In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals.

Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration.

At-Home Saliva Sampling in Healthy Adults Using CandyCollect, a Lollipop-Inspired Device.

Respiratory infections are common in children, and there is a need for user-friendly collection methods. Here, we performed the first human subjects study using the CandyCollect device, a lollipop-inspired saliva collection device .We showed that the CandyCollect device can be used to collect salivary bacteria from healthy adults using Streptococcus mutans and Staphylococcus aureus as proof-of-concept commensal bacteria. We enrolled healthy adults in a nationwide (USA) remote study in which participants were sent study packages containing CandyCollect devices and traditional commercially available oral swabs and spit tubes. Participants sampled themselves at home, completed usability and user preference surveys, and mailed the samples back to our laboratory for analysis by qPCR. Our results showed that for participants in which a given bacterium (S. mutans or S. aureus) was detected in one or both of the commercially available methods (oral swab and/or spit tubes), CandyCollect devices had a 100% concordance with the positive result (n = 14 participants). Furthermore, the CandyCollect device was ranked the highest preference sampling method among the three sampling methods by 26 participants surveyed (combining survey results across two enrollment groups). We also showed that the CandyCollect device has a shelf life of up to 1 year at room temperature, a storage period that is convenient for clinics or patients to keep the CandyCollect device and use it any time. Taken together, we have demonstrated that the CandyCollect is a user-friendly saliva collection tool that has the potential to be incorporated into diagnostic assays in clinic visits and telemedicine.

Iron Availability Modulates the Response of Endosymbiotic Dinoflagellates to Heat Stress.

Warming and nutrient limitation are stressors known to weaken the health of microalgae. In situations of stress, access to energy reserves can minimize physiological damage. Because of its widespread requirements in biochemical processes, iron is an important trace metal, especially for photosynthetic organisms. Lowered iron availability in oceans experiencing rising temperatures may contribute to the thermal sensitivity of reef-building corals, which rely on mutualisms with dinoflagellates to survive. To test the influence of iron concentration on thermal sensitivity, the physiological responses of cultured symbiotic dinoflagellates (genus Breviolum; family Symbiodiniaceae) were evaluated when exposed to increasing temperatures (26 to 30°C) and iron concentrations ranging from replete (500 pM Fe') to limiting (50 pM Fe') under a diurnal light cycle with saturating radiance. Declines in photosynthetic efficiency at elevated temperatures indicated sensitivity to heat stress. Furthermore, five times the amount of iron was needed to reach exponential growth during heat stress (50 pM Fe' at 26-28°C vs. 250 pM Fe' at 30°C). In treatments where exponential growth was reached, Breviolum psygmophilum grew faster than B.minutum, possibly due to greater cellular contents of iron and other trace metals. The metal composition of B.psygmophilum shifted only at the highest temperature (30°C), whereas changes in B.minutum were observed at lower temperatures (28°C). The influence of iron availability in modulating each alga's response to thermal stress suggests the importance of trace metals to the health of coral-algal mutualisms. Ultimately, a greater ability to acquire scarce metals may improve the tolerance of corals to physiological stressors and contribute to the differences in performance associated with hosting one symbiont species over another.

[Protective effect of serum containing ginseng and Moutan Cortex on HUVEC injured by H_2O_2].

This study aimed to investigate the effect of serum containing ginseng and Moutan Cortex on human umbilical vein endothelial cells(HUVEC) injured with hydrogen peroxide(H_2O_2). HUVEC injured with H_2O_2 were divided into 6 groups, namely blank group, model group, ginsenoside(TGG) group, total glucosides of Moutan Cortex(TGM) group, paeonol(P) group and TGG+TGM+P group. After 24 hours of co-culture with H_2O_2, the activities of succinate dehydrogenase(SDH) and Ca~(2+)-Mg~(2+)-ATP were detected by microenzyme labeling. The apoptosis rate, intracellular Ca~(2+) concentration, reactive oxygen species(ROS) and mitochondrial membrane potential(JC-1) were detected by flow cytometry. The expressions of mitochondrial apoptosis pathway-related proteins Bax, Bcl-2, cytochrome C, caspase-3 and caspase-9 were detected by Western blot. The results showed that H_2O_2 could significantly damage HUVEC, decrease the activity of SDH and Ca~(2+)-Mg~(2+)-ATP(P<0.01), while could increase the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(P<0.01). Serum containing ginseng and Moutan Cortex could increase the activities of SDH and Ca~(2+)-Mg~(2+)-ATP to different degrees, decrease the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(P<0.05 or P<0.01), and down-regulate the protein expressions of Bax, caspase-3, caspase-9, cytochrome C, and up-regulate the protein expression of Bcl-2. The results showed that serum containing ginseng and Moutan Cortex has a protective effect on vascular endothelial cell injury induced by ROS, and its mechanism may be related to the improvement of mitochondrial function and the inhibition of the activation of mitochondrial apoptosis pathway.

