Effect of electroacupuncture of "Jiaji" (EX-B2) on NOD-like receptor protein 3 mediated pyroptosis in spinal cord tissue of rats with acute spinal cord injury. / å¤¹è„Šç”µé’ˆå¯¹æ€¥æ€§è„Šé«“æŸä¼¤å¤§é¼ è„Šé«“ç»„ç»‡NODæ ·å—ä½“çƒ­è›‹ç™½ç»“æž„åŸŸç›¸å ³è›‹ç™½3介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Jiaji"(EX-B2) on motor function, histomorphology, and expression of NOD-like receptor protein 3 (NLRP3) and N-terminal domain of gasdermin D (GSDMD-N) in the spinal cord tissue of rats with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: Forty eight female SD rats were randomly divided into sham surgery (sham), SCI model (model), EA, and NLRP3 agonist (monosodium urate, MSU) combined with Jiaji EA (MSU+EA) groups, with 12 rats in each group which were further divided into 3 d and 7 d subgroups, with 6 rats at each time point. Two EA groups received EA stimulation of EX-B2 with a frequency of 100 Hz, electrical current of 1-2 mA for 30 min, once a day for 3 or 7 days. After 5 min, 6 h, and 24 h of modeling, rats of the MSU+EA group received intraperitoneal injection of MSU (200 µg/kg, 200 µg/mL) . The motor function was evaluated using Basso-Beattie-Bresnahan (BBB) scale, the morphological structure of rat spinal cord tissue was observed by H.E. staining. The expression of pyroptosis related factors NLRP3, cleaved Caspase-1 and GSDMD-N of the spinal cord was observed by using immunohistochemistry and Western blot separately, the expression and localization of Iba-1 and GSDMD-N in the spinal cord tissue were observed using immunofluorescence double staining method. RESULTS: Compared with the sham group, the BBB scores after modeling and on day 3 and 7 were decreased (P<0.05), while the average OD values (immunoactivity) and expression levels of NLRP3, cleaved Caspase-1 and GSDMD-N proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N (co-expression) of the spinal cord tissues on day 3 and 7 were significantly increased in the model group (P<0.05). In comparison with the model group, the BBB scores on day 3 and 7 were obviously increased (P<0.05), while the immunoactivity and expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N on day 3 and 7 significantly down-regulated in the EA group (P<0.05) but not in the MSU+EA group (P>0.05), suggesting an elimination of the effects of EA after administration of NLRP3 agonist (MSU). H.E. staining showed obvious bleeding area in the spinal cord tissue, loose tissue and inflammatory cell infiltration on day 3 after modeling, and basic absorption of the bleeding, loose tissue, obvious vacuolar changes of the white matter area, loss and contraction of neurons with infiltration of a large number of inflammatory cells, which was milder in the EA group but not in the MSU+EA group. CONCLUSIONS: EA of EX-B2 can improve the motor function of SCI rats, which may be related to its functions in inhibiting pyroptosis of microglia mediated by NLRP3/Caspase-1 signaling pathway.

Correlation Between Intracoronary Vascular Ultrasound Indexes in Patients with Coronary Heart Disease.

