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Abstract Background Neonatal septic shock represents a critical and life-threatening condition that necessitates immediate and personalized interventions. Prior research endeavors have been undertaken to inform the optimization of neonatal septic shock management, yet substantial heterogeneity prevails in the selection, measurement, and reporting of outcomes across relevant studies. The heterogeneity in outcome selections and measures impedes the comparability of results and the synthesis of evidence, thus contributing to suboptimal utilization of research findings. This protocol presents the methodology for identifying and developing a Core Outcome Set for Neonatal Septic Shock Management (COS-NSS), intended for use in both research and routine clinical practice. A rigorous four-stage approach will be employed to develop the COS-NSS. In Stage 1, a scoping review will be conducted to compile a list of currently reported outcomes for neonatal septic shock management. Stage 2 will involve an expert stakeholder meeting using a semi-structured discussion approach to elucidate all identified outcomes and outcome domains, as well as to gather any additional outcomes. Moving to Stage 3, a two-round e-Delphi survey involving a wide variety of stakeholders will be undertaken to elicit diverse perspectives on the level of importance assigned to each proposed outcome. Finally, in Stage 4, the results of the Delphi study will be discussed in a consensus meeting to determine and agree on the final list of outcomes that will constitute the COS-NSS. Discussion The stagewise approach integrates research evidence with multi-stakeholder perspectives to establish standardized outcomes that would improve consistency across neonatal septic shock trials. The development and uptake of the COS-NSS will facilitate effective comparison of studies, allowing for study synthesis and generation of high-quality evidence, thus ultimately fostering enhanced medical care for neonates suffering from septic shock. Trial registration Core Outcome Measures in Effectiveness Trials (COMET) Initiative database registration: 2766 . Registered on July 19th, 2023.

Abstract Background Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. Methods This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. Discussion The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

Available information on the microbial mechanisms associated with heavy metal (HM) passivation during co-composting amended with phosphate rock (PR) remains limited. Thus, this study investigated the dynamic changes in bacterial communities and HM-fractions (Zn, Cu, Cd, Cr and Pb) during swine manure composting with maize straw, and ascertained the bacterial influence on HM-passivation. The results demonstrated that the addition of PR improved HM-passivation, especially for Zn and Cd, with their bioavailability factors (BFs) reduced by 247.41 and 176.25%, respectively. As for bacterial communities, the proportion of Firmicutes decreased, while the proportions of Proteobacteria, Bacteroidetes, Deinococcus-Thermus and Gemmatimonadetes increased in all treatments. PR significantly changed the primary bacterial phyla in the thermophilic phase. Bacteroidetes were the main bacterial component controlling the passivation of Zn, Cu and Cr, while Deinococcus-Thermus mainly regulated the mobility of Zn and Pb, and Proteobacteria only dominated the transformation among Cd-fractions. These results may provide a reference for the use of HM-passivation techniques during composting.

Two new furan derivatives, hypofurans A and B (1 and 2), and three new cyclopentenone derivatives, hypocrenones A–C (3–5), along with seven known compounds (6–12), were isolated from a marine fungus Hypocrea koningii PF04 associated with the sponge Phakellia fusca. Among them, compounds 10 and 11 were obtained for the first time as natural products. The planar structures of compounds 1–5 were elucidated by analysis of their spectroscopic data. Meanwhile, the absolute configuration of 1 was determined as 2R,3R by the comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. All the isolates were evaluated for their antibacterial and antioxidant activity. Compounds 1, 10, and 12 all showed modest antibacterial activity against Staphylococcus aureus ATCC25923 (MIC, 32 μg/mL). In addition, compounds 1, 10 and 11 exhibited moderate DPPH radical scavenging capacity with IC50 values of 27.4, 16.8, and 61.7 µg/mL, respectively.

BACKGROUND: MicroRNAs are known to be generated from primary transcripts mainly through the sequential cleavages by two enzymes, Drosha and Dicer. The sequence of a mature microRNA, especially the 'seeding sequence', largely determines its binding ability and specificity to target mRNAs. Therefore, methods that predict mature microRNA sequences with high accuracy will benefit the identification and characterization of novel microRNAs and their targets, and contribute to inferring the post-transcriptional regulation network at a genome scale. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a method, MiRmat, to predict the mature microRNA sequence. MiRmat is essentially composed of two parts: the prediction of Drosha processing site and the identification of Dicer processing site. Based on the analysis of microRNAs from 12 species, we found that the patterns of free energy profiles are conserved among vertebrate microRNA hairpins. Therefore, we introduced in our method the free energy distribution pattern of the downstream part of pri-microRNA secondary structure and Random Forest algorithm to predict the mature microRNA sequence. Based on the evaluation on an independent test dataset from 10 vertebrates, MiRmat was shown to identify 77.8% of the Drosha processing sites and 92.8% of the Dicer sites within a deviation of 2 nt. In a more stringent evaluation by excluding the microRNAs sharing the same family between the training set and test set, MiRmat kept a rather well performance of 71.9% and 87.2% of the identification rate on the Drosha and Dicer site respectively, which represents the ability to deal with the novel microRNA family. MiRmat outperforms other state-of-the-art methods and has a high degree of efficacy for the prediction of mature microRNA sequences of vertebrates. CONCLUSION: MiRmat was developed for identifying microRNA mature sequence(s) by introducing the free energy distribution of RNA stem-loop structure and the Random Forest algorithm. We prove that MiRmat has better performance than the existing tools and is applicable among vertebrates. MiRmat is freely available at http://mcube.nju.edu.cn/jwang/lab/soft/MiRmat/.

Objective. The effects of low-intensity 630 nm semiconductor laser irradiation at 3.6 J/cm2 (LISL) on wound healing in diabetic rats were studied in this paper. Methods. 36 diabetic rats with dorsal cutaneous excisional wounds were divided into three LISL groups and a control group randomly. The three LISL groups were irradiated with LISL at 5, 10, and 20 mW/cm2 five times a week for two weeks, respectively. The process of wound healing was assessed by assessing blood glucose, calculating percentage of wound closure, histopathological evaluation, and immunohistochemical quantification. Results. Blood glucose of all groups remained at similar levels throughout the experiment. LISL could obviously promote wound contraction, fibroblasts proliferation, and collagen synthesis, alter bFGF and TGF-β1 expression, and reduce inflammatory reaction in the early and middle phases of chronic wound-healing process. However, LISL could not shorten cicatrization time, and the treatment effects were not sensitive to illuminate parameters in the later phase of the experiment. Conclusions. LISL might have auxiliary effects in the early and middle phases of wound healing in STZ-induced diabetic rats, but the reciprocity rule might not hold. The wound-healing process of early-phase diabetes rats shows typical characteristics of self-limited disease.