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Glucagon-like peptide-1 (GLP-1) plays a crucial role in regulating glucose homeostasis by stimulating insulin secretion and suppressing glucagon release. Our previous study observed that pea protein hydrolysate (PPH) exhibited the function of triggering GLP-1 secretion. However, the underlying mechanisms have not been revealed. Herein, the mechanisms of PPH-stimulated GLP-1 secretion were investigated in NCI-H716 cells. The PPH-induced GLP-1 secretion was reduced ( p < 0.05) after adding the sensing receptor antagonists NPS-2143 and 4-AMBA, indicating that activation of both calcium-sensing receptor (CaSR) and peptide-transporter 1 (PepT1) was involved in PPH-triggered GLP-1 release. Moreover, the intracellular Ca 2+ level increased by 2.01 times during the PPH-induced GLP-1 secretion. Similarly, the cAMP content also increased by 1.43 times after stimulation by PPH. The RT-qPCR results showed that PPH increased the gene expression of prohormone convertase 1/3 (PCSK-1) by 2.79-fold, which effectively promoted the conversion of proglucagon (GCG) to GLP-1. The specific pathway of PPH-induced GLP-1 secretion may involve both CaSR and PepT1 activation-induced Ca 2+ influx and cAMP generation, which effectively enhanced the enzyme activity of prohormone convertase 1/3 (PCSK-1) and ultimately promoted GLP-1 secretion.

Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug 1 . Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs 2 . Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral. Thus, the stereochemical configuration of the isosteric replacements may offer an added opportunity to improve the affinity of derived ligands for target receptors. A notable impediment to this approach is the lack of simple and scalable catalytic enantioselective syntheses of candidate isosteres from readily available precursors. Here we present a previously unknown palladium-catalysed reaction that converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes and we show that the shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings. With chiral catalysts, the Pd-catalysed reaction can be accomplished in an enantioselective fashion and subsequent transformation of the boron group provides access to a broad array of structures. We also show that the incorporation of nortricyclanes into pharmaceutical motifs can result in improved biophysical properties along with stereochemistry-dependent activity. We anticipate that these features, coupled with the simple, inexpensive synthesis of the functionalized nortricyclane scaffold, will render this platform a useful foundation for the assembly of new biologically active agents., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Soil heavy metal removal strategies are increasingly valued for effectively reducing contamination and preventing secondary pollution. In this work, a double network hydrogel (Fe 2 O 3 @LH), consisting of lignosulfonate (LS) and polyacrylamide with embedded Fe 2 O 3 nanoparticles, was synthesized successfully via a one-pot method and subsequently applied to adsorb lead (Pb) from contaminated soil. Incorporating Fe 2 O 3 into the hydrogel enhances the adsorption capacity of Fe 2 O 3 @LH for Pb(II). The Fe 2 O 3 @LH hydrogel demonstrates a maximum Pb(II) adsorption capacity of 143.11 mg g -1 , with Pb(II) removal mechanisms involving electrostatic adsorption, cation exchange, precipitation reactions, and the formation of coordination complexes, achieving a 22.3 % maximum removal efficiency in soil cultivation experiments. Additionally, the application of Fe 2 O 3 @LH markedly reduces the concentrations of cadmium (Cd) and arsenic (As) in the soil, meanwhile enhances the levels of total nitrogen (TN), soil organic matter (SOM), and cation exchange capacity (CEC) by 23.1 %, 10.6 %, and 16.9 %, respectively. Following 90 days of continuous application in the soil, the recovery rate of Fe 2 O 3 @LH remains above 75 %. The toxicity assay using zebrafish larvae indicates that Fe 2 O 3 @LH demonstrates good biosafety. This study demonstrates the considerable potential of Fe 2 O 3 @LH hydrogel for practical application in reducing Pb(II) levels in contaminated soil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Primary amines represent highly privileged chemicals for synthesis of polymers, pharmaceuticals, agrochemicals, coatings, etc. Consequently, the development of efficient and green methodologies for the production of primary amines are of great importance in chemical industry. Owing to the advantages of low cost and ease in availability, ammonia is considered as a feasible nitrogen source for synthesis of N-containing compounds. Thus, the efficient transformation of ammonia into primary amines has received much attention. In this review, the commonly applied synthetic routes to produce primary amines from ammonia were summarized, including the reductive amination of carbonyl compounds, the hydrogen transfer amination of alcohols, the hydroamination of olefins and the arylation with ammonia, in which the catalytic performance of the recent heterogeneous catalysts is discussed. Additionally, various strategies to modulate the surface properties of catalysts are outlined in conjunction with the analysis of reaction mechanism. Particularly, the amination of the biomass-derived substrates is highlighted, which could provide competitive advantages in chemical industry and stimulate the development of sustainable catalysis in the future. Ultimately, perspectives into the challenges and opportunities for synthesis of primary amines with ammonia as N-resource are discussed., (© 2024 Wiley‐VCH GmbH.)

Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has become one of the major health concerns for the elderly. Computer-aided AD diagnosis can assist doctors in quickly and accurately determining patients' severity and affected regions., Methods: In this paper, we propose a method called MADNet for computer-aided AD diagnosis using multimodal datasets. The method selects ResNet-10 as the backbone network, with dual-branch parallel extraction of discriminative features for AD classification. It incorporates long-range dependencies modeling using attention scores in the decision-making layer and fuses the features based on their importance across modalities. To validate the effectiveness of our proposed multimodal classification method, we construct a multimodal dataset based on the publicly available ADNI dataset and a collected XWNI dataset, which includes examples of AD, Mild Cognitive Impairment (MCI), and Cognitively Normal (CN)., Results: On this dataset, we conduct binary classification experiments of AD vs. CN and MCI vs. CN, and demonstrate that our proposed method outperforms other traditional single-modal deep learning models. Furthermore, this conclusion also confirms the necessity of using multimodal sMRI and DTI data for computer-aided AD diagnosis, as these two modalities complement and convey information to each other. We visualize the feature maps extracted by MADNet using Grad-CAM, generating heatmaps that guide doctors' attention to important regions in patients' sMRI, which play a crucial role in the development of AD, establishing trust between human experts and machine learning models., Conclusion: We propose a simple yet effective multimodal deep convolutional neural network model MADNet that outperforms traditional deep learning methods that use a single-modality dataset for AD diagnosis., Competing Interests: ZZ, SA, YJ, and CZ were employed by JD Health International Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Wang, Zhou, An, Dai, Jin, Zhang, Zhang and Yu.)

Electrochemical conversion from nitrate to ammonia is a key step in sustainable ammonia production. However, it suffers from low productive efficiency or high energy consumption due to a lack of desired electrocatalysts. Here we report nickel cobalt phosphide (NiCoP) catalysts for nitrate-to-ammonia electrocatalysis that display a record-high catalytic current density of -702±7 mA cm-2, ammonia production rate of 5415±26 mmol gcat-1 h-1 and Faraday efficiency of 99.7±0.2 % at -0.3 V vs. RHE, affording the estimated energy consumption as low as 22.7 kWh kgammonia-1. Theoretical and experimental results reveal that these catalysts benefit from hydrogen poisoning effects under low overpotentials, which leave behind catalytically inert adsorbed hydrogen species (HI*) at Co-hollow sites and thereupon enable ideally reactive HII* at secondary Co-P sites. The dimerization between HI* and HII* for H2 evolution is blocked due to the catalytic inertia of HI* thereby the HII* drives nitrate hydrogenation timely. With these catalysts, the continuous ammonia production is further shown in an electrolyser with a real energy consumption of 18.9 kWh kgammonia-1., (© 2024 Wiley‐VCH GmbH.)

Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies., Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models., Results: In the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings., Discussion: Aβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials., Highlights: SCD in amyloid-positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Previous studies have found that Alzheimer's disease (AD)-related plasma markers are associated with amyloid beta (Aβ) deposition, but the change of this association in different Aβ pathological stages remains unclear., Methods: Data were obtained from the SILCODE. According to the standardized uptake value ratio (SUVR) and Aβ stage classification, correlation analysis was performed among plasma biomarkers, and voxel/SUVR values in the regions of interest (ROI) and clinical scale information, respectively. Mediation analysis was used to study the possible pathways., Results: The proportion of cognitively normal (CN) and subjective cognitive decline (SCD) was the highest in stages A0 to 1, while in stages A2 to 4, the proportion of mild cognitive impairment (MCI) and AD increased. Plasma phosphorylated tau (p-tau)181 and glial fibrillary acidic protein (GFAP) levels were significantly lower in stage A0 compared to the later phases. Two pathways demonstrated fully mediated effects: positron emission tomography (PET) SUVR-plasma p-tau181-Mini-Mental State Examination (MMSE) and PET SUVR-plasma GFAP-MMSE., Discussion: This study demonstrated the role of plasma biomarkers in the early stage of AD, especially in SCD, from both the clinical diagnosis and Aβ stage dimensions., Highlights: Plasma ptau181 and GFAP level serve as indicators of early Alzheimer's disease and the pathologic Aβ staging classification. A possible ceiling effect of GFAP was observed in the mid-to-late stages of the AD course. This study confirms the role of AD plasma markers in promoting Aβ deposition at an early stage, particularly in females with subjective cognitive decline(SCD). The overlapping brain regions of plasma p-tau181, GFAP, and neurofilament light for Aβ deposition in the brain in early AD were distributed across various regions, including the posterior cingulate gyrus, rectus gyrus, and inferior temporal gyrus., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: [ 18 F]-D3FSP is a new β-amyloid (Aβ) PET imaging tracer designed to decrease nonspecific signals in the brain by reducing the formation of the N-demethylated product. However, its optimal reference region for calculating the standardized uptake value ratio (SUVR) and its relation to the well-established biomarkers of Alzheimer's disease (AD) are still unclear., Methods: We recruited 203 participants from the Greater Bay Area Healthy Aging Brain Study (GHABS) to undergo [ 18 F]-D3FSP Aβ PET imaging. We analyzed plasma Aβ 42 /Aβ 40 , p-Tau 181 , glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. We compared the standardized uptake value (SUV) of five reference regions (cerebellum, cerebellum cortex, brainstem/PONs, white matter, composite of the four regions above) and AD typical cortical region (COMPOSITE) SUVR among different clinical groups. The association of D3FSP SUVR with plasma biomarkers, imaging biomarkers, and cognition was also investigated., Results: Brainstem/PONs SUV showed the lowest fluctuation across diagnostic groups, and COMPOSITE D3FSP SUVR had an enormous effect distinguishing cognitively impaired (CI) individuals from cognitively unimpaired (CU) individuals. COMPOSITE SUVR (Referred to brainstem/PONs) was positively correlated with p-Tau 181 (p < 0.001), GFAP (p < 0.001), NfL (p = 0.014) in plasma and temporal-metaROI tau deposition (p < 0.001), and negatively related to plasma Aβ 42 /Aβ 40 (p < 0.001), temporal-metaROI cortical thickness (p < 0.01), residual hippocampal volume (p < 0.001) and cognition (p < 0.001). The voxel-wise analysis replicated these findings., Conclusion: This study suggests brainstem/PONs as an optimal reference region for calculating D3FSP SUVR to quantify cortical Aβ plaques in the brain. [ 18 F]-D3FSP could distinguish CI from CU and strongly correlates with well-established plasma biomarkers, tau PET, neurodegeneration, and cognitive decline. However, future head-to-head comparisons of [ 18 F]-D3FSP PET images with other validated Aβ PET tracers or postmortem results are crucial., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The prevalence and incidence of type 2 diabetes mellitus (T2DM) have dramatically increased. The intestinal flora and its derived metabolites are demonstrated to play vital roles in the etiology and onset of T2DM. Shouhuitongbian (SHTB) is a traditional Chinese formula to treat constipation. SHTB is composed of seven herbs and components of Colla corii asini (CCA) that are obtained from the hide of Equus asinus L.. Some of herbs in SHTB such as Aloe vera (L.) Burm.f., Cassia obtusifolia L., fruits of Lycium barbarum L., and Citrus aurantium L. have shown to improve insulin resistance (IR) and T2DM in early reports. We hypothesized that SHTB composed of these herbs has antidiabetic effects. The antidiabetic efficacy and mechanism of action of SHTB have not been previously reported., Hypothesis/purpose: To demonstrate the antidiabetic effect and elucidate the underlying mechanisms of SHTB from the perspective of gut microbiota., Study Design: The main compounds were identified and quantified by high-performance liquid chromatography (HPLC)-mass spectrometry analysis. High fat diet (HFD)-fed mice and db/db mice were used to assess the antidiabetic effects and the mechanism of SHTB. The underlying mechanisms were evaluated by enzyme-linked immunosorbent assay (ELISA), western blot analysis, quantitative real time polymerase chain reaction (qPCR) analysis, 16S rRNA high-throughput sequencing, and targeted metabolome analysis., Methods: HFD-fed mice and db/db mice were orally treated with the standard positive drug metformin (100 mg/kg/d) and with SHTB (200 and 100 mg/kg/d), which was chemically characterized according to the European Medicine Agency (EMA) guidelines. The beneficial effects of SHTB were studied by homeostasis model assessment of insulin resistance (HOMA-IR) index, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), total cholesterol (T-CHO), triglyceride (TG), and inflammation. Subsequently, 16S rDNA-based high-throughput pyrosequencing and GC-MS-based targeted metabolomics profiling were performed to analyze the gut microbiota composition and metabolites profile in the gut, respectively. Moreover, the mammalian target of rapamycin complex 1 (mTORC1) / insulin receptor substrate 1 (IRS-1) / phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) pathway was evaluated via qPCR and western blot., Results: Chemically characterized SHTB, in which six markers were quantified, effectively alleviated glucose intolerance and IR, ameliorated lipid metabolism dysfunction, and reduced inflammation. In addition, 16S rDNA sequencing found that SHTB reshaped the composition of intestinal flora, as indicated by the enrichment of Akkermansia and Parabacteroides in both HFD-fed and db/db mice. Moreover, SHTB enhanced the intestinal production of short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BSCFAs), and reduced the levels of the fecal and circulating branched-chain amino acids (BCAAs). The IRS-1/PI3K/AKT signaling pathway was upregulated after treatment with SHTB., Conclusion: Orally administration of SHTB effectively improved IR and reduced hyperglycemia in mice. Treatment with SHTB regulated the gut BCAAs-mTORC1/IRS-1/PI3K/AKT axis by enhancing the BCAAs catabolism in the gut, which attenuated the deleterious effect of BCAAs on the IRS-1 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Dietary proteins regulate glucose homeostasis via intestinal protein sensing-induced glucagon-like peptide 1 (GLP-1) secretion. However, the reported GLP-1-secreting peptides derived from dietary proteins are few, and studies regarding GLP-1-secreting peptide identification by traditional separation and purification methods are laborious. Herein, we have rapidly virtual-screened two GLP-1 secreting peptides from pea protein hydrolysates (PPHs) by peptidomic analysis and molecular docking with peptide transporter 1 (PepT1). PPH-stimulated GLP-1 secretion decreased after adding the PepT1 antagonist 4-aminobenzoic acid (4-AMBA), indicating that PepT1 activation was involved in PPH-induced GLP-1 secretion in NCI-H716 cells. Subsequently, 307 tripeptides in PPHs were obtained through peptidomic analysis. Among them, two GLP-1-secreting peptides, FLR and LRW, were identified via PepT1 activation-based molecular docking. FLR and LRW (1 mg/mL) increased GLP-1 levels to 170.20% ± 27.83% and 272.37% ± 45.96%, respectively ( p < 0.05). More importantly, molecular docking implied that the interactions between peptides and the active center of PepT1 (especially Glu595, Asn329, and Asn171 in the N-pocket and Arg27 in the C-pocket) were crucial for peptide activity in stimulating GLP-1 secretion. Our study suggested that the combination of peptidomics and PepT1 activation-based molecular docking is a promising approach for identification of GLP-1-secreting peptides.

