Life cycle exposure to titanium dioxide nanoparticles (TiO2-NPs) induces filial toxicity and population decline in the nematode Caenorhabditis elegans.

Titanium dioxide nanoparticle (TiO2-NP) exposure has raised significant concern due to their potential toxicity and adverse ecological impacts. Despite their ubiquitous presence in various environmental compartments, the long-term consequences of TiO2-NPs remain poorly understood. In this study, we combined data of in vivo toxicity and modeling to investigate the potential negative impacts of TiO2-NP exposure. We employed the nematode Caenorhabditis elegans, an environmental organism, to conduct a full life cycle TiO2-NP toxicity assays. Moreover, to assess the potential impact of TiO2-NP toxicity on population dynamics, we applied a stage-constructed matrix population model (MPM). Results showed that TiO2-NPs caused significant reductions in reproduction, survival, and growth of parental C. elegans (P0) at the examined concentrations. Moreover, these toxic effects were even more pronounced in the subsequent generation (F1) when exposed to TiO2-NPs. Furthermore, parental TiO2-NP exposure resulted in significant toxicity in non-exposed C. elegans progeny (TiO2-NPs free), adversely affecting their reproduction, survival, and growth. MPM analysis revealed decreased transition probabilities of surviving (Pi), growth (Gi), and fertility (Fi) in scenarios with TiO2-NP exposure. Additionally, the population growth rate (λmax) was found to be less than 1 in both P0 and F1, indicating a declining population trend after successive generations. Sensitivity analysis pinpointed L1 larvae as the most vulnerable stage, significantly contributing to the observed population decline in both P0 and F1 generations under TiO2-NP exposure. Our findings provide insight into the potential risk of an environmental organism like nematode by life cycle exposure to TiO2-NPs.

Diet Pattern Analysis in Alzheimer's Disease Implicates Gender Differences in Folate-B12-Homocysteine Axis on Cognitive Outcomes.

BACKGROUND & AIMS: Low plasma B12 and folate levels or hyperhomocysteinemia are related to cognitive impairment. This study explores the relationships among diet pattern, blood folate-B12-homocysteine levels, and cognition measurement in Alzheimer's disease (AD) while exploring whether a gender effect may exist. METHODS: This cross-sectional study enrolled 592 AD patients (246 males, 346 females) and the demographic data, blood biochemical profiles, Mini-Mental State Examination (MMSE), and a Food Frequency Questionnaire (FFQ) for quantitative assessment of dietary frequency were collected. Structural Equation Modeling (SEM) was employed to explore the associations among dietary patterns, blood profiles, and cognition. A least absolute shrinkage and selection operator regression model, stratified by gender, was constructed to analyze the weighting of possible confounders. RESULTS: Higher MMSE scores were related to higher frequencies of coffee/tea and higher educational levels, body mass index, and younger age. The SEM model revealed a direct influence of dietary frequencies (skimmed milk, thin pork, coffee/tea) and blood profiles (homocysteine, B12, and folate) on cognitive outcomes. At the same time, the influence of dietary pattern on cognition was not mediated by folate-B12-homocysteine levels. In males, a direct influence on the MMSE is attributed to B12, while in females, homocysteine is considered a more critical factor. CONCLUSIONS: Dietary patterns and blood profiles are both associated with cognitive domains in AD, and there are gender differences in the associations of dietary patterns and the levels of B12 and homocysteine. To enhance the quality of dietary care and nutritional status for individuals with dementia, our study results still require future validations with multi-center and longitudinal studies.

The use of individual-based FDG-PET volume of interest in predicting conversion from mild cognitive impairment to dementia.

BACKGROUND: Based on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI). METHODS: We included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer's disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration. RESULTS: The clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL. CONCLUSIONS: Our finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

Design of CMOS Analog Front-End Local-Field Potential Chopper Amplifier with Stimulation Artifact Tolerance for Real-Time Closed-Loop Deep Brain Stimulation SoC Applications.

