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Abstract 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}

Abstract 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.

Since 2018, Shandong Province has successively issued a series of pollution prevention and control programs for air pollutants from the coking industry, which plays a key role in coke production in China. However, a comprehensive assessment of the effectiveness of these measures is lacking. For a better understanding of this issue, based on the published air pollutant emission inventory for the independent coking industry and related policies formulated in Shandong in 2018, this study developed business-as-usual scenarios (BAU-2018, BAU-2025, and BAU-2035) and emission reduction optimization scenarios (ERO-2025 and ERO-2035). The emission reduction potential of PM10, SO2, NOx, PM2.5, and CO2 and their corresponding contributions to Shandong’s air quality with the air quality model (CALPUFF) were assessed under different scenarios. In terms of scenario settings, the gross domestic product of the secondary industry and the coke output of independent coking enterprises were used for linear regression to predict the coke output in 2025 and 2035. The mesoscale atmospheric data model, Weather Research and Forecasting, provided simulated three-dimensional meteorological field data for this study. Regional terrain data (90 m) were obtained from the United States Geological Survey. The resolution of the land use type data was 30 m, according to our previous research results. We adopted the MESOPUFF II chemical mechanism to simulate SO2, NOx, SO42−, NO3−, HNO3, PM10, and PM2.5 pollutants. To ensure the accuracy of the enterprise location information, we examined the enterprise latitude and longitude information one by one using Google Earth location recognition and manual visual inspection. The results showed that in the BAU-2018 scenario, the annual contribution ratios of SO2, NOx, PM10, and PM2.5 in Shandong Province were 0.06%–0.84%, 0.01%–0.63%, 0.04%–0.19%, and 0.07%–0.21%, respectively. Linyi has the highest contribution of SO2 and NOx concentrations to air quality, whereas Jining has the highest contribution of PM10 and PM2.5 concentrations to air quality. Compared with the current scenario (BAU-2018), the emission and contribution concentration of each pollutant showed an alarming decrease in the ERO-2025 scenario. Under the ERO-2035 scenario, the results showed that SO2, NOx, PM10, PM2.5, and CO2 emissions would be reduced by 60.12%, 78.24%, 75.07%, 74.20%, and 37.47%, respectively, compared with those under the BAU-2018 scenario. In the ERO-2035 scenario, the average contribution concentrations of SO2, NOx, PM10, and PM2.5 decreased by 60.74%, 78.56%, 75.00%, and 74.53%, respectively. Moreover, the results of this study showed that the comprehensive implementation of ultralow emission standards in Shandong Province had a considerable impact on air pollutant reduction in the independent coking industry, and the synergistic reduction of air pollutants and carbon dioxide showed huge potential.

Abstract 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

Summary: 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.

BackgroundMultiple 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.ObjectiveWe aimed to investigate whether PRL can serve as a neuroimaging marker for discriminating between MS and CSVD.MethodsIn 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.ResultsOur 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

Abstract Background This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age

Abstract 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.

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.

The aim of this study was to evaluate dietary chitosan oligosaccharides (COS) supplementation on meat quality, chemical composition and oxidative stability in frizzled chickens. A total of 360 one-day-old female frizzled chickens with an average body weight of 34.38 ± 1.23 g were randomly allocated to four groups with six replications (10 chickens/replication) in this 84-day experiment. The chickens in the control group (CON) fed the basal diet and the other three experimental diets were based on the basal diet with 300, 600 and 900 mg/kg COS supplementation, respectively. The results indicated that dietary COS increased growth performance, eviscerated and breast muscle yield while decreased abdominal fat yield, accompanied with increasing pH45min, pH24h, Lightness, drip loss and cooking loss in breast and thigh muscle. The scavenging activity of 2,2-diphenyl-1-picrylhydrazyl, superoxide radical, hydroxyl radical and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt, the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in breast and thigh muscle were improved by COS while malondialdehyde content was decreased. COS up-regulated the gene expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, SOD, CAT and GSH-Px in breast and thigh muscle. In conclusion, dietary COS supplementation improved meat quality by improving pH, colour, water holding capacity and anti-oxidant capacity, accompanied with decreased lipid metabolism in frizzled chickens. Dietary 600 mg/kg COS was recommended in frizzled chickens’ diet to improve meat quality.Highlights COS improves growth performance of frizzled chickens. COS improves meat quality of frizzled chickens. COS enhances anti-oxidant capacity of frizzled chickens’ meat.

