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Background and Aim: Depression in Parkinson's disease (DPD) has a high incidence rate among patients with Parkinson's disease (PD). It is a common nonmotor symptom of PD that seriously affects the quality of life of patients. Thus, improving DPD is important for improving the quality of life of patients. Psychotherapy for depression is limited for many reasons, and only a few patients are able to benefit from this therapy. Several studies have demonstrated that relaxation therapy, playing, and exercise therapy are effective treatments for depression. In recent years, virtual reality (VR) has rapidly developed as a form of rehabilitation due to its immersive characteristics and accessibility. It has also been applied in the psychological treatment of phobia and anxiety. However, no relevant research on the treatment of DPD has been conducted using VR. This study aims to assess the effects of immersive VR-assisted training on patients with DPD., Methods: This single-blind randomized controlled trial will recruit 74 patients with DPD. The patients will then be randomly allocated into two groups. The patients in the VR group (n = 37) will receive VR-assisted training (40 min) three times a week for 8 weeks. The patients in the non-VR training group (n = 37) will receive treatment as usual. The outcome measures will be assessed before intervention, and after 8 weeks, 3 months, and 6 months of the intervention. The primary outcomes will include the Hamilton Depression Scale-24. The secondary outcomes will include the 36-Item Short-Form Health Survey questionnaire, neuroinflammation factors (brain-derived neurotrophic factor, interleukin-6, and C-reactive protein), and functional magnetic resonance imaging., Discussion: The traditional treatment of depression has limited resources and requires a lot of time and energy. It is not suitable for patients with PD having mobility difficulties and residing in remote areas. VR can make up for limitations in traditional treatment methods. An advantage of VR is that it makes patients more invested in active participation. This study may provide an improved method for the clinical treatment of patients with DPD, which is suitable for clinical decision-making and future practice., Trial Registration: The study has been registered in the Chinese Clinical Trial Registry ChiCTR2200065843, November 16, 2022. https://www.chictr.org.cn/showproj.html?proj=174551 {2a and 2b}., (© 2024. The Author(s).)

Background: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease., Methods: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales., Results: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale., Conclusions: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia., (© 2024. The Author(s).)

Introduction: This study aims to explore the current status of dementia-specific diagnosis and treatment in China., Methods: This national survey was conducted in mainland China from September 2022 to February 2023, with strong support from the Cognitive Disorders Group of the Chinese Society of Neurology, Chinese Medical Association., Results: Among 2721 hospitals surveyed, 244 (8.97%) have dementia-specific clinics (DSCs) and 166 (6.10%) have dementia-specific inpatient departments (DSIDs). Almost all hospitals have brain structural imaging capabilities and basic hematological examinations, but dementia-specific medical staff (DSMS) equipped for DSCs or DSIDs are rare. The proportion of patients with cognitive impairment receiving care through a DSCs or DSIDs is low, and most patients present with advanced (moderate to severe) disease., Conclusion: The survey shows that the proportion of DSCs and DSIDs is low, and the regional distribution varies significantly. Trained DSMS and specialized facilities for the diagnosis and treatment of dementia are inadequate., Highlights: This study was a multi-center national research to comprehensively investigate the distribution and features of dementia-specific clinics and inpatient departments in mainland China, given that the limited literature was available regarding the dementia-specific centers. The study points to significant regional differences in the distribution of cognitive-specific clinics and inpatient departments in mainland China. More centers in Eastern Regions compared to Western Regions, a greater presence in provincial capitals as opposed to other cities, and a predominance of tertiary hospitals over non-tertiary ones. The aim is to provide data support for advancements in medical research within this field. Domestic dementia patients have inadequate access to specialized medical resources and expert assistance, which significantly contrasts with the growing number of dementia cases in China., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: This study aimed to evaluate the diagnostic ability of six plasma biomarkers in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and different subtypes of Parkinson's disease (PD)., Methods: Neurofilament light chain (NfL), phosphorylated tau-181, glial fibrillary acidic protein (GFAP), amyloid-β 42 (Aβ42), and amyloid-β 40 (Aβ40) levels were measured using the single-molecule array (Simoa) technique in a cohort of patients with PSP, MSA, different subtypes of PD, and healthy controls (HCs)., Results: Plasma NfL and GFAP levels were beneficial in discriminating between the disease groups and HCs. Plasma NfL, Aβ42, and Aβ40 could distinguish atypical Parkinsonian syndrome (APS) from PD and its subtypes. GFAP could discriminate APS from tremor dominant PD but could not discriminate APS from postural instability and gait disorder dominant PD. The efficacy of differentiation improved when a combination of multiple plasma biomarkers was applied., Conclusions: In this study, the plasma biomarkers NfL, GFAP, Aβ42, and Aβ40 exhibited high discriminatory diagnostic value in PD and APS, and could be used as clinically potential diagnostic biomarkers. Plasma biomarker combinations could improve the differential diagnostic efficacy in the comparisons of PD and APS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Bioelectrochemical system (BES) is a unique biotechnology for wastewater treatment and energy recovery, and extracellular electron transfer (EET) between microbe and electrode is the key to optimize the performance of BESs. Resazurin is an effective artificial compound that can promote EET in BESs, but the way how it transports electrons is not fully understood. In this study differential pulse voltammetry revealed that the redox potential of resorufin (RR) (intermediate of resazurin reduction, actual electron mediator) within Geobacter sulfurreducens biofilm was positively shifted by 100 mV than that of free RR, and this shift was attenuated by the mutation of outer-membrane cytochrome gene omcE but not by omcS and omcZ mutation, indicating that RR specifically interacted with OmcE. By using heterologously expressed OmcE monomers in Escherichia coli, it was found that RR bonded with OmcE monomers with a moderate intensity (dissociation constant of 720 nM), and their interaction obviously increased the content of α helix in OmcE monomers. Biomolecular analysis indicated that heme II of OmcE monomer might be the binding site for RR (binding energy of -7.01 kJ/mol), which were favorable for electron transfer within OmcE-RR complex. Comparative transcriptomics showed that RZ addition significantly upregulated the expression of omcE, periplasmic cytochrome gene ppcB, and outer-membrane genes omaB, ombB and omcB, thus, it was hypothesized that OmcE-bound RR might serve as potential electron acceptor of OmbB-OmaB-OmcB porin complex which passes electrons across outer membrane. Our work demonstrated a new pathway of artificial electron mediators in facilitating EET in Geobacter species, which may guide the application of electron mediator in improving the performance of BESs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The influence of the stroma on cancer progression has been underestimated, particularly the role of vascular pericytes in the tumor microenvironment. Herein, we identified 51 differentially expressed genes in tumor-derived pericytes (TPCs) by analyzing transcriptomic data from TCGA alongside our proteomic data. Using five key TPC-related genes, we constructed a prognostic risk model that accurately predicts prognosis and treatment responses in liver and lung cancers. Enrichment analyses linked these genes to blood vessel remodeling, function, and immune-related pathways. Single-cell RNA sequencing data from the GEO database validated these findings, showing significant upregulation of AKAP12 and RRAS in TPCs. Immunostaining confirmed increased expression of these genes in liver and lung tumors. Depletion of RRAS or AKAP12 in TPCs restored their blood vessel-supporting role. Overall, our findings suggest that TPC-related gene profiles can predict patient outcomes and therapeutic responses in solid cancers, and targeting these profiles could be an improved treatment strategy., Competing Interests: Declaration of competing interest None of the authors has a conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The synuclein alpha ( SNCA ) gene responsible for encoding alpha-synuclein, is believed to play a crucial role in the pathogenesis of Parkinson's disease (PD). However, the specific impact of SNCA gene single-nucleotide polymorphisms (SNPs) on brain function in PD remains unclear. Therefore, this cross-sectional retrospective study, particularly through use of imaging analysis, aimed to characterize the relationship between SNCA gene SNPs and spontaneous brain activity in PD in order to enhance our understanding of the mechanisms underlying PD pathogenesis., Methods: A total of 63 patients with PD and 73 sex- and age-matched healthy control (HC) participants were recruited from outpatient and inpatient clinics at Fujian Medical University Union Hospital from August 2017 to November 2019, and all underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scanning. All participants were also examined to determine the correlation of different genotypes with regional brain activity measured by rs-fMRI using amplitude of low-frequency fluctuation (ALFF) analysis. Multivariate regression analysis was used to calculate the correlation between the brain function data and clinical features. All rs-fMRI data were analyzed with the SPM12 software and adjusted according to the false discovery rate (FDR) at the cluster level., Results: This study included 63 patients with PD and 73 sex- and age-matched healthy participants were included in the study. The spontaneous brain activity in the right superior cerebellum (Cerebelum&#95;Crus1&#95;R), vermis (Vermis&#95;7), and left supplementary motor area (Supp&#95;Motor&#95;Area&#95;L) of patients in the PD group was weak compared to that in the HC group. The z-score ALFF of left central posterior gyrus was positively correlated with the Mini-Mental State Examination score (r=0.542; P<0.001) in the PD group. For rs11931074, the main genotypic effects were found in the left inferior cerebellum (Cerebellum&#95;9&#95;L) and right anterior cingulate and paracingulate gyri (Cingulum&#95;Ant&#95;R); for rs356219 and rs356165, the main genotypic effects were found in the left caudate nucleus (Caudate&#95;L). An interaction effect of disease with genotype was found in the right inferior parietal gyrus (Parietal&#95;Inf&#95;R) only for rs356219., Conclusions: Our study found a correlation of the SNCA SNPs rs11931074, rs356219, and rs356165 with brain functional alterations in patients with PD. Furthermore, an interaction effect was found in the right inferior parietal gyrus only for rs356219. This study may contribute to furthering the understanding of the influence of SNCA gene SNPs on brain function in patients with PD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-14/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aim: The relationship between the gut microbiota, metabolites and body fat percentage (BFP) remains unexplored. We systematically assessed the causal relationships between gut microbiota, metabolites and BFP using Mendelian randomization analysis., Materials and Methods: Single nucleotide polymorphisms associated with gut microbiota, blood metabolites and BFP were screened via a genome-wide association study enrolling individuals of European descent. Summary data from genome-wide association studies were extracted from the MiBioGen consortium and the UK Biobank. The inverse variance-weighted model was the primary method used to estimate these causal relationships. Sensitivity analyses were performed using pleiotropy, Mendelian randomization-Egger regression, heterogeneity tests and leave-one-out tests., Results: In the aspect of phyla, classes, orders, families and genera, we observed that o&#95;Bifidobacteriales [β = -0.05; 95% confidence interval (CI): -0.07 to -0.03; false discovery rate (FDR) = 2.76 × 10 -3 ], f&#95;Bifidobacteriaceae (β = -0.05; 95% CI: -0.07 to -0.07; FDR = 2.76 × 10 -3 ), p&#95;Actinobacteria (β = -0.06; 95% CI: -0.09 to -0.03; FDR = 6.36 × 10 -3 ), c&#95;Actinobacteria (β = -0.05; 95% CI: -0.08 to -0.02; FDR = 1.06 × 10 -2 ), g&#95;Bifidobacterium (β = -0.05; 95% CI: -0.07 to -0.02; FDR = 1.85 × 10 -2 ), g&#95;Ruminiclostridium9 (β = -0.03; 95% CI: -0.06 to -0.01; FDR = 4.81 × 10 -2 ) were negatively associated with BFP. G&#95;Olsenella (β = 0.02; 95% CI: 0.01-0.03; FDR = 2.16 × 10 -2 ) was positively associated with BFP. Among the gut microbiotas, f&#95;Bifidobacteriales, o&#95;Bifidobacteriales, c&#95;Actinobacteria and p&#95;Actinobacteria were shown to be significantly associated with BFP in the validated dataset. In the aspect of metabolites, we only observed that valine (β = 0.77; 95% CI: 0.5-1.04; FDR = 8.65 × 10 -6 ) was associated with BFP., Conclusions: Multiple gut microbiota and metabolites were strongly associated with an increased BFP. Further studies are required to elucidate the mechanisms underlying this putative causality. In addition, BFP, a key indicator of obesity, suggests that obesity-related interventions can be developed from gut microbiota and metabolite perspectives., (© 2024 John Wiley & Sons Ltd.)

