The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross-Sectional Studies.

OBJECTIVE: Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, the clinical evidence of this association remains lacking. METHODS: In this study, the index for diffusion tensor image analysis along the perivascular space (ALPS index) was calculated to evaluate glymphatic function. RESULTS: Overall, 289 patients with PD were enrolled in the cross-sectional study. The ALPS index was found to be negatively correlated with age, disease severity, and dyskinesia. In the longitudinal study, the information on a total of 95 PD patients with 5-year follow-up examinations was collected from the Parkinson's Progression Marker Initiative, 33 of which were classified into the low ALPS index group, and all others were classified into the mid-high ALPS index group based on the first tertile of the baseline ALPS index. The results of longitudinal regression indicated that there was a significant main group effect on autonomic dysfunction, as well as on activities of daily living. In addition, the low ALPS index group had faster deterioration in MDS-UPDRS part III and part II, Symbol Digit Modalities Test and Hopkins Verbal Learning Test. Path analysis showed that ALPS index acted as a significant mediator between tTau/ Aß1-42 and cognitive change in the Symbol Digit Modalities Test score at year 4 and year 5. INTERPRETATION: The ALPS index, an neuroimaging marker of glymphatic function, is correlated with PD disease severity, motor symptoms, and autonomic function, and is predictive of faster deterioration in motor symptoms and cognitive function. Additionally, glymphatic function may mediate the pathological role of toxic protein in cognitive decline. ANN NEUROL 2023;94:672-683.

Harnessing Gene Editing Technology for Tumor Microenvironment Modulation: An Emerging Anticancer Strategy.

Cancer is a multifaceted disease influenced by both intrinsic cellular traits and extrinsic factors, with the tumor microenvironment (TME) being crucial in its progression. To satisfy their high proliferation and aggressiveness, cancer cell always plunders large amounts of nutrition and releases various signals to the surrounding, forming a dynamic TME with special metabolic, immune, microbial and physical characteristics. Due to the neglect of interactions between tumor cell and TME, traditional cancer therapies often struggle with challenges such as drug resistance, low efficacy, and recurrence. Importantly, with the development of gene editing technologies, particularly the CRISPR-Cas system, offers promising new strategies for cancer treatment. Combined with nanomaterials strategies, CRISPR-Cas technology exhibits precision, affordability, and user-friendliness with reduced side effects, which holds great promise for profoundly altering the TME at a genetic level, potentially leading to lasting anticancer outcomes. This review will delve into how CRISPR-Cas can be leveraged to manipulate the TME, examining its potential as a transformative anticancer therapy.

LncRNA landscape and associated ceRNA network in placental villus of unexplained recurrent spontaneous abortion.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions frustrates women of childbearing age profoundly. The gene expression patterns and biological characteristics of placental villus in patients with URSA remain largely unknown. The aim of our study was to identify potential lncRNAs as well as their action mechanisms in URSA. METHOD: The ceRNA microarray was used to identify the mRNA and lncRNA expression profiles of URSA patients and normal pregnancy. Functional enrichment analyses for differentially expressed mRNAs in URSA were performed. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. Subsequently, the co-dysregulated ceRNA network of URSA was established, and the enrichment analyses for the mRNAs in the ceRNA network was implemented. qRT-PCR was performed to validated the expression of key ENST00000429019 and mRNAs in URSA. RESULTS: We found that URSA placental villus have distinct mRNA and lncRNA expression profiles through ceRNA microarray, with a total of 347 mRNAs and 361 lncRNAs differentially expressed compared with controls. The functional enrichment analysis revealed that ncRNA processing, DNA replication, cell cycle, apoptosis, cytokine-mediated signaling pathway, ECM-receptor interaction were the potentially disrupted pathways in URSA patients. Then we constructed a co-dysregulated ceRNA network and found differentially expressed mRNAs were regulated by a small fraction of hub lncRNAs. Finally, we found a key network of ENST00000429019 and three cell proliferation or apoptosis related key mRNAs (CDCA3, KIFC1, NCAPH), and validated their expression and regulation in tissue and cellular levels. CONCLUSIONS: This study identified a key ceRNA network, which might take part in URSA and correlate with cell proliferation and apoptosis. Optimistically, this study may deepen our apprehensions about the underlying molecular and biological causes of URSA and provide an important theoretical basis for future therapeutic strategies for patients with URSA.

