Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons.

BACKGROUND: SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38α, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38α are involved in the development of autism caused by Shank3 mutations or deficiency. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3-/-) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38α in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38α. T180A and Y182F mutations expressed inactive p38α. RESULTS: We found that Shank3 controls stereotypic behavior and sociability by regulating p38α activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3-/- mice. Consistently, overexpression of p38α in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38α in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3-/- mice. In contrast, activated p38α in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. LIMITATIONS: We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3-/- mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38α in AgRP neurons. CONCLUSIONS: These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38α signaling in AgRP neurons, suggesting that p38α signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism.

Postpartum uterine involution promoted by penetrating-moxibustion therapy: a randomized controlled trial. / é€ç¸æ³•ä¿ƒè¿›äº§åŽå­å®«å¤æ—§ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effect of penetrating-moxibustion therapy on postpartum uterine involution. METHODS: Eighty puerpera were randomized into an observation group and a control group, 40 cases in each one. In the control group, oxytocin injection was administered by intravenous drip, 20 U each time, once daily. In the observation group, on the base of the treatment as the control group, the penetrating-moxibustion therapy was used at Shenque (GV 8), Qihai (CV 6) and Guanyuan (CV 4), 30 min to 40 min each time, twice a day. The intervention of each group started from the first day after childbirth and lasted 3 days. The uterine volume before and after treatment, and in 42 days of postpartum, the height decrease of the fundus of the uterus, the score of visual analogue scale (VAS) for uterine contraction, the volume of lochia rubra in 1 to 3 days of treatment, and lochia duration were compared between the two groups; and the clinical effect was evaluated. RESULTS: The uterine volume in the observation group was smaller than that of the control group after treatment (P<0.01). In 1 to 3 days of treatment, the height decrease of the fundus of the uterus in the observation group was larger (P<0.01), VAS scores of uterine contraction were lower (P<0.05, P<0.01), the lochia rubra volume was less (P<0.01) than those in the control group. The duration of lochia rubra and lochia was shorter (P<0.01) in the observation group when compared with that of the control group. The favorable rate of uterine involution in the observation group was 95.0% (38/40), higher than that of the control group (75.0%, 30/40, P<0.05). CONCLUSIONS: Penetrating-moxibustion therapy accelerates the recovery of the uterine volume, relieves uterine contraction, shortens the duration of lochia, reduces the lochia volume and promotes the postpartum uterine involution.

Regulation mechanism and bioactivity characteristic of surfactin homologues with C14 and C15 fatty acid chains.

BACKGROUND: Surfactin, a green lipopeptide bio-surfactant, exhibits excellent surface, hemolytic, antibacterial, and emulsifying activities. However, a lack of clear understanding of the synthesis regulation mechanism of surfactin homologue components has hindered the customized production of surfactin products with different biological activities. RESULTS: In this study, exogenous valine and 2-methylbutyric acid supplementation significantly facilitated the production of C14-C15 surfactin proportions (up to 75% or more), with a positive correlation between the homologue proportion and fortified concentration. Subsequently, the branched-chain amino acid degradation pathway and the glutamate synthesis pathway are identified as critical pathways in regulating C14-C15 surfactin synthesis by transcriptome analysis. Overexpression of genes bkdAB and glnA resulted in a 1.4-fold and 1.3-fold increase in C14 surfactin, respectively. Finally, the C14-rich surfactin was observed to significantly enhance emulsification activity, achieving an EI24 exceeding 60% against hexadecane, while simultaneously reducing hemolytic activity. Conversely, the C15-rich surfactin demonstrated an increase in both hemolytic and antibacterial activities. CONCLUSION: This study presents the first evidence of a potential connection between surfactin homologue synthesis and the conversion of glutamate and glutamine, providing a theoretical basis for targeting the synthesis regulation and structure-activity relationships of surfactin and other lipopeptide compounds.

The Impact of Doctor-Nurse Complementary Model Combined with Disease Tracking on Stroke Patients.

