Arginine alleviates Clostridium perfringens α toxin-induced intestinal injury in vivo and in vitro via the SLC38A9/mTORC1 pathway.

Introduction: Clostridium perfringens α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear. Methods: In vivo, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). In vitro, IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms. Results and discussion: The results showed that in vivo, arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin (IL)-1ß, IL-6 and IL-17 mRNA expression. Clostridium perfringens α toxin significantly decreased jejunal mechanistic target of rapamycin (mTOR) and solute carrier family 38 member 9 (SLC38A9) mRNA expression, while arginine supplementation significantly increased mTOR and SLC38A9 mRNA expression. In vitro, arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines IL-6, C-X-C motif chemokine ligand (CXCL)10, CXCL11 and transforming growth factor-ß (TGF-ß), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-XL) and cysteinyl aspartate specific proteinase 3 (Caspase-3) and the ratio of Bax to Bcl-2. Arginine pretreatment significantly increased the α toxin-induced decrease in mTOR, SLC38A9, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (S6K) mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mTOR mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury in vivo and in vitro, which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.

Comprehensive Analysis of the Complete Mitochondrial Genome of Rehmannia chingii: An Autotrophic Species in the Orobanchaceae Family.

Rehmannia chingii is an important medicinal plant with immense value in scientific research. However, its mitochondrial genome (mitogenome) has not yet been characterized. Herein, based on whole-genome Illumina short reads and PacBio HiFi reads, we obtained the complete mitogenome of R. chingii through a de novo assembly strategy. We carried out comparative genomic analyses and found that, in comparison with the plastid genome (plastome) showing a high degree of structural conservation, the R. chingii mitogenome structure is relatively complex, showing an intricate ring structure with 16 connections, owing to five repetitive sequences. The R. chingii mitogenome was 783,161 bp with a GC content of 44.8% and contained 77 genes, comprising 47 protein-coding genes (CDS), 27 tRNA genes, and 3 rRNA genes. We counted 579 RNA editing events in 47 CDS and 12,828 codons in all CDSs of the R. chingii mitogenome. Furthermore, 24 unique sequence transfer fragments were found between the mitogenome and plastome, comprising 8 mitogenome CDS genes and 16 plastome CDS genes, corresponding to 2.39% of the R. chingii mitogenome. Mitogenomes had shorter but more collinear regions, evidenced by a comparison of the organelles of non-parasitic R. chingii, hemiparasitic Pedicularis chinensis, and holoparasitic Aeginetia indica in the Orobanchaceae family. Moreover, from non-parasitic to holoparasitic species, the genome size in the mitogenomes of Orobanchaceae species did not decrease gradually. Instead, the smallest mitogenome was found in the hemiparasitic species P. chinensis, with a size of 225,612 bp. The findings fill the gap in the mitogenome research of the medicinal plant R. chingii, promote the progress of the organelle genome research of the Orobanchaceae family, and provide clues for molecular breeding.

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.

Effects of dietary chitosan oligosaccharide on the growth, intestinal microbiota and immunity of juvenile red claw crayfish (Cherax quadricarinatus).

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.

Exercise intervention for patients with chronic low back pain: a systematic review and network meta-analysis.

