Transcriptional Landscape and Dynamics Involved in Sugar and Acid Accumulation during Apple Fruit Development.

In fleshy fruit, sugars and acids are central components of fruit flavor and quality. To date, the mechanisms underlying transcriptional regulation of sugar and acid during fruit development remain largely unknown. Here, we combined ATAC-seq with RNA-seq to investigate the genome-wide chromatin accessibility and to identify putative transcription factors related to sugar and acid accumulation during apple (Malus domestica) fruit development. By integrating the differentially accessible regions (DARs) and differentially expressed genes (DEGs), we generated a global dataset of promoter-accessibility- and expression-increased genes (PEIGs). Using this strategy, we constructed a transcriptional regulatory network enabling screening for key transcription factors and target genes involved in sugar and acid accumulation. Among these transcription factors, five fruit-specific Dof (DNA binding with one finger) genes were selected to confirm their regulatory effects, and our results showed that they could affect sugar or acid concentration by regulating the expression of sugar or acid metabolism-related genes in apple fruits. Our transcriptional regulatory network provides a suitable platform to identify candidate genes that control sugar and acid accumulation. Meanwhile, our dataset will aid in analyzing other characteristics of apple fruit that have not been illuminated previously. Overall, these findings support a better understanding of the regulatory dynamics during apple fruit development and lay a foundation for quality improvement of apple.

mHealth App to improve medication adherence among older adult stroke survivors: Development and usability study.

Background: Effective medication adherence is vital for older adult stroke survivors, yet 20-33% cease treatment within a year post-discharge, increasing risks of recurrent strokes and mortality. A mobile health (mHealth) app could be a novel tool to improve medication adherence among stroke survivors because of its potential to increase patient empowerment. A few stroke-related apps provide information and support to stroke survivors. However, none have focused on medication adherence and documented their development and evaluation process, particularly those focused on this older population. Objective: This study aims to design and develop a smartphone app called OASapp to improve medication adherence among older adult stroke survivors and evaluate its usability. Methods: OASapp was developed in a three-phase development process. Phase 1 is the exploration phase (including a cross-sectional survey, a systematic review, a search for stroke apps on the app stores of Apple App Store and Google Play Store, and a nominal group technique). In phase 2, a prototype was designed based on the Health Belief Model and Technology Acceptance Model. In phase 3, Alpha and Beta testing was conducted to validate the app. Results: Twenty-five features for inclusion in the app were collected in round one, and 14 features remained and were ranked by the participants during nominal group technique. OASapp included five core components (medication management, risk factor management, health information, communication, and stroke map). Users of OASapp were satisfied based on reports from Alpha and Beta testing. The mean Usability Metric for User Experience (UMUX) score was 71.4 points (SD 14.6 points). Conclusion: OASapp was successfully developed using comprehensive, robust, and theory-based methods and was found to be highly accepted by users. Further research is needed to establish the clinical efficacy of the app so that it can be utilized to improve clinically relevant outcomes.

Effectiveness of mobile application interventions for stroke survivors: systematic review and meta-analysis.

BACKGROUND: Although smartphone usage is ubiquitous, and a vast amount of mobile applications have been developed for chronic diseases, mobile applications amongst stroke survivors remain unclear. OBJECTIVE: This systematic review and meta-analysis aimed to determine the effectiveness of mobile applications on medication adherence, functional outcomes, cardiovascular risk factors, quality of life and knowledge on stroke in stroke survivors. METHODS: A review of the literature was conducted using key search terms in PubMed, EMBASE, Cochrane and Web of Science databases until 16 March 2023 to identify eligible randomized controlled trials (RCTs) or controlled clinical trial (CCTs) of mobile application interventions among stroke survivors. Two reviewers independently screened the literature in accordance with the eligibility criteria and collected data from the articles included. Outcomes included medication adherence,functional outcomes,cardiovascular risk factors, quality of life,and knowledge of stroke. RESULTS: Twenty-three studies involving 2983 participants across nine countries were included in this review. Sixteen trials involved health care professionals in app use, and seven trials reported measures to ensure app-based intervention adherence. Mobile applications targeting stroke survivors primarily encompassed three areas: rehabilitation, education and self-care. The participants in the studies primarily included young and middle-aged stroke survivors. Meta-analysis results demonstrated that mobile application intervention significantly improved trunk control ability (mean differences [MD] 3.00, 95% CI [1.80 to 4.20]; P < 0.00001), Fugl-Meyer assessment of upper extremity (MD 9.81, 95% CI [8.72 to 10.90]; P < 0.00001), low-density lipoprotein cholesterol (MD - 0.33, 95% CI [- 0.54 to - 0.11]; P = 0.003) and glycosylated haemoglobin A1c (HbA1c)<7 levels (MD 1.95, 95% CI [1.17 to 3.25]; P = 0.01). However, the mobile application intervention did not differ significantly in medication adherence, 10-min walk test (10 MWT), Barthel index, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, body mass index, smoking, health-related quality of life and knowledge of stroke. CONCLUSION: Our study suggested that mobile application interventions may have a potential benefit to stroke survivors, but clinical effectiveness should be established. More studies using rigorous designs are warranted to understand their usefulness. Future research should also involve more older adult stroke survivors.