Objective: The incidence of stroke worldwide is increasing year by year. With the enhancement of public health awareness, people's demand for the quality of stroke rehabilitation is getting higher and higher, so better quality care measures are needed in the treatment of stroke. Based on this, this paper explores the impact of a new type of nursing care measure, the complementary health care model combined with condition tracking, on stroke patients. Methods: 238 stroke patients were randomly divided into a conventional group (n=119) and a combined group (n=119). 238 stroke patients were randomly divided into conventional group (n=119) and combined group (n=119). The conventional group received routine care, in which doctors and nursing carried out their own work without cooperation after the patients were admitted to the hospital; the combined group received a complementary health care model and condition tracking, in which doctors and nurses jointly checked the rooms, discussed cases, jointly formulated treatments and nursing care plans, and jointly formulated the patients' discharge and rehabilitation plans after the patients were admitted to the hospital. Before the intervention, at the time of discharge, and 6 months after discharge, the neurological function of the patients in both groups was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the Fugl-Meyer (FMA) scale, the cognitive function of the patients in both groups was assessed using the Montreal Cognitive Assessment (MoCA) scale and the Measured Mental State Examination (MMSE), and the cognitive function of the patients in both groups was assessed using the General Self-Efficacy Scale (GSS) and the Montreal Cognitive Assessment (MCA) scale. General Self-Efficacy Scale (GSES) to assess self-efficacy, Exercise Adherence Questionnaire (EAQ) to assess adherence to functional exercise and Specific Quality of Life Scale (SSQoL-12) to assess the quality of life of patients in both groups, and the self-developed satisfaction with nursing care to assess patients' satisfaction with the care model. Results: Before the intervention, there was no difference in the National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer Assessment (FMA), the Montreal Cognitive Assessment (MoCA), the Mental State Examination (MMSE), the General Self-Efficacy Scale (GSES), the Exercise Adherence Questionnaire (EAQ) and the Stroke-Specific Quality of Life Scale-12 (SSQoL-12) scores between the two groups (P > .05). At discharge and six months later, NIHSS scores continued to decrease in both groups, with the joint group being lower than the conventional group (P < .05); scores for all other items continued to increase, with the joint being higher than the conventional group (P < .05). Satisfaction with care was higher in the combined group than in the conventional group (P < .05). Conclusion: The complementary healthcare model combined with condition tracking can effectively promote the prognosis of rehabilitation of stroke patients, and has a positive effect in promoting the recovery of neurological and cognitive functions, strengthening self-efficacy, and improving the quality of life, which can be promoted in the clinic.

Gut Microbiota and Aging: Traditional Chinese Medicine and Modern Medicine.

The changing composition of gut microbiota, much like aging, accompanies people throughout their lives, and the inextricable relationship between both has recently attracted extensive attention as well. Modern medical research has revealed that a series of changes in gut microbiota are involved in the aging process of organisms, which may be because gut microbiota modulates aging-related changes related to innate immunity and cognitive function. At present, there is no definite and effective method to delay aging. However, Nobel laureate Tu Youyou's research on artemisinin has inspired researchers to study the importance of Traditional Chinese Medicine (TCM). TCM, as an ancient alternative medicine, has unique advantages in preventive health care and in treating diseases as it already has formed an independent understanding of the aging system. TCM practitioners believe that the mechanism of aging is mainly deficiency, and pathological states such as blood stasis, qi stagnation and phlegm coagulation can exacerbate the process of aging, which involves a series of organs, including the brain, kidney, heart, liver and spleen. Our current understanding of aging has led us to realise that TCM can indeed make some beneficial changes, such as the improvement of cognitive impairment. However, due to the multi-component and multi-target nature of TCM, the exploration of its mechanism of action has become extremely complex. While analysing the relationship between gut microbiota and aging, this review explores the similarities and differences in treatment methods and mechanisms between TCM and Modern Medicine, in order to explore a new approach that combines TCM and Modern Medicine to regulate gut microbiota, improve immunity and delay aging.

Integrated fecal microbiota and metabolomics analysis of the orlistat intervention effect on polycystic ovary syndrome rats induced by letrozole combined with a high-fat diet.

