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Multi-principal component transition metal (TM) diborides represent a class of high-entropy ceramics (HECs) that have received considerable interest in recent years owing to their promising properties for extreme environment applications that include thermal/ environmental barriers, hypersonic vehicles, turbine engines, and next-generation nuclear reactors. While the addition of chemical disorder through the random distribution of TM elements on the cation sublattice has offered opportunities to tailor elastic stiffness and hardness, the effects of irradiation-induced structural damage on the physical properties of these complex materials have remained largely unexplored. To this end, changes in the hardness and elastic moduli of a high-entropy TM diboride (Hf0.2Nb0.2Ta0.2Ti0.2Zr0.2)B2 and three of its quaternary subsets following irradiation with 10 MeV gold (Au) ions to fluences of up to 6 × 1015 Au cm−2 are investigated at the micrometer and sub-micrometer length-scales via the dispersion of laser-generated surface acoustic waves (SAW) and nanoindentation, respectively. The nanoindentation measurements show that the TM diborides exhibit an initial increase in hardness following irradiation with energetic Au ions, with a subsequent decrease in hardness following further irradiation. One quaternary composition, (Hf1/3Ta1/3Ti1/3)B2, exhibits a notable exception to the trend and continues to exhibit an increase in hardness with ion irradiation fluence. Although differences in the absolute values of the effective elastic moduli obtained from the measured SAW dispersion and nanoindentation are observed (and attributed to microstructural variations at the measurement length-scale), both techniques yield similar trends in the form of an initial reduction and subsequent saturation in the elastic modulus with increasing ion irradiation fluence. The quaternary TM diboride (Hf1/3Ta1/3Ti1/3)B2 again exhibits a departure from this trend. The high-entropy TM diboride (Hf0.2Nb0.2Ta0.2Ti0.2Zr0.2)B2 exhibits the greatest recovery in hardness and modulus when irradiated to high ion fluences following initial changes at low fluence, indicating superior resistance to radiation-induced damage over its quaternary counterparts. Opportunities for designing HECs with superior hardness and modulus for enhanced radiation resistance (compared to their single constituent counterparts) by tailoring chemical disorder and bond character in the lattice are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by gradual loss of cognitive function. Understanding the molecular mechanisms is crucial for developing effective therapies. Methods: Data from single-cell RNA sequencing (scRNA-seq) in the GSE181279 dataset and gene chips in the GSE63060 and GSE63061 datasets were collected and analyzed to identify immune cell types and differentially expressed genes. Cell communication, pseudotime trajectory, enrichment analysis, co- expression network, and short time-series expression miner were analyzed to identify disease-specific molecular and cellular mechanisms. Results: We identified eight cell types (B cells, monocytes, natural killer cells, gamma-delta T cells, CD8+ T cells, Tem/Temra cytotoxic T cells, Tem/Trm cytotoxic T cells, and mucosal-associated invariant T cells) using scRNA-seq. AD samples were enriched in monocytes, CD8+ T cells, Tem/Temra cytotoxic T cells, and Tem/Trm cytotoxic T cells, whereas samples from healthy controls were enriched in natural killer and mucosal-associated invariant T cells. Five co-expression modules that were identified through weighted gene correlation network analysis were enriched in immune- inflammatory pathways. Candidate genes with higher area under the receiver operating characteristic curve values were screened, and the expression trend of Ubiquitin-Fold Modifier Conjugating Enzyme 1 (UFC1) gradually decreased from healthy controls to mild cognitive impairment and then to AD. Conclusion: Our study suggests that peripheral immune cells may be a potential therapeutic target for AD. Candidate genes, particularly UFC1, may serve as potential biomarkers for progression of AD. The flowchart of this study. AD, Alzheimer's disease; AUC, area under receiver operating characteristic curve; DEGs, differentially expressed genes; NC, normal control; scRNA-seq, single cell RNA-sequencing. [ABSTRACT FROM AUTHOR]

In the deep‐ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π‐conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π‐conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium‐based phosphate, identified from over 10,000 phosphates based on a polar‐axial‐symmetry screening strategy, which exhibits the highest SHG response (5.2×KH2PO4 (KDP)) with phase‐matching ability among non‐π‐conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non‐π‐conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates. [ABSTRACT FROM AUTHOR]