Lactobacillus hegangensis sp. nov., Lactobacillus suibinensis sp. nov., Lactobacillus daqingensis sp. nov., Lactobacillus yichunensis sp. nov., Lactobacillus mulanensis sp. nov., Lactobacillus achengensis sp. nov., Lactobacillus wuchangensis sp. nov., Lactobacillus gannanensis sp. nov., Lactobacillus binensis sp. nov. and Lactobacillus angrenensis sp. nov., isolated from Chinese traditional pickle and yogurt.

Fourteen Gram-stain-positive bacterial strains were isolated from Chinese traditional pickle and yogurt. The strains were characterized using a polyphasic taxonomic approach, including 16S rRNA gene sequence analysis, pheS gene sequence analysis, rpoA gene sequence analysis, fatty acid methyl ester analysis, determination of DNA G+C content, determination of average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH) and an analysis of phenotypic features. The data demonstrated that the 14 strains represented ten novel species belonging to the genus Lactobacillus, strains 73-4T, 247-3T, 143-4(a)T, 33-1T, 143-6T, 247-4T, 17-4T, 143-1T, 735-2T and M1530-1T were designated as the type strains. Strains 73-4T and 247-3T were phylogenetically related to the type strains of Lactobacillus camelliae and Lactobacillus jixianensis, having 97.0-98.9 % 16S rRNA gene sequence similarities, 83.9-87.2 % pheS gene sequence similarities and 86.8-93.3 % rpoA gene sequence similarities. Strains 143-4(a)T and 33-1T were phylogenetically related to the type strains of Lactobacillus rhamnosus, Lactobacillus paracasei and Lactobacillus casei, having 93.6-96.5 % 16S rRNA gene sequence similarities, 73.9-77.2 % pheS gene sequence similarities and 76.1-77.6 % rpoA gene sequence similarities. Strains 143-6T, 247-4T, 17-4T and 143-1T were phylogenetically related to the type strains of Lactobacillus concavus, Lactobacillus dextrinicus and Lactobacillus bayanensis, exhibiting 95.5-99.9 % 16S rRNA gene sequence similarities, 76.5-83.1 % pheS gene sequence similarities and 83.6-98.3 % rpoA gene sequence similarities. Strain 735-2T was phylogenetically related to the type strains of Lactobacillus zhaoyuanensis, Lactobacillus jiayinensis and Lactobacillus coryniformis, having 98.2-99.1 % 16S rRNA gene sequence similarities, 82.8-84.1 % pheS gene sequence similarities and 93.0-93.9 % rpoA gene sequence similarities. Strain M1530-1T was phylogenetically related to the type strains of Lactobacillus suantsaiihabitans and Lactobacillus brevis, having 99.5 and 99.0 % 16S rRNA gene sequence similarities, 90.3 and 81.7 % pheS gene sequence similarities and 97.7 and 91.1 % rpoA gene sequence similarities. The ANI and isDDH values between strains 73-4T, 247-3T, 143-4(a)T, 33-1T, 143-6T, 247-4T, 17-4T, 143-1T, 735-2T, M1530-1T and type strains of phylogenetically related species were less than 86.8 % and 33.9 % respectively, confirming that they represent ten novel species within the genus Lactobacillus. Based upon the data of polyphasic characterization obtained in the present study, ten novel species, Lactobacillus hegangensis sp. nov., Lactobacillus suibinensis sp. nov., Lactobacillus daqingensis sp. nov., Lactobacillus yichunensis sp. nov., Lactobacillus mulanensis sp. nov., Lactobacillus achengensis sp. nov., Lactobacillus wuchangensis sp. nov., Lactobacillus gannanensis sp. nov., Lactobacillus binensis sp. nov. and Lactobacillus angrenensis sp. nov., are proposed and the type strains are 73-4T (=NCIMB 15177T=CCM 8912T=CCTCC AB 2018407T), 247-3T (=NCIMB 15176T=JCM 33275T), 143-4(a)T (=NCIMB 15173T=CCM 8948T=JCM 33273T=CCTCC AB 2018390T), 33-1T (=NCIMB 15169T=CCM 8947T=JCM 33272T=CCTCC AB 2018405T), 143-6T (=NCIMB 15162T=CCM 8951T=JCM 33274T=CCTCC AB 2018411T), 247-4T (=NCIMB 15155T=CCM 8897T=LMG 31059T=CCTCC AB 2018410T), 17-4T (=NCIMB 15161T=CCM 8946T=JCM 33271T=CCTCC AB 2018406T), 143-1T (=NCIMB 15157T=CCM 8937T=CCTCC AB 2018409T), 735-2T (=NCIMB 15190T=CCM 8925T=LMG 31186T) and M1530-1T (=NCIMB 15150T=CCM 8893T=LMG 31046T=CCTCC AB 2018402T), respectively.