A short neuropeptide F analog (sNPF), III-2 may particularly regulate juvenile hormone III to influence Spodoptera frugiperda metamorphosis and development.

Allatostatin (AS) or Allatotropin (AT) is a class of insect short neuropeptide F (sNPF) that affects insect growth and development by inhibiting or promote the synthesis of juvenile hormone (JH) in different insects. III-2 is a novel sNPF analog derived from a group of nitroaromatic groups connected by different amino acids. In this study, we found that III-2 showed high insecticidal activity against S. frugiperda larvae with a LC50 of 18.7 mg L-1. As demonstrated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), III-2 particularly facilitated JH III and hindered 20E synthesis in S. frugiperda. The results of RNA-Seq and quantitative real-time polymerase chain reaction (qPCR) showed that III-2 treatment promoted the expression of key genes such as SfCYP15C1 in JH synthesis pathway and inhibited the expression of SfCYP314A1 and other genes in the 20E synthetic pathway. Significant differences were also observed in the expression of the genes related to cuticle formation. We report for the first time that sNPF compounds specifically interfere with the synthesis and secretion of a certain JH in insects, thus affecting the ecdysis and growth of insects, and leading to death. This study may provide a new plant conservation concept for us to seek the targeted control of certain insects based on specific interference with different JH.

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa.

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

S-dinotefuran affects the social behavior of honeybees (Apis mellifera)and increases their risk in the colony.

The toxic effects of neonicotinoid pesticides on honeybees is a global concern, whereas little is known about the effect of stereoisomeric pesticides among honeybee social behavior. In this study, we investigated the effects of stereoisomeric dinotefuran on honeybee social behavior. We found that honeybees exhibit a preference for consuming food containing S-dinotefuran, actively engage in trophallaxis with S-dinotefuran-consuming peers, and consequently acquire higher levels of S-dinotefuran compared with R-dinotefuran. In comparison to R-dinotefuran, S-dinotefuran stimulates honeybees to elevate their body temperature, thereby attracting more peers for trophallaxis. Transcriptome analysis revealed a significant enrichment of thermogenesis pathways due to S-dinotefuran exposure. Additionally, metabolome data indicated that S-dinotefuran may enhance body temperature by promoting lipid synthesis in the lysine degradation pathway. Consequently, body temperature emerges as a key factor influencing honeybee social behavior. Our study is the first to highlight the propensity of S-dinotefuran to raise honeybee body temperature, which prompts honeybee to preferentially engage in trophallaxis with peers exhibiting higher body temperatures. This preference may lead honeybees to collect more dinotefuran-contaminated food in the wild, significantly accelerating dinotefuran transmission within a population. Proactive trophallaxis further amplifies the risk of neonicotinoid pesticide transmission within a population, making honeybees that have consumed S-dinotefuran particularly favored within their colonies. These findings may contribute to our understanding of the higher risk associated with neonicotinoid use compared with other pesticides.

Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.

