[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.

Preparation and Characterization of Eugenol Incorporated Pullulan-Gelatin Based Edible Film of Pickering Emulsion and Its Application in Chilled Beef Preservation.

The purpose of this study was to develop a composite film composed of eugenol Pickering emulsion and pullulan-gelatin, and to evaluate its preservation effect on chilled beef. The prepared composite film was comprehensively evaluated in terms of the stability of emulsion, the physical properties of the film, and an analysis of freshness preservation for chilled beef. The emulsion size (296.0 ± 10.2 nm), polydispersity index (0.457 ± 0.039), and potential (20.1 ± 0.9 mV) proved the success of emulsion. At the same time, the films displayed good mechanical and barrier properties. The index of beef preservation also indicated that eugenol was a better active ingredient than clove essence oil, which led to the rise of potential of hydrogen, chroma and water content, and effectively inhibited microbial propagation, protein degradation and lipid oxidation. These results suggest that the prepared composites can be used as promising materials for chilled beef preservation.

Perinatal metabolic inflammation in the hypothalamus impairs the development of homeostatic feeding circuitry.

Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothalamus, specifically the arcuate nucleus (ARC), houses crucial neurons involved in regulating homeostatic feeding. These neurons include proopiomelanocortin (POMC) and agouti-related peptide (AGRP) secreting neurons. They play a vital role in sensing nutrients and metabolic hormones like insulin, leptin, and ghrelin. The neurogenesis of AGRP and POMC neurons completes at birth; however, axon development and synapse formation occur during the postnatal stages in rodents. Insulin, leptin, and ghrelin are the essential regulators of POMC and AGRP neurons. Maternal obesity and postnatal overfeeding or a high-fat diet (HFD) feeding cause metabolic inflammation, disrupted signaling of metabolic hormones, netrin-1, and neurogenic factors, neonatal obesity, and defective neuronal development in animal models; however, the mechanism is unclear. Within the hypothalamus and other brain areas, there exists a wide range of interconnected neuronal populations that regulate various aspects of feeding. However, this review aims to discuss how perinatal metabolic inflammation influences the development of POMC and AGRP neurons within the hypothalamus.

Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response.

Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

[Current situation of acupuncture and moxibustion patents in China and abroad].

The patents of acupuncture and moxibustion in China and abroad was analyzed, aiming to provide support for the innovative development of acupuncture industry. With the China Think Tank of Patent of Traditional Chinese Medicine and the PatSnap database as data sources, based on the mathematical statistics method, the application trend, legal status, patent types, transformation and distribution of major technical fields of acupuncture patents in China and abroad were analyzed. As a result, a total of 53,422 acupuncture patents were screened, involving 49 countries and 4 organizations. The patent types were mainly utility model patents. Although the application number of acupuncture patent had increased rapidly, the average patent conversion rate was generally low, approximately 4%. In the context of global economic integration, the acupuncture industry is developing at a high speed. It is suggested to take advantage of the "Belt and Road Initiative" to improve the international acceptance of acupuncture and moxibustion, adhere to the principle of attaching equal importance to the number and quality of patents, promote the in-depth cooperation of industry-university-research, and promote high-quality development of acupuncture and moxibustion.

Effects of dietary phosphorus deficiency on the growth performance, hepatic lipid metabolism, and antioxidant capacity of Yellow River Carp Cyprinus carpio haematopterus.

OBJECTIVE: The study aimed to evaluate the effects of phosphorus (P) deficiency in diets on growth performance, hepatic lipid metabolism, and antioxidant capacity in Yellow River Carp Cyprinus carpio haematopterus. METHODS: In this study, 72 healthy experimental fish (initial weight = 12.0 ± 0.1 g [mean ± SE]) were randomly selected and distributed to two groups, with three replicates in each group. The groups were fed either a P-sufficient diet or a P-deficient diet for 8 weeks. RESULT: The P-deficient feed significantly decreased the specific growth rate, feed efficiency, and condition factor of Yellow River Carp. Fish that were fed the P-deficient feed demonstrated higher contents of triglyceride, total cholesterol (T-CHO), and low-density lipoprotein cholesterol in the plasma and a higher T-CHO content in the liver compared to the P-sufficient diet group. In addition, the P-deficient diet significantly reduced the catalase activity level, decreased the glutathione content, and increased the malondialdehyde content in the liver and in the plasma. Furthermore, P deficiency in the diet significantly downregulated the messenger RNA expression of nuclear erythroid 2-related factor 2 and peroxisome proliferator-activated receptor α, whereas it upregulated the messenger RNA expression of tumor necrosis factor α and fatty acid synthase in the liver. CONCLUSION: Dietary P deficiency reduced fish growth performance, induced fat deposition and oxidative stress, and impaired liver health.