In the deep‐ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π‐conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π‐conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium‐based phosphate, identified from over 10,000 phosphates based on a polar‐axial‐symmetry screening strategy, which exhibits the highest SHG response (5.2×KH2PO4 (KDP)) with phase‐matching ability among non‐π‐conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non‐π‐conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates. [ABSTRACT FROM AUTHOR]

Background and Purpose: Gastrointestinal tumours overexpress voltage‐gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti‐tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. Experimental Approach: Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch‐clamp experiments. The anti‐tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. Key Results: High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration‐ and use‐dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down‐regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. Conclusion and Implications: Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5–63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential. [ABSTRACT FROM AUTHOR]

Spark plasma sintering (SPS) is an ultrafast sintering method for the preparation of ceramics and ceramic composites with simple geometrical shapes, with the combined application of uniaxial pressure. This study aims to propose an SPS densification method for Si3N4 ceramic balls without necessitating alterations to tools and equipment. The Si3N4 ceramic balls intended for sintering are positioned within a SiC powder bed inside the conventional die used in SPS. The study systematically investigates the effects of presintering temperature (1400°C, 1500°C, and 1600°C) and SPS temperature (1600°C, 1700°C, and 1800°C) on the sphericity, relative density, phase composition, microstructure, and mechanical properties of Si3N4 ceramic balls. Experimental findings reveal that Si3N4 ceramic balls exhibiting an optimal combination of sphericity (0.94 ± 0.02), relative density (98.4%), and mechanical properties (Vickers hardness: 17.5 ± 0.4 GPa, fracture toughness: 6.4 ± 0.1 MPa·m1/2) were successfully achieved at a pre‐sintering temperature and SPS temperature of 1600°C, coupled with the use of a SiC powder bed and SPS method. Consequently, the SPS method demonstrates its capability to fabricate Si3N4 ceramic balls with excellent performance. [ABSTRACT FROM AUTHOR]

Plant essential oils have been extensively investigated for their application in food industry due to their broad antimicrobial spectrum and safety. However, rare studies investigated their application in decontaminating rice noodles from fungal contamination. In this study, the cinnamon essential oil was screened out among 12 species of plant essential oils, and its antifungal activity against Penicillium oxalicum isolated from rice noodles was investigated. Our study revealed that cinnamon essential oil inhibited the spore germination in a concentration‐dependent manner, and a dosage of 0.025% (v/v) could entirely disable the spore germination. The disruption of the fungal plasma membrane was evidenced by the change of plasma membrane permeability and the leakage of cellular components. The cinnamon essential oil in vapor phase (0.00625% [v/v]) could totally inhibit the growth of fungi inoculated on rice noodles. In addition to the potential application in inactivating fungi germination on rice noodles, this study also demonstrated the feasibility of cinnamon essential as an environmental disinfectant. This study is the first report that cinnamon essential oil has been studied for decontaminating rice noodles from fungal contamination with P. oxalicum, which not only broadens the application field of plant essential oil but also provides an alternative approach for rice noodle preservation. [ABSTRACT FROM AUTHOR]

Hexavalent chromium (Cr (VI)) and para-chlorophenol (4-CP) are prevalent industrial wastewater contaminants that are recalcitrant to natural degradation and prone to migration in aquatic systems, thereby harming biological health and destabilizing ecosystems. Consequently, their removal is imperative. Compared to conventional chemical treatment methods, CW-MFC technology offers broader application potential. Leersia hexandra Swartz can enhance Cr (VI) and 4-CP absorption, thereby improving wastewater purification and electricity generation in CW-MFC systems. In this study, three CW-MFC reactors were designed with L. hexandra Swartz in distinct configurations, namely, stacked, multistage, and modular, to optimize the removal of Cr (VI) and 4-CP. By evaluating wastewater purification, electrochemical performance, and plant growth, the optimal influent hydraulic retention time (HRT) was determined. The results indicated that the modular configuration at an HRT of 5 days achieved superior removal rates and power generation. The modular configuration also supported the best growth of L. hexandra, with optimal photosynthetic parameters, and physiological and biochemical responses. These results underscore the potential of modular CW-MFC technology for effective detoxification of complex wastewater mixtures while concurrently generating electricity. Further research could significantly advance wastewater treatment and sustainable energy production, addressing water pollution, restoring aquatic ecosystems, and mitigating the hazards posed by Cr (VI) and 4-CP to water and human health. [ABSTRACT FROM AUTHOR]

