The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis.

INTRODUCTION: The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood. METHODS: We analyzed data from 486,297 UK Biobank participants, categorizing them by mental disorder history to identify the risk of AD and the cognitive impairment characteristics. Causation was further assessed using Mendelian randomization (MR). RESULTS: AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR] = 2.37, P < 0.01) and major depressive disorder (MDD; HR = 1.63, P < 0.001). MR confirmed a causal link between BD and AD (ORIVW = 1.098), as well as obsessive-compulsive disorder (OCD) and AD (ORIVW = 1.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance. DISCUSSION: Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention. HIGHLIGHTS: This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders. Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR] = 2.37, P < 0.01), followed by those with major depressive disorder (MDD; HR = 1.63, P < 0.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR = 2.36, P = 0.056). Two-sample Mendelian randomization (MR) confirmed a causal association between BD and AD (ORIVW = 1.098, P < 0.05), as well as AD family history (proxy-AD, ORIVW = 1.098, P < 0.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive-compulsive disorder (OCD) spectrum and AD (ORIVW = 1.050, P < 0.05). Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks.

Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

Seasonal migration pattern of an important rice pest, Nilaparvata lugens (Hemiptera: Delphacidae), on Hainan Island, China.

The brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) (BPH), is a major, regionally migratory pest of rice in Asia. Despite intensive migratory studies, the seasonal migratory pattern of this species in the year-round breeding region (i.e., Hainan Island) remains largely unknown. To understand the migration dynamics, we conducted relevant research based on BPH light trap catches on Hainan in 2017-2022. Results showed that the occurrence dynamics of BPH in Hainan oscillated in different years and seasons. Overall, there are 4 migration peak periods on Hainan, with outbound peak periods in April-May and August-September and inbound peak periods in June and October. Trajectory and wind fields showed that in August-September, Hainan had complex meteorological conditions, and the outbound paths of BPH were variable, mainly landing in southeastern Guangxi and southwestern Guangdong. In contrast, April-May was influenced by southeasterly winds, with a wider outbound range and a further distance, landing along northeastern Vietnam from west to east toward Guangxi and Guangdong areas with time. Wind-rain fields, trajectory, and hydrogen isotope showed that in June, southwesterly winds transported BPH northward from the Indochina peninsula, where it was hindered by rainfall in the Leizhou Peninsula area and the migrants will be "rained out" into Hainan. Identically, in October, the interactions between northeasterly winds and rainfall belts on the southwest shore of Hainan increased the opportunities for BPH to migrate southward to reach Hainan. Our results suggest that Hainan is not only an important source of BPH migrating from East Asia but also plays the role of a bridge.

Integrated analysis of gut metabolome, microbiome, and brain function reveal the role of gut-brain axis in longevity.

The role of microbiota-gut-brain axis in modulating longevity remains undetermined. Here, we performed a multiomics analysis of gut metagenomics, gut metabolomics, and brain functional near-infrared spectroscopy (fNIRS) in a cohort of 164 participants, including 83 nonagenarians (NAs) and 81 non-nonagenarians (NNAs) matched with their spouses and offspring. We found that 438 metabolites were significantly different between the two groups; among them, neuroactive compounds and anti-inflammatory substances were enriched in NAs. In addition, increased levels of neuroactive metabolites in NAs were significantly associated with NA-enriched species that had three corresponding biosynthetic potentials: Enterocloster asparagiformis, Hungatella hathewayi and Oxalobacter formigenes. Further analysis showed that the altered gut microbes and metabolites were linked to the enhanced brain connectivity in NAs, including the left dorsolateral prefrontal cortex (DLPFC)-left premotor cortex (PMC), left DLPFC-right primary motor area (M1), and right inferior frontal gyrus (IFG)-right M1. Finally, we found that neuroactive metabolites, altered microbe and enhanced brain connectivity contributed to the cognitive preservation in NAs. Our findings provide a comprehensive understanding of the microbiota-gut-brain axis in a long-lived population and insights into the establishment of a microbiome and metabolite homeostasis that can benefit human longevity and cognition by enhancing functional brain connectivity.

