The frequency of online psychotherapy, including pure online (PO: videoconference [PO-VC], telephone [PO-TEL], asynchronous therapist-guided [PO-Async]), or blended (BLD) modalities, has grown exponentially, yet how the therapeutic alliance (TA), a key outcome predictor, compares across these formats and face-to-face (FTF) treatment remains unclear. To compare the TA strength and the TA–outcome association across FTF, PO, and BLD modalities, a systematic narrative review (Preferred Reporting Items for Systematic Reviews and Meta-Analyses/Synthesis Without Meta-analysis [PRISMA/SWiM]) was performed by searching PubMed, PsycARTICLES, and Web of Science. Studies were deemed eligible if they quantitatively compared TA across at least two modalities in adults with depressive or anxiety disorders. PO arms were classified as telepsychotherapy (PO-VC/TEL) or therapist-guided digital interventions (PO-Async). The findings were synthesized by direction and consistency. Nine studies, including three primary randomized controlled trials (RCTs) and six secondary analyses, were finally included in this study. TA strength was broadly comparable across all three modalities. One study found significantly lower patient-rated working alliance inventory (WAI) scores at Week 2 in PO-Async versus FTF, resolving by Week 8. The TA–outcome association was mixed, varying by modality, rater perspective, and timepoint. The results showed that TA was broadly equivalent across FTF, PO, and BLD formats, although asynchronous PO might show a transient week-2 lag. The TA–outcome association was less consistent in PO/BLD than in FTF. As a preliminary hypothesis, digital delivery may shift the functional emphasis of the alliance from affective bonding toward task/goal engagement.
Murine double minute 2 (MDM2) and murine double minute 4 (MDMX) are critical for the regulation of tumor protein 53 (p53) function and apoptosis. This study compares the Mdm2/x gene sequences and functional variations of subterranean zokors from the High Plateau and the Loess Plateau. The findings reveal the molecular mechanisms by which Mdm2/x variations drive adaptation to extremely high-altitude conditions—including low oxygen, cold temperatures, and perpetual darkness in underground environments. We cloned and analyzed Mdm2/x sequences from two distinct ecological groups of subterranean rodents, Myospalax baileyi (plateau zokor) and Myospalax cansus (Gansu zokor), and reconstructed phylogenetic trees for a series of subterranean rodents and mammals, as well as the aboveground laboratory rat and humans. We found that MDM2/X in M. baileyi and M. cansus are involved in the p53-dependent low apoptosis rate, and the variations of phosphorylation sites at the C-terminus of MDM2 contribute to upregulation of p53 transcription and protein expression. We propose that gene evolutionary mechanisms enable survival under these severe combined pressures, and believe that our findings provide critical insight into how genetic modifications drive physiological resilience in Earth’s most challenging ecosystems.
Non-pharmacological pain management approaches, including acupoint hot compress, may provide valuable support for women dealing with pain during the latent stage of labor, but the evidence supporting this effect is limited. We investigated whether acupoint hot compress reduced labor pain among primiparous parturients with planned vaginal delivery. We conducted a randomized controlled trial (RCT) at nine obstetric centers across China. Primiparous women aged 20–34 years, at 37–41 weeks’ gestation with singletons and with planned vaginal delivery, were randomly assigned (1:1) to receive standard obstetrical care with acupoint hot-compress therapy or standard obstetrical care alone. The acupoint hotcompress therapy, involving the medial malleolar, plantar, and lumbosacral regions, was provided for parturients in the latent phase of the first stage of labor at (42±2) °C for 4 h, starting 1 h after the onset of regular uterine