Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA-H19 Driven Wnt/ß-Catenin Signaling Regulatory Axis.

Objectives: Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods: The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results: In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/ß-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/ß-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/ß-catenin signaling through promoting H19 expression. Conclusion: Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/ß-catenin regulatory axis.

Multi-pathways-mediated mechanisms of selenite reduction and elemental selenium nanoparticles biogenesis in the yeast-like fungus Aureobasidium melanogenum I15.

Selenium (Se) plays a critical role in diverse biological processes and is widely used across manufacturing industries. However, the contamination of Se oxyanions also poses a major public health concern. Microbial transformation is a promising approach to detoxify Se oxyanions and produce elemental selenium nanoparticles (SeNPs) with versatile industrial potential. Yeast-like fungi are an important group of environmental microorganisms, but their mechanisms for Se oxyanions reduction remain unknown. In this study, we found that Aureobasidium melanogenum I15 can reduce 1.0 mM selenite by over 90% within 48 h and efficiently form intracellular or extracellular spherical SeNPs. Metabolomic and proteomic analyses disclosed that A. melanogenum I15 evolves a complicated selenite reduction mechanism involving multiple metabolic pathways, including the glutathione/glutathione reductase pathway, the thioredoxin/thioredoxin reductase pathway, the siderophore-mediated pathway, and multiple oxidoreductase-mediated pathways. This study provides the first report on the mechanism of selenite reduction and SeNPs biogenesis in yeast-like fungi and paves an alternative avenue for the bioremediation of selenite contamination and the production of functional organic selenium compounds.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves as a significant indicator of malignant tumor transformation. The Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer cells. Key enzymes involved in this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, and PKM2. Moreover, the expression of transcriptional regulatory factors and proteins, such as FOXM1, p53, NF-κB, HIF1α, and c-Myc, can also influence cancer progression. Furthermore, lncRNAs, miRNAs, and circular RNAs play a vital role in directly regulating the Warburg effect. Additionally, gene mutations, tumor microenvironment remodeling, and immune system interactions are closely associated with the Warburg effect. Notably, the development of drugs targeting the Warburg effect has exhibited promising potential in tumor treatment. This comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.

Opening-closing six-qi acupuncture combined with western medication for primary hypertension of liver yang hyperactivity:a randomized controlled trial. / "å¼€é˜–å ­æ°”é’ˆæ³•"è”åˆè¥¿è¯æ²»ç–—è‚é˜³ä¸Šäº¢åž‹åŽŸå‘æ€§é«˜è¡€åŽ‹ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of opening-closing six-qi acupuncture combined with western medication for primary hypertension of liver yang hyperactivity, and explore its action mechanism. METHODS: A total of 96 patients with primary hypertension of liver yang hyperactivity were randomly divided into an acupuncture group (48 cases) and a western medication group (48 cases, 2 cases eliminated, 1 case discontinued). The western medication group was given felodipine sustained-release tablets orally, 5 mg each time, once a day. The acupuncture group was treated with opening-closing six-qi acupuncture at tender points of shaoyang and yangming areas of the head on the basis of the western medication group, once every other day. A total of 4 weeks were required in both groups. The blood pressure before treatment and after 2, 4 weeks of treatment, the TCM syndrome score and serum levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), homocysteine (Hcy) before and after treatment were observed, and the clinical efficacy was evaluated in the two groups. RESULTS: After 2, 4 weeks of treatment, the systolic blood pressure(SBP)and diastolic blood pressure(DBP) in both groups were decreased compared with those before treatment(P<0.05)；except for DBP after 2 weeks of treatment, the SBP and DBP in the acupuncture group were lower than those in the western medication group(P<0.05). After treatment, the TCM syndrome scores and serum levels of hs-CRP, IL-6, Hcy were decreased compared with those before treatment in the two groups(P<0.05), those in the acupuncture group were lower than those in the western medication group(P<0.05).The total effective rate of the acupuncture group was 95.8% (46/48), which was higher than 73.3% (33/45) in the western medication group(P<0.05). CONCLUSIONS: Opening-closing six-qi acupuncture combined with western medication could lower blood pressure, improve symptoms in patients with primary hypertension of liver yang hyperactivity.Its mechanism may be related to down-regulation of inflammatory factors.

