Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora.Methods The 25 SD rats were randomly divided into five groups:the Sham group,the BDL group,the negative control adenovirus(NC adv)group,the miR-199a-5p adv group and the miR-199a-5p sponge adv group.The pathological changes of liver tissue and the degree of liver fibrosis were ob-served by HE,Masson and Sirius Red staining.The levels of aspartate aminotransferase(AST),alanine amin-otransferase(ALT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum of rats were determined by a fully automatic biochemical analyzer.The mRNA expression level of miR-199a-5p in liver tissue of rats was detec-ted by qRT-PCR.The protein expression levels of α-smooth muscle actin(α-SMA)and collagen type 1 alpha 1(COL1A1)in liver tissue of rats were detected by double immunofluorescence staining and Western blot experi-ment.Rat feces were collected for 16S rRNA high-throughput sequencing.Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P＜0.01).Compared with the NC adv group,the degree of liver injury and collagen deposition were relatively serious,the levels of AST,ALT,TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(all P＜0.05).However,the results of miR-199a-5p sponge adv intervention were opposite(all P＜0.05).The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota,changed composition of intestinal microbiota,while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(all P＜0.05).Conclusion miR-199a-5p promotes liver fibrosis of BDL rats,and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.

The 19 th Chinese Symposium of Burns and Wounds was successfully held in Foshan of Guangdong Province from June 20 th to 22 nd in 2024. There were more than 700 delegates attending the academic event. The theme of the congress was expansion, integration and standardization, which could promote academic exchanges, multi-disciplinary fusion, and standardization of clinical treatment of burns and wounds. A total of nearly 200 famous experts and scholars had their speeches on the two-day keynote forum and special academic seminars including critical care, wound repair, scar prevention and treatment, rehabilitation nursing, and disciplinary integration sessions. The congress ended successfully with abundant fruits and friendship.

Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

Objective To investigate the differences in efficacy and safety in the treatment of patients with cerebral palsy at different grades of the Gross Motor Function Classification System (GMFCS) by selective posterior rhizotomy (SPR). Methods Relevant literatures on SPR treatment for cerebral palsy were retrieved from Pubmed, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database. Clinical trials on SPR treatment for cerebral palsy were included for Meta-analysis. At least two researchers independently screened the literatures, extracted data, and assessed the quality of the literatures. Data analysis was performed by Review Manager 5.4 software. Results A total of 2, 726 literatures were retrieved, and 8 literatures were finally included after screening. The results of the Meta-analysis showed that the gross motor function and self-care ability of patients with cerebral palsy at all GMFCS grades improved significantly after surgery, and muscle tone decreased significantly after surgery (P < 0.05). In comparison of the improvement in gross motor function before and after SPR, patients with grades Ⅱ and Ⅲ of GMFCS benefited the most, followed by those with grade Ⅰ, and those with grades Ⅳ and V benefited less. In terms of improving self-care ability, patients with grade Ⅰ benefited the most, followed by those with grade Ⅲ, and those with grades Ⅱ and IV benefited less. No significant adverse reactions were reported in previous literatures. Conclusion SPR is a relatively safe and effective treatment option for patients with cerebral palsy. Patients at grades Ⅱ and Ⅲ of GMFCS benefit the most from SPR, and patients at grades Ⅳ and V with poor preoperative physical status can also benefit from SPR.

Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].

Intraoperative acquired pressure injury is one of the common complications in surgical patients,with a high incidence and delayed postoperative recovery.This paper reviews the judgment,staging criteria and research status of risk prediction models of intraoperative acquired pressure injury in surgical patients.We also compare the construction methods,verification methods and independent risk factors of the models,and analyze the disadvantages,with an aim to provide bases for the prediction,warning and pre-control of the risk of intraoperative acquired pressure injury in surgical patients.

OBJECTIVE To analyze the influential factors for dose-corrected trough concentration （C/D） of amisulpride， and to provide reference for rational use of it in clinic. METHODS The results of the last serum concentration monitoring and relevant medical data of schizophrenic inpatients who were monitored for the treatment of amisulpride in the Mental Health Center of the First Hospital of Hebei Medical University from March to November 2021 were collected retrospectively and analyzed the effects of age， sex， body mass index （BMI）， serum creatinine level， and combined medication on the C/D value of amisulpride. RESULTS A total of 133 schizophrenic inpatients were included， and median dose of amisulpride was 600.00 mg/d， median serum concentration was 332.57 ng/mL， and median value of C/D was 0.61 ng·d/（mL·mg）. The serum concentration of 49 patients was within the recommended range of relevant guideline （100-320 ng/mL）， and 27 patients exceeded the laboratory warning concentration （640 ng/mL）. There was no statistical significance in drug dose， serum concentration or C/D value among the patients of different genders （P＞0.05）. The serum concentration of minor patients was significantly lower than that of adult patients （P＜0.05）， but there was no statistical significance in drug dose or C/D value between minor patients and adult patients （P＞0.05）. The C/D value of amisulpride in obese patients （BMI＞28 kg/m2） was significantly lower than that in normal patients （BMI 18.5- 23.9 kg/m2）； the combination of olanzapine， sodium valproate and benzodiazepines did not affect the C/D value of amisulpride （P＞0.05）； the level of serum creatinine in patients was not related to the dose of amisulpride （r＝0.081， P＞0.05）， but was positively related to the C/D value of the drug （r＝0.285， P＜0.05）. CONCLUSIONS The age， BMI and serum creatinine level of patients are closely related to the C/D value of amisulpride. In the clinical treatment of schizophrenia with amisulpride， we should fully consider the patient’s age， body mass， serum creatinine and other factors， and develop a personalized drug regimen for patients to ensure the safety and effectiveness of treatment.

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.