Hepatic fibrosis （HF） is an abnormal repair process that occurs after chronic liver injury. It is characterized by excessive accumulation of extracellular matrix in the liver， resulting in fibrous tissue hyperplasia， which may further develop into cirrhosis and even liver cancer. Currently， there is a lack of specific anti-HF drugs in clinical practice. Traditional Chinese medicine （TCM） has advantages in the treatment of HF， including multi-component and multi-target interventions with high safety， and can significantly delay the progression of HF. It has therefore become a current research hotspot. Nuclear factor erythroid 2-related factor 2 （Nrf2）， as a key transcription factor involved in antioxidant stress， can effectively intervene in the progression of HF by activating the expression of downstream antioxidant enzymes and detoxification genes. This article systematically reviews the mechanisms by which active components of Chinese medicine （such as flavonoids， polysaccharides， and saponins） and TCM compound prescriptions （such as Haobie Yangyin Ruanjian prescription and Biejia Xiaozheng pills） exert anti-fibrotic effects through activation of the Nrf2 signaling pathway， including enhancing antioxidant capacity， inhibiting inflammatory responses， reducing hepatocyte apoptosis， improving mitochondrial function， and inhibiting the ferroptosis pathway. In addition， this article points out the current shortcomings in research based on the Nrf2 signaling pathway and proposes corresponding suggestions to promote related studies. It also provides an important theoretical basis for the development of novel anti-HF Chinese medicine targeting Nrf2.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective To investigate the spatial distribution patterns and environmental determinants of Lagotis brachystachya Maxim.,a keystone species in Tibetan medicine("Zhi Da Sa Zeng"),under contemporary climatic conditions in China;To provide references for the sustainable utilization of its resources and the ecological protection of alpine grassland areas.Methods Based on the maximum entropy model,the selected species distribution data and environmental factors were added to MaxEnt 4.3.1 software for modeling.The geographical detector was applied to quantify the factors influencing the spatial differentiation of the suitable areas,employing both factor detection and interaction detection functionalities.Additionally,an overlay analysis with land cover types was conducted to quantify the distribution characteristics of grassland within the potential suitable areas for Lagotis brachystachya Maxim..Results Under the current climatic conditions,dominant environmental drivers included elevation,monthly average temperature difference between day and night,average precipitation in June,wind speed in September,solar radiation in August,average precipitation in May,average precipitation in October,among which elevation demonstrated the strongest explanatory power(q=0.37)in habitat suitability analysis.The model prediction results showed that the potential suitable area for Lagotis brachystachya Maxim.was 5.31×105 km2.Considering the type of surface coverage,the main suitable habitat for Lagotis brachystachya Maxim.was grassland,with an area of 4.34×105 km2.The high suitable grassland of areas were mainly distributed in Qinghai Province(Yushu Tibetan Autonomous Prefecture,Huangnan Tibetan Autonomous Prefecture,Golog Tibetan Autonomous Prefecture,Hainan Tibetan Autonomous Prefecture,Haibei Tibetan Autonomous Prefecture),Sichuan Province(Ganzi Tibetan Autonomous Prefecture,Aba Qiang Autonomous Prefecture),Xizang Autonomous Region(Naqu City,Shigatse City,Changdu City),and Gansu Province(Gannan Tibetan Autonomous Prefecture).Conclusion This study can provide references for the protection of wild resources and the selection of domestication and cultivation areas for Lagotis brachystachya Maxim..

Inflammatory bowel disease(IBD)is a chronic and recurrent intestinal disease,and has become a major global health issue.Individuals with IBD face an elevated risk of developing colorectal cancer(CRC),and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC.This review covers the pathogenesis of IBD and CRC,focusing on mitochondrial dysfunction,and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function.Additionally,recent advancements in the phar-macological modulation of mitochondrial dysfunction for treating IBD and CRC,encompassing mitochondrial damage,release of mitochondrial DNA(mtDNA),and impairment of mitophagy,are thoroughly summarized.The review also provides a systematic overview of natural compounds(such as flavonoids,alkaloids,and diterpenoids),Chinese medicines,and intestinal microbiota,which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function.In the future,it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function,which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective To analyze the spatial distribution patterns of the potential suitable habitats for Cremastrae Pseudobulbus Pleiones Pseudobulbus,including Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe under current climatic conditions,and the factors influencing the spatial differentiation of their habitats.Methods Based on the maximum entropy(MaxEnt)model,a species distribution model was established using the screened species distribution data and environmental variable data.The factor detection and interaction detection of geographical detector were applied to quantify the factors influencing the spatial differentiation of the suitable areas.By overlaying the suitable areas with land cover types,the distribution characteristics of forest land and arable land in the potential suitable areas were quantified.Results Under the current climatic scenario,environmental variables such as solar radiation intensity,precipitation and temperature were closely related to the spatial distribution of Cremastrae Pseudobulbus Pleiones Pseudobulbus.The potential suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 2.20×106 km2,2.75×106 km2 and 7.22×105 km2,respectively.Considering land cover types,the actual possible suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 1.86×106 km2,2.20×106 km2 and 5.77×105 km2,respectively.Among these,the area of forest land was 1.17×106 km2,1.34×106 km2 and 3.67×105 km2,respectively,and the area of arable land was 6.95×105 km2,8.64×105 km2 and 2.10×105 km2,respectively.Conclusion This study can provide a basis for the protection and sustainable utilization of wild resources of the original plant materials of Cremastrae Pseudobulbus Pleiones Pseudobulbus.

Objective To analyze the spatial distribution pattern of the potential suitable habitats for Cordyceps under current climatic conditions in China based on space characteristics and biological traits;To explore the key environmental factors affecting the spatial differentiation of its habitats.Methods The Maximum Entropy model was utilized as a predictive tool to synthesize the distribution data of Cordyceps and its associated species Polygonum viviparum and Polygonum macrophyllum,along with environmental variable data.Factor detectors and interaction detectors of geographic detectors were used to conduct geographic exploration of spatial differentiation factors in the suitable habitats of Cordyceps.Furthermore,by overlaying the potential suitable habitats of Cordyceps with surface cover types and the suitable areas of Polygonum viviparum and Polygonum macrophyllum,the specific distribution range of the potential suitable habitats for Cordyceps was refined.Results Under the current climatic conditions,altitude,the precipitation amount of the warmest season,the highest temperature in February,and the precipitation in July are the key environmental factors influencing the distribution of Cordyceps.The potential suitable habitats for Cordyceps reaches 1.18×106 km2,and considering surface cover types,the actual potential suitable habitats for Cordyceps is 7.33×105 km2.Taking into account the associated relationships between species,the actual potential suitable habitats for Cordyceps is 7.27×105 km2.Conclusion The results of this study can reflect the ecological needs of Cordyceps,promote its sustainable utilization of resources,and provide reference for maintaining biodiversity and ecosystem integrity.