Since its emergence in the 1980s, the human immunodeficiency virus (HIV) has caused a global pandemic, posing a severe threat to human life and health as well as social development. Although pre-exposure prophylaxis (PrEP) effectively curbs HIV transmission and antiretroviral therapy (ART) significantly extends the lifespan of patients, vaccines remain a pivotal tool for blocking transmission and ending the pandemic. The high genetic variability of HIV-1, the glycan shield of its envelope glycoproteins, and the long-term persistence of latent reservoirs have repeatedly led to bottlenecks in traditional vaccine strategies. In recent years, mRNA technology has offered a novel approach to addressing these challenges, leveraging advantages such as sequence programmability, short production cycles, native conformational expression of antigens, and self-adjuvant effects. In recent years, mRNA vaccine technology has emerged as a transformative solution to longstanding vaccinology challenges, characterized by its sequence programmability, rapid production cycles, native conformational antigen expression, and intrinsic self-adjuvanting properties. Unlike traditional platforms reliant on pathogen culture or recombinant proteins, mRNA vaccines can be expeditiously designed and updated based solely on viral genomic sequences. Lipid nanoparticle (LNP)-encapsulated mRNA facilitates endogenous antigen expression and presentation, simultaneously eliciting potent humoral and cellular immune responses. Within this landscape, self-amplifying mRNA (saRNA) further extends in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar inHIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective The aim of this study was to investigate the correlation between the interaction of uric acid and inflammatory factors and hyperuricemia in overweight/obese patients. Methods The personnel with hyperuricemia who underwent physical examination in our hospital from September 2021 to September 2022 were selected as the study subjects, and they were divided into 100 cases of overweight group and 90 cases of obese group according to the BMI index; 120 cases of healthy and non-hyperuricemic personnel were randomly selected as the control group; venous blood of the three groups was collected in 5 mL after 8 h of fasting, and were tested respectively for serum uric acid, lipid indexes and inflammatory factors: IL-6, IL-2, IFN-γ, TNF-α, IL-4, IL-10. Results Glucose, triglycerides, total cholesterol, and LDL were significantly higher in the obese group versus the overweight group (P<0.001), while HDL was significantly lower than the control group (P<0.001), and these changes were more pronounced in the obese group (P<0.001).The Pearson correlation coefficient pointed out that the levels of serum uric acid in patients with hyperuricosuric acid were significantly associated with the pro-inflammatory factors IL- 6, IL-2, IFN-γ, and TNF-α were significantly positively correlated (P<0.001), whereas they were significantly negatively correlated with the anti-inflammatory factors IL-4, IL-10 (P<0.001). Conclusion High uric acid levels in overweight/obese patients can cause enhanced inflammatory responses and reduced expression levels of anti-inflammatory factors, and the interaction between uric acid and pro-inflammatory factors aggravates the condition of patients with hyperuricemia.

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

Objective To analyze the medication rules of traditional Chinese medicine compound patents for the prevention and treatment of urinary tract infection(UTI)through data mining technology.Methods The patents of traditional Chinese medicine compounds for the prevention and treatment of UTI in patent announcement module of China National Intellectual Property Administration website as data sources.The statistical analysis platforms of Excel 2021,IBM SPSS Modeler 18.0 and IBM SPSS Statistics 27.0 were used for frequency of use,medicinal properties,association rule analysis,and systematic clustering analysis and finally visualized by Cytoscape 3.7.2,RStudio.Results Through screening,a total of 179 compound patents met the inclusion criteria,involving 466 kinds of Chinese materia medica,and the top 5 high-frequency drugs were Pugongying,Huangbai,Gancao,Jinyinhua,Bianxu.The medicinal properties are mainly cold and mild;The medicinal taste is characterized by sweetness,bitterness,and bitterness;The main meridians of drugs are liver,lung and kidney meridians.Common couplet medicines included Qumai-Bianxu,Gancao-Bianxu and the three herb drug combinations included Cheqianzi-Qumai-Bianxu,Gancao-Qumai-Bianxu.A total of 5 high-frequency combinations of traditional Chinese medicine were obtained by cluster analysis.Conclusion This study preliminarily reveals the compatibility and medication rules of traditional Chinese medicine in the treatment of UTI,which provides data support for the optimization of clinical syndrome differentiation and treatment system and the development of new prescriptions.

