperatures. A total of 432 1-day-old (d) Arbor Acres chickens with a male/female ratio of 1:1 were randomly divided into the following 4 treatment groups: the male thermoneutral group, the female thermoneutral group, the male heat stress group, and the female heat stress group. The chickens in the thermoneutral groups were kept at a comfortable temperature from 1 to 42 d, while chickens in the heat stress groups were kept at a comfortable temperature from 1 to 28 d and at a high ambient temperature from d 29 to 42. The body composition retention data were obtained by comparative slaughter method, and the models were constructed by the Gompertz model. The results revealed significant variation in body protein content (BPC) and body fat deposition efficiency (BFE) between both genders and the 2 temperatures. Moreover, a noteworthy interaction between gender and temperature was observed in terms of the BPC and protein deposition efficiency (BPE). The following equations for body protein and body fat deposition in the thermoneutral groups were obtained: Body protein weight of male broilers: [Formula: see text] ; Body protein weight of female broilers: [Formula: see text] ; Body fat weight of male broilers: [Formula: see text] ; Body fat weight of female broilers: [Formula: see text] . Where t means age (d). The following equations for body protein and body fat deposition in the heat stress groups were obtained: Body protein weight of male broilers: [Formula: see text] ; Body protein weight of female broilers: [Formula: see text] ; Body fat weight of male broilers: [Formula: see text] ; Body fat weight of female broilers: [Formula: see text] . Where t means age (d). In addition, no significant difference in amino acid content was found between different genders and temperatures. The amino acid pattern could be divided into 2 stages: 0 to 14 d and 15 to 42 d. Our equations and patterns enable a deeper understanding of the nutritional requirements in broiler chickens under various temperature conditions. This enables researchers to develop more accurate feeding programs to fulfill the growth and health requirements of broiler chickens.

SGLT2 inhibitor improves kidney function and morphology by regulating renal metabolism in mice with diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a secondary complication of diabetes mellitus and a leading cause of chronic kidney disease. AIM: To investigate the impact of long-term canagliflozin treatment on DKD and elucidate its underlying mechanism. METHODS: DKD model was established using high-fat diet and streptozotocin in male C57BL/6J mice (n = 30). Mice were divided into five groups and treated for 12 weeks. 1) normal control mice, 2) DKD model, 3) mice treated low-dose of canagliflozin, 4) high-dose of canagliflozin and 5) ß-hydroxybutyrate. Mice kidney morphology and function were evaluated, and a metabolomics analysis was performed. RESULTS: Canagliflozin treatment reduced blood creatinine and urine nitrogen levels and improved systemic insulin sensitivity and glucose tolerance in diabetic mice. Additionally, a decrease in histological lesions including collagen and lipid deposition in the kidneys was observed. ß-hydroxybutyrate treatment did not yield a comparable outcome. The metabolomics analysis revealed that canagliflozin induced alterations in amino acid metabolism profiles in the renal tissue of diabetic mice. CONCLUSION: Canagliflozin protects the kidneys of diabetic mice by increasing the levels of essential amino acids, promoting mitochondrial homeostasis, mitigating oxidative stress, and stimulating the amino acid-dependent tricarboxylic acid cycle.

Levodopa improved different motor symptoms in patients with Parkinson's disease by reducing the functional connectivity of specific thalamic subregions.

BACKGROUND: The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. METHODS: Resting-state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. RESULTS: The PD on state exhibited decreased FC between the right pre-motor thalamus and the right postcentral gyrus, as well as the right lateral pre-frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre-frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. CONCLUSIONS: This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post-central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients.

Maternal inulin alleviates high-fat diet-induced lipid disorder in offspring by epigenetically modulating hypothalamus feeding circuit-related genes.