Background: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care., Objective: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants., Design: Cluster-randomized controlled trial., Setting(s) and Participants: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China., Methods: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated., Results: The length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451-0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity., Conclusions: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment., Registration: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) aggregation and neuroinflammation, leading to progressive synaptic loss and cognitive decline. Recent evidence suggests that Galectin-3 (Gal-3) plays a critical role in Aβ pathogenesis. However, strategies to simultaneously target Gal-3 and Aβ are currently insufficient. This study evaluates the therapeutic efficacy of (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one (D30), in reducing Gal-3 and Aβ pathogenesis., Materials and Methods: We applied exogenous oligomeric Aβ and used 5 × FAD mice to assess the impact of Aβ on Gal-3 deposition, microglial activation, and cognitive function. Thy1-EGFP mice were employed to observe dendritic spines. Comprehensive evaluations of D30's effects included behavioral studies, transcriptomic analysis, Western blotting, and immunofluorescent staining. The interaction between D30 and Gal-3 was examined using fluorescence resonance energy transfer (FRET) and microscale thermophoresis (MST)., Key Findings: D30 effectively reduced Aβ monomer production by inhibiting Amyloid Precursor Protein (APP) and presenilin 1 (PS1) expression, and decreased Aβ aggregation. Treatment with D30 improved cognitive functions, reversed dendritic spine loss, and increased PSD95 expression in 5 × FAD mice. Additionally, D30 significantly lowered Gal-3 levels in both plasma and hippocampal tissues. D30 binds to Gal-3 and disrupts the interaction between Gal-3 and TREM2, as confirmed by FRET and MST., Significance: Our findings underscore the interaction between Gal-3 and Aβ in AD and its role in systemic inflammation using the 5 × FAD mouse model. Being able to target and regulate Gal-3 together with Aβ is crucial for preventing neuroinflammation and protecting synapses, D30 emerged as a novel compound with promising potential for AD treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Antimicrobial peptides (AMPs) offer a potential solution to the antibiotic crisis owing to their antimicrobial properties, and the human gut biome may be a source of these peptides. However, the potential AMPs and AMP resistance genes (AMPRGs) of gut microbes in different age groups have not been thoroughly assessed. Here, we investigated the potential development of AMPs and the distribution pattern of AMPRGs in the gut microbiome at different ages by analyzing the intestinal metagenomic data of healthy individuals at different life stages (CG: centenarians group n = 20; OAG: older adults group: n = 15; YG: young group: n = 15). Age-related increases were observed in the potential AMPs within the gut microbiome, with centenarians showing a greater diversity of these peptides. However, the gut microbiome of the CG group had a lower level of AMPRGs compared to that of the OAG group, and it was similar to the level found in the YG group. Additionally, conventional probiotic strains showed a significant positive correlation with certain potential AMPs and were associated with a lower detection of resistance genes. Furthermore, comparing potential AMPs with existing libraries revealed limited similarity, indicating that current machine learning models can identify novel peptides in the gut microbiota. These results indicate that longevity may benefit from the diversity of AMPs and lower resistance genes. Our findings help explain the age advantage of the centenarians and identify the potential for antimicrobial peptide biosynthesis in the human gut microbiome, offering insights into the development of antimicrobial peptide resistance and the screening of probiotic strains., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Multiple sclerosis (MS) and Cerebral Small Vessel Disease (CSVD) exhibit some similarities in Magnetic resonance imaging (MRI), potentially leading to misdiagnosis and delaying effective treatment windows. It is unclear whether CSVD can be detected with Paramagnetic Rim Lesions (PRL), which is special in MS., Objective: We aimed to investigate whether PRL can serve as a neuroimaging marker for discriminating between MS and CSVD., Methods: In this retrospective study, 49 MS and 104 CSVD patients underwent 3.0 T Magnetic resonance imaging (MRI). Visual assessment of 37 MS patients and 89 CSVD patients with or without lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH), central vein sign (CVS), and PRL. The distribution and number of PRL were then counted., Results: Our study found that PRL was detected in over half of the MS patients but was entirely absent in CSVD patients (78.38 vs. 0%, p  < 0.0001), and PRL showed high specificity with good sensitivity in discriminating between MS and CSVD (sensitivity: 78.38%, specificity: 100%, AUC: 0.96)., Conclusion: Paramagnetic Rim Lesions is a special imaging feature in MS, absent in CSVD. Detection of PRL can be very helpful in the clinical management of MS and CSVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Zhang, Li, Guo, Chen, Chen, Li, Wang, Chen and Fu.)