BACKGROUND: This study aimed to compare the characteristics of the gut microbiota and their metabolite profiles between polycystic ovary syndrome (PCOS) and orlistat-treated PCOS rats (ORL-PCOS), which could help to better understand the underlying mechanism of the effect of orlistat on PCOS. METHODS: PCOS rat models were established using letrozole combined with a high-fat diet. Ten rats were randomly selected as a PCOS control group (PCOS). The other three groups (n = 10/group) were additionally supplemented with different doses of orlistat (low, medium, high). Then, fecal samples of the PCOS and ORL-PCOS groups were analysed by 16S rRNA gene sequencing and untargeted metabolomics. Blood samples were collected to detect serum sex hormones and lipids. RESULTS: The results showed that orlistat attenuated the body weight gain, decreased the levels of T, LH, the LH/FSH ratio, TC, TG and LDL-C; increased the level of E2; and improved estrous cycle disorder in PCOS rats. The bacterial richness and diversity of the gut microbiota in the ORL-PCOS group were higher than those in the PCOS group. The ratio of Firmicutes to Bacteroidetes was decreased with orlistat treatment. Moreover, orlistat treatment led to a significant decrease in the relative abundance of Ruminococcaceae and Lactobacillaceae, and increases in the abundances of Muribaculaceae and Bacteroidaceae. Metabolic analysis identified 216 differential fecal metabolites in total and 6 enriched KEGG pathways between the two groups, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction and vitamin digestion and absorption. Steroid hormone biosynthesis was the pathway with the most significant enrichment. The correlations between the gut microbiota and differential metabolites were calculated, which may provide a basis for understanding the composition and function of microbial communities. CONCLUSIONS: Our data suggested that orlistat exerts a PCOS treatment effect, which may be mediated by modifying the structure and composition of the gut microbiota, as well as the metabolite profiles of PCOS rats.

Explore the Mechanism of Astragalus mongholicus Bunge against Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Verification.

Objective: Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods: First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results: Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions: Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.

Expression profiling of the mitogen-activated protein kinase gene family reveals their diverse response pattern in two different salt-tolerant Glycyrrhiza species.

BACKGROUND: Mitogen-activated protein kinases (MPKs) play important role in response to environmental stress as crucial signal receptors or sensors. Our previous study indicated that salt stress acts as a positive factor to stimulate the production of pharmacodynamic metabolites in the medicinal plant Glycyrrhiza uralensis. Currently, little is known about the MPK gene family and their functions in the medicinal plant G. uralensis. OBJECTIVE: Identification, comprehensive bioinformatic analysis, expression profiling, and response pattern under salt stress of the G. uralensis GuMPK gene family. METHODS: Genome-wide investigation and expression profiling of the MPK gene family in G. uralensis, and their phylogenetic relationships, evolutionary characteristics, gene structure, motif distribution, promoter cis-acting element, and expression pattern under salt stress in two different salt-tolerant Glycyrrhiza species were performed. RESULTS: A total of 20 G. uralensis GuMPK genes were identified and categorized into five groups, and had conserved gene structure and motif distribution. Expression profiling of GuMPK genes suggested their potentially diverse functions in plant growth and in response to phytohormones and environmental stress, particularly GuMPK1, 2, 5, and 10 as key components for G. uralensis in response to abiotic stress. Further expression analysis under NaCl treatment in two different salt-tolerant Glycyrrhiza species displayed the MPKs' different response patterns, emphasizing the role of MPK2, 5, 7, and 16 as potentially crucial genes for Glycyrrhiza to respond to salt stress. CONCLUSION: Our results provide a genome-wide identification and expression profiling of MPK gene family in G. uralensis, and establish the foundation for screening key responsive genes and understanding the potential function and regulatory mechanism of GuMPKs in salt responsiveness.

Ultrasound-assisted green synthesis of gold nanoparticles using citrus peel extract and their enhanced anti-inflammatory activity.

Ultrasound and plant extract are two green approaches that have been used to synthesize gold nanoparticles (AuNPs); however, how the combination of ultrasound and citrus peel extract (CPE) affects the structure characteristics and the bioactivity of AuNPs remains unknown. Here we investigated the effects of ultrasound conditions on the particle size, stability, yield, phenolic encapsulation efficacy, and the anti-inflammatory activity of AuNPs. The results showed that temperature was positively correlated to the particle size and the anti-inflammatory activity of synthesized AuNPs. Increasing the power intensity significantly decreased the particle size, while increased the change of total phenolic content (ΔTPC) in the reaction mixture. The increase of ΔTPC caused the enhanced anti-inflammatory activity of AuNPs. The AuNPs synthesized with or without ultrasound treatment were characterized using UV-Vis, DLS, SEM, TEM, EDS, XRD, and FT-IR. The result verified the formation of negatively charged, spherical, stable, and monodispersed AuNPs. AuNPs synthesized with ultrasound (AuNPs-U) has smaller particle size (13.65 nm vs 16.80 nm), greater yield and anti-inflammatory activity (IC50, 82.91 vs 157.71 µg/mL) than its non-ultrasound counterpart (AuNPs-NU). HPLC analysis showed that hesperidin was the key reductant for the synthesis of AuNPs. AuNPs-U also inhibited the mRNA and protein expression of iNOS and COX-2 in the LPS-induced Raw 264.7 cells. Our research elucidates the relationship between the reaction conditions and the structure characteristics and the anti-inflammatory activity of AuNPs synthesized using CPE with the help of ultrasound, thereafter, provides a feasible and economic way to synthesize AuNPs that can be used to ameliorate inflammation.

