Enhanced solidification/stabilization (S/S) of fluoride in smelting solid waste-based phosphogypsum cemented paste backfill utilizing biochar: Mechanisms and performance assessment.

Phosphogypsum (PG) cemented paste backfill (CPB) is a primary non-hazardous method for treating PG. However, using traditional binders like cement increases global carbon emissions and mining operational costs while complicating the reduction of fluoride leaching risks. This study introduces a novel PG-based CPB treatment method using steel slag (SS) and ground granulated blast furnace slag (GGBFS) as binders, calcium oxide as an exciter, with biochar serving as a fluoride-fixing agent. We investigated the effect of biochar addition on the hydration and solidification/stabilization (S/S) of fluoride in SS and GGBFS-PG-based materials (SSPC). The results indicated that the optimal strength and performance for fluoride S/S were achieved with a biochar addition of 0.2 wt%. Compared to the control group without biochar, the strength increased by 54.3%, and F leaching decreased by 39.4% after 28 days of curing for SSPC. The addition of 0.2 wt% biochar facilitated heterogeneous nucleation and acted as a microfiller, enhancing SSPC's properties. However, excessive biochar reduced the compactness of SSPC. Additionally, the distribution of fluoride was strongly correlated with P, Ca, Fe, and Al, suggesting that fluoride S/S is linked to the formation of stable hydration products like fluorapatite, fluorite, and complexes such as [AlF6]3- and [FeF6]3-. These findings offer a promising approach for the safe treatment of PG and the beneficial reuse of solid waste from SS and GGBFS.

High extinction risk in large foraminifera during past and future mass extinctions.

There is a strong relationship between metazoan body size and extinction risk. However, the size selectivity and underlying mechanisms in foraminifera, a common marine protozoa, remain controversial. Here, we found that foraminifera exhibit size-dependent extinction selectivity, favoring larger groups (>7.4 log10 cubic micrometer) over smaller ones. Foraminifera showed significant size selectivity in the Guadalupian-Lopingian, Permian-Triassic, and Cretaceous-Paleogene extinctions where the proportion of large genera exceeded 50%. Conversely, in extinctions where the proportion of large genera was <45%, foraminifera displayed no selectivity. As most of these extinctions coincided with oceanic anoxic events, we conducted simulations to assess the effects of ocean deoxygenation on foraminifera. Our results indicate that under suboxic conditions, oxygen fails to diffuse into the cell center of large foraminifera. Consequently, we propose a hypothesis to explain size distribution-related selectivity and Lilliput effect in animals relying on diffusion for oxygen during past and future ocean deoxygenation, i.e., oxygen diffusion distance in body.

Higher triglyceride­glucose index is associated with increased risk of stroke among middle-aged and elderly Chinese: a national longitudinal study.

Stroke is a severe cerebrovascular disease. This study aimed to determine the association between triglyceride­glucose (TyG) index and stroke among middle-aged and elderly Chinese. Data was extracted from China Health and Retirement Longitudinal Study survey 2015 and survey 2018. Logistic regression, trend test and subgroup analysis were conducted to assess the association. Possible nonlinear relationships were explored with restricted cubic spline (RCS). Propensity score matching (PSM) was conducted to attenuate the effect of confounding factors. ORs of stroke was positively associated with TyG index. The ORs in RCS analysis also increased with the rising TyG, though p for non-linearity was bigger than 0.05. After PSM, the ORs in the full adjusted models were 1.28 (1.01, 1.62). TyG was suggested as an independent risk factor for stroke in the middle aged and elderly Chinese.

Construction and Biological Evaluation of Different Nanoshell Thickness Ni@SiO2 Nanotubes as Good Protein Separation Carriers for Bovine Hemoglobin.