Background: Although many risk factors for residual pain following percutaneous vertebroplasty or kyphoplasty (PVP or PKP) have been reported in many studies, research methods and cohorts differ greatly. A previous meta-analysis identified patient- and operation-specific risk factors for residual pain. This study aimed to examine the available data and identify significant risk factors for residual pain after PVP or PKP., Methods: PubMed, EMBASE, Web of Science, and the Chinese Wanfang Database were searched for relevant research in English and Chinese, and full-text publications including patients with and without residual pain were compared. Only studies presenting odds ratios from multivariate analysis of residual pain data were considered. To evaluate the impact of the results of the selected articles, Review Manager 5.4 was used., Results: Twelve publications including a total of 3120 patients met the requirements. The meta-analysis examined 10 factors associated with residual pain and categorized them as either patient- or operation-associated factors. Thoracolumbar fascia injury, intravertebral vacuum cleft, depression, and number of fractured vertebrae were all significant patient-associated parameters for residual pain. Significant operation-associated risk factors included bone cement distribution and intraoperative facet joint injury., Conclusions: In this meta-analysis, we identified several significant risk factors for residual pain after PVP or PKP. These findings may be helpful for patient counseling and surgical planning., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To explore the complementary relationship between magnetic resonance imaging (MRI) radiomic and plasma biomarkers in the early diagnosis and conversion prediction of Alzheimer's disease (AD), our study aims to develop an innovative multivariable prediction model that integrates those two for predicting conversion results in AD. This longitudinal multicentric cohort study included 2 independent cohorts: the Sino Longitudinal Study on Cognitive Decline (SILCODE) project and the Alzheimer Disease Neuroimaging Initiative (ADNI). We collected comprehensive assessments, MRI, plasma samples, and amyloid positron emission tomography data. A multivariable logistic regression analysis was applied to combine plasma and MRI radiomics biomarkers and generate a new composite indicator. The optimal model's performance and generalizability were assessed across populations in 2 cross-racial cohorts. A total of 897 subjects were included, including 635 from the SILCODE cohort (mean [SD] age, 64.93 [6.78] years; 343 [63%] female) and 262 from the ADNI cohort (mean [SD] age, 73.96 [7.06] years; 140 [53%] female). The area under the receiver operating characteristic curve of the optimal model was 0.9414 and 0.8979 in the training and validation dataset, respectively. A calibration analysis displayed excellent consistency between the prognosis and actual observation. The findings of the present study provide a valuable diagnostic tool for identifying at-risk individuals for AD and highlight the pivotal role of the radiomic biomarker. Importantly, built upon data-driven analyses commonly seen in previous radiomics studies, our research delves into AD pathology to further elucidate the underlying reasons behind the robust predictive performance of the MRI radiomic predictor., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Xianfeng Yu et al.)

The explosive growth of dialogue data has aroused significant interest among scholars in abstractive dialogue summarization. In this paper, we propose a novel sequence-to-sequence framework called DS-SS (Dialogue Summarization with Factual-Statement Fusion and Dialogue Segmentation) for summarizing dialogues. The novelty of the DS-SS framework mainly lies in two aspects: 1) Factual statements are extracted from the source dialogue and combined with the source dialogue to perform the further dialogue encoding; and 2) A dialogue segmenter is trained and used to separate a dialogue to be encoded into several topic-coherent segments. Thanks to these two aspects, the proposed framework may better encode dialogues, thereby generating summaries exhibiting higher factual consistency and informativeness. Experimental results on two large-scale datasets SAMSum and DialogSum demonstrate the superiority of our framework over strong baselines, as evidenced by both automatic evaluation metrics and human evaluation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Sleep disturbances frequently affect Alzheimer's disease (AD), with up to 65% patients reporting sleep-related issues that may manifest up to a decade before AD symptoms., Objective: To construct a nomogram that synthesizes sleep quality and cognitive performance for predicting cognitive impairment (CI) conversion outcomes., Methods: Using scores from three well-established sleep assessment tools, Pittsburg Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and Epworth Sleepiness Scale, we created the Sleep Composite Index (SCI), providing a comprehensive snapshot of an individual's sleep status. Initially, a CI conversion prediction model was formed via COX regression, fine-tuned by bidirectional elimination. Subsequently, an optimized prediction model through COX regression, depicted as a nomogram, offering predictions for CI development in 5, 8, and 12 years among cognitively unimpaired (CU) individuals., Results: After excluding CI patients at baseline, our study included 816 participants with complete baseline and follow-up data. The CU group had a mean age of 66.1±6.7 years, with 36.37% males, while the CI group had an average age of 70.3±9.0 years, with 39.20% males. The final model incorporated glial fibrillary acidic protein, Verbal Fluency Test and SCI, and an AUC of 0.8773 (0.792-0.963)., Conclusions: In conclusion, the sleep-cognition nomogram we developed could successfully predict the risk of converting to CI in elderly participants and could potentially guide the design of interventions for rehabilitation and/or cognitive enhancement to improve the living quality for healthy older adults, detect at-risk individuals, and even slow down the progression of AD., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Objective: To explore the association between the apolipoprotein E (APOE) genotype and objectively assessed cognitive function., Methods: In this cross-sectional study, 537 participants underwent a neuropsychological assessment for cognitive function and blood testing for APOE genotype. Based on cognitive test results, participants were stratified into two cohorts: Cognitively Unimpaired participants (CU) and Cognitively Impaired participants (CI). The CI group was further divided into Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Furthermore, we conducted age stratification, categorizing participants into three age groups: age 1: <65 years, age 2: 65-75 years, and age 3: >75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-β levels were measured in a cohort of 294 participants to investigate potential interactions involving ε4 carrier status, diagnosis, sex, or plasma markers., Results: The APOE genotypic distribution among the 537 participants was characterized as follows: ε2/ε2 (5 participants), ε2/ε3 (67), ε2/ε4 (13), ε3/ε3 (330), ε3/ε4 (113), and ε4/ε4 (9). Allele frequencies were: ε3 at 78.21%, ε4 at 13.41%, and ε2 at 8.38%. Notably, the ε4 carrier frequency was markedly elevated in the AD group at 81.8% when compared to MCI at 32.8% and CU at 21.3% ( p < 0.05). Within the Cognitively Unimpaired (CU) cohort, the sole discernible contrast between ε4+ and ε4- emerged in STT-B ( p < 0.05). Within the CI group, ε4 carriers showed statistically poorer scores as compared to non-ε4 carriers in several cognitive tests ( p < 0.05). Age stratification result revealed that, among ε4 carriers, cognitive function scores within the age 3 group were significantly inferior to those of age 1 and age 2 groups ( p < 0.05). Plasma amyloid-β detection was applied to the 294 participants. We tested plasma amyloid-β (Aβ42) and plasma amyloid-β (Aβ40) levels and calculated the Aβ42/Aβ40 ratio. We found that among female ε4 carriers, both Aβ42 and the Aβ42/Aβ40 ratio were notably lower than their male counterparts ( p < 0.05)., Conclusions: The ε3/ε3 was the most prevalent among participants, succeeded by ε3/ε4 and ε2/ε3. The least prevalent were ε2/ε4, ε4/ε4, and ε2/ε2 genotypes. The ε3 was predominant, followed by the ε4 and ε2. Individuals with the ε4 allele exhibited significant cognitive impairment, with an especially high prevalence in AD group at 81.8%. The study unveils a pronounced correlation between the ε4 allele and cognitive deficits, implying its potential role in the advancement and severity of cognitive disorders, notably Alzheimer's disease. Cognitive function declines with age in individuals carrying the ε4, and women are more affected by ε4.

