GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Paternal genetic structure analysis of the modern Han populations based on Y-SNP and Y-STR.

The Han populations represent the largest ethnic group in China. Previous studies have primarily focused on investigating their genetic origins, migration and integration, as well as paternal genetic relationships within specific regional Han populations. However, a comprehensive analysis of the global paternal genetic structure of Han populations is lacking. In this study, we performed Y-chromosome sequencing on 362 unrelated male samples from Chinese Han individuals collected from Qinghai, Sichuan and Liaoning provinces. We then integrated relevant data from reported studies. Our final dataset comprised 1830 samples from 16 Han populations across 15 provinces in China, encompassing information on 89 Y-SNPs and 16 Y-STRs. Statistical analyses were conducted to assess Y-STR haplotype diversity (HD) and Y-SNP haplogroup frequencies. Additionally, we employed principal component analysis (PCA), phylogenetic tree and haplotype network to explore genetic differentiation within Han populations and the genetic relationships between Han populations and ethnic minorities surrounding them. Our results demonstrated that the O-M175 haplogroup represents the predominant paternal lineage in Han populations, with frequencies ranging from 60.53% (Qinghai Han) to 92.7% (Guangdong Han). Moreover, the subclades downstream of O-M175 showed distinct regional variations in their distribution patterns. The O2-M122 haplogroup was prevalent in all Han populations and demonstrated a gradual decline in frequency from north to south. Conversely, the distribution frequency of the O1b-M268 haplogroup decreased from south to north, particularly showed significant presence among Han populations in the Lingnan region. Haplogroup O1a-M119 distributed more frequently in the central Han populations. Our findings revealed that Chinese Han populations can be categorized into three subgroups: northern, central, and southern. Notably, there were significant differences among Han in Qinghai and other regions. Regarding the genetic relationships between Han populations and surrounding ethnic minorities, we observed a closer genetic affinity between different Han populations, but northern Han demonstrated a stronger relationship with the Hui ethnic group, while southern Han exhibited a closer connection with the Gelao and Li ethnic groups. In summary, this study presented a systematic analysis of haplogroup distribution, genetic substructure of Han populations and genetic relationships between Han populations and surrounding ethnic minorities based on 89 Y-SNPs and 16 Y-STRs systematically. Our research supplemented valuable insights into population genetics and forensic genetics, and provided data support for the forensic application of Y chromosome. The integration of Y-SNP haplogroups with Y-STR haplotypes offers enhanced understanding of the genetic substructure within Han populations, which holds significance for both population genetics research and forensic science applications.

High gain differentiator based neuro-adaptive arbitrary order sliding mode control design for MPE of standalone wind power system.

In this paper, we introduce a novel Maximum Power Point Tracking (MPPT) controller for standalone Wind Energy Conversion Systems (WECS) with Permanent Magnet Synchronous Generators (PMSG). The primary novelty of our controller lies in its implementation of an Arbitrary Order Sliding Mode Control (AOSMC) to effectively overcome the challenges caused by the measurement noise in the system. The considered model is transformed into a control-convenient input-output form. Additionally, we enhance the control methodology by simultaneously incorporating Feedforward Neural Networks (FFNN) and a high-gain differentiator (HGO), further improving the system performance. The FFNN estimates critical nonlinear functions, such as the drift term and input channel, whereas the HGO estimates higher derivatives of the system outputs, which are subsequently fed back to the control inputs. HGO reduces sensor noise sensitivity, rendering the control law more practical. To validate the proposed novel control technique, we conduct comprehensive simulation experiments compared against established literature results in a MATLAB environment, confirming its exceptional effectiveness in maximizing power extraction in standalone wind energy applications.

Identifying Qingkailing ingredients-dependent mesenchymal-epithelial transition factor-axiation "π" structuring module with angiogenesis and neurogenesis effects.

OBJECTIVE: To explore the functional role of the drug-dependent mesenchymal-epithelial transition (Met)-axiation "π" structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia. METHODS: We used a Glutathione S-transferase (GST)-pull down assay, isothermal titration calorimetry assay, and other related methods to identify the relationships among Met, inositol polyphosphate phosphatase like 1 (Inppl1), and death associated protein kinase 3 (Dapk3) in this allosteric module. The biological effects of the modules of neurons generation composed of Met, Inppl1, and Dapk3 were measured through Western blot, apoptosis analysis, and double immunofluorescence labeling. RESULTS: The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex; Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region. Thus, we obtained a "π" structuring module considered a neural regeneration module. The biological effects of angiogenesis and neurogenesis modules composed of Met, Inppl1, and Dapk3 were also verified. CONCLUSION: The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.

