Identification of the principal neuropeptide MIP and its action pathway in larval settlement of the echiuran worm Urechis unicinctus.

BACKGROUND: Larval settlement and metamorphosis represent critical events in the life history of marine benthic animals. Myoinhibitory peptide (MIP) plays a pivotal role in larval settlement of marine invertebrates. However, the molecular mechanisms of MIP involved in this process are not well understood. RESULTS: In this study, we evaluated the effects of thirteen MIP mature peptides on triggering the larval settlement of Urechis unicinctus (Xenopneusta, Urechidae), and determined that MIP2 was the principal neuropeptide. Transcriptomic analysis was employed to identify differentially expressed genes (DEGs) between the MIP2-treated larvae and normal early-segmentation larvae. Both cAMP and calcium signaling pathways were enriched in the DEGs of the MIP2-treated larvae, and two neuropeptide receptor genes (Spr, Fmrfar) were up-regulated in the MIP2-treated larvae. The activation of the SPR-cAMP pathway by MIP2 was experimentally validated in HEK293T cells. Furthermore, fourteen cilia-related genes, including Tctex1d2, Cfap45, Ift43, Ift74, Ift22, Cav1 and Mns1, etc. exhibited down-regulated expression in the MIP2-treated larvae. Whole-mount in situ hybridization identified two selected ciliary genes, Tctex1d2 and Cfap45, were specially expressed in circumoral ciliary cells of the early-segmentation larvae. Knocking down Tctex1d2 mRNA levels by in vivo RNA interference significantly increased the larval settlement rate. CONCLUSION: Our findings suggest that MIP2 inhibits the function of the cilia-related genes, such as Tctex1d2, through the SPR-cAMP-PKA pathway, thereby inducing larval settlement in U. unicinctus. The study contributes important data to the understanding of neuropeptide regulation in larval settlement.

Network Pharmacology Analysis, Molecular Docking Integrated Experimental Verification Reveal the Mechanism of Gynostemma pentaphyllum in the Treatment of Type II Diabetes by Regulating the IRS1/PI3K/Akt Signaling Pathway.

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3ß and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

Prediction of protein-coding small ORFs in multi-species using integrated sequence-derived features and the random forest model.

Proteins encoded by small open reading frames (sORFs) can serve as functional elements playing important roles in vivo. Such sORFs also constitute the potential pool for facilitating the de novo gene birth, driving evolutionary innovation and species diversity. Therefore, their theoretical and experimental identification has become a critical issue. Herein, we proposed a protein-coding sORFs prediction method merely based on integrative sequence-derived features. Our prediction performance is better or comparable compared with other nine prevalent methods, which shows that our method can provide a relatively reliable research tool for the prediction of protein-coding sORFs. Our method allows users to estimate the potential expression of a queried sORF, which has been demonstrated by the correlation analysis between our possibility estimation and codon adaption index (CAI). Based on the features that we used, we demonstrated that the sequence features of the protein-coding sORFs in the two domains have significant differences implying that it might be a relatively hard task in terms of cross-domain prediction, hence domain-specific models were developed, which allowed users to predict protein-coding sORFs both in eukaryotes and prokaryotes. Finally, a web-server was developed and provided to boost and facilitate the study of the related field, which is freely available at http://guolab.whu.edu.cn/codingCapacity/index.html.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Nomogram to predict the probability of clinical pregnancy in women with poor ovarian response undergoing in vitro fertilization/ intracytoplasmic sperm injection cycles.