BACKGROUND: Coagulation factor VIII (FVIII) and von Willebrand factor (VWF) circulate as a noncovalent complex, but each has its distinct functions. Binding of FVIII to VWF results in a prolongation of FVIII's half-life in circulation and modulates FVIII's immunogenicity during hemophilia therapy. However, the biological effect of FVIII and VWF interaction on VWF homeostasis is not fully understood. OBJECTIVES: To determine the effect of FVIII in VWF proteolysis and homeostasis in vivo. METHODS: Mouse models, recombinant FVIII infusion, and patients with hemophilia A on a high dose FVIII for immune tolerance induction therapy or emicizumab for bleeding symptoms were included to address this question. RESULTS: An intravenous infusion of a recombinant B-domain less FVIII (BDD-FVIII) (40 and 160 µg/kg) into wild-type mice significantly reduced plasma VWF multimer sizes and its antigen levels; an infusion of a high but not low dose of BDD-FVIII into Adamts13+/- and Adamts13-/- mice also significantly reduced the size of VWF multimers. However, plasma levels of VWF antigen remained unchanged following administration of any dose BDD-FVIII into Adamts13-/- mice, suggesting partial ADAMTS-13 dependency in FVIII-augmented VWF degradation. Moreover, persistent expression of BDD-FVIII at ∼50 to 250 U/dL via AAV8 vector in hemophilia A mice also resulted in a significant reduction of plasma VWF multimer sizes and antigen levels. Finally, the sizes of plasma VWF multimers were significantly reduced in patients with hemophilia A who received a dose of recombinant or plasma-derived FVIII for immune tolerance induction therapy. CONCLUSION: Our results demonstrate the pivotal role of FVIII as a cofactor regulating VWF proteolysis and homeostasis under various (patho)physiological conditions.

[Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review].

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Fast and low-dose medical imaging generation empowered by hybrid deep-learning and iterative reconstruction.

Fast and low-dose reconstructions of medical images are highly desired in clinical routines. We propose a hybrid deep-learning and iterative reconstruction (hybrid DL-IR) framework and apply it for fast magnetic resonance imaging (MRI), fast positron emission tomography (PET), and low-dose computed tomography (CT) image generation tasks. First, in a retrospective MRI study (6,066 cases), we demonstrate its capability of handling 3- to 10-fold under-sampled MR data, enabling organ-level coverage with only 10- to 100-s scan time; second, a low-dose CT study (142 cases) shows that our framework can successfully alleviate the noise and streak artifacts in scans performed with only 10% radiation dose (0.61 mGy); and last, a fast whole-body PET study (131 cases) allows us to faithfully reconstruct tumor-induced lesions, including small ones (<4 mm), from 2- to 4-fold-accelerated PET acquisition (30-60 s/bp). This study offers a promising avenue for accurate and high-quality image reconstruction with broad clinical value.

High-Impact Performance and Thermal Properties of Polyimine Nanocomposites Reinforced by Silicon Carbide Nano-Whiskers.

Polymer nanocomposites, which combine the advantages of polymers and fillers, are widely used in the field of automobile and aviation. Polyimine (PI) is an emerging thermoset material with remarkable properties, such as malleability, recyclability, and self-healing. Silicon carbide nano-whiskers (SiCw), as a cheap and high-hardness filler material, are chosen to enhance the properties of polyimine matrix. Silicon carbide nano-whisker-reinforced polyimine (PI-SiCw) nanocomposites were successfully fabricated by heat pressing, which was confirmed by FTIR and XPS tests. According to the results of mechanical tests, the mechanical properties of PI-SiCw nanocomposites were obviously improved. For example, with the addition of 0.5% SiCw, bending strength and bending elongation at break can be simultaneously increased by 33% and 148%, respectively. Surprisingly, the impact strength of PI-SiCw nanocomposites with 2% SiCw was increased by 154% compared to the matrix. SEM and EDS tests showed that the evenly distributed SiCw in the polyimine matrix enhanced the mechanical properties of PI-SiCw nanocomposites according to the mechanism of whiskers pulling out and the bridging principle. According to the TGA test results, the PI composites with SiCw retain a higher weight percentage at 800 °C. The reason was the combined effect of the good thermal stability of SiCw and their strong interactions with the PI matrix. As a result, introducing SiCw into the PI matrix imparts a slight improvement in thermal stability. This article presents an avenue of cost-effective research to enhance the mechanical properties of polyimine composites.

The SnRK2.3-AREB1-TST1/2 cascade activated by cytosolic glucose regulates sugar accumulation across tonoplasts in apple and tomato.