Relationships Between Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease: Indication from Gut Microbiota Alterations.

Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alterations is rarely studied. In this study, we aim to investigate whether there were consistent changes between RBD and PD in gut microbiota, and found some specific biomarkers in RBD that might indicate phenoconversion to PD. Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among idiopathic RBD (iRBD), PD with RBD, PD without RBD and normal controls (NC). Enterotype distribution indicated iRBD, PD with RBD and PD without RBD were Ruminococcus-dominant while NC were Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Through clinical correlation analysis, Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD (RBD-HK). Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD. Our study indicates that RBD had similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be potential hallmarks of phenoconversion of RBD to PD.

Moxibustion modulates working memory in patients with amnestic mild cognitive impairment: a functional magnetic resonance imaging study.

OBJECTIVE: To investigate the correlation between changes in brain activity associated with working memory and assessment scales of memory scores in amnestic mild cognitive impairment (aMCI) before and after moxibustion therapy. METHODS: aMCI patients were randomized into the moxibustion treatment (MT) group and the placebo moxibustion (PM) group. Each group received either moxibustion therapy or a placebo moxibustion for eight weeks. Neuropsychological performance and functional brain responses to a working memory task were assessed at baseline and at the end of treatment. Memory function was evaluated individually by the Rivermead behavioral memory test (RBMT), and working memory was assessed by the N-back task. RESULTS: Compared with the PM group, RBMT score changes were significant ( < 0.05). In the MT group, the accuracy of the N-back texts increased compared with those before the intervention. After moxibustion intervention, the right insula, postcentral gyrus, precentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, calcarine sulcus, posterior cingulate gyrus, middle frontal gyrus and anterior frontal gyrus were significantly activated (= 0.01, Cluster-level Family-Wise Error = 0.05). Pearson correlation analysis showed that the insula, lingual gyrus and posterior cingulate gyrus were associated with changes in N-back score. Spearman correlation analysis showed that the postcentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, and posterior cingulate gyrus were correlated with RBMT score changes. CONCLUSION: Moxibustion treatment improved memory in aMCI patients and was associated with the activation of the brain region of the insula, lingual gyrus, posterior cingulate gyrus, postcentral gyrus, superior temporal gyrus, and thalamus, which may be an important mechanism by which moxibustion improves the memory function.

Melatonin alleviates cisplatin-induced mice spermatogenesis defects.

Cisplatin (CDDP) is a chemotherapeutic drug that is used to treat many different types of tumors. However, it also has significant adverse effects on male reproduction, which are partially mediated oxidative damage. Melatonin (MLT) is a promising antioxidant that can be used for reproductive protection. In this paper, we investigated the effect of CDDP on spermatogenesis, as well as MLT's potential role in reproductive protection. CDDP (5 mg/kg BW) significantly reduced male mice testosterone levels and decreased sperm vitality and progressive motility. Additionally, a lower percentage of stage VII and VIII seminiferous tubules were observed in CDDP-treated mice. MLT administration significantly alleviated CDDP-induced testicular damages, CDDP-induced lowered male fertility in vivo, and enhanced in vitro embryonic development of two cells and blastocysts. These changes may be due to CDDP-mediated spermatogenesis defects in germ cell and Leydig cell proliferation, which are reflected in abnormal PCNA, SYCP3, and CYP11A1 expression levels and can be improved by MLT. CDDP treatment significantly decreased the total antioxidant capacity (TAC), as well as SOD and GSH levels, and increased MDA levels in mice testis, leading to increased apoptosis of germ cells and increased BAX/BCL2 ratios in mice testis. MLT treatment may reduce germ cell apoptosis by reducing oxidative damage in mice testis. This study demonstrated that CDDP affects sperm fertility by altering germ cell and Leydig cell proliferation via increased oxidative damage and that MLT can attenuate these damages. Our work provides potential information for further research on the toxic effects of CDDP and the protective effects of MLT on male reproduction.

Comparison of Unilateral Biportal Endoscopy Decompression and Microscopic Decompression Effectiveness in Lumbar Spinal Stenosis Treatment: A Systematic Review and Meta-analysis.