Purpose: Chronic low back pain (CLBP) is an aging and public health issue that is a leading cause of disability worldwide and has a significant economic impact on a global scale. Treatments for CLBP are varied, and there is currently no study with high-quality evidence to show which treatment works best. Exercise therapy has the characteristics of minor harm, low cost, and convenient implementation. It has become a mainstream treatment method in clinics for chronic low back pain. However, there is insufficient evidence on which specific exercise regimen is more effective for chronic non-specific low back pain. This network meta-analysis aimed to evaluate the effects of different exercise therapies on chronic low back pain and provide a reference for exercise regimens in CLBP patients. Methods: We searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to 10 May 2022. Inclusion and exclusion criteria were used for selection. We collected information from studies to compare the effects of 20 exercise interventions on patients with chronic low back pain. Results: This study included 75 randomized controlled trials (RCTs) with 5,254 participants. Network meta-analysis results showed that tai chi [standardized mean difference (SMD), -2.11; 95% CI, -3.62 to -0.61], yoga (SMD, -1.76; 95% CI -2.72 to -0.81), Pilates exercise (SMD, -1.52; 95% CI, -2.68, to -0.36), and sling exercise (SMD, -1.19; 95% CI, -2.07 to -0.30) showed a better pain improvement than conventional rehabilitation. Tai chi (SMD, -2.42; 95% CI, -3.81 to -1.03) and yoga (SMD, -2.07; 95% CI, -2.80 to -1.34) showed a better pain improvement than no intervention provided. Yoga (SMD, -1.72; 95% CI, -2.91 to -0.53) and core or stabilization exercises (SMD, -1.04; 95% CI, -1.80 to -0.28) showed a better physical function improvement than conventional rehabilitation. Yoga (SMD, -1.81; 95% CI, -2.78 to -0.83) and core or stabilization exercises (SMD, -1.13; 95% CI, -1.66 to -0.59) showed a better physical function improvement than no intervention provided. Conclusion: Compared with conventional rehabilitation and no intervention provided, tai chi, toga, Pilates exercise, sling exercise, motor control exercise, and core or stabilization exercises significantly improved CLBP in patients. Compared with conventional rehabilitation and no intervention provided, yoga and core or stabilization exercises were statistically significant in improving physical function in patients with CLBP. Due to the limitations of the quality and quantity of the included studies, it is difficult to make a definitive recommendation before more large-scale and high-quality RCTs are conducted.

A participatory approach to understand the attitudes and perceptions towards priority endemic cattle diseases among dairy farmers and animal health experts in Henan province, China.

The dairy industry is threatened by a variety of endemic diseases and emerging diseases, and various control programs have been initiated in China. The increased application of evidence to policymaking can help improve the efficiency of disease control programs; however, the relevant research literature is currently lacking. The objective of this study was to gain an in-depth understanding of the attitudes and perceptions towards priority endemic diseases among dairy farmers and animal health experts by taking Henan province of China as the example and using semi-structured interviews and focus group discussions, respectively. This study involved 24 farmers and 27 animal health experts from December 2019 to January 2021. The diseases considered by farmers to be of significance to their animals are different from those considered priorities by the participating experts and the government list. From the perspective of the individual farmers, the effects of zoonotic disease risks such as bovine brucellosis and tuberculosis appear to be less pronounced than "visible" losses at the farm level, contrary to the opinion of experts. Participating experts believed that poor on-farm biosecurity measures posed challenges to the control and eradication of priority endemic diseases; however, there are gaps in farmers' understanding of biosecurity principles, and low motivations to take such disease prevention measures. Several other challenges to the control and eradication of priority endemic diseases also emerged in the data, including the lack of diagnostic tools applicable in the field as well as differential diagnostic tools to differentiate natural infection from vaccination, lack of effective and commercially available vaccines against single or multiple pathogen(s) or new genotypes/serotypes, weak early warning and information networks and insufficient economic compensation. A holistic understanding of people's perceptions of disease control would facilitate the implementation of inclusive and engaging disease control strategies, thereby increasing the efficiency of disease control.

"Exogenous boron alleviates salt stress in cotton by maintaining cell wall structure and ion homeostasis".