A Gene-Editable Palladium-Based Bioorthogonal Nanoplatform Facilitates Macrophage Phagocytosis for Tumor Therapy.

Macrophage phagocytosis of tumor cells has emerged as an attractive strategy for tumor therapy. Nevertheless, immunosuppressive M2 macrophages in the tumor microenvironment and the high expression of anti-phagocytic signals from tumor cells impede therapeutic efficacy. To address these issues and improve the management of malignant tumors, in this study we developed a gene-editable palladium-based bioorthogonal nanoplatform, consisting of CRISPR/Cas9 gene editing system-linked Pd nanoclusters, and a hyaluronic acid surface layer (HBPdC). This HBPdC nanoplatform exhibited satisfactory tumor-targeting efficiency and triggered Fenton-like reactions in the tumor microenvironment to generate reactive oxygen species for chemodynamic therapy and macrophage M1 polarization, which directly eliminated tumor cells, and stimulated the antitumor response of macrophages. HBPdC could reprogram tumor cells through gene editing to reduce the expression of CD47 and adipocyte plasma membrane-associated protein, thereby promoting their recognition and phagocytosis by macrophages. Moreover, HBPdC induced the activation of sequestered prodrugs via bioorthogonal catalysis, enabling chemotherapy and thereby enhancing tumor cell death. Importantly, the Pd nanoclusters of HBPdC were sufficiently cleared through basic metabolic pathways, confirming their biocompatibility and biosafety. Therefore, by promoting macrophage phagocytosis, the HBPdC system developed herein represents a highly promising antitumor toolset for cancer therapy applications.

Identifying Parkinson's disease with mild cognitive impairment by using combined MR imaging and electroencephalogram.

OBJECTIVES: To analyse the changes of quantitative electroencephalogram (qEEG) and cortex structural magnetic resonance (MR) imaging in Parkinson's disease with mild cognitive impairment (PD-MCI) and to explore the "composite marker"-based machine learning model in identifying PD-MCI. METHODS: Retrospective analysis of patients with PD identified 36 PD-MCI and 35 PD with normal cognition (PD-NC). QEEG features of power spectrum and structural MR features of cortex based on surface-based morphometry (SBM) were extracted. Support vector machine (SVM) was established using combined features of structural MR and qEEG to identify PD-MCI. Feature importance evaluation algorithm of mean impact value (MIV) was established to sort the vital characteristics of qEEG and structural MR. RESULTS: Compared with PD-NC, PD-MCI showed a statistically significant difference in 5 leads and waves of qEEG and 7 cortical region features of structural MR. The SVM model based on these qEEG and structural MR features yielded an accuracy of 0.80 in the training set and had a high prediction accuracy of 0.80 in the test set (sensitivity was 0.78, specificity was 0.83, area under the receiver operating characteristic curve was 0.77), which was higher than the model built by the feature separately. QEEG features of theta wave in C3 had a marked impact on the model for classification according to the MIV algorithm. CONCLUSIONS: PD-MCI is characterized by widespread structural and EEG abnormality. "Composite markers" could be valuable for the individualized diagnosis of PD-MCI by machine learning. KEY POINTS: • Explore the brain abnormalities in Parkinson's disease with mild cognitive impairment by using the quantitative electroencephalogram and cortex structural MR simultaneously. • Multimodal features based support vector machine for identifying Parkinson's disease with mild cognitive impairment has an acceptable performance. • Theta wave in C3 is the most influential feature of qEEG and cortex structure MR imaging in identifying Parkinson's disease with mild cognitive impairment using support vector machine.

Nanosized Phase-Changeable "Sonocyte" for Promoting Ultrasound Assessment.

Despite the ability of microbubble contrast agents to improve ultrasound diagnostic performance, their application potential is limited due to low stability, fast clearance, and poor tissue permeation. This study presents a promising nanosized phase-changeable erythrocyte (Sonocyte), composed of liposomal dodecafluoropentane coated with multilayered red blood cell membranes (RBCm), for improving ultrasound assessments. Sonocyte is the first RBCm-functionalized ultrasound contrast agent with uniform nanosized morphology, and exhibits good stability, systemic circulation, target-tissue accumulation, and even ultrasound-responsive phase transition, thereby satisfying the inherent requirement of ultrasound imaging. It is identified that Sonocyte displays similar sensitivity as microbubble SonoVue, a clinical ultrasound contrast agent, for effectively detecting normal parenchyma and hepatic necrosis. Importantly, compared with SonoVue lacking of ability to detect tumors, Sonocyte can identify tumors with high sensitivity and specificity due to superior tumor accumulation and penetration. Therefore, Sonocyte exhibits superior capabilities over SonoVue, endowing with a great clinical application potential.