BACKGROUND: Poor ovarian response (POR) is associated with decreased clinical pregnancy rates, emphasizing the need for developing clinical prediction models. Such models can improve prognostic accuracy, personalize medical interventions, and ultimately enhance live birth rates among patients with POR. OBJECTIVE: This study aims to develop and validate a prognostic model for predicting clinical pregnancy outcomes in individuals with POR undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS: A retrospective cohort of 969 patients with POR undergoing fresh embryo transfer cycles at the Reproductive Center of Fujian Maternal and Child Health Center from January 2018 to January 2022 was included. The cohort was randomly divided into model (n = 678) and validation (n = 291) groups in a 7:3 ratio. A single-factor analysis was performed on the model group to identify variables influencing clinical pregnancy. Optimal variables were selected using LASSO regression, and a clinical prediction model was constructed using multivariate logistic regression analysis. The model's calibration and discrimination were assessed using receiver operating characteristic (ROC) and calibration curves, while the clinical utility was evaluated using decision curve analysis. RESULTS: Multivariate logistic regression analysis revealed that the age of the women (odds ratio [OR] 0.936, 95% confidence interval [CI] 0.898-0.976, P = 0.002), body mass index (BMI) ≤ 24 (OR 2.748, 95% CI 1.724-4.492, P < 0.001), antral follicle count (AFC) (OR 1.232, 95% CI 1.073-1.416, P = 0.003), anti-Müllerian hormone (AMH) (OR 1.67, 95% CI 1.178-2.376, P = 0.004), number of mature oocytes (OR 1.227, 95% CI 1.075-1.403, P = 0.003), number of embryos transferred (OR 1.692, 95% CI 1.132-2.545, P = 0.011), and transfer of high-quality embryos (OR 3.452, 95% CI 1.548-8.842, P = 0.005) were independent predictors of clinical pregnancy in patients with POR. According to the receiver operating characteristic (ROC) analysis, the prediction model exhibited an area under the curve (AUC) of 0.752 (0.714, 0.789) in the model group and 0.765 (0.708, 0.821) in the validation group. The clinical decision curve demonstrated that the model held maximum clinical utility in both cohorts when the threshold probability of clinical pregnancy ranged from 6-81% to 12-82%, respectively. CONCLUSION: Clinical pregnancy outcomes in patients with POR who underwent IVF/ICSI treatment were influenced by several independent factors, including the age of the women, BMI, AFC, AMH, number of mature oocytes, number of embryos transferred, and transfer of high-quality embryos. A clinical prediction model based on these factors exhibited favorable clinical predictive and applicative value. Therefore, this model can serve as a valuable tool for clinical prognosis, intervention, and facilitating personalized medical treatment.

Demand creation for HIV testing services: A systematic review and meta-analysis.

BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

α-Synuclein induces prodromal symptoms of Parkinson's disease via activating TLR2/MyD88/NF-κB pathway in Schwann cells of vagus nerve in a rat model.

BACKGROUND: Increasing evidence suggests that patients with Parkinson's disease (PD) present with peripheral autonomic dysfunction (AutD) that even precedes motor deficits, through which α-synuclein can spread to the central nervous system. However, the pathological mechanisms underlying AutD in prodromal PD remain unclear. Here, we investigated the role of α-synuclein and its interplay with the activation of Schwann cells (SCs) of the vagus nerve in AutD. METHODS: Rats were subjected to injection with adeno-associated viruses containing the human mutated A53T gene (AAV-A53T) or an empty vector into the left cervical vagus nerve and evaluated for gastrointestinal symptoms, locomotor functions, intestinal blood flow, and nerve electrophysiology. Further, we examined the impact of α-synucleinopathy on vagus nerves, SCs, and central nervous system neurons using electron microscopy, immunofluorescence, immunohistochemistry, and western blot. Finally, the role of Toll-like receptor 2 (TLR2) in regulating the neuroinflammation in the vagus nerve via MyD88 and NF-κB pathway was determined using genetic knockdown. RESULTS: We found that rats injected with AAV-A53T in the vagus nerve exhibited prominent signs of AutD, preceding the onset of motor deficits and central dopaminergic abnormalities by at least 3 months, which could serve as a model for prodromal PD. In addition, reduced intestinal blood flow and decreased nerve conduction velocity were identified in AAV-A53T-injected rats, accompanied by disrupted myelin sheaths and swollen SCs in the vagus nerve. Furthermore, our data demonstrated that p-α-synuclein was deposited in SCs but not in axons, activating the TLR2/MyD88/NF-κB signaling pathway and leading to neuroinflammatory responses. In contrast, silencing the TLR2 gene not only reduced inflammatory cytokine expression but also ameliorated vagal demyelination and secondary axonal loss, consequently improving autonomic function in rats. CONCLUSIONS: These observations suggest that overexpression of α-synuclein in the vagus nerve can induce symptoms of AutD in prodromal PD, and provide support for a deeper understanding of the pathological mechanisms underlying AutD and the emergence of effective therapeutic strategies for PD.