Salt stress is considered one of the major abiotic stresses that impair agricultural production, while boron (B) is indispensable for plant cell composition and has also been found to alleviate salt stress. However, the regulatory mechanism of how B improves salt resistance via cell wall modification remains unknown. The present study primarily focused on investigating the mechanisms of B-mediated alleviation of salt stress in terms of osmotic substances, cell wall structure and components and ion homeostasis. The results showed that salt stress hindered plant biomass and root growth in cotton. Moreover, salt stress disrupted the morphology of the root cell wall as evidenced by Transmission Electron Microscope (TEM) analysis. The presence of B effectively alleviated these adverse effects, promoting the accumulation of proline, soluble protein, and soluble sugar, while reducing the content of Na+ and Cl- and augmenting the content of K+ and Ca2+ in the roots. Furthermore, X-ray diffraction (XRD) analysis demonstrated a decline in the crystallinity of roots cellulose. Boron supply also reduced the contents of chelated pectin and alkali-soluble pectin. Fourier-transform infrared spectroscopy (FTIR) analysis further affirmed that exogenous B led to a decline in cellulose accumulation. In conclusion, B offered a promising strategy for mitigating the adverse impact of salt stress and enhancing plant growth by countering osmotic and ionic stresses and modifying root cell wall components. This study may provide invaluable insights into the role of B in ameliorating the effects of salt stress on plants, which could have implications for sustainable agriculture.

Enrichment of Isaria felina Culture with Selenium Enhances its in vivo Antitumor Effects on H22 Hepatoma via Decreasing the Expression of VEGF.

BACKGROUND: The polysaccharide extract of C. sinensis, Isaria felina (IF), has antitumor effects. Selenium (Se) can improve disease prevention and reduce the toxicity of toxic elements, but the effect of Se-enriched IF on hepatoma remains unknown. OBJECTIVE: To determine the organic transformation of Se and compare the antitumor effects between Se-enriched IF (IF-Se) and IF on xenograft H22 hepatoma-bearing mice. METHODS: Se was added to the solid-state culture medium, and the organic Se content was detected by HPLC-ICP-MS. Forty-two Kunming mice were randomly divided into seven groups to test the antitumor effects of low- (300 mg/kg) and high- (600 mg/kg) doses of IF-Se and IF through xenograft. Huai'er granules were administered as the positive control. In addition, interleukin (IL)-2 and vascular endothelial growth factor (VEGF) expressions were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method. RESULTS: The conversion rate in the IF-Se70, IF-Se140, and IF-Se280 groups were 91.5%, 93.4%, and 89.3%, respectively. Therefore, IF-Se140 was used to carry out the subsequent experiments. The tumor inhibition rates of IF-Se were significantly higher compared with IF (P < 0.05). Moreover, the spleen coefficient, IL-2, and VEGF expression levels significantly decreased (all Ps < 0.05), and the thymus coefficient significantly increased (P < 0.05) in the high-dose IF-Se group compared with the model control group. CONCLUSION: The inhibitory effects of IF on H22 hepatoma-bearing mice were enhanced after Se enrichment. Therefore, Se-enriched IF might be a new strategy for treating hepatoma.

Microbiome modulation by a precision biotic in broilers chickens: a commercial study validation.

Precision biotics (PBs) are chemically synthesized complex glycans that modulate specific microbiome metabolic functions. The objective of the present study was to evaluate the effect of the supplementation of PB on the growth performance, and cecal microbiome modulation of broiler chickens raised under commercial conditions. A total of 190,000-day-old Ross 308 straight-run broilers were randomly assigned to 2 dietary treatments. There were 5 houses per treatment with 19,000 birds per house. In each house, there were 6 rows of battery cages with 3 tiers. The 2 dietary treatments included a control diet (a commercial broiler diet) and a PB supplemented diet at 0.9 kg/MT. On a weekly basis, 380 birds were randomly selected for body weight (BW) determination. At 42 d of age, the BW and feed intake (FI) of each house were recorded, the feed conversion ratio (cFCR) was calculated and corrected with the final BW, and the European production index (EPI) was calculated. Additionally, 8 birds per house (40 birds/experimental group) were randomly selected to collect cecal content for microbiome analysis. The supplementation of PB significantly improved (P < 0.05) the BW of the birds at 7, 14, and 21 d and numerically improved the BW of the birds by 64 and 70 g at 28 and 35 d of age, respectively. At 42 d, the PB numerically improved BW by 52 g, and significantly improved (P < 0.05) the cFCR by 2.2 points and the EPI by 13 points. The functional profile analysis showed a clear and significant difference in the cecal microbiome metabolism between control vs. PB supplemented birds. A higher abundance of pathways was modulated by PB which were associated with amino acid fermentation and putrefaction, particularly from lysine, arginine, proline, histidine, and tryptophane which led to a significant increase (P = 0.0025) in the Microbiome Protein Metabolism Index (MPMI) compared to nonsupplemented birds. In conclusion, the supplementation of PB efficiently modulated pathways related to protein fermentation and putrefaction, resulting in higher MPMI and improved growth performance of broilers.