This study aimed to compare the safety and effectiveness between unilateral biportal endoscopy (UBE) technique and microscopic decompression (MD) technique in lumbar spinal stenosis treatment. PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, and other databases were used to conduct extensive literature searches. RevMan ver. 5.3 software was used for the statistical analysis. Eleven studies were included with 930 patients, including 449 patients in the UBE group and 521 in the MD group. Both techniques revealed similar operative times at -1.77 minutes (95% confidence interval [CI], -7.59 to 4.05 minutes; p =0.55), the postoperative dural expansion area at -1.27 (95% CI, -19.30 to 16.77; p =0.89), the postoperative complications at 0.76 (95% CI, 0.47 to 1.22; p =0.26), the preoperative Visual Analog Scale (VAS) for leg pain, and the last follow-up (>12 months) VAS for leg pain at -0.04 (95% CI, -0.14 to 0.06; p =0.47), the preoperative Oswestry Disability Index (ODI), and the last follow-up (>12 months) ODI scores at -0.18 (95% CI, -0.76 to 0.40; p =0.54), and patient satisfaction (the modified MacNab score) at 1.15 (95% CI, 0.54 to 2.42; p =0.72). However, intraoperative bleeding was lower following the UBE technique at -52.78 mL (95% CI, -93.47 to -12.08 mL; p =0.01) and was shorter following the UBE technique at -3.06 (95% CI, -3.84 to -2.28; p <0.01). UBE and MD technology have no significant differences in efficacy or safety in the treatment of patients with lumbar spinal stenosis based on this meta-analysis. However, the UBE technique has less intraoperative bleeding and a shorter hospital stay. It has a slight advantage and is a better surgical option than the MD technique. It can be an alternative minimally invasive spinal surgery method.

HIF-1α inhibitor YC-1 suppresses triple-negative breast cancer growth and angiogenesis by targeting PlGF/VEGFR1-induced macrophage polarization.

Triple negative breast cancer (TNBC) is an invasive and metastatic phenotype of breast cancer with limited treatment options. Published studies have demonstrated an inhibitory effect of HIF-α inhibition by its inhibitor YC-1 (lificiguat) on growth and angiogenesis of TNBC. However, the underlying mechanism remains poorly understood. In the current paper, our results show that HIF-1α inhibitor significantly inhibited TNBC growth by increasing cellular apoptosis and decreasing MVD, independent of a cell-autonomous mechanism in both endothelial and tumor cells. Genetic screening and in vivo experiments showed that a large number of M2-polarized TAMs accumulated in the hypoxic peri-necrotic region (PNR), where placental growth factor (PlGF) and its ligand, vascular endothelial growth factor receptor-1 (VEGFR-1) were upregulated. Furthermore, YC-1 skewed the polarization of TAMs away from M2 to M1 phenotype, therefore inhibiting TNBC angiogenesis and growth. This effect was further abrogated by VEGFR-1 neutralization and TAM depletion following clodronate liposome injection. These findings provide preclinical evidence for an indirect mechanism underlying YC-1-induced suppression of TNBC growth and angiogenesis, thereby offering a treatment option for TNBC.

Evaluation of the Common bile duct (CBD) Diameter After Laparoscopic Cholecystectomy (LC) and Laparoscopic Common Bile Duct Exploration (LCBDE): A Retrospective Study.