[Auricular acupuncture of magnetic pellet combined with catheter balloon dilatation in treatment of post-stroke cricopharyngeus muscle dysfunction: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy on post-stroke cricopharyngeus muscle dysfunction treated with auricular acupuncture of magnetic pellet combined with catheter balloon dilatation, and the effect on the adverse reaction during catheter balloon dilatation and the patients' quality of life. METHODS: A total of 106 patients with post-stroke cricopharyngeus muscle dysfunction were randomly divided into an observation group (53 cases, 3 cases dropped off, 1 case excluded) and a control group (53 cases, 5 cases dropped off). The catheter balloon dilatation was provided in the control group, once a day. In the observation group, on the base of the treatment as the control group, auricular acupuncture of magnetic pellet was added. Before catheter balloon dilatation, the magnetic pellet was pressed at Yanhou (TG3), Xin (CO15), Naogan (AT3,4i), etc. These auricular points were pressed 5 min, as well as in every morning and evening for another 5 min, totally 3 times a day. The auricular acupuncture of magnetic pellet was applied on the ears alternatively each time, once every 3 days. One session treatment contained 6 days and 4 sessions of treatment were required in both groups. Before and after treatment, the scores of standardized swallowing assessment (SSA), Rosenbek penetration-aspiration scale (PAS) and swallowing quality of life (SWAL-QOL) were observed in both groups. Separately, on day 1 (T1) of treatment, in 2 weeks into treatment (T2) and on the last day of treatment (T3), the score of visual analogue scale (VAS) was recorded in both groups. The incidence of nausea and vomiting and the clinical efficacy were compared between the two groups. RESULTS: After treatment, SSA and PAS scores were reduced (P<0.05) and SWAL-QOL scores were increased (P<0.05) in both groups compared with those before treatment, and the changes in the observation group were larger than those in the control group (P<0.05). At T2 and T3, VAS scores were lower than those at T1 in both groups (P<0.05), while VAS score at each time point in the observation group was lower than that of the control group (P<0.05). The incidence of nausea and vomiting in the observation group was 51.0% (25/49), lower than the control group (79.2%, 38/48, P<0.05). The total effective rate was 95.9% (47/49) in the observation group, better than the control group (87.5%, 42/48, P<0.05). CONCLUSION: Auricular acupuncture of magnetic pellet combined with catheter balloon dilatation effectively improve the swallowing function, relieve the discomforts during the dilatation and promote the quality of life in patients with post-stroke cricopharyngeus muscle dysfunction.

Mindfulness-based intervention in Chinese pregnant women with recurrent miscarriage: A non-randomized controlled study.

OBJECTIVE: Pregnant women with recurrent miscarriage have high rates of anxiety and depression. Mindfulness-based interventions have shown benefits in improving mental health in diverse populations; however, few studies have explored their efficacy in pregnant women with recurrent miscarriage, which was investigated in the present study. DESIGN: A nonrandomized controlled study was carried out from August 2019 to November 2020. SETTING: The study was conducted at a regional teaching hospital in Guangzhou, China that provides leading care for recurrent miscarriage. PARTICIPANTS: A total of 158 pregnant women with recurrent miscarriage were recruited and allocated to the intervention group (n = 79) or the control group (n = 79); 131 women completed the study. INTERVENTION: The mindfulness-based intervention consisted of a 1-h education session and daily mindfulness exercises guided by audio recordings during hospitalization. MEASUREMENTS AND FINDINGS: Study outcomes included perceived stress measured with the Perceived Stress Scale; symptoms of anxiety and depression measured with the Self-rating Anxiety Scale and Edinburgh Postnatal Depression Scale, respectively; and positive and negative affect measured with the Positive Affect and Negative Affect Scale - Revised, respectively. Compared to the control group, participants in the intervention group showed significant decreases in perceived stress, depression symptoms, and negative affect and an increase in positive affect after the intervention. Anxiety increased significantly in the control group during the study but remained unchanged in the intervention group. KEY CONCLUSIONS: A mindfulness-based intervention can reduce psychological symptoms and improve mental health in pregnant women with recurrent miscarriage. IMPLICATIONS FOR PRACTICE: A mindfulness-based intervention should be incorporated into routine care to help improve the mental health of pregnant women with recurrent miscarriage.