Efficacy of acupuncture combined with oral Chinese medicine in the treatment of arrhythmia: A meta-analysis.

BACKGROUND: At present, Western medicine treatment methods for arrhythmia emerge in an endless stream, but the accompanying side effects are also exposed, which brings pressure on medical resources and social economy. In recent years, the advantages of acupuncture combined with traditional Chinese medicine (TCM) in the control of arrhythmia have become increasingly prominent. Neiguan (PC6) is the collateral point in pericardium meridian; acupuncture at Neiguan can nourish the heart and calm the mind, and also plays an important role in treating arrhythmias. There is currently a lack of evidence-based medical evidence for the combination of acupuncture and TCM in the treatment of arrhythmia. This study aimed to investigate the effect of acupuncture combined with oral TCM in the treatment of arrhythmia. METHODS: Randomized controlled trials published from the inception of databases to June 2022 were reviewed by searching the PubMed, Cochrane Library, Embase, CNKI, VIP, and WanFang databases. Review Manager 5.4.1 was used for the meta-analysis after the reviewers scanned the literature, extracted information, and identified the risk of bias. RESULTS: Eleven randomized controlled trials with 804 patients were reviewed, including 402 and 402 patients in the treatment and control groups, respectively. The results of the meta-analysis showed a significant benefit of acupuncture plus oral TCM in terms of clinical effectiveness compared with oral TCM alone (n = 696; relative risk (RR), 1.22; 95% confidence interval (CI) 1.14 to 1.30; P < .00001) and in lowering the number of premature beats in 24 hours (n = 374; standard mean difference, -10,55; 95% confidence interval (95% CI) -14.61 to -6.49; P < .00001). Acupuncture plus oral TCM was also found to improve the conversion rate (n = 168; RR, 1.32; 95% CI, 1.14-1.52; P = .0002) and increase the left ventricular ejection fraction (n = 250; mean difference, 6.57; 95% CI, 4.11-9.04; P < .00001), but it had no significant increase in adverse events (n = 262; RR, 0.57; 95% CI 0.30-1.09; P = .09). CONCLUSION: Compared with oral TCM alone, acupuncture combined with oral TCM showed a clear benefit in treating arrhythmias and had no increase in adverse events.

Research on Rapid and Low-Cost Spectral Device for the Estimation of the Quality Attributes of Tea Tree Leaves.

Tea polyphenols, amino acids, soluble sugars, and other ingredients in fresh tea leaves are the key parameters of tea quality. In this research, a tea leaf ingredient estimation sensor was developed based on a multi-channel spectral sensor. The experiment showed that the device could effectively acquire 700-1000 nm spectral data of tea tree leaves and could display the ingredients of leaf samples in real time through the visual interactive interface. The spectral data of Fuding white tea tree leaves acquired by the detection device were used to build an ingredient content prediction model based on the ridge regression model and random forest algorithm. As a result, the prediction model based on the random forest algorithm with better prediction performance was loaded into the ingredient detection device. Verification experiment showed that the root mean square error (RMSE) and determination coefficient (R2) in the prediction were, respectively, as follows: moisture content (1.61 and 0.35), free amino acid content (0.16 and 0.79), tea polyphenol content (1.35 and 0.28), sugar content (0.14 and 0.33), nitrogen content (1.15 and 0.91), and chlorophyll content (0.02 and 0.97). As a result, the device can predict some parameters with high accuracy (nitrogen, chlorophyll, free amino acid) but some of them with lower accuracy (moisture, polyphenol, sugar) based on the R2 values. The tea leaf ingredient estimation sensor could realize rapid non-destructive detection of key ingredients affecting tea quality, which is conducive to real-time monitoring of the current quality of tea leaves, evaluating the status during tea tree growth, and improving the quality of tea production. The application of this research will be helpful for the automatic management of tea plantations.