Increasing evidence supports the existence of fetal-originated adult diseases. Recent research indicates that the intrauterine environment affects the fetal hypothalamic energy intake center. Inulin is a probiotic that can moderate metabolic disorders, but whether maternal inulin intervention confers long-term metabolic benefits to lipid metabolism in offspring in their adult lives and the mechanism involved are unknown. Here, we used a maternal overnutrition model that was induced by excess energy intake before and during pregnancy and lactation and maternal inulin intervention was performed during pregnancy and lactation. The hypothalamic genome methylation in offspring was analyzed using a methylation array. The results showed that maternal inulin treatment modified the maternal high-fat diet (HFD)-induced increases in body weight, adipose tissue weight, and serum insulin and leptin levels and decreases in serum adiponectin levels. Maternal inulin intervention regulated the impairments in hypothalamic leptin resistance, induced the methylation of Socs3, Npy, and Il6, and inhibited the methylation of Lepr in the hypothalamus of offspring. In conclusion, maternal inulin intervention modifies offspring lipid metabolism, and the underlying mechanism involves the methylation of genes in the hypothalamus feeding circuit.

Jiangtang Decoction Ameliorates Diabetic Kidney Disease Through the Modulation of the Gut Microbiota.

Purpose: This study aimed to elucidate the impact of Jiangtang decoction (JTD) on diabetic kidney disease (DKD) and its association with alterations in the gut microbiota. Methods: Using a diabetic mouse model (KK-Ay mice), daily administration of JTD for eight weeks was undertaken. Weekly measurements of body weight and blood glucose were performed, while kidney function, uremic toxins, inflammation factors, and fecal microbiota composition were assessed upon sacrifice. Ultra-structural analysis of kidney tissue was conducted to observe the pathological changes. Results: The study findings demonstrated that JTD improve metabolism, kidney function, uremic toxins and inflammation, while also exerting a modulatory effect on the gut microbiota. Specifically, the genera Rikenella, Lachnoclostridium, and unclassified_c_Bacilli exhibited significantly increased abundance following JTD treatment, accompanied by reduced abundance of norank_f_Lachnospiraceae compared to the model group. Importantly, Rikenella and unclassified_c_Bacilli demonstrated negative correlations with urine protein levels. Lachnoclostridium and norank_f_Lachnospiraceae were positively associated with creatinine (Cr), indoxyl sulfate (IS) and interleukin (IL)-6. Moreover, norank_f_Lachnospiraceae exhibited positive associations with various indicators of DKD severity, including weight, blood glucose, urea nitrogen (UN), kidney injury molecule-1 (KIM-1) levels, trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) and IL-17A production. Conclusion: These findings suggested that JTD possess the ability to modulate the abundance of Rikenella, Lachnoclostridium, unclassified_c_Bacilli and norank_f_Lachnospiraceae within the gut microbiota. This modulation, in turn, influenced metabolic processes, kidney function, uremic toxin accumulation, and inflammation, ultimately contributing to the amelioration of DKD.

Mini-open Pedicle Subtraction Osteotomy versus Standard Posterior Approach for Ankylosing Spondylitis-related Spinal Kyphosis: A Comparative Study.

OBJECTIVE: Surgical strategy for spinal kyphosis in patients with ankylosing spondylitis (AS) has been challenging. Pedicle subtraction osteotomy (PSO) through a minimally invasive (MI) approach has been developed with promising clinical outcomes. We aimed to compare the effectiveness and safety of PSO via an MI approach and a standard posterior approach (SPA) for treating AS-related spinal kyphosis. METHODS: A total of 41 patients with AS-related spinal kyphosis who underwent PSO through an MI approach (MI surgery [MIS] group: n = 25) or SPA (SPA group: n = 16) between January 2015 and July 2020 were retrospectively included. Spinopelvic parameters were evaluated before the surgery, immediately after the surgery, and at the 2-year follow-up. Clinical data including operative time, estimated blood loss, blood transfusion, level of fusion, incision length, bed rest period, length of hospitalization, and surgical complications were compared between the two groups. The Scoliosis Research Society outcomes instrument-22 (SRS-22) was administered to assess patients' quality of life at the latest follow-up. Comparisons between the two groups were performed using independent sample t-test or Chi-square test. RESULTS: Characteristics and baseline kyphosis of the two groups were matched. At the 2-year follow-up, in the MIS group, the average correction values of the sagittal vertical axis and global kyphosis (GK) were 9.5 cm and 44.3°, respectively. Compared with the SPA group, the MIS group had similar correction values and correction losses after surgery. No obvious differences were observed in any radiographic parameters, except for GK, immediately after surgery and at the 2-year follow-up between the two groups (p > 0.05). The MIS group had a significantly shorter operative time, lesser blood loss, lesser transfusion volume, shorter fusion level, and lesser time to mobilization than did the SPA group. Higher average functional activity scores of SRS-22 were obtained in the MIS group than in the SPA group. CONCLUSION: Mini-open PSO may be an effective alternative to the SPA for treating AS-related spinal kyphosis, with comparable correction effect, lesser surgical trauma and faster recovery. This comparative study may provide valuable guidance for surgical decision-making and patient counseling.