Effect of Combined Statin and Antihypertensive Therapy in Patients with Hypertension: A Systematic Review and Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to explore the preventive effects of combined statin and antihypertensive therapy on major cardiovascular outcomes in patients with hypertension. METHODS: PubMed, Embase, and the Cochrane Library databases and reference lists of published studies were systematically searched throughout October 9, 2019. Studies designed as randomized controlled trials and investigating the effects of combined statin and antihypertensive therapy versus antihypertensive therapy alone were included. Data abstraction and quality of included studies were assessed by 2 independent authors. The summary results were calculated using relative risks (RRs) with 95% CIs employing a random-effects model. RESULTS: A total of 8 randomized controlled trials including 38,618 patients were finally enrolled. The summary RRs indicated that the combined therapy significantly reduced the risk of major adverse cardiovascular events compared with antihypertensive therapy alone (RR 0.79; 95% CI 0.71-0.88; p < 0.001). Furthermore, the patients in the combined therapy group also experienced less myocardial infarction (RR 0.67; 95% CI 0.53-0.84; p = 0.001) and stroke risks (RR 0.82; 95% CI 0.72-0.94; p = 0.005), while no significant difference was observed between combined therapy and antihypertensive therapy alone regarding cardiac death (RR 0.96; 95% CI 0.84-1.08; p = 0.465) and all-cause mortality (RR 0.95; 95% CI 0.86-1.04; p = 0.277). CONCLUSION: These findings suggested that combined statin and antihypertensive therapy was associated with more cardiovascular benefits compared with antihypertensive therapy alone.

Integrin αvß3-Specific Hydrocyanine for Cooperative Targeting of Glioblastoma with High Sensitivity and Specificity.

Glioblastoma is a highly malignant brain tumor with poor prognosis and survival rate because of a lack of effective diagnostic methods. Hydrocyanines are a type of reactive oxygen species (ROS)-responsive fluorescent probes, allowing for distinguishing tumor cells from normal cells based on their different intracellular levels of ROS. However, their diagnostic applications for glioblastoma have been limited because of the inability to discriminate between tumor cells and other tissues with high ROS production, leading to high false-positive diagnosis. Therefore, tumor-responsive and -specific hydrocyanines with cooperative targeting ability have great potential for improving the diagnosis and treatment of glioblastoma. Integrin αvß3 plays a critical role in the progression and angiogenesis of glioblastoma and has become a promising target for diagnosing glioblastoma. Herein, we identify a specific peptide ligand for integrin αvß3, Arg-Trp-(d-Arg)-Asn-Arg (RWrNR), which shows high binding affinity to human glioblastoma U87MG cells. Importantly, hydro-Cy5-RWrNR conjugation allowed for distinguishing U87MG cells from normal cells in response to intracellular ROS. Particularly, hydro-Cy5-RWrNR could not only selectively accumulate in orthotopic U87MG tumor with minimal background fluorescence but also effectively discriminate between glioblastoma and inflammatory tissues for the first time, leading to detection of glioblastoma in vivo with high target-to-background ratios and minimal background fluorescence. Therefore, hydro-Cy5-RWrNR is the first integrin αvß3-specific hydrocyanine probe and has great potential in precise tumor diagnosis because of its cooperative targeting of integrin αvß3 and ROS.

Synergistic Amplification of Oxidative Stress-Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF-Fe2.

Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal-organic framework (MOF)-Fe2+ (MD@Lip) has been developed, which can efficiently stimulate ROS-mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF-Fe2+ , but also generate an acidic microenvironment to activate a MOF-Fe2+ -based Fenton reaction. Importantly, MD@Lip promotes DCA-mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H2 O2 ), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF-Fe2+ , leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome-based combination therapy of DCA and MOF-Fe2+ provides a promising oxidative stress-associated antitumor strategy for the management of malignant tumors.

