Structure and dynamics of microbial communities associated with the resurrection plant Boea hygrometrica in response to drought stress.

MAIN CONCLUSION: The resurrection plant Boea hygrometrica selectively recruits and assembles drought-specific microbial communities across the plant-soil compartments, which may benefit plant growth and fitness under extreme drought conditions. Plant-associated microbes are essential for facilitating plant growth and fitness under drought stress. The resurrection plant Boea hygrometrica in natural habitats with seasonal rainfall can survive rapid desiccation, yet their interaction with microbiomes under drought conditions remains unexplored. This study examined the bacterial and fungal microbiome structure and drought response across plant-soil compartments of B. hygrometrica by high-throughput amplicon sequencing of 16S rRNA gene and internal transcribed spacer. Our results demonstrated that the diversity, composition, and functional profile of the microbial community varied considerably across the plant-soil compartments and were strongly affected by drought stress. Bacterial and fungal diversity was significantly reduced from soil to endosphere and belowground to aboveground compartments. The compartment-specific enrichment of the dominant bacteria phylum Cyanobacteriota and genus Methylorubrum in leaf endosphere, genera Pseudonocardia in rhizosphere soil and Actinoplanes in root endosphere, and fungal phylum Ascomycota in the aboveground compartments and genera Knufia in root endosphere and Cladosporium in leaf endosphere composed part of the core microbiota with corresponding enrichment of beneficial functions for plant growth and fitness. Moreover, the recruitment of dominant microbial genera Sphingosinicella and Plectosphaerella, Ceratobasidiaceae mycorrhizal fungi, and numerous plant growth-promoting bacteria involving nutrient supply and auxin regulation was observed in desiccated B. hygrometrica plants. Our results suggest that the stable assembled drought-specific microbial community of B. hygrometrica may contribute to plant survival under extreme environments and provide valuable microbial resources for the microbe-mediated drought tolerance enhancement in crops.

RGD-p21Ras-scFv expressed prokaryotically on a pilot scale inhibits ras-driven colorectal cancer growth by blocking p21Ras-GTP.

BACKGROUND: Ras gene mutation and/or overexpression are drivers in the progression of cancers, including colorectal cancer. Blocking the Ras signaling has become a significant strategy for cancer therapy. Previously, we constructed a recombinant scFv, RGD-p21Ras-scFv by linking RGD membrane-penetrating peptide gene with the anti-p21Ras scFv gene. Here, we expressed prokaryotically RGD-p21Ras-scFv on a pilot scale, then investigated the anti-tumor effect and the mechanism of blocking Ras signaling. METHODS: The E. coli bacteria which could highly express RGD-p21Ras-scFv was screened and grown in 100 L fermentation tank to produce RGD-p21Ras-scFv on optimized induced expression conditions. The scFv was purified from E. coli bacteria using His Ni-NTA column. ELISA was adopted to test the immunoreactivity of RGD-p21Ras-scFv against p21Ras proteins, and the IC50 of RGD-p21Ras-scFv was analyzed by CCK-8. Immunofluorescence colocalization and pull-down assays were used to determine the localization and binding between RGD-p21Ras-scFv and p21Ras. The interaction forces between RGD-p21Ras-scFv and p21Ras after binding were analyzed by molecular docking, and the stability after binding was determined by molecular dynamics simulations. p21Ras-GTP interaction was detected by Ras pull-down. Changes in the MEK-ERK /PI3K-AKT signaling paths downstream of Ras were detected by WB assays. The anti-tumor activity of RGD-p21Ras-scFv was investigated by nude mouse xenograft models. RESULTS: The technique of RGD-p21Ras-scFv expression on a pilot scale was established. The wet weight of the harvested bacteria was 31.064 g/L, and 31.6 mg RGD-p21Ras-scFv was obtained from 1 L of bacterial medium. The purity of the recombinant antibody was above 85%, we found that the prepared on a pilot scale RGD-p21Ras-scFv could penetrate the cell membrane of colon cancer cells and bind to p21Ras, then led to reduce of p21Ras-GTP (active p21Ras). The phosphorylation of downstream effectors MEK-ERK /PI3K-AKT was downregulated. In vivo antitumor activity assays showed that the RGD-p21Ras-scFv inhibited the proliferation of colorectal cancer cell lines. CONCLUSION: RGD-p21Ras-scFv prokaryotic expressed on pilot-scale could inhibited Ras-driven colorectal cancer growth by partially blocking p21Ras-GTP and might be able to be a hidden therapeutic antibody for treating RAS-driven tumors.

