Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

Improving feed intake and rumen fermentation in lambs using mixed-dimensional attapulgite clay to adsorb naturally occurring mycotoxins.

This experiment was conducted to evaluate the effects of including a mixed-dimensional attapulgite clay (MDA) into a naturally moldly diet for Hu lambs. Fifty male Hu lambs with similar initial body weight (28.24 ±â€…1.80 kg) were randomly allocated into five dietary treatments: a basal diet containing naturally occurring mycotoxins with 0, 0.5, 1.0, and 2.0 kg/t MDA, and basal diet with a commercial mycotoxin adsorbent Solis with montmorillonite as the major component at 1 kg/t. Both MDA and Solis increased average daily gain (ADG) and dry matter intake (DMI; P ≤ 0.004), and there was no difference in growth performance between MDA and Solis (P ≥ 0.26). The final body weight, DMI, and ADG were linearly increased with increasing MDA supplementation (P < 0.01). Lambs treated with both MDA and Solis demonstrated greater apparent digestibility of dry matter (DM), organic matter (OM), and energy compared with the control group (P ≤ 0.03), and there were no differences in nutrient digestibilities between MDA and Solis (P ≥ 0.38). Digestibility of CP was linearly increased with the increasing MDA supplementation (P = 0.01). Neither MDA nor Solis affected rumen total volatile fatty acid (TVFA) concentration (P ≥ 0.39), but decreased the acetate-to-propionate ratio and molar proportion of n-butyrate (P ≤ 0.01), and MDA also increased the concentration of ammonia (P = 0.003). Besides, increasing MDA supplementation linearly reduced the acetate-to-propionate ratio and molar proportion of n-butyrate (P = 0.01), but linearly and quadratically increased the concentration of ammonia (P ≥ 0.003). These results showed that the incorporation of MDA into a naturally moldy diet of Hu lambs yielded comparable results to the Solis product, with higher growth performance and nutrient digestibility but lower acetate-to-propionate ratio observed. In conclusion, including ≥ 1 kg/t of MDA in high mycotoxin risk diets for growing lambs improves feed intake and rumen fermentation.

The issue of mycotoxin-contaminated animal feed has consistently presented a significant challenge in relation to animal health and production. The mixed-dimensional attapulgite clay (MDA) has been proven effective in binding polar mycotoxins such as aflatoxin, while also effectively adsorbing hydrophobic or weakly polar mycotoxins such as zearalenone (ZEN) and ochratoxin. Therefore, this study was undertaken to assess the impact of MDA inclusion in mycotoxin-contaminated diets on performance and rumen fermentation variables in lambs. The results indicated that MDA not only significantly improved the growth performance and nutrient digestibility of Hu lambs but also enhanced the molar proportion of propionate and ammonia concentration, and reduced the acetate to propionate ratio and the molar proportion of n-butyrate.

Post-discharge Follow-up of Standardized Management for Patients with Post-stroke Cognitive Impairment.

Context: Severe cases of stroke can lead to cognitive impairment or even dementia. The most critical factor related to cognitive impairment after strokes is patients' lack of understanding about or attention to their conditions. Strengthening standardized management post-stroke has become a common goal for clinical workers and patients. Objective: The study intended to explore, during post-discharge follow-up, the effectiveness of standardized management of patients with post-stroke cognitive impairment, which could provide guidance for patients and doctors to improve patients' follow-up plans. Design: The research team conducted a randomized controlled trial. Setting: The study took place at Huangshi Central Hospital, an Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, in Huangshi, Hubei, China. Participants: Participants were 112 patients with post-stroke cognitive impairment at the hospital between February 2021 and March 2023. Intervention: The research team randomly divided the participants into two groups, using a random-number-table method: (1) a control group with 56 participants who received routine management and (2) an intervention group with 56 participants who received standardized management. Outcome Measures: At baseline and 6 months postintervention, the research team measured participants': (1) cognitive function using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), (2) quality of life (QoL) using the World Health Organization Quality of Life-Bref (WHOQOL-BREF) questionnaire, and (3) self-efficacy using the General Self-Efficacy Scale (GSES). At one and 6 months postintervention, the team analyzed participants' medication adherence using the Morisky Medication Adherence Scale (MMAS-8). Results: At baseline, no significant difference (P > .05) existed between the groups in the scores: (1) for cognitive function on the MMSE or MoCA, (2) for the physiological, psychological, social, and environmental domains and the total score on the WHOQOL-BREF, or (3) for self-efficacy on the GSES scores. At 6 months postintervention, the intervention group's scores were significantly higher than those of the control group: (1) on the MMSE and MoCA (both P < .001), (2) on the four domains and total score on the WHOQOL-BREF (all P < .001), and (3) on the GSES (P < .001). At one month and six months postintervention, the intervention group's score for medication adherence on the MMAS-8 was significantly higher than those of the control group (both P < .001). Conclusions: Standardized management for patients with post-stroke cognitive impairment provided beneficial outcomes in improving their cognitive function, QoL, self-efficacy, and medication adherence, and the research team highly recommends it for wide application in clinical practice.