contractions. The primary outcome measured was labor pain at 3 and 5 h after the onset of regular uterine contractions, with labor pain at 1 h used as the baseline. Pain intensity was assessed using the visual analog scale (VAS) and expressed as no pain (0), mild pain (range 1–3), moderate pain (range 4–6), or severe pain (range 7–10). The secondary outcomes were the durations of the first, second, and third stages of labor, maternal blood loss quantified at 0 and 2 h postpartum, and depression symptoms identified using the Edinburgh postnatal depression scale (EPDS) within 48 h postpartum, as well as newborn Apgar scores. All statistical analyses were based on the modified intention-to-treat (ITT) population. Between April 2024 and May 2025, 580 women were randomly assigned to the acupoint hot-compress intervention group and the standard-care control group. Of the 564 women included in the modified ITT population, baseline characteristics were comparable between the two groups, with the exception of baseline labor pain. Compared with parturients in the control group, those in the intervention group who underwent acupoint hot compress from the latent phase of the first stage had reduced labor-pain intensity (3 h: odds ratio [OR]=0.46, 95
Arsenic exposure is known to cause cognitive deficits, although the underlying mechanisms are yet to be explored. In this study, we investigated the role of nerve growth factor (NGF), a neuroprotective factor, in arsenic-induced cognitive impairment. In mouse models exposed to 25 and 50 mg/L sodium arsenite (NaAsO2), we observed neuronal damage accompanied by the downregulation of NGF, decreased phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), reduced phosphorylation of the mitochondrial fission protein dynamin-related protein 1 (Drp1), and downregulation of the mitochondrial fusion protein optic atrophy 1 (OPA1). Similarly, the downregulation of NGF, inactivation of the PI3K/AKT signaling pathway, mitochondrial dynamics imbalance (dysregulation of mitochondrial fission and fusion processes), and increased apoptosis were observed in HT-22 cells exposed to 4 µmol/L NaAsO2. NGF overexpression mitigated these arsenic-induced alterations, while the protective effect of NGF against arsenic toxicity was reduced by LY294002, a PI3K/AKT pathway inhibitor. These findings suggest that a decrease in NGF mediates the arsenic-disrupted mitochondrial dynamics via inhibiting the PI3K/AKT pathway, ultimately impairing cognitive function.
血管免疫母细胞性 T 细胞淋巴瘤 (AITL) 常携带 TET2、 DNMT3A、 IDH2等表观调控基因突变, 此类突变在克隆性造血 (CH) 和髓系肿瘤中同样高频存在, 提示淋巴、 髓系恶性肿瘤可能具备共同细胞起源。 既往 AITL 合并骨髓增生异常肿瘤 (MDS) 和急性髓系白血病 (AML) 病例大多为异时发病, 二者克隆同源的直接分子证据较为匮乏。 本文报道 1 例同步确诊 AITL 伴原始细胞增多的骨髓增生异常肿瘤-2 (MDS-IB2) 的87岁男性患者。 患者以全身瘙痒红斑皮损和全血细胞减少为首发表现, 皮肤活检确诊 AITL, 骨髓穿刺结合流式细胞学确诊 MDS-IB2, PET-CT 提示全身骨髓和淋巴结同步出现肿瘤浸润。 对皮肤淋巴瘤组织与配对骨髓样本进行靶向二代测序, 两份标本均检出 IDH2 p.R140Q 和 ASXL1 p.R1415X 共有致病突变; 淋巴病灶独有 TP53、 CIITA、 NOTCH1 突变, 骨髓髓系病灶特有 SRSF2、 STAG2、 BCOR 突变。 分子检测证实两类肿瘤起源于携带早期克隆造血突变的同一造血干祖细胞, 后续各自获得谱系特异性突变, 发生分支克隆演化。 本文汇总既往相关病例, 多数患者在 AITL 发病数月至数年后继发髓系肿瘤, 部分病例经分子检测证实两类肿瘤共享克隆造血相关突变。 本例同步发病病例, 为 AITL 与髓系肿瘤存在共同克隆起源提供了关键直接分子证据。
Pseudorabies virus (PRV), known as porcine herpesvirus type I, belongs to the α-herpesvirus subfamily of the herpesviridae family. Its virions are oval or round, with a genome of approximately 143 000 bp and a high guanine-cytosine (GC) content of 73% (Pomeranz et al., 2005). While swine are the natural host and the virus has caused significant economic loss to the pig industry, PRV can infect other mammals, causing acute infectious diseases characterized by neurological symptoms (He et al., 2019; Cheng et al., 2020). Young pigs are more susceptible to PRV and the infection in piglets is nearly 100% fatal, whereas adult pigs exhibit reproductive disorders such as abortion, stillbirths, and reduced fertility, ultimately decreasing farm productivity (Zuckermann, 2000). Due to its global impact, PRV is classified as a Class B infectious disease by the World Organization for Animal Health (WOAH).