Nitrogen-rich Ce-N compounds under high pressure.

Four high-pressure N-rich compounds (Pmn21-CeN7, Amm2-CeN9, P1̄-CeN10, and P1̄-II-CeN10) are proposed using first-principles calculations. Novel polymeric units (a heart shaped layered structure, chain-like N8 rings, and two new banded structures) in four cerium nitrides are reported for the first time in this study. The analyses of electronic structures and bonding properties show that the charge transfer between Ce and N atoms promotes the formation of the Ce-N ionic bond and N-N covalent bond, which play an important role in stabilizing the nitrogen skeleton. Four new phases possess high energy densities (3.24-3.86 kJ g-1), indicating that they are favorable high-energy density materials. Moreover, P1̄-CeN10 possesses ultra-incompressibility along the [1 0 0] direction. Finally, infrared and Raman spectra are analyzed to provide guidance for experimental synthesis.

Prognostic value of systemic immune-inflammation index and monocyte-to-HDL-cholesterol ratio in early cardio-cerebral complications in elderly patients with acute severe carbon monoxide poisoning.

To investigate how effectively systemic immune-inflammation index (SII) and Monocyte-to-HDL-cholesterol ratio (MHR) predict the development of early cardio-cerebral complications in elderly patients who have experienced acute severe carbon monoxide poisoning (ASCMP). A retrospective analysis was conducted on 77 elderly patients with ASCMP admitted to the emergency department of Harrison International Peace Hospital from November 2020 to March 2022. The prevalence of early-onset complications among the 77 individuals was 38.96%. Binary Logistics regression analysis showed that SII and MHR were independent influencing factors of early cardio-cerebral complications in elderly patients with ASCMP. The complication group had a longer length of stay, a greater mortality rate, and a higher incidence of delayed encephalopathy after acute carbon monoxide poisoning (p < .05) than the non-complication group. The area under the curve (AUC) of SII and MHR in predicting early cardio-cerebral complications in elderly patients with ASCMP were 0.724 and 0.796, respectively, with 80.0% and 63.3% sensitivity, and 61.7% and 87.2% specificity. The incidence of early cardio-cerebral complications in elderly patients who had ASCMP is high and the prognosis is poor. SII and MHR can be utilized as independent predictors of early cardio-cerebral complications in elderly patients with ASCMP, allowing doctors to diagnose and treat cardio-cerebral complications earlier and improve prognosis.

Linggui Zhugan Decoction Improves High Glucose-Induced Autophagy in Podocytes.

Objective To explore the influence of Linggui Zhugan Decoction (LGZGD) on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg-1 (low dose), 8.4 g·kg-1 (medium dose), and 12.6 g·kg-1 (high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Podocytes, MPC5 and AB8.13, were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry,, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the best effect. Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate (P < 0.05) and higher survival rate (P > 0.05) compared to the high dose group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2. High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes (P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3Ⅱ/Ⅰ, and P62 expressions were increased in MPC5 cells treated with high glucose, and reversed after adminstration of low and medium doses of LGZGD (P < 0.05). Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.

[Comparison of multi-type chemical compounds in fruits of Lycium and correlations between compounds and traits].

To comprehensively reveal and utilize the plant resources of Lycium in China, this study determined and compared the content of monosaccharides, polysaccharides, proteins, carotenoids, organic acids, and phenols in the dried fruits of 8 different Lycium species. Furthermore, the traits including the hundred-fruit weight, shape index, and the ratio of seed to fruit were measured, and the correlations between the content of chemical compounds and fruit traits were assessed. The results showed that L. truncatum, L. barbarum var. auranticarpum, and L. dasystemum var. rubricaulium were the species with high content of monosaccharides. L. barbarum and L. barbarum var. auranticarpum were the species with high content of total polysaccharides, and L. barbarum was the species with high content of carotenoids. L. yunnanense and L. chinense var. potaninii had high content of soluble proteins. L. truncatum, L. dasystemum, and L. barbarum showed high content of organic acids and phenols. L. barbarum and L. barbarum var. auranticarpum demonstrated high fruit weight, while L. yunnanense and L. chinense had high ratios of seed to fruit. The multivariate statistical analysis indicated that polysaccharides, carotenoids, hundred-fruit weight, ratio of seed to fruit, scopolamine, fructose, 5-O-feruloylquinic acid, kaempferol-3-O-rutinoside, scopoletin, cryptochlorogenic acid, and caffeic acid were the main differential compounds in the fruits among different species of Lycium. Moreover, the results of correlation ananysis showed strong correlations between fruit traits and compound content. Specifically, the hundred-fruit weight had positive correlations with the content of total polysaccharides and scopola-mine. The ratio of seed to fruit was negatively correlated with the content of rutin, kaempferol-3-O-rutinoside, fructose, and glucose and positively correlated with the content of succinic acid, soluble proteins, and zeaxanthin. The results implied that chemical compounds presented different distribution patterns in the fruits of 8 Lycium species. This study provides a basis for the comprehensive development and utilization, targeted breeding, and value-added application of Lycium plants.

