Pattern of heterogeneity in normal brain ageing: screening for mild cognitive impairment and its risk of progression with a radiomics model.

PURPOSE: This study aimed to develop a normal brain ageing model based on magnetic resonance imaging and radiomics, therefore identifying radscore, an imaging indicator representing white matter heterogeneity and exploring the significance of radscore in detecting people's cognitive changes. METHODS: Three hundred sixty cognitively normal (CN) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 105 CN subjects from the Parkinson's Progression Markers Initiative database were used to develop the model. In ADNI, 230 mild cognitive impairment (MCI) subjects were matched with 230 CN old-aged subjects to evaluate their heterogeneity difference. One hundred four MCI subjects with 48 months of follow-up were divided into low and high heterogeneity groups. Kaplan-Meier survival curve analysis was used to observe the importance of heterogeneity results for predicting MCI progression. RESULTS: The area under the receiver operating characteristic curve of the model in the training, internal test and external test sets was 0.7503, 0.7512 and 0.7514, respectively. There was a significantly positive correlation between age and radscore of CN subjects (r = 0.501; P < .001). The radscore of MCI subjects was significantly higher than that of matched CN subjects (P < .001). The median radscore ratios of MCI to CN from four age groups (66-70y, 71-75y, 76-80y and 81-85y) were 1.611, 1.760, 1.340 and 1.266, respectively. The probability to progression of low and high heterogeneity groups had a significant difference (P = .002). CONCLUSION: When radscore is significantly higher than that of normal ageing, it is necessary to alert the possibility of cognitive impairment and deterioration.

Utilisation of Lactiplantibacillus plantarum and propionic acid to improve silage quality of amaranth before and after wilting: fermentation quality, microbial communities, and their metabolic pathway.

Objective: The aim of this study was to investigate the effects of Lactiplantibacillus plantarum (L. plantarum) and propionic acid (PA) on fermentation characteristics and microbial community of amaranth (Amaranthus hypochondriaus) silage with different moisture contents. Methods: Amaranth was harvested at maturity stage and prepared for ensiling. There were two moisture content gradients (80%: AhG, 70%: AhS; fresh material: FM) and three treatments (control: CK, L. plantarum: LP, propionic acid: PA) set up, and silages were opened after 60 d of ensiling. Results: The results showed that the addition of L. plantarum and PA increased lactic acid (LA) content and decreased pH of amaranth after fermentation. In particular, the addition of PA significantly increased crude protein content (p < 0.05). LA content was higher in wilted silage than in high-moisture silage, and it was higher with the addition of L. plantarum and PA (p < 0.05). The dominant species of AhGLP, AhSCK, AhSLP and AhSPA were mainly L. plantarum, Lentilactobacillus buchneri and Levilactobacillus brevis. The dominant species in AhGCK include Enterobacter cloacae, and Xanthomonas oryzae was dominated in AhGPA, which affected fermentation quality. L. plantarum and PA acted synergistically after ensiling to accelerate the succession of dominant species from gram-negative to gram-positive bacteria, forming a symbiotic microbial network centred on lactic acid bacteria. Both wilting and additive silage preparation methods increased the degree of dominance of global and overview maps and carbohydrate metabolism, and decreased the degree of dominance of amino acid metabolism categories. Conclusion: In conclusion, the addition of L. plantarum to silage can effectively improve the fermentation characteristics of amaranth, increase the diversity of bacterial communities, and regulate the microbial community and its functional metabolic pathways to achieve the desired fermentation effect.

Groundwater suitability assessment for irrigation and drinking purposes by integrating spatial analysis, machine learning, water quality index, and health risk model.

An in-depth understanding of nitrate-contaminated surface water and groundwater quality and associated risks is important for groundwater management. Hydrochemical characteristics and driving forces of groundwater quality and non-carcinogenic risks of nitrate were revealed by the integrated approaches of self-organizing map analysis, spatial visualization by geography information system, entropy and irrigation water quality indices, and human health risk model. Groundwater samples were categorized into two clusters by SOM analysis. Cluster I including three samples were Ca-SO4 type and cluster II of remaining 136 samples were Ca-HCO3 type. Hydrochemical compositions of two cluster samples were dominated by water-rock interaction: (1) calcite and gypsum dissolution for cluster I samples and (2) calcite dissolution, silicate weathering, and positive cation exchange for cluster II samples. Nitrate contamination occurred in both cluster I and II samples, primarily induced by agricultural nitrogen fertilizer. The EWQI results showed that 90.97% in total groundwater samples were suitable for drinking purpose, while the IWQI results demonstrated that 65.03% in total groundwater samples were appropriate for irrigation purpose. The HHR model and Monte Carlo simulation indicated that the non-carcinogenic nitrated risk was highest in children. Exposure frequency was the most sensitive factor (86.33% in total) influencing the total non-carcinogenic risk, indicated by sensitivity analysis. Compared with the two clusters of groundwater, surface water has a shorter circulation cycle and lower ion concentrations resulting in better water quality. This study can provide scientific basis for groundwater quality evaluation in other parts of the world.