RepSox, a small molecule inhibitor of the TGFß receptor, induces brown adipogenesis and browning of white adipocytes.

Unlike white adipose tissue (WAT), brown adipose tissue (BAT) is mainly responsible for energy expenditure via thermogenesis by uncoupling the respiratory chain. Promoting the differentiation of brown fat precursor cells and the browning of white fat have become a research hotspot for the treatment of obesity and associated metabolic diseases. Several secreted factors and a number of small molecules have been found to promote brown adipogenesis. Here we report that a single small-molecule compound, RepSox, is sufficient to induce adipogenesis from mouse embryonic fibroblasts (MEFs) in fibroblast culture medium. RepSox is an inhibitor of the transforming growth factor-beta receptor I (TGF-ß-RI), other inhibitors of TGF-ß pathway such as SB431542, LY2157299, A83-01, and Tranilast are also effective in inducing adipogenesis from MEFs. These adipocytes express brown adipocyte-specific transcription factors and thermogenesis genes, and contain a large number of mitochondria and have a high level of mitochondrial respiratory activity. More interestingly, RepSox has also been found to promote the differentiation of the brown fat precursor cells and induce browning of the white fat precursor cells. These findings suggest that inhibitors of TGF-ß signaling pathway might be developed as new therapeutics for obesity and type 2 diabetes.

Impact of Recurrent Weight Gain Thresholds on Comorbid Conditions Progression Following Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: Defining recurrent weight gain after metabolic bariatric surgery poses a significant challenge. Our study aimed to standardize recurrent weight gain measurements in patients undergoing laparoscopic sleeve gastrectomy (LSG) and ascertain its association with comorbidity progression. METHODS: We conducted a retrospective data analysis on 122 patients who underwent LSG, tracking their progress over 2-7 years. Data on weight, blood pressure measurements, and laboratory tests were collected, focusing on the postoperative period to identify nadir weight, total weight loss, and recurrent weight gain. RESULTS: Significant weight loss and comorbidity remission were noted, with diabetes, hypertension, and dyslipidemia showing substantial remission rates of 85.71%, 68.24%, and 85.37%, respectively. The median recurrent weight gain was 6.30 kg within 12 months of the nadir. Progression proportion of diabetes, hypertension, and dyslipidemia were 8.20%, 44.26%, and 40.98%, respectively. Hypertension progression was strongly associated with a recurrent weight gain ≥ 10 kg and ≥ 20% of maximum weight loss. Dyslipidemia progression was significantly correlated with recurrent weight gain ≥ 10 kg and ≥ 20% of maximum weight loss. Diabetes progression was significantly correlated with recurrent weight gain ≥ 10% of pre-surgery body weight and ≥ 25% of maximum weight loss. A ≥ 10% weight gain of maximum weight loss did not significantly impact the progression of these conditions. CONCLUSION: Recurrent weight gain ≥ 20% of maximum weight loss can be treated as a specific threshold indicating comorbidity progression post-LSG. Standardizing the measurement of recurrent weight gain can help healthcare providers to implement targeted management strategies to optimize long-term health outcomes.