Alzheimer's disease (AD) starts decades before cognitive symptoms develop. Easily accessible and cost-effective biomarkers that accurately reflect AD pathology are essential for both monitoring and therapeutics of AD. Neurofilament light chain (NfL) levels in blood and cerebrospinal fluid are increased in AD more than a decade before the expected onset, thus providing one of the most promising blood biomarkers for monitoring of AD. The clinical practice of employing single-molecule array (Simoa) technology for routine use in patient care is limited by the high costs. Herein, we developed a microarray chip-based high-throughput screening method and screened an attractive self-assembling peptide targeting NfL. Through directly "imprinting" and further analyzing the sequences, morphology, and affinity of the identified self-assembling peptides, the Pep-NfL peptide nanosheet with high binding affinity toward NfL ( K D = 1.39 × 10 -9 mol/L), high specificity, and low cost was characterized. The superior binding ability of Pep-NfL was confirmed in AD mouse models and cell lines. In the clinical setting, the Pep-NfL peptide nanosheets hold great potential for discriminating between patients with AD ( P < 0.001, n = 37), mild cognitive impairment ( P < 0.05, n = 26), and control groups ( n = 30). This work provides a high-throughput, high-sensitivity, and economical system for noninvasive tracking of AD to monitor neurodegeneration at different stages of disease. The obtained Pep-NfL peptide nanosheet may be useful for assessing dynamic changes in plasma NfL concentrations to evaluate disease-modifying therapies as a surrogate end point of neurodegeneration in clinical trials.

Background: Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC)., Methods: We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines., Results: PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells., Conclusion: Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Breast milk is vital for the growth and development of preterm infants. However, in Neonatal Intensive Care Units (NICUs), mothers often encounter significant challenges in breastfeeding. Objective: This study aims to systematically evaluate the barriers to breastfeeding in NICUs, thereby providing evidence-based support for clinical practices. Methods: A comprehensive search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, up to September 2023. Meta-analysis was performed using Stata 15.0, applying fixed or random effects models to calculate odds ratios (OR) and their 95% confidence intervals (CI). Study quality was assessed using the Newcastle-Ottawa Scale for cases and cohorts and the Agency for Healthcare Research and Quality standards for cross-sectional studies. Heterogeneity was evaluated using Cochran's chi-squared test (Cochran's Q) and I 2 statistics, and publication bias was assessed through funnel plots and symmetry tests. Results: A total of 32 studies were included, encompassing 96,053 preterm infants. The main barriers to breastfeeding in preterm infants included: low gestational age (OR = 1.36, 95% CI: 1.06-1.75), lower maternal education (OR = 1.64, 95% CI: 1.39-1.93), insufficient breast milk (OR = 2.09, 95% CI: 1.39-1.93), multiple births (OR = 1.615, 95% CI: 1.18-2.210), smoking (OR = 2.906, 95% CI: 2.239-3.771), and single motherhood (OR = 1.439, 95% CI: 1.251-1.654). Conclusion: This study underscores the need for individualized breastfeeding support strategies in NICUs, taking into account the diverse backgrounds of mothers. Future research should focus on unraveling the underlying mechanisms affecting breastfeeding in preterm infants, with the goal of enhancing breastfeeding rates and improving developmental outcomes.

Long-lived individuals have been extensively studied as a model to investigate the role of the gut microbiota in aging, but their gut fungi remain almost unexplored. Here, we recruited a community-dwelling cohort of 251 participants (24-108 years, including 47 centenarians) from Guangxi in China to characterize the gut mycobiome signatures. We found gut mycobiome markedly varied during aging and determined aging as a predominant factor driving these variations. For long-lived individuals, core taxa, including Penicillium and Aspergillus , were maintained and Candida enterotype was enriched when compared with old counterparts. Individuals with this enterotype were more likely to possess Bacteroides enterotype enriched in young and centenarians. Moreover, the drivers from Candida enterotype were positively linked with the bacteria components dominated in Bacteroides enterotype. We also identified potentially beneficial yeasts-enriched features to differentiate long-lived individuals from others. Our findings suggest that the gut mycobiome develops with aging, and long-lived individuals possess unique fungal signatures., Competing Interests: The authors declare no competing interests in this paper., (© 2024 The Author(s).)

Introduction: The emergence of multidrug-resistant Klebsiella pneumoniae ( K. pneumoniae ) and the decline of effective antibiotics lead to the urgent need for new antibacterial agents. The aim of this study is to investigate the therapeutic effect of antimicrobial peptides against gentamicin-resistant (RT) K. pneumoniae and to screen effective antimicrobial peptides., Methods: In this study, the RT strains were induced by gradient gentamicin, and the RT strains were selected by detecting the expression levels of efflux pump genes, porin genes, and biofilm formation genes of the strains combined with their effects on the cells. Then the effects of four antimicrobial peptides on the efflux pump activity, biofilm formation level and cell condition after infection were detected to explore the effects of antimicrobial peptides on RT strains. Finally, the RT strain was used to induce a mouse model of pneumonia, and the four antimicrobial peptides were used to treat pneumonia mice for in vivo experiments. The pathological changes in lung tissues in each group were detected to explore the antimicrobial peptide with the most significant effect on the RT strain in vivo., Results: The results showed that the minimal inhibitory concentrations of the RT strains (strain C and strain I) were significantly higher than those of the wild-type strain, and the expression of efflux pump, porin and biofilm formation genes was significantly increased. The antimicrobial peptides could effectively inhibit the biofilm formation and efflux pump protein function of the RT strains. In addition, the antimicrobial peptides showed promising antibacterial effects both in vitro and in vivo ., Discussion: Our study provided a theoretical basis for the treatment of gentamicin resistant K. pneumoniae infection with antimicrobial peptides, and found that KLA was significantly superior to LL37, Magainin I, KLA and Dermaseptin (10 μg/mL in cells, 50 μg in mice)., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chen et al.)