Impact of thyroid autoimmunity on pregnancy outcomes in euthyroid women following fresh/frozen-thawed embryo transfer.

OBJECTIVE: To investigate whether thyroid autoimmunity (TAI) is associated with assisted reproductive technology (ART) outcomes in euthyroid women undergoing fresh embryo transfer (ET) and frozen-thawed embryo transfer (FET). DESIGN: A retrospective cohort study. Pregnancy and neonatal outcome after fresh ET or FET were compared between the positive and negative thyroid autoimmune antibody groups. PATIENTS: A total of 5439 euthyroid women who started their ART cycle at our centre between 2015 and 2019 were included. RESULTS: The thyroid antibody positive group had a greater mean age than the thyroid antibody negative group (32(29,35) vs. 31(28,34), p < .001). Women with positive thyroid antibody presented with a higher prevalence of diminished ovarian reserve (DOR) (9.1% vs. 7.1%, p = .026) and lower number of oocyte retrieved (9(5,15) vs. 10(6,15), p = .020), but difference was not significant after adjusting for age. The pregnancy rate, live birth rate, pregnancy loss rate, preterm delivery rate and low birthweight rate between the thyroid antibody positive and thyroid antibody negative groups were comparable both in fresh ET cycles and FET cycles. Subanalysis of the treatment outcomes when using a stricter threshold of TSH of 2.5 mIU/L showed no difference to that achieved when using an upper limit of 4.78 mIU/L. CONCLUSIONS: The present study reveals that patients with anti-thyroid peroxidase antibodies (TPOAbs) and/or antithyroglobulin antibodies (TgAbs) showed no significant differences in pregnancy outcomes following fresh ET and FET when compared with patients with negative thyroid antibodies.

Polychaete Bioturbation Alters the Taxonomic Structure, Co-occurrence Network, and Functional Groups of Bacterial Communities in the Intertidal Flat.

Polychaetes are important benthic macrofauna that lives in sediments, usually in intertidal flats with high organic content and high sulfide. It has been suggested that polychaete bioturbation could perform environmental remediation. During the process, the microbial community plays important roles. Here, we used high-throughput sequencing technology to study the bioturbation effects on the bacterial community in the polychaete (Perinereis aibuhitensis) burrows at different tidal positions in intertidal flat. The results showed that the bacterial communities were dramatically influenced by the polychaete bioturbation. The ACE, Chao, and Shannon indices of the polychaete burrows increased in summer. Dominant phyla in the polychaete burrows were Proteobacteria, Campilobacterota, Desulfobacterota, Chloroflexi, and Bacteroidota, and the dominant bacterial families were Sulfurvaceae, Flavobacteriaceae, Rhodobacteraceae, Woeseiaceae, Desulfobulbaceae, and Sulfurimonadaceae. Results of linear discriminant analysis effect size (LEfSe) showed that groups that include organic matter degraders, such as Bacteroidota, Flavobacteriaceae, Rhodobacteraceae, Woeseiaceae, and groups that include sulfur oxidizers, such as Campilobacterota, Sulfurovaceae, Rhodobacteraceae, Desulfobulbaceae, and Sulfurimonadaceae, were significantly increased due to the polychaete bioturbation. The polychaete bioturbation reduced the complexity of the bacterial co-occurrence network while increased its modularity and homogeneity. The polychaete bioturbation also changed the functional groups, which significantly enhanced in functional groups of aerobic nitrite oxidation, nitration, dark thiosulfate oxidation, dark sulfur oxidation, and dark sulfite oxidation, while nitrogen respiration and nitrate respiration decreased. These results provide insight into the impact of bacterial communities under the intertidal polychaete bioturbation.