The transcribed centromeric gene OsMRPL15 is essential for pollen development in rice.

Centromeres consist of highly repetitive sequences that are challenging to map, clone, and sequence. Active genes exist in centromeric regions, but their biological functions are difficult to explore owing to extreme suppression of recombination in these regions. In this study, we used the CRISPR/Cas9 system to knock out the transcribed gene Mitochondrial Ribosomal Protein L15 (OsMRPL15), located in the centromeric region of rice (Oryza sativa) chromosome 8, resulting in gametophyte sterility. Osmrpl15 pollen was completely sterile, with abnormalities appearing at the tricellular stage including the absence of starch granules and disrupted mitochondrial structure. Loss of OsMRPL15 caused abnormal accumulation of mitoribosomal proteins and large subunit rRNA in pollen mitochondria. Moreover, the biosynthesis of several proteins in mitochondria was defective, and expression of mitochondrial genes was upregulated at the mRNA level. Osmrpl15 pollen contained smaller amounts of intermediates related to starch metabolism than wild-type pollen, while biosynthesis of several amino acids was upregulated, possibly to compensate for defective mitochondrial protein biosynthesis and initiate consumption of carbohydrates necessary for starch biosynthesis. These results provide further insight into how defects in mitoribosome development cause gametophyte male sterility.

Jintiange proteins promote osteogenesis and inhibit apoptosis of osteoblasts by enhancing autophagy via PI3K/AKT and ER stress pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiger bone, which had long been used in traditional Chinese medicine, had the action of removing wind and alleviating pain, strengthening the sinews and bones, and often used to treat bone impediment, and atrophic debility of bones in TCM clinical practice. As a substitute of natural bone tiger, artificial tiger bone Jintiange (JTG), has been approved by the State Food and Drug Administration of China for relief the symptom of osteoporosis, such as lumbago and back pain, lassitude in loin and legs, flaccidity and weakness legs, and walk with difficulty based on TCM theory. JTG has similar chemical profile to natural tiger bone, and contains mineral substance, peptides and proteins, and has been shown to protect bone loss in ovariectomized mice and exert the regulatory effects on osteoblast and osteoclast activities. But how the peptides and proteins in JTG modulate bone formation remains unclear. AIM: To investigate the stimulating effects of JTG proteins on osteogenesis and explore the possible underlying mechanisms. MATERIALS AND METHODS: JTG proteins were prepared from JTG Capsules by extracting calcium, phosphorus and other inorganic elements using SEP-PaktC18 desalting column. MC3T3-E1 cells were treated with JTG proteins to evaluate their effects and explore the underlying mechanisms. Osteoblast proliferation was detected by CCK-8 method. ALP activity was detected using a relevant assay kit, and bone mineralized nodules were stained with alizarin red-Tris-HCl solution. Cell apoptosis was analyzed by flow cytometry. Autophagy was observed by MDC staining, and autophagosomes were observed by TEM. Nuclear translocations of LC3 and CHOP were detected by immunofluorescence and observed under a laser confocal microscope. The expression of key proteins related to osteogenesis, apoptosis, autophagy and PI3K/AKT and ER stress pathways was analyzed by Western Blot analysis. RESULTS: JTG proteins improved osteogenesis as evidenced by the alteration of proliferation, differentiation and mineralization of MC3T3-E1 osteoblasts, inhibited their apoptosis, and enhanced autophagosome formation and autophagy. They also regulated the expression of key proteins of PI3K/AKT and ER stress pathways. In addition, PI3K/AKT and ER stress pathway inhibitors could reverse the regulatory effects of JTG proteins on osteogenesis, apoptosis, autophagy and PI3K/AKT and ER stress pathways. CONCLUSION: JTG proteins increased the osteogenesis and inhibited osteoblast apoptosis by enhancing autophagy via PI3K/AKT and ER stress signaling pathways.