Background: Coronary atherosclerosis is a serious and progressive condition characterized by the accumulation of plaques, consisting of fat, cholesterol, and other substances, within the arteries that supply blood to the heart. These plaques can harden and narrow the arteries, leading to reduced blood flow to the heart muscle. Objective: The primary objective of this study is to investigate the correlation between specific cardiovascular parameters and intracoronary vascular ultrasound indexes in patients diagnosed with coronary heart disease. This investigation aims to explore the relationships between intracoronary vascular ultrasound measurements and three key cardiovascular parameters: epicardial fat pad thickness, mono-platelet polymer levels, and small dense low-density lipoprotein cholesterol (sdLDL-C) levels. Methods: In this investigation, we applied a comprehensive method to evaluate atherosclerotic plaque characteristics in patients with diverse stages of coronary heart disease (CHD), contrasting these profiles with those of healthy individuals. Our study included 80 acute myocardial infarction (AMI) patients, 145 with unstable angina pectoris (UAP), 175 with stable angina pectoris (SAP), and 100 controls. We utilized intravascular ultrasound (IVUS), an advanced imaging technique that surpasses traditional angiography by providing detailed, high-resolution images of both the coronary artery lumen and wall, including plaque composition. This approach is pivotal for assessing plaque stability, a key factor in the risk of rupture and subsequent cardiovascular events, indicated by features like lipid-rich cores and thin fibrous caps. During IVUS, we quantified parameters such as plaque area, load, and the remodeling index, the latter offering insights into vascular adaptation to plaque buildup. Additionally, we conducted a correlation analysis between IVUS indices and three cardiovascular markers: epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels. The goal was to ascertain the predictive value of these markers in tandem with IVUS for determining the stability of coronary artery atherosclerotic plaques. This integrative approach enhances understanding of plaque formation and destabilization, potentially informing more effective CHD prevention and management strategies. Results: Our study revealed distinct variations in key parameters across patient groups with different forms of CHD and healthy controls. Notably, we observed significant differences in gender distribution, hypertension, and diabetes mellitus prevalence among these groups. In terms of IVUS indexes and cardiovascular parameters, the SAP group exhibited markedly different results compared to the AMI and UAP groups. Specifically, the SAP patients showed the lowest values for EMMA, plaque area, plaque burden, reconstruction index, and positive remodeling. Additionally, they exhibited the thickest fibrous caps. In contrast, the AMI and UAP groups presented similar outcomes in these aspects. Regarding the epicardial fat pad thickness, the positive rate of monocyte-platelet aggregates, and the levels of sdLDL-C, there were no significant differences between the AMI and UAP groups. However, these parameters were notably higher in the AMI and UAP groups compared to the SAP group. Crucially, we established a significant correlation between the thickness of the epicardial fat pad, the positive rate of monocyte-platelet aggregates, and the sdLDL-C levels with plaque loading rate and remodeling index. These correlations underscore the potential utility of these parameters as indicators of plaque stability and cardiovascular risk in patients with CHD. This highlights the complexity of atherosclerotic disease progression and underscores the importance of a multifaceted approach to assessing and managing CHD. Conclusion: Our research delineates the critical role of the remodeling index, epicardial fat pad thickness, monocyte-platelet aggregates, and sdLDL-C levels as key prognostic tools for assessing coronary plaque stability in coronary artery disease (CAD). These biomarkers collectively provide an enhanced perspective on plaque vulnerability, an essential aspect in the genesis of acute coronary events. Clinically, these findings are pivotal. They offer a refined approach to CAD management and risk evaluation, allowing for the precise identification of patients at increased risk of plaque rupture, a precursor to acute coronary syndromes. This precision facilitates the adoption of more individualized treatment strategies, focusing on aggressive interventions for high-risk patients and more conservative management for those with stable plaques.

Effect of acupuncture on BDNF signaling pathways in several nervous system diseases.

In recent years, the understanding of the mechanisms of acupuncture in the treatment of neurological disorders has deepened, and considerable progress has been made in basic and clinical research on acupuncture, but the relationship between acupuncture treatment mechanisms and brain-derived neurotrophic factor (BDNF) has not yet been elucidated. A wealth of evidence has shown that acupuncture exhibits a dual regulatory function of activating or inhibiting different BDNF pathways. This review focuses on recent research advances on the effect of acupuncture on BDNF and downstream signaling pathways in several neurological disorders. Firstly, the signaling pathways of BDNF and its function in regulating plasticity are outlined. Furthermore, this review discusses explicitly the regulation of BDNF by acupuncture in several nervous system diseases, including neuropathic pain, Parkinson's disease, cerebral ischemia, depression, spinal cord injury, and other diseases. The underlying mechanisms of BDNF regulation by acupuncture are also discussed. This review aims to improve the theoretical system of the mechanism of acupuncture action through further elucidation of the mechanism of acupuncture modulation of BDNF in the treatment of neurological diseases and to provide evidence to support the wide application of acupuncture in clinical practice.

