Based on ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) technology and molecular docking, the bitter-tasting substances(hereafter referred to as "bitter substances") in Cistanche deserticola extract were investigated, and the bitter taste and efficacy relationship was explored to lay the foundation for future research on de-bittering and taste correction. Firstly, UPLC-Q-Orbitrap HRMS was used for the qualitative analysis of the constituents of C. deserticola, and 69 chemical components were identified. These chemical components were then subjected to molecular docking with the bitter taste receptor, leading to the screening of 20 bitter substances, including 6 phenylethanol glycosides, 5 flavonoids, 3 phenolic acids, 2 cycloalkenyl ether terpenes, 2 alkaloids, and 2 other components. Nine batches of fresh C. deserticola samples were collected from the same origin but harvested at different months. These samples were divided into groups based on harvest month and plant part. The bitterness was quantified using an electronic tongue, and the content of six potential bitter-active compounds(pineconotyloside, trichothecene glycoside, tubulin A, iso-trichothecene glycoside, jinshihuaoside, and jingnipinoside) was determined by high-performance liquid chromatography(HPLC). The total content of phenylethanol glycosides, polysaccharides, alkaloids, flavonoids, and phenolic acids was determined using UV-visible spectrophotometry. Chemometric analyses were then conducted, including Pearson's correlation analysis, gray correlation analysis, and orthogonal partial least squares discriminant analysis(OPLS-DA), to identify the bitter components in C. deserticola. The results were consistent with the molecular docking findings, and the two methods mutually supported each other. Finally, network pharmacological predictions and analyses were performed to explore the relationship between the targets of bitter substances and their efficacy. The results indicated that key targets of the bitter substances included EGFR, PIK3CB, and PTK2. These substances may exert their bitter effects by acting on relevant disease targets, confirming that the bitter substances in C. deserticola are the material basis of its bitter taste efficacy. In conclusion, this study suggests that the phenylethanol glycosides, primarily pineconotyloside, mauritiana glycoside, and gibberellin, are the material basis for the "bitter taste" of C. deserticola. The molecular docking technique plays a guiding role in the screening of bitter substances in traditional Chinese medicine(TCM). The bitter substances in C. deserticola not only contribute to its bitter taste but also support the concept of the "taste-efficacy" relationship in TCM, providing valuable insights and references for future research in this area.
Molecular Docking Simulation ; Taste ; Chromatography, High Pressure Liquid ; Cistanche/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mass Spectrometry

Objective To analyze the expression and diagnostic value of procalcitonin(PCT),white blood cell count(WBC),and C-reactive protein(CRP)in respiratory infections in the intensive care unit(ICU),and their correlation with the clinical pulmonary infection score(CPIS).Methods A total of 105 patients with respiratory infections admitted to the ICU from March 2019 to June 2024 were selected as the observation group,while 117 patients with no respiratory infection in the ICU were selected as the control group.PCT levels in both groups were measured using the Zybio-Q7 immunoquantitative analyzer,WBC levels were measured using XT-4000i white blood cell analyzer,and CRP levels were measured using the immunoturbidimetric method.The relationship between the expression of PCT,WBC and CRP and the clinical characteristics and CPIs score of respiratory infection in ICU were analyzed.Results The proportion of patients in the observation group with ICU stay>15 days and mechanical ventilation>7 days was significantly higher than that in the control group(P<0.05).Compared to the control group,the levels of PCT,WBC,CRP and CPIS score in the observation group were elevated,with statistically significant differences(P<0.05).Multivariate logistic regression analysis showed that ICU stay>15 days(OR=4.087),PCT(OR=6.543),WBC(OR=2.652),and CRP(OR=8.964)were risk factors for the occurrence of respiratory infections in the ICU.Pearson correlation analysis indicated a positive correlation between PCT and CPIS scores(r=0.925,P=0.001),a positive correlation between WBC and CPIS scores(r=0.739,P=0.001);and a positive correlation between CRP and CPIS scores(r=0.948,P=0.001).The ROC curve demonstrated that the combined diagnostic value of the three markers for ICU respiratory infections was higher than that of PCT,WBC,or CRP alone(P=0.002).Conclusion The combination of PCT,WBC,and CRP has high diagnostic value for ICU respiratory infections and is positively correlated with CPIs scores.Therefore,the above indicators can provide a reliable basis for the early diagnosis of respiratory infection in ICU.