A CMOS analog front-end (AFE) local-field potential (LFP) chopper amplifier with stimulation artifact tolerance, improved right-leg driven (RLD) circuit, and improved auxiliary path is proposed. In the proposed CMOS AFE LFP chopper amplifier, common-mode artifact voltage (CMAV) and differential-mode artifact voltage (DMAV) removal using the analog template removal method are proposed to achieve good signal linearity during stimulation. An improved auxiliary path is employed to boost the input impedance and allow the negative stimulation artifact voltage passing through. The common-mode noise is suppressed by the improved RLD circuit. The chip is implemented in 0.18-µm CMOS technology and the total chip area is 5.46-mm2. With the improved auxiliary path, the measured input impedance is larger than 133 MΩ in the signal bandwidth and reaches 8.2 GΩ at DC. With the improved RLD circuit, the measured CMRR is 131 - 144 dB in the signal bandwidth. Under 60-µs pulse width and 130-Hz constant current stimulation (CCS) with ±1-V CMAV and ±50-mV DMAV, the measured THD at the SC Amp output of fabricated AFE LFP chopper amplifier is 1.28%. The measurement results of In vitro agar tests have shown that with ±1.6-mA CCS pulses injecting to agar, the measured THD is 1.69%. Experimental results of both electrical and agar tests have verified that the proposed AFE LFP chopper amplifier has good stimulation artifact tolerance. The proposed CMOS AFE LFP chopper amplifier with analog template removal method is suitable for real-time closed-loop deep drain stimulation (DBS) SoC applications.

Cingulate white matter mediates the effects of fecal Ruminococcus on neuropsychiatric symptoms in patients with amyloid-positive amnestic mild cognitive impairment.

BACKGROUND: Microbiota-gut-brain axis interacts with one another to regulate brain functions. However, whether the impacts of gut dysbiosis on limbic white matter (WM) tracts contribute to the neuropsychiatric symptoms (NPS) in patients with amyloid-positive amnestic mild cognitive impairment (aMCI+), have not been explored yet. This study aimed to investigate the mediation effects of limbic WM integrity on the association between gut microbiota and NPS in patients with aMCI+. METHODS: Twenty patients with aMCI + and 20 healthy controls (HCs) were enrolled. All subjects underwent neuropsychological assessments and their microbial compositions were characterized using 16S rRNA Miseq sequencing technique. Amyloid deposition inspected by positron emission tomography imaging and limbic WM tracts (i.e., fornix, cingulum, and uncinate fasciculus) detected by diffusion tensor imaging were additionally measured in patients with aMCI+. We employed a regression-based mediation analysis using Hayes's PROCESS macro in this study. RESULTS: The relative abundance of genera Ruminococcus and Lactococcus was significantly decreased in patients with aMCI + versus HCs. The relative abundance of Ruminococcus was negatively correlated with affective symptom cluster in the aMCI + group. Notably, this association was mediated by WM integrity of the left cingulate gyrus. CONCLUSIONS: Our findings suggest Ruminococcus as a potential target for the management of affective impairments in patients with aMCI+.

Vascularized Toe Proximal Interphalangeal Joint Transfer in Posttraumatic Fingers: Analysis of Prognostic Factors for Suboptimal Outcomes.

Background: Posttraumatic finger osteoarthritis of the proximal interphalangeal joint (PIPJ) is a difficult problem. Over the past decade, we have reported several methods for improving the outcomes of vascularized toe joint transfer (VJT). In this study, we focused on determining poor prognostic factors which lead to a suboptimal outcome. Methods: A consecutive series of patients with posttraumatic osteoarthritis of the PIPJ who received VJT between January 2008 and January 2021 were enrolled in this study. The senior surgeon (Y.-T.L.) performed the surgery in all cases. In this retrospective study, we reexamine the initial trauma-related soft tissue and bony structure injuries of the recipient finger, to assess the baseline tissue quality before VJT. The injuries were classified into five major categories according to their anatomic region. The functional outcome parameters (including range of motion, percentage of use, and extensor lag of the transferred PIPJ) were collected. Univariate and multivariate linear regression analyses were performed using the generalized estimated equation model to identify the correlation between the injury category involved and functional outcome. Results: A total of 59 digits were enrolled. Our results revealed that the fingers with previous vascular injury that received revascularization procedures had relatively suboptimal functional outcomes. These fingers had a significantly lower percentage of use both before (ß = -0.222, P = 0.006) and after (ß = -0.177, P = 0.006) receiving secondary procedures to improve functional outcome. Conclusions: Patients with prior revascularization surgery were associated with a poor functional outcome after VJT.