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and continues to present significant challenges in early diagnosis, precise subtyping, and prognosis assessment. In recent years, the field of biomarker research has undergone a profound paradigm shift from static concentration measurements to functional activity detection. The most revolutionary breakthrough is the α-synuclein seed amplification assay (α-Syn-SAA), which enables ultrasensitive and specific detection of pathological α-Syn in both clinical and prodromal stages, thus providing an unprecedented window for early intervention. Substantial progress has also been made in the development of biomarkers such as neurofilament light chain (NfL), Alzheimer's disease-related biomarkers, and genetic biomarkers, as well as in detection technologies based on peripheral samples. The integrated application of cutting-edge technologies, such as real-time quaking-induced conversion (RT-QuIC), high-resolution mass spectrometry, and high-field magnetic resonance imaging (MRI), is advancing the field into a new stage characterized by a focus on pathological activity, multi-omics integration, and non- or minimally invasive approaches. In this review, we explore recent advances in PD biomarkers, focusing on core pathophysiological markers. We examine the potential of multi-omics and artificial intelligence (AI) to enhance diagnostic, subtyping, and prognostic accuracy, while also outlining the pivotal role and future directions of biomarkers in advancing precision medicine for PD.
The blood–brain barrier (BBB) is a vital physiological structure that maintains the microenvironmental homeostasis in the central nervous system (CNS). Imbalances in its permeability play a key role in various neurological disorders, including stroke, neurodegenerative diseases, and brain tumors. The development of precise techniques for assessing BBB permeability is therefore paramount for elucidating the mechanisms of neurological diseases, overcoming drug development challenges, and achieving precise diagnosis and treatment of CNS disorders. This review systematically summarizes the latest advances in the assessment of BBB permeability. Regarding in vitro models, platforms have evolved from the traditional transwell system to microfluidic chips incorporating fluid shear forces and subsequently to highly biomimetic brain organoids, with continuous improvements in the ability to simulate the neurovascular unit (NVU) microenvironment. For in vivo assessment, we detail the principles and applications of imaging techniques, including dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), positron emission tomography (PET), near-infrared II (NIR-II) fluorescence imaging (FI), and two-photon microscopy (TPM), highlighting their complementary strengths in macroscopic quantification, molecular targeting, and microscopic dynamic observation. The integration of multi-modal technologies and precise quantitative assessment is a prominent trend. Future investigations will focus on artificial intelligence (AI)-driven personalized permeability assessment, the development of novel intelligent probes, and the dynamic real-time monitoring of the BBB, thereby providing powerful methodological support for neurological disease research.
OBJECTIVES:Cystine stones account for 1%‒2% of adult and up to 10% of pediatric kidney stones. They result from cystinuria, an autosomal recessive disorder caused by mutations in solute carrier family 3 member 1 (SLC3A1) and SLC7A9, which encode the renal cystine transporter subunits. These mutations impair cystine reabsorption, raising urinary cystine levels and driving stone formation. Current diagnostic options remain limited in terms of detecting molecular dysfunctions. Thus, we aimed to develop a nonradioactive, cell-based method for the functional assessment of cystine transporters and mutation-specific pathologies. METHODS:Using human embryonic kidney 293 (HEK293) cells transiently co-expressing wild-type or mutant SLC3A1 and SLC7A9, we developed an integrated approach that combined a selenocystine-based fluorescence uptake assay with AlphaFold3-based structural predictions to rapidly and accurately assess cystine transporter function and the molecular impact of genetic mutations. RESULTS:The affinity of the SLC3A1/SLC7A9 complex was comparably apparent for selenocystine (Michaelis constant Km=(156.3±24.2) μmol/L) and cystine (literature Km approximately 200 μmol/L). Using operational thresholds (mild >60%, moderate 20%‒60%, severe <20% residual activity), the assay differentiated the functional impacts of eight clinically characterized variants, including SLC7A9 A70V, A182T, G105R, R333W, V170M, A354T, and P482L, and SLC3A1 M467T, with categorical assignments consistent with previously published radioisotope-based functional data. AlphaFold3 modeling, combined with molecular docking, provides mechanistic interpretations of the dysfunction observed in the P482L and A354T mutants. CONCLUSIONS:The integrated approach employed in this work, which combines a sensitive selenocystine fluorescence assay with artificial intelligence (AI)-powered structural analysis, enables the rapid, precise diagnosis of cystinuria variants. This platform is compatible with standard microplate-reader infrastructure and offers potential utility in variant-interpretation pipelines and future genotype-guided therapeutic decision-making, pending prospective clinical validation.