Objective To explore the acceptability of routine biochemical test results for serum samples with varying degrees of chylous high triglyceride(TG).Methods Blood samples of 69 patients with different degrees of lipids were collected,including 33 patients with mild to moderate lipids(1.7 mmol/L≤TG<5.6 mmol/L)and 36 patients with severe lipids(TG≥5.6 mmol/L).Twenty-nine biochemical tests were detected before and after high-speed centrifugation.The result acceptability before high speed centrifugation of serum was compared with the results after high speed centrifugation as the gold standard[TG and total cholesterol(TC)before centrifugation].The acceptable criteria were subject to the following three conditions at the same time.Firstly,correlation coefficient(R2)was greater than or equal to 0.95.Secondly,the slope of linear re-gression equation was 1.00±0.05.Thirdly,for the same index,the number of samples whose result bias be-fore and after centrifugation was less than 1/2 total allowable error(TEa)in more than 90%of the total sam-ple numbers.Results Firstly,in the mild to moderate lipemia group,22 tests met the criteria,7 tests did not,including total protein(TP),albumin(ALB),TG,aspartate aminotransferase(AST),carbon dioxide(CO2),α-L-fucosidase(AFU),lactate dehydrogenase(LDH)(bias<10%),and the coincidence rate was 75.9%.In the severe lipemia group,12 tests met the criteria,17 tests did not,including pre-albumin(PA),AFU,γ-glu-tamyltransferase(γ-GT),LDH,AST,TC,direct bilirubin(DBIL),CO2,5'-nucleotidase(5'-NT),small and low-density lipoprotein cholesterol(sd-LDL-C),high density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),adenosine deaminase(ADA),cystatin C(CysC),glycosylated albumin(GA),total bilirubin(TBIL)(bias>10%),the coincidence rate was 41.4%,and there was a statistically sig-nificant difference in the coincidence rate between the two groups(P<0.05).Secondly,there was no statisti-cally significant difference in the acceptability of results between continuous monitoring method and endpoint method detection methods(P>0.05).Conclusion Most test results of direct determination with mild or moderate lipemia samples are acceptable,and the bias of unacceptable tests is small(<10%),so it is recom-mended to issue a test report without further sample treatment.However,due to the large number of unacceptable tests and larger bias(>10%),severe lipemia samples should be determined after high-speed centrifugation.

Objective:To explore the correlative factors for insomnia severity in chronic insomnia patients using MemTrax memory test.Methods:Two hundred and twenty-two chronic insomnia patients (insomnia≥3 days per week with a duration≥3 months) recruited from Center for Preventive Treatment of Diseases, Guangdong Provincial Hospital of Chinese Medicine or through in-hospital advertisements from April 2024 to September 2024 were chosen. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality over the last month; according to PSQI score, these patients were divided into mild insomnia group (scores of 7-10), moderate insomnia group (scores of 11-15) and severe insomnia group (scores of 16-21). MemTrax memory test was used to record the picture recognition accuracy and picture recognition reaction time, and MemTrax comprehensive index (MTx-Cp) was calculated; Patients' Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder-7 scale(GAD-7) were used to evaluate the depression and anxiety status of these patients in recent 2 weeks. The clinical data, MemTrax test results, PHQ-9 and GAD-7 scores of patients with different degrees of chronic insomnia were compared. Spearman rank correlation analysis was used to investigate the correlation between insomnia severity and clinical data such as cognitive memory function in chronic insomnia patients.Results:Among the 220 chronic insomnia patients, 54 had mild insomnia, 111 had moderate insomnia, and 55 had severe insomnia. Severe insomnia patients had significantly higher percentages of those>50 years old and those using hypnotics compared with mild insomnia patients and moderate insomnia patients ( P<0.05). Compared with the mild insomnia patients and moderate insomnia patients, the severe insomnia patients exhibited significantly lower picture recognition accuracy (90%[86%, 94%], 88%[82%, 94%], 84%[78%, 92%]), significantly lower MTx-Cp (88.55±18.67, 84.41±20.93, 76.69±17.43), and significantly higher PHQ-9 score (9[6, 11], 9[6, 15], 12[8, 16], P<0.05). Moreover, severe insomnia patients had significantly longer picture recognition reaction time and higher GAD-7 score than mild insomnia patients (1.11[1.03, 1.24] s vs. 1.04[0.90, 1.15] s; 7[5, 13] vs. 6[3, 9], P<0.05). Spearman rank correlation analysis showed that insomnia severity in chronic insomnia patients was positively correlated with age, PHQ-9 score, GAD-7 score, and picture recognition reaction time, and negatively correlated with picture recognition accuracy and MTx-Cp ( P<0.05). Conclusion:Insomnia severity in patients with chronic insomnia is correlated with age, cognitive memory function, depression and anxiety.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.