A novel type lavandulyl flavonoid from Sophora flavescens as potential anti-hepatic injury agent that inhibit TLR2/NF-κB signaling pathway.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens, which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. AIM OF THE STUDY: This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl4)-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. MATERIALS AND METHODS: The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1ß (IL-1ß), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1ß and cyclooxygenase-2 (COX2) in hepatic tissues were detected. RESULTS: The lavandulyl flavonoid (kurarinol A, 1) and the EtOAc extract from S. flavescens showed protective effects on CCl4-injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What's more, we found that treatment with kurarinol A (1) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1ß in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1ß, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. CONCLUSION: These findings demonstrated that the novel compound (kurarinol A, 1) possessed notable hepatoprotective activity against CCl4. It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl4, and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.

Sambucus williamsii Hance maintains bone homeostasis in hyperglycemia-induced osteopenia by reversing oxidative stress via cGMP/PKG signal transduction.

BACKGROUND: Sambucus williamsii Hance (SWH) has effectively been adopted to treat joint and bone disorders. Diabetes-induced osteopenia (DOP) is caused primarily by impaired bone formation as a result of hyperglycemia. We had previously demonstrated that SWH extract accelerated fracture healing and promoted osteoblastic MC3T3-E1 cell proliferation and osteogenic differentiation. This study assessed the impacts of SWH extract on diabetes-induced bone loss and explored the mechanisms underlying its osteoprotective effects. METHODS: This work employed MC3T3-E1 cell line for evaluating how SWH extract affected osteogenesis, oxidative stress (OS), and the underlying mechanism in vitro. Streptozotocin-induced osteopenia mouse model was applied with the purpose of assessing SWH extract's osteoprotection on bone homeostasis in vivo. RESULTS: The increased OS of MC3T3-E1 cells exposed to high glucose (HG) was largely because of the upregulation of pro-oxidant genes and the downregulation of antioxidant genes, whereas SWH extract reduced the OS by modulating NADPH oxidase-4 and thioredoxin-related genes by activating cyclic guanosine monophosphate (cGMP) production and increasing the level of cGMP-mediated protein kinase G type-2 (PKG2). The oral administration of SWH extract maintained bone homeostasis in type 1 diabetes mellitus (T1DM) mice by enhancing osteogenesis while decreasing OS. In bones from hyperglycemia-induced osteopenia mice and HG-treated MC3T3-E1 cells, the SWH extract achieved the osteoprotective effects through activating the cGMP/PKG2 signaling pathway, upregulating the level of antioxidant genes, as well as downregulating the level of pro-oxidant genes. CONCLUSION: SWH extract exerts osteoprotective effects on hyperglycemia-induced osteopenia by reversing OS via cGMP/PKG signal transduction and is a potential therapy for DOP.

Constructing 3D flower-like LaFe bimetal oxides with abundant mesoporous and controllable active sites for high-efficient phosphorus removal: Synthesis, mechanism, and application.

The design of high-performance porous adsorbents for phosphorus removal is a persistently hot topic to maintain a sustainable aquatic ecosystem. In the present study, a self-templating strategy using LaFe cyanometallates (CMs) as precursors was adopted to prepare porous LaFe bimetal oxides with optimizable structure and composition for phosphate adsorption. The results showed that a high supplied LaIII/FeII ratio enabled an adequate coordination polymerization in the preparation of LaFe CM precursor and led to a striking three-dimensional (3D) structure of "twin lotus flower" with high coordinated water content, which resulted in a 3D flower-like LaFe oxide with high surface area and high porosity (mainly in mesopore). The LaFe oxide of LaFe15T possessing the optimal La/Fe ratio (1.5: 1) exhibited the most superior performance of phosphate adsorption, where La was confirmed to be the main active site for phosphate capture via ligand exchange mechanism. The batch and column tests of phosphate adsorption showed that the 3D flower-like LaFe oxides are effective adsorbents for phosphate removal. Therefore, the structure optimization in the template preparation stage is an effective strategy to design porous LaFe bimetal oxides as high-performance phosphorus removal materials.

Current situation of acupuncture and moxibustion patents in China and abroad / 中国针灸

The patents of acupuncture and moxibustion in China and abroad was analyzed, aiming to provide support for the innovative development of acupuncture industry. With the China Think Tank of Patent of Traditional Chinese Medicine and the PatSnap database as data sources, based on the mathematical statistics method, the application trend, legal status, patent types, transformation and distribution of major technical fields of acupuncture patents in China and abroad were analyzed. As a result, a total of 53,422 acupuncture patents were screened, involving 49 countries and 4 organizations. The patent types were mainly utility model patents. Although the application number of acupuncture patent had increased rapidly, the average patent conversion rate was generally low, approximately 4%. In the context of global economic integration, the acupuncture industry is developing at a high speed. It is suggested to take advantage of the "Belt and Road Initiative" to improve the international acceptance of acupuncture and moxibustion, adhere to the principle of attaching equal importance to the number and quality of patents, promote the in-depth cooperation of industry-university-research, and promote high-quality development of acupuncture and moxibustion.

