Critical factors in soil organic carbon mineralization induced by drying, wetting and wet-dry cycles in a typical watershed of Loess Plateau.

As global climate change progresses, soil will experience prolonged periods of both drought and heavy rainfall, leading to a more frequent drought-re-wetting process that may impact the ecosystem's carbon (C) cycle. However, understanding the extent to which different water conditions and wet-dry cycles alter the process of soil organic carbon (SOC) mineralization remains limited. Therefore, our study focused on the dammed land unique to the Loess Plateau, silted by check dams constructed for erosion control. We implemented three water gradients-drought (30% WHC), water stress (100% WHC), and wet-dry cycling (30-100%)-indoors to observe the SOC mineralization process five times. We identified a transient excitation effect of the wet-dry cycles on SOC mineralization. Soil mineralization decreased gradually with the alternation of wet-dry cycles. The wet-dry cycles not only significantly impacted the contents of SOC and TN but also stimulated the activities of enzymes related to C and N cycles. As the cycle frequency increased, the utilization of C sources by soil microorganisms gradually decreased, and the dominance of carbohydrates, amines, and acids evolved into a single acid, esters, or alcohols. Phosphatase and Chloroflexi were the main factors influencing SOC mineralization under drought stress, while TN and Ascomycota were the primary factors under water stress. SOC and Gemmatimonadetes were the main limiting factors for SOC mineralization under the wet-dry cycles. Additionally, we quantified the direct and interactive contributions of each factor to SOC mineralization. The direct contributions of drought stress, water stress, and the wet-dry cycles to SOC mineralization were 0.961, 0.736, and 0.942, respectively. This study contributes to a more comprehensive understanding of the mechanisms underlying SOC mineralization in the Loess Plateau under changing conditions.

Associations between multiple urinary metals and metabolic syndrome: Exploring the mediating role of liver function in Chinese community-dwelling elderly.

BACKGROUND: Multiple metals exposure has been revealed to be related to metabolic syndrome (MetS). However, the associations and interactions between multiple metals exposure and MetS are remains controversial, and the potential mechanism of the above-mentioned is still unclear. METHODS: The associations between urinary metals and the MetS were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Bayesian kernel machine regression (BKMR) model and quantile-based g-computation (qgcomp) were applied to explore the mixed exposure and interaction effect of metals. Mediation analysis was used to explore the role of liver function. RESULTS: In the single metal model, multiple metals were significantly associated with MetS. RCS analysis further verified the associations between 8 metals and MetS. BKMR model and qgcomp showed that zinc (Zn), iron (Fe), and tellurium (Te) were the main factors affecting the overall effect. In addition, mediation analysis indicated that serum alanine aminotransferase (ALT) mediated 21.54% and 13.29% in the associations of vanadium (V) and Zn with the risk of MetS, respectively. CONCLUSIONS: Elevated urinary concentration of Zn, V, Te, copper (Cu), molybdenum (Mo), and thallium (Tl) were related to the increased risk of MetS. Conversely, Fe and selenium (Se) may be protective factors for MetS in mixed exposure. Liver function may play a key role in the association of V and Zn exposure with MetS.

Unraveling the impact of environmental provisions in preferential trade agreements on green total factor energy efficiency.

Environmental provisions in Preferential Trade Agreements (PTAs) have increased in recent years, however, their impact on green total factor energy efficiency (GTFEE) remains underexplored. Utilizing comprehensive data on countries' engagement with PTAs' environmental provisions, along with environmental legislative information and green trade data, this study employs various quantitative and qualitative research methods to investigate heterogeneity influence, mechanism, nonlinear relationship, and combined effect of PTAs' environmental provisions on GTFEE. The empirical results indicate that: (1) Environmental provisions within PTAs significantly enhance the GTFEE of participating countries, which is more pronounced in North-South PTAs, particularly when these provisions are closely tied to trade issues. (2) Environmental provisions in PTAs improve the GTFEE by promoting environmental legislation, facilitating green goods trade, and fostering cleaner energy structures in participating countries. (3) As the number of PTAs' environmental provisions increases in participating countries, their effect on GTFEE follows a pattern of initial inhibition, followed by promotion, and ultimately insignificance. (4) The combined effect of different types of environmental provisions in PTAs reveals three primary pathways contributing to improved GTFEE: the "environment", the "environment-trade synergy", and the "trade-safeguard synergy".