BACKGROUND: Nickel nanomaterials play an important role in biological applications, but they have high toxicity and poor biocompatibility. To overcome these defects, we coated the surface of Ni nanotubes with different thicknesses of SiO2 to reduce cytotoxicity, improve biocompatibility, and broaden their biological application value. OBJECTIVE: This study aimed to construct Ni nanotubes with different thicknesses of SiO2 nanoshells; investigate the effects of silicon layer thickness, incubation time, and cell line category on the cytotoxicity of the as-synthesized materials, and evaluate the biocompatibility of the materials by biological enzymes. The Ni@SiO2-NH2 was selected for use as an adsorbent for the adsorption and purification of histidine-rich proteins, such as Bovine Hemoglobin (BHb). METHODS: Magnetic Ni nanotubes were prepared by the template-chemical deposition method. A modified version of the Stöber process was used for the SiO2 coating of Ni@SiO2 nanotubes, and adjusted by changing the volume of TEOS for different thicknesses of SiO2 nanoshells. RESULTS: Different cell lines containing tumor cells and normal cells were used in the toxicity experiment, which confirmed the low cytotoxicity and good biocompatibility of Ni@SiO2. To achieve high efficiency of immobilization and purification of histidine- rich proteins, Ni@SiO2-NH2 was obtained by introducing the amino functional group. The Ni@SiO2-NH2 was found to possess lower cytotoxicity and higher adsorption capacity compared to other synthesized materials. Besides, the Ni@SiO2-NH2 also exhibited good selectivity of histidine-rich proteins. CONCLUSION: This work has not only provided ideas for reducing the cytotoxicity and improving the biocompatibility of biological nanomaterials, but also laid a foundation for subsequent biological applications.

Relationship between Structural Defects and Free Electrons in Icosahedral Nanoclusters.

According to the classic superatom model, metal nanoclusters with a "magic number" of free valence electrons display high stability, manifesting as the closed-shell-dependent electronic robustness. The icosahedral nanobuilding blocks containing eight free electrons were the most common in constructing metal nanoclusters; however, the structure defect-dependent variations of the free electron count in icosahedral configurations are still far from thorough research. Here, we reported a hydride-containing [Pt2Ag15(SAdm)4(DPPOE)4H]2+ nanocluster with two largely defective Pt1Ag8 icosahedral cores. Together with previously reported complete or slightly defective icosahedra in metal nanoclusters, the largely defective Pt1Ag8 core provided important clues to reveal the evolutionary mode of structural defects and free electrons in icosahedral nanoclusters; the free electron count of icosahedron was reduced two-by-two (i.e., from 8e to 6e and then to 4e) accompanied by the structure defection. Overall, the work presented a novel Pt2Ag15 nanocluster with a largely defective core structure that enables an atomic-level understanding of the relationship between structural defects and free electrons in icosahedral nanoclusters.

Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.

Adapting cytoskeleton-mitochondria patterning with myocyte differentiation by promyogenic PRR33.

Coordinated cytoskeleton-mitochondria organization during myogenesis is crucial for muscle development and function. Our understanding of the underlying regulatory mechanisms remains inadequate. Here, we identified a novel muscle-enriched protein, PRR33, which is upregulated during myogenesis and acts as a promyogenic factor. Depletion of Prr33 in C2C12 represses myoblast differentiation. Genetic deletion of Prr33 in mice reduces myofiber size and decreases muscle strength. The Prr33 mutant mice also exhibit impaired myogenesis and defects in muscle regeneration in response to injury. Interactome and transcriptome analyses reveal that PRR33 regulates cytoskeleton and mitochondrial function. Remarkably, PRR33 interacts with DESMIN, a key regulator of cytoskeleton-mitochondria organization in muscle cells. Abrogation of PRR33 in myocytes substantially abolishes the interaction of DESMIN filaments with mitochondria, leading to abnormal intracellular accumulation of DESMIN and mitochondrial disorganization/dysfunction in myofibers. Together, our findings demonstrate that PRR33 and DESMIN constitute an important regulatory module coordinating mitochondrial organization with muscle differentiation.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Carotid artery transplantation of brain endothelial cells enhances neuroprotection and neurorepair in ischaemic stroke rats.