Magnolol Supplementation Alters Serum Parameters, Immune Homeostasis, Amino Acid Profiles, and Gene Expression of Amino Acid Transporters in Growing Pigs.

This study investigated whether dietary supplementation with magnolol affects growth performance, anti-inflammatory abilities, serum and muscle amino acid profiles, and metabolisms in growing pigs. A total of 42 seventy-days-old growing barrows (Duroc × Landrace × Yorkshire) were randomly allocated into two dietary groups: Con, control group (basal diet); and Mag, magnolol group (basal diet supplemented with 400 mg/kg of magnolol). The results revealed that dietary supplementation with magnolol had no effect (p > 0.05) on growth performance. However, magnolol supplementation remarkably increased (p < 0.05) the serum content of albumin, total protein, immunoglobulin G, immunoglobulin M, and interleukin-22. In addition, dietary magnolol supplementation altered the amino acid (AA) profiles in serum and dorsal muscle and particularly increased (p < 0.05) the serum content of arginine and muscle glutamate. Simultaneously, the mRNA expression of genes associated with AA transport in jejunum (SLC38A2, SLC1A5, and SLC7A1) and ileum (SLC1A5 and SLC7A1) was higher (p < 0.05) in the Mag group than in the Con group. Additionally, the serum metabolomics analysis showed that the addition of magnolol significantly enhanced (p < 0.05) arginine biosynthesis, as well as D-glutamine and D-glutamate metabolism. Overall, these results suggested that dietary supplementation with magnolol has the potential to improve the accumulation of AAs, protein synthesis, immunity, and body health in growing pigs by increasing intestinal absorption and the transport of AAs.

Xanthoceras sorbifolia Husk Extract Incorporation for the Improvement in Physical and Antioxidant Properties of Soy Protein Isolate Films.

With the increasing awareness of ecological and environmental protection, the research on eco-friendly materials has experienced a considerable increase. The objective of our study was to explore a novel soy protein isolate (SPI) film functionalized with antioxidants extracted from Xanthoceras sorbifolia husk (XSHE) as bio-based active packaging films. The films were evaluated in light of their structure, physical machinery, and antioxidant performance using advanced characterization techniques. The FTIR and microscopy results revealed the hydrogen-bond interaction between the SPI and XSHE and their good compatibility, which contributed to the improvement in various properties of the composite films, such as tensile strength (TS), UV blocking, and the water barrier property. As the XSHE content increased to 5%, the TS of the films dramatically increased up to 7.37 MPa with 47.7% and the water vapor permeability decreased to 1.13 × 10-10 g m m-2 s-1 Pa-1 with 22.1%. Meanwhile, the introduction of XSHE caused further improvement in the antioxidant capacity of films, and the release of active agents from films was faster and higher in 10% ethanol than it was in a 50% ethanol food simulant. Overall, SPI-based films functionalized with XSHE demonstrated promising potential applications in food packaging.

Factors Affecting the Prognosis of Patients with Acute Cerebrovascular Occlusion with High National Institutes of Health Stroke Scale Scores Treated with SWIM Technology.