TREM2 modulates microglia phenotypes in the neuroinflammation of Parkinson's disease.

Neuroinflammation and overactivated microglia underlies the pathogenesis of Parkinson's disease (PD). Furthermore, microglia could polarize into classic inflammatory M1 and immunosuppressive M2 phenotype. Thus, inhibiting the overactivated inflammatory M1 microglia by promoting the transformation of microglia to the protective M2 phenotype provides potential therapy for PD, but the mechanism that modulates microglia polarization remains unknown. Triggering receptor expressed on myeloid cells-2 (TREM2) is a recently identified immune receptor expressed by the microglia in the brain. Emerging evidence indicates that TREM2 enhances the phagocytosis function of microglia and suppress inflammation. Based on these evidence, we hypothesized that TREM2 might play a protective role through regulating microglia polarization. Here, we employ a lentiviral strategy to overexpress or suppress TREM2 on microglia and found that TREM2 was essential for M2 microglia polarization. Knockdown of TREM2 in BV2 microglia inhibited M2 polarization and lead to exaggeration of M1 microglial inflammatory responses, whereas overexpression of TREM2 promoted M2 polarization and alleviated microglial inflammation. We also observed that the TREM2 level was higher in the midbrain of PD mice, which was accompanied by an elevated level of Arginase-1 and increased proinflammatory cytokines, suggesting that TREM2 is an important factor in switching the microglia phenotypes. Taken together, these findings indicate that TREM2 plays a crucial role in altering the proinflammatory M1 microglia to M2 phenotype and has beneficial effects in the immune pathogenesis of PD.

Association Between Plasma Homocysteine and Microalbuminuria in Untreated Patients with Essential Hypertension: a Case-Control Study.

BACKGROUND/AIMS: Kidney function is critical for homocysteine (Hcy) clearance, and plasma Hcy levels are frequently increased in patients with renal failure. Microalbuminuria (MAU) is an important marker of early renal damage caused by hypertension. At present, there is insufficient evidence on the relationship between Hcy and microalbuminuria. METHODS: This is a 1: 2 matched, hospital-based case-control study. At initial visit, out of 1535 outpatients with no prior history of medication, 450 qualified subjects were selected based on inclusion and exclusion criteria. The concentration of Hcy in the serum was evaluated using a cyclic enzyme method. MAU was defined by a urine albumin/creatinine ratio (UACR) between 30 µg/mg and 300 µg/mg. RESULTS: A total of 450 patients were included in this study (150 in the MAU group and 300 in the non-MAU group). The MAU group had higher mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), heart rate (HR) and plasma Hcy levels than did the non-MAU group. The area under the receiver operating characteristics (ROC) curves was 0.772 (95% CI: 0.724-0.819, P < 0.001) with a cut-off value of 15.0, and the sensitivity and specificity of Hcy in predicting the MAU status in hypertensive patients were 49.3% and 92.3%, respectively. Multiple logistic regression modelling suggested that patients with a higher Hcy level (> 15 µmol/L) were more likely to have MAU (95% CI: 5.650-16.543, P < 0.001). The other predictive factor for MAU was 24-h mean SBP (95% CI: 0.941-0.993, P = 0.015). CONCLUSION: This matched case-control study indicates that Hcy may increase the susceptibility of essential hypertensive subjects to MAU.

Lysine-Specific Demethylase 1 (LSD1) Inhibitor S2101 Induces Autophagy via the AKT/mTOR Pathway in SKOV3 Ovarian Cancer Cells.