In this study, the hydrothermal corrosion behavior of zirconium nitride (ZrN) ceramics used as a surrogate nuclear fuel of UN, which were added with different amounts of CrN/Cr2N (0, 10, 20, and 30 vol.%), was investigated with the objective of increasing the loss‐of‐coolant accident (LOCA) tolerance of pressurized water reactor fuel. The ZrN‐based ceramic samples with a density exceeding 98% were fabricated by using a spark plasma sintering system at 1700°C and applied stress of 30 MPa. Following 30 min of hydrothermal corrosion at 300°C, the oxidation layer thickness of pure ZrN ceramics was 9.11 ± 1.96 µm, whereas that of 30 vol.% CrN/Cr2N‐ZrN was only 1.23 ± 0.3 µm, which indicated that CrN/Cr2N offered an excellent protection effect for ZrN. This work can, thus, provide engineering design guidance for the UN with high uranium density to increase the LOCA tolerance of current nuclear power generation systems. [ABSTRACT FROM AUTHOR]

This work investigated the formation mechanism and the effects of temperature on the microstructure and shear strength of vacuum‐brazed SiAlON ceramic/WC‐Co cemented carbide joints using an Ag–Cu–Ti active filler as the interlayer. The diffusion of Ti elements toward substrates and their subsequent reaction during the brazing process led to the formation of TiN, TiC, and Ti5Si3 phases, where the featured reaction layers were established. A continuous reaction layer of TiN in the SiAlON substrate side and TiC in the WC substrate side were formed. The ceramic phases (Ti5Si3 TiN, and TiC) were distributed in a brazed intermediate layer. The highest shear strength of the brazed joints obtained at 850°C was 325.28 ± 20.27 MPa, demonstrating the feasibility of the Ag–Cu–Ti active filler in producing robust joints. [ABSTRACT FROM AUTHOR]

This study investigated the synthesis mechanism of tantalum boride (TaB2) powder via the boron/carbothermal reduction method, based on thermodynamic calculations and experimental results. The insufficient presence of the intermediate product B2O3 leads to the emergence of TaC and Ta3B4, while in the presence of a sufficient boron source in the reaction system, the primary products formed include TaB2, TaC, and B2O3, with TaC subsequently reacting with B2O3 and carbon to yield TaB2. TaB2 powder was successfully synthesized at 1500°C with the addition of an excess of 20 wt% B4C. The particle size of the powder was approximately 298 nm, and the oxygen content and carbon content in the powder were 0.6 and 0.1 wt.%, respectively. [ABSTRACT FROM AUTHOR]

Diamond‐like (DL) metal chalcogenides have attracted significant attention in recent years because of their complex structural compositions and exceptional nonlinear optical (NLO) capabilities in the infrared (IR) range. Despite notable advancements in this field, there is still a lack of systematic research on high‐performance and simply composed IR‐NLO chalcogenides with DL structures. In this study, the insightful structural characteristics and IR‐NLO properties of a ternary Ag‐based chalcogenide Ag2GeS3 are investigated for the first time at both experimental and theoretical levels. The compound belongs to the non‐centrosymmetric Cmc21 space group (No.36) and displays a 3D DL structure comprising highly oriented [AgS4] and [GeS4] tetrahedra. Due to its distinct structure, the compound may produce significant second harmonic generation (SHG) response (5.6 × AgGaS2 at 2050 nm), the biggest value reported among Ag‐based IR‐NLO chalcogenides to date, and phase matchability in the IR range with a calculated birefringence of Δn = 0.09 at 2050 nm. According to theoretical calculations, the combined impacts of the distorted [AgS4] and [GeS4] NLO‐active motifs inside the 3D DL framework provide the SHG tensor d24 of Ag2GeS3 at 51.9 pm V−1 at 2050 nm. The prospective uses of Ag2GeS3 in the field of IR‐NLO are highlighted in this work. [ABSTRACT FROM AUTHOR]