The Effect of Perioperative Comprehensive Nursing on Patients Undergoing Ovary Endometriosis Laparoscopic Surgery.

Objective: To assess the effectiveness of perioperative nursing interventions in improving outcomes and satisfaction for patients undergoing laparoscopic surgery for ovarian endometriosis. Methods: From July 2021 to September 2022, 80 patients with endometriosis underwent laparoscopic surgery at Shijiazhuang Fourth Hospital and were randomly assigned to the conventional (n=40) and experimental (n=40) groups. During the perioperative period, patients in the conventional group received standard nursing interventions, while patients in the experimental group received comprehensive nursing interventions. The two groups were compared in terms of postoperative clinical indicators, self-rated anxiety scale (SAS) and self-rated depression scale (SDS) scores, nursing compliance, complications, and nursing satisfaction. Results: comprehensive nursing resulted in better postoperative clinical indices (time to get out of bed, hospital stay) versus routine nursing (all P < .001). The comprehensive nursing led to significantly lower SAS and SDS scores versus routine nursing. The nursing compliance of the patients in the experimental group was significantly higher than that of the patients in the conventional group (P < .001). Comprehensive nursing was associated with a significantly lower incidence of complications versus routine nursing (P < .001). Comprehensive nursing contributed to significantly higher nursing satisfaction versus routine nursing (P < .001). Conclusion: Comprehensive perioperative nursing interventions for patients with ovarian endometriosis undergoing laparoscopic surgery considerably accelerate patient recovery and enhance nursing compliance, as well as minimize patient negative emotions and improve patient satisfaction with nursing.  The comprehensive approach addresses the specific needs of patients during the recovery period, minimizing postoperative complications, accelerating patient recovery, and improving overall quality of life. By integrating psychological support, tailored strategies for pain management, early mobilization, and prompt intervention for complications, this intervention sets a benchmark for holistic care in gynecological surgery.

The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

Trichoderma guizhouense NJAU4742 augments morphophysiological responses, nutrient availability and photosynthetic efficacy of ornamental Ilex verticillata.

Winterberry holly (Ilex verticillata [L.] A. Gray), a deciduous shrub producing glossy bright red berries, is a valuable ornamental and medicinal plant with good market prospects. However, the growth and development of I. verticillata are significantly affected by various stresses, and environmentally hazardous agrochemicals are often used to mitigate them. Trichoderma spp., ubiquitous soil-borne eco-friendly plant growth-promoting fungi, are potent biostimulants and biofertilizers and viable alternatives to agrochemicals for healthy and sustainable agriculture. In this study, the temporal efficacy of different dosages of the filamentous fungus Trichoderma guizhouense NJAU4742 in promoting morphophysiological responses of I. verticillata and the physicochemical properties and enzymatic activities of the substrate were investigated. Different concentrations of the strain T. guizhouense NJAU4742 spore suspension (C [0%], T1 [5%, v/m], T2 [10%, v/m] and T3 [15%, v/m]) were injected in the substrate contained in a pot in which 1-year-old I. verticillata was planted for temporal treatment (15, 45 and 75 days) under open-air conditions. The beneficial effects of T2 and/or T3 treatment for a long duration (75 days) were evident on the different root, aerial and photosynthetic traits; total contents of nitrogen (N), phosphorus (P) and potassium (K) in different tissues and the physicochemical properties of the substrate and its enzymatic activities (urease and invertase). Overall, the study revealed the potency of strain T. guizhouense NJAU4742 as a sustainable solution to improve the growth and development and ornamental value of I. verticillata.