Research Progress in Traditional Applications, Phytochemistry, Pharmacology, and Safety Evaluation of Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR) belongs to the family Cynomoriaceae. It is a perennial succulent parasitic herb with a reddish-brown coloration, predominantly submerged in sand and lacking chlorophyll. Traditionally, it has been used in ethnic medicine to treat various diseases, such as gastric ulcers, indigestion, bowel movements, and improving sexual function. To comprehensively collect CSR data, extensive literature searches were conducted using medical, ecological, and scientific databases such as Google Scholar, PubMed, Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI). This article summarizes and categorizes research on the uses, phytochemical characteristics, pharmacological activities, and toxicity of ethnic medicine, with the aim of establishing a solid foundation and proposing new avenues for exploring and developing potential applications of CSR. So far, a total of 98 compounds have been isolated and identified from CSR, including flavonoids, terpenes, steroids, and other compounds. It is worth noting that flavonoids and polysaccharides have significant antioxidant and anti-inflammatory properties. In addition, these compounds also show good application prospects in anti-tumor, antioxidant, anti-aging, anti-fatigue, anti-diabetes, and other aspects. Although extensive progress has been made in the basic research of CSR, further research is still needed to enhance the understanding of its mechanism of action and explore more unknown compounds. Our review indicates that CSR has broad prospects and deserves further research.

The azole biocide climbazole induces oxidative stress, inflammation, and apoptosis in fish gut.

Climbazole is an azole biocide that has been widely used in formulations of personal care products. Climbazole can cause developmental toxicity and endocrine disruption as well as gut disturbance in aquatic organisms. However, the mechanisms behind gut toxicity induced by climbazole still remain largely unclear in fish. Here, we evaluate the gut effects by exposing grass carp (Ctenopharyngodon idella) to climbazole at levels ranging from 0.2 to 20 µg/L for 42 days by evaluating gene transcription and expression, biochemical analyses, correlation network analysis, and molecular docking. Results showed that climbazole exposure increased cyp1a mRNA expression and ROS level in the three treatment groups. Climbazole also inhibited Nrf2 and Keap1 transcripts as well as proteins, and suppressed the transcript levels of their subordinate antioxidant molecules (cat, sod, and ho-1), increasing oxidative stress. Additionally, climbazole enhanced NF-κB and iκBα transcripts and proteins, and the transcripts of NF-κB downstream pro-inflammatory factors (tnfα, and il-1ß/6/8), leading to inflammation. Climbazole increased pro-apoptosis-related genes (fadd, bad1, and caspase3), and decreased anti-apoptosis-associated genes (bcl2, and bcl-xl), suggesting a direct reaction to apoptosis. The molecular docking data showed that climbazole could form stable hydrogen bonds with CYP1A. Mechanistically, our findings suggested that climbazole can induce inflammation and oxidative stress through CYP450s/ROS/Nrf2/NF-κB pathways, resulting in cell apoptosis in the gut of grass carp.

Therapeutic potential of natural flavonoids in pulmonary arterial hypertension: A review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

Effects of Aloe Gel on Lactating Women with Nipple Trauma.

Background: To investigate the efficacy of aloe gel in reducing pain and promoting wound healing in postpartum women with nipple trauma. Method: There were 80 postpartum women who took part in this study having developed nipple trauma during breastfeeding in the obstetrics department of a tertiary grade A hospital in Suzhou from January to December 2021. Postpartum women with nipple trauma whose hospital bed numbers ranged between 15 and 33 were included in the test group, whereas those whose hospital bed numbers ranged between 35 and 53 were included in the control group. Both groups received health education and breastfeeding guidance. The control group applied lanolin cream to their nipple trauma, whereas the test group used aloe gel. We used a nipple trauma severity assessment table to determine the severity of nipple trauma in lactating women and a Visual Analogue Scale (VAS) to determine the level of nipple pain and referred to the Traditional Chinese Medicine Standard for Diagnosis and Therapeutic Efficacy for Diseases and Syndromes to determine the healing time of their wounds. Results: The test group scored 3.70 ± 1.24 and 1.65 ± 0.74 points on the VAS on the first and third days following the intervention, whereas the control group scored 4.30 ± 0.94 and 2.23 ± 1.07 points, respectively. It took 3.75 ± 1.08 days and 4.45 ± 1.15 days for the nipple pain to completely disappear in the test group and the control group, respectively. The healing period for nipple trauma was 5.28 ± 1.26 days for the test group and 6.03 ± 1.61 days for the control group. All of the aforementioned distinctions were statistically significant (p < 0.05). Conclusions: Aloe gel can significantly alleviate the pain associated with nipple trauma in lactating women, accelerate wound healing, and reduce the duration of nipple trauma.

The Application of Preoperative Computed Tomography Angiography and Color Ultrasound Assisted Lower Limb Perforator Flap Design in the Repair of Lower Limb Soft Tissue Defects.