[Research progress of acupuncture-moxibustion in treatment of spinal cord injury through mediating inflammatory reaction].

Inflammatory reaction after spinal cord injury (SCI) is the main obstacle to the recovery of neural function. In the occurrence and development of SCI, the complex regulatory mechanisms are involved in inflammatory reaction, including the activation of inflammatory cells (e.g.macrophages and microglia), and the release of cytokines (e.g. tumor necrosis factor, interleukin and chemokines). Acupuncture-moxibustion is significantly effective in clinical treatment of SCI, and its mechanism is related to adjusting the function of inflammatory cells after SCI, modulating the expression of cytokines and the activation of NLRP3 inflammatory bodies, as well as the expression of high mobility group protein B1 and calcitonin gene related peptide. This article summarizes the research progress of mechanism of inflammatory reaction after SCI and the effects of acupuncture-moxibustion intervention in recent years so that the new ideas can be provided to clarify the pathogenesis of SCI and the effect of acupuncture-moxibustion intervention.

Site-directed mutagenesis identified the key active site residues of 2,3-oxidosqualene cyclase HcOSC6 responsible for cucurbitacins biosynthesis in Hemsleya chinensis.

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.

A comprehensive review of antitumor properties of Angelica species and their antitumor-responsible constituents and the underlying molecular mechanisms involved in tumor inhibition.

Angelica species have been traditionally used for their medicinal properties. Recent studies have suggested their potential use as anticancer agents, making them an area of interest for further research. The review aims to summarize the current understanding of the potential anticancer effects of Angelica species and to provide insights for further research in this area. We searched for "Angelica" related information on Google Scholar, PubMed, ScienceDirect, Wiley, Science Citation Index Finder, and Springer link by searching keywords such as "Angelica," "Angelica phytochemical," "Angelica antitumor effect," "Angelica molecular mechanisms," and "Angelica clinical application." Included articles focused on the Angelica plant's anticancer properties and clinical studies, while non-cancer-related biological or phytochemical investigations were excluded. We conducted a comprehensive search of books, journals, and databases published between 2001 and 2023, identifying 186 articles for this narrative review. The articles were analyzed for their potential anticancer properties and therapeutic applications. Active compounds in the Angelica genus, such as coumarins, furanocoumarins, phthalides, and polysaccharides, exhibit anticancer properties through various mechanisms. Specific species, like A. archangelica, Angelica sinensis, A. gigas, and A. ksiekie, have the potential as anticancer agents by targeting cellular pathways, generating reactive oxygen species, and inducing apoptotic cell death. Further research into the properties of the Angelica genus is needed for developing new treatments for cancer. Phytochemicals from Angelica species possess potential as anticancer agents, requiring further research for the development of effective, low-cost, and low-toxicity cancer treatments compared to synthetic antitumor drugs.

The extended day length promotes earlier flowering of bermudagrass.

Day length is a very critical environmental factor affecting plant growth and development. The extension of light application time has been shown to promote flowering in the long-day plant and to shorten breeding time in some crops. However, previous research on the regulation of bermudagrass flowering by light application time is scarce. Therefore, this study investigated the effect of day length on the growth and flowering of bermudagrass by prolonging the light application time in a controlled greenhouse. Three different light application times were set up in the experiment: 22/2 h (22 hours light/2 hours dark), 18/6 h (18 hours light/6 hours dark), 14/10 h (14 hours light/10 hours dark). Results showed that extending the light application time not only promoted the growth of bermudagrass (plant height, fresh weight, dry weight) but also its nutrient uptake (nitrogen (N) and phosphorous (P) content). In addition, daily light integrals were different when flowering under different light application times. Most importantly, under the 22/2 h condition, flowering time was successfully reduced to 44 days for common bermudagrass (Cynodon dactylon [L.] pers) genotype A12359 and 36 days for African bermudagrass (Cynodon transvaalensis Burtt-Davy) genotype ABD11. This study demonstrated a successful method of bermudagrass flowering earlier than usual time by manipulating light application time which may provide useful insights for bermudagrass breeding.