Background: The relationship between inflammatory dietary patterns and the risk of depression/anxiety has not been clearly established due to differences in study populations, geographic regions, sex, and methods of calculating the inflammatory index., Methods: We drew upon a prospective cohort in the UK Biobank and calculated the energy-adjusted dietary inflammatory index (E-DII). The follow-up time was defined from the date of completing the last dietary survey questionnaire to the date of diagnosis of depression, anxiety, phobic anxiety, other types of anxiety, death, loss to follow-up, or the respective censoring dates for England (September 30, 2021), Scotland (July 31, 2021), and Wales (February 28, 2018). The final follow-up times end on September 30, 2021, July 31, 2021, and February 28, 2018, for England, Scotland, and Wales, respectively. During the follow-up process, if a participant develops the condition, dies, or is lost to follow-up, the follow-up is terminated. We used Cox regression to evaluate the connection between E-DII and depression/anxiety. We employed restricted cubic spline curves for nonlinear relationships. We also conducted mediation analyses to explore whether biological age mediated the relationship between E-DII and depression. Additionally, we investigated whether genetic susceptibility modified the relationship between E-DII and depression through interaction modeling., Results: In the final analysis, we included a total of 151,295, 159,695, 165,649, and 160,097 participants for the analysis of depression, all types of anxiety, specific phobia anxiety, and other types of anxiety, respectively. For every one-unit increase in E-DII, the risk of experiencing depression and anxiety increased by 5 % and 4 %, respectively. We identified a "J"-shaped nonlinear relationship (P for nonlinear = 0.003) for both depression and anxiety. A significant association with an elevated risk of depression was observed when E-DII exceeded 0.440, and an increased risk of anxiety was noted when E-DII was more than -0.196. Mediation analysis demonstrated that PhenoAge age acceleration (AA) (For depression, proportion of mediation = 9.6 %; For anxiety, proportion of mediation = 10.1 %) and Klemera-Doubal method Biological Age (KDM AA) (For depression, proportion of mediation = 2.9 %; For anxiety, proportion of mediation = 5.1 %) acted as mediators between E-DII and the development of depression and anxiety (P < 0.05)., Conclusions: Diets with pro-inflammatory characteristics are associated with a heightened risk of depression and anxiety. Furthermore, the association of pro-inflammatory diets and depression is mediated by biological age., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dyes pollution is well known for their hazardous impacts on human health and the environment. The removal of dyes from wastewater has become an important issue. In this study, magnetic micrometer-sized particles AL-CTS@MNPs were synthesized from alkaline lignin (AL) and chitosan (CTS) by "one-pot method". The adsorbent presented higher selectivity adsorption effect on anionic dyes than amphoteric and cationic dyes, and even no adsorption effect on cationic methylene blue (MB), which showed that the anionic dyes could be better separated from the other two types of dyes. The adsorption isotherms of the dyes were highly consistent with the Langmuir model, and the maximum adsorption capacity was 329.50 mg/g for methyl orange (MO) and 20.00 mg/g for rhodamine B (RhB). AL-CTS@MNPs showed good adsorption of anionic dyes (MO) in the pH range of 3-9. Meanwhile, the adsorbent AL-CTS@MNPs were also characterized, showing rough surface with specific surface areas of 37.38 m 2 /g, pore diameter of 95.8 nm and porosity of 17.62 %. The particle sizes were ranged from 800 μm to 1300 μm. The electrostatic attraction and π-π* electron donor-acceptor interactions were the main forces between the adsorbent and anionic dyes. While the electrostatic repulsive force between the adsorbent and the cationic dyes resulted in the non-absorption of MB by AL-CTS@MNPs. Subsequently, the adsorbent maintained a removal rate of >95 % after five adsorption-desorption cycles, demonstrating its excellent stability and recoverability. Ultimately, the prepared AL-CTS@MNPs illuminated good prospect on complex components dyes wastewater treatment., Competing Interests: Declaration of competing interest The authors declare no competing financial interest. The co-authors have reviewed the manuscript and approved it for submission to this journal for consideration., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Prodromal Parkinson's disease (PD) carriers of dual leucine-rich repeat kinase 2 (LRRK2) and glucosylceramidase β (GBA) variants are rare, and their biomarkers are less well developed., Objective: This study aimed to investigate the biomarkers for diagnosing the prodromal phase of LRRK2-GBA-PD (LRRK2-GBA-prodromal)., Methods: We assessed the clinical and whole-brain white matter microstructural characteristics of 54 prodromal PD carriers of dual LRRK2 (100% M239T) and GBA (95% N409S) variants, along with 76 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort., Results: By analyzing the four values of 100 nodes on 20 fiber bundles, totaling 8000 data points, we identified the smallest p value in the fractional anisotropy (FA) value of the 38th segment of left corticospinal tract (L-CST) with differences between LRRK2-GBA-prodromal and HCs (p = 8.94 × 10 -9 ). The FA value of the 38th node of the L-CST was significantly lower in LRRK2-GBA-prodromal (FA value, 0.65) compared with HCs (FA value, 0.71). The receiver-operating characteristic curve showed a cut-off value of 0.218 for the FA value of L-CST, providing sufficient sensitivity (79.2%) and specificity (72.2%) to distinguish double mutation prodromal PD from the healthy population., Conclusion: L-CST, especially the 38th node, may potentially serve as a biomarker for distinguishing individuals with double mutation prodromal PD from the healthy population., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Bacterial adhesion plays a vital role in forming and shaping the structure of electroactive biofilms that are essential for the performance of bioelectrochemical systems (BESs). Type IV pili are known to mediate cell adhesion in many Gram-negative bacteria, but the mechanism of pili-mediated cell adhesion of Geobacter species on anode surface remains unclear. Herein, a minor pilin PilV2 was found to be essential for cell adhesion ability of Geobacter sulfurreducens since the lack of pilV2 gene depressed the cell adhesion capability by 81.2% in microplate and the anodic biofilm density by 23.1 % at -0.1 V and 37.7 % at -0.3 V in BESs. The less cohesiveness of mutant biofilms increased the charge transfer resistance and biofilm resistance, which correspondingly lowered current generation of the pilV2-deficient strain by up to 63.2 % compared with that of the wild-type strain in BESs. The deletion of pilV2 posed an insignificant effect on the production of extracellular polysaccharides, pili, extracellular cytochromes and electron shuttles that are involved in biofilm formation or extracellular electron transfer (EET) process. This study demonstrated the significance of pilV2 gene in cell adhesion and biofilm formation of G. sulfurreducens, as well as the importance of pili-mediated adhesion for EET of electroactive biofilm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: To document the prevalence of skin problems associated with insulin pump use and identify contributing factors among children with type 1 diabetes mellitus in China., Methods: In total, 461 children were recruited from an online community (i.e., a Wechat group) of pediatric patients with T1DM. A self-developed questionnaire was filled in by parents, collecting the information on social demographics, disease, and insulin pump therapy related characteristics and skin problems. We applied the Mann-Whitney U test, Chi square test and logistic regression analysis to identify the factors associated with skin problems., Results: Of the 461 responders, 308 (66.8 %) children were reported to have skin problems. More specifically, 38.8 % had pigmentation changes, 22.3 % allergy/dermatitis, 20.2 % scaring, 11.5 % pain, 10.8 % infection, 10.6 % subcutaneous lipohypertrophy, and 6.1 % lipoatrophy. Logistic regression analysis showed that independent associated factors of skin problems were the caregiver's educational level as college or above, patient having skin allergies, and using the Brand 2 insulin pump (p values < 0.05)., Conclusions: The present study documents the prevalence of skin problems and identifies associated factors, such as caregiver's education, patients skin allergies, and using a specific brand of pump. Health education should address these factors in addition to the traditionally emphasized factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Increasing evidence suggests an association between exercise duration and Parkinson's disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson's risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson's risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson's disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson's risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson's disease. In a multifactorial Cox model, using the World Health Organization-recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43-0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34-0.57; P < 0.001) exhibited a lower risk of developing Parkinson's disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56-1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson's risk., (© 2024. The Author(s).)

Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1β, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK-ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products., (© 2023 American Society for Photobiology.)