Malassezia infection associated with stucco keratosis.

We report a case of a 20-year-old young woman with a large stucco keratosis in the mons veneris, one of the clinical variants of Seborrheic keratoses (SKs). Periodic acid-Schiff staining revealed a large number of Malassezia spores in the stratum corneum. After oral antifungal treatment with itraconazole for 4 weeks, the benign tumor was completely cleared without residue or recurrence, which may open a new perspective for exploring the pathogenesis of SKs.

The prevalence and risk factors study of cognitive impairment: Analysis of the elderly population of Han nationality in Hunan province, China.

OBJECTIVE: A large number of studies have found that the prevalence of cognitive impairment varies in different regions. However, data on cognitive impairment in the Chinese population is still lacking. The goal of this study was to assess the prevalence of cognitive impairment among the elderly in a region of China and explore the associated risk factors. METHODS: We performed a population-based cross-sectional survey from April to June 2022. Residents come from three villages and six urban communities in the county-level city of Liuyang in southern China (N = 3233) and the coverage rate of our study population reached 73%. Participants were assessed with a series of clinical examinations and neuropsychological measures. A total of 2598 participants were selected after filtering out those under 60 years old or with incomplete data. Patients with cognitive impairment included those with mild cognitive impairment (MCI) or dementia who met standard diagnostic criteria. RESULTS: The prevalence of cognitive impairment, MCI, and dementia among participants aged 60 years and older were 21.48% (95% CI, 19.90-23.10), 15.70% (95% CI, 14.30-17.10), and 5.77 (95% CI, 4.90-6.70), respectively. And residents in villagers were more likely to have cognitive impairment than in urban communities (p < 0.001). Age growth and education level were independent influencing factors for cognitive impairment in all populations (p < 0.001). For lifestyles factors, both smoking and drinking reduced the risk of cognitive impairment (p < 0.05), but when further quantified, the link disappeared. Moreover, having cerebrovascular disease and severe vision impairment were risk factors (p < 0.05). CONCLUSION: A representative prevalence of cognitive impairment, MCI, and dementia was found in the elderly Han Chinese population in Southern China. And we further explored the role of known risk factors, particularly in physical activity, smoking, and alcohol consumption.

A detection model of cognitive impairment via the integrated gait and eye movement analysis from a large Chinese community cohort.

INTRODUCTION: Whether the integration of eye-tracking, gait, and corresponding dual-task analysis can distinguish cognitive impairment (CI) patients from controls remains unclear. METHODS: One thousand four hundred eighty-one participants, including 724 CI and 757 controls, were enrolled in this study. Eye movement and gait, combined with dual-task patterns, were measured. The LightGBM machine learning models were constructed. RESULTS: A total of 105 gait and eye-tracking features were extracted. Forty-six parameters, including 32 gait and 14 eye-tracking features, showed significant differences between two groups (P < 0.05). Of these, the Gait_3Back-TurnTime and Dual-task cost-TurnTime patterns were significantly correlated with plasma phosphorylated tau 181 (p-tau181) level. A model based on dual-task gait, dual-task smooth pursuit, prosaccade, and anti-saccade achieved the best area under the receiver operating characteristics curve (AUC) of 0.987 for CI detection, while combined with p-tau181, the model discriminated mild cognitive impairment from controls with an AUC of 0.824. DISCUSSION: Combining dual-task gait and dual-task eye-tracking analysis is feasible for the detection of CI. HIGHLIGHTS: This is the first study to report the efficiency of integrated parameters of dual-task gait and eye-tracking for cognitive impairment (CI) detection in a large cohort. We identified 46 gait and eye-tracking features associated with CI, and two were correlated to plasma phosphorylated tau 181. We constructed the model based on dual-task gait, smooth pursuit, prosaccade, and anti-saccade, achieving the best area under the curve of 0.987 for CI detection.