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes.

Rationale: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. Objectives: Define high-risk COPD subtypes using both genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. Methods: We defined high-risk groups based on PRS and TRS quantiles by maximizing differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups. Measurements and Main Results: We examined two high-risk omics-defined groups in non-overlapping test sets (n=1,133 NHW COPDGene, n=299 African American (AA) COPDGene, n=468 ECLIPSE). We defined "High activity" (low PRS/high TRS) and "severe risk" (high PRS/high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signaling processes compared to a low-risk (low PRS, low TRS) reference subgroup. "High activity" but not "severe risk" participants had greater prospective FEV 1 decline (COPDGene: -51 mL/year; ECLIPSE: - 40 mL/year) and their proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Conclusions: Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection.

CAZ Composite Photocatalysts for H2 Production and Degradation under Visible Light.

g-C3N4/Ag-ZnO (CAZ) composite photocatalysts were synthesized successfully by the hydrothermal method. The photocatalytic performance of photocatalysts was assessed through experiments measuring both hydrogen (H2) production and the degradation of methylene blue (MB). The H2 production rate of 60% CAZ reached 2.450 mmol·g-1·h-1, which was 8.5 times that of g-C3N4. 25% CAZ degraded 99.14% of MB dye within 40 min, and its degradation rate constant was 12.4 times that of g-C3N4. CAZ composite photocatalysts have good synergistic properties in degradation and hydrogen production and exhibit better photocatalytic performance. A Z-scheme photocatalytic system mechanism of CAZ has been proposed for the enhanced H2 production and photocatalytic degradation rate.

On-surface conversion reaction realizes advanced red phosphorus/carbon anode for high-performance lithium-ion batteries.

Red phosphorus (RP), the one of the most prospective anodes in lithium-ion batteries (LIBs), has been severely limited due to the intrinsic defects of massive volume expansion and low electronic conductivity. The vaporization-condensation-conversion (VCC), which confines RP nanoparticles into carbon host, is the most widely used method to address the above drawbacks and prepare RP/C nanostructured composites. However, the volume effect-dominated RP caused by the inevitably deposition of RP vapor on the surface of carbon material suffers from the massive volume change and unstable solid electrolyte interface (SEI) film. Herein, we propose a simple interfacial modification method to eliminate the superficial RP and yield stable surface composed of ion-conducting Li3PS4 solid electrolyte, endowing RP/AC composites excellent cycling performance and ultrafast reaction kinetics. Therefore, the RP/AC@S composites exhibit 926 mAh/g after 320 cycles at 0.2 A/g (running over 181 days), with 81.6 % capacity retention and a corresponding capacity decay rate of as low as 0.059 %. When coupled with LiFePO4 cathode, the full cells present superior cycling performance (62.1 mAh/g after 500 cycles at 1 A/g) and excellent rate capability (81.1 mAh/g at 1.0 A/g).

Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis. METHODS: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis. RESULTS: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region. CONCLUSION: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.

Application and Quality of Model-Based Meta-Analysis in Pharmaceutical Research: A Systematic Cross-Sectional Analysis and Practical Considerations.