BACKGROUND: Common Bile duct (CBD) measurement is a crucial aspect in the evaluation of the biliary tree. Whether the CBD undergoes any compensatory change in diameter after laparoscopic cholecystectomy or laparoscopic common bile duct exploration is still up for discussion. The aim of this study was to investigate CBD diameter changes after laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) on magnetic resonance cholangiopancreatography (MRCP). MATERIALS AND METHODS: Our retrospective study is divided into 2 sections. The first part assessing CBD diameter changes after laparoscopic cholecystectomy due to gallstones or gallbladder polyps, involved 85 patients, who underwent MRCP procedures. These patients aged between 30 and 85 were divided into an interval LC group (group A, n=56) and a remote LC group (group B, n=29). In group A, the common CBD diameters were measured at their widest portions on MRCP obtained before and after laparoscopic cholecystectomy. Measurements of the CBD diameters were repeated on MRCP obtained twice after the surgery in group B.Section 2 consisted of 38 patients who had choledocholithiasis and were treated with laparoscopic CBD exploration and T-tube placement. These patients aged 26 to 86 formed the interval LCBDE group (group C). The CBD widest diameters were measured on MRCP before LCBDE and after T-tube cholangiography for these individuals.Patients in groups A and C were further divided into 5 and those in group B into 4 age-related subgroups to facilitate statistical analysis. The Pearson correlation test was performed to find any relationship between CBD diameters and age in groups A and B. Paired sample T test was used to compare the significant difference between the 2 sets of CBD diameters in each study group and their subgroups. RESULTS: In the interval LC group, the post-LC mean CBD diameter was significantly wider when compared with the preoperative mean diameter ( P <0.05). There was a significant difference between the first and second post-LC means CBD diameter in the remote LC group ( P <0.05). In group C, the mean CBD diameter measured on T-tube cholangiography after LCBDE was significantly smaller than the preoperative dilated mean diameter ( P <0.05). CONCLUSIONS: This study demonstrated significant dilation occurring in the common bile duct diameter after laparoscopic cholecystectomy. Furthermore, our remote LC group also supported that claim by showing significant dilation between the first and second post-cholecystectomy CBD diameter values. And lastly, our interval LCBDE sample's initial dilation of the CBD diameters was reduced after surgery and stone extraction.

Circ_SIPA1L1 Promotes Osteosarcoma Progression Via miR-379-5p/MAP3K9 Axis.

Background: Osteosarcoma (OS) is a common malignant bone tumor. Circular RNAs (circRNAs) exert important roles in the pathogenesis of human cancers, including OS. In this study, the authors focused on the role and mechanism of circRNA signal-induced proliferation-associated 1 like 1 (circ_SIPA1L1) in OS. Methods: The enrichment of SIPA1L1, circ_SIPA1L1, microRNA-379-5p (miR-379-5p), and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The colony formation capacity was assessed through colony formation assay. Transwell assays were used to detect the migration and invasion abilities. Western blot assay was used to measure the expression of metastasis-related proteins and MAP3K9. The target interactions between the genes in circ_SIPA1L1/miR-379-5p/MAP3K9 axis were predicted by StarBase and confirmed by dual-luciferase reporter assay. The in vivo role of circ_SIPA1L1 was verified by murine xenograft assay. Results: Circ_SIPA1L1 abundance was aberrantly elevated in OS tissues and cell lines. Circ_SIPA1L1 accelerated the proliferation and metastasis abilities of OS cells. Circ_SIPA1L1 promoted the malignant behaviors of OS cells through elevating MAP3K9 level. MiR-379-5p directly bound to circ_SIPA1L1 and MAP3K9. MiR-379-5p interference rescued the abilities of proliferation and metastasis in OS cells, which were suppressed by the silencing of circ_SIPA1L1. Circ_SIPA1L1 promoted the development of OS via miR-379-5p/MAP3K9 in vivo. Conclusion: Circ_SIPA1L1 promoted the progression of OS via miR-379-5p/MAP3K9 axis.

Dexmedetomidine Attenuates Lipopolysaccharide-Induced Sympathetic Activation and Sepsis via Suppressing Superoxide Signaling in Paraventricular Nucleus.

Sympathetic overactivity contributes to the pathogenesis of sepsis. The selective α2-adrenergic receptor agonist dexmedetomidine (DEX) is widely used for perioperative sedation and analgesia. We aimed to determine the central roles and mechanisms of DEX in attenuating sympathetic activity and inflammation in sepsis. Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide (LPS) in rats. Effects of DEX were investigated 24 h after injection of LPS. Bilateral microinjection of DEX in the paraventricular nucleus (PVN) attenuated LPS-induced sympathetic overactivity, which was attenuated by the superoxide dismutase inhibitor DETC, cAMP analog db-cAMP or GABAA receptor antagonist gabazine. Superoxide scavenger tempol, NADPH oxidase inhibitor apocynin, adenylate cyclase inhibitor SQ22536 or PKA inhibitor Rp-cAMP caused similar effects to DEX in attenuating LPS-induced sympathetic activation. DEX inhibited LPS-induced superoxide and cAMP production, as well as NADPH oxidase, adenylate cyclase and PKA activation. The roles of DEX in reducing superoxide production and NADPH oxidase activation were attenuated by db-cAMP or gabazine. Intravenous infusion of DEX inhibited LPS-induced sympathetic overactivity, NOX activation, superoxide production, TNF-α and IL-1ß upregulation in the PVN and plasma, as well as lung and renal injury, which were attenuated by the PVN microinjection of yohimbine and DETC. We conclude that activation of α2-adrenergic receptors with DEX in the PVN attenuated LPS-induced sympathetic overactivity by reducing NADPH oxidase-dependent superoxide production via both inhibiting adenylate cyclase-cAMP-PKA signaling and activating GABAA receptors. The inhibition of NADPH oxidase-dependent superoxide production in the PVN partially contributes to the roles of intravenous infusion of DEX in attenuating LPS-induced sympathetic activation, oxidative stress and inflammation.