Natural background levels, source apportionment and health risks of potentially toxic elements in groundwater of highly urbanized area.

Identifying the natural background levels (NBLs), threshold values (TVs), sources and health risks of potentially toxic elements in groundwater is crucial for ensuring the water security of residents in highly urbanized areas. In this study, 96 groundwater samples were collected in urban area of Sichuan Basin, SW China. The concentrations of potentially toxic elements (Li, Fe, Cu, Zn, Al, Pb, B, Ba and Ni) were analyzed for investigating the NBLs, TVs, sources and health risks. The potentially toxic elements followed the concentration order of Fe > Ba > B > Al > Zn > Li > Cu > Ni > Pb. The NBLs and TVs indicated the contamination of potentially toxic elements mainly occurred in the northern and central parts of the study area. The Positive Matrix Factorization (PMF) model identified elevated concentrations of Fe, Al, Li, and B were found to determine groundwater quality. The primary sources of Fe, Al, Pb, and Ni were attributed to the dissolution of oxidation products, with Fe additionally affected by anthropogenic reduction environments. Li and B were determined to be originated from the weathering of tourmaline. High levels of Ni and Cu concentrations were derived from electronic waste leakage, while excessive Ba and Zn were linked to factory emissions and tire wear. The reasonable maximum exposure (RME) of hazard index (HI) was higher than safety standard and reveal the potential health risks in the southwestern study area. Sensitivity analysis demonstrated the Li concentrations possessed the highest weight contributing to health risk. This study provides a valuable information for source-specific risk assessments of potentially toxic elements in groundwater associated with urban areas.

Maritime Freight Carbon Emission in the U.S. using AIS data from 2018 to 2022.

Global maritime emissions, a 3% contributor to greenhouse gases, anticipate a surge of 90-130% by 2050. Regulatory challenges persist due to international governance gaps. Legislative strides, including the EU Emission Trading System, highlight global efforts. In the U.S., despite legislative commitment, consensus hurdles impede cross-regional carbon management. Prevailing top-down emissions estimation methods warrant scrutiny. This paper unveils U.S. maritime emissions intricacies, focusing on carbon accounting, transfer, and compensation for cargo and tanker vessels. Leveraging AIS data (2018-2022), an activity-based/bottom-up approach navigates emissions calculations, aiming to reshape understanding and foster strategic reductions. The study bridges gaps in U.S. maritime emission research, promising insights into transfer and compensation dynamics. By concentrating on high-impact vessel types, it contributes to emissions mitigation strategies, steering towards a sustainable U.S. maritime future.

Comparison between morphometry and radiomics: detecting normal brain aging based on grey matter.

Objective: Voxel-based morphometry (VBM), surface-based morphometry (SBM), and radiomics are widely used in the field of neuroimage analysis, while it is still unclear that the performance comparison between traditional morphometry and emerging radiomics methods in diagnosing brain aging. In this study, we aimed to develop a VBM-SBM model and a radiomics model for brain aging based on cognitively normal (CN) individuals and compare their performance to explore both methods' strengths, weaknesses, and relationships. Methods: 967 CN participants were included in this study. Subjects were classified into the middle-aged group (n = 302) and the old-aged group (n = 665) according to the age of 66. The data of 360 subjects from the Alzheimer's Disease Neuroimaging Initiative were used for training and internal test of the VBM-SBM and radiomics models, and the data of 607 subjects from the Australian Imaging, Biomarker and Lifestyle, the National Alzheimer's Coordinating Center, and the Parkinson's Progression Markers Initiative databases were used for the external tests. Logistics regression participated in the construction of both models. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the two model performances. The DeLong test was used to compare the differences in AUCs between models. The Spearman correlation analysis was used to observe the correlations between age, VBM-SBM parameters, and radiomics features. Results: The AUCs of the VBM-SBM model and radiomics model were 0.697 and 0.778 in the training set (p = 0.018), 0.640 and 0.789 in the internal test set (p = 0.007), 0.736 and 0.737 in the AIBL test set (p = 0.972), 0.746 and 0.838 in the NACC test set (p < 0.001), and 0.701 and 0.830 in the PPMI test set (p = 0.036). Weak correlations were observed between VBM-SBM parameters and radiomics features (p < 0.05). Conclusion: The radiomics model achieved better performance than the VBM-SBM model. Radiomics provides a good option for researchers who prioritize performance and generalization, whereas VBM-SBM is more suitable for those who emphasize interpretability and clinical practice.