[Effect of 2-phenylethyl-beta-glucopyranoside isolated from Huaizhong No. 1 Rehmannia glutinosa on hypoxic pulmonary hypertension by regulating PI3K/Akt/m TOR/HIF-1α pathway].

The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.

Influence of Gut Microbiota and its Metabolites on Progression of Metabolic Associated Fatty Liver Disease.

Metabolic associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes. Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD. Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms, identify diagnostic markers, and develop drugs or probiotics for the treatment of MAFLD. Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.

[Effect and mechanism of Poria cocos polysaccharides on myocardial cell apoptosis in rats with myocardial ischemia-reperfusion injury by regulating Rho-ROCK signaling pathway].

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1ß(IL-1ß) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1ß and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1ß and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.

Solanesol alleviates CFA-induced chronic inflammatory pain via inhibition of proinflammatory cytokines in spinal glial cells.

Solanesol, an aliphatic terpene alcohol predominantly found in solanaceous plants, has gained recognition for its anti-inflammatory, antibacterial, and neuroprotective properties. This study investigates the potential efficacy of solanesol in alleviating chronic inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into the left hind paw. Behavioral assessments revealed a significant reduction in mechanical and thermal hypersensitivity following solanesol administration, accompanied by a partial alleviation of concomitant anxiety-like behaviors. Mechanistically, Western blot analysis demonstrated a substantial decrease in the levels of TNF-α and IL-1ß after solanesol administration. Immunohistochemical staining further revealed a notable suppression of microglial and astrocytic activation induced by CFA injection. These findings collectively suggest that solanesol holds promise as a latent therapeutic agent for the treatment of chronic inflammatory pain.

Endometrial Elasticity is an Ultrasound Marker for Predicting Clinical Pregnancy Outcomes after Embryo Transfer.

Endometrial elasticity is a potential new marker for assessing endometrial receptivity and pregnancy outcomes based on endometrial thickness and type. Currently, little research has been conducted on the elasticity of the endometrium using shear wave elasticity imaging (SWEI). This study aimed to explore whether endometrial elasticity is an ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer. A total of 245 infertile women underwent ultrasonography before embryo transfer at the Peking University Third Hospital. We compared the endometrial elasticity and sub-endometrial blood flow rate using SWEI in the groups with different pregnancy outcomes. Trends in clinical pregnancy outcomes across the quartiles of endometrial elasticity in the fundus of the uterus (E1) were assessed. Logistic regression analysis was performed to obtain odds ratios for clinical pregnancy outcomes based on the quartiles of E1, with or without adjusting for potential confounding variables. Women in the clinical pregnancy group had higher E1 values and sub-endometrial blood flow rates in the uterine fundus than those in the non-pregnancy group. Women in the highest quartile of E1 had the most favorable clinical pregnancy rates. Endometrial elasticity measured using SWEI is a promising ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer.

Automated insulin delivery in children with type 1 diabetes during physical activity: a meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.

Three months use of Hybrid Closed Loop Systems improves glycated hemoglobin levels in adolescents and children with type 1 diabetes: A meta-analysis.

