mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

Objective To rexplore the content structure characteristics and psychometric properties of assessment scales for funda-mental movement skills(FMS)in school-aged children,based on International Classification of Functioning,Dis-ability and Health-Children and Youth Version(ICF-CY)framework.Methods Literatures on assessment scales for FMS in school-aged children were retrieved from PubMed,Science Di-rect,Web of Science,EMBase,PsycINFO,CNKI and Wanfang data from inception to July,2025.The contents of the included scales were analyzed using the ICF-CY linking rule.The COSMIN RoB tool was used to assess the psychometric properties of the scales,and the GRADE system was applied to evaluate the overall quality of evi-dence.Results A total of 29 studies were included,involving six assessment scales:Bruininks-Oseretsky Test of Motor Profi-ciency-2(BOT-2),Canadian Assessment of Movement Skill and Agility(CAMSA),K?rperkoordinationstest für Kinder(KTK),Movement Assessment Battery for Children-2(MABC-2),Motorische Basiskompetenzen test Battery(MOBAK),and Test of Gross Motor Development-3(TGMD-3).In the ICF-CY linking analysis,all six tools addressed joint mobility functions(b710)and joint stability functions(b715),while five of them also in-volved hand and arm use(d445).The number of linked items ranged from 5 to 11.BOT-2 and TGMD-3 linked to 11 items,showing broad coverage;BOT-2 focused more on the body function dimension,whereas TGMD-3 em-phasized activity and participation dimensions,especially the performance of hand function in daily activities.In bias risk assessment,TGMD-3 showed the lowest risk(50%rated A and 50%rated B),while MABC-2 had the highest proportion of C ratings(55.6%),followed by BOT-2(33.3%).In evidence grading,TGMD-3 was rated high quality,KTK moderate,BOT-2 and CAMSA low,and MABC-2 and MOBAK very low.Conclusion TGMD-3 is recommended as the primary tool for assessing FMS in school-aged children for broad coverage of ICF-CY items,strong psychometric properties and high evidence quality.KTK,with moderate evidence quali-ty,may serve as a secondary option,but should be used cautiously in China.Although CAMSA is easy to admin-ister,its validity and reliability are low,so it is only suitable for rapid classroom screening.BOT-2,despite cover-ing more ICF-CY items,has a higher bias risk and low evidence quality.MOBAK and MABC-2 have very low evidence quality and are not recommended for current use.

Objective To rexplore the content structure characteristics and psychometric properties of assessment scales for funda-mental movement skills(FMS)in school-aged children,based on International Classification of Functioning,Dis-ability and Health-Children and Youth Version(ICF-CY)framework.Methods Literatures on assessment scales for FMS in school-aged children were retrieved from PubMed,Science Di-rect,Web of Science,EMBase,PsycINFO,CNKI and Wanfang data from inception to July,2025.The contents of the included scales were analyzed using the ICF-CY linking rule.The COSMIN RoB tool was used to assess the psychometric properties of the scales,and the GRADE system was applied to evaluate the overall quality of evi-dence.Results A total of 29 studies were included,involving six assessment scales:Bruininks-Oseretsky Test of Motor Profi-ciency-2(BOT-2),Canadian Assessment of Movement Skill and Agility(CAMSA),K?rperkoordinationstest für Kinder(KTK),Movement Assessment Battery for Children-2(MABC-2),Motorische Basiskompetenzen test Battery(MOBAK),and Test of Gross Motor Development-3(TGMD-3).In the ICF-CY linking analysis,all six tools addressed joint mobility functions(b710)and joint stability functions(b715),while five of them also in-volved hand and arm use(d445).The number of linked items ranged from 5 to 11.BOT-2 and TGMD-3 linked to 11 items,showing broad coverage;BOT-2 focused more on the body function dimension,whereas TGMD-3 em-phasized activity and participation dimensions,especially the performance of hand function in daily activities.In bias risk assessment,TGMD-3 showed the lowest risk(50%rated A and 50%rated B),while MABC-2 had the highest proportion of C ratings(55.6%),followed by BOT-2(33.3%).In evidence grading,TGMD-3 was rated high quality,KTK moderate,BOT-2 and CAMSA low,and MABC-2 and MOBAK very low.Conclusion TGMD-3 is recommended as the primary tool for assessing FMS in school-aged children for broad coverage of ICF-CY items,strong psychometric properties and high evidence quality.KTK,with moderate evidence quali-ty,may serve as a secondary option,but should be used cautiously in China.Although CAMSA is easy to admin-ister,its validity and reliability are low,so it is only suitable for rapid classroom screening.BOT-2,despite cover-ing more ICF-CY items,has a higher bias risk and low evidence quality.MOBAK and MABC-2 have very low evidence quality and are not recommended for current use.

mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

BACKGROUND:Kaempferol has anti-osteoporotic effects,but the mechanisms by which kaempferol regulates gut microbiota and metabolites to prevent and treat osteoporosis remain unclear.OBJECTIVE:To exploring the potential mechanisms by which kaempferol inhibit osteoporosis based on gut microbiota and comprehensive targeted metabolomics.METHODS:Eighteen female Sprague-Dawley rats were randomly divided into three groups:sham operation group,model group,and kaempferol group,with 6 rats in each group.Animal models of osteoporosis were made in the latter two groups through removal of bilateral ovaries.Eight weeks after modeling,the sham operation and model groups were gavaged with distilled water,and the kaempferol group was gavaged with 40 mg/kg kaempferol.Continuous administration in each group was carried out for 12 weeks.Rat fecal samples were collected for 16S rDNA amplicon sequencing to observe changes in the gut microbiota structure.Serum samples were subjected to comprehensive targeted metabolomics analysis using ultra-high performance liquid chromatography-tandem mass spectrometry technology,along with a proprietary database and multivariate statistical analysis.RESULTS AND CONCLUSION:After 12 weeks of continuous intervention,the results of 16S rDNA amplicon sequencing showed that compared with the sham operation group,the abundance of gut microbiota increased in the model group.Compared with the model group,kaempferol group exhibited a statistically significant increase in the abundance of the genus Latilactobacillus(P=0.021),while the abundances of Pantoea(P=0.034),Enterorhabdus(P=0.000),Monoglobus(P=0.024),Butyricimonas(P=0.034),Rothia(P=0.043),and Clostridia(P=0.004)were significantly downregulated.After 12 weeks of continuous intervention,the results of the serum samples analyzed by broad-targeted metabolomics revealed that 120 and 79 metabolites were identified between the sham operation and model groups and between the model and kaempferol groups,respectively.Among the three groups,there were 17 overlapping differentially expressed metabolites,including Cis-aconitic acid,barbituric acid,L-homocitrulline,3,4,5-trimethoxycinnamic acid,L-3-phenyllactic acid,cyclo(pro-pro),L-phenylalanine-L-serine,proline-isoleucine,L-donoraminoacetic acid-L-phenylalanineacetic acid,and phenylalanine-aspartic acid.Most of them belong to amino acids and their metabolites,glycerophospholipids and fatty acyls.The Kyoto Encyclopedia of Genes and Genomes pathways involved in the differential metabolites were mainly enriched in D-amino acid metabolism,histidine metabolism,propionate metabolism,lysine degradation,fatty acid metabolism and sphingolipid metabolism.After 12 weeks of continuous intervention,combined analysis revealed that genera such as Enterorhabdus,Latilactobacillus,Rothia,and Ruminococcus were closely associated with differential serum metabolites.To conclude,kaempferol may exert its anti-osteoporotic effects by modulating the abundance,diversity,and structure of gut microbiota,thereby regulating the metabolism of amino acids,their metabolites,and fatty acids.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC₅₀), IC₅₀, 2×IC₅₀, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC₅₀), 20 (IC₅₀) and 40 (2×IC₅₀) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe²⁺, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
Ferroptosis/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism* ; Breast Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Female ; Cell Line, Tumor ; Tumor Suppressor Protein p53/metabolism* ; Amino Acid Transport System y+/metabolism* ; Humans ; Reactive Oxygen Species/metabolism* ; Animals ; Mice ; Cell Proliferation/drug effects* ; Mitochondria/metabolism* ; Coenzyme A Ligases/metabolism* ; Cell Movement/drug effects* ; Benzopyrans

Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80％and 125％.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.

This study was aimed at surveying the distribution of Himalayan marmots in Gaotai County,Zhangye City,Gan-su Province,and analyzing the risk of plague occurrence,to provide a scientific basis for plague prevention and control in the area.On the basis of preliminary evidence,we used a combined approach of on-site investigation and Global Positioning System(GPS)positioning to survey the distribution and natural geographical landscape characteristics of the Himalayan marmot in Gaotai County.Population information and customs in the marmot distribution area were investigated through methods such as data retrieval and household visits.Himalayan marmots were captured through bow-shaped trapping,and blood,liver,spleen,heart,lung,kidney,femur,and surface-intermediate host samples were collected.Pathological and serological tests were conducted according to the Plague Diagnosis Criteria(WS279-2008).In Xinba Town,Gaotai County,Himalayan marmots were found in 16 villages(53.33％).Heping Village had the largest distribution area(100％),and was followed by Zhaoyi Village(79.17％)and Xishang Village(55.32％),whereas the other areas had values below 50％.Regarding the direct threats posed by marmots,Heping Village,Dongda Vil-lage,and Zhaoyi Village had values of 100％,Xishang Village had a value of 90.59％,and the other areas had values below 50％.The flea infestation rate on marmots'bodies was 59.62％,and the flea index was 1.48％(77/52).The main surface-in-termediate hosts were steppe ticks,body lice,Xenopsylla siberica,and Nosopsyllus laeviceps,accounting for 72.31％(517/715),16.92％(121/715),6.43％(46/715),and 4.20％(30/715),respectively,with steppe ticks being the dominant species.A total of 52 liver and spleen tissue samples from marmots,and 715 surface-intermediate hosts samples,were collected for bacterial culture.No Yersinia pestis was found.RIHA testing for plague F1 antigen was negative in all samples.Additionally,52 blood serum samples from marmots were collected,and IHA testing for plague-specific F1 antibodies was negative in all samples.The natural plague foci of marmots in the Qilian Mountains and Altyn Mountains is affected by factors including con-tinuing increases in temperature and grassland degradation.As a result,the marmot plague hosts continually migrate to sur-rounding non-epidemic areas,particularly in Gaotai County,Zhangye City.Local residents often hunt wild rabbits and mar-mots,thus posing a risk of human plague outbreaks if animal plague occurs.This county is recommended to be included in the province's plague surveillance and epidemic source investigation.Additionally,efforts should be strengthened in health educa-tion,medical personnel training,and management of key individuals and emergency reserves.If necessary,protective measures should be taken in marmot and flea control,to prevent the occurrence and spread of plague.