Accelerating spliced alignment of long RNA sequencing reads using parallel maximal exact match retrieval.

The genomics landscape has undergone a revolutionary transformation with the emergence of third-generation sequencing technologies. Fueled by the exponential surge in sequencing data, there is an urgent demand for accurate and rapid algorithms to effectively handle this burgeoning influx. Under such circumstances, we developed a parallelized, yet accuracy-lossless algorithm for maximal exact match (MEM) retrieval to strategically address the computational bottleneck of uLTRA, a leading spliced alignment algorithm known for its precision in handling long RNA sequencing (RNA-seq) reads. The design of the algorithm incorporates a multi-threaded strategy, enabling the concurrent processing of multiple reads simultaneously. Additionally, we implemented the serialization of index required for MEM retrieval to facilitate its reuse, resulting in accelerated startup for practical tasks. Extensive experiments demonstrate that our parallel algorithm achieves significant improvements in runtime, speedup, throughput, and memory usage. When applied to the largest human dataset, the algorithm achieves an impressive speedup of 10.78 × , significantly improving throughput on a large scale. Moreover, the integration of the parallel MEM retrieval algorithm into the uLTRA pipeline introduces a dual-layered parallel capability, consistently yielding a speedup of 4.99 × compared to the multi-process and single-threaded execution of uLTRA. The thorough analysis of experimental results underscores the adept utilization of parallel processing capabilities and its advantageous performance in handling large datasets. This study provides a showcase of parallelized strategies for MEM retrieval within the context of spliced alignment algorithm, effectively facilitating the process of RNA-seq data analysis. The code is available at https://github.com/RongxingWong/AcceleratingSplicedAlignment.

Electro-scalp acupuncture regulates the expression of CYP27a1/b1, CYP24a and related inflammatory cytokines in ischemic cortex of rats with middle cerebral artery occlusion. / ç”µå¤´é’ˆè°ƒæŽ§å¤§è„‘ä¸­åŠ¨è„‰æ “å¡žå¤§é¼ ç¼ºè¡€å¤§è„‘çš®å±‚åŒºCYP27a1/b1、CYP24aåŠç›¸å ³ç‚Žæ€§ç»†èƒžå› å­è¡¨è¾¾çš„ç ”ç©¶.

OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.

Butyrate and Propionate are Negatively Correlated with Obesity and Glucose Levels in Patients with Type 2 Diabetes and Obesity.

Background: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases. To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial. This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity. Methods: A total of 12 patients with T2D and obesity and 8 age- and sex-matched healthy individuals with BMI <24 kg/m2 were enrolled in this study. Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline. Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline. The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition. Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry. Results: Butyrate concentration significantly increased from baseline after obvious weight loss (P<0.05). Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) (P<0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG (P<0.05). No association was found between acetate and obesity. Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity.

Preventive effect of Cleome spinosa against cucumber Fusarium wilt and improvement on cucumber growth and physiology.

Cucumber wilt is an important soil borne disease in cucumber production, which seriously affects the development of the cucumber industry. Cleome spinosa also has pharmacological effects such as antibacterial, analgesic, anti-inflammatory, and insect repellent. To study the control effect and mechanism of Cleome spinosa fumigation on cucumber wilt disease, different concentrations of Cleome spinosa fragments were applied on cucumber plants infected with Fusarium oxysporum. Cleome spinosa fumigation significantly reduced the incidence rate of cucumber Fusarium wilt. Under the fumigation treatment of 7.5 g kg-1 Cleome spinosa fragments, the preventive effects were 74.7%. Cleome spinosa fragments fumigation can promote cucumber growth and synthesis of photosynthetic pigments, thereby improving individual plant yield and fruit quality. At 7.5 g kg-1 Cleome spinosa fragments fumigation treatment, the plant height and individual plant yield of cucumber increased by 20.3% and 34.3%, respectively. Cleome spinosa fumigation can enhance the activity of antioxidant enzymes in cucumber, maintain a balance of reactive oxygen species metabolism, and enhance the plant disease resistance. Moreover, Cleome spinosa can also regulate the activities of Mg2+-ATPase and Ca2+-ATPase, enhancing its resistance to Fusarium oxysporum. Moreover, number of bacteria and fungi significantly decreased under Cleome spinosa fumigation. Those results suggested that Cleome spinosa could effectively restrain cucumber Fusarium wilt. This study will provide a new idea for the further use of biological fumigation to prevent soil-borne diseases.