BACKGROUND S2101 is one of the most potent LSD1 inhibitors, which can inhibit ovarian cancer cells viability. This study aimed to detect the mechanism behind the anticancer properties of S2101 in SKOV3 ovarian cells. MATERIAL AND METHODS Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. Cellular apoptosis and autophagy were evaluated by flow cytometric analysis using Annexin-V/PI staining methods and Green fluorescent protein (GFP)-fused-LC3 (GFP-LC3), respectively. Western blotting was performed for analyzing the Bax, Bcl-2, mTOR, p- mTOR, p62, LC3-I, LC3-II, AKT, and p-AKT protein expression. RESULTS Our results show that the proportion of early apoptotic and late apoptotic cells increased significantly for cells treated with S2101 at a concentration of 100 µM for 48 h. Treatment of S2101 in SKOV3 cells resulted in upregulation of Bax and downregulation of Bcl-2 in a time-dependent manner, indicating that S2101 can induce apoptosis in SKOV3. There was a downward trend in the expression of p62 when the SKOV3cells were treated with 100 µm S2101 for 12 h, 24 h and 48 h. The conversion of LC3-I to LC3-II was increased significantly at 24 h and 48 h. Autophagy was induced by S2101 in SKOV3 cells, evidenced by an increase in punctuate localization of GFP-LC3 and a change in expression of autophagy-related proteins. CONCLUSIONS S2101 treatment decreased the levels of phosphorylated AKT and mTOR. S2101 inhibits SKOV3 cells viability and induces apoptosis and autophagy. The AKT/mTOR signaling pathway was found to be affected by S2101.

MCP-1 and CCR2 gene polymorphisms in Parkinson's disease in a Han Chinese cohort.

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR2) play important roles in neuroinflammation and they have been shown to be involved in Parkinson's disease (PD) pathogenesis. In addition, several studies have suggested a role for the MCP-1 and CCR2 genotypes in cognitive impairment and depression, which are common non-motor symptoms in PD patients. In this study, a cohort of 521 PD patients and 556 cases of healthy controls were recruited to investigate the association between the MCP-1 2518A/G (rs1064211) and CCR2 V64I (rs1799864) gene polymorphisms and PD risk in the Chinese population. We also analyze the influence of these genotypes on the cognitive function and depression in PD patients by comparing Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC), Wechsler Memory Scale-Chinese Revision (WMS-RC) and Hamilton Depression Rating Scale (HAMD) ratings in 217 PD patients. Our results showed no significant differences in the genotype frequency between the PD group and the control group (P > 0.05). In addition, we also failed to find an influence of the MCP-1 and CCR2 genotypes on MMSE scores, MoCA scores, WAIS-RC scores, WMS-RC scores and HAMD scores in PD patients (P > 0.05). The MCP-1 and CCR2 gene polymorphisms may not be genetic risk factors for PD in the Han Chinese population, and they do not appear to influence cognitive function and depression in PD patients.

Cerebrospinal fluid alpha-synuclein as a biomarker for Parkinson's disease diagnosis: a systematic review and meta-analysis.

To date, there are no definitive biomarkers for Parkinson's disease (PD) diagnosis. The detection of cerebrospinal fluid (CSF) alpha (α)-synuclein in PD patients has yielded promising but inconclusive results. To determine the performance of CSF α-synuclein as a diagnostic biomarker of PD and whether CSF α-synuclein can discriminate PD from other neurodegenerative diseases, a systematic search of all relevant studies investigating reproducible CSF α-synuclein quantification methods was conducted in electronic databases. A total of 17 studies that included 3311 patients were included in this systemic review and meta-analysis. The mean CSF α-synuclein concentration was significantly lower in PD patients compared to normal/neurological controls [weighted mean difference (WMD) -0.31; 95% CI, -0.45, -0.16; p < 0.0001] and patients with Alzheimer's disease (AD) [WMD -0.15; 95% CI, -0.26, -0.04; p < 0.0001]. There was no significant difference between PD patients and dementia with Lewy bodies (DLB) patients [WMD -0.03; 95% CI, -0.16, 0.09; p = 0.58] or patients with multiple system atrophy (MSA) [WMD 0.05; 95% CI, -0.04, 0.13; p = 0.25]. Sensitivity and specificity of CSF α-synuclein in the diagnosis of PD was 0.88 (95% CI, 0.84-0.91) and 0.40 (95% CI, 0.35-0.45), respectively. The positive and negative likelihood ratios of CSF α-synuclein in the diagnosis of PD were 1.41 (95% CI, 1.24-1.60), and 0.29 (95% CI, 0.15-0.56), respectively. The corresponding summary receiver operating characteristic (SROC) curve showed an area under the curve (AUC) of 0.73. The concentration of CSF α-synuclein may be a biomarker for the diagnosis of PD. The use of α-synuclein alone however is not sufficient as a single biomarker and it must therefore be used in conjunction with other documented and reliable biomarkers.

