The global prevalence of type 2 diabetes mellitus (T2DM) is rising, significantly increasing the risk of cognitive impairment and dementia. Although exercise improves cognitive function in T2DM, few studies have compared different exercise modalities. This network meta-analysis assessed their effects on global cognitive function in patients with T2DM. This study systematically searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases from their inception to October 10, 2025, and included randomized controlled trials (RCTs) evaluating the effects of exercise interventions on global cognitive function in patients with T2DM. Standardized mean differences (SMDs) and 95

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation of alpha-synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1 alpha, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

Mesenchymal stem cell replacement therapy represents a promising therapeutic strategy for Parkinson's disease (PD), but the key cytokines involved in symptom relief are unknown. This study was designed as a single-arm, open-label exploratory clinical trial (ChiCTR2400086970) and enrolled 35 PD patients with an average age of 67.54 ± 8.29 years, disease duration of 6.97 ± 4.88 years, and an average UPDRS score of 84.57 ± 25.31. Following human umbilical cord mesenchymal stem cell (hUC-MSC) treatment, significant symptom improvement was observed in all patients. Neuromelanin levels in the substantia nigra increased, and cerebrospinal fluid analysis revealed a significant elevation in docosatetraenoyl ethanolamide (DEA) during the symptom remission period. Mechanistic studies based on PD mouse model demonstrated that hUC-MSCs exposed to cerebrospinal fluid up-regulated NCS1 expression, which targeted intermediate selective nerve cells and oligodendrocytes, activated endocannabinoid pathways, promoted DEA synthesis, regulated calcium metabolism, supported glutaminergic nerve cell proliferation, and enhanced NRG signaling between astrocytes and glutaminergic neurons. Our findings suggest that hUC-MSC infusion is safe and is associated with clinically meaningful improvements in PD patients, warranting further confirmation in randomized controlled trials.

OBJECTIVE:To evaluate the effects of virtual reality (VR) and whole-body vibration (WBV) training on muscle strength and balance-related functional outcomes in older adults. METHODS:PubMed, Web of Science, the Cochrane Library, CNKI, and Embase were searched from inception to March 2026. Randomised controlled trials assessing VR or WBV training in samples with a mean participant age of ≥60 years were included. Outcomes were the Timed Up and Go (TUG) test, handgrip strength, Tinetti score, five-times sit-to-stand test, and gait speed. Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Subgroup analyses and Bucher-adjusted indirect comparisons were used to explore potential relative effects. RESULTS:Thirty-two trials involving 1359 participants were included. VR training reduced TUG completion time (MD = -1.13, 95% CI -1.70 to -0.55, p = 0.0001) and improved handgrip strength (MD = 3.49, 95% CI 0.46 to 6.52, p = 0.02), Tinetti scores (MD = 0.84, 95% CI 0.46 to 1.21, p < 0.0001), and gait speed (MD = 0.16, 95% CI 0.07 to 0.24, p = 0.0003). WBV training reduced TUG completion time (MD = -3.92, 95% CI: -6.36 to -1.48, p = 0.002) and five-times sit-to-stand completion time (MD = -1.20, 95% CI -2.03 to -0.38, p = 0.004). CONCLUSIONS:VR and WBV training may improve functional mobility and dynamic balance in older adults, although their effects may vary across functional domains. Because direct head-to-head trials are lacking, comparative findings should be interpreted as exploratory evidence.