Model-based meta-analysis (MBMA) can be used in assisting drug development and optimizing treatment in clinical practice, potentially reducing costs and accelerating drug approval. We aimed to assess the application and quality of MBMA studies. We searched multiple databases to identify MBMA in pharmaceutical research. Eligible MBMA should incorporate pharmacological concepts to construct mathematical models and quantitatively examine and/or predict drug effects. Relevant information was summarized to provide an overview of the application of MBMA. We used AMSTAR-2 and PRISMA 2020 checklists to evaluate the methodological and reporting quality of included MBMA, respectively. A total of 143 MBMA studies were identified. MBMA was increasingly used over time for one or more areas: drug discovery and translational research (n = 8, 5.6%), drug development decision making (n = 42, 29.4%), optimization of clinical trial design (n = 46, 32.2%), medication in special populations (n = 15, 10.5%), and rationality and safety of drug use (n = 71, 49.7%). The included MBMA covered 17 disease areas, with the top three being nervous system diseases (n = 19, 13.2%), endocrine/nutritional/metabolic diseases (n = 17, 11.8%), and neoplasms (n = 16, 11.1%). Of these MBMA studies, 138 (96.5%) were rated as very low quality. The average rate of compliance with PRISMA was only 51.4%. Our findings suggested that MBMA was mainly used to evaluate the efficacy and safety of drugs, with a focus on chronic diseases. The methodological and reporting quality of MBMA should be further improved. Given AMSTAR-2 and PRISMA checklists were not specifically designed for MBMA, adapted assessment checklists for MBMA should be warranted.

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy.

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46 %, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

Prognostic Value of Left Atrial Volume and Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Patients with Coronary Artery Disease and Severe Left Ventricular Dysfunction Underwent CABG.

RATIONALE AND OBJECTIVES: This study aims to investigate whether the combination of Left atrial volume (LAV) and late gadolinium enhancement (LGE) is helpful in stratifying the risk in CABG patients with CAD with EF≤ 35%. MATERIALS AND METHODS: We conducted a retrospective analysis involving 205 CAD patients with EF≤ 35% who underwent CABG. All patients underwent gadolinium-enhanced CMR before surgery. The CMR images were analyzed for LAV, biventricular function, LGE, and left ventricular myocardial strain. Primary endpoint events included all-cause mortality, revascularization, re-hospitalization due to myocardial infarction or heart failure, and stroke after CABG. Multivariable Cox analysis was performed to identify independent risk factors for adverse outcomes. Kaplan-Meier curve analysis with the log-rank test was employed to evaluate survival estimates. RESULTS: A total of 55 patients reached the primary endpoints. Univariate Cox proportional hazard regression analysis showed that LAV index (LAVi), left ventricular EF (LVEF), right ventricular EF, LGE percent, and global longitudinal strain were significantly associated with the primary outcome (all P < 0.05). Multivariable analysis showed that LAVi (hazard ratio [HR] 1.05, [95% confidence interval (CI) 1.02-1.07], P < 0.001) and LGE percent (HR 1.10, [95% CI 1.06-1.15], P < 0.001) were independently associated with the primary outcome. Kaplan-Meier analysis indicated a significant increase in the risk of endpoint occurrence when patients exhibited LAVi≥ 51.0 mL/m2 and LGE≥ 11.6% (both P < 0.05). CONCLUSION: For CAD patients with LVEF≤ 35%, the combination of LAVi and LGE percent demonstrated good predictive value for adverse events after CABG. CMR is a helpful tool to risk-stratify patients with severe left ventricular dysfunction undergoing CABG.

Corrigendum: Machine learning to construct sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with uveal melanoma.

[This corrects the article DOI: 10.3389/fendo.2022.1056310.].

Structured learning in time-dependent Cox models.

Cox models with time-dependent coefficients and covariates are widely used in survival analysis. In high-dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time-dependent Cox models lack flexibility in enforcing specific sparsity patterns (ie, covariate structures). We propose a flexible framework for variable selection in time-dependent Cox models, accommodating complex selection rules. Our method can adapt to arbitrary grouping structures, including interaction selection, temporal, spatial, tree, and directed acyclic graph structures. It achieves accurate estimation with low false alarm rates. We develop the sox package, implementing a network flow algorithm for efficiently solving models with complex covariate structures. sox offers a user-friendly interface for specifying grouping structures and delivers fast computation. Through examples, including a case study on identifying predictors of time to all-cause death in atrial fibrillation patients, we demonstrate the practical application of our method with specific selection rules.