Atractylodin induces programmed necrosis of non-small cell lung cancer A549 cells and inhibits xenograft growth in nude mice by activating the RIPK1/RIPK3/MLKL signaling pathway / 中国肿瘤生物治疗杂志

@#目的：探讨苍术素（ATR）通过调节受体相互作用蛋白激酶（RIPK）1/RIPK3/混合谱系激酶结构域样（MLKL）信号通路对非小细胞肺癌（NSCLC）A549细胞程序性死亡及裸鼠移植瘤生长的影响。方法：使用0~160 μmol/L的ATR处理A549细胞，MTT法检测细胞存活率以确定后续实验给药浓度。使用ATR和/或RIPK1抑制剂Nec-1（necrostatin-1）、caspase抑制剂Z-VAD-FMK处理A549细胞，验证ATR是否诱导A549细胞发生程序性坏死。将A549细胞分为对照组、ATR-L组、ATR-M组、ATR-H组（分别用0、10、20、40 μmol/L ATR处理）、ATR+Nec-1组（40 μmol/L ATR+50 μmol/L Nec-1处理），处理24 h后，采用PI单染及Hoechst33342/PI双染法检测细胞死亡情况、透射电镜观察细胞死亡形态、DCFH-DA荧光探针法检测细胞内ROS水平、JC-1染色法检测线粒体膜电位、WB法检测细胞中RIPK1/RIPK3/MLKL信号通路相关蛋白质的表达水平。构建A549细胞裸鼠移植瘤模型，用10 mg/kg ATR（溶于玉米油中）对裸鼠灌胃给药5周，观察ATR对移植瘤生长的影响，WB法检测移植瘤组织中RIPK1/RIPK3/MLKL信号通路相关蛋白质的表达水平。结果：10~160 μmol/L的ATR可显著抑制A549细胞增殖，选择10、20、40 μmol/L的ATR进行后续实验。ATR组A549细胞存活率显著低于对照组（P<0.01）和ATR+Nec-1组（P<0.01），而ATR+z-VAD组细胞存活率显著低于z-VAD组（P<0.01），说明ATR可诱导A549细胞发生程序性坏死而非凋亡。与对照组比较，ATR处理组A549细胞发生肿胀，线粒体内脊消失呈空泡化，细胞内容物向外泄漏，细胞核聚集，表现为坏死特征，ATR-L组、ATR-M组、ATR-H组A549细胞死亡率、ROS水平及p-RIPK1、p-RIPK3、p-MLKL表达水平均显著升高，线粒体膜电位显著降低（均P<0.01），且呈药物浓度依赖性；与ATR-H组比较，ATR+Nec-1组细胞死亡率、ROS及p-RIPK1、p-RIPK3、p-MLKL表达水平降低，线粒体膜电位显著升高（均P<0.01）。裸鼠移植瘤实验结果显示，与对照组比较，ATR组裸鼠移植瘤体积、移植瘤质量均降低（P<0.05，或P<0.01），而与瘤组织中p-RIPK1、p-RIPK3、p-MLKL蛋白表达水平均显著升高（均P<0.01）。结论：ATR可能通过激活RIPK1/RIPK3/MLKL信号通路诱导A549细胞发生程序性坏死，抑制A549细胞及其裸鼠移植瘤的生长。

Specific serum autoantibodies predict the development and progression of Alzheimer's disease with high accuracy.

Autoimmunity plays a key role in the pathogenesis of Alzheimer's disease (AD). However, whether autoantibodies in peripheral blood can be used as biomarkers for AD has been elusive. Serum samples were obtained from 1,686 participants, including 767 with AD, 146 with mild cognitive impairment (MCI), 255 with other neurodegenerative diseases, and 518 healthy controls. Specific autoantibodies were measured using a custom-made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states. As a result, seven candidate AD-specific autoantibodies were identified, including MAPT, DNAJC8, KDM4D, SERF1A, CDKN1A, AGER, and ASXL1. A classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out-performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001). This study indicated that AD onset and progression are possibly accompanied by an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.

Clinical features of progressive supranuclear palsy.

Background: Progressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China. Method: Clinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD. Results: Throughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD. Conclusion: PSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND AND AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID. METHODS: In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022. RESULTS: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%). INTERPRETATION: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

Simulation Methods for MEMS S&A Devices for 2D Fuze Overload Loading.