BACKGROUND: Longer outpatient studies have demonstrated that hybrid closed loop (HCL) use has led to a concomitant reduction in glycated hemoglobin(HbA1c) by 0.3%-0.7%. However, reports have also indicated that HbA1c levels are not declined in the long-term use of HCL. Therefore, we wonder that 3 months use of HCL could improve glycated hemoglobin levels in adolescents and children with T1D. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Pediatrics or Child or Adolescent", "Insulin Infusion Systems" and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of HCL on HbA1c in adolescents, and children with T1D. RESULTS: Nine studies involving 927 patients were identified. Three months use of HCL show a beneficial effect on HbA1c management (p <0.001) as compared to standard of care in adolescents and children with T1D, without evidence of heterogeneity between articles (I2 = 40%, p = 0.10). HCL did significantly increase the overall average percentage of hypoglycemic time between 70 and 180 mg/dL (TIR) (p <0.001; I2 = 51%). HCL did not show a beneficial effect on hypoglycemic time <70 mg/dL and <54 mg/dL (p >0.05). The overall percentage of hyperglycemic time was significantly decreased in HCL group compared to the control group when it was defined as >180 mg/dL (p <0.001; I2 = 83%), >250 mg/dL (p = 0.007, I2 = 86%) and >300 mg/dL (p = 0.005; I2 = 76%). The mean glucose level was significantly decreased by HCL (p <0.001; I2 = 58%), however, no significant difference was found in coefficient of variation of sensor glucose (p = 0.82; I2 = 71%) and daily insulin dose (p = 0.94; I2 <0.001) between the HCL group and the control group. CONCLUSIONS: HCL had a beneficial effect on HbA1c management and TIR without increased hypoglycemic time as compared to standard of care in adolescents and children with T1D when therapy duration of HCL was not less than three months. TRIAL NUMBER AND REGISTRY URL: CRD42022367493; https://www.crd.york.ac.uk/PROSPERO, Principal investigator: Zhen-feng Zhou, Date of registration: October 30, 2022.

Bougie approach improves first-attempt success rate compared to stylet approach in patients with difficult airway needing endotracheal intubation: a meta-analysis.

INTRODUCTION: Bougies and stylets are widely acknowledged as effective tools for managing endotracheal intubation, uncertainties persist regarding the comparative efficacy and safety of bougie versus stylet approaches in endotracheal intubation. EVIDENCE ACQUISITION: A comprehensive electronic search was conducted on the Cochrane Library, PubMed, and Embase databases from inception to December 9, 2023, using the keywords "endotracheal intubation," "bougie," and "stylet." This meta-analysis aims to evaluate and compare the performance of bougies and stylets in patients undergoing endotracheal intubation. EVIDENCE SYNTHESIS: A total of 12 articles, encompassing 2534 participants, were included in this meta-analysis. The bougie approach did not exhibit superiority in first-attempt success rate (83.6% vs. 81.7%; OR, 1.06, 95% CI, 0.49 to 2.29; P=0.89) and total intubation success rate (99.3% vs. 97.6%; OR, 2.32, 95% CI, 0.44 to 12.34; P=0.32, I2>50%, P<0.001). However, in patients with difficult airways, the bougie approach demonstrated a superior first-attempt success rate compared to the stylet approach (93.8% vs. 76.4%; OR, 5.25, 95% CI, 2.74 to 10.05; P<0.001). There was no significant difference in complications between the bougie and stylet approaches (P>0.05). CONCLUSIONS: For patients with difficult airway characteristics, our recommendation is to perform endotracheal intubation (ETI) using the bougie approach over the stylet approach, as it has been associated with a better first-attempt success rate. Notably, the advantages of using a bougie may be less pronounced for patients without signs of a difficult airway.

How mesenchymal stem cells transform into adipocytes: Overview of the current understanding of adipogenic differentiation.

Mesenchymal stem cells (MSCs) are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts, chondrocytes and adipocytes. The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes, in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes. Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis. However, the mechanism underlying the adipogenic differentiation of MSCs is not fully understood. Here, the current knowledge of adipogenic differentiation in MSCs is reviewed, focusing on signaling pathways, noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation. Finally, the relationship between maladipogenic differentiation and diseases is briefly discussed. We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Effect of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation on gastrointestinal reactions of malignant tumor patients undergoing chemotherapy. / éš”å§œç¸è”åˆæ¿é’ˆå¯¹æ¶æ€§è‚¿ç˜¤åŒ–ç–—æ‚£è€ èƒƒè‚ é“ååº”çš„å½±å“.