Development and validation of a nomogram model for predicting clinical pregnancy in endometriosis patients undergoing fresh embryo transfer.

PURPOSE: To construct and validate a nomogram model for predicting clinical pregnancy in individuals with endometriosis undergoing fersh embryo transfer (ET). METHODS: A retrospective analysis was conducted on 1630 individuals with endometriosis who underwent in vitro fertilization (IVF) with fresh embryo transfer at the Reproductive Medicine Center of Fujian Maternity and Child Health Hospital from January 2018 to January 2022. The research population was sorted into two groups through random sampling, namely, the model group (n = 1141) and the validation group (n = 489), with a ratio of 7:3. Univariate analysis was utilized to determine the influencing factors for clinical pregnancy in the model group. The LASSO algorithm was utilized to select the optimal matching factors, which were then included in a multifactorial forward stepwise logistic regression to determine independent influencing factors and develop a nomogram. The discrimination, accuracy, and clinical efficacy of the prediction model were analyzed utilizing the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve. RESULTS: Through multivariate-logistic-regression analysis, these factors were identified as independent influencing factors for the clinical pregnancy in endometriosis patients undergoing fresh embryo transfer: female age (OR = 0.933, 95% CI = 0.902-0.965, P < 0.001), ASRM stage (OR = 0.384, 95% CI = 0.276-0.532, P < 0.001), postoperative to IVF duration (OR = 0.496, 95% CI = 0.356-0.688, P < 0.001), antral follicle count (AFC) (OR = 1.076, 95% CI = 1.013-1.161, P = 0.045), anti-Müllerian hormone (AMH) (OR = 1.202, 95% CI = 1.073-1.35, P = 0.002), Gonadotrophin-releasing hormone (GnRH) agonist protocol (OR = 1.536, 95% CI = 1.109-2.131, P = 0.01), number of oocytes retrieved (OR = 1.154, 95% CI = 1.067-1.249, P < 0.001), number of high-quality cleavage embryos (OR = 1.261, 95% CI = 1.164-1.369, P < 0.001), and number of embryos transferred (OR = 1.957, 95% CI = 1.435-2.679, P < 0.001). A prediction model for estimating the clinical pregnancy probability in individuals with endometriosis was constructed per these identified independent factors. The ROC showed an area under the curve (AUC) of 0.807 (95% CI = 0.782-0.832) in the model group and 0.800 (95% CI = 0.761-0.84) in the validation group. The Hosmer-Lemeshow test demonstrated no statistically significant difference between predicted and actual clinical pregnancy probabilities (P > 0.05). The clinical decision curve demonstrated that both the model and the validation groups achieved maximum net benefit at threshold probability values of 0.08-0.96 and 0.16-0.96, indicating good clinical efficacy within this range of threshold probabilities. CONCLUSION: Female age, ASRM stage, postoperative to IVF duration, stimulation protocol, AFC, AMH, number of oocytes retrieved, number of high-quality cleavage embryos and number of transferred embryos are independent influencing factors for the clinical pregnancy rate in individuals with endometriosis receiving fresh embryo transfer. The nomogram model based on these factors demonstrates good clinical predictive value and efficacy, providing a basis for clinical prognosis, intervention, and individualized medical treatment planning.

Exploring the Mechanism of Chuanxiong Rhizoma against Thrombosis Based on Network Pharmacology, Molecular Docking and Experimental Verification.