Objective: We aimed to explore the factors affecting the prognosis of patients with acute cerebrovascular occlusion with high National Institutes of Health Stroke Scale (NIHSS) scores treated with the SWIM (Solitaire™ stent retriever-assisted thrombectomy with immediate mechanical aspiration) technique using an intracranial support catheter. Methods: A retrospective analysis was conducted in 72 patients with acute cerebrovascular occlusion who underwent SWIM surgery in the Affiliated Hospital of Chengde Medical University in China between January 2020 and June 2022. The patients were divided into a good prognosis group (Modified Rankin Score [mRS] 0 to 2; n = 30) and a poor prognosis group (mRS score 3 to 6; n = 42) on their mRS scores 3 months after surgery. The THRIVE (TICI, hemorrhage, reocclusion, infarction, vessel, and embolism) score at different time points before and after the SWIM procedure and the postoperative revascularization rate were compared in the 2 NIHSS score groups. Univariate and logistic regression analyses were performed to identify the risk factors that affected the prognosis of patients with acute cerebrovascular occlusion treated with the SWIM procedure. Results: The NIHSS score difference at various time points after SWIM surgery in patients with low to moderate NIHSS scores was significantly higher than in patients with high NIHSS scores (P < .05). The postoperative revascularization rate in patients with high NIHSS scores was 74.36%, which was not significantly different from that in patients with low to moderate scores (84.85%; P > .05). The poor prognosis in patients with acute cerebrovascular occlusion after SWIM surgery was related to age, hypertension, NIHSS score, Glasgow Coma Scale (GCS) score, Essen Stroke Risk Score (ESRS), onset-to-treatment time (OTT) and Alberta Collateral Grading Scale (ACGS) score (P < .05). Logistic regression analysis showed that age, admission NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure (P < .05). Conclusion: The prognosis in patients with acute cerebrovascular occlusion with high NIHSS scores after SWIM surgery was poor. Advanced age, high NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure. Overall, incorporating these findings into clinical practice promotes personalized approaches, interdisciplinary collaboration and timely interventions to optimize outcomes in patients undergoing the SWIM procedure for acute cerebrovascular occlusion.

Dietary Supplementation with Rutin Alters Meat Quality, Fatty Acid Profile, Antioxidant Capacity, and Expression Levels of Genes Associated with Lipid Metabolism in Breast Muscle of Qingyuan Partridge Chickens.

Consumer demand for tasty and quality meat has been quickly increasing. This study investigated how dietary supplemented rutin affects meat quality, muscle fatty acid profile, and antioxidant capacity in the Chinese indigenous Qingyuan partridge chicken. A cohort of 180 healthy 119-day-old chickens was subjected to a randomized assignment into three groups, identified as the control, R200, and R400 groups, with respective supplementation of 0, 200, and 400 mg/kg of rutin. The results revealed insignificance in growth performance, namely, average daily gain, average daily feed intake, and feed-to-gain ratio, across the various treatment groups (p > 0.05). Nevertheless, dietary rutin supplementation increased (p < 0.05) breast muscle yield and intramuscular fat content in breast muscle and decreased (p < 0.05) drip loss in breast muscle. Rutin supplementation increased (p < 0.05) the content of high-density lipoprotein but decreased (p < 0.05) the contents of glucose, triglyceride, and total cholesterol in serum. Rutin supplementation increased (p < 0.05) the levels of DHA (C22:6n-3), total polyunsaturated fatty acids (PUFAs), n-3 PUFAs, decanoic acid (C10:0), the activity of Δ5 + Δ6 (22:6 (n - 3)/18:3 (n - 3)), and the ratio of PUFA/SFA in breast muscle but decreased (p < 0.05) the level of palmitoleic acid (C16:1n-7), the ratio of n-6/n-3 PUFAs, and the activity of Δ9 (16:1 (n - 7)/16:0). Rutin treatment also reduced (p < 0.05) the contents of malondialdehyde in serum and breast muscle, and increased (p < 0.05) the catalase activity and total antioxidant capacity in serum and breast muscle and the activity of total superoxide dismutase in serum. Additionally, rutin supplementation downregulated the expression of AMPKα and upregulated the expression of PPARG, FADS1, FAS, ELOVL7, NRF2, and CAT in breast muscle (p < 0.05). Convincingly, the results revealed that rutin supplementation improved meat quality, fatty acid profiles, especially n-3 PUFAs, and the antioxidant capacity of Qingyuan partridge chickens.