Background: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD., Methods: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, firstly, we optimized the STGC-GCAM model to enhance classification accuracy. Secondly, we identified novel AD-associated biomarkers using the optimized model. Thirdly, we validated the imaging biomarkers using Kaplan-Meier analysis. Lastly, we performed correlation analysis and causal mediation analysis to confirm the physiological significance of the identified biomarkers., Results: The STGC-GCAM model demonstrated great classification performance (The average area under the curve (AUC) values for different categories were: CN vs MCI = 0.98, CN vs AD = 0.95, MCI vs AD = 0.96, stable MCI vs progressive MCI = 0.79). Notably, the model identified specific brain regions, including the sensorimotor network (SMN), visual network (VN), and default mode network (DMN), as key differentiators between patients and CN individuals. These brain regions exhibited significant associations with the severity of cognitive impairment (p < 0.05). Moreover, the topological features of important brain regions demonstrated excellent predictive capability for the conversion from MCI to AD (Hazard ratio = 3.885, p < 0.001). Additionally, our findings revealed that the topological features of these brain regions mediated the impact of amyloid beta (Aβ) deposition (bootstrapped average causal mediation effect: β = -0.01 [-0.025, 0.00], p < 0.001) and brain glucose metabolism (bootstrapped average causal mediation effect: β = -0.02 [-0.04, -0.001], p < 0.001) on cognitive status., Conclusions: This study presents the STGC-GCAM framework, which identifies FC biomarkers using a large multi-site fMRI dataset., (© 2024. The Author(s).)

Flaxseed has been recognized as a superfood worldwide due to its abundance of diverse functional phytochemicals and nutrients. Various studies have shown that flaxseed consumption is beneficial to human health, though methods of processing flaxseed may significantly affect the absorption and metabolism of its bioactive components. Hence, flaxseed was subjected to various processing methods including microwaving treatment, microwave-coupled dry milling, microwave-coupled wet milling, and high-pressure homogenization. In vitro digestion experiments were conducted to assess the impact of these processing techniques on the potential gastrointestinal fate of flaxseed oil. Even though more lipids were released by the flaxseed at the beginning of digestion after it was microwaved and dry-milled, the full digestion of flaxseed oil was still restricted in the intestine. In contrast, oil droplets were more evenly distributed in wet-milled flaxseed milk, and there was a greater release of fatty acids during simulated digestion (7.33 ± 0.21 μmol/mL). Interestingly, wet-milled flaxseed milk showed higher oxidative stability compared with flaxseed powder during digestion despite the larger specific surface area of its oil droplets. This study might provide insight into the choice of flaxseed processing technology for better nutrient delivery efficiency.

The chemical stability of edible oils rich in polyunsaturated fatty acids (PUFAs) is a major challenge within the food and supplement industries, as lipid oxidation reduces oil quality and safety. Despite appearing homogeneous to the human eye, bulk oils are actually multiphase heterogeneous systems at the nanoscale level. Association colloids, such as reverse micelles, are spontaneously formed within bulk oils due to the self-assembly of amphiphilic molecules that are present, like phospholipids, free fatty acids, and/or surfactants. In bulk oil, lipid oxidation often occurs at the oil-water interface of these association colloids because this is where different reactants accumulate, such as PUFAs, hydroperoxides, transition metals, and antioxidants. Consequently, the efficiency of antioxidants in bulk oils is governed by their chemical reactivity, but also by their ability to be located close to the site of oxidation. This review describes the impact of minor constituents in bulk oils on the nature of the association colloids formed. And then the formation of mixed reverse micelles (LOOH, (co)surfactants, or antioxidations) during the peroxidation of bulk oils, as well as changes in their composition and structure over time are also discussed. The critical importance of selecting appropriate antioxidants and surfactants for the changes of interface and colloid, as well as the inhibition of lipid oxidation is emphasized. The knowledge presented in this review article may facilitate the design of bulk oil products with improved resistance to oxidation, thereby reducing food waste and improving food quality and safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intestinal fungi, which are important parts of the gut microbiota, have the ability to produce specialized metabolites that significantly contribute to maintaining the balance of the gut microbiota and promoting the health of the host organism. In the present study, two new glycosides, including fusintespyrone A (1) and cerevisterolside A (4), as well as ten known compounds were isolated from the intestinal fungus Fusarium sp. LE06. The structures of the new compounds were elucidated by a combination of spectroscopic methods, such as mass spectrometry (MS) and nuclear magnetic resonance (NMR), along with chemical reactions and calculations of NMR and ECD spectra. Compounds 1-3 showed significant growth inhibition against Aspergillus fumigatus, Fusarium oxysporum, and Verticillium dahliae with MIC values in the range of 1.56-6.25 μg ml -1 ., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Microstructural alterations in the brain networks of Parkinson's disease (PD) patients are correlated with gait impairments. Evaluate microstructural alterations in the white matter (WM) fiber bundle tracts using neurite orientation dispersion and density imaging (NODDI) technique in PD versus healthy controls (HC). In this study, 24 PD patients and 29 HC were recruited. NODDI and high-resolution 3D structural images were acquired for each participant. The NODDI indicators, including the intracellular neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), were compared between the two groups. Diffusion-weighted (DW) images were preprocessed using MRtrix 3.0 software and the orientation distribution function to trace the main nerve fiber tracts in PD patients. Quantitative gait and clinical assessment scales were used to compare the medication "ON" and "OFF" states of PD patients. The NDI, ODI, and ISO values of the WM fiber bundles were significantly higher in PD patients compared to HC. Fiber bundles, including the anterior thalamic radiation, corticospinal tract, superior longitudinal fasciculus, forceps major, cingulum, and inferior longitudinal fasciculus, were found to be significantly affected in PD. The NDI changes of PD patients were well correlated with stride lengths in the "ON" state; ODI changes were correlated with the stride time in the "ON" and "OFF" states and ISO changes were correlated with the stride time and cadence in the "ON" state. In conclusion, combination of NODDI technique and gait parameters can help detect gait impairment in PD patients early and accurately., (© 2024. The Author(s).)