Photothermal hydrogel platform for prevention of post-surgical tumor recurrence and improving breast reconstruction.

BACKGROUND: As one of the leading threats for health among women worldwide, breast cancer has high morbidity and mortality. Surgical resection is the major clinical intervention for primary breast tumor, nevertheless high local recurrence risk and breast tissue defect remain two main clinical dilemmas, seriously affecting survival and quality of life of patients. EXPERIMENTAL: We developed a thermoresponsive and injectable hybrid hydrogel platform (IR820/Mgel) by integration of co-loaded porous microspheres (MPs) and IR820 for preventing postoperative recurrence of breast cancer via photothermal therapy and promoting subsequent breast reconstruction. RESULTS: Our results suggested that IR820/Mgel could quickly heated to more than 50.0 â„ƒ under NIR irradiation, enabling killing effect on 4T1 cells in vitro and prevention effect on post-surgical tumor recurrence in vivo. In addition, the hydrogel platform was promising for its minimal invasion and capability of filling irregularly shaped defects after surgery, and the encapsulated MPs could help to increase the strength of gel to realize a long-term in situ function in vivo, and promoted the attachment and anchorage property of normal breast cells and adipose stem cells. CONCLUSIONS: This photothermal hydrogel platform provides a practice paradigm for preventing locally recurrence of breast cancer and a potential option for reconstruction of breast defects.

Effect and Safety of Penetrating Moxibustion in Treatment of Migraine without Aura: A Randomized Controlled Trial.

OBJECTIVE: To observe the clinical effect of penetrating moxibustion on migraine without aura (MO) patients. METHODS: Totally 60 MO patients from the Acupuncture Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine were collected from November 2015 to February 2017. All patients were assigned to a treatment group and a control group using a random number table, 30 cases in each group. The treatment group was treated with penetrating moxibustion, and the control group was treated with mild moxibustion, thrice a week for 4 consecutive weeks. The total effective rate, Visual Analogue Scale (VAS) scores, headache intensity, and Migraine Specific Quality of Life Questionnaire (MSQ) scores of patients after treatment were compared between the two groups. The moxibustion sensation and reaction after moxibustion were observed, and the adverse reactions were evaluated. All patients were followed up at 4 and 16 weeks after treatment. RESULTS: The total effective rate of the treatment group was significantly higher than that of the control group (93.33% vs. 80.00%, P<0.05). The improvement of VAS scores, headache intensity, and the role restrictive and role preventive scores in MSQ in the treatment group was better than those in the control group (P<0.05). The person-time of moxibustion sensations of itching, numbness and cold as well as flushing and sweating after moxibustion in the treatment group was all significantly higher than that in the control group (P<0.01). There was no significant difference in safety evaluation between the two groups (P>0.05). CONCLUSIONS: Penetrating moxibustion can significantly relieve pain and improve quality of life of MO patients. After penetrating moxibustion, flushing and sweating of patients were obvious, and the curative effect was superior to the mild moxibustion.

Berberine improves intralipid-induced insulin resistance in murine.

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 µM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.