BackgroundAlzheimer's disease (AD) is the primary cause of dementia and represents a significant public health concern in aging populations. Existing evidence indicates geographic and sex-related differences in AD prevalence; however, comparability across time periods and diagnostic criteria is limited, and data from lower-resource regions remain scarce. This study synthesized evidence on reported AD prevalence from 1980 to 2024 and examined temporal, geographic, demographic, and methodological variation.MethodsPubMed, Web of Science, and Embase were systematically searched from inception to December 31, 2024, for observational studies reporting AD prevalence in general or community-based populations. Eligible studies reported prevalence estimates with 95% confidence intervals or provided sufficient data for calculation. Studies with sample sizes below 100 and non-original reports were excluded. Two reviewers independently screened studies and extracted data; disagreements were resolved by a third reviewer. Pooled reported prevalence was estimated using a random-effects model. The review was prospectively registered in PROSPERO (CRD420251111597).ResultsFifty-two studies from 19 countries met the inclusion criteria. The pooled reported prevalence of AD was 4.43 per 100 population (95% CI 3.47–5.50). Prevalence was higher among females (4.65 per 100, 95% CI 3.37–6.13) than males (2.30 per 100, 95% CI 1.71–2.97). By survey period, reported prevalence was 3.52 per 100 for 1980–1989, 4.21 for 1990–1999, 4.12 for 2000–2009, and 6.78 for 2010–2024. Adjusted meta-regression did not identify a significant association between survey year and reported prevalence. Estimates also varied by WHO region, Human Development Index (HDI) level, sample size, and study design.ConclusionsReported AD prevalence was substantial and varied by demographic, geographic, and methodological factors. Although prevalence was highest in the most recent survey period, meta-regression did not indicate a consistent global increase over time. Given the extremely high between-study heterogeneity, these findings should be interpreted with caution. More standardized, age-comparable, and geographically representative studies are needed, particularly in underrepresented and lower-resource settings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251111597, identifier CRD420251111597.

BackgroundType 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI) are prevalent conditions in the aging population, with growing evidence indicating a synergistic detrimental effect on brain function when comorbid. However, the distinct neurofunctional signatures of comorbid T2DM-MCI remain poorly characterized.ObjectiveThis study aimed to investigate the characteristic brain activation patterns and functional network connectivity in elderly patients with comorbid T2DM-MCI, compared to those with T2DM alone or MCI alone.MethodsIn this cross-sectional study,75 elderly participants (T2DM = 25, MCI = 25, T2DM-MCI = 25) underwent functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, a 2-back task, single walking, and a dual-task (2-back while walking), followed by 8-min resting-state recording. Task-evoked cortical activation and resting-state functional connectivity were analyzed and compared across groups.ResultsDuring cognitive tasks, the T2DM-MCI group showed significantly reduced activation in prefrontal and motor cortices compared to single-disease groups. Dual-task performance specifically revealed hypoactivation in ventrolateral prefrontal and occipital regions in T2DM-MCI. Resting-state analysis demonstrated globally diminished functional connectivity in T2DM-MCI, particularly within prefrontal-motor networks and interhemispheric connections, whereas no significant differences were found between T2DM and MCI groups alone.ConclusionsComorbid T2DM-MCI exhibits a unique dual-pathology profile characterized by concurrent reductions in task-evoked activation and resting-state network connectivity, suggesting compromised neural efficiency from synergistic metabolic and neurodegenerative processes. These impairments may serve as sensitive biomarkers for early detection of diabetes-associated cognitive decline.Trial registration: The Chinese Clinical Trial Registry (ChiCTR) registration # ChiCTR2400084469 (https://www.chictr.org.cn).

The Notch signaling pathway is a highly conserved cell-cell communication system that plays central roles in stem-cell maintenance, tissue homeostasis, cell-fate determination, and metabolic regulation. Because exercise induces coordinated adaptations across the nervous, muscular, cardiovascular, and metabolic systems, Notch signaling has emerged as a potential mediator of exercise-associated plasticity. However, whether exercise directly activates or suppresses Notch signaling in a causal, tissue-specific, and intensity-dependent manner remains unresolved. In this narrative review, we synthesize evidence on canonical and non-canonical Notch signaling, its functions in neural and metabolic regulation, and its potential intersections with exercise-related neurogenesis, muscle remodeling, redox balance, and metabolite signaling. We contend that the current evidence is best understood within a context-dependent framework rather than through a universal model of exercise-induced Notch activation. In particular, categories such as "moderate" and "high-intensity" exercise should be interpreted as individualized physiological domains defined relative to markers including lactate and ventilatory thresholds, cardiorespiratory reserve, and baseline fitness. We further propose that exercise-derived metabolites, including lactate, ketone bodies, and shifts in cellular NAD+/AMP status, may modulate Notch-related signaling indirectly or in a cell-type-specific manner; however, these interactions should currently be regarded as hypothesis-generating rather than established linear pathways. Across tissues, the strongest mechanistic evidence pertains to Notch biology in neural stem cells, synaptic plasticity-associated signaling, and skeletal-muscle stem-cell regulation, whereas direct human exercise studies assessing Notch pathway activation remain scarce. We therefore propose a context-dependent working model in which Notch acts as a potential integrator of exercise-responsive neural and metabolic cues, while also emphasizing major limitations, conflicting findings, and the safety concerns associated with systemic pharmacological modulation of this pathway. Overall, this perspective positions Notch signaling as a plausible, though not yet universally validated, component of exercise-associated adaptation and a priority target for future mechanistic investigation.