Objective: The goal of this study was to explore the application effect of preoperative computed tomography (CT) angiography and color ultrasound-assisted design of lower limb perforator flaps in the repair of lower limb soft tissue defects. Repair of soft tissue defects in the lower limbs is a challenging surgical task, and accurate preoperative location of vascular structures and detailed design of the surgical plan are crucial to the success of the surgery. This study aims to improve the accuracy and effectiveness of lower limb perforator flap repair surgery by introducing CT angiography and color ultrasound technology. Methods: Sixty-four patients who underwent lower limb soft tissue defect repair with perforator flaps were enrolled at our hospital from February 2020 to February 2023. According to their admission time, they were divided into two groups: 32 patients admitted before June 31, 2022, were included in the control group, and preoperative color Doppler ultrasound was used to assist in designing the lower limb perforator flap; 32 patients admitted after June 31, 2022, were included in the study group, and preoperative CT angiography and color Doppler ultrasound were used to assist in designing the lower limb perforator flap. Specifically, we conducted detailed records and analyzes of patients' age distribution, gender ratio, and relevant medical history. This demographic information will help reveal whether there are differences in the effectiveness of preoperative CT angiography and color ultrasound-assisted lower extremity perforator flap design among different patient groups. By considering these key factors, we can more accurately assess the actual utility of new technologies in different patient groups and provide more specific guidance for clinical practice.The therapeutic effects of the two groups of patients were recorded. The differences between the preoperative CT angiography measurements and intraoperative actual measurements of the study group were compared. Clinical indicators, sensory function in the graft area, flap survival rate, flap complication rate, and donor area complication rate were compared between the two groups. The satisfaction of patients in the two groups with the recovery of the surgical area was also compared. Results: The treatment success rate of the study group was higher than that of the control group (P < .05). There was no significant difference in the preoperative CT angiography measurements (shallow branch localization, shallow branch starting diameter, shallow branch length, deep branch starting diameter) and intraoperative actual measurements of the study group (P > .05). The operation time and intraoperative blood loss of the study group were shorter than those of the control group (P < .05), and there was no significant difference in flap harvesting area and length of hospital stay between the two groups (P > .05). There was a difference in sensory function in the graft area between the two groups, with a higher proportion of S4 grade in the study group and better recovery compared to the control group (P < .05). There was no significant difference in satisfaction evaluation between the two groups (P > .05). Conclusion: Preoperative CT angiography and color ultrasound-assisted design of lower limb perforator flaps have shown significant clinical advantages in repairing lower limb soft tissue defects, improving treatment effects and surgical efficiency. In clinical practice, this technology is expected to reduce surgical complexity, shorten surgical time, reduce the risk of intraoperative bleeding, and achieve effective defect repair while maintaining or improving the patient's sensory function.However, there are some limitations to the study, such as the relatively small sample size and single-center nature. Future research can optimize the operation process of this technology, expand the scope of research, and explore its application in the repair of soft tissue defects caused by specific causes. This technology may provide more precise and effective options for personalized treatment, especially for patients who need to preserve more sensory function.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Natural compounds target programmed cell death (PCD) signaling mechanism to treat ulcerative colitis: a review.

Ulcerative colitis (UC) is a nonspecific inflammatory bowel disease characterized by abdominal pain, bloody diarrhea, weight loss, and colon shortening. However, UC is difficult to cure due to its high drug resistance rate and easy recurrence. Moreover, long-term inflammation and increased disease severity can lead to the development of colon cancer in some patients. Programmed cell death (PCD) is a gene-regulated cell death process that includes apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. PCD plays a crucial role in maintaining body homeostasis and the development of organs and tissues. Abnormal PCD signaling is observed in the pathological process of UC, such as activating the apoptosis signaling pathway to promote the progression of UC. Targeting PCD may be a therapeutic strategy, and natural compounds have shown great potential in modulating key targets of PCD to treat UC. For instance, baicalin can regulate cell apoptosis to alleviate inflammatory infiltration and pathological damage. This review focuses on the specific expression of PCD and its interaction with multiple signaling pathways, such as NF-κB, Nrf2, MAPK, JAK/STAT, PI3K/AKT, NLRP3, GPX4, Bcl-2, etc., to elucidate the role of natural compounds in targeting PCD for the treatment of UC. This review used (ulcerative colitis) (programmed cell death) and (natural products) as keywords to search the related studies in PubMed and the Web of Science, and CNKI database of the past 10 years. This work retrieved 72 studies (65 from the past 5 years and 7 from the past 10 years), which aims to provide new treatment strategies for UC patients and serves as a foundation for the development of new drugs.