Electrospun nanofibers electrostatically adsorb heterotrophic nitrifying and aerobic denitrifying bacteria to degrade nitrogen in wastewater.

Nanofibers were prepared by electrospinning a mixture of polycaprolactone and silica, and modified to improve the hydrophilicity and stability of the material and to degrade nitrogenous wastewater by adsorbing heterotrophic nitrifying aerobic denitrifying (Ochrobactrum anthropic). The immobilized bacteria showed highly efficient simultaneous nitrification-denitrification ability, which could convert nearly 90 % of the initial nitrogen into gaseous nitrogen under aerobic conditions, and the average TN removal rate reached 5.59 mg/L/h. The average ammonia oxidation rate of bacteria immobilized by modified nanofibers was 7.36 mg/L/h, compared with 6.3 mg/L/h for free bacteria and only 4.23 mg/L/h for unmodified nanofiber-immobilized bacteria. Kinetic studies showed that modified nanofiber-immobilized bacteria complied with first-order degradation kinetics, and the effects of extreme pH, temperature, and salinity on immobilized bacteria were significantly reduced, while the degradation rate of free bacteria produced larger fluctuations. In addition, the immobilized bacterial nanofibers were reused five times, and the degradation rate remained stable at more than 80 %. At the same time, the degradation rate can still reach 50 % after 6 months of storage at 4 °C. It also demonstrated good nitrogen removal in practical wastewater treatment.

Physiological mechanism beneath the inhibition of Cleome spinosa against the morphology and reproduction of Fusarium oxysporum.

Fusarium oxysporum is a soil-borne plant pathogen that can cause various plant diseases including cucumber wilt. An experiment was conducted to explore the physiological mechanism underlying the inhibitory activity of Cleome spinosa against the morphology and reproduction of F. oxysporum. Different concentrations of C. spinosa extracts. -0 (Z0), 5 (Z5), 15 (Z15), 30 (Z30), 45 (Z45), and 60 (Z60) mg·mL-1 were applied to F. oxysporum. Cleome spinosa extract significantly reduced the colony diameter (89.7 %) and dry mass (78.9 %) of F. oxysporum under the Z45 treatment. Moreover, spore formation was also significantly inhibited by C. spinosa extract. The spore number and germination rate decreased by 73.5 % and 83.0 %, respectively, under the Z45 treatment. The number of mycelia in the unit field of view was significantly reduced, and the mycelia were wizened with rough surfaces and more bends under the Z45 treatment. Hence, C. spinosa extracts severely damaged the morphology of F. oxysporum mycelia. Additionally, F. oxysporum could not adjust to the osmotic changes caused by C. spinosa extract, leading to membrane injury and electrolyte leakage. Finally, they impaired the antioxidant system in F. oxysporum, resulting in cell membrane injury.

Latent profiles of nurses' moral resilience and compassion fatigue.

BACKGROUND: Compassion fatigue is often associated with moral distress in the nursing practice among registered nurses. Moral resilience is an important ability to maintain, restore, or promote their physical and mental health in response to ethical dilemmas in nursing. Moral resilience can be utilized as a potential solution to aid registered nurses in effectively managing compassion fatigue. AIM: To identify latent profiles of moral resilience among registered nurses and to explore the relationships of these profiles with compassion fatigue. RESEARCH DESIGN: From August 2022 to December 2022, 569 nurses were recruited in two general hospitals, in China. A Rushton Moral Resilience Scale and the Chinese version of Compassion Fatigue-Short Scale were given to the participants. A latent profile analysis was conducted to explore moral resilience latent profiles. Predictors of profiles membership was evaluated using multinomial logistic regression analysis, and the compassion fatigue scores of each latent profile were compared using a one-way analysis of variance. ETHICAL CONSIDERATIONS: We obtained ethical approval from the Institution Review Board of Xiangya School of Nursing, Central South University (IRB No. E202293, approved 15/July/2022). RESULTS: A four-profile moral resilience model best fit the data. Different levels and shapes differentiated the four profiles: high moral resilience (28.7%), moderate moral resilience (52.3%), low responses and high efficacy (16.2%), and low moral resilience (2.8%). Nurses with bachelor's degrees were more likely to belong to the high moral resilience (OR = 0.118, p = .038) and moderate moral resilience (OR = 0.248, p = .045); Nurses who were divorced or separated (OR = 11.746, p = .025) and very dissatisfied with their work (OR = 0.001, p = .049) were more probably belonging to low moral resilience. Nurses who had received ethical training in the hospital were more likely involved in high moral resilience (OR = 5.129, p = .003) and low responses and high efficacy (OR = 5.129, p = .003). In each profile of moral resilience, compassion fatigue was experienced differently by the participants (F = 13.05, p < .001). CONCLUSIONS: Developing and implementing interventions tailored to each nurse's moral resilience profile would maximize interventions' effectiveness and reduce nurses' compassion fatigue.