Mechanism of Yiqi Yangying Heluo Formula in the Treatment of IgA Nephropathy by Affecting Gd-IgA1 Based on BAFF Molecular Level and T Lymphocyte Immunity.

Background: Galactose-deficient IgA1 (Gd-IgA1) is a critical initiating factor in the pathogenesis of IgA nephropathy (IgAN), which plays an important role in the diagnosis and evaluation of this disease. Moreover, the whole pathogenesis process has an intimate association with the immune response of T and B lymphocytes and their inflammatory factors. There is no specific therapy for IgAN at present. Yiqi Yangyin Formula can significantly reduce urinary protein and hematuria in patients with IgAN. Yiqi Yangying Heluo Formula (YYHF) is optimized on the basis of the above prescription, but its specific mechanism remains to be further studied. Methods: The effect of YYHF on urinary protein and urinary red blood cell count in patients with IgAN was observed by a self-controlled clinical study before and after treatment. On this basis, flow cytometry was used to detect the proportion of T lymphocyte subsets in peripheral blood of patients with IgAN before and after treatment and healthy controls. Meanwhile, the levels of Gd-IgA1, B cell activation factor (BAFF), and their cytokines (IL-4, IL-6, and IL-17) in peripheral blood were detected by enzyme-linked immunosorbent assay. The changes in mechanism-related indicators of the two groups were observed and subject to correlation analysis. Results: (1) Compared with the levels before treatment, 24-hour urinary protein content decreased by 47.7% and urinary red blood cell number decreased by 67% in patients with IgAN intervened by YYHF after 48 weeks of follow-up. (2) Compared with the healthy control group, patients with IgAN showed a significantly increased proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg, obviously reduced proportion of Th2 cells and Treg cells, and evidently elevated levels of Gd-IgA1, BAFF, and their cytokines (IL-4, IL-6, and IL-17) in the peripheral blood. (3) Following 48 weeks of follow-up after intervention treatment with YYHF, the levels of Gd-IgA1, BAFF, IL-6, and IL-17 were significantly lower, but the level of IL-4 was higher in peripheral blood of patients with IgAN than those before treatment and after 24 weeks of treatment; simultaneously, the proportion of Th1 cells, Th17 cells, Th1/Th2, Th1/Treg, Th2/Treg, and Th17/Treg decreased while that of Th2 cells and Treg cells increased after 48 weeks of follow-up compared with that before treatment in peripheral blood of patients with IgAN. (4) The results of correlation analysis revealed that the level of Gd-IgA1 in peripheral blood of patients with IgAN was positively correlated with the level of BAFF, as well as the proportion of Th1 cells, Th17 cells, Th1/Th2, IL-6, and IL-17 levels, and negatively correlated with the proportion of Treg cells. In addition, the level of Gd-IgA1 in peripheral blood was positively correlated with proteinuria, yet without correlation with hematuria. Conclusion: YYHF can reduce the quantitative level of 24 h urinary protein and urinary red blood cell count in patients with IgAN. Patients with IgAN have obvious T cell immune imbalance. YYHF can significantly reduce the level of Gd-IgA1 in patients with IgAN, and its mechanism may be explained by the reduced level of BAFF in peripheral blood and improved immune balance of T cells.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Comparative Analysis of Aristolochic Acids in Aristolochia Medicinal Herbs and Evaluation of Their Toxicities.

Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the Aristolochia genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in Aristolochia plants, except for AAs Ι and ΙΙ, still remain unclear. In this study, a total of 52 batches of three medicinal herbs belonging to the Aristolochia family were analyzed for their AA composition profiles and AA contents using the UPLC-QTOF-MS/MS approach. The studied herbs were A. mollissima Hance (AMH), A. debilis Sieb.etZucc (ADS), and A. cinnabaria C.Y.Cheng (ACY). Chemometrics methods, including PCA and OPLS-DA, were used for the evaluation of the Aristolochia medicinal herbs. Additionally, cytotoxicity and genotoxicity of the selected AAs and the extracts of AMH and ADS were evaluated in a HepG2 cell line using the MTT method and a Comet assay, respectively. A total of 44 AAs, including 23 aristolochic acids and 21 aristolactams (ALs), were detected in A. mollissima. Moreover, 41 AAs (23 AAs and 18 ALs) were identified from A. debilis Sieb, and 45 AAs (29 AAs and 16 ALs) were identified in A. cinnabaria. Chemometrics results showed that 16, 19, and 22 AAs identified in AMH, ADS, and ACY, respectively, had statistical significance for distinguishing the three medicinal herbs of different origins. In the cytotoxicity assay, compounds AL-BΙΙ, AAΙ and the extract of AMH exhibited significant cytotoxicities against the HepG2 cell line with the IC50 values of 0.2, 9.7 and 50.2 µM, respectively. The results of the Comet assay showed that AAΙ caused relatively higher damage to cellular DNA (TDNA 40-95%) at 50 µM, while AAΙΙ, AMH and ADS extracts (ranged from 10 to 131 µM) caused relatively lower damage to cellular DNA (TDNA 5-20%).

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series.

BACKGROUND: Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG. METHODS: Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored. RESULTS: A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31-42), and their median birth weight was 2765 g (range 1300-3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient's films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1-23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25-100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2-17) and 8 M (range 4-22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up. CONCLUSION: Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.

Early Adoption of Anti-SARS-CoV-2 Pharmacotherapies Among US Veterans With Mild to Moderate COVID-19, January and February 2022.

Importance: Older adults and individuals with medical comorbidities are at increased risk for severe COVID-19. Several pharmacotherapies demonstrated to reduce the risk of COVID-19-related hospitalization and death have been authorized for use. Objective: To describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Affairs (VA) health care system. Design, Settings, and Participants: This cohort study assessed outpatient veterans with risk factors for severe COVID-19 who tested positive for SARS-CoV-2 during January and February 2022. The setting was the VA health care system, the largest integrated health care system in the US. Exposures: Demographic characteristics, place of residence, underlying medical conditions, and COVID-19 vaccination. Main Outcomes and Measures: The odds of receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir were estimated using multivariable logistic regression. Results: Among 111 717 veterans included in this study (median [IQR] age, 60 [46-72] years; 96 482 [86.4%] male, 23 362 [20.9%] Black, 10 740 [9.6%] Hispanic, 75 973 [68.0%] White) who tested positive for SARS-CoV-2 during January to February 2022, 4233 (3.8%) received any COVID-19 pharmacotherapy, including 2870 of 92 396 (3.1%) in January and 1363 of 19 321 (7.1%) in February. Among a subset of 56 285 veterans with documented COVID-19-related symptoms in the 30 days preceding a positive SARS-CoV-2 test, 3079 (5.5%) received any COVID-19 pharmacotherapy. Untreated veterans had a median (IQR) age of 60 (46-71) years and a median (IQR) of 3 (2-5) underlying medical conditions. Veterans receiving any treatment were more likely to be older (aged 65 to 74 years vs 50 to 64 years: adjusted odds ratio [aOR], 1.66 [95% CI, 1.52-1.80]; aged at least 75 years vs 50 to 64 years: aOR, 1.67 [95% CI, 1.53-1.84]) and have a higher number of underlying conditions (at least 5 conditions vs 1 to 2 conditions: aOR, 2.17 [95% CI, 1.98-2.39]). Compared with White veterans, Black veterans (aOR, 0.65 [95% CI, 0.60-0.72]) were less likely to receive treatment; and compared with non-Hispanic veterans, Hispanic veterans (aOR, 0.88 [95% CI, 0.77-0.99]) were less likely to receive treatment. There were 16 546 courses of sotrovimab, nirmatrelvir, and molnupiravir allocated across the VA during this period. Conclusions and Relevance: In this cohort study of veterans who tested positive for SARS-CoV-2 during January and February when supply of outpatient COVID-19 pharmacotherapies was limited, prescription of these pharmacotherapies was underused, and many veterans with risk factors for severe COVID-19 did not receive treatment. Veterans from minority racial and ethnic groups were less likely to receive any pharmacotherapy.