Identification of candidate genes and residues for improving nitrogen use efficiency in the N-sensitive medicinal plant Panax notoginseng.

BACKGROUND: Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. RESULTS: Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. CONCLUSIONS: N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration.

Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(l-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.

Sinapine targeting PLCß3 EF hands disrupts Gαq-PLCß3 interaction and ameliorates cardiovascular diseases.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCß3 axis acting as a core node of RAAS. PLCß3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development. PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCß3 axis and its molecular mechanism. STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCß3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms. METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods. RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCß3. The underlying mechanism for blocking the Gαq-PLCß3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCß3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system. CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCß3 interaction blockade by targeting the PLCß3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.

Research progress on the structure, derivatives, pharmacological activity, and drug carrier capacity of Chinese yam polysaccharides: A review.

Chinese yam is a traditional Chinese medicine that has a long history of medicinal and edible usage in China and is widely utilised in food, medicine, animal husbandry, and other industries. Chinese yam polysaccharides (CYPs) are among the main active components of Chinese yam. In recent decades, CYPs have received considerable attention because of their remarkable biological activities, such as immunomodulatory, antitumour, hypoglycaemic, hypolipidaemic, antioxidative, anti-inflammatory, and bacteriostatic effects. The structure and chemical alterations of polysaccharides are the main factors affecting their biological activities. CYPs are potential drug carriers owing to their excellent biodegradability and biocompatibility. There is a considerable amount of research on CYPs; however, a systematic summary is lacking. This review summarises the structural characteristics, derivative synthesis, biological activities, and their usage as drug carriers, providing a basis for future research, development, and application of CYPs.

Microplastics removal mechanisms in constructed wetlands and their impacts on nutrient (nitrogen, phosphorus and carbon) removal: A critical review.

Microplastics (MPs) are now prevalent in aquatic ecosystems, prompting the use of constructed wetlands (CWs) for remediation. However, the interaction between MPs and CWs, including removal efficiency, mechanisms, and impacts, remains a subject requiring significant investigation. This review investigates the removal of MPs in CWs and assesses their impact on the removal of carbon, nitrogen, and phosphorus. The analysis identifies crucial factors influencing the removal of MPs, with substrate particle size and CWs structure playing key roles. The review highlights substrate retention as the primary mechanism for MP removal. MPs hinder plant nitrogen uptake, microbial growth, community composition, and nitrogen-related enzymes, reducing nitrogen removal in CWs. For phosphorus and carbon removal, adverse effects of MPs on phosphorus elimination are observed, while their impact on carbon removal is minimal. Further research is needed to understand their influence fully. In summary, CWs are a promising option for treating MPs-contaminated wastewater, but the intricate relationship between MPs and CWs necessitates ongoing research to comprehend their dynamics and potential consequences.

Recent Progress Regarding Jasmonates in Tea Plants: Biosynthesis, Signaling, and Function in Stress Responses.

Tea plants have to adapt to frequently challenging environments due to their sessile lifestyle and perennial evergreen nature. Jasmonates regulate not only tea plants' responses to biotic stresses, including herbivore attack and pathogen infection, but also tolerance to abiotic stresses, such as extreme weather conditions and osmotic stress. In this review, we summarize recent progress about jasmonaic acid (JA) biosynthesis and signaling pathways, as well as the underlying mechanisms mediated by jasmontes in tea plants in responses to biotic stresses and abiotic stresses. This review provides a reference for future research on the JA signaling pathway in terms of its regulation against various stresses of tea plants. Due to the lack of a genetic transformation system, the JA pathway of tea plants is still in the preliminary stages. It is necessary to perform further efforts to identify new components involved in the JA regulatory pathway through the combination of genetic and biochemical methods.

Acupuncture for cervical dystonia associated with anxiety and depression: A case report.

BACKGROUND: Cervical dystonia (CD) is a type of muscle tone disorder that usually occurs in the neck muscles. Due to the intermittent or continuous involuntary contraction of the neck muscles, the head and neck are twisted and skewed and some postural abnormalities occur. Long-term abnormal posture or pain can cause negative emotions in patients, which can affect their quality of life. CASE SUMMARY: This case report included a 37-year-old woman who was diagnosed with CD associated with anxiety and depression; the accompanying symptoms were head and neck tilt of approximately 90° to the right and mental abnormality. After two courses of acupuncture treatment, the patient's head and neck can be maintained in a normal position, and the negative emotions can be relieved. CONCLUSION: This case indicates that acupuncture can effectively improve CD and the emotional state and quality of life of patients, making it an effective alternative treatment for the condition.