Fourty-nine years old woman co-infected with SARS-CoV-2 and Mycoplasma: A case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the outbreak of respiratory illness known as coronavirus disease 2019 (CoVID-19). Mycoplasma is an uncommon co-infected pathogen with SARS-CoV-2 and has not yet been reported. Computed tomography (CT), used as an accessory examination, may play a more significant role in this co-infection. CASE SUMMARY: A 49-year-old female presented with a cough, expectoration and chest congestion followed by elevated C-reactive protein and erythrocyte sedimentation rate. CT images showed ground-glass opacities in bilateral lower lobes and a patchy and striate shadow in the right upper lobe. Immunoglobulin M antibody of Mycoplasma pneumoniae was positive and real-time fluorescence polymerase chain reaction of sputum was positive for SARS-CoV-2 nucleic acid. The diagnosis of CoVID-19 was made based on laboratory results, chest CT images, clinical manifestations and epidemiologic characteristics. She was treated with combination therapy for 17 d and showed a marked reCoVery. CONCLUSION: Co-infection with SARS-CoV-2 and Mycoplasma in CoVID-19 patients appears to be uncommon. CT is an acceptable method for the primary diagnosis and treatment should be initiated as soon as possible. Combination therapy with antiviral, anti-inflammatory, traditional Chinese herbal medicine and interferon inhalation may be a reference for further progress in treating this co-infection.

Characterization of the Aroma of an Instant White Tea Dried by Freeze Drying.

The aroma of an instant white tea (IWT) was extracted through simultaneous distillation-extraction (SDE) and analyzed by sensory evaluation, gas chromatography-mass spectrometry-olfactometry (GC-MS-O), aroma reconstruction, omission test and synergistic interaction analysis. Sensory evaluation showed the IWT was dominated with floral and sweet notes. The SDE extract had the aroma similar to the IWT. The main volatile components in the SDE extract were benzyl alcohol, linalool, hotrienol, geraniol, α-terpineol, coumarin, camphene, benzeneacetaldehyde, 2-hexanone, cis-jasmin lactone and phenylethyl alcohol. GC-MS-O and aroma reconstruction experiments showed 16 aroma-active compounds. Linalool, trans-ß-damascenone and camphene were the major contributors to floral, sweet and green notes based on flavor dilution analysis and omission test. Linalool and trans-ß-damascenone had synergistic effect to promote floral and sweet notes. Camphene and trans-ß-damascenone had synergistic effect to reduce green and sweet notes. The study helps to understand the aroma of IWT and antagonism interactions among aroma-active volatiles.

An RNAi supplemented diet as a reverse genetics tool to control bluegreen aphid, a major pest of legumes.

Aphids are important agricultural pests causing major yield losses worldwide. Since aphids can rapidly develop resistance to chemical insecticides there is an urgent need to find alternative aphid pest management strategies. Despite the economic importance of bluegreen aphid (Acyrthosiphon kondoi), very few genetic resources are available to expand our current understanding and help find viable control solutions. An artificial diet is a desirable non-invasive tool to enable the functional characterisation of genes in bluegreen aphid and discover candidate target genes for future use in RNA interference (RNAi) mediated crop protection against aphids. To date no artificial diet has been developed for bluegreen aphid, so we set out to develop a suitable diet by testing and optimising existing diets. Here, we describe an artificial diet for rearing bluegreen aphid and also provide a proof of concept for the supplementation of the diet with RNAi molecules targeting the salivary gland transcript C002 and gap gene hunchback, resulting in bluegreen aphid mortality which has not yet been documented in this species. Managing this pest, for example via RNAi delivery through artificial feeding will be a major improvement to test bluegreen aphid candidate target genes for future pest control and gain significant insights into bluegreen aphid gene function.

Fucoidan affects oral squamous cell carcinoma cell functions in vitro by regulating FLNA-derived circular RNA.

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types, with a high annual incidence. Although chemotherapy contributes to suppressing OSCC tumorigenesis, the available treatments result in poor prognosis because of local recurrence and regional lymph node metastasis. Thus, it is necessary to discover novel and safe drugs with greater effectiveness and fewer side effects. Fucoidan is a component of the cell wall of brown seaweed that has been shown to produce a wide range of biological activities. The present study aimed to investigate the effectiveness of fucoidan in treating OSCC. In in vitro studies, we found that fucoidan inhibited OSCC growth and suppressed migration and invasion of OSCC cells. In addition, the potential interaction between fucoidan and filamin A (FLNA)-derived circular RNA (circFLNA) was predicted using bioinformatics databases and then confirmed in OSCC samples and cell lines. Indeed, fucoidan increased the expression of circFLNA in OSCC cell lines. Furthermore, both fucoidan and circFLNA could mediate the expression of key proteins related to cell growth, apoptosis, migration, and invasion. In conclusion, our research demonstrated that fucoidan might be considered as a potential natural drug in the treatment of OSCC patients by targeting circFLNA.