Chuanxiong rhizoma (CX) has been utilized for centuries as a traditional herb to treat blood stasis syndromes. However, the pharmacological mechanisms are still not completely revealed. This research was aimed at exploring the molecular mechanisms of CX treatment for thrombosis. Network pharmacology was used to predict the potential anti-thrombosis mechanism after correlating the targets of active components with targets of thrombosis. Furthermore, we verified the mechanism of using CX to treat thrombosis via molecular docking and in vitro experiments. Network pharmacology results showed that a total of 18 active ingredients and 65 targets of CX treatment for thrombosis were collected, including 8 core compounds and 6 core targets. We revealed for the first time that tissue factor (TF) had a close relationship with most core targets of CX in the treatment of thrombosis. TF is a primary coagulation factor in physiological hemostasis and pathological thrombosis. Furthermore, core components of CX have strong affinity for core targets and TF according to molecular docking analysis. The in vitro experiments indicated that Ligustilide (LIG), the representative component of CX, could inhibit TF procoagulant activity, TF mRNA and protein over-expression in a dose-dependent manner in EA.hy926 cells through the PI3K/Akt/NF-κB signaling pathway. This work demonstrated that hemostasis or blood coagulation was one of the important biological processes in the treatment of thrombosis with CX, and TF also might be a central target of CX when used for treating thrombosis. The inhibition of TF might be a novel mechanism of CX in the treatment of thrombosis.

How climate, landscape, and economic changes increase the exposure of Echinococcus Spp.

BACKGROUND: Echinococcosis is a global enzootic disease influenced by different biological and environmental factors and causes a heavy financial burden on sick families and governments. Currently, government subsidies for the treatment of patients with echinococcosis are only a fixed number despite patients' finical income or cost of treatment, and health authorities are demanded to supply an annual summary of only endemic data. The risk to people in urban areas or non-endemic is increasing with climate, landscape, and lifestyle changes. METHODS: We conducted retrospective descriptive research on inpatients with human echinococcosis (HE) in Lanzhou hospitals and analyzed the healthcare expenditure on inpatient treatment and examined the financial inequalities relating to different levels of gross domestic product. The livestock losses were also estimated by infection ratio. The occurrence records of Echinococcus spp. composed of hospitalized patients and dogs infected in the Gansu province were collected for Ecological niche modeling (ENM) to estimate the current suitable spatial distribution for the parasite in Gansu province. Then, we imported the resulting current niche model into future global Shared Socioeconomic Pathways scenarios for estimation of future suitable habitat areas. RESULTS: Between 2000 to 2020, 625 hospitalized HE patients (51% men and 49% women) were identified, and 48.32 ± 15.62 years old. The average cost of hospitalization expenses per case of HE in Gansu Province was ï¿¥24,370.2 with an increasing trend during the study period and was negative with different counties' corresponding gross domestic product (GDP). The trend of livestock losses was similar to the average cost of hospitalization expenses from 2015 to 2017. The three factors with the strongest correlation to echinococcosis infection probability were (1) global land cover (GLC, 56.6%), (2) annual precipitation (Bio12, 21.2%), and (3) mean temperature of the Wettest Quarter (Bio12, 8.5% of variations). We obtained a robust model that provides detail on the distribution of suitable areas for Echinococcus spp. including areas that have not been reported for the parasite. An increasing tendency was observed in the highly suitable areas of Echinococcus spp. indicating that environmental changes would affect the distributions. CONCLUSION: This study may help in the development of policies for at-risk populations in geographically defined areas and monitor improvements in HE control strategies by allowing targeted allocation of resources, including spatial analyses of expenditure and the identification of non-endemic areas or risk for these parasites, and a better comprehension of the role of the environment in clarifying the transmission dynamics of Echinococcus spp. Raising healthcare workers' and travelers' disease awareness and preventive health habits is an urgent agenda. Due to unpredictable future land cover types, prediction of the future with only climatic variables involved needs to be treated cautiously.

Anti-inflammatory action of geniposide promotes wound healing in diabetic rats.