Correlation between TCM Constitutional Types and Lung Carcinoma in Various Geographical Areas: A Systematic Review and Meta-Analysis.

Background: Lung carcinoma is a serious disorder that negatively influences the quality of life of sufferers. Despite the growing number of investigations into the management and prognosis of lung carcinoma, few research studies have been conducted to demonstrate the association between TCM constitution and lung carcinoma. Methods: We searched PubMed, EMBASE, Science Net, Cochrane Library, China National Knowledge Infrastructure, VIP database, Wanfang database, and China Biomedical Literature Database for Chinese and English versions until January 31, 2021. We also manually searched for Chinese lung cancer, Chinese physical medicine, Chinese medical trial registries, and unpublished surveys or references. The literature was screened against inclusive and exclusive criteria, and two investigators' results were independently summarized. The primary outcome was a ratio of body type. Single-group rates were meta-analyzed using Stata 14.0 statistical software, bias was estimated by funnel plotting, and sources of heterogeneity were evaluated by subgroup and sensitivity examinations. Results: 18 randomized controlled trials were totally included to compare the single-group ratio and 95% confidence interval of nine constitution types of lung cancer, namely, mild constitution (ES = 0.12, 95% CI (0.08, 0.15), P < 0.0001), Qi deficiency constitution (ES = 0.20, 95% CI (0.15, 0.26), P < 0.0001), Qi depression constitution (ES = 0.09, 95% CI (0.07, 0.12), P < 0.0001), damp-heat constitution (ES = 0.05, 95% CI (0.03, -0.06), P < 0.0001), phlegm dampness constitution (ES = 0.05, 95% CI (0.03, -0.06), P < 0.0001), special constitution (ES = 0.01, 95% CI (0.01, 0.02), P=0.993), blood stasis constitution (ES = 0.05, 95% CI (0.04, 0.07), P < 0.0001), Yang deficiency constitution (ES = 0.16, 95% CI (0.12, 0.19), P < 0.0001), and Yin deficiency constitution (MD = 0.15, 95% CI (0.11, 0.18), P < 0.0001). Conclusion: This study showed that Qi deficiency, Yang deficiency, and Yin vacuity were the predominant types of physical conditions of lung cancer cases.

Effect of exogenous l-aspartate nano­calcium on root growth, calcium forms and cell wall metabolism of Brassica napus L.