Evaluate the groundwater quality and human health risks for sustainable drinking and irrigation purposes in mountainous region of Chongqing, Southwest China.

Groundwater is crucial for agriculture and domestic consumption. This research investigated the hydrogeochemical properties and contaminant sources of groundwater within the mountainous terrain of northern Chongqing, with the objective of evaluating its appropriateness for irrigation and potable use. The hydrochemical type of the groundwater was HCO3 - Ca, dominated by silicate and calcite dissolutions. High NO3- (29.03% exceeds 10 mg/L) were attributed to the overuse of agricultural fertilizers. A comprehensive evaluation was conducted to determine the groundwater suitability for agricultural and potable uses. The results showed that groundwater in the southwestern region, particularly within the Yangtze River mainstem watershed, exhibited less suitability for irrigation owing to its lower mineralization, in contrast to the northeastern region near the Daning River watershed. But this trend is reversed for drinking purposes. Overall, the groundwater was appropriate for both drinking (93.55% were classified as excellent) and irrigation (70.98% were classified as low restriction) purposes in the study area. Deterministic and probabilistic noncarcinogenic health risk analyses centered on nitrate exposure revealed that infants (with 13.79% of samples >1) were at greater risk than children (8.58%), adult males (6.98%), and adult females (5.24%). This underscores the urgency to reduce nitrogen fertilizer usage and improve water management in the region. This research will provide guidance for the sustainable groundwater management in mountainous regions.

[Pollution Characteristics and Ecological Risk Assessment of Microplastics in the Yangtze River Basin].

The Yangtze River, the largest river in China, has not been comprehensively studied for its basin's microplastic pollution status. Therefore, a comprehensive investigation and assessment system of microplastics was developed at the river basin scale to characterize the spatial distribution and composition of microplastics in the Yangtze River Basin in order to analyze their influencing factors and assess their ecological risks. The results showed that the microplastic abundance in the study area ranged from 21 to 44 080 n·m-3, with an average abundance of 4 483 n·m-3. The spatial distribution of microplastic abundance was higher in the tributaries than in the main streams (except the Ganjiang Basin), with the Chengdu of the Minjiang Basin being the tributary area with the highest abundance of microplastics detected. The size of microplastics in the river basin was concentrated in the 0-1 mm range; the shapes were mainly fiber and fragment; and the colors were mainly colored and transparent. Further, introducing the diversity index of microplastics, it was found that both the Simpson index and the Shannon-Wiener index could quantify the diversity of microplastic characteristic composition in the river basin, but there were certain differences in the changing trends between the two. Regression analysis showed that anthropogenic activities were significantly and positively correlated with microplastic abundance (P<0.05), and among the eight anthropogenic activity factors, civilian vehicle ownership and tourism income were the most strongly correlated with microplastic abundance, indicating that transportation and tourism were the main factors influencing microplastic distribution. From the perspective of the potential ecological risk index of microplastics, microplastics in the Yangtze River Basin posed a certain ecological risk, with 68.97% of the area falling within risk zones III and IV, with the ecological risk of microplastics in Taihu Lake warranting more widespread attention.

Water quality's responses to water energy variability of the Yangtze River.

River energy serves as an indicator of pollutant-carrying capacity (PCC), influencing regional water quality dynamics. In this study, MIKE21 hydrodynamics-water quality models were developed for two scenarios, and grid-by-grid numerical integration of energy was conducted for the Yangtze River's mainstream. Comparison of predicted and measured values at monitoring points revealed a close fit, with average relative errors ranging from 5.17 to 8.37%. The concept of PCC was introduced to assess water flow's ability to transport pollutants during its course, elucidating the relationship between river energy and water quality. A relationship model between Unit Area Energy (UAE) and PCC was fitted (R2 = 0.8184). Temporally, reservoir construction enhanced the smoothness of UAE distribution by 74.47%, attributable to peak shaving and flow regulation. While this flood-drought season energy transfer reduced PCC differences, it concurrently amplified pollutant retention by 40.95%. Spatially, energy distribution fine-tuned PCC values, showcasing binary variation with energy changes and a critical threshold. Peak PCC values for TP, NH3-N, and COD were 2.46, 2.26, and 54.09 t/(km·a), respectively. These insights support local utility regulators and decision-makers in navigating low-carrying capacity, sensitive areas, enhancing targeted water protection measures for increased effectiveness and specificity.