Summary: 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.

BackgroundAs 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.MethodsA 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.ResultsIn 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.ConclusionThe 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.

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.

Abstract 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.

Abstract Background Nuclear acetyl-CoA pools govern histone acetylation that controls synaptic plasticity and contributes to cognitive deterioration in patients with Alzheimer’s disease (AD). Nuclear acetyl-CoA pools are generated partially from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). However, the underlying mechanism of histone acetylation dysregulation in AD remains poorly understood. Methods We detected ACSS2 expression and histone acetylation levels in the brains of AD patients and 5 × FAD mice. When we altered ACSS2 expression by injecting adeno-associated virus into the dorsal hippocampus of 5 × FAD mice and replenished ACSS2 substrate (acetate), we observed changes in cognitive function by Morris water maze. We next performed RNA-seq, ChIP-qPCR, and electrophysiology to study molecular mechanism underlying ACSS2-mediated spatial learning and memory in 5 × FAD mice. Results We reported that ACSS2 expression and histone acetylation (H3K9, H4K12) were reduced in the hippocampus and prefrontal cortex of 5 × FAD mice. Reduced ACSS2 levels were also observed in the temporal cortex of AD patients. 5 × FAD mice exhibited a low enrichment of acetylated histones on the promoters of NMDARs and AMPARs, together with impaired basal and activity-dependent synaptic plasticity, all of which were rescued by ACSS2 upregulation. Moreover, acetate replenishment enhanced ac-H3K9 and ac-H4K12 in 5 × FAD mice, leading to an increase of NMDARs and AMPARs and a restoration of synaptic plasticity and cognitive function in an ACSS2-dependent manner. Conclusion ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD. Graphical Abstract Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment.

BackgroundPrevious 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.MethodsThe 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.ResultsIn 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

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.

BackgroundUterine 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 materialsWe 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.ResultsThis 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.ConclusionThis 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.

ObjectiveEvidence 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 methodsThis 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.ResultsDuring 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.ConclusionBoth 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.

Neonatal genital prolapse is a rare situation. This report presents a unique case involving a pair of premature female twins who both developed vaginal wall prolapse without any neurological deficits. Multiple factors such as selective intrauterine growth restriction, feeding intolerance, extrauterine growth retardation, and elevated intra-abdominal pressure after birth may have contributed to the development of this phenomenon. Notably, the severity of prolapse was more pronounced in the twin with lower birth weight and smaller for gestational age. After a five-month follow-up period, the twins’ prolapsed vaginal wall fully retracted due to a combination of conservative treatment and enhanced nutritional support.

Abstract Background The aim of this study was to determine the proportion of hidden blood loss (HBL) in patients treated with minimally invasive surgery, and to compare the HBL between patients treated with percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF). Methods From January 2017 to January 2019, a total of 119 patients with thoracolumbar fractures were included in the analysis, of which 58 cases received PPSF and 61 cases received MWPSF. The clinical information and demographic results were collected and compared. And the HBL of the patients is calculated by the combination formulas of Nadler, Gross and Sehat. Results Compared with the PPSF group, operation time of MWPSF is shorter. The fluoroscopy times are 13.6 ± 3.0 in PPSF group and 5.6 ± 1.6 in MWPSF group (p

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

With a series of redevelopment activities, such as land consolidation and urban renewal, many cities in China have experienced land de-urbanization phenomena. These include the conversion of construction land into green spaces (such as parks, forests, and lawns), blue spaces (such as rivers, lakes, and wetlands), and farmland. However, there is currently limited research on diverse land de-urbanization types and pathways. This study focuses on investigating the land de-urbanization in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) from 2014 to September 2023 using the Continuous Change Detection and Classification (CCDC) method. The results demonstrate that the GBA experienced 72.74 square kilometers of de-urbanization during the study period, primarily through the conversion of construction land to land with low plant coverage, including grassland and farmland. There were significant differences in the quantity and spatial agglomeration of de-urbanization between cities and within individual cities. Temporally, de-urbanization predominantly occurred in the period of 2016 to 2021, with a sharp decline in 2022. The temporal changes were significantly influenced by urban renewal policies and the impact of the COVID-19 pandemic. In terms of spatial clustering characteristics, the de-urbanization process in the GBA exhibited spatial agglomeration but was primarily characterized by low-level clustering. This study also examines the correlations between de-urbanization and factors including location and the stage of urbanization. The analysis showed that de-urbanization within cities tended to concentrate near the main urban roads within a range of 10–30 km from city centers. The trend of de-urbanization followed a pattern that is consistent with the Northam curve, where de-urbanization tends to increase during the rapid urbanization phase and decline as urbanization reaches a mature stage. Overall, this study provides valuable insights for the redevelopment of construction land within the context of ecological civilization construction. It also offers suggestions for urban land development and redevelopment in metropolitan areas.