Parental cadmium exposure during the spawning period reduces cadmium sensitivity through the antioxidant system in rare minnow (Gobiocypris rarus) larvae.

Cadmium (Cd) is a noxious heavy metal widely dispersed in aquatic systems. Parental Cd exposure of fish species at environmental concentrations has been shown to cause deformities and stunted growth in their offspring. However, the long-term effects and the mechanisms underlying parental Cd exposure in fish species on Cd sensitivity in their offspring remain unclear. To explore the impacts of parental Cd exposures on Cd sensitivity, rare minnow (Gobiocypris rarus) larvae whose parents were exposed to Cd at 0, 5 or 10 µg/L for 28 days were established. Results showed that parental Cd exposure in rare minnow increased the Cd content of its larvae. In terms of malformation rate, mortality rate and total length at 7 days of rare minnow larvae, parental Cd exposure at 5 or 10 µg/L reduced Cd sensitivity. Further mechanistic investigation demonstrated that parental Cd exposure significantly upregulated the expression of antioxidant gene regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-кB) in rare minnow larvae. In addition, parental Cd exposure significantly elevated the level of reactive oxygen species (ROS) and malondialdehyde (MDA), but markedly decreased catalase (CAT), superoxide dismutase (SOD) and oxidized glutathione (GST) activity. The impact of parental Cd exposure to metallothionein (MT) content and the expression of MT mRNA, a detoxifying metallothionein, showed that parental Cd exposure of rare minnow induced oxidative stress in the larvae. Meanwhile, these results indicated that parental Cd exposure in rare minnow reduced the Cd sensitivity of the larvae via activating the Nrf2-mediated antioxidant system. This project helps us to further understand the toxicological mechanism of Cd in fish species and properly assess its potential ecological risk.

Asprosin in the Paraventricular Nucleus Induces Sympathetic Activation and Pressor Responses via cAMP-Dependent ROS Production.

Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP-PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.

An infrared thermographic analysis of the sensitization acupoints of women with primary dysmenorrhea.

OBJECTIVE: To explore the sensitization acupoints of women with primary dysmenorrhea (PD) by comparing infrared radiation temperatures between acupoints and non-acupoints. METHODS: We tested 10 acupoints of every woman with PD and healthy subjects on premenstrual, menstrual, and postmenstrual days using an infrared imaging device. The primary outcome was the absolute value of body surface temperature difference (AVTD) between the left and right sides of the same testing point. RESULTS: A total of 58 PD patients and 57 healthy volunteers completed the test from May 2016 to May 2017. Compared with the healthy group, we observed a significant reduction and increase in the AVTD in Taichong (LR3) and Sanyinjiao (SP6), respectively, during menstrual days in the PD group (= 0.01; = 0.04); while during postmenstrual days, all AVTDs of Shuiquan (KI5), Diji (SP8), and Xuehai (SP10) were diminished in the PD group (= 0.01; = 0.03; = 0.01, respectively). No significant differences in AVTD were detected at any other points or testing times. CONCLUSIONS: Compared with the healthy group, the AVTDs of Taichong (LR3), Sanyinjiao (SP6), Shuiquan (KI5), Diji (SP8), and Xuehai (SP10) at menstruation-relevant points of PD patients were sensitized, providing a reference for the selection of acupoints in the treatment of PD.

Determination of components in Radix paeoniae rubra based on QAMS.