Ultrasonic AccV: a potential indicator of peripheral arteriosclerosis in patients with chronic obstructive pulmonary disease.

OBJECTIVE: This study aimed to investigate the risk factors for peripheral arteriosclerosis (PAS) and peripheral artery disease (PAD) in chronic obstructive pulmonary disease (COPD) patients and potential ultrasound indicators that could be used to improve detection. METHOD: Outpatients seeking care between January 1, 2017, and December 31, 2020, in The First Affiliated Hospital of China Medical University were prospectively recruited. Subjects were divided into COPD and non-COPD (control) groups, and the COPD group was further divided into PAD and non-PAD subgroup, at the same time, PAS and non-PAS subgroup. Indicators of PAD -ankle-brachial index (ABI), indicators of PAS- pulse wave velocity (PWV), and ultrasound indices -peak systolic blood flow velocity (PSV) and blood flow acceleration velocity (AccV) were compared. RESULT: Sixty-nine (61.6%) of 112 enrolled subjects had COPD. COPD patients had higher age, and blood pressure (BP)lower than controls. Seventeen (24.6%) COPD patients had PAD, the prevalence of PAD increases with the decrease of lung function, and seven (16.3%) non-COPD patients had PAD, however, there was no significant statistical difference between COPD and non-COPD groups. Fifty (72.5%) COPD patients had PAS, and thirty-four (79.1%) non-COPD patients had PAS, however, there was also no significant difference. The PAS subgroup had higher age, body mass index(BMI), body fat percentage(BFP), lower FEV1 and FEV1/FVC, as well as higher levels of right brachial artery and left dorsalis pedis artery AccV. Factors that correlated with ABI were 6MWD, post-bronchodilator FEV1, FEV1/ FVC, and maximal middle expiratory flow between 75% and 25% of FVC. Age, BP, and 6MWD, but not pulmonary function, were associated with brachial-ankle PWV (baPWV). There was a positive correlation between baPWV and radial artery AccV bilaterally. CONCLUSION: Radial artery AccV correlated well with baPWV, which suggests that ultrasound could be used to assess both morphological and functional changes in vessels, may serving as a better method to identify PAS in high-risk COPD patients.

New insight into identifying sediment phosphorus sources in multi-source polluted urban river: Effect of environmental-induced microbial community succession on stability of microbial source tracking results.

Identifying sediment phosphorus sources, the key to control eutrophication, is hindered in multi-source polluted urban rivers by the lack of appropriate methods and data resolution. Community-based microbial source tracking (MST) offers new insight, but the bacterial communities could be affected by environmental fluctuations during the migration with sediments, which might induce instability of MST results. Therefore, the effects of environmental-induced community succession on the stability of MST were compared in this study. Liangxi River, a highly eutrophic urban river, was selected as the study area where sediment phosphorus sources are difficult to track because of multi-source pollution and complicated hydrodynamic conditions. Spearman correlation analysis (P < 0.05) was conducted to recognize a close relationship between sediment, bacterial communities and phosphorus, verifying the feasibility of MST for identify sediment phosphorus sources. Two distinct microbial community fingerprints were constructed based on whether excluded 113 vulnerable species, which were identified by analyzing the differences of microorganisms across a concentration gradient of exogenous phosphorus input in microbial environmental response experiment. Because of the lower unknown proportion and relative standard deviations, MST results were more stable and reliable when based on the fingerprints excluding species vulnerable to phosphorus. This study presents a novel insight on how to identify sediment phosphorus sources in multi-source polluted urban river, and would help to develop preferential control strategies for eutrophication management.

Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia.

Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation-such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) -had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, 50.4 vs 23.5 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.

Facile synthesis of nitrogen-doped carbon dots for ultrasensitive detection of anticancer drug gefitinib based on IFE.

Gefitinib, a highly significant antitumor drug, is now commonly employed in clinical settings as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer, colon cancer, and breast cancer. Herein, a convenient, rapid, and accurate fluorescence method based on nitrogen-doped carbon dots (NCDs) was designed for ultrasensitive detection of gefitinib. The NCDs were easily synthesized through one-pot hydrothermal process using p-phenylenediamine and D-glutamic acid as the precursors. The sensing strategy relied on the fluorescence of NCDs at 345 nm, which was selectively reduced by gefitinib based on the inner filter effect (IFE). With a broad linear range of 0.025-30 µg/mL and a low limit of detection of 5.5 ng/mL, the probe was successfully applied to the detection of gefitinib in human serum samples, demonstrating strong practicality, affordability, and high accuracy. The proposed sensor is simple in design, fast in detection and cost-effective, and exhibits promising application in drug real-time analysis.