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.

Abstract. Background:. Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. Methods:. Middle-aged wild-type (WT) C57BL/6 and CX3CR1−/− mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. Results:. CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1−/− S group, the CX3CR1−/− SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. Conclusions:. These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

IntroductionParkinson’s disease (PD), as a common neurodegenerative disease, currently has no effective therapeutic approaches to delay or stop its progression. There is an urgent need to further define its pathogenesis and develop new therapeutic targets. An increasing number of studies have shown that members of the sirtuin (SIRT) family are differentially involved in neurodegenerative diseases, indicating their potential to serve as targets in therapeutic strategies. Mitochondrial SIRT4 possesses multiple enzymatic activities, such as deacetylase, ADP ribosyltransferase, lipoamidase, and deacylase activities, and exhibits different enzymatic activities and target substrates in different tissues and cells; thus, mitochondrial SIRT4 plays an integral role in regulating metabolism. However, the role and mechanism of SIRT4 in PD are not fully understood. This study aimed to investigate the potential mechanism and possible regulatory targets of SIRT4 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice.MethodsThe expression of the SIRT4 protein in the MPTP-induced PD mouse mice or key familial Parkinson disease protein 7 knockout (DJ-1 KO) rat was compared against the control group by western blot assay. Afterwards, quantitative proteomics and bioinformatics analyses were performed to identify altered proteins in the vitro model and reveal the possible functional role of SIRT4. The most promising molecular target of SIRT4 were screened and validated by viral transfection, western blot assay and reverse transcription quantitative PCR (RT-qPCR) assays.ResultsThe expression of the SIRT4 protein was found to be altered both in the MPTP-induced PD mouse mice and DJ-1KO rats. Following the viral transfection of SIRT4, a quantitative proteomics analysis identified 5,094 altered proteins in the vitro model, including 213 significantly upregulated proteins and 222 significantly downregulated proteins. The results from bioinformatics analyses indicated that SIRT4 mainly affected the ribosomal pathway, propionate metabolism pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway and peroxisome pathway in cells, and we screened 25 potential molecular targets. Finally, only fatty acid binding protein 4 (FABP4) in the PPAR signaling pathway was regulated by SIRT4 among the 25 molecules. Importantly, the alterations in FABP4 and PPARγ were verified in the MPTP-induced PD mouse model.DiscussionOur results indicated that FABP4 in the PPAR signaling pathway is the most promising molecular target of SIRT4 in an MPTP-induced mouse model and revealed the possible functional role of SIRT4. This study provides a reference for future drug development and mechanism research with SIRT4 as a target or biomarker.

Ionic liquids have been extensively studied as solvents or catalysts for oxidative desulfurization (ODS) of diesel fuel, but it is still a challenge to reduce the desulfurization time and steps. In this work, a new highly efficient desulfurization system composed of CoFe2O4 magnetic nanoparticle, [HMIM]Br-FeCl3 and H2O2 was developed for the ODS of FCC diesel fuel. The desulfurization performances were investigated including desulfurization time, temperature, volume ratio of IL/oil, O/S molar ratio, dosage of CoFe2O4, FeCl3 content in ILs, regeneration, and reuse of catalyst and solvent. Owing to the coupled catalytic roles of CoFe2O4 magnetic nanoparticle and [HMIM]Br-FeCl3, where Co2+ and Fe3+ interact with H2O2 to produce •OH radical that converts S-compounds into sulfone and sulfoxide compounds, such a desulfurization system is highly effective in removing S-compound in diesel fuel. The S-content in FCC diesel fuel was reduced from the original 272.8 ppm to 0.5 ppm with 99.82% S-removal efficiency after one step within 8 min under the optimal conditions of 25 °C, 8 min, V(IL/oil) = 1:10, O/S = 20, 5 wt% CoFe2O4 dosage and n([HMIM]Br)/n(FeCl3) = 1:1; the desulfurization performance is much better in desulfurization time and steps than other desulfurization systems reported previously. The desulfurization system can be regenerated and reused without remarkable loss of desulfurization activity. A desulfurization mechanism was proposed.

