Comparison of downsizing strategy (HANGZHOU Solution) and standard annulus sizing strategy in type 0 bicuspid aortic stenosis patients undergoing transcatheter aortic valve replacement: Rationale and design of a randomized clinical trial.

BACKGROUND: There has not been a consensus on the prothesis sizing strategy in type 0 bicuspid aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Modifications to standard annular sizing strategies might be required due to the distinct anatomical characteristics. We have devised a downsizing strategy for TAVR using a self-expanding valve specifically for patients with type 0 bicuspid AS. The primary aim of this study is to compare the safety and efficacy of downsizing strategy with the Standard Annulus Sizing Strategy in TAVR for patients with type 0 bicuspid AS. TRIAL DESIGN: It is a prospective, multi-center, superiority, single-blinded, randomized controlled trial comparing the Down Sizing and Standard Annulus Sizing Strategy in patients with type 0 bicuspid aortic stenosis undergoing transcatheter aortic valve replacement. Eligible participants will include patients with severe type 0 bicuspid AS, as defined by criteria such as mean gradient across aortic valve ≥40 mmHg, peak aortic jet velocity ≥4.0 m/s, aortic valve area (AVA) ≤1.0 cm², or AVA index ≤0.6 cm2/m2. These patients will be randomly assigned, in a 1:1 ratio, to either the Down Sizing Strategy group or the Standard Sizing Strategy group. In the Down Sizing Strategy group, a valve one size smaller will be implanted if the "waist sign" manifests along with less than mild regurgitation during balloon pre-dilatation. The primary end point of the study is a composite of VARC-3 defined device success, absence of both permanent pacemaker implantation due to high-degree atrioventricular block and new-onset complete left bundle branch block. CONCLUSION: This study will compare the safety and efficacy of Down Sizing Strategy with the Standard Annulus Sizing Strategy and provide valuable insights into the optimal approach for sizing in TAVR patients with type 0 bicuspid AS. We hypothesize that the Down Sizing Strategy will demonstrate superiority when compared to the Standard Annulus Sizing Strategy. (Down Sizing Strategy (HANGZHOU Solution) vs Standard Sizing Strategy TAVR in Bicuspid Aortic Stenosis (Type 0) (TAILOR-TAVR), NCT05511792).

Single-cell multiomics guided mechanistic understanding of Fontan-associated liver disease.

The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Individuals with a Fontan circulation (FC) exhibit central venous hypertension and face life-threatening complications of hepatic fibrosis, known as Fontan-associated liver disease (FALD). The fundamental biology and mechanisms of FALD are little understood. Here, we generated a transcriptomic and epigenomic atlas of human FALD at single-cell resolution using multiomic snRNA-ATAC-seq. We found profound cell type-specific transcriptomic and epigenomic changes in FC livers. Central hepatocytes (cHep) exhibited the most substantial changes, featuring profound metabolic reprogramming. These cHep changes preceded substantial activation of hepatic stellate cells and liver fibrosis, suggesting cHep as a potential first "responder" in the pathogenesis of FALD. We also identified a network of ligand-receptor pairs that transmit signals from cHep to hepatic stellate cells, which may promote their activation and liver fibrosis. We further experimentally demonstrated that activins A and B promote fibrotic activation in vitro and identified mechanisms of activin A's transcriptional activation in FALD. Together, our single-cell transcriptomic and epigenomic atlas revealed mechanistic insights into the pathogenesis of FALD and may aid identification of potential therapeutic targets.

Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance.

Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A.

Study on CO source identification and spontaneous combustion warning concentration in the return corner of working face in shallow buried coal seam.