EbMYBP1, a R2R3-MYB transcription factor, promotes flavonoid biosynthesis in Erigeron breviscapus.

Erigeron breviscapus, a traditional Chinese medicinal plant, is enriched in flavonoids that are beneficial to human health. While we know that R2R3-MYB transcription factors (TFs) are crucial to flavonoid pathway, the transcriptional regulation of flavonoid biosynthesis in E. breviscapus has not been fully elucidated. Here, EbMYBP1, a R2R3-MYB transcription factor, was uncovered as a regulator involved in the regulation of flavonoid accumulation. Transcriptome and metabolome analysis revealed that a large group of genes related to flavonoid biosynthesis were significantly changed, accompanied by significantly increased concentrations of the flavonoid in EbMYBP1-OE transgenic tobacco compared with the wild-type (WT). In vitro and in vivo investigations showed that EbMYBP1 participated in flavonoid biosynthesis, acting as a nucleus-localized transcriptional activator and activating the transcription of flavonoid-associated genes like FLS, F3H, CHS, and CHI by directly binding to their promoters. Collectively, these new findings are advancing our understanding of the transcriptional regulation that modulates the flavonoid biosynthesis.

The discovery of potentially active diterpenoids to inhibit the pyroptosis from Callicarpa arborea.

Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent-clerodane diterpenoids from Callicarpa arborea, shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent-clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1-25) or a 6/6- (26-66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1ß secretion in J771A.1 cells, revealed 28 compounds with an IC50 below 10.5 µM. Compound 1 was the most potent with an IC50 of 0.68 µM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine.

Genetic manipulation of bermudagrass photosynthetic biosynthesis using Agrobacterium-mediated transformation.

Bermudagrass is one of the most extensively used warm-season grasses. It is widely used in landscaping, stadium construction and soil remediation due to its excellent regeneration, trampling and stress tolerances. However, studies on its regulatory mechanism and variety improvement by genetic engineering are still at a standstill, owing to its genetic variability and intrinsic limits linked with some resistance to Agrobacterium infection. In this study, we established a higher efficient Agrobacterium-mediated transformation via screening for vital embryogenic callus and improving infection efficiency. The superior callus was light yellow, hard granular and compact, determined with a differentiation rate of more than 95%. The optimized infestation courses by gentle shaking, vacuuming and sonicating were used. The infested calluses were co-cultured for 3 days, followed by desiccation treatments for 1 day to get higher infection efficiency. Then the CdHEMA1 gene, essential for chlorophyll biosynthesis, was cloned and transferred into bermudagrass to validate the aforementioned optimization procedures integrally. Molecular-level analyses indicated that the CdHEMA1 gene had successfully integrated and was greatly increased in transgenic seedlings. Results of the photosynthetic capacity assessment showed that CdHEMA1 overexpression may considerably enhance the contents of photosynthetic pigments, OJIP curve and reaction center density (RC/CSo) to absorb (ABS/CSo, ABS/CSM) and capture (TRo/CSo) more light energy, hence improve the performance indices PIABS and PICS compared to the wild type. The successful completion of this project would provide a solid platform for further gene function study and molecular breeding of bermudagrass.

Physiological integration between Bermudagrass ramets improves overall salt resistance under heterogeneous salt stress.