Abstract Population-based studies reveal that apolipoprotein E (APOE) ε4 gene allele is closely associated with late-life depression (LLD). However, its exact role and underlying mechanism remain obscure. The current study found that aged apoE4-targeted replacement (TR) mice displayed obvious depression-like behavior when compared with age-matched apoE3-TR mice. Furthermore, apoE4 increased stress-induced depression-like behaviors, accompanied by declines in the hippocampal 5-HT (1A) radioligand [18F] MPPF uptake evidenced by positron emission tomography (PET). In [18F]-fluorodeoxyglucose PET ([18F]-FDG PET) analyses, the FDG uptake in the prefrontal cortex, temporal cortex and hippocampus of apoE4-TR mice significantly declined when compared with that of apoE3-TR mice after acute stress. Further biochemical analysis revealed that ATP levels in the prefrontal cortex of apoE4-TR mice decreased during aging or stress process and ATP supplementation effectively rescued the depression-like behaviors of elderly apoE4-TR mice. In primary cultured astrocytes from the cortex of apoE-TR mice, apoE4, when compared with apoE3, obviously decreased the mitochondrial membrane potential, mitochondrial respiration, and glycolysis in a culture time-dependent manner. Our findings highlight that apoE4 is a potential risk factor of depression in elderly population by impairing the glucose metabolism, reducing ATP level, and damaging mitochondrial functions in astrocytes, which indicates that in clinical settings ATP supplementation may be effective for elderly depression patients with apoE4 carrier.

Abstract SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants—alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 μg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a “spike protein-CD147-CyPA signaling axis”: Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), is a highly contagious and fatal viral disease, posing a significant threat to the swine industry. Heat shock protein 90 kDa alpha class A member 1 (HSP90AA1) is a very conservative chaperone protein that plays an important role in signal transduction and viral proliferation. However, the role of HSP90AA1 in CSFV infection is unknown. In this study, we found that expression of HSP90AA1 could be promoted in PK-15 and 3D4/2 cells infected by CSFV. Over-expression of HSP90AA1 could inhibit CSFV replication and functional silencing of HSP90AA1 gene promotes CSFV replication. Further exploration revealed that HSP90AA1 interacted with CSFV NS5A protein and reduced the protein levels of NS5A. Since NS5A has an important role in CSFV replication and is closely related to type I IFN and NF-κB response, we further analyzed whether HSP90AA1 affects CSFV replication by regulating type I IFN and NF-κB pathway responses. Our research found HSP90AA1 positively regulated type I IFN response by promoting STAT1 phosphorylation and nuclear translocation processes and promoted the nuclear translocation processes of p-P65. However, CSFV infection antagonizes the activation of HSP90AA1 on JAK/STAT and NF-κB pathway. In conclusion, our study found that HSP90AA1 overexpression significantly inhibited CSFV replication and may inhibit CSFV replication by interacting with NS5A and activating JAK/STAT and NF-κB signaling pathways. These results provide new insights into the mechanism of action of HSP90AA1 in CSFV infection, which abundant the candidate library of anti-CSFV.

PU.1, a transcription factor member of the E26 transformation-specific family, affects the function of a variety of immune cells in several physiological and pathological conditions. Previous studies studying the role of PU.1 in pathological conditions have mainly focused on immune system-related cancers, and a series of articles have confirmed that PU.1 mutation can induce a variety of immune cell-related malignancies. The underlying mechanism has also been extensively validated. However, the role of PU.1 in other major immune system-related diseases, namely, systemic autoimmune diseases, is still unclear. It was only in recent years that researchers began to gradually realize that PU.1 also played an important role in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE). This review article summarizes the findings of recent studies that investigated the role of PU.1 in various autoimmune diseases and the related underlying mechanisms. Furthermore, it presents new ideas and provides insight into the role of PU.1 as a potential treatment target for autoimmune diseases and highlights existing research problems and future research directions in related fields.

