Elevated MMP1 Expression in Carcinoma-Associated Fibroblasts of Breast Cancer Contributes to Tumor Progression and Unfavorable Prognosis.

OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer. METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments. RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment. CONCLUSION: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.

Machine learning-directed electrical impedance tomography to predict metabolically vulnerable plaques.

The characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low-density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning-directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL-rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six-point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL-rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training.

Metabolites 13,14-Dihydro-15-keto-PGE2 Participates in Bifidobacterium animalis F1-7 to Alleviate Opioid-Induced Constipation by 5-HT Pathway.

SCOPE: People suffer from constipation caused by many factors, including constipation (Opioid-Induced Constipation, OIC) during analgesic treatment. Microorganisms may be a potent solution to this problem, but the mechanism is still unclear. METHODS AND RESULTS: Based on models in vivo and in vitro, the potential mechanism involving Bifidobacterium animalis F1-7 (B. animalis F1-7), screened in the previous studies, is explored through non-targeted metabonomics, electrophysiological experiment and molecular level docking. The results showed that B. animalis F1-7 effectively alleviates OIC and promotes the expression of chromogranin A (CGA) and 5-hydroxytryptamine (5-HT). The metabolite 13,14-dihydro-15-keto-PGE2 related to B. animalis F1-7 is found, which has a potential improvement effect on OIC at 20 mg kg BW-1 in vivo. At 30 ng mL-1 it effectively stimulates secretion of CGA/5-HT (408.95 ± 1.18 ng mL-1 ) by PC-12 cells and changes the membrane potential potassium ion current without affecting the sodium ion current in vitro. It upregulates the target of free fatty acid receptor-4 protein(FFAR4/ß-actin, 0.81 ± 0.02). CONCLUSION: The results demonstrate that metabolite 13,14-dihydro-15-keto-PGE2 participated in B. animalis F1-7 to alleviate OIC via the 5-HT pathway.

Down-regulated Wnt7a and GPR124 in early-onset preeclampsia placentas reduce invasion and migration of trophoblast cells.

OBJECTIVES: Preeclampsia (PE) is a disease specific to pregnancy that causes 9-10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells. METHODS: Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation. RESULTS: In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=-0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis. CONCLUSIONS: Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction.

A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy.

The current cardiac pacemakers are battery dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest surgery (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and health care burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a lightweight microtubular pacemaker for intravascular implantation and pacing. The radio frequency was used to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a nonbeating heart and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Metagenomic insights into bacterial communities and functional genes associated with texture characteristics of Kazakh artisanal fermented milk Ayran in Xinjiang, China.

The complex microflora of traditional fermented milk is crucial to milk coagulation mainly through acid and protease production; however, it is still unclear which microbes and proteases significantly influence the texture of Ayran, a Kazakh artisanal fermented milk in Xinjiang, China. In this study, fifty-nine samples of Ayran were collected and investigated on texture properties. Finally, six Ayran samples with different texture features were screened out, and the taxonomic and functional attributes of their microbiota were characterized by metagenomics. The results showed that the hardness of the fermented milk in Yili Kazakh Autonomous Prefecture was significantly higher than that in other pasture areas. Lactobacillus and Lactococcus were the core genera that affected the coagulation quality of milk. Furthermore, we found that the proline iminopeptidase pip (EC 3.4.11.5) gene of Lactobacillus helveticus and Limosilactobacillus fermentum and the dipeptidase E pepE (EC 3.4.13.21) gene of Lactococcus lactis were most associated with the coagulation quality of fermented milk. Furthermore, positive correlations were observed among the hardness of fermented milk, the activity of the proteases, and the corresponding functional gene expressions.

Probiotics Alleviate Food Protein Allergy in Mice by Activating TLR4 Signaling Pathway.

SCOPE: Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. METHODS AND RESULTS: In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. CONCLUSION: The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.

Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating AHR/NRF2/NLRP3 Inflammasome Pathways through Indole-3-lactic Acid Production.