Cognitive deterioration and memory decline associated with the progression of Alzheimer's disease (AD) primarily results from synaptic failure. However, current understanding of the upstream regulatory mechanisms controlling synaptic plasticity remains limited. Salt-inducible kinase 3 (SIK3) is central to the signal pathway and is involved in neuronal regulation of sleep duration in mice. We speculated that the SIK3 cascade signaling pathway might contribute to the pathogenesis of AD. Thus, the present study employed AD transgenic mouse models, Morris Water Maze, virus-mediated gene transfer, electrophysiology, co-immunoprecipitation, western blotting, quantitative polymerase chain reaction, immunofluorescence, ChIP-qPCR, Golgi-Cox staining and dendritic spine analysis to investigate this connection. Our results revealed that SIK3 mRNA/protein expression was significantly reduced in middle-aged AD transgenic mouse models and AD patients. Conditional deletion of SIK3 gene in dorsal hippocampal neurons of 5×FAD mice further accelerated cognitive deterioration and impaired synaptic plasticity. In hippocampal neuronal cultures, SIK3 formed a complex with HDAC4, directly phosphorylated HDAC4 and regulated its nuclear cytoplasmic shuttle. Overexpression of SIK3 could facilitate the expression of synaptic plasticity-related genes by directly repressing mef2c or involving the recruitment of histone deacetylase to promoter regions of target genes through regulation of p-HDAC4, and vice versa. Moreover, up-regulation of SLP-S, the truncated fragment of SIK3, in dorsal hippocampal neurons, restored the synaptic plasticity and alleviates the cognitive impairment in 5×FAD mice. Collectively, these findings revealed a novel and important role of SIK3-HDAC4 regulation of synaptic plasticity and propose a new target for therapeutic approaches of cognitive deficits associated with AD., (© 2023. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants., Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088)., Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0-15.0] vs. 15.0 days [14.0-15.0], P  = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred., Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies., Funding: Fujian Akeylink Biotechnology Co., Ltd., Competing Interests: GZ, JM, TZ, YT, WenhY, XY, and HT are employees and GZ, JM, TZ, YT, HT, FH, HongmL, and GL are shareholders of Fujian Akeylink Biotechnology, Co., Ltd. FH, ZH, HongmL, and GL are employees and shareholders of Fujian Cosunter Pharmaceutical Co., Ltd. ZW, XiaC, ML, XT, and ZhuL from Tigermed and HF from Zenith Medical Research provided paid expert service and received consulting fees from Fujian Akeylink Biotechnology. All other authors declare no competing interests., (© 2024 The Author(s).)

Background: As a rare neurodegenerative disease, sporadic Creutzfeldt-Jakob disease (sCJD) is poorly understood in the elderly populace. This study aims to enunciate the multidimensional features of sCJD in this group., Methods: A case of probable sCJD was reported in a 90-year-old Chinese man with initial dizziness. Then, available English literature of the elderly sCJD cases (aged 80 years and over) was reviewed and analyzed. Patients (15 cases) were subdivided and compared geographically., Results: In the elderly sCJD cohort, the onset age was 84.9 ± 4.5 years and the median disease duration was 6.8 months, with respiratory infection/failure as the commonest death cause. Various clinical symptoms were identified, with cognitive disorder (86.7%) as the commonest typical symptom and speech impairment (66.7%) as the most atypical one. Restricted hyperintensities were reported in 60.0% cases on DWI, periodic sharp wave complexes in 73.3% cases on electroencephalogram, and cerebral hypoperfusion/hypometabolism in 26.7% cases on molecular imaging. The sensitive cerebrospinal fluid biomarkers were total tau (83.3%), 14-3-3 protein (75.0%), and PrP RT-QuIC (75.0%). Neuropathological profiles in the cerebral cortex revealed vacuolar spongiosis, neuronal loss, gliosis, and aging-related markers, with synaptic deposit as the commonest PrP pattern (60.0%). The polymorphic PRNP analysis at codon 129 was M/M (90.9%), with MM1 and MM2C as the primary molecular phenotypes. Latency to first clinic visit, hyperintense signals on DWI, and disease duration were significantly different between the patient subgroups., Conclusion: The characteristics of sCJD are multidimensional in the elderly, deepening our understanding of the disease and facilitating an earlier recognition and better care for this group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liao, Hu, Chen, Huang, Dong, Chen, Chen and Chen.)

Amyloid-beta (Aβ) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Aβ phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aβ phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Aβ phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aβ pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: LHPP was recently shown to be a risk gene for major depressive disorder. LHPP has been proven to dephosphorylate the residues of histidine, serine, threonine, and tyrosine. However, much remains unknown about how LHPP contributes to depression., Methods: In the current study, we addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing, and electrophysiology., Results: We found that levels of LHPP were upregulated in glutamatergic neurons of the ventral hippocampus in mice that displayed stress-induced depression-like behaviors. Knockout of LHPP in glutamatergic neurons of the brain improved the spontaneous activity of LHPP flox/flox ·CaMKIIαCre+ (conditional knockout) mice. Adeno-associated virus-mediated LHPP knockdown in the ventral hippocampus enhanced resistance against chronic social defeat stress in mice. Manipulations of LHPP levels impacted the density of dendritic spines and excitability of CA1 pyramidal neurons by mediating the expressions of BDNF (brain-derived neurotrophic factor) and PSD95 via the modulation of the dephosphorylation of CaMKIIα and ERK. Notably, compared with wild-type LHPP, human mutant LHPP (E56K, S57L) significantly increased the activity of the CaMKIIα/ERK-BDNF/PSD95 signaling pathway. Finally, esketamine, not fluoxetine, markedly alleviated the LHPP upregulation-induced depression-like behaviors., Conclusions: These findings provide evidence that LHPP contributes to the pathogenesis of depression via threonine and serine hydrolases, thereby identifying LHPP as a potential therapeutic target in treating patients with major depressive disorder., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Ethylene oxide (EO) is a commonly used compound with known health risks. However, the specific association between EO exposure and the development of depressive symptoms has not been well established. Therefore, this study aimed to examine the potential association between EO exposure, as indicated by hemoglobin adduct of ethylene oxide (HbEO) levels, and the occurrence of depressive symptoms., Methods: We employed logistic regression, restricted cubic spline, and subgroup analysis to investigate the association between EO exposure and the occurrence of depressive symptoms. Additionally, we conducted a mediating effect analysis to explore the potential factors influencing the association between EO exposure and depressive symptoms., Results: Elevated HbEO levels were associated with the development of depressive symptoms. After adjusting for potential confounders, the highest quartile of HbEO levels showed an odds ratio (OR) of 3.37 [95 % confidence interval (CI): 1.87-6.10, P = 0.002] compared with the lowest quartile. Additionally, a linear association was observed between HbEO levels and the risk of depressive symptoms. We also revealed that the levels of several inflammatory factors and triglycerides mediated the association between EO exposure and the occurrence of depressive symptoms., Conclusions: Higher levels of EO exposure were related to an increased risk of developing depressive symptoms. The analysis also suggested that the inflammatory response might play a mediating role in the pathway from EO exposure to depressive symptoms., Competing Interests: Declaration of competing interest All authors declare that there are no additional disclosures and conflicts of interest to report., (Copyright © 2023. Published by Elsevier B.V.)

Background: Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson's disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively., Methods: The study consisted of three parts: a case-control study, a cross-sectional study, and a longitudinal cohort study. The case-control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression., Results: In the case-control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p  = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p  = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: β  = -5.42, p  < 0.001, interaction p time × genotype  < 0.001) and non-motor symptoms (NMSS score: β  = -4.78, p  = 0.030, interaction p time × genotype  < 0.001)., Conclusion: Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Zeng, Wang, Chen, Cai, Chen, Wang, Ye and Chen.)