Coal spontaneous combustion is a common problem faced by many coal mines. Spontaneous combustion in goaf releases a large amount of harmful gases, polluting the environment while causing a large amount of wasted resources, and even endangering the lives of workers. Due to the collapse of the interior of the mining area, it is impossible to measure the internal gas composition directly. In order to more accurately predict the spontaneous combustion state inside the mining airspace, this paper obtains the CO generation law and the main source of the working face through the combination of laboratory experiments and on-site monitoring. The CO concentration prediction model of the return corner is established with CO as the index gas. Finally, the safe concentration and warning concentration of the working face are calculated according to the example, which provides theoretical basis for the prediction of spontaneous combustion of coal.

An investigation into the HIF-dependent intestinal barrier protective mechanism of Qingchang Wenzhong decoction in ulcerative colitis management.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease affecting the colon and rectum with an etiology that remains elusive. Traditional Chinese medicine (TCM) has been widely used on long-term UC treatment to better maintain the efficacy than traditional aminosalicylic acid or glucocorticosteroids and to ease financial burden of patients. Qingchang Wenzhong Decoction (QCWZD) is a modern TCM decoction with established clinical efficacy but the mechanism of its protection on intestinal barrier function remains unclear. AIM OF THE STUDY: Current findings highlight that the activation of the hypoxia inducible factor (HIF) pathway can facilitate the repair of intestinal epithelium barrier. This study is to investigate the protective effects of QCWZD and its HIF-targeted ingredients on hypoxia-dependent intestinal barrier. METHODS: The mice model of UC was induced by dextran sulfate sodium (DSS). Disease activity index (DAI) and histopathology scores and colon length were used to measure the severity of colitis. The DAO activity in serum and protein expression of tight junction (TJ) proteins were detected to explore the function of intestinal barrier. The protein levels of HIF-1α and its downstream gene heme oxygenase-1 (HO-1) were measured as well. HIF-targeted active ingredients in QCWZD were selected by network pharmacology and molecular docking. Protective effects of six constituents on HIF-related anti-oxidative and barrier protective pathway were evaluated by lipopolysaccharide (LPS)-induced HT29 and RAW264.7 cells, through the measurement of the production of ROS and mRNA level of pro-inflammatory cytokines. HIF-1α knockdown was carried out to explore the correlation of protection effects with HIF-related pathway of the active ingredients. RESULTS: QCWZD effectively alleviated colitis induced by DSS and demonstrated a protective effect on intestinal barrier function by upregulating HIF-related pathways. Six specific ingredients in QCWZD, targeting HIF, successfully reduced the production of cellular ROS and proinflammatory cytokines in LPS-induced cells. It is noteworthy that the barrier protection provided by these molecules is intricately linked with the HIF-related pathway. CONCLUSIONS: This study elucidates the HIF-related molecular mechanism of QCWZD in protecting the function of the epithelial barrier. Six compounds targeting the activation of the HIF-dependent pathway were demonstrated to unveil a novel therapeutic approach for managing UC.

Highly sensitive and repeatable recording photopolymer for holographic data storage containing N-methylpyrrolidone.

The low photosensitivity of phenanthraquinone-doped poly(methyl methacrylate) (PQ/PMMA) severely limits its recording speed for holographic data storage. A high-performance holographic recording medium based on a unique combination of N-methylpyrrolidone (NMP) regulated PQ/PMMA has been developed. A NMP-PQ/PMMA photopolymer with high sensitivity, high diffraction efficiency and negligible volume shrinkage was successfully fabricated by tuning the composition of the PMMA matrix by varying the ratio of NMP to monomers. The photosensitivity is increased by 6.9 times (from 0.27 cm J-1 to 1.86 cm J-1), the diffraction efficiency is increased from 60% to > 80%, and volume shrinkage is decreased by a factor of 2 (from 0.4% to 0.2%). Further investigation revealed that the addition of NMP significantly reduced the molecular weight of PMMA and increased the amount of MMA residuals, while also improving the solubility of PQ molecules. More interestingly, for the first time, the NMP-PQ/PMMA material could record data information repeatedly at least 6 times. The present study elucidates that the introduction of NMP not only modulates the molecular weight of PMMA but also enables the residual monomer MMA to more easily combine with PQ to form a photoproduct for improved holographic performance.

