Clinical application of voriconazole in pediatric patients: a systematic review.

The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (Ctrough) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of Ctrough, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the Ctrough of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target Ctrough compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.

Translation, cross-cultural adaptation, and measurement properties of the Traditional Chinese version of the Fear of Falling Avoidance Behavior Questionnaire in Taiwanese community-dwelling adults.

PURPOSE: This study aimed to translate the Fear of Falling Avoidance Behavior Questionnaire (FFABQ) into Traditional Chinese (FFABQ-TC) and to evaluate the psychometric properties of FFABQ-TC in Taiwanese adults. METHODS: We translated and culturally adapted the FFABQ into Traditional Chinese, ensuring linguistic accuracy and cultural relevance. A total of 230 Taiwanese community-dwelling adults participated in the study. Test-retest reliability was assessed in 30 participants, while 200 participants were included in the validity analysis. Known-groups validity was investigated by comparing the FFABQ-TC scores between fallers and non-fallers. Convergent validity was examined by correlating FFABQ-TC scores with Activities-specific Balance Confidence Scale (ABC), Geriatric Fear of Falling Measure (GFFM), and Timed-Up-and-Go (TUG) test. RESULTS: The FFABQ-TC demonstrated excellent test-retest reliability (Intraclass Correlation Coefficient = 0.884) and excellent internal consistency (Cronbach's alpha = 0.930). Known-groups analysis revealed that FFABQ-TC significantly differentiated between fallers and non-fallers. Convergent validity was examined and showed significant correlations of FFABQ-TC with the ABC, the GFFM, and TUG. CONCLUSION: The psychometric properties of FFABQ-TC was established in Taiwanese adults for assessing FOF-related avoidance behaviors. The translated and adapted FFABQ-TC is a reliable and valid clinical tool for evaluating fall risk in this population.

The current evidence supports the reliability and validity of the Traditional Chinese version of the Fear of Falling Avoidance Behavior Questionnaire (FFABQ-TC) in Taiwanese community-dwelling adults.FFABQ-TC is recommended as a reliable measurement to determine fall risk in clinical and research settings.

Endogenous stem cell mobilization and localized immunosuppression synergistically ameliorate DSS-induced Colitis in mice.

BACKGROUND: Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. METHODS: Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. RESULTS: The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. CONCLUSION: This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.

Association of waist circumference and BMI with premature death in young and middle-aged population.

Introduction: Premature death is a global health indicator, significantly impacted by obesity, especially in young and middle-aged population. Both body mass index (BMI) and waist circumference (WC) assess obesity, with WC specifically indicating central obesity and showing a stronger relationship with mortality. However, despite known associations between BMI and premature death, as well as the well-recognized correlation between WC and adverse health outcomes, the specific relationship between WC and premature death remains unclear. Therefore, focusing on young and middle-aged individuals, this study aimed to reliably estimate independent and combined associations between WC, BMI and premature death, thereby providing causal evidence to support strategies for obesity management. Methods: This study involved 49,217 subjects aged 18-50 years in the United States from 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Independent and combined associations between WC and BMI with premature death across sex and age stratum were examined by Cox regression. Survey weighting and inverse probability weighting (IPW) were further considered to control selection and confounding bias. Robustness assessment has been conducted on both NHANES and China Health and Retirement Longitudinal Study (CHARLS) data. Results: A linear and positive relationship between WC and all-cause premature death was found in both males and females, with adjusted HRs of 1.019 (95%CI = 1.004-1.034) and 1.065 (95%CI = 1.039-1.091), respectively. Nonlinear relationships were found with respect to BMI and all-cause premature death. For females aged 36-50 with a BMI below 28.6 kg/m2, the risk of premature death decreased as BMI increased, indicated by adjusted HRs of 0.856 (95%CI = 0.790-0.927). Joint analysis showed among people living with obesity, a larger WC increased premature death risk (HR = 1.924, 95%CI = 1.444-2.564). Discussion: WC and BMI exhibited prominent associations with premature death in young and middle-aged population. Maintaining an appropriate WC and BMI bears significant implications for preventing premature death.

Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

The Value of Perioperative Immunotherapy for Non-Small Cell Lung Cancer: A Pool- and Meta-Analysis.

Purpose: This study aimed to analyze the efficacy and safety of neoadjuvant and adjuvant immunotherapies for non-small cell lung cancer (NSCLC). Methods: Electronic literature searches were conducted in PubMed, OVID, Web of SCI, Embase, Cochrane Library, and the Chinese National Knowledge Infrastructure databases. The deadline for literature update and retrieval is February 16, 2024. Studies presented at meetings were also screened. Randomized controlled trials (RCTs) and single-arm trials were included, and the data were extracted according to the inclusion and exclusion criteria. Data analysis was performed using Stata (16.0) software. Results: A total of 5850 patients in 11 RCTs and 6 single-arm trial studies involving neoadjuvant and/or adjuvant immune checkpoint inhibitor (ICI)-based therapies were included. Regarding neoadjuvant therapy, the overall complication rate after surgery reached 35% (95% CI, 0.21-0.49). Higher rates of pathological complete response (OR = 7.83; 95% CI, 5.95-10.31; P < .001) and major pathological response (OR = 5.13; 95% CI, 3.56-7.40; P < .001) were found in the resectable NSCLC patients who received neoadjuvant therapy with ICIs combined with chemotherapy compared with patients treated with chemotherapy alone. Of note, compared with chemotherapy, neoadjuvant ICIs combined with chemotherapy significantly improved the overall survival (OS) (HR = 0.65; 95% CI, 0.52-0.82; P < .001) and event-free survival (EFS) (HR = 0.59; 95% CI, 0.52-0.67; P < .001) in patients with resectable NSCLC. Regarding adjuvant therapy, a lower risk of disease progression or death (HR = 0.78; 95% CI, 0.69-0.90; P < .001) was found in the adjuvant ICI group compared with the adjuvant chemotherapy-alone group. In terms of safety, perioperative immunotherapy combined with chemotherapy did not increase toxicity compared with chemotherapy alone. Conclusion: In patients with resectable NSCLC, perioperative immunotherapy was safe and efficacious. Perioperative immunotherapy combined with chemotherapy improved the pathologic response and EFS/DFS/OS over chemotherapy alone without increasing toxicity.

Lightweight cotton diseases real-time detection model for resource-constrained devices in natural environments.

Cotton, a vital textile raw material, is intricately linked to people's livelihoods. Throughout the cotton cultivation process, various diseases threaten cotton crops, significantly impacting both cotton quality and yield. Deep learning has emerged as a crucial tool for detecting these diseases. However, deep learning models with high accuracy often come with redundant parameters, making them challenging to deploy on resource-constrained devices. Existing detection models struggle to strike the right balance between accuracy and speed, limiting their utility in this context. This study introduces the CDDLite-YOLO model, an innovation based on the YOLOv8 model, designed for detecting cotton diseases in natural field conditions. The C2f-Faster module replaces the Bottleneck structure in the C2f module within the backbone network, using partial convolution. The neck network adopts Slim-neck structure by replacing the C2f module with the GSConv and VoVGSCSP modules, based on GSConv. In the head, we introduce the MPDIoU loss function, addressing limitations in existing loss functions. Additionally, we designed the PCDetect detection head, integrating the PCD module and replacing some CBS modules with PCDetect. Our experimental results demonstrate the effectiveness of the CDDLite-YOLO model, achieving a remarkable mean average precision (mAP) of 90.6%. With a mere 1.8M parameters, 3.6G FLOPS, and a rapid detection speed of 222.22 FPS, it outperforms other models, showcasing its superiority. It successfully strikes a harmonious balance between detection speed, accuracy, and model size, positioning it as a promising candidate for deployment on an embedded GPU chip without sacrificing performance. Our model serves as a pivotal technical advancement, facilitating timely cotton disease detection and providing valuable insights for the design of detection models for agricultural inspection robots and other resource-constrained agricultural devices.