A review of biosensor for environmental monitoring: principle, application, and corresponding achievement of sustainable development goals.

Human health/socioeconomic development is closely correlated to environmental pollution, highlighting the need to monitor contaminants in the real environment with reliable devices such as biosensors. Recently, variety of biosensors gained high attention and employed as in-situ application, in real-time, and cost-effective analytical tools for healthy environment. For continuous environmental monitoring, it is necessary for portable, cost-effective, quick, and flexible biosensing devices. These benefits of the biosensor strategy are related to the Sustainable Development Goals (SDGs) established by the United Nations (UN), especially with reference to clean water and sources of energy. However, the relationship between SDGs and biosensor application for environmental monitoring is not well understood. In addition, some limitations and challenges might hinder the biosensor application on environmental monitoring. Herein, we reviewed the different types of biosensors, principle and applications, and their correlation with SDG 6, 12, 13, 14, and 15 as a reference for related authorities and administrators to consider. In this review, biosensors for different pollutants such as heavy metals and organics were documented. The present study highlights the application of biosensor for achieving SDGs. Current advantages and future research aspects are summarized in this paper.Abbreviations: ATP: Adenosine triphosphate; BOD: Biological oxygen demand; COD: Chemical oxygen demand; Cu-TCPP: Cu-porphyrin; DNA: Deoxyribonucleic acid; EDCs: Endocrine disrupting chemicals; EPA: U.S. Environmental Protection Agency; Fc-HPNs: Ferrocene (Fc)-based hollow polymeric nanospheres; Fe3O4@3D-GO: Fe3O4@three-dimensional graphene oxide; GC: Gas chromatography; GCE: Glassy carbon electrode; GFP: Green fluorescent protein; GHGs: Greenhouse gases; HPLC: High performance liquid chromatography; ICP-MS: Inductively coupled plasma mass spectrometry; ITO: Indium tin oxide; LAS: Linear alkylbenzene sulfonate; LIG: Laser-induced graphene; LOD: Limit of detection; ME: Magnetoelastic; MFC: Microbial fuel cell; MIP: Molecular imprinting polymers; MWCNT: Multi-walled carbon nanotube; MXC: Microbial electrochemical cell-based; NA: Nucleic acid; OBP: Odorant binding protein; OPs: Organophosphorus; PAHs: Polycyclic aromatic hydrocarbons; PBBs: Polybrominated biphenyls; PBDEs: Polybrominated diphenyl ethers; PCBs: Polychlorinated biphenyls; PGE: Polycrystalline gold electrode; photoMFC: photosynthetic MFC; POPs: Persistent organic pollutants; rGO: Reduced graphene oxide; RNA: Ribonucleic acid; SDGs: Sustainable Development Goals; SERS: Surface enhancement Raman spectrum; SPGE: Screen-printed gold electrode; SPR: Surface plasmon resonance; SWCNTs: single-walled carbon nanotubes; TCPP: Tetrakis (4-carboxyphenyl) porphyrin; TIRF: Total internal reflection fluorescence; TIRF: Total internal reflection fluorescence; TOL: Toluene-catabolic; TPHs: Total petroleum hydrocarbons; UN: United Nations; VOCs: Volatile organic compounds.

Association of Cognition and Brain Reserve in Aging and Glymphatic Function Using Diffusion Tensor Image-along the Perivascular Space (DTI-ALPS).