Jin-Tian-Ge ameliorates ovariectomy-induced bone loss in rats and modulates osteoblastogenesis and osteoclastogenesis in vitro.

BACKGROUND: Tiger bone, which had been one of the most famous traditional Chinese medicine for 2000 years, was originate from the skeleton of Panthera tigris L., and had the actions of anti-inflammatory, analgesic, immune-regulatory and promoting healing of bone fracture, and was used for the treatment of osteoporosis and rheumatoid arthritis. Jin-Tian-Ge (JTG), the artificial tiger bone powder, were prepared from skeletons of several farmed animals to substitute the natural tiger bone, and has been used for the treatment of osteoporosis in clinical practice. However, the characteristic and mechanism of action of JTG for the therapy of osteoporosis need to be further evidenced by using modern pharmacological methods. The aim of this work is to investigate the bone-protective effects of JTG, and explore the possible underlying mechanism. METHODS: Ovariectomy (OVX) rats were orally administrated JTG or estradiol valerate (EV) for 12 weeks. We investigated the pharmacodynamic effects of JTG on anti-bone loss in OVX rats, and also investigated the role of JTG in promoting osteogenesis and inhibiting osteoclast differentiation. RESULTS: JTG increased the bone mineral density (BMD), improved the bone microarchitecture and biomechanical properties in ovariectomized rast, whereas reversed the bone high turnover in OVX rats as evidenced by serum biochemical markers in OVX rats. JTG increased osteogenic differentiation of BMSCs in vitro, and up-regulated the expression of the key proteins of BMP and Wnt/ß-catenin pathways. JTG also inhibited the osteoclastogenesis of BMM as evidenced by the alteration of the TRAP activity, F-actin construction and the expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, Cathepsin K (Ctsk) and matrix metallopeptidase 9 (MMP9) of OCs induced with RANKL and LPS, reduced the expression and phosphorylation of NF-κB in OCs. CONCLUSIONS: JTG prevented bone loss in OVX rats and increased osteogenic differentiation of BMSCs through regulation of the BMP and Wnt/ß-catenin pathway, inhibited osteoclastogenesis by suppressing the NF-κB pathway, suggesting that JTG had the potentials for prevention and treatment of osteoporosis by modulating formation and differentiation of osteoblast and osteoclast.

Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3ß Pathway.

Monotropein (Mon) is a kind of iridoid glycoside plant secondary metabolite primarily present in some edible and medicinal plants. The aim of this study was to investigate the effect of Mon on lipopolysaccharide (LPS)-induced inflammatory bone loss in mice and osteoclasts (OCs) derived from bone marrow-derived macrophages (BMMs), and explore the mechanisms underlying the effect of Mon on LPS-induced osteoclastogenesis. It was found that Mon markedly attenuated deterioration of the bone micro-architecture, enhanced tissue mineral content (TMC) and bone volume/total volume (BV/TV), reduced structure model index (SMI) and trabecular separation/spacing (Tb.Sp) in the bone tissue and decreased the activities of tartrate resistant acid phosphatase-5b (TRACP-5b), receptor activator NF-κB (RANK), and receptor activator NF-κB ligand (RANKL) as well as the serum levels of interleukin 6 (IL-6) and interleukin 1ß (IL-1ß) in LPS-treated mice. In addition, Mon treatment reduced the number of TRAP positive OCs in the bone tissue of LPS-treated mice and also exerted a stronger inhibitory effect on formation, differentiation, and F-actin ring construction of OCs derived from BMMs. Mon significantly inhibited the expression of the nuclear factor of activated T-cells c1 (NFATc1) and the immediate early gene (C-Fos) and nuclear translocation of NFATc1 in LPS-treated OCs, thereby inhibiting the expression of matrix metalloproteinase-9 (MMP-9), cathepsin K (CtsK), and TRAP. Mon significantly inhibited the expression of TRAF6, phosphorylation of P65, and degradation of IKBα, thus inhibiting the activation of NF-κB pathway in LPS-induced inflammatory mice and OCs derived from BMMs, and also inhibited LPS-induced phosphorylation of protein kinase B (Akt) and Glycogen synthase kinase 3ß (GSK-3ß) in OCs derived from BMMs. In conclusion, these results suggested that Mon could effectively inhibit osteoclastogenesis both in vitro and in vivo and therefore may prove to be potential option for prevention and treatment of osteoclastic bone resorption-related diseases.