Background: The prevalence of Type 1 Diabetes is increasing in pediatrics and diabetes education plays one of the most important role in the management of diabetes, especially in children. However, the related evidence concerned diabetes education is rare in children and adolescents. Therefore, we aimed to investigate the status of diabetes education in hospital, which could help us know the reality of diabetes education. Methods: We choose a nurse who is mainly responsible for diabetes education and management in each hospital to fill out the questionnaire. Overall, 98 nurses were enrolled from tertiary children's specialized hospitals and pediatric wards of general tertiary hospitals from Jan 2018 to Dec 2019. Results: Of 98 nurses enrolled, 61 (63.3%) nurses from 98 hospitals responded, 39 (63.9%) of them received specialized training in diabetes. There were no differences in education characteristics among regions of China. There were 26(42.6%) hospitals have a full-time nurse for diabetes education or nurses with endocrinology training increased with the number of cases/year (P=0.02 and P=0.009). The use of game-based education, knowledge assessment at discharge did not vary among hospital volumes, and the presence of a psychiatrist (P=0.41, P=0.65, and P=0.85, respectively). Diet management education is the most common (23.0%) difficulty in children diabetes education. Conclusion: The level of diabetes education in children and adolescents varied among hospitals, but not among regions in China. There was a lack of resources provided for children and adolescents diabetes education in terms of training and specialized services.

This study aimed to evaluate the effect of diets supplementing with various levels of thymol and carvacrol eutectic (TCE) on growth performance, serum biochemical parameters, intestinal morphology, and the expression of intestinal nutrient absorption, barrier function- and inflammation-related genes in broiler chickens. A total of 640 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into four groups (8 replicates/group, 20 broilers/replicate). Birds in the four experimental groups were fed a basal diet with TCE at 0, 30, 60, or 120 mg/kg. The results showed that the growth performance of birds during 22–42 d or 1–42 d, serum IgE and IgG content at 21 d of age, jejunal and ileal morphology, ileal MUC2, OCLN, and IL-10 mRNA expression were significantly increased compared with the control group (p < 0.05), and the ileal IL-6 mRNA expression quadratically decreased (p < 0.05) with increasing dietary TCE supplemented dosage, and its expression showed a linear downward trend (0.05 < p < 0.1). Meanwhile, compared with the other three groups, birds fed diets with 30 mg/kg TCE presented better (p < 0.05) growth performance, intestinal morphology, and function. These results indicated that the optimal supplementation amount of TCE in the broiler diets was 30 mg/kg.

The objective of the study was to investigate the levels of plasma exosome-derived fragile site-associated tumor suppressor (FATS) and evaluate its prognostic predictive ability in ovarian cancer (OC) patients. Exosome-rich fractions were isolated from the plasma of 90 patients with OC enrolled in this study. The levels of plasma exosome-derived FATS were detected by ELISA. The levels of exosome-derived FATS in OC patients were significantly lower as compared to the healthy controls (P < 0.001). The levels of plasma exosome-derived FATS were higher in OC patients with low grade (1/2), and Federation International of Gynecology and Obstetrics (FIGO) Stages I/II than those in high grade (3/4) and Stages III/IV of the disease (p = 0.003; p < 0.001), respectively. The levels of plasma exosome-derived FATS were significantly higher in OC patients with no lymph node metastasis or no ascites as compared to those with lymph node metastasis or ascites, respectively (both p < 0.001). The levels of plasma exosome-derived FATS were higher in OC patients having CA-125 below 35 U/ml as compared to those with CA-125 greater than 35 U/ml (p < 0.001). Among all enrolled OC patients, both 5-DFS and 5-OS were shorter in patients with lower plasma exosome-derived FATS levels than those with higher levels (both p < 0.001). The area under the receiver operating characteristic curve of plasma exosome-derived FATS was 0.85 (95% CI: 0.76-0.91) for 5-DFS and 0.91 (95% CI: 0.83-0.96) for 5-OS prediction in patients with OC. Plasma exosome-derived FATS levels in OC patients were significantly downregulated. Low levels of plasma exosome-derived FATS had a significant relationship with FIGO Stages III/IV, high grade, ascites, higher levels of CA-125, lymph node metastasis, and prognosis of OC patients. Thus, our findings may provide insights for the development of a new strategy OC treatment.

Local full-waveform inversion (FWI) methods use redatumed seismic responses of virtual receivers within the subsurface to build the local objective function based on the convolution-type representation theorem. The Marchenko method is widely used to obtain the redatumed data. The method only requires a smoothed velocity model with correct kinematic characteristics of seismic responses for redatuming of the single-sided reflection data. However, the standard Marchenko method is insensitive to lateral propagation of the wavefield. By injecting the standard Marchenko redatumed wavefield along the boundary of the target, the local wavefield propagation modeling produces errors, which affects the accuracy of the local FWI. In this paper, a method to obtain more accurate Green’s functions is proposed by incorporating vertical seismic profile data (VSP) into the calculation process of the Marchenko source-receiver redatuming. This method allows one to obtain the accurate laterally propagating waveform, resulting in a significant improvement of lateral resolution. The proposed method is applied to a benchmark model dataset and compared with the local FWI based on standard Marchenko redatuming.