The glymphatic system is a fluid-clearance pathway that clears cerebral waste products, and its dysfunction has been associated with protein aggregation diseases such as Alzheimer's disease. To understand how the glymphatic system changes with aging, we enrolled 433 cognitive unimpaired participants (236 women and 197 men, 13-88 years) and evaluated the glymphatic function by calculating diffusion tensor imaging analysis along the perivascular space (ALPS) index and explored how the ALPS index is associated with cortical atrophy and cognitive decline in older people. We found a significant inverse correlation between ALPS index and age (ρ = -0.45, p < 0.001), with a peak value in people in their thirties. A higher ALPS index indicated a better cortical reserve in regions coincided with the default mode network. Declines in mental manipulation and short-term memory performance in the older participants were associated with a lower ALPS index and cortical atrophy in the amygdala, anterior and posterior cingulate, thalamus and middle frontal regions. Our findings highlight that the ALPS index could be used to evaluate brain reserve and cognitive reserve in older people.

Gray matter reserve determines glymphatic system function in young-onset Alzheimer's disease: Evidenced by DTI-ALPS and compared with age-matched controls.

BACKGROUND: The diffusion tensor imaging analysis along the perivascular space (ALPS)-index can be used to model the glymphatic system in vivo. AIM: This study explores putative mechanisms between prediction of ALPS-index and cognitive outcomes in young-onset Alzheimer's disease (YOAD) and age-matched controls (CTLs) and analyzes whether the link was mediated by the integrity of ALPS-index-anchored cerebral gray matter (GM). METHODS: We enrolled 130 patients with YOAD and 137 CTLs. All participants underwent three-dimensional T1 -weighted MRI, diffusion tensor imaging and cognitive tests. We constructed GM regions correlated with the ALPS-index in the YOAD and CTL groups. For the GM regions significantly correlated with the ALPS-index and cognitive measures, we extracted a 4-mm radius sphere. In the YOAD and CTL groups, we used mediator analysis to explore the ALPS-index as predictor, GM partitions as mediators, and significant cognitive test scores as outcomes. RESULTS: Patient group had significantly lower ALPS-index. The ALPS-index was associated with GM volume in the cerebellar gray, dorsolateral prefrontal, thalamus, superior frontal, amygdala and hippocampus, and these coherent regions coincided with those showing GM atrophy in the YOAD group. Mediation analysis of the YOAD group suggested that the relationships between the ALPS-index and cognitive performance were fully mediated by the integrity of ALPS-index coherent GM areas. DISCUSSION: Reserved GM mediates the link between the glymphatic system and cognition. Our findings suggest that GM integrity rather than the glymphatic system could serve as a direct cognitive test scores predictor in patients with YOAD.

Clinical significance of fractional anisotropy in cerebral white matter regional vulnerability caused by carbon monoxide poisoning: A systematic review and meta-analysis.

Carbon monoxide poisoning (COP) can lead to various cerebral white matter (WM) lesions across different disease phases and clinical manifestations, and fractional anisotropy (FA) of diffusion tensor imaging has been widely applied to investigate WM injury in these patients. Here we conducted a systematic review and meta-analysis to investigate the utility of FA in evaluating the regional vulnerability of WM injury caused by COP and explore differences between different disease phases and patient subtypes. We systematically searched PubMed, Medline, Scopus and reference lists of appropriate publications to identify relevant studies. Eight studies with 217 patients with COP and 207 healthy controls (HCs) were included. Eight regions of interest were available to investigate regional vulnerability. The results showed the most significant decrease in FA in orbitofrontal subcortical regions. Comparisons of different disease phases revealed lower FA in the centrum semiovale and corpus callosum in the acute phase, while in the chronic phase, only FA in the centrum semiovale remained significantly decreased. Analysis of different patient subtypes showed that the FA values in the splenium of the corpus callosum were significantly decreased in the patients with delayed neurologic sequelae (DNS) but not in the mixed population (with and without DNS). In conclusion, this meta-analysis highlights the frontal-subcortical regional vulnerability in COP. FA changes in the corpus callosum across different disease phases reflect alterations in underlying microstructures. Extended corpus callosum injury involving the splenium could be an imaging biomarker of the occurrence of DNS.

Co-contaminants of ethinylestradiol and sulfamethoxazole in groundwater exacerbate ecotoxicity and ecological risk and compromise the energy budget of C. elegans.