Noninvasive focused ultrasound-mediated delivery of rAAV9-EGFP vectors for neuronal targeting in rats.

OBJECTIVE: To evaluate the synergistic potential of Focused Ultrasound (FUS) in conjunction with microbubbles (MB) and recombinant adeno-associated virus serotype 9 (rAAV9) vectors for targeted gene delivery to neuronal cells in rats, optimizing gene expression conditions and assessing any adverse effects. METHODS: The parameters for permeability enhancement of the rat's blood-brain barrier (BBB) were established using FUS+MB, with MRI scans and Evans Blue (EB) dye assisting in the evaluation. Rats underwent FUS-mediated transfection using rAAV9-Syn-EGFP vectors produced via a triple-transfection in HEK293T cells. Following this, the uptake and expression of GFP in targeted brain regions were evaluated using confocal fluorescence microscopy at various time intervals. Inflammatory responses post-FUS treatment were tracked by observing levels of GFAP, a marker for astrocytic activation, and TNF-α, a pro-inflammatory cytokine. Motor behavior effects post-intervention were gauged using the Rotarod test across multiple groups over a span of four weeks. RESULTS: FUS+MB affected BBB permeability, with optimal results at 4 W for 200 s showing 85 % permeability and evident Gd-DTPA leakage. Settings beyond these resulted in tissue damage. Control groups exhibited a basal GFP expression of 2 % ± 0.5 %, whereas FUS+MB with rAAV-EGFP injections substantially increased GFP expression to about 67 % ± 6 % in targeted neurons. This GFP expression peaked at three weeks post-treatment and remained evident six months later. Following FUS treatment, both GFAP and TNF-α levels underwent fluctuations before eventually nearing their baseline values. The Rotarod test revealed no significant behavioral differences post-treatments among the groups. CONCLUSIONS: Combining FUS+MB with rAAV offers an innovative approach to enhance therapeutic delivery to the central nervous system (CNS) by transiently adjusting BBB permeability.

A novel approach for melanoma detection utilizing GAN synthesis and vision transformer.

BACKGROUND AND OBJECTIVE: Melanoma, a malignant form of skin cancer, is a critical health concern worldwide. Early and accurate detection plays a pivotal role in improving patient's conditions. Current diagnosis of skin cancer largely relies on visual inspections such as dermoscopy examinations, clinical screening and histopathological examinations. However, these approaches are characterized by low efficiency, high costs, and a lack of guaranteed accuracy. Consequently, deep learning based techniques have emerged in the field of melanoma detection, successfully aiding in improving the accuracy of diagnosis. However, the high similarity between benign and malignant melanomas, combined with the class imbalance issue in skin lesion datasets, present a significant challenge in further improving the diagnosis accuracy. We propose a two-stage framework for melanoma detection to address these issues. METHODS: In the first stage, we use Style Generative Adversarial Networks with Adaptive discriminator augmentation synthesis to generate realistic and diverse melanoma images, which are then combined with the original dataset to create an augmented dataset. In the second stage, we utilize a vision Transformer of BatchFormer to extract features and detect melanoma or non-melanoma skin lesions on the augmented dataset obtained in the previous step, specifically, we employed a dual-branch training strategy in this process. RESULTS: Our experimental results on the ISIC2020 dataset demonstrate the effectiveness of the proposed approach, showing a significant improvement in melanoma detection. The method achieved an accuracy of 98.43%, an AUC value of 98.63%, and an F1 value of 99.01%, surpassing some existing methods. CONCLUSION: The method is feasible, efficient, and achieves early melanoma screening. It significantly enhances detection accuracy and can assist physicians in diagnosis to a great extent.

Xanthohumol Promotes Skp2 Ubiquitination Leading to the Inhibition of Glycolysis and Tumorigenesis in Ovarian Cancer.

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.

[Effect of Huanglian Jiedu Decoction on TREM2/Akt/GSK3ß pathway in cerebral cortex of APP/PS1 transgenic mice].