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack. Purified passage 1 endothelial cells (P1-BMECs) were prepared from mouse brain tissue. Adult rats were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. Then, the rats were treated with 5 × 105 P1-BMECs through carotid artery infusion or tail vein injection. We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats, including reducing infarct size and alleviating neurological deficits in behavioural tests. Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain. Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis. Carotid artery transplantation of BMECs significantly increased the number of surviving neurons, decreased the cerebral infarction volume, and alleviated neurological deficits. In addition, we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis, as measured by doublecortin (DCX) and Ki67 double staining within 2 weeks after ischaemic injury. We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis, neurogenesis, and neurological function recovery in adult rats after ischaemic stroke. Our results suggest that carotid injection of BMECs may be a promising new approach for treating acute brain injuries.

Melting curve of two-dimensional Yukawa systems predicted by isomorph theory.

The analytical expression for the conditions of the solid-fluid phase transition, i.e., the melting curve, for two-dimensional (2D) Yukawa systems is derived theoretically from the isomorph theory. To demonstrate that the isomorph theory is applicable to 2D Yukawa systems, molecular dynamical simulations are performed under various conditions. Based on the isomorph theory, the analytical isomorphic curves of 2D Yukawa systems are derived using the local effective power-law exponent of the Yukawa potential. From the obtained analytical isomorphic curves, the melting curve of 2D Yukawa systems is directly determined using only two known melting points. The determined melting curve of 2D Yukawa systems well agrees with the previous obtained melting results using completely different approaches.

[Improvement of the mastication function of orthodontics combined with restoration in the treatment of deep overbite with severe lower anterior teeth attrition].

PURPOSE: To observe the effect of orthodontics combined with restoration on masticatory function in deep overbite patients with severe lower anterior teeth attrition. METHODS: From January 2018 to January 2022, a total of 164 deep overbite patients with severe lower anterior teeth attrition were collected and divided into two groups according to different treatment plans: control group(72 patients, with restoration treatment) and experimental group(92 patients, with orthodontics combined with restoration treatment). The chewing efficiency of the two groups was evaluated, temporomandibular joint dysfunction index (DI), muscle palpation index (PI) and cranio-mandibular index (CMI) were calculated. The satisfaction with facial esthetic, the Chinese version of Oral Health Impact Scale-14(OHIP-14) and the repair satisfaction score were evaluated, the occurrence of adverse events between the two groups was compared. SPSS 23.0 software package was used for statistical analysis. RESULTS: After treatment, the chewing efficiency of the experimental group was significantly improved compared to the control group, while the DI, PI, and CMI were significantly reduced compared to the control group(P＜0.05). Compared with the control group, the satisfaction degree with facial esthetic and restoration in the experimental group was significantly higher, while the OHIP-14 score was significantly lower after treatment(P＜0.05). The incidence of adverse events in the experimental group was significantly decreased compared with the control group (6.52% vs 25.00%, P＜0.05). CONCLUSIONS: Combination of orthodontics and restoration treatment can enhance the effectiveness of restoration treatment for deep overbite with severe lower anterior teeth attrition, improve the mastication function and temporomandibular joint balance,satisfaction and quality of life of patients, as well as reduce the risk of adverse events.

The association between the dietary inflammatory index and allergic rhinitis: a case-control study.