Ethinylestradiol (EE2) and sulfamethoxazole (SMX) are among pharmaceuticals and personal care products (PPCPs) and regarded as emerging contaminants in groundwater worldwide. However, the ecotoxicity and potential risk of these co-contaminants remain unknown. We investigated the effects of early-life long-term co-exposure to EE2 and SMX in groundwater on life-history traits of Caenorhabditis elegans and determined potential ecological risks in groundwater. L1 larvae of wild-type N2 C. elegans were exposed to measured concentrations of EE2 (0.001, 0.75, 5.1, 11.8 mg/L) or SMX (0.001, 1, 10, 100 mg/L) or co-exposed to EE2 (0.75 mg/L, no observed adverse effect level derived from its reproductive toxicity) and SMX (0.001, 1, 10, 100 mg/L) in groundwater. Growth and reproduction were monitored on days 0 - 6 of the exposure period. Toxicological data were analyzed using DEBtox modeling to determine the physiological modes of action (pMoAs) and the predicted no-effect concentrations (PNECs) to estimate ecological risks posed by EE2 and SMX in global groundwater. Early-life EE2 exposure significantly inhibited the growth and reproduction of C. elegans, with lowest observed adverse effect levels (LOAELs) of 11.8 and 5.1 mg/L, respectively. SMX exposure impaired the reproductive capacity of C. elegans (LOAEL = 0.001 mg/L). Co-exposure to EE2 and SMX exacerbated ecotoxicity (LOAELs of 1 mg/L SMX for growth, and 0.001 mg/L SMX for reproduction). DEBtox modeling showed that the pMoAs were increased growth and reproduction costs for EE2 and increased reproduction costs for SMX. The derived PNEC falls within the range of detected environmental levels of EE2 and SMX in groundwater worldwide. The pMoAs for EE2 and SMX combined were increased growth and reproduction costs, resulting in lower energy threshold values than single exposure. Based on global groundwater contamination data and energy threshold values, we calculated risk quotients for EE2 (0.1 - 123.0), SMX (0.2 - 91.3), and combination of EE2 and SMX (0.4 - 341.1). Our findings found that co-contamination by EE2 and SMX exacerbates toxicity and ecological risk to non-target organisms, suggesting that the ecotoxicity and ecological risk of co-contaminants of pharmaceuticals should be considered to sustainably manage groundwater and aquatic ecosystems.

Neuropsychiatric Symptoms and Caregiver Stress in Parkinson's Disease with Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

BACKGROUND: A better understanding of factors associated with caregiver burden might facilitate the construction of coping strategies to improve their clinical outcomes and the comprehensive care model for dementia. OBJECTIVE: To investigate the cognitive and neuropsychiatric domains that contribute to caregiver burden in three types of neurodegenerative disorders: Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal disease (FTD). METHODS: Eight hundred and fourteen patients and their caregivers were invited to participate; among them, 235 had PD with cognitive impairment; 429 had AD, and 150 had FTD. The evaluation protocol included the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, the Chinese Version Verbal Learning Test, the modified Trail Making Test B, semantic fluency, and a geriatric depression score. Statistical comparisons of the cognitive tests, NPI total scores, and caregiver burden among the three diagnosed types of dementia, matched for a Clinical Dementia Rating (CDR) of 0.5 or 1, were performed, and multivariate linear regression models were used to evaluate the parameter significance. RESULTS: Caregivers for patients with PD and FTD showed significant burden increments when the CDR scores changes from 0.5 to 1. For CDR = 0.5, the PD group had significantly lower caregiver burdens than the AD group, but the NPI total scores were significantly higher. Factors related to caregiver burden were the presence of delusion among all diagnosis groups, while the impact of NPI total scores related to caregiver burden was the highest in FTD, followed by AD and PD. CONCLUSIONS: At the mild to moderate stages, our results suggested different degrees of significance in terms of the cognitive test scores or NPI subdomains for predicting caregiver stress among the three types of dementia.

Dietary Transfer of Zinc Oxide Nanoparticles Induces Locomotive Defects Associated with GABAergic Motor Neuron Damage in Caenorhabditis elegans.