Connected ramets of colonal plants often suffer from different environmental conditions such as light, nutrient, and stress. Colonal Bermudagrass (Cynodon dactylon [L.] Pers.) can form interconnected ramets and this connection facilitates the tolerance to abiotic stress, which is a kind of physiological integration. However, how bermudagrass responds to heterogeneously distributed salt stress needs to be further elucidated. Here, we demonstrated that severance of stolons aggravated the damage of salt-stressed ramets, displaying higher relative electrolytic leakage (EL), lower content of chlorophyll, higher accumulation of Na+ , and serious oxidative damages. This finding implied the positive effects of the physiological integration of bermudagrass on salt tolerance. The unstressed ramets connected with the stressed one were mildly injured, implying the supporting and sacrifice function of the unstressed ramets. Physiological integration did not mediate the translocation of Na+ among ramets, but induced a higher expression of salt overly sensitive (SOS) genes in the stressed ramets, consequently reducing the accumulation of Na+ in leaves and roots. In addition, physiological integration upregulated the genes expression and enzymes activity of catalase (CAT) and peroxidase (POD) in both stressed and unstressed ramets. This granted a stronger antioxidant ability of the whole clonal plants under salt stress. Enhanced Na+ transfer and increased reactive oxygen species (ROS) scavenging are mechanisms that likely contribute to the physiological integration leading to the salt tolerance of bermudagrass.

Aspergillus aculeatus enhances potassium uptake and photosynthetic characteristics in perennial ryegrass by increasing potassium availability.

AIM: Potassium (K) is a key determinant for plant development and productivity. However, more than 90% of K in the soil exists in an insoluble form. K-solubilizing microbes play an important role in the transformation of insoluble K. Thus, the objective of this study was to evaluate K-dissolving ability of Aspergillus aculeatus (F) and growth-promoting properties in perennial ryegrass. METHODS AND RESULTS: Perennial ryegrass inoculated with A. aculeatus exhibited enhanced soluble K accompanied with higher growth rate and turf quality, compared with the noninoculated regimen. In addition, A. aculeatus also played a primary role in increasing chlorophyll content and photosynthetic capacity of the plant exposed to LK+F (K-feldspar plus A. aculeatus) treatment, compared with the CK (control, no K-feldspar and A. aculeatus), F (only A. aculeatus) and LK (only K-feldspar) groups. Furthermore, the antioxidase activities (CAT and POD) were significantly increased while the oxidative damage (EL and MDA) was dramatically decreased in the LK+F group compared to the LK (K-feldspar) group. Finally, in perennial ryegrass leaves, the genes expression levels of HAK8, HAK12 and HKT18 were obviously elevated in the LK+F group, compared to the CK, F and LK groups. CONCLUSION: We concluded that A. aculeatus could solubilize K from bound form and be considered as K-solubilizing biofertilizer through supplementing K in soil. SIGNIFICANCE AND IMPACT OF THE STUDY: Aspergillusaculeatus has the potential to be used as a biofertilizer in sustainable agriculture.

Comprehensive transcriptional analysis reveals salt stress-regulated key pathways, hub genes and time-specific responsive gene categories in common bermudagrass (Cynodon dactylon (L.) Pers.) roots.

BACKGROUND: Despite its good salt-tolerance level, key genes and pathways involved with temporal salt response of common bermudagrass (Cynodon dactylon (L.) Pers.) have not been explored. Therefore, in this study, to understand the underlying regulatory mechanism following the different period of salt exposure, a comprehensive transcriptome analysis of the bermudagrass roots was conducted. RESULTS: The transcripts regulated after 1 h, 6 h, or 24 h of hydroponic exposure to 200 mM NaCl in the roots of bermudagrass were investigated. Dataset series analysis revealed 16 distinct temporal salt-responsive expression profiles. Enrichment analysis identified potentially important salt responsive genes belonging to specific categories, such as hormonal metabolism, secondary metabolism, misc., cell wall, transcription factors and genes encoded a series of transporters. Weighted gene co-expression network analysis (WGCNA) revealed that lavenderblush2 and brown4 modules were significantly positively correlated with the proline content and peroxidase activity and hub genes within these two modules were further determined. Besides, after 1 h of salt treatment, genes belonging to categories such as signalling receptor kinase, transcription factors, tetrapyrrole synthesis and lipid metabolism were immediately and exclusively up-enriched compared to the subsequent time points, which indicated fast-acting and immediate physiological responses. Genes involved in secondary metabolite biosynthesis such as simple phenols, glucosinolates, isoflavones and tocopherol biosynthesis were exclusively up-regulated after 24 h of salt treatment, suggesting a slightly slower reaction of metabolic adjustment. CONCLUSION: Here, we revealed salt-responsive genes belonging to categories that were commonly or differentially expressed in short-term salt stress, suggesting possible adaptive salt response mechanisms in roots. Also, the distinctive salt-response pathways and potential salt-tolerant hub genes investigated can provide useful future references to explore the molecular mechanisms of bermudagrass.