Capture of Group A Streptococcus by Open-Microfluidic CandyCollect Device in Pediatric Patients.

Importance: Obtaining high-quality samples to diagnose streptococcal pharyngitis in pediatric patients is challenging due to discomfort associated with traditional pharyngeal swabs. This may cause reluctance to go to the clinic, inaccurate diagnosis, or inappropriate treatment for children with sore throat. Objective: Determine the efficacy of using CandyCollect, a lollipop-inspired open-microfluidic pathogen collection device, to capture Group A Streptococcus (GAS) and compare user preference for CandyCollect, conventional pharyngeal swabs, or mouth swabs among children with pharyngitis and their caregivers. Design: Participants of this cohort study were recruited over a 7-month period in 2022 - 2023. Setting: This study was conducted at an ambulatory care clinic that serves pediatric patients in the Madison, Wisconsin, metropolitan area. Participants: Study participants were diagnosed with GAS pharyngitis using a traditional pharyngeal swab via rapid antigen detection test (RADT); those testing positive were approached or reached out to about participation in the study. A total of 74 caregiver/children dyads were contacted about the study: 23 declined to participate; 21 were not eligible; and 30 willing and eligible participants were admitted into the study. A caregiver provided verbal consent and parental permission, and all children provided verbal assent. Immediately after the standard of care visit in which the throat swab was obtained, a research nurse guided participants through collecting oral samples: CandyCollect device and mouth swab (ESwab TM ). CandyCollect and mouth swab samples were analyzed for GAS by quantitative polymerase chain reaction (qPCR) at the University of Washington. Exposure: Detection of salivary GAS using qPCR analysis of samples obtained from CandyCollect devices and mouth swabs. Main Outcomes and Measures: The proportion of pediatric patients with GAS pharyngitis, as determined by a positive pharyngeal swab tested via a RADT, who were also positive using a CandyCollect and mouth swab analyzed by qPCR. Results: All child participants (30/30) were positive for GAS by qPCR on both the mouth swab and CandyCollect. Caregivers ranked CandyCollect as a good sampling method overall (27/30), and all caregivers (30/30) would recommend the CandyCollect for children 5 years and older. Twenty-three of 30 children "really like" the taste and 24/30 would prefer to use the CandyCollect if a future test was needed. All caregivers (30/30) and most children (28/30) would be willing to use the CandyCollect device at home. Conclusion and relevance: All participants tested positive for GAS on all three collection methods (pharyngeal swab, mouth swab, and CandyCollect). While both caregivers and children like the CandyCollect device, some caregivers would prefer a shorter collection time. Future work includes additional studies with larger cohorts presenting with pharyngitis of unknown etiology and shortening collection time, while maintaining the attractive form of the device. Trial Registration: Registry name: ClinicalTrials.gov ClinicalTrials.gov Identifier: NCT05175196 Weblink: https://classic.clinicaltrials.gov/ct2/show/NCT05175196. Key Points: Question: In pediatric patients with Group A Streptococcus pharyngitis, how do test results and user experience compare across three sampling methods-CandyCollect devices, mouth swabs, and pharyngeal swabs?Findings: In this cohort study of 30 children, aged 5-14 years, saliva samples were collected with CandyCollect devices and mouth swabs and analyzed via qPCR. The results show CandyCollect, a pathogen collection tool preferred by children, had 100% concordance with the results from pharyngeal swabs positive with a rapid antigen detection test performed as part of their clinical care.Meaning: With further development and testing, the CandyCollect device may potentially become an alternative sampling tool for the diagnosis of streptococcal pharyngitis.

Open-Channel Droplet Microfluidic Platform for Passive Generation of Human Sperm Microdroplets.