The widespread use of zinc oxide nanoparticles (ZnO-NPs) and their release into the environment have raised concerns about the potential toxicity caused by dietary transfer. However, the toxic effects and the mechanisms of dietary transfer of ZnO-NPs have rarely been investigated. We employed the bacteria-feeding nematode Caenorhabditis elegans as the model organism to investigate the neurotoxicity induced by exposure to ZnO-NPs via trophic transfer. Our results showed that ZnO-NPs accumulated in the intestine of C. elegans and also in Escherichia coli OP50 that they ingested. Additionally, impairment of locomotive behaviors, including decreased body bending and head thrashing frequencies, were observed in C. elegans that were fed E. coli pre-treated with ZnO-NPs, which might have occurred because of damage to the D-type GABAergic motor neurons. However, these toxic effects were not apparent in C. elegans that were fed E. coli pre-treated with zinc chloride (ZnCl2). Therefore, ZnO-NPs particulates, rather than released Zn ions, damage the D-type GABAergic motor neurons and adversely affect the locomotive behaviors of C. elegans via dietary transfer.

Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis.

Background & Aims: Sarcopenia and gut dysbiosis are common in individuals with cirrhosis. However, the association between sarcopenia and microbial alterations, and the subsequent impact on cirrhotic outcomes are poorly understood. This study aimed to identify muscle-dependent microbial changes and related risks of cirrhotic complications. Methods: From September 2018 to December 2020, 89 individuals with cirrhosis and 16 healthy volunteers were prospectively enrolled. Muscle and nutritional status, serum amino acids, and fecal microbiota were analyzed. The association between microbial signatures of sarcopenia and cirrhotic complications was investigated. Results: A decline in muscle mass and strength were associated with gut microbial alterations in individuals with cirrhosis. The greatest microbial dissimilarity was observed between those with sarcopenia (both decline in muscle mass and strength) and those with normal-muscle status (p = 0.035). Individuals with sarcopenia had lower serum levels of alanine, valine, leucine, isoleucine, proline, tryptophan and ornithine. Besides, gut microbial functions associated with amino acid biosynthesis were significantly reduced in individuals with sarcopenia and cirrhosis. Depletion of Dialister, Ruminococcus 2, and Anaerostipes were associated with cirrhotic sarcopenia, and significantly correlated with the serum levels of amino acids. Individuals with coexistent depletion of Ruminococcus 2 and Anaerostipes developed more infectious (44.4% vs. 3.0%) and non-infectious (74.1% vs. 3.0%) complications, and more hospitalizations (54 vs. 3) than those with cirrhosis with good microbial signatures (all p <0.001). In contrast, fecal enrichment of Ruminococcus 2 and Anaerostipes independently decreased the risk of 1-year complications. Conclusions: Sarcopenia-related fecal microbial alterations are associated with cirrhotic complications. These findings may facilitate measures to improve the outcomes of individuals with cirrhosis and sarcopenia by modifying gut microbiota. Impact and implications: The composition and biosynthetic functions of gut microbiota are significantly changed in individuals with sarcopenic cirrhosis. Those with a sarcopenia-related poor microbial signature, in which Ruminococcus 2 and Anaerostipes were both depleted, had significantly more infectious and non-infectious complications, as well as more hospitalizations. These findings highlight the therapeutic potential of modifying the gut microbiota of individuals with sarcopenic cirrhosis to improve their clinical outcomes.

Ecological risk assessment and corrective actions for dioxin-polluted sediment in a chemical plant's brine water storage pond.

Despite the known high toxicity of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, or dioxins), there are few case studies of PCDD/Fs contamination in sediment and there remains much to learn regarding their ecological impact. In this study, we performed an environmental risk assessment of a brine water storage pond near a chemical plant with high PCDD/Fs pollution potential before and after corrective actions. We found PCDD/F accumulation in the pond's fish and crab from the brine water storage pond, and the PCDD/Fs concentrations in biota higher than Taiwan's food safety standard (3.5 pg-TEQ/g). Furthermore, we found a high degree of pollution using different indices, including contamination factor (CF), modified degree of contamination (mCd), and pollution index (PI), in the pond's sediment. Before corrective actions, we also found high risk in the PCDD/F contamination in the sediment using various biological risk indices, including potential ecological risk index (RI) and risk quotient (RQ). After the corrective actions, including institutional/engineering control and remediation, the CF, mCd, and PI had decreased by 20-41 % and RI and RQ by 41-56 %. In addition, despite the slight reduction of pollution and risk index values in the whole pond, significant reduction was observed in the sediment of highly polluted area A owing to the lower disturbing suction dredging. In conclusion, the corrective actions used in this study helped decrease the pollution and ecological risk associated with this site's PCDD/Fs polluted sediment to some extent, suggesting that contamination and risk could be reduced to acceptable levels if these corrective actions are continued.