Parkinson’s disease (PD) is characterized by progressive degeneration of the nigrostriatal dopaminergic system and α-synuclein (α-syn) pathology, with disease progression driven by convergent mechanisms including neuroinflammation, mitochondrial injury, oxidative stress, and regulated cell-death programs such as ferroptosis. Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) constitute a key signaling system in the central nervous system, influencing not only neuronal survival and glial states but also intersecting with networks governing redox homeostasis and iron metabolism. Accumulating evidence indicates that, beyond classical neurotrophic actions, FGF–FGFR signaling can modulate mitochondrial quality control, glial inflammatory activation, and lipid peroxidation-related processes, thereby reshaping cellular susceptibility to ferroptotic injury. This review summarizes current advances in understanding FGF signaling networks in Parkinson’s disease, synthesizes their potential mechanistic links to the interplay among neuroinflammation, mitochondrial dysfunction, and redox imbalance as well as to ferroptosis regulation, and discusses the experimental basis and translational challenges of targeting the FGF pathway as a disease-modifying therapeutic strategy.

Background:Falls are a major concern in geriatric health, and impairments in executive function (EF), gait, and postural control are important fall-related risk factors. Interactive motor-cognitive training (IMCT) has shown promise as an intervention to mitigate these risks. This study aims to assess the acute effects of IMCT programs with three levels of cognitive load (high, medium, and low) on EF, spatio-temporal gait parameters, and postural control in middle-aged and older adults. Methods:In this single-blind, parallel-group randomized controlled trial, 42 participants (58.1 ± 9.9 years) were randomly allocated to a low cognitive load group (LCG), medium cognitive load group (MCG), or high cognitive load group (HCG). Each group completed a 30-min IMCT session using the SpeedCourt system. EF, postural control, and single/dual-task gait performance were assessed before and after the intervention. Results:Multivariate analysis showed significant between-group differences in EF (Pillai V = 0.804, p = 0.015, ηp 2  = 0.402) and gait performance (Pillai V = 1.201, p < 0.001, ηp 2  = 0.601); no significant changes were observed in postural control (Pillai V = 0.543, p = 0.323, ηp 2  = 0.271). The MCG showed greater improvement in Stroop neutral reaction time than the LCG and HCG, while 2-back accuracy improved relatively more in the LCG. The MCG also showed greater improvement in dual-task gait velocity, whereas the LCG showed a greater increase in correct responses during dual-task walking. Discriminant function analysis identified Stroop neutral reaction time, 2-back accuracy, gait velocity, and correct responses as the most sensitive variables. Conclusion:A single session of IMCT with different cognitive loads was associated with immediate changes in selected EF and dual-task gait outcomes in middle-aged and older adults. Moderate cognitive load appeared most favorable for processing-speed-related Stroop performance and dual-task gait velocity, whereas low cognitive load was associated with greater gains in dual-task correct responses.