Soluble sugars are the core components of fruit quality, and the degree of sugar accumulation is largely determined by tonoplast-localized sugar transporters. We previously showed that two classes of tonoplast sugar transporters, MdERDL6 and MdTST1/2, coordinately regulate sugar accumulation in vacuoles. However, the mechanism underlying this coordination remains unknown. Here we discovered that two transcription factors, MdAREB1.1/1.2, regulate MdTST1/2 expression by binding their promoters in apple. The enhanced MdAREB1.1/1.2 expression in MdERDL6-1-overexpression plants resulted in an increase in MdTST1/2 expression and sugar concentration. Further studies established that MdSnRK2.3, whose expression could be regulated by expressing MdERDL6-1, could interact with and phosphorylate MdAREB1.1/1.2, thereby promoting the MdAREB1.1/1.2-mediated transcriptional activation of MdTST1/2. Finally, the orthologous SlAREB1.2 and SlSnRK2.3 exhibited similar functions in tomato fruit as in their apple counterparts. Together, our findings provide insights into the regulatory mechanism of tonoplast sugar transport exerted by SnRK2.3-AREB1-TST1/2 for fruit sugar accumulation.

Description of apps targeting stroke patients: A review of apps store.

Background: As a principal cause of mortality and disability worldwide, stroke imposes considerable burdens on society and effects on the lives of patients, families, and communities. Owing to their growing global popularity, health-related applications (apps) offer a promising approach to stroke management but show a knowledge gap regarding mobile apps for stroke survivors. Methods: This review was conducted across the Android and iOS app stores in September-December 2022 to identify and describe all apps targeting stroke survivors. Apps were included if they were designed for stroke management and contained at least one of the following components: medication taking, risk management, blood pressure management, and stroke rehabilitation. Apps were excluded if they were unrelated to health, not in Chinese or English, or the targeted users were healthcare professionals. The included apps were downloaded, and their functionalities were investigated. Results: The initial search yielded 402 apps, with 115 eligible after title and description screening. Some apps were later excluded due to duplicates, registration problems, or installation failures. In total, 83 apps were included for full review and evaluated by three independent reviewers. Educational information was the most common function (36.1%), followed by rehabilitation guidance (34.9%), communication with healthcare providers (HCPs), and others (28.9%). The majority of these apps (50.6%) had only one functionality. A minority had contributions from an HCP or patients. Conclusion: With the widespread accessibility and availability of smartphone apps across the mHealth landscape, an increasing number of apps targeting stroke survivors are being released. One of the most important findings is that the majority of the apps were not specifically geared toward older adults. Many of the currently available apps lack healthcare professionals' and patients' involvement in their development, and most offer limited functionality, thus requiring further attention to the development of customized apps.

Transmembrane protein 147, as a potential Sorafenib target, could expedite cell cycle process and confer adverse prognosis in hepatocellular carcinoma.

TMEM147 was identified as a core component of ribosome-bound translocon complex at ER/NE. So far, sparse studies reported its expression profiling and oncological implications in hepatocellular carcinoma (HCC) patients. Here we inspected TMEM147 expression levels in HCC cohorts from public databases and tumor tissues. TMEM147 was augmented at transcriptional levels (p < 0.001) and protein levels in HCC patients. A series of bioinformatics tools implemented in R studio were orchestrated in TCGA-LIHC to evaluate the prognostic significance, compile relevant gene clusters, and explore the oncological functions and therapy responses. It is suggested that TMEM147 could predict poor clinical outcomes effectively and independently (p < 0.001, HR = 2.231 for overall survival (OS) vs. p = 0.04, HR = 2.296 for disease-specific survival), and was related to risk factors including advanced histologic tumor grade (p < 0.001), AFP level (p < 0.001) and vascular invasion (p = 0.007). Functional enrichment analyses indicated that TMEM147 was involved in cell cycle, WNT/MAPK signaling pathways and ferroptosis. Expression profiling in HCC cell lines, mouse model, and a clinical trial revealed that TMEM147 was a considerable target and marker for adjuvant therapy in vitro and in vivo. Subsequentially, in vitro wet-lab experimentation authenticated that TMEM147 would be downregulated by Sorafenib administration in hepatoma cells. Lentivirus-mediated overexpression of TMEM147 could promote cell cycle progression from S phase into G2/M phase, and enhance cell proliferation, thus attenuating drug efficacy and sensitivity of Sorafenib. Further explorations into TMEM147 may inspire a fresh perspective to predict clinical outcomes and improve therapeutic efficacy for HCC patients.

Association between adolescents' socioeconomic status and working memory updating functioning: Role of parental educational involvement.