Daily Physical Activity Measured by Wearable Smartwatch for Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the SMART TAVR Study.

BACKGROUND: This study aims to evaluate limited data about daily physical activity patterns, influential factors, and their association with 1-year mortality or rehospitalization after transcatheter aortic valve replacement (TAVR) through smartwatches. METHODS: Consecutive severe aortic stenosis patients undergoing elective transfemoral TAVR in a Chinese tertiary hospital were enrolled from July 2021 to May 2022 and received a Huawei smartwatch at least 1 day before TAVR. The primary outcome was a composite of all-cause mortality or hospital readmission within 1 year. Linear mixed-effects models were applied to determine influential factors of daily step counts, and Cox proportional hazard regression models were to estimate the association between baseline step counts within 1 month since discharge and composite outcome from months 2 to 12. The dose-response association was assessed using restricted cubic spline curves. RESULTS: A total of 222 participants and 59 469 valid monitoring person-day records were included (mean age, 72.7 years; 61% women). Step counts increased rapidly within the first 2 months (P<0.001), followed by a slower increase for those without composite outcomes (P=0.029) and a gradual decrease for those who developed composite outcomes (P<0.001). In multivariate linear mixed models, a 1-m increase in baseline 6-minute walk test and a 1-month delay after discharge were associated with 4 (95% CI, 1-7) and 170 (95% CI, 145-194) additional step counts, respectively. In restricted cubic spline analysis, the hazard ratio declined progressively until ≈5000 steps per day, after which they leveled. Below 5000 steps, the adjusted hazard ratio of composite outcome associated with each 1000-step count increase was 0.67 (0.50-0.89; P=0.007). However, above 5000 steps, step counts were not significantly associated with the composite outcome (P=0.645), with a hazard ratio of 1.12 (0.70-1.79). CONCLUSIONS: Daily step counts rapidly increased within the first 2 months post-TAVR. Increased physical activity was associated with a lower risk of 1-year mortality or rehospitalization after TAVR for patients with daily step counts below 5000. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04454177.

Molecular mechanisms of Chengshi Beixie Fenqing Decoction based on network pharmacology: pivotal roles of relaxin signaling pathway and its associated target proteins against Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease that affects the quality of life of middle-aged and older men. We investigated the therapeutical effects of Chengshi Beixie Fenqing Decoction (CBFD), a classic traditional Chinese medicine prescription, on BPH through in vivo model and network pharmacology. Bioactives in CBFD were detected through UPLC-Q-Tof-MS/MS and GC-MS, and filtered by the modified Lipinski's rule. Target proteins associated with the filtered compounds and BPH are selected from public databases. Venn diagram identified the overlapping target proteins between the bioactives-interacted target proteins and the BPH-targeted proteins. The bioactive-protein interactive networking of BPH was analyzed through the KEGG pathway on STRING to identify potential ligand-target and visualized the rich factors on the R packet. After that, the molecular docking test (MDT) was performed between bioactives and target proteins. It showed that the mechanism of CBFD against BPH was related to 104 signaling pathways of 42 compounds. AKT1, 6-demethyl-4'-methyl-N-methylcoclaurine and relaxin signaling pathways were selected as a hub target, key bioactivitie and hub signaling pathway, respectively. In addition, three major compounds, 6-demethyl-4'-methyl-N-methylcoclaurine, isoliensinine and liensinine, had the highest affinity on MDT for the three crucial target proteins, AKT1, JUN and MAPK1. These proteins were associated with the relaxin signaling pathway, which regulated the level of nitric oxide and is implicated in both BPH development and CBFD. We concluded that the three key bioactivities found in Plumula nelumbinis of CBFD may contribute to improving BPH condition by activating the relaxin signaling pathways.Communicated by Ramaswamy H. Sarma.

Real world experience on the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis in Taiwan.