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS., Methods and Materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed us to pinpoint research hotspots and create visual representations, resulting in the retrieval of 2489 pertinent articles., Results: This literature review covers 2489 articles on uterine leiomyosarcoma (uLMS) from the past 20 years. Key findings include an average annual publication rate of 8.75, with a 6.07% yearly growth rate and an average citation count of 17.22. Core+Zone 2 sources contributed 1079 articles and 207 reviews, displaying a 4.98% annual growth rate. The analysis identified top journals, influential authors, and core sources, such as the prevalence of publications from the United States and the dominance of GYNECOLOGIC ONCOLOGY and HENSLEY ML . Bradford's Law and Lotka's Law highlighted core sources and author productivity, respectively. Thematic mapping and factorial analysis revealed research clusters, including etiology, diagnosis, treatment advancements, and surgical approaches, with prominent themes such as gemcitabine and docetaxel. Overall, this comprehensive analysis provides insights into uLMS literature trends and influential factors., Conclusion: This thorough bibliometric analysis, in its whole, illuminates the field's guiding principles while also revealing the subtle patterns within the uLMS literature. The knowledge gained here contributes to the current discussion in uLMS and related scientific fields and provides a solid basis for future research paths., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Chen, Li, Chen, Huang, Zhu, Han, Zheng, Chen and Yu.)

Alzheimer's disease (AD) is a common cause of dementia, characterised by cerebral amyloid-β deposition, pathological tau and neurodegeneration. The prodromal stage of AD (pAD) refers to patients with mild cognitive impairment (MCI) and evidence of AD's pathology. At this stage, disease-modifying interventions should be used to prevent the progression to dementia. Given the inherent heterogeneity of MCI, more specific biomarkers are needed to elucidate the underlying AD's pathology. Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology, their clinical applications are limited by their high costs and invasiveness, particularly in low-income areas in China. Therefore, to improve the early detection of Alzheimer's disease (AD) pathology through cost-effective screening methods, a panel of 45 neurologists, psychiatrists and gerontologists was invited to establish a formal consensus on the screening of pAD in China. The supportive evidence and grades of recommendations are based on a systematic literature review and focus group discussion. National meetings were held to allow participants to review, vote and provide their expert opinions to reach a consensus. A majority (two-thirds) decision was used for questions for which consensus could not be reached. Recommended screening methods are presented in this publication, including neuropsychological assessment, peripheral biomarkers and brain imaging. In addition, a general workflow for screening pAD in China is established, which will help clinicians identify individuals at high risk and determine therapeutic targets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Evidence on the individual and combined relationship of physical activity (PA) and fish oil supplement use on the incidence of Parkinson's disease (PD) risk remains lacking., Materials and Methods: This UK population-based prospective cohort study, involving 385,275 UK Biobank participants, collected PA and fish oil supplement data via touchscreen questionnaires. Using Cox proportional hazards models and restricted cubic splines to examined the associations between use of fish oil supplements, PA and PD risk., Results: During a median 12.52-year follow-up, 2,131 participants incident PD. Analysis showed that fish oil supplement users had a lower PD risk [hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.82-0.98]. The adjusted HRs for the PD incidence were 0.96 (95% CI, 0.95-0.98) for total PA; 0.93 (95% CI, 0.90-0.96) for moderate PA; 0.95 (95% CI, 0.91-0.99) for vigorous PA and 0.93 (95% CI, 0.89-0.98) for walking activity. Significant interactions were found between fish oil supplement use and total PA ( P for interaction = 0.011), moderate PA ( P for interaction = 0.015), and walking activity ( P for interaction = 0.029) in relation to PD incidence., Conclusion: Both fish oil supplement use and PA were associated with a reduced risk of PD, and the effect of PA in reducing the risk of PD was more pronounced when fish oil supplement was used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Shi, Zheng, Li, Chen, Zou, Hong, Chen, Zeng, Ye, Chen, Chen, Wang and Cai.)

This study aimed to evaluate the effects of diets supplemented with various levels of complex antioxidants ( CA ) containing tertiary butylhydroquinone ( TBHQ ) and tea polyphenols ( TP ) on growth performance, meat quality of breast and leg muscles, serum biochemistry, and antioxidant capacity of serum, liver, breast meat, jejunum, and ileum in broilers. A total of 600 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into three groups (10 replicates/group, 20 broilers/replicate). Birds in the three experimental groups were fed a basal diet with CA at 0, 300, and 500 mg/kg. The results showed that supplementing with 300 mg/kg CA significantly increased ( p < 0.05) 42 d BW and 22-42 d ADG, and markedly decreased ( p < 0.05) 22-42 d F: G ratio in comparison to the control group. Birds fed a diet with 300 mg/kg CA had a higher ( p < 0.05) pH of chicken meat at 24 h and 48 h post mortem and lower ( p < 0.05) yellowness values (b*) of chicken meat at 45 min and 24 h post mortem, along with a lower ( p < 0.05) cooking loss. Supplementing with 300 mg/kg CA significantly increased ( p < 0.05) serum and liver T-SOD activity, serum T-AOC level, as well as jejunual GST activity, and significantly decreased ( p < 0.05) liver MDA content when compared with the control group. These results indicate that diet supplementation with 300 mg/kg CA containing TBHQ and TP could improve growth performance and meat quality by increasing the antioxidant capacity of broilers.

Background: This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks)., Methods: The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum., Results: The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups., Conclusions: Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system., (© 2024. The Author(s).)

The clinical applications of the association of cortical thickness and white matter fiber with freezing of gait (FoG) are limited in patients with Parkinson's disease (PD). In this retrospective study, using white matter fiber from diffusion-weighted imaging and cortical thickness from structural-weighted imaging of magnetic resonance imaging, we investigated whether a machine learning-based model can help assess the risk of FoG at the individual level in patients with PD. Data from the Parkinson's Disease Progression Marker Initiative database were used as the discovery cohort, whereas those from the Fujian Medical University Union Hospital Parkinson's Disease database were used as the external validation cohort. Clinical variables, white matter fiber, and cortical thickness were selected by random forest regression. The selected features were used to train the support vector machine(SVM) learning models. The median area under the receiver operating characteristic curve (AUC) was calculated. Model performance was validated using the external validation cohort. In the discovery cohort, 25 patients with PD were defined as FoG converters (15 men, mean age 62.1 years), whereas 60 were defined as FoG nonconverters (38 men, mean age 58.5 years). In the external validation cohort, 18 patients with PD were defined as FoG converters (8 men, mean age 66.9 years), whereas 37 were defined as FoG nonconverters (21 men, mean age 65.1 years). In the discovery cohort, the model trained with clinical variables, cortical thickness, and white matter fiber exhibited better performance (AUC, 0.67-0.88). More importantly, SVM-radial kernel models trained using random over-sampling examples, incorporating white matter fiber, cortical thickness, and clinical variables exhibited better performance (AUC, 0.88). This model trained using the above mentioned features was successfully validated in an external validation cohort (AUC, 0.91). Furthermore, the following minimal feature sets that were used: fractional anisotropy value and mean diffusivity value for right thalamic radiation, age at baseline, and cortical thickness for left precentral gyrus and right dorsal posterior cingulate gyrus. Therefore, machine learning-based models using white matter fiber and cortical thickness can help predict the risk of FoG conversion at the individual level in patients with PD, with improved performance when combined with clinical variables., (© 2024. The Author(s).)