An experimental testing system for the two-dimensional (2D) fuze overload loading process was designed to address the loading issues of recoil overload and centrifugal overload in fuze safety and arming (S&A) device. By incorporating centrifuge rotation energy storage, impact acceleration simulation, and equivalent centrifugal rotation simulation, a block equipped with a fuze S&A device accelerated instantly upon having impact from a centrifuge-driven impact hammer, simulating recoil overload loading. The impact hammer was retracted instantaneously by adopting an electromagnetic brake, which resulted in the centrifugal rotation of the block around its track, to simulate the centrifugal overload loading. The dynamic equations of the experimental testing system and the equations of impact hammer motions were established, whereby the rotation speed of the centrifuge and the braking force of the electromagnetic brake were calculated and selected. A dynamic model of the collision between the impact hammer and block was established using ANSYS/LS-DYNA software for simulation analysis. The acceleration curves of the recoil overload and centrifugal overload with variations in the centrifuge speed, cushion material, and buffer thickness were obtained, which verified the feasibility of the proposed loading simulation method. Two-dimensional overload loading simulation tests were performed using the developed experimental testing system, and the acceleration curves of the recoil overload and centrifugal overload were measured. The test results indicated that the proposed system can accomplish 2D overload loading simulations for a recoil overload of several 10,000× g and centrifugal overload of several 1000× g.

Toxicity assessment of a novel biopesticide guvermectin and identification of its transformation products in soils.

Guvermectin is a novel biopesticide often used as seed soaking to promote the rice yield. However, its biotoxicity and degradation behavior in soils were still not disclosed, which posed a knowledge gap to guide its rational application. Therefore, the degradation behaviors of guvermectin in four typical soils under aerobic and anaerobic conditions were investigated in the laboratory. The results showed that guvermectin was degraded fast with DT50 ranging from 0.95 to 10.10 d, and the degradation rate was higher in aerobic condition than that in anaerobic condition. Eight transformation products were screened using UPLC-QTOF/MS. The acute toxicities tests of guvermectin to Coturnix coturnix japonica and Apis mellifera were measured by biological laboratory experiments, and the acute and chronic toxicities of transformation products to Danio rerio, Daphnia magna Straus and Green algae were predicted by ECOSAR software. The results showed that guvermectin has low toxic to quail and honeybee (LD50 2000 mg a.i./kg body weight, LD50 Ëƒ 100 µg a.i./bee), and its transformation products were also low toxic class to Danio rerio, Daphnia magna Straus and Green algae (LC50/EC50 > 100 mg a.i./L). However, the nucleoside-like metabolites may pose a potential risk due to their similarity to genetic material, which should be concerned. The findings provided important environmental risk assessment data for the rational use of guvermectin.

Characteristics of autonomic dysfunction in neuronal intranuclear inclusion disease.

Background: This study aimed to investigate the features of autonomic dysfunction (AutD) in a large cohort of patients with neuronal intranuclear inclusion disease (NIID). Methods: A total of 122 patients with NIID and 122 controls were enrolled. All participants completed the Scales for Outcomes in Parkinson's Disease-Autonomic Questionnaire (SCOPA-AUT) and genetic screening for GGC expanded repeats within the NOTCH2NLC gene. All patients underwent neuropsychological and clinical assessments. SCOPA-AUT was performed to compare AutD between patients and controls. The associations between AutD and disease-related characteristics of NIID were studied. Results: 94.26% of patients had AutD. Compared with controls, patients had more severe AutD in total SCOPA-AUT, gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor and sexual domains (all p < 0.05). The area under the curve (AUC) value for the total SCOPA-AUT (AUC = 0.846, sensitivity = 69.7%, specificity = 85.2%, cutoff value = 4.5) was high in differentiating AtuD of patients with NIID from controls. The total SCOPA-AUT was significantly and positively associated with age (r = 0.185, p = 0.041), disease duration (r = 0.207, p = 0.022), Neuropsychiatric Inventory (NPI) (r = 0.446, p < 0.01), and Activities of Daily Living (ADL) (r = 0.390, p < 0.01). Patients with onset-of-AutD had higher SCOPA-AUT scores than patients without onset-of-AutD (p < 0.001), especially in the urinary system (p < 0.001) and male sexual dysfunction (p < 0.05). Conclusion: SCOPA-AUT can be used as a diagnostic and quantitative tool for autonomic dysfunction in NIID. The high prevalence of AutD in patients suggests that NIID diagnosis should be considered in patients with AutD, especially in those with unexplained AutD alone. AutD in patients is related to age, disease duration, impairment of daily living ability, and psychiatric symptoms.