Introduction: Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan. Methods: Between January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration. Result: The primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter (n = 36), 0.13 liter (n = 32), 0.04 liter (n = 26), and - 0.004 liter (n = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George's respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study. Conclusion: Our real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects.

Angiotensin-(1-7) attenuates SARS-CoV2 spike protein-induced interleukin-6 and interleukin-8 production in alveolar epithelial cells through activation of Mas receptor.

BACKGROUND: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis. METHODS: HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1-7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells. FINDINGS: SARS-CoV-2 SP (5 µg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 µg/mL), or angiotensin-(1-7) (10 µM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1-7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 µM) or SiRNA knockdown. INTERPRETATION: SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1-7). Angiotensin-(1-7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1-7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP.

In silico screening-based discovery of benzamide derivatives as inhibitors of Rho-associated kinase-1 (ROCK1).

As a pivotal node in modulating various cell behaviors, Rho-associated kinase-1 (ROCK1) has attracted significant attention as a promising therapeutic target in a variety of diseases. Benzamide has been widely reported as a ROCK1 inhibitors in recent years. To better understand its pharmacological properties and to explore its potential inhibitors, a series of ROCK1 inhibitors derived from N-methyl-4-(4-pyrazolidinyl) benzamides (MPBs) were investigated by using three-dimensional quantitative structure-activity relationship (3D-QSAR) models, pharmacophore models, molecular docking, and molecular dynamics (MD) simulation. The comparative Molecular Field Analysis (CoMFA) model (q2 = 0.616, R2 = 0.972, ONC = 4, and r2pred = 0.983) and the best Comparative Molecular Similarity Indices Analysis (CoMSIA) model (q2= 0.740, R2 = 0.982, ONC = 6, and r2pred = 0.824) exhibited reliable predictability with satisfactory validation parameters. In the subsequent virtual screening, VS03 and VS05 were identified to have superior predicted activities and higher docking scores, meanwhile they demonstrated to be reasonably stable in the binding pocket through MD simulations. These results provide a significant theoretical direction for the rational design and development of novel ROCK1 inhibitors.Communicated by Ramaswamy H. Sarma.

Lysosomal dysfunction in carbon black-induced lung disorders.

Carbon black (CB), a component of environmental particulate pollution derived from carbon sources, poses a significant threat to human health, particularly in the context of lung-related disease. This study aimed to investigate the detrimental effects of aggregated CB in the average micron scale on lung tissues and cells in vitro and in vivo. We observed that CB particles induced lung disorders characterized by enhanced expression of inflammation, necrosis, and fibrosis-related factors in vivo. In alveolar epithelial cells, CB exposure resulted in decreased cell viability, induction of cell death, and generation of reactive oxidative species, along with altered expression of proteins associated with lung disorders. Our findings suggested that the damaging effects of CB on the lung involved the targeting of lysosomes. Specifically, CB promoted lysosomal membrane permeabilization, while lysosomal alkalization mitigated the harmfulness of CB on lung cells. Additionally, we explored the protective effects of alkaloids derived from Nelumbinis plumula, with a focus on neferine, against CB-induced lung disorders. In conclusion, these findings contribute to a deeper understanding of the pathophysiological effects of CB particles on the lungs and propose a potential therapeutic approach for pollution-related diseases.

Fatigue-Free and Skin-like Supramolecular Ion-Conductive Elastomeric Interphases for Stable Lithium Metal Batteries.