OBJECTIVES: To observe the efficacy and safety of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with malignant tumors. METHODS: Patients with malignant tumors and suffering from chemotherapy were randomly divided into control group (35 cases, 4 cases dropped off) and observation group (35 cases, 2 cases dropped off). The patients of the control group were treated by orally taking ondansetron hydrochloride tablets 8 mg/time, 3 times a day for 3 d, and those of the observation group treated by ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation of Zusanli(ST36), Neiguan(PC6), Tianshu(ST25), Zhongwan(CV12) and Guanyuan(CV4) once a day for a total of 3 d, based on the treatment of the control group. The patients' gastrointestinal reaction degree after the 1st , 2nd and the 3rd day of treatment were recorded. The Karnofsky performance status (KPS) score (0-100 points) was used for assessing the patients' quality of life. The TCM syndrome score (4 grades：no, mild, medium and severe, i.e. 0, 2, 4 and 6 points) was given according to the patients' severity of symptoms of spleen (stomach) qi deficiency (nausea and vomiting, abdominal distension after eating, belching, loss of appetite, weakness and laziness to speak, fatigue, and loose stool). The safety of the treatment was assessed by examining the patients' blood routine, liver function and kidney function, and the adverse reactions including blisters, allergies, burns and fainting during acupuncture treatment. RESULTS: After the 2nd and 3rd day of treatment, the patients conditions of vomiting and nausea in the observation group were significantly better than those of the control group (P<0.05). The TCM syndrome score and KPS score were significantly decreased in comparison with those of pre-treatment in both groups (P<0.05), and the TCM syndrome score was obviously lower in the observation group than in the control group (P<0.05). No significant differences were found between the two groups in the KPS score after the treatment , and in the levels of white blood cells (WBC), hemoglobin (HGB), platelets (PLT), absolute neutrophil count (ANC), alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine(Cr), and blood urea nitrogen (BUN). CONCLUSIONS: The use of ginger-partitioned moxibustion combined with ringheaded thumb-tack needle stimulation is safe for CINV patients, and can effectively relieve nausea and vomiting and alleviate digestive symptoms.

Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

Mice harboring the T316N variant in the GABAAR γ2 subunit exhibit sleep-related hypermotor epilepsy phenotypes and hypersynchronization in the thalamocortical pathway.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by seizures that predominantly occur during sleep. The pathogenesis of these seizures remains unclear. We previously detected rare variants in GABRG2, which encodes the γ2 subunit of γ-aminobutyric acid type A receptor (GABAAR), in patients with SHE and demonstrated that these variants impaired GABAAR function in vitro. However, the mechanisms by which GABRG2 variants contribute to seizure attacks during sleep remain unclear. METHODS: In this study, we designed a knock-in (KI) mouse expressing the mouse Gabrg2 T316N variant, corresponding to human GABRG2 T317N variant, using CRISPR/Cas9. Continuous video-electroencephalogram monitoring and in vivo multichannel electrophysiological recordings were performed to explore seizure susceptibility to pentylenetetrazol (PTZ), alterations in the sleep-wake cycle, spontaneous seizure patterns, and synchronized activity in the motor thalamic nuclei (MoTN) and secondary motor cortex (M2). Circadian variations in the expression of total, membrane-bound, and synaptic GABAAR subunits were also investigated. RESULTS: No obvious changes in gross morphology were detected in Gabrg2T316N/+ mice compared to their wild-type (Gabrg2+/+) littermates. Gabrg2T316N/+ mice share key phenotypes with patients, including sleep fragmentation and spontaneous seizures during sleep. Gabrg2T316N/+ mice showed increased susceptibility to PTZ-induced seizures and higher mortality after seizures. Synchronization of the local field potentials between the MoTN and M2 was abnormally enhanced in Gabrg2T316N/+ mice during light phase, when sleep dominates, accompanied by increased local activities in the MoTN and M2. Interestingly, in Gabrg2+/+ mice, GABAAR γ2 subunits showed a circadian increase on the neuronal membrane and synaptosomes in the transition from dark phase to light phase, which was absent in Gabrg2T316N/+ mice. CONCLUSION: We generated a new SHE mouse model and provided in vivo evidence that rare variants of GABRG2 contribute to seizure attacks during sleep in SHE.

Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway.

Introduction: Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated. Methods: CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured. Results: Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. Discussion: The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.

A New Strategy for Obesity Treatment: Revealing the Frontiers of Anti-obesity Medications.

Obesity dramatically increases the risk of type 2 diabetes, fatty liver, hypertension, cardiovascular disease, and cancer, causing both declines in quality of life and life expectancy, which is a serious worldwide epidemic. At present, more and more patients with obesity are choosing drug therapy. However, given the high failure rate, high cost, and long design and testing process for discovering and developing new anti-obesity drugs, drug repurposing could be an innovative method and opportunity to broaden and improve pharmacological tools in this context. Because different diseases share molecular pathways and targets in the cells, anti-obesity drugs discovered in other fields are a viable option for treating obesity. Recently, some drugs initially developed for other diseases, such as treating diabetes, tumors, depression, alcoholism, erectile dysfunction, and Parkinson's disease, have been found to exert potential anti-obesity effects, which provides another treatment prospect. In this review, we will discuss the potential benefits and barriers associated with these drugs being used as obesity medications by focusing on their mechanisms of action when treating obesity. This could be a viable strategy for treating obesity as a significant advance in human health.