The microbial compositions and metabolites of fermented sauerkraut with and without the addition of microorganisms have been compared. The OTU clustering, nonvolatile compounds, volatile compounds and associations between bacterial taxa and metabolites were analyzed by 16S rRNA high-throughput sequencing technology, ultra performance liquid chromatography (UPLC), gas chromatography ion mobility mass spectrometry (GC-IMS) and the O2PLS model studies. The results showed that at the phylum level, the microbial species in the four sauerkraut types consisted mainly of the phyla Firmicutes and Proteobacteria, but different modes of microbial addition formed their own unique microbial communities. There were significant differences in the microbial communities among different northeast China sauerkraut samples, and different microbial communities exerted similar effects to inhibit Firmicutes production. At the genus level, sauerkraut without added microorganisms had the lowest microbial diversity. A total of 26 amino acids and 11 organic acids were identified and were more abundant in nonmicrobially fermented sauerkraut; 88 volatile organic compounds were identified in the 4 types of sauerkraut, with the microbially fermented sauerkraut being richer in alcohols, esters and acids. Different brands of sauerkraut contain their own unique flavor compounds. Cystine and tyrosine, ascorbic acid and acetic acid, and alcohols and esters are closely related to a wide range of microorganisms in sauerkraut. Elucidating the correlations among microbiota and metabolites will help guide future improvements in sauerkraut fermentation processes.

The potential applications of shale oil as a substitute energy source are adversely influenced due to its high nitrogen content. In this work, four imidazolium ionic liquids (ILs), i.e., 1-butyl-3-methylimidazolium chloride ([Bmim]Cl), 1-butyl-3-methylimidazolium acetate ([Bmim]Ac), 1-butyl-3-methylimidazolium acetate/ZnAc2 ([Bmim]Ac/ZnAc2) and 1-butyl-3-methylimidazolium chloride/ZnAc2 ([Bmim]Cl/ZnAc2), were used to extract the basic nitrides and neutral nitrides from shale oil. The influence of extraction time, temperature, properties of N-compounds, ILs structure, mass ratio of IL/oil, multiple cycles of denitrogenation, physical mixing of ILs and ILs recyclability on extractive denitrogenation was systematically investigated. The denitrogenation performance of all ILs was determined and investigated from micro-level view with σ-profile. It was observed that, ILs composed of anions with weaker HB acceptor capacity, have the higher N-extraction efficiency to the neutral nitrogen compounds with weaker HB acceptor capacity. More than 96% N-extraction efficiency was achieved at the end of a single extraction cycle for time < 10 min under 40 °C and 1 : 1 of IL: oil (w/w), especially 100% N-extraction efficiency was realized for carbazole and indole. The N-extraction efficiency up to 60.1% and 53.7% for real shale oil was realized by [Bmim]Ac and [Bmim]Ac/ZnAc2, respectively, which are about 10% better than other non-hydrodenitrogenation technologies. Moreover, [Bmim]Ac and [Bmim]Ac/ZnAc2 exhibited almost the same extractive denitrogenation performance after regeneration. This work has developed a new approach to lessen the nitrogen content of shale oil effectively and economically.

China is the largest producer and exporter of coke globally, which means that it is very important to understand the characteristics of air pollutants and carbon emissions from China’s independent coking industry. This study was the first to establish a bottom-up inventory of the air pollutants and carbon emissions of China’s independent coking industry during 2001–2018 based on continuous emission monitoring system online monitoring data and unit-based corporate information. Based on the developed emission inventory, four scenarios were established to analyze potential emissions reduction of air pollutants and carbon dioxide (CO2) in future. The emissions of particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), black carbon (BC) and organic carbon (OC) decreased by 62.11%, 63.41%, 72.85%, 63.41% and 63.41%, respectively. CO2, carbon monoxide (CO), volatile organic compounds (VOCs) and nitrogen oxides (NOX) emissions increased by 355.51%, 355.51%, 355.51% and 99.74%, respectively. In 2018, PM10, PM2.5, SO2, NOx, BC, OC, CO, VOCs and CO2 emissions were, respectively. 45.20, 16.91, 63.84, 117.71, 5.07, 5.92, 554.91, 1026.58 Gg, and 176.88 Tg. Shanxi province made the greatest contributions to the total emissions of air pollutants and CO2 from this industry by 25.01%. The emission source that contributed most to PM2.5 (SO2 and NOX) emissions was coke pushing (quenching and the coke oven chimney respectively) in 2018. Under the ULE scenario (2018–2035), PM2.5 and SO2 emissions will reduce by more than 30%. Under the PCP scenario, PM2.5 and SO2 emissions will reduce by more than 55%. Under the CBP scenario, CO2 emissions will peak at 197.99 Tg in 2025 and decrease to 70% of the peak in 2035. The results showed the emission characteristics of air pollutants and CO2, future emission with several scenarios and cooperative reduction potential in China’s independent coking industry, which provides scientific support for the development of pollution control strategies.