The current study aimed to establish simple and quick quality evaluation method of Chishao based on QAMS. Oxypaeoniflorin is used as a marker in the Chishao root. Based on it, the content of other components could be obtained by establishing the mathematical relationship. UPLC method was used to collect data, and the detection wavelengths were 230nm (benzoic acid, paeoniflorin), 263nm (hydroxy paeoniflorin) 274nm (gallic acid, paeoniflorin, catechin), respectively. The stationary phase was an Agilent ZORBAX SB-C18 and the mobile phase was acetonitrile -0.1% formic acid-water. The gradient elution method was adopted at the certain flow rate (0.3 mL/min). The column temperature set 40oC, and the injection volume was 1µL. Multiple reaction monitoring mode was selected for data collection. The linear ranges of benzoic acid, paeoniflorin, hydroxy-paeoniflorin, gallic acid, catechin and paeoniflorinhad good linearity (r ≥0.9995). The UPLC method was established to determine the content of paeoniflorin, benzoic acid, catechin, gallic acid, paeoniflorin, andhydroxy-paeoniflorin in Radix Paeoniae Rubra. In the current study, the method for the chemical components in Radix Paeoniae Rubra to provide the evaluation basis of medicinal effects.

Predictive Factors for Adjacent Vertebral Fractures After Percutaneous Kyphoplasty in Patients With Osteoporotic Vertebral Compression Fracture.

BACKGROUND: Adjacent vertebral fracture (AVF) seemed to be a frequent and severe complication in osteoporotic vertebral compression fracture (OVCF) patients receiving percutaneous vertebroplasty  or percutaneous kyphoplasty (PKP), resulting in poor long-term outcome and recurrence of pain-related symptoms. Nonetheless, its mechanism remains unclear. OBJECTIVES: To investigate the potential predictor of AVF after PKP and figure out whether the intervertebral disc plays a role during the process of AVF. STUDY DESIGN: Retrospective study. SETTING: Department of Orthopedic, an affiliated hospital of a medical university. METHODS: Clinical data of OVCF patients receiving PKP were reviewed in our hospital from January 2016 to December 2020. Four hundred and forty-five patients were recruited who met the abovementioned criteria in this study. The clinical data, including age, gender, bone mineral density (BMD), vertebral height, vertebral kyphosis angle, cement volume, cement distribution, as well as adjacent disc degeneration extent, were recorded for each patient. Independent-sample t tests and chi-squared tests were performed to compare these indexes. Bivariate correlation tests and multiple linear regression analyses were performed among potential predictors. Receiver operator characteristic (ROC) analysis and Kaplan-Meier plotter were applied to evaluate the diagnostic efficiency of parameters for predicting the occurrence of AVF. RESULTS: Patients in both groups gained obvious improvements in symptomatic and radiographic indexes after first PKP. Statistically significant difference (P < 0.05) was only found between 2 groups with respect to BMD, kyphosis angle at last follow-up before second PKP, cement distribution, and disc degeneration grade. The ROC analysis showed that BMD = 15.5° was highly predictive of AVF after PKP (sensitivity, 92.2%; specificity, 24.6%; area under curve, 0.569, P = 0.109). Statistically significant difference of AVF incidence amongst patients with different cement distribution (P = 0.018) and similar trend was also found amongst patients with different disc degeneration (P = 0.000). Statistically significant difference was noted in terms of disc degeneration grade between 2 adjacent discs in AVF group. LIMITATIONS: The main limitation is the retrospective nature of this study. CONCLUSIONS: The risk of AVF should be focused, especially when OVCF patients with the following predictors: (1) BMD < -3.45; (2) kyphosis angle at last follow-up > 15.5°; (3) I or II cement distribution; and (4) IV or V disc degeneration. More prophylactic treatment should be prescribed for these patients to avoid the occurrence of AVF.

MXene monolayer Mn2ZnN2: a promising robust intrinsic half-metallic nanosheet.

Two-dimensional half-metallic ferromagnets are promising in spintronics. In recent years, the half-metallicity and the magnetic properties of the MXene materials have been the research hotspots of new materials due to their unique crystal characteristics and wide applications. In this paper, the MXene nanosheet Mn2ZnN2was predicted as a kind of robust intrinsic half-metallic nanosheet whose magnetic moment per unit is the integer 6.00µBbased on the first principles calculations. The half-metallic character and the magnetic moment of this nanosheet mainly result from the spin-polarized Mn-ions induced by the crystal field. If the absolute biaxial compression strain is lower than 3.0%, the half-metallicity remains well and the magnetic moment per unit is always 6.00µB, indicating that its half-metallicity and magnetic properties are stable within a certain pressure range. More importantly, the magnetic moment per unit is elevated from 6.00µBto 9.00µBand the half-metallic energy gap increases evidently after an electron is removed from this nanosheet, suggesting that the half-metallicity and magnetic properties of this nanosheet may be improved via tuning its charge state.