Circular RNAs (circRNAs) are key post-transcriptional regulators with critical roles in pathogenesis, yet existing tools for their precise manipulation and functional analysis in living cells remain to be developed. A compelling therapeutic target in this field is the circRNA cerebellar degeneration-related protein 1 antisense (CDR1as), functioning as an oncogenic sponge for microRNA-7 (miR-7). Herein, we report a novel multifunctional zeolitic imidazolate framework-8 (ZIF-8)-based nanoplatform for the simultaneous disruption and real-time monitoring of the CDR1as/miR-7 regulatory axis. This system, named DZ/MB@ZIF-8, co-encapsulates a designed set of DNAzymes (DZs) for the catalytic cleavage of CDR1as as well as a molecular beacon (MB) for reporting on miR-7 activity. Following cellular uptake and lysosomal trafficking, the acidic microenvironment triggers nanoplatform disassembly, concurrently releasing the therapeutic and sensing components along with essential Zn2+ cofactors for DZ activation. This system demonstrates efficient CDR1as degradation, which liberates miR-7 and inhibits the expression of its downstream oncogenic targets. Crucially, this therapeutic effect is directly correlated with a turn-on fluorescent signal from the MB, enabling the real-time, live-cell readout of circRNA regulation. This work establishes a versatile theranostic strategy that merges targeted gene regulation with intrinsic biosensing, offering a powerful platform for probing circRNA function and advancing RNA-based therapeutics.
Point-of-care testing (POCT) is changing the way diagnostic information is generated, interpreted, and used. Its value extends well beyond shortening turnaround time. A meaningful POCT result should support a defined clinical or public-health action, such as early triage, treatment selection, disease surveillance, referral, or longitudinal follow-up. In this sense, POCT is best understood as a distributed extension of laboratory medicine rather than a simplified replacement for the central laboratory (Banfi et al., 2024; Plebani et al., 2025).
Programmable RNA-cleaving DNAzymes (RCDs) represent a unique class of catalytic nucleic acids that couple molecular recognition with enzyme-like activity. While DNAzymes have traditionally been explored for targeted gene regulation, recent advances in nanotechnology have repositioned them as programmable biosensing modules with stimuli-responsive therapeutic potential. When integrated into metal-oxide scaffolds, DNA-framework architectures, or metal-organic frameworks, DNAzymes form hybrid platforms that create confined catalytic microenvironments, provide enriched cofactor availability, and facilitate microenvironment-responsive activation. These engineered systems can function as nanoscale biosensing modules that respond to pH, redox gradients, metal ions, or microRNA signatures and convert these biological cues into catalytic outputs. Beyond enhancing analytical performance, such platforms may also reshape tumor immunometabolism. Through the selective cleavage of metabolic or immune-regulatory transcripts, DNAzyme nanocatalysts can directly reprogram glycolysis, redox balance, oxygen tension, and mitochondrial activity, and these metabolic changes in turn alleviate immunosuppression and promote innate and adaptive immune activation. This review outlines the mechanistic foundations of DNAzyme catalysis, summarizes recent nanoengineering strategies that endow DNAzymes with programmable sensing and stimuli-responsive functions, and discusses how these systems bridge biosensing and catalytic immunometabolic functions. We conclude with perspectives on translational challenges and opportunities, endorsing programmable DNAzyme nanocatalysts as emerging preclinical platforms for biosensing-guided immunometabolic intervention.