Combinations of scalp acupuncture location for the treatment of post-stroke hemiparesis: A systematic review and Apriori algorithm-based association rule analysis.

Background: Post-stroke hemiparesis strongly affects stroke patients' activities of daily living and health-related quality of life. Scalp acupuncture (SA) is reportedly beneficial for post-stroke hemiparesis. However, there is still no standard of SA for the treatment of post-stroke hemiparesis. Apriori algorithm-based association rule analysis is a kind of "if-then" rule-based machine learning method suitable for investigating the underlying rules of acupuncture point/location selections. This study aimed to investigate the core SA combinations for the treatment of post-stroke hemiparesis by using a systematic review and Apriori algorithm-based association rule analysis. Methods: We conducted a systematic review to include relevant randomized controlled trial (RCT) studies investigating the effects of SA treatment in treating patients with post-stroke hemiparesis, assessed by the Fugl-Meyer Assessment (FMA) score. We excluded studies using herbal medicine or manual acupuncture. Results: We extracted 33 SA locations from the 35 included RCT studies. The following SA styles were noted: International Standard Scalp Acupuncture (ISSA), WHO Standard Acupuncture Point Locations (SAPL), Zhu's style SA, Jiao's style SA, and Lin's style SA. Sixty-one association rules were investigated based on the integrated SA location data. Conclusions: SAPL_GV20 (Baihui), SAPL_GV24 (Shenting), ISSA_MS6_i (ISSA Anterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_MS7_i (ISSA Posterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_PR (ISSA Parietal region, comprised of ISSA_MS5, ISSA_MS6, ISSA_MS7, ISSA_MS8, and ISSA_MS9), and SAPL_Ex.HN3 (Yintang) can be considered the core SA location combination for the treatment of post-stroke hemiparesis. We recommend a core SA combination for further animal studies, clinical trials, and treatment strategies.

Thermoelectric Energy Micro Harvesters with Temperature Sensors Manufactured Utilizing the CMOS-MEMS Technique.

This study develops a TEMH (thermoelectric energy micro harvester) chip utilizing a commercial 0.18 µm CMOS (complementary metal oxide semiconductor) process. The chip contains a TEMH and temperature sensors. The TEMH is established using a series of 54 thermocouples. The use of the temperature sensors monitors the temperature of the thermocouples. One temperature sensor is set near the cold part of the thermocouples, and the other is set near the hot part of the thermocouples. The performance of the TEMH relies on the TD (temperature difference) at the CHP (cold and hot parts) of the thermocouples. The more the TD at the CHP of the thermocouples increases, the higher the output voltage and output power of the TEMH become. To obtain a higher TD, the cold part of the thermocouples is designed as a suspended structure and is combined with cooling sheets to increase heat dissipation. The cooling sheet is constructed of a stack of aluminum layers and is mounted above the cold part of the thermocouple. A finite element method software, ANSYS, is utilized to compute the temperature distribution of the TEMH. The TEMH requires a post-process to obtain the suspended thermocouple structure. The post-process utilizes an RIE (reactive ion etch) to etch the two sacrificial materials, which are silicon dioxide and silicon substrate. The results reveal that the structure of the thermocouples is completely suspended and does not show any injury. The measured results reveal that the output voltage of the TEMH is 32.5 mV when the TD between the CHP of the thermocouples is 4 K. The TEMH has a voltage factor of 8.93 mV/mm2K. When the TD between the CHP of the thermocouples is 4 K, the maximum output power of the TEMH is 4.67 nW. The TEMH has a power factor of 0.31 nW/mm2K2.

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress.