[Study on alleviating neuroinflammatory injury in ischemic stroke rats by electrical stimulation with scalp acupuncture based on IFN-γ mediated JAK/STAT1 signaling pathway].

OBJECTIVE: To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway. METHODS: Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot. RESULTS: Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (P<0.01), while the expression level of IL-10 was decreased (P<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (P<0.01), the percentage of cerebral infarction volume was decreased (P<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (P<0.01), while the expression level of IL-10 was increased (P<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (P<0.05, P<0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (P<0.01, P<0.05). CONCLUSION: Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.

[Effects of electro-scalp acupuncture on inflammatory response and microglial polarization in the ischemic cortex of rats with ischemic stroke].

OBJECTIVE: To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1ß, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. METHODS: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1ß, and IL-10 in the ischemic cortex. RESULTS: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1ß in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1ß, and IL-10 in the ischemic cortex (P<0.01, P<0.05). CONCLUSION: ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.

First Report of Leaf Spot on Soybean Caused by Epicoccum sorghinum in Heilongjiang Province, China.

Soybean (Glycine max (Linn.) Merr.) is one of the important oil crops in China. In September 2022, a new soybean leaf spot disease was found in Zhaoyuan County, Suihua City, Heilongjiang Province, China. Symptoms of the initial formation of irregular brown lesions on the leaves, dark brown inside, the periphery is yellow, vein chlorotic yellow, severe leaf spots connected into pieces, late fall off, not the same as previously reported soybean leaf spot (Fig. 1A). The leaf samples of infected plants were collected, and the leaf tissue (5 × 5 mm) was cut from the edge of the lesion, and then surface sterilized with 3% sodium hypochlorite for 5 min, rinsed with sterile distilled water for 3 times, and inoculated on potato dextrose agar (PDA) at 28°C. Isolates growing around the tissues from samples were subcultured on PDA, and 3 isolates were obtained using the single-spore isolation method. The fungal hyphae were white or grayish white in early stage, and the hyphae with light green concentric ring appeared on the front of the colony after 3 days, appeared orange, pink or white convex, irregular shape, reddish brown on the front of the colony for 10 days and black spherical pycnidium can be produced in the hyphae layer for 15 days (Fig.1D, E). Conidia were oval, hyaline, unicellular, aseptate, and 2.3 to 3.7 × 4.1 to 6.8 µm (n=30, Fig. 1F). Chlamydospores were subglobose, light brown, unicellular or multicellular, and 7.2 to 14.7 × 12.2 to 43.9 µm (n=30, Fig. 1H, I). Pycnidia mostly spheroid, brown, and 47.1 to 114.4 × 72.6 to 167.4 µm (n=30, Fig. 1G). A cetyl trimethyl ammonium bromide method was used to extract DNA from 7-day-old. Internal transcribed spacer (ITS), RNA polymerase II (RPB2) and ß-tubulin (TUB) gene were amplified using ITS1/ITS4 (White et al. 1990), RPB2-5F/RPB2-7cR (Liu et al. 1999) and BT2a/Bt2b (O'Donnell et al. 1997) primers respectively. The sequences obtained by polymerase chain reaction (PCR) were sequenced and the results showed that the DNA sequences of the 3 isolates were identical. Therefore, the sequence of isolate DNES22-01, DNES22-02 and DNES22-03 was submitted to GenBank. According to BLAST search, the ITS (OP884646), RPB2 (OP910000) and TUB (OP909999) sequences showed 99.81% similarity to Epicoccum sorghinum strain LC12103 (MN215621.1), 99.07% to strain P-XW-9A (MW446946.1), and 98.85% with the strain UMS (OM048108.1), respectively. Phylogenetic analysis by maximum likelihood method (MEGA7.0) generated based on the ITS, RPB2 and TUB sequences indicated that the isolates formed a supported clade to the related E. sorghinum type sequences. Isolates was found to be most closely related to E. sorghinum and far from other species. Based on morphological and phylogenetic characteristics, isolates DNES22-01, DNES22-02 and DNES22-03 was identified as E. sorghinum (Bao et al. 2019; Chen et al. 2021; Zhang et al. 2022). At the 4-leaf-stage, 10 soybean plants were inoculated by spraying with a conidial suspension (1 × 106 spores·ml-1). Sterile water served as a control. The test was repeated 3 times. All samples were incubated in a growth chamber at 27°C. Symptoms typical developed on the leaves after 7 days, but control samples remained healthy (Fig.1B, C). The fungus was reisolated from symptomatic tissues and identified as E. sorghinum by morphology characteristics and molecular characterization. To our knowledge, this is the first report of E. sorghinum causing leaf spot on soybean in Heilongjiang, China. The results can provide the basis for future studies on the occurrence, prevention, and management of this disease.