The heterogeneity and continuous cracking of the static solid electrolyte interphase (SEI) are one of the most critical barriers that largely limit the cycle life of lithium (Li) metal batteries. Herein, we report a fatigue-free dynamic supramolecular ion-conductive elastomeric interphase (DSIEI) for a highly efficient and dendrite-free lithium metal anode. The soft phase poly(propylene glycol) backbone with loosely Li+-O coordinating interaction was responsible for fast ion transport. Simultaneously, the supramolecular quadruple hydrogen bonds (H-bonds) in the hard phases endow the elastomeric interphase with mechanical enhancement, while gradient H-bonds can dissipate strain energy via the sequential bonding cleavage. Such a design affords superior mechanical robustness, high ionic conductivity, gradient energy dissipation, and high Li+ transference number. Besides, anion enrichment in DSIEI assists in situ construction of a lithium fluoride-rich inner layer upon cycling. The resultant biomimetic bilayer structure enables the symmetric cells with superior cyclability of over 600 h at a high current density of 10 mA cm-2. Moreover, the DSIEI allows stable operation of the full cells under constrained conditions of limited lithium excess, a high-loading LiNi0.8Co0.1Mn0.1O2 cathode, and a low negative/positive capacity (N/P) ratio. This work presents a powerful strategy for deigning artificial SEI and achieving high-energy-density Li metal batteries.

Parenting styles and obsessive-compulsive symptoms in college students: the mediating role of perfectionism.

Introduction: Obsessive-compulsive symptoms is a common psychological phenomenon among early adulthood college students, which are closely related to their parents' parenting styles. Theoretical and some empirical studies have suggested the mediating role of perfectionism in this process, but this has not been confirmed, and the binary perspective of positive-negative perfectionism has not been addressed in this issue. Methods: This study aimed to investigate the mediating role of perfectionism in the relationship between parenting styles and obsessive-compulsive symptoms among college students. A total of 661 college students participated in this study. Results: Negative perfectionism mediated the relationship between negative parenting style and obsessive-compulsive symptoms among college students. Negative parenting style predicted obsessive-compulsive symptoms through its positive predictive effect on negative perfectionism. However, the mediating effect of positive perfectionism was not significant in this process. Discussion: This study provides further evidence of the mechanisms underlying the occurrence of obsessive-compulsive symptoms, and offers new ideas for interventions for OCD.

Optimization of Neferine Purification Based on Response Surface Methodology and Its Anti-Metastasis Mechanism on HepG2 Cells.

Liver cancer continues to be a focus of scientific research due to its low five-year survival rate. One of its main core issues is the high metastasis of cells, for which there is no effective treatment. Neferine was originally isolated from Plumula nelumbinis and demonstrated to have a good antitumor effect. In order to extract high-purity Neferine in a more efficient and environmentally friendly manner, response surface methodology (RSM) was used to optimize the isolation and purification procedures in this study. The extract conditions of a 7:3 ratio for the eluent of dichloromethane: methanol, 1:60 for the mass ratio of the extract amount: silica gel, and 3 mL/min of the elution flow rate were shown to be the optimal conditions. These conditions resulted in the highest yield of 6.13 mg per 66.60 mg of starting material, with productivity of 8.76% and purity of 87.04%. Compared with the previous methods, this method can prepare Neferine in large quantities more quickly. We subsequently evaluated the antitumor activity of the purified Neferine against HepG2 hepatic cancer cells. The purified Neferine was found to inhibit the proliferation of HepG2 cells through the CCK-8 assay, with an IC50 of 33.80 µM in 24 h, 29.47 µM in 48 h, 24.35 µM in 72 h and 2.78 µM in 96 h of treatment. Neferine at a concentration of 3 µM could significantly inhibit the migration and invasion abilities of the HepG2 cells in vitro. We also explored the mechanism of action of Neferine via Western blot. We showed that Neferine could reduce RhoA expression by effectively inhibiting the phosphorylation of MYPT1, thereby effectively exerting anti-metastasis activity against HepG2 cells. Thus, we have optimized the isolation procedures for highly pure Neferine by response surface methodology (RSM) in this study, and purified Neferine is shown to play an essential role in the anti-metastasis process of liver cancer cells. The Neferine purification procedure may make a wide contribution to the follow-up development of other anti-metastasis lead compounds.

Evolution of Detecting Early Onset of Alzheimer's Disease: From Neuroimaging to Optical Immunoassays.