Sperm cryopreservation is important for individuals undergoing infertility treatment, and for those who wish to preserve fertility potential, prior to treatments like chemotherapy, radiation therapy, gender-affirming medical interventions, elective fertility delay, or individuals in high-risk professions such as the military. Current methods for sperm cryopreservation result in approximately 30-50% decrease in sperm motility. However, recent studies have shown that ultra-rapid freezing (vitrification) is a valuable approach for maintaining sperm quality after freeze-thawing processes in the clinical laboratory setting and requires submicroliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample. Here, we present a method that leverages open-channel droplet microfluidics to autonomously generate sub-microliter to microliter volumes of purified human sperm samples. Using a novel, open-channel droplet generator, we found no change in sperm movement and kinematic data after exposure to device and reagents in our platform. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories.

Enhanced capillary pumping using open-channel capillary trees with integrated paper pads.

The search for efficient capillary pumping has led to two main directions for investigation: first, assembly of capillary channels to provide high capillary pressures, and second, imbibition in absorbing fibers or paper pads. In the case of open microfluidics (i.e., channels where the top boundary of the fluid is in contact with air instead of a solid wall), the coupling between capillary channels and paper pads unites the two approaches and provides enhanced capillary pumping. In this work, we investigate the coupling of capillary trees-networks of channels mimicking the branches of a tree-with paper pads placed at the extremities of the channels, mimicking the small capillary networks of leaves. It is shown that high velocities and flow rates (7 mm/s or 13.1 µl/s) for more than 30 s using 50% (v/v) isopropyl alcohol, which has a 3-fold increase in viscosity in comparison to water; 6.5 mm/s or 12.1 µl/s for more than 55 s with pentanol, which has a 3.75-fold increase in viscosity in comparison to water; and >3.5 mm/s or 6.5 µl/s for more than 150 s with nonanol, which has a 11-fold increase in viscosity in comparison to water, can be reached in the root channel, enabling higher sustained flow rates than that of capillary trees alone.

Miniaturizing chemistry and biology using droplets in open systems.

Open droplet microfluidic systems manipulate droplets on the picolitre-to-microlitre scale in an open environment. They combine the compartmentalization and control offered by traditional droplet-based microfluidics with the accessibility and ease-of-use of open microfluidics, bringing unique advantages to applications such as combinatorial reactions, droplet analysis and cell culture. Open systems provide direct access to droplets and allow on-demand droplet manipulation within the system without needing pumps or tubes, which makes the systems accessible to biologists without sophisticated setups. Furthermore, these systems can be produced with simple manufacturing and assembly steps that allow for manufacturing at scale and the translation of the method into clinical research. This Review introduces the different types of open droplet microfluidic system, presents the physical concepts leveraged by these systems and highlights key applications.

At-home saliva sampling in healthy adults using CandyCollect, a lollipop-inspired device.

Respiratory infections are common in children, and there is a need for user-friendly collection methods. Here, we performed the first human subjects study using the CandyCollect device, a lollipop inspired saliva collection device. 1 We showed the CandyCollect device can be used to collect salivary bacteria from healthy adults using Streptococcus mutans and Staphylococcus aureus as proof-of-concept commensal bacteria. We enrolled healthy adults in a nationwide (USA) remote study in which participants were sent study packages containing CandyCollect devices and traditional commercially available oral swabs and spit tubes. Participants sampled themselves at home, completed usability and user preference surveys, and mailed the samples back to our laboratory for analysis by qPCR. Our results showed that for participants in which a given bacterium ( S. mutans or S. aureus ) was detected in one or both of the commercially available methods (oral swab and/or spit tubes), CandyCollect devices had a 100% concordance with the positive result (n=14 participants). Furthermore, the CandyCollect device was ranked the highest preference sampling method among the three sampling methods by 26 participants surveyed (combining survey results across two enrollment groups). We also showed that the CandyCollect device has a shelf life of up to 1 year at room temperature, a storage period that is convenient for clinics or patients to keep the CandyCollect device and use it any time. Taken together, we have demonstrated that the CandyCollect is a user-friendly saliva collection tool that has the potential to be incorporated into diagnostic assays in clinic visits and telemedicine.

The effect of Taohong Siwu decoction combined with antihypertensive medicine in the treatment of hypertension: Meta-analysis.