[Research on regularity of traditional Chinese medicine in treatment of Alzheimer's disease based on data mining].

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.

SWL-1 Reverses Fluconazole Resistance in Candida albicans by Regulating the Glycolytic Pathway.

Candida albicans is a ubiquitous clinical fungal pathogen. Prolonged use of the first-line antifungal agent fluconazole (FLC) has intensified fungal resistance and limited its effectiveness for the treatment of fungal infections. The combined administration of drugs has been extensively studied and applied. SWL-1 is a lignin compound derived from the Traditional Chinese Medicine Schisandra chinensis. In this study, we show that SWL-1 reverses resistance to fluconazole in C. albicans when delivered in combination, with a sharp decrease in the IC50 of fluconazole from >200 to 3.74 ± 0.25 µg/ml, and also reverses the fluconazole resistance of C. albicans in vitro, with IC50 from >200 to 5.3 ± 0.3 µg/ml. Moreover, killing kinetics curves confirmed the synergistic effects of fluconazole and SWL-1. Intriguingly, when SWL-1 was administered in combination with fluconazole in a mouse model of systemic infection, the mortality of mice was markedly decreased and fungal colonization of the kidney and lung was reduced. Further mechanistic studies showed that SWL-1 significantly decreased intracellular adenosine 5'-triphosphate (ATP) levels and inhibited the function of the efflux pump responsible for fluconazole resistance of C. albicans. Proteomic analysis of the effects of SWL-1 on C. albicans showed that several enzymes were downregulated in the glycolytic pathway. We speculate that SWL-1 significantly decreased intracellular ATP levels by hindering the glycolysis, and the function of the efflux pump responsible for fluconazole resistance of C. albicans was inhibited, resulting in restoration of fluconazole sensitivity in FLC-resistant C. albicans. This study clarified the effects and mechanism of SWL-1 on C. albicans in vitro and in vivo, providing a novel approach to overcoming fungal resistance.

A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.

miR-29 family regulates the puberty onset mediated by a novel Gnrh1 transcription factor TBX21.

Gonadotropin-releasing hormone (GnRH) is the ultimate signal by which the neuroendocrine system controls the puberty onset and fertility in mammals. The pulsatile release of GnRH is regulated by numerous extracellular and intracellular factors, including miRNAs. Here, we report a novel regulation mechanism mediated by miR-29 family. We found that the absence of miR-29s resulted in elevated expression of Gnrh1 in GT1-7 cells. Through in silico and wet analysis, we identified Tbx21, a target gene of miR-29, as the main effector. As a transcription activator, TBX21 stimulates the expression of Gnrh1 directly by binding to its promoter region, and indirectly by activating the expression of Dlx1, another transcription activator of Gnrh1. Stereotactic brain infusion of miR-29 inhibitor into the hypothalamus caused earlier puberty onset in prepubertal female mice than that of intact controls. The female mice with ectopic expression of Tbx21 in the hypothalamus were affected in both puberty onset and fertility, as they had higher level of serum LH and FSH, larger litter size but steeper decline of fertility compared with those of controls. Our results revealed that miR-29-3p and its target Tbx21 played a role in regulating the mammalian puberty onset and reproduction by modulating the Gnrh1 expression.

[Professor LI Xiao-ning's experience for post-stroke dysphagia treated with penetrating-needling and swallowing technique of acupuncture].