Dipeptidyl Peptidase IV (DPP-IV) inhibitory peptides are attracting increasing attention, owing to their potential role in glycemic regulation by preventing the inactivation of incretins. However, few reviews have summarized the current understanding of DPP-IV inhibitory peptides and their knowledge gaps. This paper reviews the production, identification and structure-activity relationships (SAR) of DPP-IV inhibitory peptides. Importantly, their bioavailability and hypoglycemic effects are critically discussed. Unlike the traditional method to identifying peptides after separation step by step, the bioinformatics approach identifies peptides via virtual screening that is more convenient and efficient. In addition, the bioinformatics approach was also used to investigate the SAR of peptides. Peptides with proline (Pro) or alanine (Ala) residue at the second position of N-terminal are exhibit strong DPP-IV inhibitory activity. Besides, the bioavailability of DPP-IV inhibitory peptides is related to their gastrointestinal stability and cellular permeability, and in vivo studies showed that the glucose homeostasis has been improved by these peptides. Especially, the intestinal transport of DPP-IV inhibitory peptides and cell biological assays used to evaluate their potential role in glycemic regulation are innovatively summarized. For further successful development of DPP-IV inhibitory peptides in glycemic regulation, future study should elucidate their SAR and in vivo hypoglycemic effects .

Both plasma biomarkers and brain network topology have shown great potential in the early diagnosis of Alzheimer's disease (AD). However, the specific associations between plasma AD biomarkers, structural network topology, and cognition across the AD continuum have yet to be fully elucidated. This retrospective study evaluated participants from the Sino Longitudinal Study of Cognitive Decline cohort between September 2009 and October 2022 with available blood samples or 3.0-T MRI brain scans. Plasma biomarker levels were measured using the Single Molecule Array platform, including β-amyloid (Aβ), phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). The topological structure of brain white matter was assessed using network efficiency. Trend analyses were carried out to evaluate the alterations of the plasma markers and network efficiency with AD progression. Correlation and mediation analyses were conducted to further explore the relationships among plasma markers, network efficiency, and cognitive performance across the AD continuum. Among the plasma markers, GFAP emerged as the most sensitive marker (linear trend: t = 11.164, p = 3.59 × 10 -24 ; quadratic trend: t = 7.708, p = 2.25 × 10 -13 ; adjusted R 2  = 0.475), followed by NfL (linear trend: t = 6.542, p = 2.9 × 10 -10 ; quadratic trend: t = 3.896, p = 1.22 × 10 -4 ; adjusted R 2  = 0.330), p-tau181 (linear trend: t = 8.452, p = 1.61 × 10 -15 ; quadratic trend: t = 6.316, p = 1.05 × 10 -9 ; adjusted R 2  = 0.346) and Aβ42/Aβ40 (linear trend: t = -3.257, p = 1.27 × 10 -3 ; quadratic trend: t = -1.662, p = 9.76 × 10 -2 ; adjusted R 2  = 0.101). Local efficiency decreased in brain regions across the frontal and temporal cortex and striatum. The principal component of local efficiency within these regions was correlated with GFAP (Pearson's R = -0.61, p = 6.3 × 10 -7 ), NfL (R = -0.57, p = 6.4 × 10 -6 ), and p-tau181 (R = -0.48, p = 2.0 × 10 -4 ). Moreover, network efficiency mediated the relationship between general cognition and GFAP (ab = -0.224, 95% confidence interval [CI] = [-0.417 to -0.029], p = .0196 for MMSE; ab = -0.198, 95% CI = [-0.42 to -0.003], p = .0438 for MOCA) or NfL (ab = -0.224, 95% CI = [-0.417 to -0.029], p = .0196 for MMSE; ab = -0.198, 95% CI = [-0.42 to -0.003], p = .0438 for MOCA). Our findings suggest that network efficiency mediates the association between plasma biomarkers, specifically GFAP and NfL, and cognitive performance in the context of AD progression, thus highlighting the potential utility of network-plasma approaches for early detection, monitoring, and intervention strategies in the management of AD., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Oxygen evolution reaction (OER) plays key roles in electrochemical energy conversion devices. Recent advances have demonstrated that OER catalysts through lattice oxygen-mediated mechanism (LOM) can bypass the scaling relation-induced limitations on those catalysts through adsorbate evolution mechanism (AEM). Among various catalysts, IrO x , the most promising OER catalyst, suffers from low activities for its AEM pathway. Here, it is demonstrated that a pre-electrochemical acidic etching treatments on the hybrids of IrO x and Y 2 O 3 (IrO x /Y 2 O 3 ) switch the AEM-dominated OER pathway to LOM-dominated one in alkali electrolyte, delivering a high performance with a low overpotential of 223 mV at 10 mA cm -2 and a long-term stability. Mechanism investigations suggest that the pre-electrochemical etching treatments create more oxygen vacancies in catalysts due to the dissolution of yttrium and then provide highly active surface lattice oxygen for participating OER, thereby enabling the LOM-dominated pathway and resulting in a significantly increased OER activity in basic electrolyte., (© 2023 Wiley-VCH GmbH.)

Glucose and energy metabolism disorders are the main reasons induced type 2 diabetes (T2D) and obesity. Besides providing energy, dietary nutrients could regulate glucose homeostasis and food intake via intestinal nutrient sensing induced gut hormone secretion. However, reviews regarding intestinal protein sensing are very limited, and no accurate information is available on their underlying mechanisms. Through intestinal protein sensing, dietary proteins regulate glucose homeostasis and food intake by secreting gut hormones, such as glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP). After activating the sensory receptors, such as calcium-sensing receptor (CaSR), peptide transporter-1 (PepT1), and taste 1 receptors (T1Rs), protein digests induced Ca 2+ influx and thus triggered gut hormone release. Additionally, research models used to study intestinal protein sensing have been emphasized, especially several innovative models with excellent physiological relevance, such as co-culture cell models, intestinal organoids, and gut-on-a-chips. Lastly, protein-based dietary strategies that stimulate gut hormone secretion and inhibit gut hormone degradation are proposed for regulating glucose homeostasis and food intake.