Objective: Calycosin is the main bioactive extract of Astragali Radix with anti-inflammation, antioxidant, and anticancer properties. Here, our study evaluated the protective effects and mechanisms of calycosin on intestinal mucosal barrier under gastrectomy. Methods: After receiving gastrectomy, the rats were administrated with 20 mg/kg, 40 mg/kg, or 80 mg/kg calycosin. Endotoxin, bacterial translocation, and intestinal bacterial flora were assayed. Intestinal injury was detected via hematoxylin and eosin staining. Tight junction indicators (occludin, claudin, and ZO-1) and apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3) were examined in intestinal tissues. Inflammatory indicators (IL-1ß, IL-6, and TNF-α) were examined in serum or intestinal specimens via ELISA. Apoptosis was assessed via TUNEL staining. IgA + B cells in intestinal tissues and sIgA in intestinal lumen were examined through immunohistochemistry and ELISA, respectively. Oxidative stress indicators (TSH, SOD, CAT, GSH-Px, and MDA) were also detected via ELISA. Results: Our results showed that calycosin administration decreased endotoxin levels in peripheral blood, intestine, and portal vein blood; lowered the bacterial translocation ratio; and regained the balance among intestinal bacterial flora (comprising bifidobacterium, lactic acid bacillus, enterobacter, enterococcus, aerobic bacteria, and anaerobic bacteria) in the rats with gastrectomy. After calycosin treatment, intestinal mucosal damage of the rats with gastrectomy was ameliorated, with the increase in expression of tight junction proteins. Additionally, calycosin reduced intestinal inflammation, apoptosis, secretion of sIgA, and oxidative stress in the rats with gastrectomy. Conclusion: Altogether, our findings demonstrate that calycosin may improve intestinal mucosal barrier function under gastrectomy via reducing bacterial translocation, inflammation, and oxidative stress.

Sensory and autonomic innervation of the local tissues at traditional acupuncture point locations GB14, ST2 and ST6.

OBJECTIVE: To visualize and compare the sensory and autonomic innervation of the local tissues at the sites of different traditional acupuncture points in the rat forehead and face by histochemical examination. METHODS: GB14 (Yangbai), ST2 (Sibai) and ST6 (Jiache) were selected as the representative traditional acupuncture points in this study, and the local tissues at these sites were dissected in rats after perfusion followed by double or triple fluorescent histochemical staining. Here, calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT) were used to label the sensory, sympathetic and parasympathetic nerve fibers, respectively. RESULTS: The CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers were simultaneously demonstrated in the local tissues at GB14, ST2 and ST6. Although the three kinds of nerve fibers ran in parallel or intermingled with each other, by the analysis from the view of three-dimensional reconstruction, it was clear that each of them distributed in an independent pattern to their corresponding target tissues including the blood vessels, hair follicles, arrector pili and subcutaneous muscles, as well as sebaceous glands. CONCLUSION: Our study demonstrated the sensory and autonomic innervation of the local tissues at GB14, ST2 and ST6, providing neurochemical evidence indicating that the CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers form a neural network at these point locations that may respond to acupuncture stimulation.

Uncontrollable bleeding after tooth extraction from asymptomatic mild hemophilia patients: two case reports.

BACKGROUND: Uncontrollable bleeding after tooth extraction usually occurs in patients with coagulation diseases, including hemophilia, von Willebrand's disease, vitamin K deficiency, platelet deficiency, and taking anticoagulant drugs. Hemophilia A is an X-linked recessive disorder caused by insufficiency of coagulation factor VIII. Mild hemophilia, defined by factor level between 0.05 and 0.40 IU/mL, is characterized by uncontrollable hemorrhage after trauma or invasive operations. Some mild hemophiliacs may remain undiagnosed until late adulthood. Therefore, surgical management of these patients may be relatively neglected. These case reports describe two uncontrollable bleeding patients with unknown mild hemophilia A after tooth extraction. CASE PRESENTATION: This paper reports 2 cases of persistent bleeding after tooth extraction under local anesthesia which could not be completely stopped by routine treatments. Both of them denied prior illness and injury, allergies, anticoagulant medication history, systemic and family illness. The APTT and other coagulation screening tests of the two patients before surgery were normal. Finally, they were diagnosed with mild hemophilia A via coagulation factor assays. The patients acquired complete hemostasis by receiving coagulation factor supplement therapy in hematologic department. CONCLUSION: Mild hemophilia is marked by subclinical, asymptomatic and even normal coagulation test results. The purpose of these case reports is to bring dental professionals' attention that APTT test alone cannot be used to exclude mild hemophilia, and provide reasonable evaluation and treatment procedures of bleeding patients after tooth extraction.