This study investigates whether family owners consider the stages of CEO tenure in their use of firm performance to assess CEOs. Integrating insights on family owners' long-term orientation and stages of CEO tenure, we theorize that family owners rely more on firm performance to make CEO replacement decisions during the mid-stage of CEO tenure than during the early and late stages. Moreover, we predict that they hold nonfamily CEOs more accountable for firm performance than family CEOs only during the mid-stage of CEO tenure. Using data from family-controlled firms in Taiwan, we found empirical evidence supportive of our theoretical predictions. [ABSTRACT FROM AUTHOR]

The aqueous reprocessing of spent nuclear fuel generates a considerable amount of plutonium alongside contaminated stainless steel, necessitating meticulous handling for safe decommission and long‐term management. The present work investigated the co‐immobilization of CeO2 (as an inactive surrogate for PuO2) with metallic Fe and Cr (representing a simplified stainless steel) within a zirconolite ceramic wasteform, nominally targeting Ca1−xCexZrTi2−2xFexCrxO7. After sintering at 1400°C under an air atmosphere, the zirconolite phase constituted 90.8–95.1 wt.% of the product across the solid solution range of 0.05 ≤ x ≤ 0.25, alongside perovskite and baddeleyite secondary phases in varying proportion; no evidence of the unincorporated CeO2 or metallic and oxidized Fe or Cr were identified. Above x = 0.30 CeO2 was detected inferring, the solubility limit was reached. A polytype transformation from zirconolite 2M to 3T was confirmed by X‐ray diffraction and selected area electron diffraction results, with the relative fraction of the 3T phase gradually increasing to 49.5 wt.% at x = 0.30. Deconvolution of X‐ray photoelectron spectroscopy data revealed the partial reduction of Ce4+–Ce3+, whereas Fe and Cr species maintained trivalent, in agreement with the targeted substitution scheme. Benefitting from the excellent chemical flexibility of zirconolite structured compounds, the co‐immobilization approach may be an effective disposal pathway for Pu‐containing wastes and contaminated stainless steel residues. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to examine the imaging features of hepatic inflammatory pseudotumors (IPTs) associated with IgG4-related and IgG4-unrelated conditions and to enhance the approach toward distinguishing between these two types of IPTs. Methods: A retrospective study was conducted, involving 20 patients diagnosed with hepatic IPTs. Imaging procedures were conducted within a timeframe of 4 weeks prior to hepatectomy or biopsy. The imaging features were then analyzed and compared using chi-squared analysis. Results: Seventeen (81.0%) IPTs were located in the hepatic subcapsular area; six (66.7%) IgG4-related IPTs were distributed around the hepatic hilum; and eleven (91.7%) IgG4-unrelated and three (33.3%) IgG4-related IPTs had unclear boundaries. All lesions exhibited similar characteristics in CT scans, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI), with the apparent diffusion coefficient (ADC) values slightly higher than the surrounding liver tissue. Delayed hypoenhancement, observed in five cases (55.6%), was exclusively present in IgG4-related IPTs. The remaining IPT lesions displayed progressive enhancement, septal and marginal enhancement, and persistent enhancement. Central enhancement was absent in three IgG4-related IPTs (33.3%) and ten IgG4-unrelated IPTs (83.3%). The duct-penetrating sign was identified in two IgG4-unrelated IPTs (16.7%) and seven IgG4-related IPTs (77.8%). Furthermore, seven patients with IgG4-related IPTs had additional lesions outside the liver. Conclusions: IgG4-related lesions are frequently found in the vicinity of the hepatic hilum; they display the duct-penetrating sign and affect other organs as well. Both groups exhibited progressive or persistent contrast enhancement in typical IPT lesions, but delayed hypoenhancement was only observed in the IgG4-related IPT group. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement. Critical relevance statement: Differences in imaging features differentiate IgG4-related and -unrelated inflammatory pseudotumors (IPT). IgG4-related lesions are frequently near the hepatic hilum, display duct-penetrating sign, and affect other organs. Only the IgG4-related group demonstrated delayed hypoenhancement. IgG4-unrelated IPT lesions often exhibited indistinct boundaries lacking central enhancement. Key Points: Compared with IgG 4-unrelated IPTs, IgG4-related IPTs show delayed hypoenhancement and affect other organs. IgG4-unrelated IPTs have unclear boundaries and lack central enhancement. Improved IPT diagnostic capabilities can help minimize additional, potentially unnecessary, interventions. [ABSTRACT FROM AUTHOR]