BACKGROUND: Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine. Recent research has shown that the practical components of THSWD have specific curative effects on various cardiovascular diseases, including hypertension, suggesting THSWD could effectively lower blood pressure (BP) with fewer side effects. However, little information is available regarding the effectiveness of THSWD combined with antihypertensive medicine on hypertension. OBJECTIVE: This meta-analysis aimed to study the efficacy and safety of THSWD in treating hypertension. METHODS: According to the search strategy, 8 databases were searched, including China Knowledge Network (CNKI), Wanfang Database, VIP Database, Pubmed, China Biomedical Literature Database (CBM), web of science, EMBASE and Cochrane Library, for the randomized controlled trial of THSWD on hypertension. 9 RCTs were included and 827 patients were involved. This meta-analysis used RevMan 5.4 to evaluate the articles. RESULTS: This review included 9 RCTs. All studies were THSWD with the antihypertensive drug compared with single antihypertensive western medicine. The total effective rate of THSWD combined with corresponding western medicine was significantly improved (Relative risk = 1.26; 95% CI: 1.16-1.37, P < .00001), which could effectively reduce the systolic BP (MD = -15.28 mm Hg; 95% CI: -20.17 to -10.40, P < .00001=, diastolic BP (MD = -9.70 mm Hg; 95% CI: -12.66 to -6.73, P < .00001), Triglycerides (MD = -1.48, 95%CI: -2.09 to -0.87, P < .00001), total cholesterol (MD = -1.43, 95% CI: -1.63 to -1.24, P < .00001) and low density lipoprotein cholesterol (MD = -0.93, 95% CI: -1.07 to -0.80, P < .00001). Compared with the single routine western medicine group, THSWD combined with the corresponding western medicine increased serum high-density lipoprotein (MD = 0.41, 95% CI: 0.35 to 0.46, P < .00001). CONCLUSION: THSWD combined with antihypertensive drugs in treating hypertension was curative in lowering BP, improving blood lipid levels and reducing the incidence of adverse reactions compared to antihypertensive medications treatment. However, more high-quality studies are needed due to the biased results and the small number of studies for further verification of the effectiveness of THSWD, and providing a new treatment for clinical reference.

Evaluation of Persistent Efficacy of Diabetes Remission and Decline of Cardiovascular Risk After Laparoscopic Sleeve Gastrectomy: a Preliminary 1-Year Study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a relative safe procedure in bariatric surgery. However, relatively few studies had been assessed its comprehensive efficacies. In the current study, the efficacies of LSG were comprehensively explored on glycemic control and cardiovascular disease (CVD) risk reduction. METHODS: A total of 95 obese patients, who owned body mass index (BMI) of more than 35, were recruited. All of them primarily underwent LSG from 2014 to 2016. Type 2 diabetes mellitus (T2DM) remission was defined as levels of glycated hemoglobin (A1C) and fasting blood glucose (FBG) of less than 6.4% and 125 mg/dL, respectively. The further efficacies of LSG on CVD and coronary heart disease (CHD) risks were explored by using original- and recalibrated Framingham 10-year CHD risk scores and the other 3 well-established CVD risk prediction models. RESULTS: Systolic blood pressure (SBP), serum FBG, A1C, triglyceride (TG), BMI, and body weight showed significantly declined and high-density lipoprotein-cholesterol (HDL) displayed twice higher than beginning level after LSG. The 71 of 95 patients with obesity were T2DM; 62 of them exhibited persistent DM remission until 1 year after LSG. Cardiovascular age, general cardiovascular risk (GCVR), and atherosclerotic cardiovascular disease risk (ASCVD) also showed significant decrements after LSG. We also observed significant reductions in estimated CVD and CHD risks. CONCLUSION: LSG resulted in a persistent T2DM remission and corrected metabolic abnormalities. Subsequently, LSG also benefits declined risks of CVD and 10-year CHD developments. LSG may be helpful for primary CVD care in obese patients with BMI of more than 35.

6M50LSG Scoring System Increased the Proportion of Adequate Excess Body Weight Loss for Suspected Poor Responders After Laparoscopic Sleeve Gastrectomy in Asian Population.