Objectives: The pathological progression of Parkinson’s disease (PD) involves alterations across multiple neural cell types, and glial–neuronal communication substantially influences neuronal function. Oligodendrocytes (OLs) have been implicated in PD pathology, but the underlying regulatory mechanisms remain incompletely understood. Methods: In this study, single-nucleus RNA sequencing and spatial transcriptomics were used to characterize OL-associated changes and explore potentially relevant mechanisms in the substantia nigra pars compacta (SNpc) of MPTP-induced parkinsonian mice. Molecular validation was subsequently performed in an exercise intervention cohort. Results: These analyses revealed a significant reduction in OL abundance in the SNpc, accompanied by enrichment of ferroptosis-related pathways. Aerobic exercise partially restored the expression of the OL marker gene Plp1 and the antioxidant pathway-related molecules Nrf2 and Gpx4, while reducing ferroptosis-related oxidative stress. These changes were associated with improvements in PD-like pathological phenotypes. Exploratory untargeted metabolomics further identified candidate alterations in metabolites and pathways related to redox homeostasis, energy metabolism, and myelin-associated processes after MPTP treatment and exercise intervention. Conclusions: Collectively, exercise-associated improvements in MPTP-induced PD-like phenotypes coincided with reductions in OL/myelin-related injury and ferroptosis-related stress. These findings suggest that OL-associated ferroptosis-related stress may represent one of several processes contributing to neuronal injury in PD and may be responsive to aerobic exercise. This study provides a theoretical basis for further investigation of exercise-based rehabilitation strategies and potential therapeutic targets for PD.

To evaluate whether baseline habitual physical activity (PA), modeled as continuous moderate-to-vigorous PA (MVPA), is associated with acute glycemic responses to different exercise modalities, and whether acute response is associated with 12-week glycemic status in older adults with type 2 diabetes. A total of 23 participants completed the acute crossover phase of the study, while the final longitudinal analysis for the 12-week intervention included 22 participants due to incomplete data from one individual. Continuous glucose monitoring quantified time in range (TIR, 3.9–10.0 mmol/L). Acute responses were analyzed using linear mixed models including modality, baseline MVPA, and modality × MVPA interaction terms, adjusted for age and sex. Associations between acute 24-h TIR after the mixed session and 12-week mean TIR were tested using Pearson correlation and HbA1c-adjusted partial correlation; stability was evaluated with leave-one-out cross-validation (LOOCV). Adherence interaction analyses were exploratory. Evidence for effect modification by baseline MVPA in the acute phase was limited (Mixed × MVPA: β = -0.263, 95

Exosomes derived from various cellular sources play a pivotal role in mediating and regulating bone and cartilage regeneration for conditions such as bone defects, fractures, cartilage repair, osteoporosis, and osteoarthritis. As essential intercellular communication vehicles, exosomes transmit long non-coding RNAs (lncRNAs) to modulate cellular behaviors in the bone microenvironment, which has been a central focus of contemporary research.This review consolidates existing evidence on exosome-derived lncRNAs in bone remodeling, revealing their regulatory roles through signaling pathway networks on osteoclasts, osteoblasts, and related bone/cartilage lineage cells, including mesenchymal stem cells, chondrocytes, and osteoclasts. Exosome-encapsulated lncRNAs that regulate osteogenic differentiation of bone marrow mesenchymal stem cells, osteoclast activity, bone-vascular coupling, and bone metastasis show promise as minimally invasive biomarkers for diagnosis, risk stratification, and therapeutic monitoring of bone metabolic disorders. Moreover, harnessing exosomes as natural, engineerable delivery vehicles can advance the development of bone-targeted, precise, and low-toxicity therapeutic strategies to complement existing pharmacologic and regenerative treatments.

Open reusable biomechanical datasets from generally healthy children and adolescents remain limited, particularly for studies requiring full-body three-dimensional motion capture with synchronized ground reaction force data. Here we describe a laboratory dataset from 43 participants aged 13–18 years, containing more than 4,600 C3D motion-capture records and corresponding force-platform files across locomotor, obstacle-crossing, jumping, functional-screening, sit-to-stand, active range-of-motion, and simulated abnormal-gait tasks. The simulated abnormal-gait trials comprise genu-varum and stroke-like compensation conditions performed by healthy participants, rather than recordings of patients with gait pathology. These simulations have not been clinically validated and should not be used for pathological normative modeling or as diagnostic reference data; instead, they are intended as controlled movement-variation conditions for methodological development and benchmarking. Trial-level metadata, task-standardization tables, marker-label documentation, quality-control reports, manuscript tables, and reproducibility scripts accompany the dataset. The release is intended to support pediatric and adolescent movement research, sports biomechanics, clinical screening method development, musculoskeletal modeling, ground reaction force estimation, and machine-learning benchmarks, with key limitations for reuse documented in the Technical Validation and Usage Notes sections.