MiR-25 promotes ovarian cancer proliferation and motility by targeting LATS2.

Ovarian cancer (OC) is a major cancer-related mortality among women. Recent studies suggest that many microRNAs (miRNAs) were dysregulated and involved in tumorigenesis of OC. The present study investigated the role of miR-25 in the development and progression of OC. The expression of miR-25 was increased in OC tissues and cell lines. Inhibition of miR-25 remarkably suppressed proliferation, migration, and invasion of OC cells. Large tumor suppressor 2 (LATS2), a tumor suppressor, was confirmed to be a direct target of miR-25 in OC cells. Moreover, restoration of LATS2 significantly attenuated the oncogenic effects of miR-25. Together, our data suggest an oncogenic role of miR-25 in OC and a potentially novel diagnostic and therapeutic target for OC treatment.

A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment.

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127-functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.

Microfluidic synthesis of hemin@ZIF-8 nanozyme with applications in cellular reactive oxygen species detection and anticancer drug screening.

Zeolitic imidazolate framework-8 (ZIF-8) encapsulating enzymatically active biomolecules has emerged as a novel biocompatible nanozyme and offers significant implications for bioanalysis of various biomarkers towards early diagnosis of severe diseases such as cancers. However, the rapid, continuous and scalable synthesis of these nanozymes still remains challenging. In this work, we proposed a novel microfluidic approach for rapid and continuous synthesis of hemin@ZIF-8 nanozyme. By employing a distinctive combination of zigzag-shaped channel and spiral channel with sudden expansion structures, we have enhanced the mixing efficiency within the chip and achieved effective encapsulation of hemin in ZIF-8. The resulting hemin@ZIF-8 nanoparticles exhibit peroxidase-like activity and are capable of detecting free H2O2 with a limit of detection (LOD) as low as 45 nM, as well as H2O2 secreted by viable cells with a detection threshold of approximately 10 cells per mL. By leveraging this method, we achieved successful detection of cancer cells and effective screening of anticancer drugs that induce oxidative stress injury in cancer cells. This innovative microfluidic strategy offers a new avenue for synthesizing functional nanocomposites to facilitate the development of next-generation diagnostic tools for early disease detection and personalized medicine.

The association of CSF biomarkers and cognitive decline with choroid plexus volume in early Parkinson's disease.

OBJECTIVE: This study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume. METHODS: Data on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects. RESULTS: At baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aß1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aß1-42/αsyn ratio. CONCLUSION: CP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins.

Neuronavigated repetitive transcranial magnetic stimulation improves depression, anxiety and motor symptoms in Parkinson's disease.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a potential treatment option for Parkinson's disease patients with depression (DPD), but conflicting results in previous studies have questioned its efficacy. Method: To investigate the safety and efficacy of neuronavigated high-frequency rTMS at the left DLPFC in DPD patients, we conducted a randomized, double-blind, sham-controlled study (NCT04707378). Sixty patients were randomly assigned to either a sham or active stimulation group and received rTMS for ten consecutive days. The primary outcome was HAMD, while secondary outcomes included HAMA, MMSE, MoCA and MDS-UPDRS-III. Assessments were performed at baseline, immediately after treatment, 2 weeks, and 4 weeks post-treatment. Results: The GEE analysis showed that the active stimulation group had significant improvements in depression, anxiety, and motor symptoms at various time points. Specifically, there were significant time-by-group interaction effects in depression immediately after treatment (ß, -4.34 [95% CI, -6.90 to -1.74; P = 0.001]), at 2 weeks post-treatment (ß, -3.66 [95% CI, -6.43 to -0.90; P = 0.010]), and at 4 weeks post-treatment (ß, -4.94 [95% CI, -7.60 to -2.29; P < 0.001]). Similarly, there were significant time-by-group interaction effects in anxiety at 4 weeks post-treatment (ß, -2.65 [95% CI, -4.96 to -0.34; P = 0.024]) and in motor symptoms immediately after treatment (ß, -5.72 [95% CI, -9.10 to -2.34; P = 0.001] and at 4 weeks post-treatment (ß, -5.43 [95% CI, -10.24 to -0.61; P = 0.027]). Conclusion: The study suggested that neuronavigated high-frequency rTMS at left DLPFC is effective for depression, anxiety, and motor symptoms in PD patients.