In this study, the effectors and mechanisms of Bifidobacterium bifidum FL-276.1 and B. bifidum FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both FL-276.1 and FL-228.1 significantly alleviated DSS-induced colitis, whether they were supplemented from the beginning of the experiment (whole course intervention) or after the DSS induction started (partial intervention). Aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid 2-related factor 2 (NRF2) pathways were activated in mice colons, while the NLR family pyrin domain containing 3 (NLRP3) was downregulated under the whole course intervention modes. Indole-3-lactic acid, an AHR ligand produced by FL-276.1 and FL-228.1, could regulate the AHR/NRF2/NLRP3 pathway in Caco-2 monolayers, thus upregulating the tight junction proteins and protecting the integrity of the epithelial barrier. These results are conducive to promoting clinical trials and product development of probiotics for alleviating colitis.

Protective effects of Bifidobacterium bifidum FL-228.1 on dextran sulfate sodium-induced intestinal damage in mice.

PURPOSE: Numerous studies have found that probiotics benefit the intestinal barrier. However, the prophylactic effects of probiotics on the intestinal barrier, i.e., if probiotics exert protective effects in healthy individuals to defend them against harmful elements, have seldomly been reported. The present study aimed to investigate the possible mechanisms of potential strains with the function of preventing intestinal barrier damage. METHODS: This study investigated nine potential probiotic strains using in vitro and in vivo models on their intestinal barrier-protecting properties. Transcriptomic was then employed to decipher the underlying mechanisms of action of the strains. RESULTS: The results showed that the strains, to varying degrees, regulated the ratio of interleukin (IL)-10 and IL-12 in peripheral blood mononuclear cells (PBMCs), increased the transepithelial electrical resistance (TEER) values, and decreased Caco-2 cell monolayers permeability. Correspondingly, the strains showed different prophylactic efficacies in protecting mice from dextran sulfate sodium (DSS)-induced intestinal barrier damage. Remarkably, Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best prophylactic efficacies in protecting mice from DSS-induced intestinal barrier damage. Further research suggested that FL-228.1 exerted its prophylactic effects by enhancing mucin 2 (Muc2) production and Claudin (Cldn)-4 in the colon. Furthermore, the transcriptomic and protein-protein interactions (PPI) analyses indicated that the inhibition of NLRP3 and the activation of PPARγ and TLR2 could be involved in protecting the intestinal barrier by FL-228.1. CONCLUSION: Bifidobacterium bifidum FL-228.1 may be developed as a promising probiotic for the prevention of intestinal barrier damage via PPARγ/NLRP3/ TLR2 pathways by enhancing Muc2 and Cldn-4.

Bifidobacterium animalis KV9 and Lactobacillus vaginalis FN3 alleviated ß-lactoglobulin-induced allergy by modulating dendritic cells in mice.

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, ß-lactoglobulin (ß-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of ß-LG-specific immunoglobulins E (ß-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8-IFN-γ+ T cells in the spleen increased, while CD3+CD8-IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce ß-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.

New Mutations in cls Lead to Daptomycin Resistance in a Clinical Vancomycin- and Daptomycin-Resistant Enterococcus faecium Strain.

Daptomycin (DAP), a last-resort antibiotic for treating Gram-positive bacterial infection, has been widely used in the treatment of vancomycin-resistant enterococci (VRE). Resistance to both daptomycin and vancomycin leads to difficulties in controlling infections of enterococci. A clinical multidrug-resistant Enterococcus faecium EF332 strain that shows resistance to both daptomycin and vancomycin was identified, for which resistance mechanisms were investigated in this work. Whole-genome sequencing and comparative genomic analysis were performed by third-generation PacBio sequencing, showing that E. faecium EF332 contains four plasmids, including a new multidrug-resistant pEF332-2 plasmid. Two vancomycin resistance-conferring gene clusters vanA and vanM were found on this plasmid, making it the second reported vancomycin-resistant plasmid containing both clusters. New mutations in chromosomal genes cls and gdpD that, respectively, encode cardiolipin synthase and glycerophosphoryl diester phosphodiesterase were identified. Their potential roles in leading to daptomycin resistance were further investigated. Through molecular cloning and phenotypic screening, two-dimensional thin-layer chromatography, fluorescence surface charge test, and analysis of cardiolipin distribution patterns, we found that mutations in cls decrease surface negative charges of the cell membrane (CM) and led to redistribution of lipids of CM. Both events contribute to the DAP resistance of E. faecium EF332. Mutation in gdpD leads to changes in CM phospholipid compositions, but cannot confer DAP resistance. Neither mutation could result in changes in cellular septa. Therefore, we conclude that the daptomycin resistance of E. faecium EF332 is conferred by new cls mutations. This work reports the genetic basis for vancomycin and daptomycin resistance of a multidrug-resistant E. faecium strain, with the finding of new mutations of cls that leads to daptomycin resistance.