Bone remodeling imbalance represents the fundamental pathological basis of osteoporosis. Exercise is broadly regarded as a valuable non-pharmacological strategy for preventing and managing osteoporosis; however, the precise molecular mechanisms through which exercise modulates bone metabolism remain incompletely understood. Mitophagy has recently been recognized as an important mediator linking exercise to the regulation of bone remodeling. This review centers on the "exercise-mitophagy-bone remodeling" axis, systematically outlining the biological processes and regulatory determinants of mitophagy within the bone microenvironment. Evidence suggests that mitophagy facilitates bone formation by preserving mitochondrial quality, attenuating oxidative stress, and optimizing cellular energy metabolism. Moreover, it exerts stage-specific inhibitory effects on bone resorption during osteoclast differentiation. Particular emphasis is placed on the mechanisms by which exercise activates mitophagy-related signaling pathways via metabolic, mechanical, and hypoxic stimuli. In addition, exercise may enhance the efficiency of this regulatory axis by maintaining vitamin D and calcium homeostasis and modulating estrogen signaling pathways. The differential effects of exercise modalities and durations on these processes are also critically evaluated. Finally, this review addresses current limitations in existing research and highlights future directions, including the optimization of exercise interventions targeting mitophagy and the integration of multi-omics approaches. These findings offer a theoretical basis for designing precise exercise regimens and combined therapeutic approaches in the management of osteoporosis.

OBJECTIVES:To comparatively evaluate the effects of different exercise and cognitive interventions on fall prevention in older adults and to provide evidence-based guidance for clinical practice. STUDY DESIGN:Bayesian network meta-analysis. METHODS:This study systematically searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database up to December 27, 2025, to identify randomized controlled trials (RCTs) on exercise and cognitive interventions for fall prevention in older adults. Data analyses were conducted using R 4.4.3 and Stata 16.0, with intervention effects expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The surface under the cumulative ranking curve (SUCRA) was used to rank the relative effectiveness of interventions. RESULTS:A total of 47 randomized controlled trials involving 12,384 participants were included. Compared with usual care, exercise combined with cognitive training (ECT; 8 trials, n = 872, OR = 0.42, 95% CI: 0.24-0.67), cognitive training (CT; 5 trials, n = 549, OR = 0.50, 95% CI: 0.24-0.97), mind-body exercise (MBE; 27 trials, n = 3,078, OR = 0.61, 95% CI: 0.43-0.87), and multimodal exercise (ME; 15 trials, n = 2,280, OR = 0.66, 95% CI: 0.51-0.85) all demonstrated significant fall prevention effects in older adults. SUCRA rankings indicated that ECT had the highest probability of being the most effective intervention (88.5%), followed by MBE (76.6%), CT (69.8%), and ME (61.2%). CONCLUSION:This Bayesian network meta-analysis suggests that ECT may be the most effective intervention, with MBE, CT, and ME also showing benefits. The SUCRA rankings reflect probabilistic ordering rather than absolute effect sizes, and therefore should be interpreted with caution. Clinical interventions should be tailored to individual characteristics and functional needs.

Background and Objective:Tumor therapy is still a tough clinical challenge, and cancer immunotherapy has drawn increasing attention. T cells and natural killer (NK) cells play crucial roles in the immune response. Induced pluripotent stem cell (iPSC) technology opens up a new way to produce functionally improved universal iPSC-derived chimeric antigen receptor (CAR) T (CAR-iT) and iPSC-derived CAR-NK (CAR-iNK) cells. This study aims to comprehensively review the generation and clinical applications of iPSC-derived universal CAR-iT and CAR-iNK cells to explore their potential and future directions in cancer immunotherapy. Methods:We searched EBSCO, PubMed, and Web of Science databases for relevant literature from 1975 to 2024 on the transformation of iPSCs into universal immune cells. Key Content and Findings:iPSC technology enables the generation of enhanced CAR-iNK cells. Genetic modifications can boost the antitumor activity of iPSC-derived immune cells. CAR-iT cells have cytotoxicity issues. In contrast, CAR-iNK cells have advantages as they can be sourced from different origins and enhanced via genetic engineering. Conclusions:This review outlines iPSC technology's application in oncology, iNK cells' properties, and the pros and cons of CAR cells in cancer treatment. It also focuses on the current clinical status and modification strategies of CAR-iT and CAR-iNK therapies, facilitating the development of future effective off-the-shelf blood cell therapies.