PURPOSE: We aimed to evaluate the efficacy of the predictive tool, 6M50LSG scoring system, to identify suspected poor responders after laparoscopic sleeve gastrectomy (LSG). METHODS: The 6M50LSG scoring system has been applied since 2019. Suspected poor responders are defined by EBWL at 1 month < 19.5% or EBWL at 3 months < 37.7% based on the 6M50LSG scoring system. Our analysis included 109 suspected poor responders. Based on the date of LSG, the patients were separated into two groups: the 2016-2018 group (before group, BG, with regular care) and the 2019-2020 group (after group, AG, with upgrade medical nutrition therapy). RESULTS: At the end of the study, the AG group had a significantly higher proportion of adequate weight loss, which was defined as EBWL ≥ 50% at 6 months after LSG, than that in the BG group (18.92% in BG vs. 48.57% in AG, p = 0.003). The AG group demonstrated significantly more 3-months-TWL (BG: 15.22% vs. AG: 17.54%, p < 0.001) and 6-months-TWL (BG: 21.08% vs. AG: 25.65%, p < 0.001). In multivariate analyses and adjustments, the scoring system (AG) resulted in significantly higher chances of adequate weight loss in suspected poor responders (adjusted OR 3.392, 95% CI = 1.345-8.5564, p = 0.010). One year after LSG, suspected poor responders in AG had a significantly higher weight loss than those in BG (BG vs. AG: TWL 27.17% vs. 32.20%, p = 0.014) . CONCLUSION: This study confirmed that the 6M50LSG scoring system with upgraded medical nutrition therapy increased the proportion of suspected poor responders with adequate weight loss after LSG.

Gastrointestinal involvement in systemic sclerosis: An updated review.

The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the highest incidence reported in people aged 44 to 55. Females are 5 times more likely than males to suffer from SSc. Morbidity and mortality rates associated with SSc are predominantly elevated among patients with GI manifestations. Esophageal and intestinal manifestations impact 90% and 40% to 70% of patients with systemic scleroderma, respectively. SSc patients are known to suffer from small bowel hypomotility and small intestinal bacterial overgrowth, which cause malabsorption and malnutrition, ultimately contributing to the 50% mortality rate. Fecal incontinence is a common symptom of SSc that can lead to depression. SSc patients may suffer from gastrointestinal complications that can negatively impact their quality of life on a daily basis. Multidisciplinary approaches are necessary for systematically managing gastrointestinal complications associated with SSc. A prospective study should focus on developing targeted therapies to improve recovery patterns and prognosis in cases of SSc. This article summarizes the epidemiology, commonly reported clinical manifestations, complications, and available treatments for treating GI pathology in SSc patients.

CandyCollect: at-home saliva sampling for capture of respiratory pathogens.

Streptococcus pyogenes is a major human-specific bacterial pathogen and a common cause of a wide range of symptoms from mild infection such as pharyngitis (commonly called strep throat) to life-threatening invasive infection and post-infectious sequelae. Traditional methods for diagnosis include collecting a sample using a pharyngeal swab, which can cause discomfort and even discourage adults and children from seeking proper testing and treatment in the clinic. Saliva samples are an alternative to pharyngeal swabs. To improve the testing experience for strep throat, we developed a novel lollipop-inspired sampling platform (called CandyCollect) to capture bacteria in saliva. The device can be used in clinics or in the home and shipped back to a lab for analysis, integrating with telemedicine. CandyCollect is designed to capture bacteria on an oxygen plasma treated polystyrene surface embedded with flavoring substances to enhance the experience for children and inform the required time to complete the sampling process. In addition, the open channel structure prevents the tongue from scraping and removing the captured bacteria. The flavoring substances did not affect bacterial capture and the device has a shelf life of at least 2 months (with experiments ongoing to extend the shelf life). We performed a usability study with 17 participants who provided feedback on the device design and the dissolving time of the candy. This technology and advanced processing techniques, including polymerase chain reaction (PCR), will enable user-friendly and effective diagnosis of streptococcal pharyngitis.

[Determination of metal elements in Achyranthis bidentatae radix from various habitats].