[Analysis on the distribution of pressure- and heat-sensitive acupoints in patients with allergic rhinitis].

OBJECTIVE: To explore the distribution of pressure- and heat-sensitive acupoints of the Large Intestine of Hand-Yangming, Stomach Meridian of Foot-Yangming and the Lung Meridian of Hand-Taiyin below the elbow and knee joints in patients with allergic rhinitis, so as to explore the positive reaction points at the body surface of allergic rhinitis. METHODS: Thirty variant rhinitis volunteer subjects and 30 healthy subjects were recruited in the present study. The subcutaneous induration, reaction points of emptiness-like feeling or pressing pain below the elbow- and knee-joints along the Large Intestine Meridian, Stomach Meridian and the Lung Meridian were inspected first, then re-examined by using heat-sensitized moxibustion method and a hand-held pain threshold tester (mechanical pressure), respectively. The frequency and coincidence rate of pressing-pain sensitive and heat-sensitive points were analyzed. RESULTS: In the 30 patients with allergic rhinitis, 10 positive reaction points as Kongzui (LU6), Chize (LU5), Hegu (LI4), Quchi (LI11), Shousanli(LI10), Zusanli (ST36), Shangjuxu (ST37), Fenglong (ST40), Xiajuxu (ST39), and non-acupoint of the Lung Meridian were found. Among them, the duration of heat-sensitive reaction in the LU6, LI10, ST37, ST40, and ST39 regions was obviously shorter in patients than in healthy subjects (P<0.01,P<0.005). The heat-sensitive forms of the positive reaction points were mainly heat transmission, heat-penetration and local reaction. The mechanical pain thresholds of the positive reaction points (LI4, LU6, LI10, LI11 and non-acupoint of the Lung Meridian) at the upper limbs and those (ST36, ST37 and ST40) at the lower limbs were evidently lower in patients than in healthy volunteer subjects (P<0.05). The pressure- and heat-sensitive acupoints were basically coincide in the patients, but being higher in patients than in healthy subjects in the frequency of occurrence. The mechanical pain threshold of the pressure-sensitive acupoints in patients was remarkably lower on the left side than on the right side of the upper limb, and obviously higher on the left side than on the right side of the lower limb (P<0.05). No significant differences were found between the right and left sides in the pain threshold in healthy subjects (P>0.05). CONCLUSION: There is a high overlap in the distribution of pressure- and heat-sensitive acupoints of the Lung, Large Intestine and Stomach meridians below the elbow and knee joints in patients with allergic rhinitis, and there is an imbalance between the left and right limbs in the mechanical pain threshold of the pressure- and heat-sensitive acupoints, but needing being further confirmed.

[Ultrasound-guided suprascapular nerve block combined with acupuncture for the treatment of calcified tendinitis of rotator cuff].

OBJECTIVE: To explore the method and effect of ultrasound-guided suprascapular nerve block combined with acupuncture in the treatment of calcified tendinitis of rotator cuff. METHODS: From January 2015 to December 2017, total 30 patients with calcified tendinitis, including 23 cases of supraspinatus tendon, 5 cases of infraspinatus tendon and 2 cases of subscapular tendon, were treated with ultrasound-guided suprascapular nerve block combined with acupuncture. There were 7 males and 23 females, ranging in age from 36 to 71 years old, with an average of 51.6 years old. There were 17 cases on the right and 13 cases on the left. VAS pain score, Constant-murley score, UCLA score and X-ray examination were used to evaluate the clinical results before and after surgery. RESULTS: The mean follow-up was 14.3 months (6 to 30 months). The preoperative VAS score was 3.82±1.13, Constant-Murley score was 36.91±7.95 and UCLA score was 11.35±2.17. The final follow-up scores were 1.32±1.06, 90.61±2.89 and 33.22±1.51, respectively. The final follow-up scores were improved significantly(P<0.05). CONCLUSIONS: Conservative treatment of calcified rotator cuff tendinitis is ineffective. Suprascapular nerve block guided by ultrasound combined with acupuncture has a good therapeutic effect. It is a minimally invasive, economic, safe and effective method, which is worth promoting.