Biomaterials-mediated radiation-induced diseases treatment and radiation protection.

In recent years, the intersection of the academic and medical domains has increasingly spotlighted the utilization of biomaterials in radioactive disease treatment and radiation protection. Biomaterials, distinguished from conventional molecular pharmaceuticals, offer a suite of advantages in addressing radiological conditions. These include their superior biological activity, chemical stability, exceptional histocompatibility, and targeted delivery capabilities. This review comprehensively delineates the therapeutic mechanisms employed by various biomaterials in treating radiological afflictions impacting the skin, lungs, gastrointestinal tract, and hematopoietic systems. Significantly, these nanomaterials function not only as efficient drug delivery vehicles but also as protective agents against radiation, mitigating its detrimental effects on the human body. Notably, the strategic amalgamation of specific biomaterials with particular pharmacological agents can lead to a synergistic therapeutic outcome, opening new avenues in the treatment of radiation- induced diseases. However, despite their broad potential applications, the biosafety and clinical efficacy of these biomaterials still require in-depth research and investigation. Ultimately, this review aims to not only bridge the current knowledge gaps in the application of biomaterials for radiation-induced diseases but also to inspire future innovations and research directions in this rapidly evolving field.

Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance.

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.

Synthetic MRI and diffusion-weighted imaging for differentiating nasopharyngeal lymphoma from nasopharyngeal carcinoma: combination with morphological features.

OBJECTIVES: To investigate the feasibility of synthetic MRI (syMRI), diffusion-weighted imaging (DWI), and their combination with morphological features for differentiating nasopharyngeal lymphoma (NPL) from nasopharyngeal carcinoma (NPC). METHODS: Sixty-nine patients with nasopharyngeal tumours (NPL, n = 22; NPC, n = 47) who underwent syMRI and DWI were retrospectively enrolled between October 2020 and May 2022. syMRI and DWI quantitative parameters (T1, T2, PD, ADC) and morphological features were obtained. Diagnostic performance was assessed by independent sample t-test, chi-square test, logistic regression analysis, receiver operating characteristic curve (ROC), and DeLong test. RESULTS: NPL has significantly lower T2, PD, and ADC values compared to NPC (all P < .05), whereas no significant difference was found in T1 value between these two entities (P > .05). The morphological features of tumour type, skull-base involvement, Waldeyer ring involvement, and lymph nodes involvement region were significantly different between NPL and NPC (all P < .05). The syMRI (T2 + PD) model has better diagnostic efficacy, with AUC, sensitivity, specificity, and accuracy of 0.875, 77.27%, 89.36%, and 85.51%. Compared with syMRI model, syMRI + Morph (PD + Waldeyer ring involvement + lymph nodes involvement region), syMRI + DWI (T2 + PD + ADC), and syMRI + DWI + Morph (PD + ADC + skull-base involvement + Waldeyer ring involvement) models can further improve the diagnostic efficiency (all P < .05). Furthermore, syMRI + DWI + Morph model has excellent diagnostic performance, with AUC, sensitivity, specificity, and accuracy of 0.986, 95.47%, 97.87%, and 97.10%, respectively. CONCLUSION: syMRI and DWI quantitative parameters were helpful in discriminating NPL from NPC. syMRI + DWI + Morph model has the excellent diagnostic efficiency in differentiating these two entities. ADVANCES IN KNOWLEDGE: syMRI + DWI + morphological feature method can differentiate NPL from NPC with excellent diagnostic performance.

The correlation between drivers' road familiarity and glance behavior using real vehicle experimental data and mathematical models.