Multi-store collaborative delivery optimization based on Top-K order-split.

Regarding the fulfillment optimization of online retail orders, many researchers focus more on warehouse optimization and distribution center optimization. However, under the background of new retailing, traditional retailers carry out online services, forming an order fulfillment model with physical stores as front warehouses. Studies that focus on physical stores and consider both order splitting and store delivery are rare, which cannot meet the order optimization needs of traditional retailers. To this end, this study proposes a new problem called the "Multi-Store Collaborative Delivery Optimization (MCDO)", in which not only make the order-split plans for stores but also design the order-delivery routes for them, such that the order fulfillment cost is minimized. To solve the problem, a Top-K breadth-first search and a local search are integrated to construct a hybrid heuristic algorithm, named "Top-K Recommendation & Improved Local Search (TKILS)". This study optimizes the search efficiency of the breadth-first search by controlling the number of sub-orders and improving the initial solution of the local search using a greedy cost function. Then achieve the joint optimization of order-split and order-delivery by improving the local optimization operators. Finally, extensive experiments on synthetic and real datasets validate the effectiveness and applicability of the algorithm this study proposed.

Knockdown of FBLN2 suppresses TGF-ß1-induced MRC-5 cell migration and fibrosis by downregulating VTN.

Idiopathic pulmonary fibrosis (IPF) is a common chronic and progressive lung disease. Fibulin-2 (FBLN2) is upregulated in patients with IPF; however, its exact role in IPF remains unclear. The present study aimed to investigate the role and the regulatory mechanism of FBLN2 in TGF-ß1-induced fibrogenesis using human lung fibroblast-derived MRC-5 cells. Cell transfection was performed to regulate FBLN2 expression. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the expression levels of FBLN2 and vitronectin (VTN). Cell viability and migration were determined via the Cell Counting Kit-8 and wound healing assays, respectively. Immunofluorescence was performed to detect α-smooth muscle actin (α-SMA)-positive cells. The STRING database was used to predict the interaction between FBLN2 and VTN, which was verified via the protein immunoprecipitation assay. The results demonstrated that inhibition of FBLN2 notably inhibited TGF-ß1-induced proliferation and migration, as well as downregulating the protein expression levels of MMP2 and MMP9 in MRC-5 cells. In addition, inhibition of FBLN2 suppressed the expression levels of α-SMA, collagen type 1 α1 and fibronectin. FBLN2 was demonstrated to bind to VTN and negatively regulate its expression. Furthermore, overexpression of VTN partly abolished the inhibitory effects of FBLN2 knockdown on TGF-ß1-induced proliferation, migration and fibrosis, as well as the activity of focal adhesion kinase (FAK) signaling. Taken together, the results of the present study suggest that FBLN2 knockdown can attenuate TGF-ß1-induced fibrosis in MRC-5 cells by downregulating VTN expression via FAK signaling. Thus, FBLN2 may be a potential therapeutic target for IPF treatment.

Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of cardiometabolic diseases in a Chinese natural population: A cross-sectional study.