Room-Temperature Annealing-Free Gold Printing via Anion-Assisted Photochemical Deposition.

Metal patterning via additive manufacturing has been phasing-in to broad applications in many medical, electronics, aerospace, and automotive industries. While previous efforts have produced various promising metal-patterning strategies, their complexity and high cost have limited their practical application in rapid production and prototyping. Herein, a one-step gold printing technique based on anion-assisted photochemical deposition (APD), which can directly print highly conductive gold patterns (1.08 × 107 S m-1 ) under ambient conditions without post-annealing treatment, is introduced. Uniquely, the APD uses specific ion effects with projection lithography to pattern Au nanoparticles and simultaneously sinter them into tunable porous gold structures. The significant influence of kosmotropic or chaotropic anions in the precursor ink on tuning the morphologies and conductivities of the printed patterns by employing a series of different ions, including Cl- ions, in the printing process is presented. Additionally, the resistance stabilities and the electrochemical properties of the APD-printed gold patterns are carefully investigated. The high conductivity and excellent conformability of the printed Au electrodes are demonstrated with reliable performance in electrophysiological signal delivery and acquisition for biomedical applications. This work exploits the potential of photochemical-deposition-based metal patterning in flexible electronic manufacturing.

Phage_UniR_LGBM: Phage Virion Proteins Classification with UniRep Features and LightGBM Model.

Phage, the most prevalent creature on the planet, serves a variety of critical roles. Phage's primary role is to facilitate gene-to-gene communication. The phage proteins can be defined as the virion proteins and the nonvirion ones. Nowadays, experimental identification is a difficult process that necessitates a significant amount of laboratory time and expense. Considering such situation, it is critical to design practical calculating techniques and develop well-performance tools. In this work, the Phage_UniR_LGBM has been proposed to classify the virion proteins. In detailed, such model utilizes the UniRep as the feature and the LightGBM algorithm as the classification model. And then, the training data train the model, and the testing data test the model with the cross-validation. The Phage_UniR_LGBM was compared with the several state-of-the-art features and classification algorithms. The performances of the Phage_UniR_LGBM are 88.51% in Sp,89.89% in Sn, 89.18% in Acc, 0.7873 in MCC, and 0.8925 in F1 score.

Bifidobacterium bifidum relieved DSS-induced colitis in mice potentially by activating the aryl hydrocarbon receptor.

Inflammatory bowel disease (IBD) characterized by relapsed intestinal inflammation and barrier function disruption is still a great therapeutic challenge. This study aimed to screen probiotics that have the potential to help alleviate IBD and further elucidate their mechanism of action. Caco-2 cell differentiated monolayers and RAW264.7 cells stimulated by lipopolysaccharide (LPS) were used for probiotic screening in vitro, and then the efficacies of the obtained six bacterial strains were evaluated in mice with dextran sulfate sodium (DSS)-induced colitis. The results showed that all of the strains at varying degrees could increase the transepithelial electrical resistance (TEER) value, decrease the influx of FITC-dextran in Caco-2 cell monolayers and attenuate the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated RAW264.7 cells. In vivo experiments indicated that Bifidobacterium bifidum FL-276.1 (FL-276.1) and Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best efficacies to ameliorate body weight loss, colon shortening, and intestinal barrier disruption. Accordingly, in FL-276.1 and FL-228.1 groups, the genes of zonula occludens-1 (ZO-1), claudin-4, occludin and mucin 2 (Muc2) in mouse colonic tissues were significantly upregulated, while TNF-α, IL-1ß and IL-6 were downregulated. Further results showed that strains FL-276.1 and FL-228.1 could activate the aryl hydrocarbon receptor (AhR) in the intestine. Our study showed that the two Bifidobacterium bifidum strains, FL-276.1 and FL-228.1, ameliorated DSS-induced colitis by enhancing the intestinal barrier and anti-inflammation potentially via the AhR pathway.

