Objective To analyze the spatial distribution patterns and influencing factors of potential suitable habitats for Saussurea medusa under current climatic conditions.Methods The maximum entropy(MaxEnt)model with 125 selected distribution spots data and 9 environmental factors data of Saussurea medusa as input variables for modeling.Quantitative analysis was conducted on the influencing factors of spatial differentiation in the suitable habitat area of Saussurea medusa using geographic detector factor detection and interaction detection tools.Based on land use type data and national nature reserve distribution data,the distribution range of each land use type in the suitable habitat areas for Saussurea medusa,as well as the distribution pattern of high,medium and low suitable habitat areas in national nature reserves were refined.Results Key environmental determinants included elevation,precipitation in the warmest quarter,and solar radiation in April and May.The total potential suitable habitat area spanned 1.33×106 km2,accounting for 13.89%of China's mainland.Grasslands(67.70%),forests(19.19%),barren land(5.90%),snow-covered areas(2.59%)and croplands(2.08%)dominated the suitable habitats,with 34.98%overlapping national nature reserves.Conclusion The results of this study can provide basis for understanding the ecological needs and resource conservation of Saussurea medusa.

Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

Objective To investigate the spatial distribution patterns and environmental determinants of Lagotis brachystachya Maxim.,a keystone species in Tibetan medicine("Zhi Da Sa Zeng"),under contemporary climatic conditions in China;To provide references for the sustainable utilization of its resources and the ecological protection of alpine grassland areas.Methods Based on the maximum entropy model,the selected species distribution data and environmental factors were added to MaxEnt 4.3.1 software for modeling.The geographical detector was applied to quantify the factors influencing the spatial differentiation of the suitable areas,employing both factor detection and interaction detection functionalities.Additionally,an overlay analysis with land cover types was conducted to quantify the distribution characteristics of grassland within the potential suitable areas for Lagotis brachystachya Maxim..Results Under the current climatic conditions,dominant environmental drivers included elevation,monthly average temperature difference between day and night,average precipitation in June,wind speed in September,solar radiation in August,average precipitation in May,average precipitation in October,among which elevation demonstrated the strongest explanatory power(q=0.37)in habitat suitability analysis.The model prediction results showed that the potential suitable area for Lagotis brachystachya Maxim.was 5.31×105 km2.Considering the type of surface coverage,the main suitable habitat for Lagotis brachystachya Maxim.was grassland,with an area of 4.34×105 km2.The high suitable grassland of areas were mainly distributed in Qinghai Province(Yushu Tibetan Autonomous Prefecture,Huangnan Tibetan Autonomous Prefecture,Golog Tibetan Autonomous Prefecture,Hainan Tibetan Autonomous Prefecture,Haibei Tibetan Autonomous Prefecture),Sichuan Province(Ganzi Tibetan Autonomous Prefecture,Aba Qiang Autonomous Prefecture),Xizang Autonomous Region(Naqu City,Shigatse City,Changdu City),and Gansu Province(Gannan Tibetan Autonomous Prefecture).Conclusion This study can provide references for the protection of wild resources and the selection of domestication and cultivation areas for Lagotis brachystachya Maxim..

Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P＜0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE)rats.Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control,model,electroacupuncture shallow needling,and dexamethasone groups using the random number table method(n=6 rats per group).A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine,and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters,lung function,and lung morphology compared to the control group.From the sixth day of maternal conception,the control group received cervicodorsal subcutaneous injection with 0.9%sodium chloride solution(1 mg/kg once per day),and the remaining groups were similarly injected with nicotine(1 mg/kg once per day).Concurrent with the nicotine injections,the electroacupuncture shallow needling group received electroacupuncture interventions at the"Zusanli"(ST 36)acupoint on both sides once a day for 20 min.In contrast,the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days),with a later dose of 0.75 mg/kg once per day for 4 days.Following successful model establishment,four offspring per rat were retained in each group using the random number table method.Until the 21st day after the birth of the offspring,using the random number table method,one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight,lung weight,and lung index;simultaneously,one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine,with the parameters of forced vital capacity(FVC),functional residual capacity(FRC),dynamic lung compliance(Cdyn),peak expiratory flow(PEF),peak inspiratory flow(PIF),and airway resistance(RL);concurrently,one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue,alveolar numbers,and mean alveolar septal thickness;additionally,one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE.Results Compared with the control group,the body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,alveolar number,platform crossing times,target quadrant time percentage,and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P<0.01).In contrast,PIF,RL,average thickness of alveolar septa,and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P<0.01).Compared with the model group,both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,and alveolar numbers(P<0.05,P<0.01),along with significant decreases in PIF,RL values,and mean alveolar septal thickness(P<0.01).However,in the Morris water maze experiment,compared with the model group,the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P<0.01),coupled with reduced latency period(P<0.01),whereas the dexamethasone group showed no significant differences compared to the model group.Compared to the electroacupuncture shallow needling group,the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage,coupled with increased latency period(P<0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function.However,offspring receiving late,small-dose,short-course dexamethasone exhibited inferior learning and memory capabilities,whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).