Effects of manual lymphatic drainage on total knee replacement: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Total knee joint replacement (TKR) is an effective method for the treatment of severe knee osteoarthritis. With an increasing number of surgeries, complications such as lower limb edema, pain, and limited mobility have caused a heavy burden. Manual lymphatic drainage (MLD) may be a solution to solve the problem. The study aims to evaluate the efficacy of MLD in reducing knee edema, pain, and improving range of motion (ROM) in patients after TKR. METHODS: A search was conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIPs, WanFang database, and Google Scholar from inception to June 2023. Only randomized controlled trials (RCTs) that compared the effects of MLD and non-MLD (or another physiotherapy) on improving knee edema, pain, and ROM after TKR were included. Stata 16.0 was used for meta-analysis. GRADE was used to assess the quality of evidence. RESULTS: In total, 7 RCTs with 285 patients were identified. There were no significant differences found in the ROM of knee flexion (standardized mean difference (SMD) = 0.03, 95% confidence interval (CI): -0.22, 0.28, P = 0.812) and the ROM of knee extension (SMD= -0.30, 95%CI: -0.64, 0.04, P = 0.084). No differences were observed in the lower extremity circumference after TKR (SMD= -0.09, 95%CI: -0.27, 0.09, P = 0.324). For postoperative pain, there was no significant advantage between the MLD and non-MLD groups (SMD= -0.33, 95%CI: -0.71, 0.04, P = 0.083). CONCLUSIONS: Based on the current evidence from RCTs, manual lymphatic drainage is not recommended for the rehabilitation of patients following total knee replacement.

SLC12A3: A Novel Prognostic Biomarker of Clear Cell Renal Cell Carcinoma.

Objective: Clear renal cell carcinoma (ccRCC) is a common and deadly urinary system tumor. The TNM system determines treatment and prognosis based on cancer advancement. While nephron-sparing surgery is an option for localized ccRCC, advanced cases are challenging, and molecular-targeted therapy is crucial. Methods: Here, we implemented microarray datasets to identify a total of 119 differentially expressed genes (DEGs) and ten hub genes by a protein-protein interaction network (PPI) and performed module analysis through STRING and Cytoscape. Results: Data from this analysis shed light on a positive correlation between SLC12A3 (solute carrier family 12 member 3) and tumor-correlated cells. SLC12A3 can predict prognosis and immune infiltration levels in KIRC patients. Conclusion: Our findings demonstrated that SLC12A3 expression accounts for favorable prognosis and increased immune infiltration of various cell types. This could lead to potential therapeutic aims and biomarkers for KIRC (kidney renal clear cell carcinoma).

Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

Maternal exposure to 4-vinylcyclohexene diepoxide during pregnancy leads to disorder of gut microbiota and bile acid metabolism in offspring.

Our previous study reveals that maternal exposure to 4-vinylcyclohexene diepoxide (VCD) during pregnancy causes insufficient ovarian follicle reserve and decreased fertility in offspring. The present study aims to further explore the reasons for the significant decline of fecundity in mice caused by VCD, and to clarify the changes of gut microbiota and microbial metabolites in F1 mice. The ovarian metabolomics, gut microbiota and microbial metabolites were analyzed. The results of ovarian metabolomics analysis showed that maternal VCD exposure during pregnancy significantly reduced the concentration of carnitine in the ovaries of F1 mice, while supplementation with carnitine (isovalerylcarnitine and valerylcarnitine) significantly increased the number of ovulation. The results of 16 S rDNA-seq and microbial metabolites analysis showed that maternal VCD exposure during pregnancy caused disordered gut microbiota, increased abundance of Parabacteroides and Flexispira bacteria that are involved in secondary bile acid synthesis. The concentrations of NorDCA, LCA-3S, DCA and other secondary bile acids increased significantly. Our results indicate that maternal exposure to VCD during pregnancy leads to disorder in gut microbiota and bile acid metabolism in F1 mice, accompanying with decreased ovarian function, providing further evidence that maternal exposure to VCD during pregnancy has intergenerational deleterious effects on offspring.