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.

Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs).Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy (“ON” time without troublesome dyskinesia, “OFF” time, “ON” time, “UPDRS-III,” and “UPDRS-II”) and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of “ON” time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%).Conclusions: This network meta-analysis shows that apomorphine increased “ON” time without troublesome dyskinesia and decreased “OF” time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased “ON” time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.

Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. Materials and Methods: From July 2020 to November 2021, a total of 35 HCC patients were enrolled and received HAIC with oxaliplatin plus raltitrexed. The overall survival (OS) and time to progression (TTP) were primary and secondary endpoints, respectively. The tumor response was assessed by the modified response evaluation criteria in solid tumors (mRECIST), and the adverse events were investigated using the common terminology criteria for adverse events version 5.0 (CTCAE 5.0). Results: The median OS and TTP were 10 months (95% confidence interval (CI): 5.5–14.6) and 3.5 months (95% CI: 2.3–4.7), respectively. By means of multivariate analysis, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was found to be an independent prognostic factor for better survival. No patients experienced toxicity-related death. Thrombocytopenia, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) elevation were the most common toxicities. No grade 3 or higher adverse events related to HAICROX were observed. Conclusion: HAICROX showed valuable efficacy and tolerable toxicity in advanced HCC patients who progressed on TACE or were ineligible for TACE. HAICROX is a promising treatment for advanced-stage HCC patients with TACE failure or ineligibility.

Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are associated with pronounced sleep disorders or cognitive dysfunction in neurodegenerative diseases. However, the effects of LRRK2 deficiency on sleep rhythms and sleep deprivation-related cognitive changes, and the relevant underlying mechanism, remain unrevealed. In this study, Lrrk2-/- and Lrrk2+/+ mice were subjected to normal sleep (S) or sleep deprivation (SD). Sleep recording, behavioral testing, Golgi-cox staining, immunofluorescence, and real-time PCR were employed to evaluate the impacts of LRRK2 deficiency on sleep behaviors and to investigate the underlying mechanisms. The results showed that after SD, LRRK2-deficient mice displayed lengthened NREM and shortened REM, and reported decreased dendritic spines, increased microglial activation, and synaptic endocytosis in the prefrontal cortex. Meanwhile, after SD, LRRK2 deficiency aggravated cognitive impairments, especially in the recall memory cued by fear conditioning test. Our findings evidence that LRRK2 modulates REM/NREM sleep and its deficiency may exacerbate sleep deprivation-related cognitive disorders by perturbing synaptic plasticity and microglial synaptic pruning in mice.

To reflect the volatile differences of dried citrus peel as affected by cultivars and drying methods, the volatile compounds of dried citrus peel of two cultivars (Citrus reticulata “Chachi” and Citrus reticulata “Ponkan”), prepared under three drying methods (sun-drying (SD), hot-air-drying (AD), and freeze-drying (FD)), were analyzed by GC-MS, odor activity values (OAVs), and GC-IMS. GC-MS data indicated that SD was favorable to preserve terpenic alcohols (linalool, α-terpineol and terpinene-4-ol), β-cymene, methyl methanthranilate, and monoterpenes; while AD was favorable to preserve aliphatic aldehydes and sesquiterpenes; and SD was more similar with AD in GC-MS analysis of volatile profile (of higher MW) for both cultivars from the PCA outcome. Furthermore, significant difference in volatile isomeric composition of different samples was also clearly demonstrated through extracted ion chromatogram (EIC) by GC-MS analysis. GC-IMS analysis showed the favorability of FD to preserve ketones, phenols, esters, and aromatic aldehydes; and SD was more similar with FD in GC-IMS analysis of volatile profile (of smaller MW) for both cultivars from the PCA outcome. Moreover, the OAVs indicate that 2-methoxy-4-vinylphenol contributed much to the flavor of dried Ponkan peel, while 2-methoxy-4-vinylphenol, methyl methanthranilate, and methyl anthranilate played an important role in the flavor of dried Chachi peel; and the highest OAVs for monoterpenes were observed at SD for both cultivars. Thus, the combination of GC-MS and GC-IMS analyses with PCA in this paper suggested the superiority of SD to preserve volatiles and characteristic aroma in dried citrus peel, and that SD contributed much to the quality of dried Chachi peel.