Background and objective: Allergic rhinitis (AR) is a common chronic inflammatory disease that significantly impacts the quality of life of patients. However, there is limited research on the relationship between the Dietary Inflammatory Index (DII) and the risk of AR. Our study aimed to assess the association between DII and AR in a sample of adults from North China. Methods: In a case-control study, we selected 166 cases of AR and 166 age- and gender-matched controls. Dietary intake was assessed using a validated food frequency questionnaire. The energy-adjusted DII (E-DII) scores were calculated based on the quantity of diet components with inflammatory or anti-inflammatory potential. We used conditional logistic regression models to examine the association between E-DII and AR. Results: Our findings indicate a positive correlation between E-DII and AR risk. After controlling for confounders, individuals in the highest E-DII tertile exhibited a 4.41-fold increased risk of AR compared to those in the lowest tertile (OR 4.41, 95% CI 2.31-8.41). Additionally, stratified analysis showed that E-DII was positively associated with AR subtype (seasonal vs. perennial), duration (≤6 years vs. >6 years), severity (mild vs. moderate-severe), and onset time (intermittent vs. persistent). Furthermore, individuals in the highest E-DII tertile had higher intake of total fat, SFA, PUFAs, and n-6 PUFAs. Conclusion: In conclusion, we realized that there is a positive association between the E-DII score and AR. The consumption of diets abundant in anti-inflammatory nutrients and low in pro-inflammatory nutrient contents is recommended as a preventative strategy against AR.

Model-based population pharmacokinetic and exposure response analyses for safety and efficacy of nivolumab as adjuvant treatment in subjects with resected oesophageal or gastroesophageal junction cancer.

AIMS: Nivolumab is approved as adjuvant treatment in subjects with resected oesophageal or gastroesophageal junction cancer (EC/GEJC) based on results from the pivotal CheckMate 577 trial. We present a model-based clinical pharmacology profiling and benefit-risk assessment of nivolumab as adjuvant treatment in subjects with resected EC/GEJC supporting a less frequent dosing regimen. METHODS: Population pharmacokinetic (popPK) analysis was conducted to characterize nivolumab pharmacokinetics (PK) using clinical data from 1493 subjects from seven monotherapy clinical studies across multiple solid tumours. The exposure-response (E-R) analyses included data from 756 patients from CheckMate 577. E-R relationships for efficacy and safety were characterized by evaluating the relationship between nivolumab exposure and disease-free survival (DFS) for efficacy; and time to first occurrence of Grade ≥2 immune-mediated adverse events (Gr2 + IMAEs) for safety. RESULTS: Nivolumab exposure was found to be associated with both DFS and risk of Gr2 + IMAEs. However, the hazard ratios (HRs) (95% confidence interval [CI]) at the 5th and 95th percentiles of nivolumab exposure were similar for DFS and Gr2 + IMAEs, indicating flat E-R relationships within the exposure range produced by the studied regimen. Model-predicted probability of DFS and Gr2 + IMAEs were similar between the two regimens of 240 mg every 2 weeks or 480 mg every 4 weeks for 16 weeks followed by 480 mg Q4W up to 1 year. CONCLUSIONS: The analyses demonstrated a flat E-R relationship over the range of exposures produced by the studied regimen and supported the approval of an alternative dosing regimen with less frequent dosing in patients with adjuvant EC/GEJC.

Wildfires increasingly threaten oil and gas wells in the western United States with disproportionate impacts on marginalized populations.

The western United States is home to most of the nation's oil and gas production and, increasingly, wildfires. We examined historical threats of wildfires for oil and gas wells, the extent to which wildfires are projected to threaten wells as climate change progresses, and exposure of human populations to these wells. From 1984-2019, we found that cumulatively 102,882 wells were located in wildfire burn areas, and 348,853 people were exposed (resided ≤ 1 km). During this period, we observed a five-fold increase in the number of wells in wildfire burn areas and a doubling of the population within 1 km of these wells. These trends are projected to increase by late century, likely threatening human health. Approximately 2.9 million people reside within 1 km of wells in areas with high wildfire risk, and Asian, Black, Hispanic, and Native American people have disproportionately high exposure to wildfire-threatened wells.

Perirenal fat thickness contributes to the estimated 10-year risk of cardiovascular disease and atherosclerotic cardiovascular disease in type 2 diabetes mellitus.