Multilocus Distance-Regulated Sensor Array for Recognition of Polyphenols via Machine Learning and Indicator Displacement Assay.

Developing new strategies to construct sensor arrays that can effectively distinguish multiple natural components with similar structures in mixtures is an exceptionally challenging task. Here, we propose a new multilocus distance-modulated indicator displacement assay (IDA) strategy for constructing a sensor array, incorporating machine learning optimization to identify polyphenols. An 8-element array, comprising two fluorophores and their six dynamic covalent complexes (C1-C6) formed by pairing two fluorophores with three distinct distance-regulated quenchers, has been constructed. Polyphenols with diverse spatial arrangements and combinatorial forms compete with the fluorophores by forming pseudocycles with quenchers within the complexes, leading to varying degrees of fluorescence recovery. The array accurately and effectively distinguished four tea polyphenols and 16 tea varieties, thereby demonstrating the broad applicability of the multilocus distance-modulated IDA array in detecting polyhydroxy foods and natural medicines.

Naringenin prevents non-alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in MCD diet-fed mice.

Non-alcoholic steatohepatitis (NASH) is a severe inflammatory phase of the non-alcoholic fatty liver disease (NAFLD) spectrum and can progress to advanced stages of NAFLD if left untreated. This study uses multi-omics data to elucidate the underlying mechanism of naringenin's reported benefit in alleviating (NASH). Male mice were fed a NASH-inducing (methionine-choline-deficient) MCD diet with or without naringenin supplementation for 6 weeks. Naringenin prevented NASH-induced histopathological liver damage and reversed the abnormal levels of hepatic triglyceride (TG)/total cholesterol (TC), serum TG/TC, serum alanine aminotransferase/aspartate transaminase, and hepatic malondialdehyde and glutathione. Importantly, naringenin intervention significantly modulated the relative abundance of gut microbiota and the host metabolomic profile. We detected more than 700 metabolites in the serum and found that the gut genus levels of Anaeroplasma and the [Eubacterium] nodatum group were closely associated with xanthine, 2-picoline, and securinine, respectively. Tuzzerella alterations showed the highest number of associations with host endogenous metabolites such as FAHFA (8:0/10:0), FFA (20:2), carnitine C8:1, tridecanedioic acid, securinine, acetylvaline, DL-O-tyrosine, and Phe-Asn. This study indicates that the interplay between host serum metabolites and gut microbiota may contribute to the therapeutic effect of naringenin against NASH.

Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.

Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.

Genetically predicted plasma levels of amino acids and metabolic dysfunction-associated fatty liver disease risk: a Mendelian randomization study.

BACKGROUND: Emerging metabolomics-based studies suggested links between amino acid metabolism and metabolic dysfunction-associated fatty liver disease (MAFLD) risk; however, whether there exists an aetiological role of amino acid metabolism in MAFLD development remains unknown. The aim of the present study was to assess the causal relationship between circulating levels of amino acids and MAFLD risk. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) to evaluate the causal relationship between genetically predicted circulating levels of amino acids and the risk of MAFLD. In the discovery MR analysis, we used data from the largest MAFLD GWAS (8434 cases and 770,180 controls), while in the replication MR analysis, we used data from a GWAS on MAFLD (1483 cases and 17,781 controls) where MAFLD cases were diagnosed using liver biopsy. We used Wald ratios or inverse variance-weighted (IVW) methods in the MR main analysis and weighted median and MR-Egger regression analyses in sensitivity analyses. Furthermore, we performed a conservative MR analysis by restricting genetic instruments to those directly involved in amino acid metabolism pathways. RESULTS: We found that genetically predicted higher alanine (OR = 1.43, 95% CI 1.13-1.81) and lower glutamine (OR = 0.83, 95% CI 0.73-0.96) levels were associated with a higher risk of developing MAFLD based on the results from the MR main and conservative analysis. The results from MR sensitivity analyses and complementary analysis using liver proton density fat fraction as a continuous outcome proxying for MAFLD supported the main findings. CONCLUSIONS: Novel causal metabolites related to MAFLD development were uncovered through MR analysis, suggesting future potential for evaluating these metabolites as targets for MAFLD prevention or treatment.