ALS-plus related clinical and genetic study from China.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. An increasing number of researchers have found extra motor features in ALS, which are also called ALS-plus syndromes. Besides, a great majority of ALS patients also have cognitive impairment. However, clinical surveys of the frequency and genetic background of ALS-plus syndromes are rare, especially in China. METHODS: We investigated a large cohort of 1015 patients with ALS, classifying them into six groups according to different extramotor symptoms and documenting their clinical manifestations. Meanwhile, based on their cognitive function, we divided these patients into two groups and compared demographic characteristics. Genetic screening for rare damage variants (RDVs) was also performed on 847 patients. RESULTS: As a result, 16.75% of patients were identified with ALS-plus syndrome, and 49.5% of patients suffered cognitive impairment. ALS-plus group had lower ALSFRS-R scores, longer diagnostic delay time, and longer survival times, compared to ALS pure group. RDVs occurred less frequently in ALS-plus patients than in ALS-pure patients (P = 0.042) but showed no difference between ALS-cognitive impairment patients and ALS-cognitive normal patients. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus symptoms than ALS-cognitive normal group (P = 0.001). CONCLUSION: In summary, ALS-plus patients in China are not rare and show multiple differences from ALS-pure patients in clinical and genetic features. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus syndrome than ALS-cognitive normal group. Our observations correspond with the theory that ALS involves several diseases with different mechanisms and provide clinical validation.

Mendelian randomization analyses of smoking and Alzheimer's disease in Chinese and Japanese populations.

Background: Previous epidemiological studies have reported controversial results on the relationship between smoking and Alzheimer's disease (AD). Therefore, we sought to assess the association using Mendelian randomization (MR) analysis. Methods: We used single nucleotide polymorphisms (SNPs) associated with smoking quantity (cigarettes per day, CPD) from genome-wide association studies (GWAS) of Japanese population as instrumental variables, then we performed two-sample MR analysis to investigate the association between smoking and AD in a Chinese cohort (1,000 AD cases and 500 controls) and a Japanese cohort (3,962 AD cases and 4,074 controls), respectively. Results: Genetically higher smoking quantity showed no statistical causal association with AD risk (the inverse variance weighted (IVW) estimate in the Chinese cohort: odds ratio (OR) = 0.510, 95% confidence interval (CI) = 0.149-1.744, p = 0.284; IVW estimate in the Japanese cohort: OR = 1.170, 95% confidence interval CI = 0.790-1.734, p = 0.434). Conclusion: This MR study, for the first time in Chinese and Japanese populations, found no significant association between smoking and AD.

Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease.

Inadequate osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are key factors in the pathogenesis of osteoporosis. Patients with Alzheimer's disease (AD) have a higher incidence of osteoporosis than healthy adults, but the underlying mechanism is not clear. Here, we show that brain-derived extracellular vesicles (EVs) from adult AD or wild-type mice can cross the blood-brain barrier to reach the distal bone tissue, while only AD brain-derived EVs (AD-B-EVs) significantly promote the shift of the BMSC differentiation fate from osteogenesis to adipogenesis and induce a bone-fat imbalance. MiR-483-5p is highly enriched in AD-B-EVs, brain tissues from AD mice, and plasma-derived EVs from AD patients. This miRNA mediates the anti-osteogenic, pro-adipogenic, and pro-osteoporotic effects of AD-B-EVs by inhibiting Igf2. This study identifies the role of B-EVs as a promoter of osteoporosis in AD by transferring miR-483-5p.

A detection model for cognitive dysfunction based on volatile organic compounds from a large Chinese community cohort.