Recognition of handwritten Uchen Tibetan characters input has been considered an efficient way of acquiring mass data in the digital era. However, it still faces considerable challenges due to seriously touching letters and various morphological features of identical characters. Thus, deeper neural networks are required to achieve decent recognition accuracy, making an efficient, lightweight model design important to balance the inevitable trade-off between accuracy and latency. To reduce the learnable parameters of the network as much as possible and maintain acceptable accuracy, we introduce an efficient model named HUTNet based on the internal relationship between floating-point operations per second (FLOPs) and Memory Access Cost. The proposed network achieves a ResNet-18-level accuracy of 96.86%, with only a tenth of the parameters. The subsequent pruning and knowledge distillation strategies were applied to further reduce the inference latency of the model. Experiments on the test set (Handwritten Uchen Tibetan Data set by Wang [HUTDW]) containing 562 classes of 42,068 samples show that the compressed model achieves a 96.83% accuracy while maintaining lower FLOPs and fewer parameters. To verify the effectiveness of HUTNet, we tested it on the Chinese Handwriting Data sets Handwriting Database 1.1 (HWDB1.1), in which HUTNet achieved an accuracy of 97.24%, higher than that of ResNet-18 and ResNet-34. In general, we conduct extensive experiments on resource and accuracy trade-offs and show a stronger performance compared with other famous models on HUTDW and HWDB1.1. It also unlocks the critical bottleneck for handwritten Uchen Tibetan recognition on low-power computing devices.

The aim of this study was to evaluate the in situ insulinotropic effects of pea protein hydrolysates (PPHs) mediated by active glucagon-like peptide-1 7-36 (active GLP-1) using a 2D and dual-layered coculture cell model. Following this model, a mixed Caco-2 and NCI-H716 cell monolayer was differentiated on the apical side to study the effects of PPHs on active GLP-1 levels; meanwhile, the beta-TC-6 cells were seeded on the basolateral side to investigate the insulin responses induced by active GLP-1. The in situ DPP-4 half-maximal inhibitory concentration (IC 50 ) of PPHs, PPHs-120G, and PPHs-120I was 2.94, 3.43, and 2.26 mg/mL, respectively. They directly stimulated active GLP-1 secretion in NCI-H716 cells by 3.03 ± 0.21, 1.99 ± 0.03, and 2.24 ± 0.02 times, respectively. Insulin release in beta-TC-6 cells was directly stimulated by PPHs but not by PPHs-120G and PPHs-120I. Interestingly, PPHs-120G and PPHs-120I indirectly stimulated insulin release in this coculture cell model by enhancing active GLP-1 concentrations. More importantly, PPHs, PPHs-120G, and PPHs-120I increase active GLP-1 levels by their dual function of stimulating active GLP-1 secretion and DPP-4 inhibition. This study suggests that the 2D and dual-layered coculture cell model supports a more comprehensive assessment of in situ insulinotropic effects of protein hydrolysates mediated by active GLP-1.

The purpose of this study is to compare the incidence of anastomotic leakage or stenosis, anastomotic bleeding, anastomosis time, postoperative exhaust time, pneumonia, gastroesophageal reflux, hospitalization and mental state after laparoscopic radical gastrectomy, so as to provide a reliable basis for the safety selection of the 2 clinical anastomosis methods and postoperative care. This study retrospectively analyzed the clinical data of 160 gastric cancer patients treated by our medical team from February 2021 to December 2021. We divided them into side-to-side anastomosis with linear stapler (linear stapler) and end-to-side anastomosis with circular stapler (circular stapler), analyzed the incidence and clinical efficacy of anastomotic complications after laparoscopic radical total gastrectomy. There was a statistically significant difference between linear stapler and the circular stapler in the incidence of anastomotic complications such as the incidence of anastomotic stenosis; The incidence of anastomotic leakage, incidence of anastomotic bleeding, without statistical significant; At the anastomosis time, time of first postoperative discharge, incidence of pneumonia, length of hospital stay, without statistical significant; The incidence of gastroesophageal reflux without statistical significant; The Anxiety Self-rating Scale score, depression self-rating scale score points, the linear stapler was significantly lower than the postoperative circular stapler. The study showed that the anastomotic complications (absolute odds ratio of 1.08; 95% CI 1.02-1.15). This 2 protocol can be used safely and effectively common methods for gastric cancer. The linear stapler after laparoscopic radical total gastrectomy was better than the circular stapler, and was better than the circular stapler in terms of postoperative exhaust time, the incidence of pneumonia and the hospital time. However, the anastomosis time was longer than that of the circular stapler, and fees are also relatively expensive., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

There is currently no appropriate cell model suitable for evaluating the insulinotropic effects of DPP-4 inhibitory peptides (DPP-4IPs) mediated by active glucagon-like peptide-1 7-36 (active GLP-1). The study aims to evaluate the transepithelial transport of IPYWTY on its in situ insulinotropic effects by using a 2D and dual-layered coculture cell model that consists of Caco-2 and NCI-H716 cells on the apical (AP) side and β-TC-6 cells on the basolateral (BL) side. During transportation, IPYWTY was absorbed in its intact form through PepT1 and paracellular transport. Meanwhile, it was degraded to several peptide fragments, including PYWTY, YWTY, WTY, and IPY, which decreased its in situ DPP-4 inhibitory activity. IPYWTY does not directly stimulate insulin release in β-TC-6 cells, while it increased the active GLP-1 level from 76.57 ± 15.16 to 95.63 ± 1.99 pM (1.25 times) in NCI-H716 cells. Interestingly, IPYWTY indirectly increased insulin levels from 426.91 ± 6.07 to 573.94 ± 2.97 μIU/mL (1.34 times) in the 2D and dual-layered coculture cell model for its dual function of stimulating active GLP-1 secretion and DPP-4 inhibition. These results suggested that the 2D and dual-layered coculture cell model is an alternative strategy for effectively evaluating the insulinotropic effects of DPP-4IPs mediated by active GLP-1.

Hydrogen spillover from the metal to the support opens a fresh avenue to design dual-active site catalysts for selective hydrogenation. However, very limited knowledge has been obtained to reveal the relationship between the capacity of hydrogen spillover and catalytic performance of hydrogenation. Herein, hydrogen spillover-dependent selective hydrogenation has been demonstrated on WO 3 -supported ppm-level Pd (PdHD/WO 3 ), where the *H species generated and spilled from Pd to WO 3 are readily utilized for addition of a reactant. The WO 3 supports with a hexagonal phase and a suitable oxygen defect concentration can enhance the capacity of hydrogen spillover, significantly accelerating the catalytic activity of PdHD/WO 3 . For the hydrogenation of 4-chloronitrobenzene, the PdHD/WO 3 catalysts with the highest capacity of hydrogen spillover yielded a turnover frequency (TOF) of 47,488 h -1 (33 times higher than that of traditional Pd/C). Meanwhile, benefiting from the hydrogen spillover, the unique adsorption of 4-chloronitrobenzene via the nitro group on the oxygen vacancy of WO 3 guaranteed >99.9% selectivity of 4-chloroaniline during the whole hydrogenation. This work thus helps to create an effective method for fabricating cost-effective nanocatalysts with an extremely low Pd loading for the ideal hydrogenation with extremely high activity and selectivity.