The Chinese medical mechanism of Huanglian Jieduo Decoction on treating Alzheimer's disease(AD) characterized by "toxin damaging brain collateral" is still unclear. This study aims to explore the mechanism of Huanglian Jieduo Decoction on regulating triggering receptor expressed on myeloid cells 2(TREM2)/protein kinase B(Akt)/glycogen synthase kinase 3ß(GSK3ß) pathway to improve the cognitive deficit in APP/PS1 transgenic mice. APP/PS1 mice of approximately nine months old were randomly divided into the model group, the low, medium, and high(2.5, 5, and 10 g·kg~(-1)) groups of Huanglian Jiedu Decoction, and 0.75 mg·kg~(-1) donepezil hydrochloride group, and the C57BL/6J mice with the same age were taken as the normal group. After one month of continuous oral administration, a Morris water maze was performed to detect the learning and memory ability of mice. Hematoxylin-eosin(HE) staining was applied to observe the morphology of neuronal cells in the cortical area of mice. Immunofluorescence was used to detect the protein expressions of ß-amyloid(Aß_(1-42)), CD86, and arginase 1(Arg1). The mRNA levels of interleukin(IL)-1ß, IL-6, and IL-10 in the cortex of mice were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expressions of TREM2, phosphoinositide-3 kinase(PI3K), Akt, GSK3ß, and beta-catenin(ß-catenin) in mouse cortex were determined by Western blot. The results indicated that the escape latency of the model group was significantly prolonged, and the residence time in the target quadrant and the number of crossing the platform were significantly reduced compared with the normal group. Mice in the model group had a significantly lower number of neurons in the cortex and showed nuclear pyknosis and a significant increase in the expressions of Aß_(1-42) and CD86. The mRNA levels of IL-1ß and IL-6 in tissue were significantly increased, IL-10 were increased, while Arg1 were significantly decreased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin in the cortex were significantly down-regulated. Compared with the model group, the escape latency of the mice in the administration group was significantly shortened, and the number of crossing the platform and the residence time in the target quadrant were significantly increased. Furthermore, the number of neurons in the cortex of mice was increased, and nuclear pyknosis was improved. Aß_(1-42) deposition was decreased significantly. The mRNA levels of IL-1ß, IL-6 and CD86 were significantly decreased, while IL-10 and Arg1 levels were significantly increased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin protein in the cortex of each administration group was significantly up-regulated compared with the model group. In conclusion, Huanglian Jiedu Decoction reduced the expression of Aß_(1-42) and neuroinflammation to a neuro-protective effect, thereby improving the learning and memory ability in APP/PS1 mice, which may be related to the TREM2/Akt/GSK3ß signaling pathway.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-ADmini randomized controlled trial.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (ßLifestyle×Time = 1.11, P = 0.038; ßLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

The boom era of emerging contaminants: A review of remediating agricultural soils by biochar.

Emerging contaminants (ECs) are widely sourced persistent pollutants that pose a significant threat to the environment and human health. Their footprint spans global ecosystems, making their remediation highly challenging. In recent years, a significant amount of literature has focused on the use of biochar for remediation of heavy metals and organic pollutants in soil and water environments. However, the use of biochar for the remediation of ECs in agricultural soils has not received as much attention, and as a result, there are limited reviews available on this topic. Thus, this review aims to provide an overview of the primary types, sources, and hazards of ECs in farmland, as well as the structure, functions, and preparation types of biochar. Furthermore, this paper emphasizes the importance and prospects of three remediation strategies for ECs in cropland: (i) employing activated, modified, and composite biochar for remediation, which exhibit superior pollutant removal compared to pure biochar; (ii) exploring the potential synergistic efficiency between biochar and compost, enhancing their effectiveness in soil improvement and pollution remediation; (iii) utilizing biochar as a shelter and nutrient source for microorganisms in biochar-mediated microbial remediation, positively impacting soil properties and microbial community structure. Given the increasing global prevalence of ECs, the remediation strategies provided in this paper aim to serve as a valuable reference for future remediation of ECs-contaminated agricultural lands.