Verification of the beta oscillations in the subthalamic nucleus of the MPTP-induced parkinsonian minipig model.

The development of the closed-loop deep brain stimulator (DBS) for clinical trials requires verification of its safety and effectiveness in a large animal model. Due to the financial and ethical challenges of using non-human primates, it is reasonable to use an alternative large animal model. It was reported that minipigs are suitable for the establishment of the MPTP-induced parkinsonian model. However, there is currently no evidence of whether beta oscillations, the symptom-related biomarker, exist in the subthalamic nucleus (STN) of the parkinsonian minipig model. This study was to verify whether the beta oscillations could be recorded in the STN of the parkinsonian minipig model. Parkinsonism was induced by injections of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Through a protocol involving up to nine subcutaneous or intramuscular injections, delivering a cumulative dose of 8-10 mg/kg MPTP, the minipigs developed notable movement disturbance. By stereotactic surgery and microelectrode recording, beta oscillations were recorded in the STN of the MPTP-injected minipigs. Immunohistochemistry of the tyrosine hydroxylase (TH) was performed in the substantia nigra pars compacta (SNc) of each animal. Compared with the control animal injected with saline, the TH-positive cells in the SNc were significantly reduced in the MPTP-injected minipigs. This study showed that beta oscillations could be recorded in the STN of the MPTP-induced parkinsonian minipig model. This large animal model is suitable as an alternative pre-clinical model for developing closed-loop DBS in the future.

Seasonal influence on pollution index and risk of multiple compositions of microplastics in an urban river.

Emerging contaminant microplastics (MPs) are getting worldwide attention for their ubiquitous occurrence and potential risk to the environment. However, the seasonal influence on freshwater MP pollution remains poorly understood. To better understand and evaluate the riverine MPs in different seasons, this study conducted the risk assessment of MPs in an urban river, Houjin River, during the different seasons. The present study found that the MPs (0.1-5 mm, mostly 0.1-2 mm) were more abundant in the dry season (183.33 ± 128.95 items/m3) compared with the wet season (102.08 ± 45.80 items/m3). Similarly, the mixture of different MPs polymers was more diverse in the dry season. The related pollution indices such as the contamination factor (CF) and pollution load index (PLI) showed that average CF and PLI were 5.15 and 2.10 in the dry season, which significantly decreased to 1.58 and 1.25, respectively, in the wet season (p < 0.05). Additionally, significant difference of the average risk quotient (RQ) was observed, which was 0.037 in the dry season and 0.021 in the wet season (p < 0.05). To sum up, the results of this study indicate the seasonal effects on the pollution and risk of multiple compositions of MPs in the urban river, suggesting higher impacts of riverine MPs pollution in the dry season, as well as the potential increase of MPs, may lead to environmental risk in the future.

Cognitive Decline Related to Diet Pattern and Nutritional Adequacy in Alzheimer's Disease Using Surface-Based Morphometry.

Dietary pattern (DP) results in nutrition adequacy and may influence cognitive decline and cortical atrophy in Alzheimer's disease (AD). The study explored DP in 248 patients with AD. Two neurobehavioral assessments (intervals 13.4 months) and two cortical thickness measurements derived from magnetic resonance images (intervals 26.5 months) were collected as outcome measures. Reduced rank regression was used to assess the groups of DPs and a linear mixed-effect model to explore the cortical neurodegenerative patterns. At screening, underweight body mass index (BMI) was related to significant higher lipid profile, impaired cognitive function, smaller cortical thickness, lower protein DP factor loading scores and the non-spouse caregiver status. Higher mini-mental state examination (MMSE) scores were related to the DP of coffee/tea, compared to the lipid/sugar or protein DP group. The underweighted-BMI group had faster cortical thickness atrophy in the pregenual and lateral temporal cortex, while the correlations between cortical thickness degeneration and high HbA1C or low B12 and folate levels were localized in the medial and lateral prefrontal cortex. The predictive model suggested that factors related to MMSE score were related to the caregiver status. In conclusion, normal or overweight BMI, coffee/tea DP group and living with a spouse were considered as protective factors for better cognitive outcomes in patients with AD. The influence of glucose, B12 and folate on the cortical degeneration was spatially distinct from the pattern of AD degeneration.