The development of an enantioselective catalytic Suzuki-Miyaura reaction that applies to meso 1,2-diborylcycloalkanes is described. This reaction provides a modular route to enantiomerically enriched substituted carbocycles and heterocycles that retain a synthetically versatile boronic ester. With appropriately constructed substrates, compounds bearing additional stereogenic centers and fully substituted carbon atoms can be generated in a straightforward fashion. Preliminary mechanistic experiments suggest that substrate activation arises from the cooperative effect of vicinal boronic esters during the transmetalation step.

Cobalt (Co) as a substitute of noble-metal catalysts shows high catalytic capability for production of the widely used primary amines through the reductive amination. However, the synthesis of Co catalysts usually involves the introduction of organic compounds and the high-temperature pyrolysis, which is complicated and difficult for large-scale applications. Herein, we demonstrated a facile and efficient strategy for the preparation of Co catalysts through the in situ reconstruction of cobalt borate (CoBO x ) during the reductive amination, delivering a high catalytic activity for production of benzylamine from benzaldehyde and ammonia. Initially, CoBO x was transformed into Co(OH) 2 through the interaction with ammonia and subsequently reduced to Co nanoparticles by H 2 under the reaction environments. The in situ generated Co catalysts exhibited a satisfactory activity and selectivity to the target product, which overmatched the commonly used Co/C, Pt or Raney Ni catalysts. We anticipate that such an in situ reconstruction of CoBO x by reactants during the reaction could provide a new approach for the design and optimization of catalysts to produce primary amines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang and Ma.)

Introduction: Constipation is one of the common non-motor symptoms in Parkinson's disease that significantly impacts patient quality of life. Probiotics supplementation may improve constipation symptoms, but its effect on the gut microbiota population is unclear., Methods: In this randomized controlled study, 46 PD patients with constipation according to Rome Ⅲ criteria were recruited. The number of complete bowel movements per week, degree of defecation effort, Bristol stool Scale (BSS), Patient Assessment of Constipation symptom (PAC-SYM) and Patient assessment of constipation quality of life questionnaire (PAC-QOL) were collected pre- and post-intervention to evaluate the constipation symptoms. In addition, fresh feces of subjects before and after intervention and healthy controls were collected for 16s rRNA gene V3-V4 region sequencing to compare bacterial flora differences., Results: Compared with the control group, the treatment group increased the average number of complete bowel movements per week (1.09 ± 1.24 vs. 0.04 ± 0.64, P &lt; 0.001). Probiotics supplementation reduced the BSS score (0.65 ± 0.93 vs. -0.17 ± 0.94, P = 0.004), PAC-SYM score (4.09 ± 6.31 vs. -1.83 ± 4.14, P &lt; 0.001), PAC-QOL score (10.65 ± 16.53 vs. 0.57 ± 12.82, P = 0.042), and degree of defecation effort score (1.00 ± 0.80 vs. 0.00 ± 0.30, P &lt; 0.001). The improvement rate of constipation in the probiotics group was significantly higher than that in the control group (52.2% vs. 8.7%, P = 0.001). PD patients showed intestinal flora disorders compared to healthy controls. After 12 weeks of probiotics treatment, g&#95;Christensenella&#95;sp.&#95;Marseille-P2437 significantly increased, while g&#95;Eubacterium&#95;oxidoreducens&#95;group, g&#95;Eubacterium&#95;hallii&#95;group and s&#95;Odoribacter&#95;sp.&#95;N54.MGS-14 decreased (p &lt; 0 0.05)., Conclusions: Probiotics treatment can effectively improve the constipation symptoms of PD patients and positively affected the gut microbiota., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Carbon neutrality initiative has stimulated the development of the sustainable methodologies for hydrogen generation and safe storage. Aqueous-phase reforming methanol and H 2 O (APRM) has attracted the particular interests for their high gravimetric density and easy availability. Thus, to efficiently release hydrogen and significantly suppress CO generation at low temperatures without any additives is the sustainable pursuit of APRM. Herein, we demonstrate that the dual-active sites of Pt single-atoms and frustrated Lewis pairs (FLPs) on porous nanorods of CeO 2 enable the efficient additive-free H 2 generation with a low CO (0.027%) through APRM at 120 °C. Mechanism investigations illustrate that the Pt single-atoms and Lewis acidic sites cooperatively promote the activation of methanol. With the help of a spontaneous water dissociation on FLPs, Pt single-atoms exhibit a significantly improved reforming of *CO to promote H 2 production and suppress CO generation. This finding provides a promising path towards the flexible hydrogen utilizations., (© 2022. The Author(s).)

Metal-organic framework (MOF) materials, NU-1000(Zr) and Fe(III)-doped NU-1000(Zr), were prepared through the hydrothermal method and used to remove methylbenzene in this work. The pore structure, crystal structure, adsorption capacity, adsorption heat, and adsorption density of Fe(III)-doped NU-1000(Zr) were analyzed based on the experimental and Giant Canonical Monte Carlo (GCMC) simulation methods. The results show that Fe 3+ has a uniform distribution and a stable structure after NU-1000(Zr) was modified with Fe 3+ . The adsorption-penetration experiments of NU-1000 doped with different concentrations of Fe 3+ have shown that the adsorption capacity of methylbenzene on the material surface is up to 231 mg g -1 at Fe/Zr = 0.1, which is due to the less doping of Fe elements and more defective sites in the structure. The GCMC simulation shows that NU-1000(Zr) and Fe(III)-NU-1000(Zr) adsorbed methylbenzene through π-π interaction, and the adsorption effect is good and close to the experimental result. The conclusions of this paper provide important support for the modification of MOF materials and the removal of methylbenzene.

Background: The INFOGEST model is a standardized general in vitro digestion study, but it cannot accurately simulate the fatty acid release process of lipids in the stomach and small intestine. In this study, the internationally universal INFOGEST 2019 was used as the basic model and flaxseed oil emulsion was used as the research object. In various improvement models, the effect of fatty acid release rate on the oxidation stability of flaxseed oil was assessed by adding rabbit stomach extract and changing the order of bile salts addition., Results: With the presence of rabbit gastric extract, flaxseed oil emulsion flocculation and coalescence in stomach were reduced, and the absolute value of ζ-potential increased. Moreover, the release rate of fatty acids in the small intestine increased by 12.14%. The amount of lipid oxidation product (i.e. hexanal) in the gastric and intestinal phases increased by 0.08 ppb. In addition, the fatty acid release rate in the small intestine phase increased by 5.85% and the hexanal content increased by 0.011 ppb in the digestion model of adding bile salts before adjusting the pH in the small intestine phase compared with the model of adjusting the pH first and then adding bile salts., Conclusion: The results obtained from this study will contribute to finding the most suitable static digestion model for simulating digestion and oxidation of lipid during lipid gastrointestinal digestion. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Pea protein hydrolysates (PPHs) possess good hypoglycemic effects; however, their dipeptidyl peptidase-4 (DPP-4) inhibitory activity is poorly understood, and none of the DPP-4 inhibitory peptides have been identified from PPHs. This paper aims to rapidly screen these peptides from PPHs by combining peptidomics and molecular docking. In this study, 543 peptides were identified by peptidomics, and four peptides (IPYWTY, IPYWT, LPNYN, and LAFPGSS) with DPP-4 half-maximal inhibitory concentration (IC 50 ) values <100 μM were screened for the first time. Significantly, peptide IPYWTY exhibited the most potent DPP-4 inhibitory activity (IC 50 = 11.04 μM) mainly because it formed hydrophobic interactions with the S1 pocket in DPP-4. These results indicated that combining peptidomics and molecular docking is an effective strategy for rapidly screening DPP-4 inhibitory peptides.

