The lung collaterals form a network that branches from the lung meridian, traversing the lung system and extending across the body′s surface. Lung collateral disease refers to the structural alterations or dysfunction in these collaterals caused by external or internal pathogens. Research into the structural and physiological functions of children′s lung collaterals, as well as the pathogenesis and syndrome differentiation for treating lung collateral diseases in children, holds significant value in guiding the prevention and treatment of pediatric respiratory conditions. Drawing on the theory of collateral disease, the clinical insights of both historical and contemporary physicians, and modern research findings—while considering the unique physiological and pathological characteristics of children′s respiratory systems—this study provides a foundational summary of the morphology and spatial distribution of children′s lung collaterals. The characteristics of these collaterals are highlighted as thin, sparse, short, narrow, brittle, and tender. From this structural understanding, the unique physiological functions of children′s lung collaterals are analyzed. The study further explores the interactions between pathogenic factors and lung collaterals, elucidating the pathogenesis and progression of children′s lung collateral diseases. It proposes treatment principles centered on "seeking treatment in the collaterals and employing the method of unblocking collaterals, "which align with the unique features of pediatric lung collaterals. Common treatment approaches, and relevant prescriptions for managing these diseases are summarized. This paper lays the foundation for a theoretical system encompassing the structure, function, pathogenesis, and syndrome differentiation for treating children′s lung collateral diseases. It offers valuable insights for the clinical diagnosis and management of pediatric respiratory diseases linked to collateral dysfunction and serves as a reference for the systematic development of a broader theoretical framework for children′s collateral diseases.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

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*

The scientific interpretation of the theory of medicinal properties of TCM is a research hotspot in the modernization of TCM. It is of great value to clarify the property and degree of cold and heat in Chinese materia medica for guiding clinical precise medication. In recent years, the research on the cold and heat properties of Chinese materia medica has been carried out at the animal, cell and molecular levels. Based on the objective material basis of medicinal properties, from the perspective of biological effects such as thermodynamics and multiomics; with the help of infrared thermal imaging and other technologies for analysis; forming a variety of research models such as "property-structure relationship". Related research has developed from a single material component or index to a new model that tends to integrate multi-source information and multi-dimensional data. However, how to deal with the problems of large sample size, strong redundancy, high heterogeneity, and how to integrate multi-dimensional information are still research difficulties. With its powerful computing and learning ability, machine learning can show good discrimination and prediction ability in the study of cold and hot properties of Chinese materia medica, and play an important role in the study of cold and hot properties of Chinese materia medica. At present, the most widely used algorithms are linear discriminant analysis, Logistic discriminant analysis, support vector machine, decision tree, random forest and so on. The data dimension of the existing research needs to be enriched, the algorithm has room for further optimization, and a more detailed discriminant model of cold and hot properties of Chinese materia medica needs to be established.

Due to the outstanding hydrophobic and oleophobic properties, per- and polyfluoroalkyl substances (PFAS) are widely used in daily life and frequently detected in the environment. PFAS can enter the human body through water, food, and air exposure and accumulate in the human body. Epidemiological and toxicological evidence suggest that PFAS have endocrine-disrupting properties and may cause thyroid dysfunction by altering the hormonal homeostasis of the thyroid. This in turn affects the body's normal physiological functions, such as the physical growth and neurodevelopment in infants. Pregnancy and early life are special physiological stages, and the special dietary and lifestyle habits of this period make mothers and infants more likely to be exposed to PFAS and more susceptible to PFAS. Therefore, the exposure levels of PFAS and their effects on the thyroid function of mothers and infants were summarized in this review. Possible mechanisms of action by which PFAS may affect thyroid function were also summarized, aiming to provide a theoretical basis for the development of environmental standards and safety limits for PFAS.

Background Patients with post-stroke hemiplegia are likely to experience fatigue and sleep disorder.Attention and interpretation therapy(AIT)has been shown to promote psychological flexibility,thereby alleviating their stress,improving emotional management and somatopsychic adaptation.Currently,there is a lack of application of AIT in patients with post-stroke hemiplegia.Objective To explore the effect of modified AIT on fatigue and sleep quality in patients with post-stroke hemiplegia,so as to provide references for physical and mental rehabilitation nursing of post-stroke hemiplegia patients.Methods A total of 120 patients with post-stroke hemiplegia attending the rehabilitation medicine department of North China University of Science and Technology Affiliated Hospital from August 1,2021 to June 30,2022 and fulfilling the Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018 and the Chinese guidelines for diagnosis and treatment of acute intracerebral hemorrhage 2019 were enrolled.Patients were assigned into two groups using random number table methods,each with 60 cases.Control group was given chronic illness trajectory model-based nursing,while study group received modified AIT intervention.All participants were evaluated using the Chinese version of Neurological Fatigue Index for Stroke(NFI-Stroke)and Pittsburgh Sleep Quality Index(PSQI)at the baseline,after 4 weeks and 8 weeks of intervention.Results The repeated measures ANOVA on PSQI total score and scores on sleep quality,sleep time,sleep duration,sleep efficiency,sleep disturbance and daytime dysfunction revealed a significant group effect,time effect and interaction effect(Fgroup=4.281,5.598,8.814,4.351,4.302,4.091,7.608,Ftime=122.230,19.698,19.289,16.403,15.421,28.879,90.876,Finteraction=19.508,3.227,11.586,5.237,5.507,5.799,3.338,P<0.05).Significant group effect,time effect and interaction effect were reported on NFI-Stroke total score and scores on physical subscale and cognitive subscale(Fgroup=7.140,5.466,5.547,Ftime=362.192,309.817,70.888,Finteraction=21.079,13.430,13.354,P<0.05).Conclusion Modified AIT may help alleviate fatigue and improve sleep quality in patients with post-stroke hemiplegia.

With the increasing prevalence of diabetes,the prevention and treatment of diabetes nephropathy have become a worldwide problem.The molecular mechanism of the occurrence and development of diabetes nephropathy is still unclear,but many studies in recent years have shown that gut microbiota plays an important role in the progress on diabetes nephropathy.The research progress on the mechanism of gut microbiota participating in diabetes nephropathy was reviewed in this article.

Objective: To investigate the changes in the levels of interleukin-6 (IL-6) and let-7e in rats induced by coal mine dust, so as to provide the basis for the mechanism of coal worker's pneumoconiosis (CWP). Methods: Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group, coal dust group, mixed dust group (mixed coal and silica dust) and quartz group. The rats in the control group were exposed to 1 mL physiological saline by non-exposure tracheal perfusion, and the rats in the dust-exposed groups were exposed to 1 mL dust suspension. Rats were sacrificed by anesthesia after 1 month and 6 months, lung tissue was observed using hematoxylin-eosin staining, the pathological change in the lungs was scored using the Szapiel scoring system, the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay, and the expression of let-7e was determined by quantitative real-time PCR. Results: A month after exposure, a small amount of coal spots and inflammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group. The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum. Six months after exposure, there were more coal spots and slightly thickened alveolar septum in the coal dust group, and hyperplasia of pulmonary interstitial fibers, destruction of alveolar structure and silica nodules were observed in the mixed dust group. In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and silica nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P<0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust-exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05). Conclusions Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.