INTRODUCTION: We explored whether volatile organic compound (VOC) detection can serve as a screening tool to distinguish cognitive dysfunction (CD) from cognitively normal (CN) individuals. METHODS: The cognitive function of 1467 participants was assessed and their VOCs were detected. Six machine learning algorithms were conducted and the performance was determined. The plasma neurofilament light chain (NfL) was measured. RESULTS: Distinguished VOC patterns existed between CD and CN groups. The CD detection model showed good accuracy with an area under the receiver-operating characteristic curve (AUC) of 0.876. In addition, we found that 10 VOC ions showed significant differences between CD and CN individuals (p < 0.05); three VOCs were significantly related to plasma NfL (p < 0.005). Moreover, a combination of VOCs with NfL showed the best discriminating power (AUC = 0.877). DISCUSSION: Detection of VOCs from exhaled breath samples has the potential to provide a novel solution for the dilemma of CD screening.

Photodegradation of the Novel Herbicide Pyraquinate in Aqueous Solution: Kinetics, Photoproducts, Mechanisms, and Toxicity Assessment.

Pyraquinate, a newly developed 4-hydroxyphenylpyruvate dioxygenase class herbicide, has shown excellent control of resistant weeds in paddy fields. However, its environmental degradation products and corresponding ecotoxicological risks after field application remain ambiguous. In this study, we systematically investigate the photolytic behaviors of pyraquinate in aqueous solutions and in response to xenon lamp irradiation. The degradation follows first-order kinetics, and its rate depends on pH and the amount of organic matter. No vulnerability to light radiation is indicated. Ultrahigh-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry and UNIFI software analysis reveals six photoproducts generated by methyl oxidation, demethylation, oxidative dechlorination, and ester hydrolysis. Gaussian calculation suggests that activities due to hydroxyl radicals or aquatic oxygen atoms caused these reactions on the premise of obeying thermodynamic criteria. Practical toxicity test results show that the toxicity of pyraquinate to zebrafish embryos is low but increases when the compound is combined with its photoproducts.

Correlation between retinal structure and brain multimodal magnetic resonance imaging in patients with Alzheimer's disease.

Background: The retina imaging and brain magnetic resonance imaging (MRI) can both reflect early changes in Alzheimer's disease (AD) and may serve as potential biomarker for early diagnosis, but their correlation and the internal mechanism of retinal structural changes remain unclear. This study aimed to explore the possible correlation between retinal structure and visual pathway, brain structure, intrinsic activity changes in AD patients, as well as to build a classification model to identify AD patients. Methods: In the study, 49 AD patients and 48 healthy controls (HCs) were enrolled. Retinal images were obtained by optical coherence tomography (OCT). Multimodal MRI sequences of all subjects were collected. Spearman correlation analysis and multiple linear regression models were used to assess the correlation between OCT parameters and multimodal MRI findings. The diagnostic value of combination of retinal imaging and brain multimodal MRI was assessed by performing a receiver operating characteristic (ROC) curve. Results: Compared with HCs, retinal thickness and multimodal MRI findings of AD patients were significantly altered (p < 0.05). Significant correlations were presented between the fractional anisotropy (FA) value of optic tract and mean retinal thickness, macular volume, macular ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness in AD patients (p < 0.01). The fractional amplitude of low frequency fluctuations (fALFF) value of primary visual cortex (V1) was correlated with temporal quadrant peripapillary retinal nerve fiber layer (pRNFL) thickness (p < 0.05). The model combining thickness of GCL and temporal quadrant pRNFL, volume of hippocampus and lateral geniculate nucleus, and age showed the best performance to identify AD patients [area under the curve (AUC) = 0.936, sensitivity = 89.1%, specificity = 87.0%]. Conclusion: Our study demonstrated that retinal structure change was related to the loss of integrity of white matter fiber tracts in the visual pathway and the decreased LGN volume and functional metabolism of V1 in AD patients. Trans-synaptic axonal retrograde lesions may be the underlying mechanism. Combining retinal imaging and multimodal MRI may provide new insight into the mechanism of retinal structural changes in AD and may serve as new target for early auxiliary diagnosis of AD.