ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.

Chinese hamster ovary (CHO) cells are the most established and versatile mammalian expression system for the large-scale production of recombinant therapeutic proteins, owing to their genetic stability, adaptability to serum-free suspension culture, and ability to perform human-like post-translational modifications. More than 70% of biologics approved by the U.S. Food and Drug Administration rely on CHO-based production platforms, underscoring their central role in modern biopharmaceutical manufacturing. Despite these advantages, CHO systems continue to face three persistent bottlenecks that limit their potential for high-yield, reproducible, and cost-efficient production: excessive metabolic burden during high-density culture, heterogeneity of glycosylation patterns, and progressive loss of long-term expression stability. This review provides an integrated analysis of recent advances addressing these challenges and proposes a forward-looking framework for constructing intelligent and sustainable CHO cell factories. In terms of metabolic regulation, excessive lactate and ammonia accumulation disrupts energy balance and reduces recombinant protein synthesis efficiency. Optimization of culture parameters such as temperature, pH, dissolved oxygen, osmolarity, and glucose feeding can effectively alleviate metabolic stress, while supplementation with modulators including sodium butyrate, baicalein, and S-adenosylmethionine promotes specific productivity (qP) by modulating apoptosis and chromatin structure. Furthermore, genetic engineering strategies—such as overexpression of MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

Glucosidases are an indispensable class of enzymes in the sugar metabolism of organisms. To investigate the biological functions and expression patterns of α-glucosidases (AGLUs) and β-glucosidases (BGLUs), we identified the two family members in the genome of melon (Cucumis melo). The number, location on chromosomes, gene structure, subcellular localization, conserved motifs, and phylogenetic relationship of the two family members were analyzed. Based on the cis-acting elements in the promoter region and protein interaction models, their functions were preliminarily predicted. Furthermore, the gene expression of the two family members was determined by qRT-PCR. The results showed that the melon genome contained five AGLU family members on five chromosomes, and all of the five members were located in the extracellular matrix, with the amino acid sequence lengths ranging from 899 aa to 1 060 aa. The melon genome carried 18 BGLU family members on 8 chromosomes, and all the members were located in the cell membrane or cytoplasm, with the amino acid lengths ranging from 151 aa to 576 aa. The qRT-PCR results showed that the expression of about 50% of the genes was down-regulated upon cold stress. CmAGLU5 and CmBGLU7 may be key members of the two families, respectively, in response to cold stress. The expression of all members of the two families was up-regulated under abscisic acid (ABA), high salt, and drought stress. In the AGLU family, CmAGLU3 was the key gene in response to ABA and high salt stress, while CmAGLU4 was the key gene in response to drought stress. In the BGLU family, CmBGLU18 was the key gene in response to ABA, while CmBGLU6 was the key gene in response to high salt and drought stress.
beta-Glucosidase/metabolism* ; Phylogeny ; alpha-Glucosidases/metabolism* ; Gene Expression Regulation, Plant ; Cucurbitaceae/enzymology* ; Multigene Family ; Cucumis melo/enzymology* ; Stress, Physiological

Objective To explore the relationship between bedtime procrastination and fear of missing out and the intervention effect of aerobic exercise on bedtime procrastination,so as to provide a theoretical basis and practical reference for remedying bedtime procrastination.Methods Totally 988 students were selected through random sampling and then surveyed with the bedtime procrastination scale and the fear of missing out scale.Correlation and regression analyses were performed to explore the relationship between bedtime procrastination and fear of missing out.A total of 36 students were recruited from the 988 students to participate in the exercise intervention and they were assigned into an exercise group and a control group by the random number table method,with 18 students in each group.The exercise group performed aerobic exercise for 12 weeks,while the control group maintained daily activities.The participants' scores on the bedtime procrastination scale and the fear of missing out scale were recorded before and after the intervention and compared.Results The fear of missing out was positively correlated with bedtime procrastination among college students(r=0.214,P<0.001),and it was an important predictive factor for bedtime procrastination(β=0.241,P<0.001).After the intervention,the scores of bedtime procrastination scale decreased in the exercise group(t=2.277,P=0.036),while there was no significant difference in the scores of the control group before and after intervention(t=-0.787,P=0.442).Conclusions A high level of fear of missing out indicates severe bedtime procrastination.And 12-week exercise intervention could remedy bedtime procrastination.
Humans ; Fear ; Exercise ; Male ; Female ; Procrastination ; Young Adult ; Cross-Sectional Studies ; Students/psychology* ; Adult ; Surveys and Questionnaires ; Adolescent

Cancer brings about an enormous threat to human health,making the exploration of its mechanisms and therapeutic strategies a current focal point and challenge in research.Bacteriophages are integral components of the human microbiome,and studies have shown their influences on tumor growth and metastasis and their pivotal role in cancer treatment.This article elucidates the mechanisms by which bacteriophages impact the occurrence and development of cancer from their interactions with cancer cells,effects on bacteria,and influence on the immune system.Additionally,it explores bacteriophage-based strategies in cancer treatment and their potential in this field.This article aims to bring new thoughts and insights to the research in this field.
Humans ; Bacteriophages ; Microbiota ; Neoplasms/therapy* ; Phage Therapy

Surface enhanced Raman scattering(SERS)is an important technique for detecting pesticide residues.However,many pesticides have small Raman scattering cross sections and low affinity for gold/silver enhancement substrates,resulting in low sensitivity for direct SERS detection.Indirect methods typically require complex surface modifications and have poor universality.Here,a dual functional composite Au@MnO2 combined with acetylcholinesterase(AChE)was proposed for SERS biosensing of pesticides.The Au@MnO2 with oxidase-like activity could oxidize 3,3′,5,5′-tetramethylbenzidine(TMB)into oxTMB with a large Raman scattering cross section,producing strong SERS signal using Au@MnO2 itself as enhancement substrate.In the presence of AChE,acetylthiocholine(ATCh)was catalytically hydrolyzed to produce thiocholine(TCh),and its reducibility could induce the decomposition of MnO2.Consequently,oxidase-like activity of Au@MnO2 was declined,less oxTMB was produced,and gold nanoparticles(AuNPs)detached from the MnO2 layer,resulting in a weakened SERS response.Organophosphorus pesticides(OPs),as inhibitors of AChE,prevented the production of TCh,thereby blocking the decomposition of MnO2 and leading to the recovery of Raman signals.Under optimized conditions,the Raman signal switching strategy was successfully used for detection of three OPs,i.e.,fenthion,chlorpyrifos,and methyl parathion,with detection limits of 4×10-11 mol/L,2×10-9 mol/L,and 3×10-9 mol/L,respectively.In actual spinach sample testing,the spiked recoveries of the three OPs ranged from 86.5%to 110.6%.This study provided a new strategy for detecting pesticide residues using SERS.