[Effect of acupuncture pretreatment of "Quchi"(LI11) and "Xuehai" (SP10) on mast cells and IL-33/ST2 in rats with urticaria].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01，P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.

Priming effects of nZVI on carbon sequestration and iron uptake are positively mediated by AM fungus in semiarid agricultural soils.

We investigated the priming effect of nanoscale zero-valent iron (nZVI) on carbon sink and iron uptake, and the possible mediation by AMF (arbuscular mycorrhizal fungi, Funneliformis mosseae) in semiarid agricultural soils. Maize seed dressings comprised of three nZVI concentrations of 0, 1, 2 g·kg-1 and was tested with and without AMF inoculation under high and low soil moistures, respectively. The ICP-OES observations indicated that both low dose of nZVI (1 g·kg-1) and high dose of nZVI (2 g·kg-1) significantly increased the iron concentrations in roots (L: 54.5-109.8 %; H: 119.1-245.4 %) and shoots (L: 40.8-78.9 %; H: 81.1-99.4 %). Importantly, the absorption and translocation rate of iron were substantially improved by AMF inoculation under the low-dose nZVI. Yet, the excess nanoparticles as a stress were efficiently relieved by rhizosphere hyphae, and the iron concentration in leaves and stems can maintain as high as about 300 mg·kg-1 while the iron translocation efficiency was reduced. Moreover, next-generation sequencing confirmed that appropriate amount of nZVI clearly improved the rhizosphere colonization of Funneliformis mosseae (p < 0.001) and the development of soil fungal community. Soil observations further showed that the hyphae development and GRSP (glomalin-related soil protein) secretion were significantly promoted (p < 0.05), with the increased R0.25 (< 0.25 mm) by 35.97-41.16 %. As a return, AMF and host plant turned to input more organic matter into soils for microbial growth and Fe uptake, and such interactions became more pronounced under drought stress. In contrast, high dose of nZVI (2 g·kg-1) tended to agglomerate on the surface of hyphae and spores, causing severe deformation and inactivation of AMF symbionts. Therefore, the priming effects of nZVI on carbon sequestration and Fe uptake in agricultural soils were positively mediated by AMF via the feedback loop of the plant-soil-microbe system for enhanced adaptation to global climate change.

Linear Regression Analysis of Sleep Quality in People with Insomnia in Wuhan City during the COVID-19 Pandemic.

Objective: COVID-19 has evolved into a major global public health event. The number of people reporting insomnia is growing exponentially during the pandemic. This study aimed to explore the relationship between aggravated insomnia and COVID-19-induced psychological impact on the public, lifestyle changes, and anxiety about the future. Methods: In this cross-sectional study, we used the questionnaires from 400 subjects who were obtained from the Department of Encephalopathy of the Wuhan Hospital of Traditional Chinese Medicine between July 2020 and July 2021. The data collected for the study included demographic characteristics of the participants and psychological scales consisting of the Spiegel Sleep Questionnaire, the Fear of COVID-19 Scale (FCV-19S), the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). The independent sample t-test and one-way ANOVA were used to compare the results. Correlation analysis of variables affecting insomnia was performed using Pearson correlation analysis. The degree of influence of the variables on insomnia was determined using linear regression, and a regression equation was derived. Results: A total of 400 insomnia patients participated in the survey. The median age was 45.75 ± 15.04 years. The average score of the Spiegel Sleep Questionnaire was 17.29 ± 6.36, that of SAS was 52.47 ± 10.39, that of SDS was 65.89 ± 8.72, and that of FCV-19S was 16.09 ± 6.81. The scores of FCV-19S, SAS, and SDS were closely related to insomnia, and the influencing degree was in the following order: fear, depression, and anxiety (OR = 1.30, 0.709, and 0.63, respectively). Conclusion: Fear of COVID-19 can be one of the primary contributors to worsening insomnia.

Mulberry leaf extract improves intestinal barrier function and displays beneficial effects on colonic microbiota and microbial metabolism in weaned piglets.