CONTEXT: As a major active iridoid glycoside from Gardenia jasminoides J. Ellis (Rubiaceae), geniposide possesses various pharmacological activities, including anti-platelet aggregation and anti-inflammatory action. OBJECTIVES: This study explores the effect of geniposide in diabetic wound model by anti-inflammatory action. MATERIALS AND METHODS: Diabetic rodent model in Wistar rats was induced by streptozotocin combined with high-fat feed. The selected rats were divided into control group, the diabetic model group and geniposide subgroups (200, 400 and 500 mg/kg), and orally administrated once daily with saline or geniposide. Wound area and histochemical indicators were measured on day 7 after continuous administration, to assess lesion retraction, inflammatory cells and fibroblasts. RESULTS: Geniposide notably enhanced lesion retraction by 1.06-1.84 times on day 7 after surgical onset in diabetic rats (p < 0.05). In the pathological experiment by HE staining, geniposide significantly reduced inflammatory cell infiltration and proliferation of fibroblasts in the central lesion regions. In diabetic rats treated with geniposide, the levels of pro-inflammatory factors (tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß)) and IL-6 were significantly reduced (p < 0.05), followed with the increment of IL-10 in a dose-dependent manner. The IC50 of geniposide on TNF-α, IL-1ß and IL-6 could be calculated as 1.36, 1.02 and 1.23 g/kg, respectively. It assumed that geniposide-induced IL-10 expression contributed to inhibiting the expression of pro-inflammatory factors. DISCUSSION AND CONCLUSIONS: Geniposide promoted diabetic wound healing by anti-inflammation and adjusting blood glucose. Further topical studies are required to evaluate effects on antibacterial activity and skin regeneration.

A comparison of paravertebral block, erector spinae plane block and the combination of erector spinae plane block and paravertebral block for post-operative analgesia after video-assisted thoracoscopic surgery: A randomised controlled trial.

BACKGROUND: This study was to determine the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) and paravertebral block (PVB) as well as the combination of PVB and ESPB (P + E) after video-assisted thoracoscopic surgery (VATS). PATIENTS AND METHODS: Patients were randomly assigned to receive ESPB, PVB or PVB combined with ESPB with 0.5% ropivacaine (20 ml). The primary outcomes were cumulative hydromorphone consumption and Visual Analogue Scale (VAS) scores at rest and while coughing at 0 h, 12 h, 24 h, 48 h and 72 h postoperatively. The secondary outcomes were effective PCA usage count and rescue analgesia requirement at the same time points. RESULTS: The median (interquartile range) hydromorphone consumption, including converted oxycodone, was significantly different at 48 h postoperatively among the three groups (ESPB, 10.24 [9.53-11.71] mg; PVB, 9.94 [9.19-10.75] mg; P + E, 9.44 [8.96-9.97] mg; P = 0.011). Hydromorphone consumption in P + E group was lower compared with that in ESPB group at 12 h, 24 h and 48 h (P < 0.001, P = 0.004 and P = 0.003, respectively). VAS scores at rest were significantly higher for ESPB group compared to P + E group at 0 h postoperatively (P = 0.009). VAS scores while coughing were significantly higher for ESPB group compared to P + E group at 0 h and 12 h postoperatively (P = 0.015 and P < 0.001) and to the PVB group at 12 h postoperatively (P = 0.002). The effective PCA usage count in P + E group was lower than in ESPB group in 0-12 h (P < 0.001). More patients needed rescue analgesia in ESPB group compared to those in P + E group in 0-12 h, 0-24 h and 0-48 h (P = 0.022, 0.035 and 0.035, respectively). CONCLUSIONS: Ultrasound-guided PVB combined with ESPB provided superior analgesia to ESPB for VATS. The combination of PVB and ESPB had a similar analgesic effect compared with PVB alone.

SMS messaging to improve retention and viral suppression in prevention of mother-to-child HIV transmission (PMTCT) programs in Kenya: A 3-arm randomized clinical trial.