OBJECTIVE: To establish an atomic absorption spectrometry method for determination of the contents of metal elements in Achyranthis Bidentatae Radix and analyze 21 batches of samples from different areas. METHODS: Fe, Mn, Ca, Mg, K, Zn and Cu were detected by atomic absorption spectrometry with hydrogen flame detector, Pb, As and Cd were detected by graphite furnace atomic absorption, Hg was detected by cold atomic absorption. RESULTS: The heavy metal contents met the requirement of Chinese Pharmacopoeia. The contents of K, Mg, Cu and Mn in the samples of geo-authentic areas were higher,while the contents of Fe, Zn, Hg and Pb in the samples of non-authentic areas were higher. CONCLUSION: This method is sample, accurate, repeatable and could be used to evaluate the quality of Achyranthis Bidentatae Radix.

Hydralazine-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Asymptomatic and Renal-Restricted Presentation.

BACKGROUND Hydralazine, a potent vasodilator widely used to treat hypertension, has been implicated in an increasing number of cases of drug-induced autoimmune diseases in recent years. However, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis secondary to hydralazine use has rarely been described and most reported cases involved multi-organ-related vasculitis, including skin and lung-kidney manifestations. ANCA-associated vasculitis is an immune-inflammatory condition characterized by necrotizing vasculitis with few or no immune deposits, predominantly affecting small vessels. The fact that the vasculitis is associated with hydralazine use and improves with discontinuation of hydralazine supports the diagnosis of hydralazine-induced disease. The case we report is a hydralazine-induced, ANCA-associated, pauci-immune crescentic glomerulonephritis with a presentation limited to the kidneys. CASE REPORT A 66-year-old woman was admitted to the hospital for worsening renal function over a month with no symptoms. Serology work-up was significantly positive for antinuclear, perinuclear ANCA, anti-histone, anti-double-stranded DNA, anti-cardiolipin, and anti-myeloperoxidase antibodies. The patient ultimately underwent a kidney biopsy, which revealed pauci-immune crescentic glomerulonephritis. Her kidney function improved with cessation of hydralazine as well as therapy with pulse steroids. CONCLUSIONS Hydralazine is commonly prescribed to treat hypertension. Healthcare providers should be aware of potentially severe hydralazine-induced ANCA-associated vasculitis, which can present with various clinical manifestations. Serologic studies have indicated that it has features that overlap with lupus. Biopsy is helpful for making a definitive diagnosis and developing individual treatment plans. Early diagnosis, cessation of the offending drug, and initiation of immunosuppressive therapy are key for favorable prognosis.

Network and 16S rRNA Sequencing-Combined Approach Provides Insightal Evidence of Vitamin K2 for Salt-Sensitive Hypertension.

Vitamin K2 (VK2), found to act to treat hypertension, has been widely used in the food and pharmaceutical industries nowadays. However, the potential targets and molecular mechanisms of VK2 for salt-sensitive hypertension have not been fully investigated. Therefore, the study aimed to investigate the potential molecular mechanisms of VK2 for salt-sensitive hypertension using network pharmacology and 16S rRNA sequencing strategy. The network pharmacology-based findings from KEGG enrichment analysis revealed that VK2-treated salt-sensitive hypertension was mechanically associated with the complement and coagulation cascades, calcium signaling pathway, renin-angiotensin system, etc. A total of 29 different bacteria in an animal experiment after VK2 supplementation were screened and functionally enriched using PICRUSt2. Additionally, 10 signaling pathways were identified in which the renin-angiotensin system was found to be the potential molecular mechanisms with the greatest change in multiple and statistical significance. Moreover, the results of the renin-angiotensin system-related protein expression exhibited VK2-inhibited renin-angiotensin system in salt-induced hypertensive mice, which significantly verified the previous biological and functional prediction analysis. Finally, spearman correlation analysis showed the different bacteria such as Dubosiella, Ileibacterium, etc., had a positive or negative correlation with renin-angiotensin system-related proteins in salt-induced mice. In conclusion, the potential molecular mechanisms of VK2 for salt-sensitive hypertension may be beneficially achieved by the specific inhibition of the renin-angiotensin system, contributing to the development for a new preventive strategy of salt-sensitive hypertension.