Alzheimer's disease (AD) is a pathological disorder defined by the symptoms of memory loss and deterioration of cognitive abilities over time. Although the etiology is complex, it is mainly associated with the accumulation of toxic amyloid-ß peptide (Aß) aggregates and tau protein-induced neurofibrillary tangles (NFTs). Even now, creating non-invasive, sensitive, specific, and cost-effective diagnostic methods for AD remains challenging. Over the past few decades, polymers, and nanomaterials (e.g., nanodiamonds, nanogold, quantum dots) have become attractive and practical tools in nanomedicine for diagnosis and treatment. This review focuses on current developments in sensing methods such as enzyme-linked immunosorbent assay (ELISA) and surface-enhanced Raman scattering (SERS) to boost the sensitivity in detecting related biomarkers for AD. In addition, optical analysis platforms such as ELISA and SERS have found increasing popularity among researchers due to their excellent sensitivity and specificity, which may go as low as the femtomolar range. While ELISA offers easy technological usage and high throughput, SERS has the advantages of improved mobility, simple electrical equipment integration, and lower cost. Both portable optical sensing techniques are highly superior in terms of sensitivity, specificity, human application, and practicality, enabling the early identification of AD biomarkers.

Effect of Layered Aminovanadic Oxalate Phosphate on Flame Retardancy of Epoxy Resin.

To alleviate the fire hazard of epoxy resin (EP), layered ammonium vanadium oxalate-phosphate (AVOPh) with the structural formula of (NH4)2[VO(HPO4)]2(C2O4)·5H2O is synthesized using the hydrothermal method and mixed into an EP matrix to prepare EP/AVOPh composites. The thermogravimetric analysis (TGA) results show that AVOPh exhibits a similar thermal decomposition temperature to EP, which is suitable for flame retardancy for EP. The incorporation of AVOPh nanosheets greatly improves the thermal stability and residual yield of EP/AVOPh composites at high temperatures. The residue of pure EP is 15.3% at 700 °C. In comparison, the residue of EP/AVOPh composites is increased to 23.0% with 8 wt% AVOPh loading. Simultaneously, EP/6 wt% AVOPh composites reach UL-94 V1 rating (t1 + t2 =16 s) and LOI value of 32.8%. The improved flame retardancy of EP/ AVOPh composites is also proven by the cone calorimeter test (CCT). The results of CCT of EP/8 wt% AVOPh composites show that the peak heat release rate (PHHR), total smoke production (TSP), peak of CO production (PCOP), and peak of CO2 production (PCO2P) decrease by 32.7%, 20.4%, 37.1%, and 33.3% compared with those of EP, respectively. This can be attributed to the lamellar barrier, gas phase quenching effect of phosphorus-containing volatiles, the catalytic charring effect of transition metal vanadium, and the synergistic decomposition of oxalic acid structure and charring effect of phosphorus phase, which can insulate heat and inhibit smoke release. Based on the experimental data, AVOPh is expected to serve as a new high-efficiency flame retardant for EP.

Widespread global disparities between modelled and observed mid-depth ocean currents.

The mid-depth ocean circulation is critically linked to actual changes in the long-term global climate system. However, in the past few decades, predictions based on ocean circulation models highlight the lack of data, knowledge, and long-term implications in climate change assessment. Here, using 842,421 observations produced by Argo floats from 2001-2020, and Lagrangian simulations, we show that only 3.8% of the mid-depth oceans, including part of the equatorial Pacific Ocean and the Antarctic Circumpolar Current, can be regarded as accurately modelled, while other regions exhibit significant underestimations in mean current velocity. Knowledge of ocean circulation is generally more complete in the low-latitude oceans but is especially poor in high latitude regions. Accordingly, we propose improvements in forecasting, model representation of stochasticity, and enhancement of observations of ocean currents. The study demonstrates that knowledge and model representations of global circulation are substantially compromised by inaccuracies of significant magnitude and direction, with important implications for modelled predictions of currents, temperature, carbon dioxide sequestration, and sea-level rise trends.