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease (AD) and associated socioeconomic burdens. Abnormal metabolism of amyloid-β (Aβ) has been proposed as a significant pathomechanism in AD, supported by results of recent clinical trials using anti-Aβ antibodies. Nonetheless, the cognitive benefits of the current treatments are limited. The etiology of AD is multifactorial, encompassing Aβ and tau accumulation, neuroinflammation, demyelination, vascular dysfunction, and comorbidities, which collectively lead to widespread neurodegeneration in the brain and cognitive impairment. Hence, solely removing Aβ from the brain may be insufficient to combat neurodegeneration and preserve cognition. To attain effective treatment for AD, it is necessary to (1) conduct extensive research on various mechanisms that cause neurodegeneration, including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level; (2) identify neuroprotective intervention targets against different neurodegeneration mechanisms; and (3) discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients. The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated, multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD. The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD, with the goal of halting or even reversing cognitive decline., Competing Interests: Xunming Ji, Johannes Boltze, and Piotr Walczak are the Editors‐in‐Chief, and Heleen van Beusekom, Andrew N. Clarkson, Paulo Henrique Rosado de Castro, Tracy D. Farr, Jukka Jolkkonen, Shen Li, Yajie Liang, Guiyou Liu, Xiaobo Mao, Joaquim Miguel Oliveira, Mike M. Modo, Pedro Ramos‐Cabrer, Karsten Ruscher, Yun Wang, Haitao Wu, Lize Xiong, Yi Yang, Marietta Zille, and Yan‐Jiang Wang are the editorial members, of Neuroprotection. They are therefore excluded from the peer‐review process and all editorial decisions related to the publication of this manuscript. The remaining authors declare no conflict of interest., (© 2023 The Authors. Neuroprotection published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

To further reform the medical and health care system, regulating multi-level treatment and rationalizing the use of medicine, and securing prescription circulation information, this study explores the evolutionary behavior of three players in terms of information security collaboration under the prescription circulation policy, analyzes the evolutionary paths, and examines the influence of key parameters on evolutionary outcomes by constructing a tripartite evolutionary game model consisting of hospitals, retail pharmacies, and healthcare service platforms. The study shows the following: (1) When the information security costs of prescription circulation increase, the willingness of hospitals to promote information collaboration weakens, the probability of control and regulation by healthcare platforms will be enhanced, and the incentive for retail pharmacies to undertake prescription circulation increases and then decreases. (2) The increased profitability of prescription drug sales can cause a decrease in the likelihood of both parties working together to promote information security. Increasing the collaborative space between hospitals and retail pharmacies is conducive to improving information security in the circulation of prescriptions. (3) A bi-directional constraint relationship exists between the circulation and control subjects. The shorter the technology spillover time from the healthcare service platform is, the higher the probability that hospitals and retail pharmacies will maintain the security of prescription information. (4) In the early stages of prescription circulation, the external regulatory action of the healthcare service platform is essential to improve the coordination of information security. Finally, combined with the tripartite evolutionary game model and simulation analysis results, it offers countermeasures and suggestions for the government to realize the prescription circulation information security collaboration.

CuFeS 2 is regarded as a promising catalyst for heterogeneous activation to remove organic contaminants in wastewater. However, effects of solvents in regulating material synthesis and catalytic activity are still not clear. Herein, we reported the role of water, ethanol, ethylene glycol (EG), glycerol, and polyethylene glycol 200 on the synthesis of CuFeS 2 micro-flowers and their performance in activating persulfate (PS) to remove imidacloprid (IMI) pesticide. The results showed that the solvent had an effect on the morphology, crystallinity, yields, specific surface areas and unpaired electrons of CuFeS 2 micro-flowers. The degradation experiments revealed the efficient catalytic activity of EG-mediated CuFeS 2 for heterogeneous PS activation. SO 4 •- and •OH were identified in EG-CuFeS 2 /PS system and •OH (90.4%) was the dominant reactive species. Meanwhile, stable 20% of η[PMSO 2 ] (the molar ratio of PMSO 2 generation to PMSO consumption) was achieved and demonstrated that Fe(IV) was also involved in the degradation process. Moreover, S 2- promoted the cycling of Fe 3+ /Fe 2+ and Cu 2+ /Cu + , enhancing the synergistic activation and reusability of the catalyst. Density functional theory (DFT) calculations verified that PS was adsorbed by Fe atom and electron transfer occurred on the catalyst surface. Three possible degradation pathways of IMI were proposed by analysis of the degradation intermediates and their toxicities were evaluated by ECOSAR. This study not only provides a theoretical foundation for catalyst design, but also promotes the industrial application of bimetallic sulfide Fenton-like catalysts for water management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although aging and apolipoprotein E (APOE) ε4 allele have been documented as two major risk factors for late-onset Alzheimer's disease (LOAD), their interaction and potential underlying mechanisms remain unelucidated. Using humanized ApoE4- and ApoE3- target replacement mice, we found the accumulation of senescent neurons and the activation of mTOR and endosome-lysosome-autophagy (ELA) system in the hippocampus of aged ApoE4 mice. Further analyses revealed that ApoE4 aggravated the profile change of hippocampal transcription and metabolism in an age-dependent manner, accompanying with an disruption of metabolism, which is presented with the downregulating activity of citrate synthase, the level of ATP and, most importantly, the level of acetyl coenzyme A (Ac-CoA); GTA supplement, an Ac-CoA substrate, reversed the senescent characteristics, decreased the activation of mTOR and ELA system, and enhanced the synaptic structure and increasing level of pre-/post-synaptic plasticity-related protein, leading to cognitive improvement in aged ApoE4 mice. These data suggest that ApoE4 exacerbates neuronal senescence due to a deficiency of acetyl-CoA, which can be ameliorated by GTA supplement. The findings provide novel insights into the potential therapeutic value of GTA supplement for the cognitive improvement in aged APOE4 carriers., (© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Purpose: To analyze the effect of different feeding types on bronchopulmonary dysplasia (BPD) in very low birth weight preterm infants. Methods: The Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Biomedical Literature Database (CBM) were searched for literature related to breastfeeding and BPD, with a search period from their inception to January 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of included studies before analyzing the data using Stata16 and RevMan5.4.1 software. Results: A total of 17 studies were included. The results showed that there was no significant difference in the frequency of BPD between human milk (HM) and donor human milk (DHM) (OR = 0.54, 95% CI: 0.29-1.03, p  = 0.07). However, DHM had a significant effect in reducing the frequency of BPD compared to preterm formula (PF) (OR = 0.62, 95% CI: 0.41-0.94, p  = 0.02). Exclusive HM also had a significant effect in reducing the frequency of BPD compared to exclusive PF (OR = 0.51, 95% CI: 0.34-0.78, p  = 0.002), as well as compared to any PF (OR = 0.57, 95% CI: 0.37-0.88, p  = 0.01). Furthermore, mainly (>50%) HM had a significant effect in reducing the frequency of BPD compared to mainly PF (OR = 0.72, 95% CI: 0.55-0.93, p  = 0.01). However, there was no statistically significant difference between any HM and exclusive PF (OR = 0.88, 95% CI: 0.62-1.23, p  = 0.46). Conclusions: Our study findings suggest that both HM and DHM have a significant protective effect in reducing the frequency of BPD occurrence compared to PF. Furthermore, even when the amount of HM is insufficient, feeding more than 50% of the HM volume still provides a protective effect against the frequency of BPD. Therefore, we recommend feeding infants with more than 50% of HM to harness the protective effect of HM against BPD occurrence.