Celastrol as an intestinal FXR inhibitor triggers tripolide-induced intestinal bleeding: Underlying mechanism of gastrointestinal injury induced by Tripterygium wilfordii.

BACKGROUND: Tripterygium wilfordii has been widely used for the treatment of rheumatoid arthritis, which is frequently accompanied by severe gastrointestinal damage. The molecular mechanism underlying the gastrointestinal injury of Tripterygium wilfordii are yet to be elucidated. METHODS: Transmission electron microscopy, and pathological and biochemical analyses were applied to assess intestinal bleeding. Metabolic changes in the serum and intestine were determined by metabolomics. In vivo (time-dependent effect and dose-response) and in vitro (double luciferase reporter gene system, DRATs, molecular docking, HepG2 cells and small intestinal organoids) studies were used to identify the inhibitory role of celastrol on intestinal farnesoid X receptor (FXR) signaling. Fxr-knockout mice and FXR inhibitors and agonists were used to evaluate the role of FXR in the intestinal bleeding induced by Tripterygium wilfordii. RESULTS: Co-treatment with triptolide + celastrol (from Tripterygium wilfordii) induced intestinal bleeding in mice. Metabolomic analysis indicated that celastrol suppressed intestinal FXR signaling, and further molecular studies revealed that celastrol was a novel intestinal FXR antagonist. In Fxr-knockout mice or the wild-type mice pre-treated with pharmacological inhibitors of FXR, triptolide alone could activate the duodenal JNK pathway and induce intestinal bleeding, which recapitulated the pathogenic features obtained by co-treatment with triptolide and celastrol. Lastly, intestinal bleeding induced by co-treatment with triptolide and celastrol could be effectively attenuated by the FXR or gut-restricted FXR agonist through downregulation of the duodenal JNK pathway. CONCLUSIONS: The synergistic effect between triptolide and celastrol contributed to the gastrointestinal injury induced by Tripterygium wilfordii via dysregulation of the FXR-JNK axis, suggesting that celastrol should be included in the quality standards system for evaluation of Tripterygium wilfordii preparations. Determining the mechanism of the FXR-JNK axis in intestinal bleeding could aid in the identification of additional therapeutic targets for the treatment of gastrointestinal hemorrhage diseases. This study also provides a new standard for the quality assessment of Tripterygium wilfordii used in the treatment of gastrointestinal disorders.

Acupressure in the treatment of patients with mild infection of COVID-19 omicron variant: A prospectively observational study.

During the coronavirus disease 2019 epidemic, acupressure has been widely used as a complementary treatment for coronavirus disease 2019 in China, but its safety and effectiveness have not been determined until now. This was a prospectively observational study containing 400 cases of mild infection of Omicron who were admitted to Chongming Flower Expo Makeshift Hospital from April 1, 2022 to May 1, 2022. Patients were assigned to receive basic treatment or a combination with acupressure treatment (5 minutes per acupoint, at least twice daily), from admission to discharge. The conversion time of viral RNA assay, the recovery time of symptoms and the clinical cure rate at day 7 were compared in 2 groups. All cases were included in the final analysis. The time to conversion of viral RNA assay (6 vs 7 days, P < .001) and time to symptom recovery (2 vs 4 days, P < .001) were markedly shortened in the acupressure treatment group compared to controls. The time to recovery from individual symptoms of coughing, a sore throat, a fever, fatigue, poor appetite, and insomnia were shorter in the treatment group compared to the control (all P < .05), but there was no statistical difference in reducing the recovery time from headache, muscle ache, anxiety, loss of taste between 2 groups (all P > .05). In addition, acupressure therapy also revealed a higher clinical cure rate at day 7 than basic treatment alone (91% vs 65%, P < .001) and reported no serious adverse events. This study provided evidence for acupressure therapy in treatment of Omicron infection concerning the viral load disappearance and the clinical symptoms improvements. Findings were expected to help guide efforts to position acupressure therapy as a therapeutic option for patients with Omicron variant.

Effect of controlling nitrogen and phosphorus release from sediment using a biological aluminum-based P-inactivation agent (BA-PIA).