BACKGROUND: Mulberry leaf extract (MLE) extracted from mulberry leaves is rich in a variety of bioactive ingredients and can be used as feed additives of weaned piglets. The present study was conducted to evaluate the effects of dietary MLE supplementation on intestinal barrier function, colon microbial numbers and microbial metabolites of weaned piglets. RESULTS: MLE supplementation increased the villus height and the villus height/crypt depth ratio in jejunum and ileum (P < 0.05), increased the mRNA expression of ZO-1, Claudin-1 and MUC-2 in the ileal mucosa (P < 0.05), and decreased the serum level of lipopolysaccharide (P < 0.01). Meanwhile, MLE reduced the mRNA expression of tumor necrosis factor-α and interleukin-1ß (P < 0.05) and increased secretory immunoglobulin A level in the ileal mucosa (P < 0.05). In addition, MLE increased the numbers of beneficial bacteria Bifidobacterium and Lactobacillus (P < 0.05) and decreased the number of potential pathogenic bacteria Escherichia coli (P < 0.05) in the colon. Correspondingly, MLE supplementation reduced the pH value of colonic digesta (P < 0.05) and altered the microbial fermentation pattern of the colon by increasing the concentrations of microbial metabolites derived from carbohydrates fermentation such as lactate, acetate, butyrate and total short-chain fatty acids (P < 0.05), and decreasing the concentrations of microbial metabolites derived from amino acid fermentation such as p-cresol, skatole, spermine, histamine and tryptamine (P < 0.05). CONCLUSION: MLE supplementation improved intestinal barrier function and displayed beneficial effects on colon microbes and microbial metabolism in weaned piglets. © 2022 Society of Chemical Industry.

The effects of Ophiocordyceps sinensis combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Ophiocordyceps sinensis (OS), a medicinal fungus, has been made into OS preparations, which are frequently used as adjunctive therapy for patients with Diabetic Kidney Disease (DKD) in China. It is necessary to assess the efficacy and safety of OS preparations in the adjunctive treatment of DKD by conducting a systematic review and meta-analysis. OBJECTIVE: Ophiocordyceps sinensis preparations were evaluated for their efficacy and safety as adjunctive therapy to conventional drugs (angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)) for DKD. METHODS: We searched seven electronic literature databases for randomized controlled trials (RCTs) comparing ACEI/ARB and OS combined with ACEI/ARB from inception up to March 2022. Two reviewers extracted data and assessed the risk of bias independently. Evidence certainty was rated using the GRADE system. Standardized mean difference (SMD) or mean difference (MD) was pooled with random effects models and was reported with corresponding 95% confidence intervals (CIs). Meta-analysis, sensitivity analysis and Egger's test were performed using R software (version 14.2) (PROSPERO registration no. CRD42021248634). RESULTS: Thirty eight RCTs involving 3167 patients met the inclusion criteria. No trials were reported with outcomes about kidney disease progression and cardiovascular events. In meta-analysis, compared with the control group of ACEI/ARB alone, OS combined with ACEI/ARB can achieve better effects in the treatment of DKD on reducing serum creatinine (Scr) [MDScr =-11.48 95% CI [-15.78, -7.18], p < 0.01], blood urea nitrogen (BUN) [MDBUN= -1.00, 95% CI [-1.44, -0.55], p < 0.01], ß2-microglobulin (ß2-MG) [SMDß2-MG= -1.32, 95% CI [-2.27, -0.37], p < 0.01], cystatin C (CysC) [MDCysC=-0.64, 95% CI [-0.83, -0.45], p < 0.01], 24-h urine proteinuria (24hUP) [SMD24hUP= -1.99, 95% CI [-2.68; -1.31], p < 0.01], urine microalbumin (UALB) [MDUALB= -37.41, 95% CI [-44.76, -30.06], p < 0.01] and decreasing urinary albumin excretion rate (UAER) [MDUAER= -24.11, 95% CI [-30.54, -17.68], p < 0.01] and albumin creatinine ratio (ACR) [SMDACR = 1.01, 95% CI [-1.73, -0.29], p < 0.01]. The OS adjuvant treatment also improved outcomes of blood pressure, blood glucose, blood lipid, inflammation and oxidative stress. No significant change in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), malondialdehyde (MDA), and transforming growth factor beta 1 (TGF-ß1) was detected. Yet, no significant difference was found about the adverse events between the two groups. CONCLUSIONS: Ophiocordyceps sinensis preparation combined with ACEI/ARB has beneficial influence on renal function, decrease proteinuria, dyslipidemia, and even oxidative stress and inflammation in DKD patients. However, there is no trial that evaluated outcomes of kidney disease progression and cardiovascular events. Future study should move beyond surrogate endpoints to actual cardiovascular or renal outcome benefits with an aim to explore effects of OS preparation in the long-term.