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.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

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.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

Objective:To investigate the changes of CTCs and the correlation between the changes of CTCs and the clinical efficacy of neoadjuvant immunotherapy for non-small cell lung cancer (NSCLC).Methods:A retrospective case-control study was conducted to collect the data of 23 patients with NSCLC who received neoadjuvant immunotherapy in the Third Xiangya Hospital from June 2018 to December 2019. They were 35-76 years old with a median age of 52 years old, including 13 male patients and 10 female patients. The CTCs value, evaluation results from response evaluation criteria in solid tumor (RECIST) and major pathological response were evaluated before treatment, after neoadjuvant immunotherapy and after operation. Mann Whitney U test was used for the comparison between the two groups, Wilcoxon test was used for the comparison of association samples, and Kruskal Wallis test was used for the comparison between multiple samples.Results:The CTCs value was positively correlated with tumor progression, that the CTCs value of ⅡB group, ⅢA group and ⅢB group was 10.69 (3.87) FU/3 ml, 12.90 (2.24) FU/3 ml and 16.04 (3.43) FU/3 ml, and the difference was statistically significant (χ 2=7.829, P=0.020). Then CTCs decreased to 7.60(4.79) FU/3 ml significantly ( Z=4.197, P=0.000), and decreased to 6.22(2.80) FU/3 ml significantly again after surgery( Z=-2.950, P=0.005). In RECIST results, the CTCs value of CR group, PR group and SD group was 12.90(3.79)FU/3 ml, 12.52(3.96) FU/3 ml and 13.58(5.11) FU/3 ml,and no significant difference before treatment (χ2=1.806, P=0.405). After neoadjuvant immunotherapy, the CTCs of CR group decreased to 6.22(3.87) FU/3 ml significantly ( Z=-4.950, P= 0.000), and also PR group to7.32(4.31) FU/3 ml ( Z=-3.180, P=0.001) or SD group to ( Z=-2.023, P=0.043). There was no significant difference between CR group and PR group ( Z=-0.838, P=0.402), but significant difference between SD group and CR/PR group ( Z=-1.922, P=0.050). After operation, the CTCs of CR, PR and SD group decreased to 6.09(3.43) FU/3 ml, 6.40(1.82) FU/3 ml and 9.20(5.16) FU/3 ml,and there was no significant difference to preparation in CR group and PR group, but significant difference in SD group ( Z=-2.023, P=0.043). There was no significant difference between CR group and PR group ( Z=-1.134, P=0.257), but significant difference between SD group and CR/PR group ( Z=-1.624, P=0.014). Before treatment,CTCs of MPR group and non-MPR group were 11.98(4.14) FU/3 ml and 13.54(4.76) FU/3 ml,and there was no significant difference between them ( Z=-1.354, P=0.176). After neoadjuvant immunotherapy, the CTCs of MPR group decreased to 6.36(2.65) FU/3 ml significantly ( Z=-2.934, P=0.001) and also in non-MPR group to 10.88(2.80) FU/3 ml ( Z=-2.840, P=0.003); but there was significant difference between MPR group and non-MPR group ( Z=-3.693, P=0.000), and also the change of CTCs between two groups ( Z=-2.770, P=0.006). After operation, the CTCs of MPR group decreased to 5.40(1.33) FU/3 ml insignificantly ( Z=-0.533, P=0.594) but significantly to 7.05(3.80) FU/3 ml in non-MPR group ( Z=-2.734, P=0.030), and significant difference between them ( Z=-1.900, P=0.011). Conclusion:The value of CTCs is negatively correlated with the efficacy (RECIST and MPR) of neoadjuvant immunotherapy for NSCLC, which can be used for clinical efficacy evaluation of neoadjuvant immunotherapy.

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.

OBJECTIVE: To perform dried blood spots thalassemia gene detection in patients with positive blood phenotypes by microarray technology, and evaluate its value in clinical detection. METHODS: DNA samples were extracted from dried blood spots of 410 patients. Microarray technology was used to detect 3 deletion and 3 non-deletion types of α-thalassemia and 19 β-thalassemia point mutations which were common gene mutions in China. RESULTS: There were 357 positive cases in all the 410 tested samples with the positive rate 87.07%, among which 299 cases (72.93%) carried deletion or point mutations of α-thalassemia, 29 cases (7.07%) carried point mutations of β-thalassemia and 29 cases (7.07%) carried gene mutations of complex αβ-thalassemia syndrome. The mutations of α-thalassemia were involved with -- CONCLUSION The most common genetic mutations are --
China ; Humans ; Mutation ; Oligonucleotide Array Sequence Analysis ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*