Stress may serve multiple roles in cerebral functioning, ranging from a highly appropriate behavioral adaptation to a critical risk factor for susceptibility to mood disorder and cognitive impairment. It is well known that E/I (excitation/inhibition) balance is essential for maintaining brain homeostasis. However, it remains largely unknown how GABAergic and Glutamatergic neurons respond to different stressful stimuli and whether the GABAergic-Glutamatergic neuron balance is related to the transition between adaptive and maladaptive behaviors. Here, we subjected 3-month-old mice to chronic mild stress (CMS) for a period of one, two, and four weeks, respectively. The results showed that the two-week CMS procedure produced adaptive effects on behaviors and cognitive performance, with a higher number of GABAergic neuron and VGluT1-positive neurons, increasing the expressions of p-GluN2B, Reelin, and syn-PSD-95 protein in the hippocampus. In contrast, the prolonged behavioral challenge (4 week) imposes a passive coping behavioral strategy and cognitive impairment, decreased the number of GABAergic neuron, hyperactivity of VGluT1-positive neuron, increased the ratio of p-GluN2B, and decreased the expression of Reelin, syn-PSD-95 in the hippocampus. These findings suggest that a moderate duration of stress probably promotes behavioral adaptation and spatial memory by maintaining a GABAergic-Glutamatergic neuron balance and promoting the expression of synaptic plasticity-related proteins in the brain.

Background and Objectives: The recurrence outcome in patients who underwent microwave ablation (MWA) with or without transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) within Milan criteria remains unclear. The aim of this retrospective study was to identify the predictive factors of recurrence in these patients. Materials and Methods: From May 2018 to April 2021, 66 patients with HCC within Milan criteria were enrolled. Local tumor progression (LTP) and recurrence-free survival (RFS) were evaluated. Univariate and multivariate analyses were used to evaluate the risk factors of recurrence. The propensity score analysis was conducted to reduce potential confounding bias. Results: During the median follow-up of 25.07 months (95% confidence interval [CI], 21.85, 28.28), the median time to LTP and RFS were 20.10 (95%CI, 14.67, 25.53) and 13.03 (95%CI, 6.36, 19.70) months. No group difference (MWA vs. MWA + TACE) was found in 1-year cumulative LTP (p = 0.575) and RFS (p = 0.515), but meaningful significant differences were found in two-year recurrence (LTP, p = 0.007 and RFS, p = 0.037). Univariate and multivariate analyses revealed that treatment received before ablation was an independent risk factor of LTP (hazard ratio [HR] 4.37, 95%CI, 1.44, 13.32) and RFS (HR 3.41, 95%CI, 1.49, 7.81). Conclusions: The LTP and RFS in the MWA group were similar to that in the MWA combined with TACE. For HCC within Milan criteria, both groups preferentially selected MWA. More endeavor and rigorous surveillance should be taken to relapse prevention, in patients who have received previous treatment.

The uterine endometrium, which lines the mammalian uterus, is essential for embryo implantation. This lining undergoes significant changes during sexual and menstrual cycles. The endometrium is also associated with hormone-related diseases such as endometriosis and endometrial cancer. Circular RNAs (circRNAs) play a role in various biological processes. Recent studies have determined that circRNAs function in both normal and pathological endometrial environments. Here, we review high-throughput studies pertaining to circRNAs as well as individual circRNAs active in the endometrium, in order to explore the myriad functions of circRNAs in the endometrium and mechanisms underlying these functions, from panoramic and individual perspectives. Owing to their abundant expression, stability, and small size, circRNAs have displayed potential usefulness as diagnostic markers and treatment targets for endometrial-related diseases. Therefore, the specific role of circRNAs in the endometrium warrants systematic investigation in the future.