The study of the effects of Na and K on the heterogeneous adsorption of hydroxyl-containing char with NO is important for the clean utilization of high alkali coal. In this paper, the effects of Na/K atoms on the adsorption of NO on the char surface were investigated at the GGA-PBE level by choosing zigzag type, armchair type, and saturated hydroxyl-containing char structures based on DFT. It was found that the adsorption stability of NO on structures with active sites was greater for sites close to the hydroxyl group than that for sites far from the hydroxyl group. The stability of char doped by Na/K is related to the char structure and the position of functional groups. The most stable Na/K doped structures are Z-OH-2 ( E ads = -350.50 kJ/mol) and A-OH-1-2 ( E ads = -339.17 kJ/mol), respectively. The participation of Na/K can increase the adsorption energy of the three structures with NO, and especially the adsorption energy of saturated char with NO is increased by as much as 5 times. The reason for that is the promotion of the hybridization of the C and NO p orbitals. The comprehensive analysis of electrostatic potential, charge transfer, and front orbitals indicates that the effects of decorated sodium and potassium atoms on the char surface are very similar. This study lays a theoretical foundation for the study of the heterogeneous reduction process.

Growing levels of mercury pollution has made countries urgently need a suitable mercury treatment technology. Among various technologies, heterogeneous oxidative mercury removal via different modified V/Ti-based SCR catalysts is considered as a promising approach due to excellent economic value and removal efficiency. Although various related modification experiments have been worked in recent years, the research on the performance, including activity and resistance, and mechanism of catalysts still needs to be improved, so it is necessary to summarize these experiments to guide further work. This article will review many modifications start from the V/Ti catalyst. Not only the performance of these catalysts, but also a lot of speculation about the mercury removal mechanism are include in our research. In addition, the characteristics of some modified catalysts have been linked with their oxidation mechanism and structural changes by comparing many studies, and finally attributed to some special properties of the corresponding modifiers. We expect this study will clarify the research progress of modified V/Ti-based SCR catalysts in mercury removal, and guide future modification so that some properties of the catalyst can be improved in a targeted manner., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this paper is described an easily synthesized chiral diazaborolidine that is inexpensive, stable, and provides excellent stereoselection across a number of reaction classes. These versatile compounds possess utility in four different classes of cycloaddition reactions, offering good yield and stereoselectivity. X-ray structure analysis provides insight about the origin of stereocontrol., (© 2022 Wiley-VCH GmbH.)

Introduction: Previous studies have shown that the long intergenic non-protein coding RNA regulator of reprogramming (linc-ROR) is abnormally expressed in a variety of malignancies and plays an important role in tumor progression. However, little is known about the role of linc-ROR in gastric cancer. In this study, the relationship between the expression of linc-ROR and clinicopathological factors in gastric cancer and its potential mechanism were explored., Materials and Methods: The cells were classified into two groups: ROR small interfering RNA(si-ROR) and the Negative control siRNA (si-NC).Linc-ROR was knockdown in si-ROR group by small interfering RNA (siRNA). Detect the expression of linc-ROR in gastric cancer tissues and normal tissues and its relationship with clinicopathologic characteristics by RT-PCR. the invasion ability was studied by wound healing assay and transwell assay. The expression levels of EMT-related molecules was detected by RT-PCR and Western blotting., Result: Showed that the expression of lincROR in gastric cancer tissues was significantly higher than that in the adjacent normal tissues. The lincROR expression level was significantly related to the tumor grade, lymph node metastasis, and TNM stage in cancer tissues. The lincROR knockdown in gastric cancer cell lines significantly inhibited cell invasion and metastasis. It affected its malignant biological behavior by activating the epithelial-mesenchymal transition through increasing expression of vimentin as well as decreasing E-cadherin levels in gastric cancer cells. The lincROR silencing significantly decreased the expression of β-catenin and c-myc., Conclusion: Linc-ROR can regulate cell invasion and metastasis by activating the epithelial-mesenchymal transition process partially through Wnt/β-catenin signal pathway in the gastric cancer cells. Link-ROR may be an important molecule for the metastasis of gastric cancer., Competing Interests: None

Introduction: Lower limb motor dysfunction is common in patients with stroke, and usually caused by brain neural connectivity disorder. Previous studies have shown that the whole-body vibration training (WBVT) significantly improves the lower limb motor function in patients with stroke and may promote nerve remodelling. The prior purpose of this study is to explore effects of WBVT on lower limb motor function and neuroplasticity in patients with stroke., Methods: A single-blind randomised controlled trial will be conducted. Sixty patients with stroke will be recruited and allocated randomly to WBVT, routine rehabilitation training (RRT) and control group (CG). The WBVT and RRT interventions will be implemented as five 25 min sessions weekly for continuous 12 weeks; the CG will remain daily habitual living styles and routine treatments, in community or hospital, and will also receive telephone follow-up and health-related lectures. Transcranial magnetic stimulation will be used to assess neural plasticity while lower limb motor function is assessed using indicators of strength, walking ability and joint activity. The assessments will be conducted at the period of baseline, week 6, week 12 as well as on 4 and 8 weeks, respectively, after intervention completion., Ethics and Dissemination: This study has been approved by the Shanghai University of Sport Research Ethics Committee (102772021RT067) and will provide data on the effects of WBVT relative to RRT in terms of the improvement of stroke patients' lower limb motor function and neural plasticity. The results of this study will be disseminated via publications in peer-reviewed journals and presentations at international conference., Trial Registration Number: ChiCTR2200055143., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coupling acid-electrolyte proton exchange membrane fuel cells for electricity generation and cathodic hydrogenation for valuable chemical production shows great potential in energy and chemical industry. The key for this promising approach is the identification of cathode electrocatalysts with acid resistance, high activity, and low fabrication cost for practical applications. Among various promising cathodic candidates for this integrative approach, the easily available and cheap Cu suffers from low acidic hydrogenation activity due to kinetically arduous proton adsorption/activation. Inspired by the kinetic advantages of the concerted proton-coupled electron transfer (CPET) over the sequential proton-electron transfer process, herein, we use phytate coordination on Cu surface to overcome the kinetic bottleneck for proton adsorption/activation through the CPET pathway in an acidic half-cell setup; this leads to 1 order of magnitude activity enhancement (36.94-fold) for nitrobenzene hydrogenation. Mechanistic analysis confirms that phytate, as proton acceptor, induces the CPET process and overcomes the above kinetic limitations by tuning the d-band center and concentrating protons on the Cu surface. Consequently, the CPET process facilitates the formation of active hydrogen intermediates for efficient cathodic hydrogenation. This work provides a promising approach to integrate electricity generation and chemical production.