BACKGROUND: Pregnant and postpartum women living with HIV (WLWH) need support for HIV and maternal child health (MCH) care, which could be provided using short message service (SMS). METHODS AND FINDINGS: We compared 2-way (interactive) and 1-way SMS messaging to no SMS in a 3-arm randomized trial in 6 MCH clinics in Kenya. Messages were developed using the Health Belief Model and Social Cognitive Theory; HIV messages were integrated into an existing MCH SMS platform. Intervention participants received visit reminders and prespecified weekly SMS on antiretroviral therapy (ART) adherence and MCH, tailored to their characteristics and timing. Two-way participants could message nurses as needed. Clinic attendance, viral load (VL), and infant HIV results were abstracted from program records. Primary outcomes were viral nonsuppression (VL ≥1,000 c/ml), on-time clinic attendance, loss to follow-up from clinical care, and infant HIV-free survival. Among 824 pregnant women randomized between November 2015 and May 2017, median age was 27 years, gestational age was 24.3 weeks, and time since initiation of ART was 1.0 year. During follow-up to 2 years postpartum, 9.8% of 3,150 VL assessments and 19.6% of women were ever nonsuppressed, with no significant difference in 1-way versus control (11.2% versus 9.6%, adjusted risk ratio (aRR) 1.02 [95% confidence interval (CI) 0.67 to 1.54], p = 0.94) or 2-way versus control (8.5% versus 9.6%, aRR 0.80 [95% CI 0.52 to 1.23], p = 0.31). Median ART adherence and incident ART resistance did not significantly differ by arm. Overall, 88.9% (95% CI 76.5 to 95.7) of visits were on time, with no significant differences between arms (88.2% in control versus 88.6% in 1-way and 88.8% in 2-way). Incidence of infant HIV or death was 3.01/100 person-years (py), with no significant difference between arms; risk of infant HIV infection was 0.94%. Time to postpartum contraception was significantly shorter in the 2-way arm than control. Study limitations include limited ability to detect improvement due to high viral suppression and visit attendance and imperfect synchronization of SMS reminders to clinic visits. CONCLUSIONS: Integrated HIV/MCH messaging did not improve HIV outcomes but was associated with improved initiation of postpartum contraception. In programs where most women are virally suppressed, targeted SMS informed by VL data may improve effectiveness. Rigorous evaluation remains important to optimize mobile health (mHealth) interventions. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02400671.

Infant rhesus macaques as a non-human primate model of Bordetella pertussis infection.

BACKGROUND: The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s-1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved. METHODS: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis. RESULTS: Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p. CONCLUSION: These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.

Atractylenolide III Ameliorates TNBS-Induced Intestinal Inflammation in Mice by Reducing Oxidative Stress and Regulating Intestinal Flora.

The present study aimed to explore the therapeutic effects of the main active ingredients of Atractylodes macrocephala on the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced mouse colitis model. TNBS-induced colitis was established in mice, which were treated with 8-ß-Hydroxyasterolide (Atractylenolide III) for 14 days. The body weight of the mice in the middle and high dose groups of Atractylenolide III was increased compared with that of the model group. The disease activity index score was significantly reduced. The activity levels of myeloperoxidase were significantly decreased following increase in the dosage of Atractylenolide III, as determined by histological analysis. Moreover, Atractylenolide III downregulated the expression levels of the inflammatory factors interleukin-1ß and tumor necrosis factor-α, and greatly suppressed the levels of the pro-oxidant markers, reactive oxygen species and malondialdehyde, while enhancing the expression levels of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. The protein expression levels of formyl peptide receptor 1 (FPR1) and nuclear respiratory factor 2 (Nrf2) were upregulated in the colonic tissues of TNBS-treated mice. This effect was effectively reversed by Atractylenolide III treatment. In vivo studies indicated that TNBS alone induced a decrease in the abundance of lactobacilli and in the biodiversity of the colon. In conclusion, the present study suggested that Atractylenolide III attenuated TNBS-induced acute colitis by regulating oxidative stress via the FPR1 and Nrf2 pathways and by affecting the development of intestinal flora.

Neuroprotective effect of targeted regulatory Nrf2 gene on rats with acute brain injury induced by carbon monoxide poisoning.