AIMS: Visceral adiposity and skeletal muscle loss may be positively correlated with cardiometabolic outcomes. This study aimed to explore the associations between the visceral fat area to skeletal muscle mass ratio (VSR) and the risk of cardiometabolic diseases in a Chinese natural population. MATERIALS AND METHODS: A total of 5158 participants were included in this study. Body composition, anthropometrical, and biochemical measurements were performed. Body composition was assessed via the direct segmental multi-frequency bioelectrical impedance analysis method. The associations between VSR and metabolic associated fatty liver disease (MAFLD), hyperglycemia, hypertension, dyslipidemia, and hyperuricemia were analysed. RESULTS: With the increase of VSR by one quartile, the odds ratio (OR) increased significantly for all five cardiometabolic diseases in both genders (ptrend  < 0.001). With regard to the highest versus the lowest quartile of VSR, the ORs for cardiometabolic diseases were significantly higher in women than in men. Restricted cubic splines showed that there were significant non-linear relationships between VSR and the risk of MAFLD, dyslipidemia, hyperglycemia, and hypertension in both genders (p for non-linearity <0.05). The risk was relatively flat until VSR reached 3.078 cm2 /kg in men and 4.750 cm2 /kg in women and started to increase rapidly afterwards. In men, however, the risk slowed down after the VSR value reached around 4 cm2 /kg. CONCLUSIONS: VSR was positively associated with cardiometabolic diseases regardless of gender. As VSR increased, the risk of cardiometabolic diseases was significantly higher in women than in men. TRIAL REGISTRATION: www.chictr.org.cn (Registration number: ChiCTR2100044305).

Establishment and Validation of a New Predictive Model for Insulin Resistance based on 2 Chinese Cohorts: A Cross-Sectional Study.

Background: Visceral adiposity plays a key role in the development of insulin resistance (IR), so surrogate index that can indicate visceral obesity may have higher predictive value for IR. This study aimed to establish and validate a new predictive model including indicator of visceral obesity for IR. Methods: The study population consisted of two cohorts. The derivation cohort was a group of 667 patients with newly diagnosed type 2 diabetes and the population undergoing a routine health checkup was the validation cohort. The predictive model was established by the logistic regression analysis. Its value for predicting IR was compared with other surrogate indices by the receiver operating characteristic curve. Results: The odds ratio (OR) of age, visceral fat area (VFA), triglyceride (TG), fasting plasma glucose (FPG), and alanine aminotransferase (ALT) for IR was 1.028 (95% CI, 1.008-1.048) (P < 0.01), 1.016 (95% CI, 1.009-1.023) (P < 0.001), 1.184 (95% CI, 1.005-1.396) (P < 0.05), 1.334 (95% CI, 1.225-1.451) (P < 0.001), and 1.021 (95% CI, 1.001-1.040) (P < 0.05). The formula of the predictive model was (0.0293 × age + 1.4892 × Ln VFA + 0.4966 × Ln TG + 2.784 × Ln FPG + 0.6906 × Ln ALT)/2. The area under the curve was the largest among all the previously reported predictors. Conclusions: This study established and validated a predicting model for IR and confirmed its predictive value in comparison with other surrogate indicators, which will offer a simple and effective tool to measure IR in future large population studies.

[Preparation and characterization of near-infrared responsive sinomenine hydrochloride reservoir microneedles].

The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 µm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 µg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb-ingredient-target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, advanced glycosylation end product (AGE)-RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

Magnesium sulfate reduces postoperative pain in women with cesarean section: A meta-analysis of randomized controlled trials.

OBJECTIVES: The use of magnesium sulfate (MgSO4 ) as an adjunct in different anesthetic regimens for cesarean section (CS) delivery often reports conflicting results. This study aimed to review the effectiveness of MgSO4 on improving postoperative analgesia after CS systematically. METHODS: PubMed, Embase, and the Cochrane library were searched for randomized controlled trials (RCTs) published from inception to February 2020. RESULTS: A total of 880 women were included (440 in each group). MgSO4 had a statistically significant effect compared to the control group on the highest VAS (weighted mean difference [WMD] = -0.74, 95% confidence interval [CI] = -1.03 to -0.46, p < 0.001, I2  = 91.7%, pheterogeneity  < 0.001) and the last VAS (WMD = -0.47, 95% CI = -0.71 to -0.23, p < 0.001, I2  = 95.0%, pheterogeneity  < 0.001). MgSO4 prolonged the time to the first use of analgesia compared to the control group (standardized mean difference [SMD] = -3.03 min, 95% CI = -4.32 to -1.74, p < 0.001, I2  = 96.3%, pheterogeneity  < 0.001). MgSO4 decreased the consumption of analgesia compared to the control group (SMD = -3.20 mg of IV morphine equivalent, 95% CI: -5.45 to -0.95, p = 0.005, I2  = 97.6%, pheterogeneity  < 0.001). DISCUSSION: MgSO4 decreases the highest VAS in women who underwent general anesthesia, spinal anesthesia, or epidural for CS (all p < 0.05). Additional MgSO4 significantly reduces postoperative pain in women undergoing CS.

Comparison of the Distinct, Host-Specific Response of Three Solanaceae Hosts Induced by Phytophthora infestans.