Currently, l-aspartate nano­calcium (Ca(L-asp)-NPs) has been sued as a calcium supplement for humans, but its effects on plants are not well elucidated. This study aimed to investigate the effect of exogenous Ca(L-asp)-NPs on the growth of rapeseed (Brassica napus L.) for the first time. Different concentrations (0, 50, 100, 150, and 200 mg L-1) of Ca(L-asp)-NPs and 1.18 g L-1 Ca(NO3)2 were used in the nutrient solution. The results indicated that Ca2+ released from Ca(L-asp)-NPs were absorbed by the roots, and had a significant effect on plant height, root length, biomass accumulation, and root structure formation, especially on the growth and development of coarse roots at 100 mg L-1 Ca(L-asp)-NPs. Calcium (Ca) accumulation, Ca-pectinate, Ca-phosphate and Ca­carbonate, and Ca-oxalate in plant roots and leaves were positively linked with Ca(L-asp)-NPs concentration. For cell wall, Ca(L-asp)-NPs treatment increased the content of pectin, and the activity of cell wall degrading enzymes in roots, such as pectin methyl-esterase (PME), cellulose enzyme (CE), polygalacturonase (PG), and ß-galactosidase (ß-Gal). For cell membrane osmotic regulation, Ca(L-asp)-NPs promoted the accumulation of soluble sugar and soluble protein. This finding suggests that 100 mg L-1 Ca(L-asp)-NPs had the best growth-promoting effect on rapeseed. This study provides a valuable reference for exogenous Ca(L-asp)-NPs as new nano Ca supplements for plant growth.

Effects of Elephantopus scaber extract on growth, proximate composition, immunity, intestinal microbiota and resistance of the GIFT strain of Nile tilapia Oreochromis niloticus to Streptococcus agalactiae.

This study aimed to investigate the effects of Elephantopus scaber extract on the GIFT (genetic improvement of farmed tilapia) strain of Nile tilapia Oreochromis niloticus. A total of 800 tilapia with an initial body weight of 1.34 ± 0.09 g each were randomly divided into five groups. The tilapia in the control group (E0 group) were fed on a basal diet only. Meanwhile, tilapia in the four experimental groups were fed on a basal diet supplemented with 1 g/kg (E1 group), 3 g/kg (E2 group), 5 g/kg (E3 group), and 7 g/kg (E4 group) of E. scaber extract for 10 weeks. Results showed that the survival rate was higher in the experimental groups than in the control group. Compared with the control group, some growth parameters (FW, WGR, SGR, VSI, and HSI) were significantly improved in the E1 group and E2 group. The crude lipid content in the dorsal muscle and liver was lower in the E1 group than in the control group. After E. scaber extract supplementation, activities of immunity-related enzymes (ACP, AKP, T-AOC, SOD, CAT, GSH-Px and LZM) in plasma, liver, spleen and head kidney, and expressions of immunity-related genes (IL-1ß, IFN-γ, TNF-α, and CCL-3) in liver, spleen and head kidney showed various degrees of improvement, while MDA content and Hsp70 expression level were decreased. The survival rate of tilapia increased in all the supplementation groups after Streptococcus agalactiae treatment. E. scaber extract addition changed the species composition, abundance, and diversity of intestinal microbiota in tilapia. These results demonstrate that E. scaber extract supplementation in diet can improve the growth, immunity, and disease resistance of GIFT against S. agalactiae. E. scaber extract supplementation can also change intestinal microbiota and reduce crude lipid content in dorsal muscle and liver. The above indicators show that the optimal dose of E. scaber extract for GIFT is 1 g/kg.

Naringin Alleviates H2O2-Inhibited Osteogenic Differentiation of Human Adipose-Derived Stromal Cells via Wnt/ß-Catenin Signaling.

Osteoporosis is an age-related systemic bone disease that places a heavy burden on patients and society. In this study, we aimed to investigate the effects of naringin (NAR) on the osteogenic differentiation of human adipose-derived stromal cells (ADSCs). The results demonstrated that NAR pretreatment effectively abated H2O2-induced cell death and ROS accumulation in ADSCs undergoing osteogenic differentiation (ADSCs-OD). In addition, we also observed that the impaired extracellular matrix mineralization and ALP activity in H2O2-stimulated ADSCs-OD were notably rescued by NAR pretreatment. Moreover, the effects of H2O2 exposure on Wnt/ß-catenin signaling in ADSCs-OD were largely reversed by NAR pretreatment. Collectively, our findings indicated that NAR could protect ADSCs-OD against H2O2-inhibited osteogenic differentiation.