Oxidative stress has been considered as an important cause of neurocyte damage induced by carbon monoxide (CO) poisoning; however, the precise mechanisms are not fully understood. The study aimed to elucidate the molecular mechanism and the neuroprotective effect of targeted regulatory nuclear factor erythroid2-related factor 2 (Nrf2) gene on acute brain injury in CO poisoning rats. An acute CO poisoning rat model was established by CO inhalation in hyperbaric oxygen chamber and followed by the administration of Nrf2 gene-loaded lentivirus. Mitochondrial membrane potential (ΔΨM), the levels of Nrf2, glutamate-cysteine ligase catalytic subunit (GCLC), catalase (CAT) and glutathione peroxidase (GSH-Px), and cell apoptosis were determined in brain tissue in rats. We found that CO poisoning could decrease ΔΨm of cells, slightly increase the expressions of Nrf2 and GCLC at mRNA and protein levels, reduce CAT and GSH-Px, and thus initiate apoptosis process. The Nrf2 gene treatment could obviously enhance the expressions of Nrf2 at mRNA and protein levels, and increase the concentrations of CAT and GSH-Px, maintain the ΔΨm of cells in brain tissue, significantly inhibit cell apoptosis as compared with the CO poisoning group (p < .05). These findings suggest that CO poisoning could induce oxidative stress and impair mitochondrial function of cells in brain tissue. The administration of Nrf2 gene could notably strengthen the antioxidant capacity of cells through regulating the downstream genes of Nrf2/antioxidant responsive element signal pathway, and positively protect cells against brain injury induced by acute severe CO poisoning.

Stable Pb(II) ion-selective electrodes with a low detection limit using silver nanoparticles/polyaniline as the solid contact.

Solid contact-based ion-selective electrodes (SC-ISEs) based on silver nanoparticles/polyaniline (Ag@PANI) as the solid contact (SC) were successfully prepared. The Ag@PANI SC showed high capacitance and excellent electron transport performance. Owing to the synergetic effects of the Ag nanoparticles and PANI, a GC/Ag@PANI-II/Pb2+-ISE (where II refers to a Ag content of 0.01 wt% in the SC layer) showed a low Pb2+ detection limit (6.31 × 10-10 M) with a slope of 29.1 ± 0.3 mV/dec, a fast response (< 5 s), and high stability. GC/Ag@PANI-II/Pb2+-ISE exhibited a Nernstian response for Pb2+ ions over a wide concentration range (10-3 to 10-9 M). After a 3-week operation, GC/Ag@PANI-II/Pb2+-ISE responded linearly to Pb2+ over the range of 10-7-10-3 M, demonstrating good long-term potential stability. Furthermore, the electrode showed excellent reproducibility and repeatability of the potential values and was successfully applied to detect the Pb2+ concentration in real samples with a recovery of 97 - 109%. Results suggest that Ag@PANI composites offer good transducer performance in trace ion detection sensors.

Compositional Changes in Grapes and Leaves as a Consequence of Smoke Exposure of Vineyards from Multiple Bushfires across a Ripening Season.

The negative effects of smoke exposure of grapes in vineyards that are close to harvest are well documented. Volatile phenols in smoke from forest and grass fires can contaminate berries and, upon uptake, are readily converted into a range of glycosylated grape metabolites. These phenolic glycosides and corresponding volatile phenols are extracted into the must and carried through the winemaking process, leading to wines with overtly smoky aromas and flavours. As a result, smoke exposure of grapes can cause significant quality defects in wine, and may render grapes and wine unfit for sale, with substantial negative economic impacts. Until now, however, very little has been known about the impact on grape composition of smoke exposure very early in the season, when grapes are small, hard and green, as occurred with many fires in the 2019-20 Australian grapegrowing season. This research summarises the compositional consequences of cumulative bushfire smoke exposure of grapes and leaves, it establishes detailed profiles of volatile phenols and phenolic glycosides in samples from six commercial Chardonnay and Shiraz blocks throughout berry ripening and examines the observed effects in the context of vineyard location and timing of smoke exposure. In addition, we demonstrate the potential of some phenolic glycosides in leaves to serve as additional biomarkers for smoke exposure of vineyards.