Macranthoidin B (MB) Promotes Oxidative Stress-Induced Inhibiting of Hepa1-6 Cell Proliferation via Selenoprotein.

The aim of this study was to investigate the role of selenoproteins in Macranthoidin B (MB) with regard to the inhibition of hepa1-6 cell proliferation. The CCK8 method was used to detect the inhibition rate in hepa1-6 cell of proliferation. The production of ROS, MDA, GSH levels, and GSH-Px and SOD activities was detected according to corresponding reagent kits. We determined the mRNA expressions of 25 selenoproteins in hepa1-6 cells via real-time quantitative PCR (qRT-PCR); moreover, the heat map and principal component analysis were used for further bioinformatics analysis. The results revealed that with an increasing concentration of MB, the inhibitory effect on hepa1-6 cell proliferation intensified. Compared with the control group, the treatment group showed significantly increased ROS levels, elevated MDA contents, and decreased GSH level, GSH-Px activity, and SOD activity. Increasing MB concentration treatment induced remarkable degradation of Txnrd1, Txnrd2, Txnrd3, Gpx1, Gpx2, Gpx3, Gpx6, Dio1, Dio2, Selt, Selp, Selh, Selk, Selw, Seln, and Dio3. Principal component analysis revealed that Txnrd 3, Selk, Selo, Selw, Selt, Dio2, Txnrd1, Dio3, Gpx6, and Dio1 were highly correlated with MB. In conclusion, MB dose dependently inhibited hepa1-6 cell proliferation and induced oxidative stress. Based on bioinformatics analysis, with MB treatment, Txnrd 3, Selk, Selo, Selw, Selt, Dio2, Txnrd1, Dio3, Gpx6, and Dio1 exhibited critical role in the inhibition of hepa1-6 cells proliferation. The functions of these selenoproteins were associated with oxidative stress.

The deposition and significance of an Ediacaran non-glacial iron formation.

Most Neoproterozoic iron formations (NIF) are closely associated with global or near-global "Snowball Earth" glaciations. Increasingly, however, studies indicate that some NIFs show no robust evidence of glacial association. Many aspects of non-glacial NIF genesis, including the paleo-environmental setting, Fe(II) source, and oxidation mechanisms, are poorly understood. Here, we present a detailed case study of the Jiapigou NIF, a major non-glacial NIF within a Neoproterozoic volcano-sedimentary sequence in North Qilian, northwestern China. New U-Pb geochronological data place the depositional age of the Jiapigou NIF at ~600 Ma. Petrographic and geochemical evidence supports its identification as a primary chemical sediment with significant detrital input. Major and trace element concentrations, REE + Y systematics, and εNd (t) values indicate that iron was sourced from mixed seawater and hydrothermal fluids. Iron isotopic values (δ56 Fe = -0.04‰-1.43‰) are indicative of partial oxidation of an Fe(II) reservoir. We infer that the Jiapigou NIF was deposited in a redox stratified water column, where hydrothermally sourced Fe(II)-rich fluids underwent oxidation under suboxic conditions. Lastly, the Jiapigou NIF has strong phosphorous enrichments, which in other iron formations are typically interpreted as signals for high marine phosphate concentrations. This suggests that oceanic phosphorus concentrations could have been enriched throughout the Neoproterozoic, as opposed to simply during glacial intervals.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.