Structure-Based Identification of Organoruthenium Compounds as Nanomolar Antagonists of Cannabinoid Receptors.

Metal complexes exhibit a diverse range of coordination geometries, representing novel privileged scaffolds with convenient click types of preparation inaccessible for typical carbon-centered organic compounds. Herein, we explored the opportunity to identify biologically active organometallic complexes by reverse docking of a rigid, minimum-size octahedral organoruthenium scaffold against thousands of protein-binding pockets. Interestingly, cannabinoid receptor type 1 (CB1) was identified based on the docking scores and the degree of overlap between the docked organoruthenium scaffold and the hydrophobic scaffold of the cocrystallized ligand. Further structure-based optimization led to the discovery of organoruthenium complexes with nanomolar binding affinities and high selectivity toward CB2. Our work indicates that octahedral organoruthenium scaffolds may be advantageous for targeting the large and hydrophobic binding pockets and that the reverse docking approach may facilitate the discovery of novel privileged scaffolds, such as organometallic complexes, for exploring chemical space in lead discovery.

In Vivo Base Editing of Scn5a Rescues Type 3 Long QT Syndrome in Mice.

BACKGROUND: Pathogenic variants in SCN5A can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants. METHODS: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the Scn5a gene. The adenine base editor was split into 2 smaller parts and delivered into the heart by adeno-associated virus serotype 9 (AAV9-ABEmax) to correct the T1307M pathogenic variant. RESULTS: Both homozygous and heterozygous T1307M mice showed significant QT prolongation. Carbachol administration induced Torsades de Pointes or ventricular tachycardia for homozygous T1307M mice (20%) but not for heterozygous or wild-type mice. A single intraperitoneal injection of AAV9-ABEmax at postnatal day 14 resulted in up to 99.20% Scn5a transcripts corrected in T1307M mice. Scn5a mRNA correction rate >60% eliminated QT prolongation; Scn5a mRNA correction rate <60% alleviated QT prolongation. Partial Scn5a correction resulted in cardiomyocytes heterogeneity, which did not induce severe arrhythmias. We did not detect off-target DNA or RNA editing events in ABEmax-treated mouse hearts. CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.

A ratiometric fluorescent probe for rapid and specific detection of hypochlorite.

Hypochlorite (ClO- ), as a kind of essential reactive oxygen species, plays a crucial role in vitro and in vivo. Here, a ratiometric fluorescent probe (TPAM) was designed and constructed for sensing ClO- based on substituted triphenylamine and malononitrile, which exhibited obvious colour transfer from orange to colourless under daylight accompanied by noticeable fluorescence change from red to green in response to ClO- . TPAM could effectively monitor ClO- with the merits of fast response, excellent selectivity, high sensitivity and a low detection limit of 0.1014 µM. 1 H NMR, mass spectra and theoretical calculations proved that ClO- caused the oxidation of the carbon-carbon double bond in TPAM, resulting in compound 1 and marked changes in colour and fluorescence. In addition, TPAM was utilized for imaging ClO- in living cells successfully with good photostability and biocompatibility.

Self-Powered Programmable van der Waals Photodetectors with Nonvolatile Semifloating Gate.

Tunable photovoltaic photodetectors are of significant relevance in the fields of programmable and neuromorphic optoelectronics. However, their widespread adoption is hindered by intricate architectural design and energy consumption challenges. This study employs a nonvolatile MoTe2/hexagonal boron nitride/graphene semifloating photodetector to address these issues. Programed with pulsed gate voltage, the MoTe2 channel can be reconfigured from an n+-n to a p-n homojunction and the photocurrent transition changes from negative to positive values. Scanning photocurrent mapping reveals that the negative and positive photocurrents are attributed to Schottky junction and p-n homojunction, respectively. In the p-n configuration, the device demonstrates self-driven, linear, rapid response (∼3 ms), and broadband sensitivity (from 405 to 1500 nm) for photodetection, with typical performances of responsivity at ∼0.5 A/W and detectivity ∼1.6 × 1012 Jones under 635 nm illumination. These outstanding photodetection capabilities emphasize the potential of the semifloating photodetector as a pioneering approach for advancing logical and nonvolatile optoelectronics.