Objective: Perirenal adipose tissue (PAT) has emerged as a potential therapeutic target for cardiovascular disease (CVD). However, the relationship between increased perirenal fat thickness (PrFT) and CVD risks in individuals with type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to evaluate the association between PrFT and the estimated 10-year risk of CVD and atherosclerotic cardiovascular disease (ASCVD) in T2DM. Method: The final analysis included 704 participants. PrFT was quantified using non-enhanced computed tomography scans, while the estimated 10-year CVD and ASCVD risk assessments were based on the Framingham and China-PAR equation risk scores, respectively. Multiple regression analysis was employed to analyze the correlation between PrFT and these risk scores. Results: Higher quartiles of PrFT displayed elevated Framingham and China-PAR equation risk scores (P<0.001). After adjusting for cardiometabolic risk factors and visceral fat area, PrFT remained significantly correlated with Framingham equation risk scores in men (ß=0.098, P=0.036) and women (ß=0.099, P=0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men (ß=0.106, P=0.009) and women (ß=0.108, P=0.007). Moreover, PrFT emerged as an independent variable associated with a high estimated 10-year risk of CVD and ASCVD, with odds ratios (ORs) of 1.14 (95% CI: 1.04-1.25, P=0.016) in men and 1.20 (95% CI: 1.11-1.31, P<0.001) in women for high estimated CVD risk, and ORs of 1.22 (95% CI: 1.08-1.41, P=0.009) in men and 1.34 (95% CI: 1.12-1.60, P<0.001) in women for high estimated 10-year ASCVD risk. Furthermore, restricted cubic spline analyses confirmed a nonlinear relationship between PrFT and high estimated CVD and ASCVD risk in both genders (P for nonlinearity and overall < 0.05). Conclusions: PrFT contributed as an independent variable to the estimated 10-year risk of CVD and ASCVD in T2DM.

Comprehensive biochemical analysis and nutritional evaluation of fatty acid and amino acid profiles in eight seahorse species (Hippocampus spp.).

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

One-pot diagnostic methods based on CRISPR/Cas and Argonaute nucleases: strategies and perspectives.

CRISPR/Cas and Argonaute (Ago) proteins, which target specific nucleic acid sequences, can be applied as diagnostic tools. Despite high specificity and efficiency, achieving sensitive detection often necessitates a preamplification step that involves opening the lid and multistep operation, which may elevate the risk of contamination and prove inadequate for point-of-care testing. Hence, various one-pot detection strategies have been developed that enable preamplification and sensing in a single operation. We outline the challenges of one-pot detection with Cas and Ago proteins, present several main implementation strategies, and discuss future prospects. This review offers comprehensive insights into this vital field and explores potential improvements to detection methods that will be beneficial for human health.

Programmable "triple attack" cancer therapy through in situ activation of disulfiram toxification combined with phototherapeutics.

Effectively and completely eliminating residual tumor cells is the key to reducing the risk of tumor metastasis and recurrence. Designing an "ideal" nanoplatform for programmable cancer therapy has great prospects for completely eliminating residual tumor cells. Herein, an intelligent nanoplatform of disulfiram (DSF)-loaded CuS-tannic acid nanohexahedrons (denoted as "DSF-CuS@TA") with thermal- and pH-sensitive degradation, as well as near-infrared (NIR-II) phototherapeutics properties, was constructed. And then, it was employed for in situ DSF toxification activation programmable "triple attack" cancer therapy. After accumulating in the tumor, DSF-CuS@TA first releases the loaded Cu(DTC)2, and simultaneously degrades and releases Cu2+ and DSF under mildly acidic stimulation to trigger instant intratumoral Cu(DTC)2 chelation, thereby achieving the "first strike." Next, under irradiation by a NIR-II laser, light energy is converted into heat to generate NIR-II photothermal therapy, thereby achieving the second strike. Subsequently, under thermal stimulation, DSF-CuS@TA degrades further, triggering the chelation of Cu(DTC)2 for a second time to reach the third strike. As expected, in vitro and in vivo studies showed that the synergistic integration of DSF-based programmed chemotherapy and NIR-II phototherapeutics could achieve effective tumor removal. Therefore, we propose a novel type of programmed therapy against cancer by designing a nanoplatform via "nontoxicity-to-toxicity" chemical chelation transformation.