OBJECTIVE: Road familiarity is an important factor affecting drivers' visual features. Analyzing the quantitative correlation between drivers' road familiarity and visual features in complex environment is of great help to improve driving safety. However, there are few relevant studies. This paper takes urban plane intersection as the environmental object to explore the correlation between drivers' glance behavior and road familiarity, and conducts research on the quantitative evaluation model of road familiarity based on this correlation. METHOD: First, a real vehicle experiment was carried out to record the eye movement data of 24 drivers with different road familiarity. The driver's visual field plane was divided into 10 areas of interest (AOIs) based on the driver's perspective. Three measures, including average glance duration, number of glances, and fixation transition probabilities between AOIs at urban plane intersections, were extracted. Finally, based on the experimental results, the driver road familiarity evaluation model was constructed using the factor analysis method. RESULTS: There are significant differences between unfamiliar and familiar drivers regarding the average glance duration toward the forward (FW) area, the left window (LW) area, the left rearview mirror (LVM) area and the left forward (LF) area, the number of glances toward the other (OT) area, and the fixation transition probabilities of LW→RF (right forward), LF→LF, LF→FW, FW→LW, FW→FW, FW→RVM (right rearview mirror). The comprehensive evaluation results show that the accuracy rate of the driver road familiarity evaluation model reached 83%. CONCLUSIONS: This paper revealed that there is a strong correlation between drivers' road familiarity and drivers' glance behavior. Based on this correlation, we can include road familiarity as a part of drivers' working status and establish a high accuracy evaluation model of driver road familiarity. The conclusion of this paper can provide some reference for the humanized design and improvement of advanced driving assistance system, which is of great significance for reducing the driving workload of drivers and improving the driving safety.

Dietary Flavonoid Quercetin Supplement Promotes Antiviral Innate Responses Against Vesicular Stomatitis Virus Infection by Reshaping the Bacteriome and Host Metabolome in Mice.

SCOPE: Active ingredients in functional foods exhibit broad-spectrum antiviral activity. The objective of this study is to investigate the protective effect of quercetin derived from bee propolis, a natural product with antiviral activity and modulating effects on the gut microbiota, against vesicular stomatitis virus (VSV) infection. METHODS AND RESULTS: Through a cellular-based study, this study demonstrates that quercetin can modulate the activity of interferon-regulating factor 3 (IRF3). In vivo, it shows that quercetin protects mice from VSV infection by enhancing interferon production and inhibiting the production of proinflammatory cytokines. The study conducts 16S rRNA-based gut microbiota and nontargets metabolomics analyses to elucidate the mechanisms underlying quercetin-mediated bidirectional communication between the gut microbiome and host metabolome during viral infection. Quercetin not only ameliorates VSV-induced dysbiosis of the intestinal flora but also alters serum metabolites related to lipid metabolism. Cross-correlations between the gut bacteriome and the serum metabolome indicate that quercetin can modulate phosphatidylcholine (16:0/0:0) and 5-acetylamino-6-formylamino-3-methyluracil to prevent VSV infection. CONCLUSION: This study systematically elucidates the anti-VSV mechanism of quercetin through gut bacteriome and host metabolome assays, offering new insights into VSV treatment and revealing the mechanisms behind a novel disease management strategy using dietary flavonoid supplements.

Unraveling the Molecular Weight Dependence of High Magnetic Field to Manipulate the Semiconducting Polymer Molecular Orientation.

The magnetic alignment of molecules, which exploits the anisotropy of diamagnetic susceptibility, provides a clean and versatile approach to the structural manipulation of semiconducting polymers. Here, the magnetic-alignment dynamics of two molecular-weight (MW) batches of a diketopyrrolopyrrole (DPP)-based copolymer (PDVT-8) were investigated. Microstructural characterizations revealed that the magnetically aligned, high-MW (Mn = 53.7 kDa) PDVT-8 film exhibited a higher degree of backbone chain alignment and film crystallinity compared with the low-MW (Mn = 17.6 kDa) PDVT-8 film grown via the same magnetic alignment method. We found that as the MW increases, the degree of preaggregation of the polymer molecules in solution significantly increases and the aggregation mode changes from H-aggregation to J-aggregation through a cooperative assembly mechanism. These events improved the responsiveness of high-MW polymer molecules to magnetic fields. Field-effect transistors based on the magnetic aligned high-MW PDVT-8 films exhibited a 6.8-fold increase in hole mobility compared to the spin-coated films, along with a mobility anisotropy ratio of 12.6. This work establishes a significant correlation among chain aggregation behavior in solution, polymer film microstructures, magnetic responsiveness, and carrier transport performance in donor-acceptor polymer systems.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Loss of AMPK activity induces organelle dysfunction and oxidative stress during oocyte aging.