Lab-on-a-Contact Lens: Recent Advances and Future Opportunities in Diagnostics and Therapeutics.

The eye is one of the most complex organs in the human body, containing rich and critical physiological information (e.g., intraocular pressure, corneal temperature, and pH) as well as a library of metabolite biomarkers (e.g., glucose, proteins, and specific ions). Smart contact lenses (SCLs) can serve as a wearable intelligent ocular prosthetic device capable of noninvasive and continuous monitoring of various essential physical/biochemical parameters and drug loading/delivery for the treatment of ocular diseases. Advances in SCL technologies and the growing public interest in personalized health are accelerating SCL research more than ever before. Here, the current status and potential of SCL development through a comprehensive review from fabrication to applications to commercialization are discussed. First, the material, fabrication, and platform designs of the SCLs for the diagnostic and therapeutic applications are discussed. Then, the latest advances in diagnostic and therapeutic SCLs for clinical translation are reviewed. Later, the established techniques for wearable power transfer and wireless data transmission applied to current SCL devices are summarized. An outlook, future opportunities, and challenges for developing next-generation SCL devices are also provided. With the rise in interest of SCL development, this comprehensive and essential review can serve as a new paradigm for the SCL devices.

Electrical impedance tomography for non-invasive identification of fatty liver infiltrate in overweight individuals.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson's correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = -0.69, p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.

Impact of Tai Chi on CRP, TNF-alpha and IL-6 in inflammation: a systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that C reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Coronavirus disease 2019 (COVID-19) patients are significantly increased, and their progressive increases are clinical warning indicators of severe and critical severity. The purpose of this meta-analysis is to evaluate the efficacy of Tai Chi on CRP, TNF-alpha and IL-6, and provide a basis for complementary treatment of COVID-19. METHODS: Five English databases (PubMed, Web of Science, Physiotherapy Evidence Database, Cochrane Library and Embase) and four Chinese electronic databases (CNKI, Wanfang, China Science and Technology Journal Database and SinoMed) were searched from inception to April 1st, 2020. Combination MeSH and free text terms were used to make up search strategy. Interventions in RCTs were Tai Chi with or without comparison (usual care, health education, drug therapy, psychosocial therapy). Revman version 5.3 was used to analyze the extracted data. Continuous outcomes were described by SMD, and the I2 test was used to assess heterogeneity. Revised Physiotherapy Evidence Database scale was used to assess methodological quality. RESULTS: Nine RCTs involving 571 participants met the inclusion criteria, and the sample size ranged from 19 to 100 per study. Tai Chi can significantly reduce TNF-alpha (Tai Chi intervention: SMD =-0.92, 95% CI: -1.32 to -0.53; Tai Chi plus drug treatment intervention: SMD =-0.63, 95% CI: -1.15 to -0.11), moreover, it could reduce the amount of IL-6 (Tai Chi intervention: SMD =-0.62, 95% CI: -1.00 to -0.23; Tai Chi plus drug treatment intervention: SMD =-2.17, 95% CI: -3.69 to -0.64) and CRP (Tai Chi plus drug treatment intervention: SMD =-1.98, 95% CI: -2.47 to -1.50) while with a high exercise amount. A low exercise amount of Tai Chi showed poor efficacy on CRP (Tai Chi intervention: SMD =-0.18, 95% CI: -0.61 to 0.25; Tai Chi plus drug treatment intervention: SMD =-0.15, 95% CI: -0.47 to 0.16) and IL-6 (Tai Chi intervention: SMD =0.15, 95% CI: -0.24 to 0.55). DISCUSSION: The strength of evidence might be limited due to relatively low methodological quality, heterogeneity and indirectness. The overall results elucidate that Tai Chi could significantly reduce TNF-alpha while it did not show the same effects in IL-6 and CRP. After subgroup analysis, Tai Chi with a high exercise amount can reduce IL-6 and CRP. Tai Chi with a high exercise amount could be suggested as a complementary intervention for people with COVID-19. TRIAL REGISTRATION: PROSPERO CRD42020177655.