Family socioeconomic status (SES) is positively associated with executive functioning. This study tested whether parental educational involvement mediates this association. Two hundred and sixty, 12-15-year-old adolescents completed working memory updating (WMU) and general intelligence tasks, and questionnaires on SES and parental educational involvement. SES and WMU ability were positively associated; there was no difference between the fathers and mothers for three types of educational involvement. The mothers' behavioural involvement positively mediated the SES-WM updating association, whereas a negative mediation was observed for the mothers' intellectual involvement. The fathers' educational involvement did not play a significant mediating role. These results might inform interventions targeting educational involvement for enhancing the cognitive development of children from low SES families.

Preoperative transcatheter arterial chemoembolization and prognosis of patients with solitary large hepatocellular carcinomas (≥5 cm): Multicenter retrospective study.

OBJECTIVES: Large hepatocellular carcinoma (LHCC) is prone to short-term recurrence and poor long-term survival after hepatectomy, and there is still a lack of effective neoadjuvant treatments to improve recurrence-free survival (RFS) and overall survival (OS). We retrospectively analyzed the efficacy of preoperative transcatheter arterial chemoembolization (TACE) in solitary LHCC (≥5 cm). MATERIALS AND METHODS: A multicenter medical database was used to analyze preoperative TACE's effects on RFS, OS, and perioperative complications in patients with solitary LHCC who received surgical treatment from January 2005 to December 2015. The patients were divided into Group A (5.0-9.9 cm) and Group B (≥10 cm), with 10 cm as the critical value, and the effect of preoperative TACE on RFS, OS and perioperative complications was assessed in each subgroup. RESULTS: In the overall population, patients with preoperative TACE had better RFS and OS than those without preoperative TACE. However, after stratifying the patients into the two HCC groups, preoperative TACE only improved the survival outcomes of patients with Group B (≥10 cm). Multivariate Cox-regression analysis showed that lack of preoperative TACE was an independent risk factor for RFS and OS in the overall population and in Group B but not in Group A. CONCLUSIONS: Preoperative TACE is beneficial for patients with solitary HCC (≥10 cm).

Distinct inflammation-related proteins associated with T cell immune recovery during chronic HIV-1 infection.

Chronic inflammation and T cell dysregulation persist in individuals infected with human immunodeficiency virus type 1 (HIV-1), even after successful antiretroviral treatment. The mechanism involved is not fully understood. Here, we used Olink proteomics to comprehensively analyze the aberrant inflammation-related proteins (IRPs) in chronic HIV-1-infected individuals, including in 24 treatment-naïve individuals, 33 immunological responders, and 38 immunological non-responders. T cell dysfunction was evaluated as T cell exhaustion, activation, and differentiation using flow cytometry. We identified a cluster of IRPs (cluster 7), including CXCL11, CXCL9, TNF, CXCL10, and IL18, which was closely associated with T cell dysregulation during chronic HIV-1 infection. Interestingly, IRPs in cluster 5, including ST1A1, CASP8, SIRT2, AXIN1, STAMBP, CD40, and IL7, were negatively correlated with the HIV-1 reservoir size. We also identified a combination of CDCP1, CXCL11, CST5, SLAMF1, TRANCE, and CD5, which may be useful for distinguishing immunological responders and immunological non-responders. In conclusion, the distinct inflammatory milieu is closely associated with immune restoration of T cells, and our results provide insight into immune dysregulation during chronic HIV-1 infection.

Medication non-adherence and associated factors among older adult stroke survivors in China.

Aim: Medication non-adherence has remained a common and costly global health issue of growing importance among older adults. This study aims to determine the prevalence and associated factors related to medication non-adherence among older adult stroke survivors in China. Methods and results: In this cross-sectional study, a total of 402 older adult stroke survivors were recruited from three tertiary hospitals in China. The results of the survey showed that 61.4% exhibited medication non-adherence. The chances of medication non-adherence among older adult stroke survivors who had primary school or less educational levels were higher than those who had senior secondary and junior college educational levels [OR (95% CI) = 0.440(0.249, 0.778)] as well as those who had a bachelor's degree or above educational levels [OR (95%CI) = 0.367(0.202, 0.667)]. Moreover, the probability of medication non-adherence with 4-5 and ≥6 types of total prescription medications per day increased by 1.993 times [OR (95% CI) = 1.993(1.190, 3.339))] and 2.233 times [OR (95%CI) = 2.233(1.159, 4.300)], respectively, as compared to when there were ≤3 types. Furthermore, medication non-adherence decreased with the increase in health literacy scores (ß = -0.641 (95% CI; (0.913, 0.965)) and BMQ specific-necessity scores (ß = -0.131 (95% CI; 0.806, 0.995)). On the other hand, when the BMQ specific-concerns score increased by one unit, medication non-adherence increased by 11.1% [OR (95% CI) = 1.111(1.044, 1.182)]. Conclusion: The present study found that patient medication adherence among older adult stroke survivors in China is problematic and associated with educational levels, total prescribed drugs per day, beliefs about medication, and health literacy scores. This indicates that measures should be taken to enhance medication adherence among such higher-risk populations.