BACKGROUND: Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, the declined oocytes showing with organelle dysfunction and oxidative stress lead to infertility. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which is important for energy homeostasis for metabolism. Little is known about the potential relationship between AMPK with oocyte aging. RESULTS: In present study we reported that AMPK was related with low quality of oocytes under post ovulatory aging and the potential mechanism. We showed the altered AMPK level during aging and inhibition of AMPK activity induced mouse oocyte maturation defect. Further analysis indicated that similar with its upstream regulator PKD1, AMPK could reduce ROS level to avoid oxidative stress in oocytes, and this might be due to its regulation on mitochondria function, since loss of AMPK activity induced abnormal distribution, reduced ATP production and mtDNA copy number of mitochondria. Besides, we also found that the ER and Golgi apparatus distribution was aberrant after AMPK inhibition, and enhanced lysosome function was also observed. CONCLUSIONS: Taken together, these data indicated that AMPK is important for the organelle function to reduce oxidative stress during oocyte meiotic maturation.

Tetris-inspired detector with neural network for radiation mapping.

Radiation mapping has attracted widespread research attention and increased public concerns on environmental monitoring. Regarding materials and their configurations, radiation detectors have been developed to identify the position and strength of the radioactive sources. However, due to the complex mechanisms of radiation-matter interaction and data limitation, high-performance and low-cost radiation mapping is still challenging. Here, we present a radiation mapping framework using Tetris-inspired detector pixels. Applying inter-pixel padding for enhancing contrast between pixels and neural networks trained with Monte Carlo (MC) simulation data, a detector with as few as four pixels can achieve high-resolution directional prediction. A moving detector with Maximum a Posteriori (MAP) further achieved radiation position localization. Field testing with a simple detector has verified the capability of the MAP method for source localization. Our framework offers an avenue for high-quality radiation mapping with simple detector configurations and is anticipated to be deployed for real-world radiation detection.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Advances in succinic acid production: the enhancement of CO2 fixation for the carbon sequestration benefits.

Succinic acid (SA), one of the 12 top platform chemicals produced from biomass, is a precursor of various high value-added derivatives. Specially, 1 mol CO2 is assimilated in 1 mol SA biosynthetic route under anaerobic conditions, which helps to achieve carbon reduction goals. In this review, methods for enhanced CO2 fixation in SA production and utilization of waste biomass for SA production are reviewed. Bioelectrochemical and bioreactor coupling systems constructed with off-gas reutilization to capture CO2 more efficiently were highlighted. In addition, the techno-economic analysis and carbon sequestration benefits for the synthesis of bio-based SA from CO2 and waste biomass are analyzed. Finally, a droplet microfluidics-based high-throughput screening technique applied to the future bioproduction of SA is proposed as a promising approach.

Different dose aspirin plus immunoglobulin (DAPI) for prevention of coronary artery abnormalities in Kawasaki disease: Study protocol for a multi-center, prospective, randomized, open-label, blinded end-point, non-inferiority trial.

BACKGROUND: Kawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease. METHODS: This is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg-1·d-1) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg-1·d-1) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography. CONCLUSIONS: There is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR2300072686.

Reactive Oxygen Species-Responsive Nanoparticles Toward Extracellular Matrix Normalization for Pancreatic Fibrosis Regression.

Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.