Three Solanaceae hosts (TSHs), S. tuberosum, N. benthamiana and S. lycopersicum, represent the three major phylogenetic clades of Solanaceae plants infected by Phytophthora infestans, which causes late blight, one of the most devastating diseases seriously affecting crop production. However, details regarding how different Solanaceae hosts respond to P. infestans are lacking. Here, we conducted RNA-seq to analyze the transcriptomic data from the TSHs at 12 and 24 h post P. infestans inoculation to capture early expression effects. Macroscopic and microscopic observations showed faster infection processes in S. tuberosum than in N. benthamiana and S. lycopersicum under the same conditions. Analysis of the number of genes and their level of expression indicated that distinct response models were adopted by the TSHs in response to P. infestans. The host-specific infection process led to overlapping but distinct in GO terms and KEGG pathways enriched for differentially expressed genes; many were tightly linked to the immune response in the TSHs. S. tuberosum showed the fastest response and strongest accumulation of reactive oxygen species compared with N. benthamiana and S. lycopersicum, which also had similarities and differences in hormone regulation. Collectively, our study provides an important reference for a better understanding of late blight response mechanisms of different Solanaceae host interactions.

Component Parts of Bacteriophage Virions Accurately Defined by a Machine-Learning Approach Built on Evolutionary Features.

Antimicrobial resistance (AMR) continues to evolve as a major threat to human health, and new strategies are required for the treatment of AMR infections. Bacteriophages (phages) that kill bacterial pathogens are being identified for use in phage therapies, with the intention to apply these bactericidal viruses directly into the infection sites in bespoke phage cocktails. Despite the great unsampled phage diversity for this purpose, an issue hampering the roll out of phage therapy is the poor quality annotation of many of the phage genomes, particularly for those from infrequently sampled environmental sources. We developed a computational tool called STEP3 to use the "evolutionary features" that can be recognized in genome sequences of diverse phages. These features, when integrated into an ensemble framework, achieved a stable and robust prediction performance when benchmarked against other prediction tools using phages from diverse sources. Validation of the prediction accuracy of STEP3 was conducted with high-resolution mass spectrometry analysis of two novel phages, isolated from a watercourse in the Southern Hemisphere. STEP3 provides a robust computational approach to distinguish specific and universal features in phages to improve the quality of phage cocktails and is available for use at http://step3.erc.monash.edu/. IMPORTANCE In response to the global problem of antimicrobial resistance, there are moves to use bacteriophages (phages) as therapeutic agents. Selecting which phages will be effective therapeutics relies on interpreting features contributing to shelf-life and applicability to diagnosed infections. However, the protein components of the phage virions that dictate these properties vary so much in sequence that best estimates suggest failure to recognize up to 90% of them. We have utilized this diversity in evolutionary features as an advantage, to apply machine learning for prediction accuracy for diverse components in phage virions. We benchmark this new tool showing the accurate recognition and evaluation of phage component parts using genome sequence data of phages from undersampled environments, where the richest diversity of phage still lies.

Proteomic analysis of urine reveals biomarkers for the diagnosis and phenotyping of abdominal-type Henoch-Schonlein purpura.

BACKGROUND: Abdominal-type Henoch-Schonlein purpura (HSP) is a common refractory disease in children. Currently, no specific diagnostic biomarker is available for HSP. METHODS: Children with abdominal type HSP were first diagnosed with three syndromes using Chinese traditional medicine. The urinary proteomes among the three syndromes of patients with abdominal type HSP and healthy controls were compared using two label-free proteomics quantifications, including data-dependent acquisition and data-independent acquisition. RESULTS: For the comparison between patients with abdominal type HSP and healthy children, a total of 75 differential urinary proteins were identified by determining the overlap of the two experiments. The ingenuity pathway analysis (IPA) analysis showed that these differential proteins were correlated with the pathogenesis of abdominal type HSP. Of these, 37 proteins were distributed in 13 solid tissues as tissue-enriched proteins. Monitoring changes in these proteins might help us detect uncommon clinical manifestations of HSP. Patients with abdominal type HSP can be further distinguished into three syndromes based on the urine proteome. Finally, a panel of six urinary proteins (P25774, P09417, Q7Z5L0, P60900, P14550 and P09668) was constructed for both the diagnosis and phenotyping of abdominal type HSP. CONCLUSIONS: Urinary protein biomarkers for the diagnosis and phenotyping of abdominal type HSP were identified, which will contribute to the personalized treatment of patients with abdominal type HSP.