抗微生物耐药 (antimicrobial resistance, AMR) 已从潜在威胁演变为全球性公共卫生危机, 其特征表现为耐药性快速上升、 抗生素创新不足以及治疗选择日益受限。 在此背景下, 绿色合成纳米材料, 尤其是药用植物介导的金属及金属氧化物纳米颗粒, 被视为一种具有可持续性的抗菌替代策略。 然而, 缺乏严格评价标准可能导致对其抗菌潜力的过度解读。 本文提出一种基于决策门控的评价框架, 从药理学合理性、 理化可重复性、 作用机制验证以及抗菌管理 (stewardship) 一致性等方面, 对绿色纳米材料在 AMR 防控中的应用进行系统评估。 研究强调, 纳米技术应作为抗菌管理的辅助策略, 通过在感染控制 (如医疗表面涂层、 伤口敷料及环境修复) 中的应用, 减少抗生素使用压力, 而非替代传统抗生素。 同时, 人工智能与计算模拟方法在纳米材料设计与机制解析中的整合作用, 有助于提升其转化潜力与可持续性。 综上所述, 本研究为绿色纳米技术在 AMR 防控中的规范化应用提供了科学依据与结构化路径。
Meat adulteration is a significant global food safety challenge, creating a pressing need for rapid and on-site detection technologies. Herein, we present an intelligent one-pot biosensing platform termed one-pot TLAMP-PfAgo assay (OTPA) that integrates the rapid amplification of turn-back loop primer-accelerated loop-mediated isothermal amplification (LAMP) (TLAMP) with the sequence-specific detection of Pyrococcus furiosus Argonaute (PfAgo). This system features a clever heat-activatable design using microcrystalline wax to spatially separate reactions within a single tube, enabling contamination-free and streamlined operation. The OTPA assay achieves sensitive and specific detection, with limits of detection as low as 3×10-4 ng/μL for pork DNA and 2×10-4 ng/μL for beef DNA within 30 min. It successfully enables duplex target identification and has been validated with commercial meat products, showing perfect concordance with standard polymerase chain reaction (PCR)-based qualitative detection. Notably, the result can be directly visualized under blue light, underscoring the substantial potential of this cost-effective and simple platform for point-of-care testing (POCT) and intelligent biosensing in food safety surveillance.
Acute myocardial infarction (AMI) remains a major global health burden and is characterized by profound cardiac inflammation, apoptotic cell death, and impaired myocardial function. While interleukin-15 (IL-15) has been implicated in immune regulation, its precise role in the pathogenesis of AMI has not been clarified. Therefore, this study sought to delineate the functional role of IL-15 in the progression of AMI, with a particular focus on its influence on macrophage-driven inflammation, efferocytosis, and metabolic reprogramming. IL-15 levels were assessed in AMI patients and murine models. To evaluate the impact of IL-15 on cardiac inflammation, apoptosis, and functional outcomes following AMI, IL-15 and IL-15 receptor α (IL-15Rα) knockout (KO) mouse models were employed. Mechanistic studies were conducted to investigate IL-15-mediated effects on macrophage efferocytosis, polarization, and metabolic remodeling, with an emphasis on nuclear factor-κB (NF-κB) signaling and glycolytic flux. Elevated IL-15 levels were detected in both the plasma of AMI patients and the cardiac tissues of murine AMI models, correlating with increased disease severity. The genetic deletion of IL-15 or IL-15Rα significantly ameliorated cardiac injury by reducing inflammation and apoptosis while preserving myocardial function. Mechanistic analyses revealed that IL-15 impaired macrophage efferocytosis via Mer tyrosine kinase (MERTK) downregulation and promoted M1 polarization via NF-κB pathway activation. Furthermore, IL-15 reprogrammed macrophage metabolism by enhancing glycolytic activity. Ultimately, IL-15 restoration exacerbated cardiac ischemic injury following AMI, serving as a critical regulator of macrophage-mediated inflammation in AMI. These findings highlight the role of IL-15 as a potential therapeutic and prognostic target for mitigating cardiac inflammation and improving myocardial recovery in AMI.