Synucleinopathies refer to a range of neurodegenerative diseases caused by abnormal α-synuclein (α-Syn) deposition, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Their pathogenesis is strongly linked to microglial dysfunction and neuroinflammation, which involves the leucine-rich-repeat kinase 2 (LRRK2)-regulated nuclear factor of activated T-cells (NFAT). Of the NFAT family, NFATc1 has been found to be increasingly translocated into the nucleus in α-syn stimulation. However, the specific role of NFATc1-mediated intracellular signaling in PD remains elusive in regulating microglial functions. In the current study, we crossbred LRRK2 or NFATc1 conditional knockout mice with Lyz2 Cre mice to generate mice with microglia-specific deletion of LRRK2 or NFATc1, and by stereotactic injection of fibrillary α-Syn, we generated PD models in these mice. We found that LRRK2 deficiency enhanced microglial phagocytosis in the mice after α-Syn exposure and that genetic inhibition of NFATc1 markedly diminished phagocytosis and α-Syn elimination. We further demonstrated that LRRK2 negatively regulated NFATc1 in α-Syn-treated microglia, in which microglial LRRK2-deficiency facilitated NFATc1 nuclear translocation, CX3CR1 upregulation, and microglia migration. Additionally, NFATc1 translocation upregulated the expression of Rab7 and promoted the formation of late lysosomes, resulting in α-Syn degradation. In contrast, the microglial NFATc1 deficiency impaired CX3CR1 upregulation and the formation of Rab7-mediated late lysosomes. These findings highlight the critical role of NFATc1 in modulating microglial migration and phagocytosis, in which the LRRK2-NFATc1 signaling pathway regulates the expression of microglial CX3CR1 and endocytic degradative Rab7 to attenuate α-synuclein immunotoxicity., (© 2023 Wiley Periodicals LLC.)

Triggering receptor expressed on myeloid cells 2 (TREM2) is strongly linked to Alzheimer's disease (AD) risk, but its functions are not fully understood. Here, we found that TREM2 specifically attenuated the activation of classical complement cascade via high-affinity binding to its initiator C1q. In the human AD brains, the formation of TREM2-C1q complexes was detected, and the increased density of the complexes was associated with lower deposition of C3 but higher amounts of synaptic proteins. In mice expressing mutant human tau, Trem2 haploinsufficiency increased complement-mediated microglial engulfment of synapses and accelerated synaptic loss. Administration of a 41-amino-acid TREM2 peptide, which we identified to be responsible for TREM2 binding to C1q, rescued synaptic impairments in AD mouse models. We thus demonstrate a critical role for microglial TREM2 in restricting complement-mediated synaptic elimination during neurodegeneration, providing mechanistic insights into the protective roles of TREM2 against AD pathogenesis., Competing Interests: Declaration of interests X.-F.C., X.S., and L. Zhong are co-inventors on a patent application related to the work in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Genetic susceptibility plays a significant role in Parkinson's disease (PD) development. Carriers of the Parkin S/N167 mutation may have an increased risk of PD and altered spontaneous brain activity., Objective: This study aims to investigate the potential pathogenesis of PD through a comparative analysis of the amplitude of low-frequency fluctuations (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI) of subjects with Parkin gene S/N 167 polymorphisms, and to examine the association between spontaneous brain activity and clinical scale scores of PD., Methods: A total of 69 PD patients and 84 healthy controls (HC) were included in the study. Each subject was genotyped for the Parkin gene S/N 167 polymorphism and underwent rs-fMRI scans. ALFF analysis was employed to evaluate the relationship among genotypes, interactive brain regions, and clinical symptoms in PD., Results: PD patients exhibited decreased ALFF values in the right anterior lobe and vermis of the cerebellum compared to HC. No significant interaction was found between the gene's main effect and the "group × genotype" effect on brain ALFF values. One-factor ANOVA revealed no significant difference in ALFF values between PD subgroups; however, the ALFF values in the right anterior lobe and vermis of the cerebellum were lower in the PD-G and PD-GA groups compared to the HC-G and HC-GA groups. Spearman correlation analysis demonstrated that ALFF values in the PD-GG and PD-GA groups were negatively associated with UPDRS-III scores in the bilateral lingual gyrus (Lingual R/L)., Conclusion: Parkin gene S/N 167 polymorphisms may influence brain functional activity in specific brain regions, and ALFF values are associated with motor symptoms in PD patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest regarding the publication of this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To explore the influence of disease and genetic factors on the white matter microstructure in patients with PD. The white matter microstructural changes in the substantia nigra-striatum system were detected by diffusion tensor imaging (DTI) using the region of interest (ROI) and diffusion tensor tracer (DTT) methods., Methods: Patients with primary Parkinson's disease (PD) without a family history of PD were selected and divided into PD-G/G and PD-G/A groups according to their parkin S/N167 polymorphism. Control groups matched for age, sex, and gene type (G/G and G/A) were also included. Three-dimensional brain volume imaging (3D-BRAVO) and DTI were performed. The microstructural changes in the substantia nigra-striatum system were evaluated by the ROI and DTT methods. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hoehn-Yahr (H-Y) staging, and the third part of the Unified Parkinson's Disease Rating (UPDRS-III) scales evaluated the cognitive and motor function impairment in patients with PD. Independent samples t -test compared normally-distributed data, and the Wilcoxon rank sum test compared measurement or categorical non-normally distributed data. Multiple regression analysis was used to analyze the correlation between various DTI indicators and the MMSE, MoCA, UPDRS-III, and H-Y scores in the PD-G/G and PD-G/A groups. P  < 0.05 was considered statistically significant., Results: The white matter microstructural changes in the nigrostriatal pathway differed significantly between the PD or PD-G/A and the control group ( P  < 0.05)The ROI method showed that the left globus pallidus radial diffusivity (RD) value was negatively correlated with the MMSE score (r = -0.404, P  = 0.040), and the left substantia nigra (LSN) fractional anisotropy (FA) value was positively correlated with the MoCA score (r = 0.405, P  = 0.040) and negatively with the H-Y stage (r = -0.479, P  = 0.013).The DTT method showed that the MMSE score was positively correlated with the right substantia nigra (RSN) FA value (r = 0.592, P  = 0.001) and negatively with its RD value (r = -0.439, P  = 0.025). The H-Y grade was negatively correlated with the number of fibers in the RSN (r = -0.406, P  = 0.040). The UPDRS-Ⅲ score was positively correlated with the mean diffusivity (r = 0.420, P  = 0.033) and RD (r = 0.396, P  = 0.045) values of the LSN, and the AD value of the RSN (r = 0.439, P  = 0.025)., Conclusion: The DTI technique detected extensive white matter fiber damage in patients with PD, primarily in those with the G/A genotype, that led to motor and cognitivesymptoms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background: Increasing evidence suggests an association between pro-inflammatory diets and cognitive function. However, only a few studies based on small sample sizes have explored the association between pro-inflammatory diets and dementia using the dietary inflammatory index (DII). Additionally, the relationship between DII and different subtypes of dementia, such as Alzheimer's dementia and vascular dementia, remains largely unexplored. Given the changes in brain structure already observed in patients with dementia, we also investigated the association between DII and magnetic resonance imaging (MRI) measures of brain structure to provide some hints to elucidate the potential mechanisms between pro-inflammatory diet and cognitive decline., Methods: A total of 166,377 UK Biobank participants without dementia at baseline were analyzed. DII calculations were based on the information collected by the 24-h recall questionnaire. Brain structural anatomy and tissue-specific volumes were measured using brain MRI. Cox proportional hazards models, competing risk models, and restricted cubic spline were applied to assess the longitudinal associations. The generalized linear model was used to assess the association between DII and MRI measurements., Results: During a median follow-up time of 9.46 years, a total of 1372 participants developed dementia. The incidence of all-cause dementia increased by 4.6% for each additional unit of DII [hazard ratio (HR): 1.046]. Besides, DII displayed a "J-shaped" non-linear association with Alzheimer's dementia (P nonlinear  = 0.003). When DII was above 1.30, an increase in DII was significantly associated with an increased risk of Alzheimer's dementia (HR: 1.391, 95%CI: 1.085-1.784, P = 0.009). For brain MRI, the total volume of white matter hyperintensities increased with an increase in DII, whereas the volume of gray matter in the hippocampus decreased., Conclusions: In this cohort study, higher DII was associated with a higher risk of all-cause dementia and Alzheimer's dementia. However, our findings suggested that the association with DII and vascular and frontotemporal dementia was not significant., (© 2023. The Author(s).)