Effect of Inonotus obliquus (Fr.) Pilat extract on the regulation of glycolipid metabolism via PI3K/Akt and AMPK/ACC pathways in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Inonotus obliquus (Fr.) Pilat is a mushroom belonging to the family Hymenochaetaceae. It is popularly called the Chaga mushroom in Russian folk medicine and has been used as a traditional medicine to treat diabetes mellitus in Eastern European and Asian countries. However, its effects on glycolipid metabolism disorders and underlying molecular mechanism of action remain unclear. AIM OF THE STUDY: I. obliquus contains abundant functional components, which provide potential medicinal value. The purpose of this study was to investigate compositions of I. obliquus extract with a high-pressure water extraction method, and investigate the anti-type 2 diabetic effects of I. obliquus extract and the possible underlying mechanisms involved. MATERIALS AND METHODS: The I. obliquus was extracted by a high-pressure water extraction method, and tested its main components by special assay kit and instrumental analysis. Type 2 diabetic C57BL/6 mice were induced by high-fat diet with low-dose STZ injection, and were daily gavaged with different doses of I. obliquus extract for 8 weeks. Glycemic, blood lipid profile, and histopathology of liver and pancreas were assessed. Underlying mechanisms related to glycemic control in liver were further performed. RESULTS: The I. obliquus extract main compounds were ß-Glucans, triterpenoids and polyphenol by determination. Oral administration of 250 mg/kg and 500 mg/kg I. obliquus extract significantly alleviated blood glucose and insulin resistance. Moreover, 250 mg/kg and 500 mg/kg of I. obliquus extract increased liver glycogen content and high-density lipoprotein cholesterol (HDL-C) levels while decreased total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels. Furthermore, the protein expression levels of phosphatidylinositol-3 kinase (PI3K), p-protein kinase B (Akt), p-adenosine monophosphate activated protein kinase (AMPK), and p-acetyl-CoA carboxylase (ACC) were upregulated, whereas sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) were downregulated after supplement with 250 mg/kg and 500 mg/kg of I. obliquus extract. Interestingly, I. obliquus extract was a dose-effect relationship within a certain range. 250 mg/kg had obvious anti-diabetes effect, and the effect of 500 mg/kg dose was the same as that of metformin. CONCLUSION: I. obliquus extract ameliorated insulin resistance and lipid metabolism disorders in diabetic mice. The hypoglycemic and hypolipidemic properties of I. obliquus extract were supposedly exerted via the regulation of the PI3K/Akt and AMPK/ACC signaling pathways.

In Vivo Intravascular Pacing Using a Wireless Microscale Stimulator.

Millions of patients worldwide are implanted with permanent pacemakers for the treatment of cardiac arrhythmias and conduction disorders. The increased use of these devices has established a growing clinical need to mitigate associated complications. Pacemaker leads, in particular, present the primary risks in most implants. While wireless power transfer holds great promise in eliminating implantable device leads, anatomical constraints limit efficient wireless transmission over the necessary operational range. We thereby developed a transmitter-centered control system for wireless power transfer with sufficient power for continuous cardiac pacing. Device safety was validated using a computational model of the system within an MRI-based anatomical model. The pacer was then fabricated to meet the acute constraints of the anterior cardiac vein (ACV) to enable intravascular deployment while maintaining power efficiency. Our computational model revealed the wireless system to operate at > 50 times below the tissue energy absorption safety criteria. We further demonstrated the capacity for ex vivo pacing of pig hearts at 60 beats per minute (BPM) and in vivo pacing at 120 BPM following pacer deployment in the ACV. This work thus established the capacity for wireless intravascular pacing with the potential to eliminate complications associated with current lead-based deep tissue implants.