Background: Insomnia is a common condition that adversely affects work productivity, and a significant proportion of individuals with acute insomnia disorder (AID) eventually develop chronic insomnia disorder (CID). However, it remains unclear whether workplace impairment and daily activity impairment occur early in the course of insomnia. Methods: This cross-sectional study included 295 AID and 305 CID participants. Multiple linear regression was used to assess associations between insomnia, workplace and daily activity impairment, and related factors (daytime sleepiness, depressive and anxiety symptoms). Restricted cubic spline (RCS) analysis was also conducted to explore nonlinear relationships. Mediation analysis was performed to assess the potential mediating effects of daytime sleepiness and depressive and anxiety symptoms between insomnia and workplace and daily activity impairment. Results: No significant differences were found between the AID and CID groups in presenteeism or productivity-loss costs (P>0.05). Insomnia severity, daytime sleepiness, and depressive and anxiety symptoms were the correlated factors of workplace and daily activity impairment (P<0.05). A nonlinear relationship between depressive symptoms and presenteeism, as well as between daytime sleepiness and daily activity impairment, was identified in both groups (Poverall<0.01, Pnonlinearity<0.05). Mediation analysis showed that in the AID group, depressive symptoms mediated the effects on absenteeism and daily activity impairment (mediation proportions: 37.02
Neuroinflammation may disrupt neurotransmitter signaling. This study investigated whether gut microbiota-induced neuroinflammation can regulate glutamate pathways in bipolar disorder (BD). Fecal microbiota transplantation (FMT) was performed to observe behavioral changes in the antibiotic-treated C57BL/6J male mouse model of bipolar depression. Gut microbial structure, circulating, and prefrontal levels of inflammatory factors, microglial activation, and transcription levels of N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4 isoxazole receptor (AMPAR) genes were measured in the “BD” and control mice. Furthermore, the effects of interleukin-1 (IL-1) receptor antagonist (IL-1RA) on the glutamate pathways were assessed. Compared with the control mice, “BD” mice displayed depression-like behaviors, with a lower diversity of gut bacteria and a decreased abundance of certain species. In addition, “BD” mice showed increased levels of inflammatory factors (e.g., IL-1β) in the serum and prefrontal cortex, microglial activation, and changes in the messenger RNA (mRNA) levels of NMDAR and AMPAR. Treatment with IL-1RA partially reversed the behavioral patterns, neuroinflammation, and transcription levels of glutamate receptors. The findings suggest that gut microbiota may influence glutamate receptor gene expression via an IL-1β-dependent pathway in a mouse model of BD, potentially contributing to neuroinflammatory mechanisms relevant to this disorder.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor that orchestrates the expression of genes involved in antioxidant defense, detoxification, and the maintenance of cellular homeostasis. This review provides a comprehensive analysis of the dual regulatory role of Nrf2 in both normal physiological and pathological conditions, focusing on the molecular mechanisms by which it modulates mitochondrial function, oxidative stress, inflammation, and autophagy. The review summarizes the current knowledge on the effects of various synthetic and natural compounds, such as flavonoids and resveratrol, on Nrf2 activity. The review also explores the therapeutic potential of Nrf2 in neurodegenerative diseases, cancers, diabetes, and other disorders, laying a foundation for the development of Nrf2-targeted pharmacological interventions.
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder with limited therapeutic options and no cure, underscoring the urgent need for novel treatment strategies. Our previous work demonstrated that an engineered strain of Clostridium butyricum-pMTL007-glucagon-like peptide-1 (C. butyricum-pMTL007-GLP-1) alleviated PD symptoms by enhancing mitophagy, though the exact molecular mechanisms remained incompletely understood. In this study, we further investigated the neuroprotective effects and underlying mechanisms of this engineered strain using an A53T α-synuclein (α-syn) transgenic mouse model of PD. Specifically, we evaluated its impact on motor function, gut α-syn expression, intestinal barrier function, gut microbial composition, and neuropathological changes, with a focus on the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. Our findings revealed that C. butyricum-pMTL007-GLP-1 ameliorated motor deficits in PD mice by reducing intestinal α-syn accumulation, restoring gut barrier function, and modulating microbial diversity—notably increasing the relative abundance of Prevotella at the genus level. Furthermore, the engineered strain attenuated neuropathological alterations by decreasing phosphorylated α-syn (p-α-syn) in the substantia nigra while upregulating tyrosine hydroxylase (TH), dopamine-transporter (DAT), and glucagon-like peptide-1-receptor (GLP-1R) expression. These neuroprotective effects were associated with suppressed proinflammatory responses and enhanced anti-inflammatory and anti-apoptotic signaling, likely mediated through PI3K/AKT/GSK-3β pathway activation. In conclusions, C. butyricum-pMTL007-GLP-1 exerts significant neuroprotective effects in PD mice by reshaping gut microbiota composition and activating the PI3K/AKT/GSK-3β pathway. These findings provide further theoretical support for the potential application of probiotic-based therapies in PD treatment.