Functional MRI and ApoE4 genotype for predicting cognitive decline in amyloid-positive individuals.

Background: In light of advancements in machine learning techniques, many studies have implemented machine learning approaches combined with data measures to predict and classify Alzheimer's disease. Studies that predicted cognitive status with longitudinal follow-up of amyloid-positive individuals remain scarce, however. Objective: We developed models based on voxel-wise functional connectivity (FC) density mapping and the presence of the ApoE4 genotype to predict whether amyloid-positive individuals would experience cognitive decline after 1 year. Methods: We divided 122 participants into cognitive decline and stable cognition groups based on the participants' change rates in Mini-Mental State Examination scores. In addition, we included 68 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) database as an external validation data set. Subsequently, we developed two classification models: the first model included 99 voxels, and the second model included 99 voxels and the ApoE4 genotype as features to train the models by Wide Neural Network algorithm with fivefold cross-validation and to predict the classes in the hold-out test and ADNI data sets. Results: The results revealed that both models demonstrated high accuracy in classifying the two groups in the hold-out test data set. The model for FC demonstrated good performance, with a mean F 1-score of 0.86. The model for FC combined with the ApoE4 genotype achieved superior performance, with a mean F 1-score of 0.90. In the ADNI data set, the two models demonstrated stable performances, with mean F 1-scores of 0.77 in the first and second models. Conclusion: Our findings suggest that the proposed models exhibited promising accuracy for predicting cognitive status after 1 year in amyloid-positive individuals. Notably, the combination of FC and the ApoE4 genotype increased prediction accuracy. These findings can assist clinicians in predicting changes in cognitive status in individuals with a high risk of Alzheimer's disease and can assist future studies in developing precise treatment and prevention strategies.

MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway.

The MYH9 (Myosin heavy chain 9), an architecture component of the actomyosin cytoskeleton, has been reported to be dysregulated in several types of cancers. However, how this molecule contributes to cancer development is still obscure. This study deciphered the molecular function of MYH9 in head and neck cancer (HNC). Cellular methods included clonogenic survival, wound-healing migration, and Matrigel invasion assays. Molecular techniques included RT-qPCR, western blot, luciferase reporter assays, and flow cytometry. Clinical association studies were undertaken by TCGA data mining, Spearman correlation, and Kaplan-Meier survival analysis. We found that MYH9 was overexpressed in tumors and associated with poor prognosis in HNC patients. MYH9 promoted cell motility along with the modulation of the extracellular matrix (fibronectin, ITGA6, fascin, vimentin, MMPs). Also, MYH9 contributed to radioresistance and was related to the expression of anti-apoptotic and DNA repairing molecules (XIAP, MCL1, BCL2L1, ATM, RAD50, and NBN). Mechanically, MYH9 suppressed cellular ROS levels, which were achieved by activating the pan-MAPK signaling molecules (Erk, p38, and JNK), the induction of Nrf2 transcriptional activity, and the up-regulation of antioxidant enzymes (GCLC, GCLM, GPX2). The antioxidant enzyme GCLC was further demonstrated to facilitate cell invasion and radioresistance in HNC cells. Thus, MYH9 exerts malignant functions in HNC by regulating cellular ROS levels via activating the MAPK-Nrf2-GCLC signaling pathway. As MYH9 contributes to radioresistance and metastasis, this molecule may serve as a prognostic biomarker for clinical application. Furthermore, an in vivo study is emergent to support the therapeutic potential of targeting MYH9 to better manage refractory cancers.