Professor LI Xiaoning's experience for post-stroke dysphagia treated with penetrating-needling and swallowing technique of acupuncture is summarized in this paper. The key pathogenesis of this disease is dysfunction of zangfu organs, impairment of the house of mental activity and dysfunction of meridian sinew. Innovatively, the anatomic structure related to swallowing is divided into three zones. Based on the distributions of heart, kidney and stomach meridians on the neck, three lines are determined. Hence, the theory of "three-zone and three-line" as well as the penetrating-needling and swallowing technique of acupuncture are put forward. In this paper, the theoretic evidences of penetrating-needling and swallowing technique of acupuncture, point selection and manipulation in treatment of post-stroke dysphagia are introduced.

Biocompatible Nanoclusters with High Heating Efficiency for Systemically Delivered Magnetic Hyperthermia.

Despite its promising therapeutic potential, nanoparticle-mediated magnetic hyperthermia is currently limited to the treatment of localized and relatively accessible cancer tumors because the required therapeutic temperatures above 40 °C can only be achieved by direct intratumoral injection of conventional iron oxide nanoparticles. To realize the true potential of magnetic hyperthermia for cancer treatment, there is an unmet need for nanoparticles with high heating capacity that can efficiently accumulate at tumor sites following systemic administration and generate desirable intratumoral temperatures upon exposure to an alternating magnetic field (AMF). Although there have been many attempts to develop the desired nanoparticles, reported animal studies reveal the challenges associated with reaching therapeutically relevant intratumoral temperatures following systemic administration at clinically relevant doses. Therefore, we developed efficient magnetic nanoclusters with enhanced heating efficiency for systemically delivered magnetic hyperthermia that are composed of cobalt- and manganese-doped, hexagon-shaped iron oxide nanoparticles (CoMn-IONP) encapsulated in biocompatible PEG-PCL (poly(ethylene glycol)- b-poly(ε-caprolactone))-based nanocarriers. Animal studies validated that the developed nanoclusters are nontoxic, efficiently accumulate in ovarian cancer tumors following a single intravenous injection, and elevate intratumoral temperature up to 44 °C upon exposure to safe and tolerable AMF. Moreover, the obtained results confirmed the efficiency of the nanoclusters to generate the required intratumoral temperature after repeated injections and demonstrated that nanocluster-mediated magnetic hyperthermia significantly inhibits cancer growth. In summary, this nanoplatform is a milestone in the development of systemically delivered magnetic hyperthermia for the treatment of cancer tumors that are difficult to access for intratumoral injection.

CTGF induces tenogenic differentiation and proliferation of adipose-derived stromal cells.

Intrasynovial tendons are paucicellular and hypovascular, resulting in a poor response to injury. Surgical repair of ruptured or lacerated tendons often lead to complications such as adhesions, repair site gapping, and repair site rupture. Adipose-derived stem cells (ASCs) have shown promise for enhancing tendon repair, as they have the capacity to differentiate into tendon fibroblasts and augment the healing response. Furthermore, connective tissue growth factor (CTGF) has been shown to promote tendon regeneration via the stimulation of endogenous tendon stem cells. Here, we evaluated the potential of CTGF to promote tenogenic differentiation of ASCs in vitro. Gene and protein expression, cell proliferation, and FAK and ERK1/2 signaling were assessed. CTGF increased tenogenic genes in mouse ASCs in a dose- and time-dependent manner. Western blot and immunostaining analyses demonstrated increases in tenogenic protein expression in CTGF-treated ASCs at all timepoints studied. CTGF increased ASC proliferation in a dose-dependent manner. CTGF induced phosphorylation of ERK1/2 within 5 min and FAK within 15 min; both signals persisted for 120 min. Blocking FAK and ERK1/2 pathways by selective inhibitors SCH772984 and PF573228, respectively, attenuated the CTGF-induced tenogenic differentiation and proliferation of ASCs. These results suggest that CTGF induces tenogenic differentiation of ASCs via the FAK and ERK1/2 pathway. Statement of clinical significance: Although prior research has led to advances in tendon operative techniques and rehabilitation methods, clinical outcomes after tendon repair remain variable, with high rates of repair site gapping or rupture. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.