Objective This meta-analysis aimed to explore the effects of multi-component exercise interventions on glycemic and lipid metabolism, physical fitness, and cognitive function in individuals with type 2 diabetes mellitus (T2DM). Methods From inception to December 28, 2024, PubMed, Web of Science, Cochrane, and Elsevier databases were systematically searched for randomized controlled trials (RCTs) investigating multi-component exercise interventions for T2DM. A total of 37 articles, comprising 3,201 participants, were included. Primary and secondary outcome measures were categorized, summarized, and analyzed using RevMan 5.4 software. Results Compared to control groups, multi-component exercise interventions produced statistically significant improvements across all measured outcomes in individuals with T2DM: (1) Glycemic control: HbA1c (standard mean difference (SMD) = −0.52, 95% confidence interval (CI) [−0.76 to −0.28]); fasting blood glucose (SMD = −0.53, 95% CI [−0.93 to −0.12]). (2) Lipid metabolism: high density lipoprotein (HDL) (SMD = 0.32, 95% CI [0.21–0.44]); low density lipoprotein (LDL) (SMD = −0.21, 95% CI [−0.33 to −0.09]); triglycerides (SMD = −0.18, 95% CI [−0.30 to −0.06]). (3) Physical fitness: upper limb strength (SMD = 0.67, 95% CI [0.51–0.83]); lower limb strength (SMD = 0.56, 95% CI [0.10–1.02]); peak oxygen consumption (SMD = 0.62, 95% CI [0.31–0.93]); body mass index (BMI) (SMD = −0.38, 95% CI [−0.67 to −0.09]). (4) Cognitive function: overall cognitive performance (SMD = 0.34, 95% CI [0.18–0.50]). (5) Quality of life: vitality (SMD = 0.37, 95% CI [0.09–0.64]); physical functioning (SMD = 0.48, 95% CI [0.20–0.75]); mental health (SMD = 0.35, 95% CI [0.07–0.63]); general health (SMD = 0.34, 95% CI [0.06–0.61]). Quality assessment indicated that the included studies were of high overall quality. Egger’s regression analysis did not reveal significant publication bias. Conclusions Multi-component exercise interventions significantly improved glycemic and lipid metabolism, physical fitness, and cognitive function in individuals with T2DM. These findings support the clinical value of incorporating multi-component exercise programs—particularly those performed at least three times per week and lasting 6 months or longer—into diabetes management strategies.

Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, presents significant heterogeneity in clinical manifestations, genetic background, and response to interventions. While conventional exercise therapies demonstrate benefits in alleviating motor and non-motor symptoms through mechanisms such as modulating alpha-synuclein aggregation, enhancing mitophagy, and reducing neuroinflammation, their efficacy varies considerably among individuals. This variability may stem from endogenous factors such as genetic background, clinical phenotypes, stages of pathological progression, as well as exogenous factors like the type, intensity, and frequency of movement. Thus, this review first discusses the necessity of precise exercise interventions for PD patients, focusing on the epidemiological burden, heterogeneity in disease mechanisms, and differences in intervention response (Why). Next, we systematically explain how to develop precise exercise intervention strategies by stratifying interventions based on genetic background, clinical phenotype, and disease stage, combined with technological aids (How). Genetically, mutations in genes such as GBA], PRKN, PINK], and SNCA dictate distinct molecular pathologies-including lysosomal dysfunction, impaired mitophagy, and alpha-synuclein aggregation-which necessitate tailored exercise regimens. For instance, patients with PRKN/PINK] mutations may benefit from moderate-intensity endurance training to support mitochondrial biogenesis without exacerbating oxidative stress, whereas carriers of GBA] mutations might require exercises focusing on enhancing lysosomal function and managing oxidative damage. Clinically, patients are stratified into tremor-dominant (TD) and postural instability/gait difficulty (PIGD) subtypes, which demand divergent exercise priorities: coordinative, rhythm-based activities like dance or Tai Chi for TD-PD to engage cerebellar circuits, versus targeted balance and strength training, potentially aided by virtual reality, for PIGD-PD to mitigate axial symptoms and fall risk. Furthermore, intervention strategies must evolve with disease progression: high-intensity exercise is prioritized in early stages to leverage neuroplasticity and potential disease modification, while mid-and late-stage management focuses on functional maintenance, fall prevention, and compensatory strategies, respectively. Critical to implementing this framework is the adoption of digital biomarkers via wearable technology (e.g., inertial sensors, smartwatches), which enables continuous, objective monitoring of gait, tremor, and physiological responses. This facilitates a closed-loop feedback system, allowing for the remote adjustment of exercise parameters (intensity, frequency, duration) in real-time, thus optimizing efficacy and ensuring safety. Finally, we detail how to configure exercise parameters through personalized adaptation (What), including exercise type, intensity, frequency and dose. Higher volumes of physical activity are associated with reduced PD risk and slower progression, though optimal thresholds remain incompletely defined. Aerobic exercise improves cardiovascular fitness and may aid clearance of pathogenic proteins; resistance training counters sarcopenia and bradykinesia; balance training reduces falls; and mind-body exercises (e. g., Tai Chi) integrate motor and cognitive components. Multimodal regimens are often most beneficial. High-intensity aerobic exercise appears particularly effective in early PD, enhancing neural connectivity and mitigating disease progression in randomized trials. Most evidence supports supervised sessions occurring 3-5 times per week, lasting 30-60 min, adapted to individual tolerance and disease stage. In conclusion, this narrative review outlines a comprehensive precision medicine framework for exercise intervention in PD, moving beyond symptomatic management towards targeting underlying pathophysiology. By stratifying patients based on genetic, phenotypic, and staging characteristics, and by leveraging digital technology for dynamic personalization, exercise therapy can be transformed into a more potent, individualized, and disease-modifying strategy. Future research must validate these biomarker-driven approaches in large-scale trials and establish definitive guidelines for translating precision exercise into clinical practice.

Clostridioides difficile has rapidly become a major cause of nosocomial infectious diarrhea worldwide due to the misuse of antibiotics. Our previous study confirmed that RT046/ST35 strain is associated with more severe clinical symptoms compared to RT012/ST54 strain. We conducted genome comparison of the RT046/ST35 and RT012/ST54 strains using whole-genome sequencing technology. The RT046/ST35 strain had a genome length of 7,869,254 bp with a GC content of 29.49

Obesity alters the adipose tissue (AT) immune microenvironment (TIME) and induces inflammation. Nevertheless, the specific time when TIME dysfunction emerges in AT remains elusive. Obesity mouse models were constructed and categorized into Lean (Ctrl), moderately obese (Mid_Ob, with body weight exceeding Ctrl by > 10%), and Obese (Ob, with body weight exceeding Ctrl by > 20%) groups. Single-nucleus RNA sequencing (snRNA-seq) and immunofluorescence localization were employed to analyze changes in cell populations, cluster marker genes, and signaling pathways in mouse epididymal white adipose tissue (eWAT). A total of 23,068 cells obtained from three mouse eWAT samples (Ctrl, Mid_Ob, and Ob) underwent snRNA-seq. Eighteen distinct clusters were identified, and seven cell types were annotated with representative markers. In-depth analysis unveiled the functions of the adipose AT-associated Krt23+fibroblast (ATAKF) cell subtype and refined the crosstalk hypothesis concerning ATAKFs, macrophages, and neutrophils. We further demonstrated that ATAKFs were present in the Mid_Ob group. Additionally, from the Mid_Ob to Ob stage, AT inflammatory factors, macrophages, and neutrophils significantly increased while neurons markedly decreased; however, these factors did not change significantly from the Ctrl to Mid_Ob stage. Cell-cell communication analysis revealed the central role of ATAKFs and their regulation of macrophages and neutrophils. Only when obesity reaches the Mid_Ob stage AT fibroblasts specifically express Krt23+, recruit neutrophils, and secrete CCL2, CCL6, and CCL9 to attract macrophages, thereby altering the eWAT TIME. ATAKFs contribute to immune microenvironment disorders during the development of mouse AT obesity. This study offers valuable resources and a foundation for understanding the timing of TIME dysfunction.