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.

Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. IMPORTANCE Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.

Dietary tea seed saponin combined with aerobic exercise attenuated lipid metabolism and oxidative stress in mice fed a high-fat diet (HFD).

Tea seed saponins (TSS) are oleanolane-type pentacyclic triterpenoid saponin mixtures with various pharmacological effects. We aimed to explore the effects of a total of 4 weeks intragastric administration of TSS (140 mg/kg·day) combined with aerobic exercise (AE) on lipid metabolism and its associated oxidative stress in HFD-induced obese mice and to investigate the possible molecular mechanisms. TSS + AE intervention significantly reduced body weight and the adiposity index (including subcutaneous, epididymal, perirenal, and abdominal adipose) in obese mice; improved dyslipidemia by lowering serum TC, TG, and LDL-c levels; and increased HDL-c levels. TSS + AE intervention significantly improved hepatic steatosis by inhibiting lipogenetic Acc, Srebp1c, and Scd1 and upregulating lipolysis genes (Pgc1α, Pgc1ß, Pparα, and Cpt1). TSS + AE intervention increased the hepatic protein expression of p-AMPK, SIRT1, and PGC-1α, as well as PPAR-γ and GLUT-4 in skeletal muscle compared with expression in the HFD group. In addition, TSS + AE also modulated oxidative stress in obese mice, which was indicated by the increased serum and liver levels of SOD, GSH, and T-AOC and decreased ROS and MDA levels. These results suggest that TSS + AE intervention can reduce fat accumulation and improve HFD-induced lipid metabolism disorders and oxidative stress. PRACTICAL APPLICATIONS: Obesity is a metabolic disease induced by excess nutritional intake and insufficient energy expenditure. Dietary modifications combined with aerobic exercise are currently an effective method for weight loss. Tea seed saponins (TSS) are a variety of biologically active oleanolane-type pentacyclic triterpenoid saponins that naturally exist in tea seeds. Few articles have focused on the effects and mechanisms of TSS combined with aerobic exercise (AE) in regulating lipid metabolism and improving oxidative damage in vivo. Using an HFD-induced obese mice model to explore the mechanism of TSS + AE in regulating lipid metabolism and its associated oxidative stress damage will help provide reliable data for the application of dietary nutrition combined with AE in anti-obesity.

Reduction of natural killer cells is associated with poor outcomes in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND AND AIMS: Natural killer (NK) cells are critical innate effectors that respond to viral infections and contribute to immunopathology. Here, we aimed to investigate the role of NK cells in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and elucidate the underlying mechanism by examining their phenotypic and functional profiles. METHODS: We included patients with HBV-ACLF (n = 37) and chronic hepatitis B (n = 19), and healthy controls (n = 13) in our study. We examined the phenotype and function of different subsets of peripheral NK cells using flow cytometry and RNA-sequencing analysis, and screened liver NK cells using immunohistochemistry. We detected inflammatory cytokines using a Luminex assay. In addition, we analyzed the relationships between these parameters and disease severity. RESULTS: Peripheral NK cells were decreased and characterized by high expression of caspase-3, Ki67, CXCR3, NKG2D, NKp46, CD107a, and GM-CSF, and typified by higher cell migration and immune response by RNA-sequencing analysis in patients with HBV-ACLF than in those with chronic hepatitis B. Accumulations of CXCL-10 and NK cells were found in the liver, and excessive production of CXCL-10 in the peripheral blood contributed to the apoptosis of NK cells in vitro. The decrease in NK cells was associated with the level of HBV DNA and disease severity and had good prognostic performance in predicting the outcome of patients with HBV-ACLF through AUROC analysis. CONCLUSION: NK cells were significantly decreased and showed dysfunction of phenotypic and functional profiles across distinct subsets in the peripheral blood of patients with ACLF. Crosstalk between CXCL-10 and NK cells may mediate the unbalanced distribution of NK cells. Understanding the dysfunction and decrease in NK cells may provide new insights into ACLF pathogenesis.