A biological aluminum-based P-inactivation agent (BA-PIA) has been developed and demonstrated to effectively remove nitrogen and phosphorus; however, whether it can control the release of nitrogen and phosphorus in sediment still needs study. This study aimed to examine the effect of BA-PIA on controlling sediment nitrogen and phosphorus release. BA-PIA was prepared by artificial aeration. The use of BA-PIA in controlling nitrogen and phosphorus release was studied using water and sediment from a landscape lake in static simulation experiments. The sediment microbial community was analyzed using high-throughput sequencing. Static simulation showed that the reduction rates of total nitrogen (TN) and total phosphorus (TP) by BA-PIA were 66.8 ± 1.46% and 96.0 ± 0.98%, respectively. In addition, capping of BA-PIA promotes the conversion of easily released nitrogen (free nitrogen) in the sediment to stable nitrogen (acid-hydrolyzable nitrogen). The content of weakly adsorbed phosphorus and iron-adsorbed phosphorus in the sediment was reduced. The relative abundance of nitrifying bacteria, denitrifying bacteria, and microorganisms carrying phosphatase genes (such as Actinobacteria) in the sediment increased by 109.78%. The capping of BA-PIA not only effectively removed the nitrogen and phosphorus in water but greatly reduced the risk of nitrogen and phosphorus release from sediment. BA-PIA was able to make up for the deficiency of the aluminum-based phosphorus-locking agent (Al-PIA) that only removes phosphorus, giving it improved application prospects.

Facile and green fabrication of tumor- and mitochondria-targeted AIEgen-protein nanoparticles for imaging-guided photodynamic cancer therapy.

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12-14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor­ and mitochondria­targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens.

Exercise Rehabilitation and Chronic Respiratory Diseases: Effects, Mechanisms, and Therapeutic Benefits.

Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body's immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.

Maternal melatonin supplementation shapes gut microbiota and protects against inflammation in early life.

BACKGROUND: Gut microbiota colonization is critical for immune education and nutrient metabolism. Research shows that melatonin has beneficial effects as a therapy for many diseases via modulating gut dysbiosis. However, it is unclear whether melatonin alters gut microbiota colonization in early life. METHODS: In the experimental group (Mel), mice were intraperitoneally injected with melatonin at 10 mg/kg body weight for embryonic days 14-16 and received drinking water containing 0.4 mg/mL melatonin until 28 days postpartum. In the control group (Ctrl), mice were injected with the same volume of 2.5% ethanol in saline and provided with standard water. Two more groups were created by treating neonatal mice with 20 mg/kg lipopolysaccharide (LPS) to induce inflammation, resulting in the groups Ctrl + LPS and Mel + LPS, respectively. We examined the gut microbiota of the neonatal mice in the Ctrl and Mel group on Days 7, 14, 21, and 28 post-birth. On Day 14, melatonin and short-chain fatty acids (SCFAs) concentrations were measured in the Ctrl and Mel group and the mice were treated with LPS to be evaluated for intestinal injury and inflammatory response 15 h post treatment. According to the result of the SCFAs concentrations, some neonatal mice were intraperitoneally injected with 500 mg/kg sodium butyrate (SB) from Days 11-13, intraperitoneally injected with 20 mg/kg LPS on Day 14, and then euthanized by carbon dioxide inhalation the next morning. Intestinal injury and inflammatory responses were evaluated in the Ctrl + LPS and SB + LPS groups, respectively. RESULTS: By Day 14, it was evident that maternal melatonin supplementation significantly increased the relative abundance of Firmicutes in the ileal [61.03 (35.35 - 76.18) % vs. 98.02 (86.61 - 99.01) %, P = 0.003] and colonic [73.88 (69.77 - 85.99) % vs. 96.16 (94.57 - 96.34) %, P = 0.04] microbiota, the concentration of melatonin (0.79 ± 0.49 ng/ml vs. 6.11 ± 3.48 ng/ml, P = 0.008) in the gut lumen, and the fecal butyric acid (12.91 ± 5.74 µg/g vs. 23.58 ± 10.71 µg/g, P = 0.026) concentration of neonatal mice. Melatonin supplementation, and sodium butyrate treatment markedly alleviated intestinal injury and decreased inflammatory factors in neonatal mice. CONCLUSION: This study suggests that maternal melatonin supplementation can shape the gut microbiota and metabolism of offspring under normal physiological conditions and protect them against LPS-induced inflammation in early life.