Rare earth (RE)-doped BaTiO3 materials are promising dielectric materials for base-metal electrode multilayer ceramic capacitors (BME-MLCCs). Thus, the fundamental understanding of their effect on dielectric properties and reliability is crucial for further improvement of its performance. Herein, according to Preisach model, the dielectric stability of Dy and Y-doped BaTiO3 MLCCs with different particle sizes was investigated in this study. First order reversal curve (FORC) analysis showed that the reversible and irreversible domain wall motion of Dy-doped samples was weaker than that of Y-doped samples. Results also showed that the higher "shell" proportion of "core-shell" structure in Dy-doping was beneficial for improving the dielectric stability and insulation resistance degradation. The findings provide a comprehensive understanding and illustrate the significant role of the "core-shell" volume ratio in the tetragonality and domain wall motion in RE-doped BaTiO3 materials, and consequently laying an important ground work to obtain high dielectric stability and reliability in BME-MLCCs. [ABSTRACT FROM AUTHOR]

The frequency of riverine floods is predicted to increase in East Asia. However, the response of coastal hypoxia (<63 μmol L−1) to floods has not been well understood. In the summer of 2020, characterized by one of the most significant Changjiang water fluxes in three decades, we conducted a cruise during the flood period on the East China Sea inner shelf. Our observations revealed severe bottom hypoxia with a maximum spatial coverage of ∼11,600 km2 and a minimum dissolved oxygen concentration (DO) of 21 μmol L−1. In the surface layer, the relationships between salinity and nitrate, dissolved inorganic carbon (DIC) indicated significant organic matter production, validated by a high‐Chlorophyll‐a (Chl a) patch (>5 μg L−1). Furthermore, the significant relationship between apparent oxygen utilization and DIC of deep waters reveals that the organic matter decomposition primarily drove the hypoxia during the flood period. Episodic wind events also influenced bottom DO and DIC, by transporting surface waters to the deep. Multiple‐years data set shows that the average Changjiang nitrate flux during flood years is about 1.4 times that during non‐flood years. The flood waters mix with estuarine waters, forming the high‐nutrient plume waters, which expanded farther offshore during the flood period. While high turbidity remained confined to the inner estuary. Consequently, the high‐Chl a area significantly expanded, which significantly exacerbated the hypoxia. Plain Language Summary: Coastal waters are severely threatened by hypoxia, which impacts the growth, reproduction, and migration of marine organisms. Nutrient inputs from river basins are one of the major controlling factors of hypoxia in coastal oceans. The frequency and intensity of floods in river basins are projected to increase in the context of global warming in East Asia. However, the relationship between floods and coastal hypoxia is not well documented. The year 2020 witnessed lots of riverine flood events across Asian countries, which provided us with an excellent opportunity to reveal the influences of flood on hypoxia development on the shelf. In 2020, the August nitrate flux of Changjiang was 1.5 times higher compared to that in non‐flood years. We observed maximum hypoxic waters covering 11,600 km2 with a minimum DO of 21 μmol L−1 on the East China Sea inner shelf. Historical data showed that the floods led to the expansion of the high‐nutrient plume area, resulting in high biological production in the plume, and a nearly doubling of the hypoxia extent in the bottom waters. With the growing risk of intensive floods, hypoxia is likely to aggravate in coastal waters. Key Points: We observed a maximum hypoxia area of ∼11,600 km2, and a minimum dissolved oxygen of 21 μmol L−1 during the flood period in 2020Significant nitrate removal and surface Chlorophyll a exceeding 29 μg L−1 suggested intense biological production during the flood periodThe expansion of high‐Chl a plume area during flood periods surpasses that of non‐flood periods, contributing to hypoxia area increase [ABSTRACT FROM AUTHOR]

Protein-protein interactions (PPIs) stabilization with molecular glues plays a crucial role in drug discovery, albeit with significant challenges. In this study, we propose a dual-site approach, targeting the PPI region and its dynamic surroundings. We conduct molecular dynamics simulations to identify critical sites on the PPI that stabilize the cyclin-dependent kinase 12 - DNA damage-binding protein 1 (CDK12-DDB1) complex, resulting in further cyclin K degradation. This exploration leads to the creation of LL-K12-18, a dual-site molecular glue, which enhances the glue properties to augment degradation kinetics and efficiency. Notably, LL-K12-18 demonstrates strong inhibition of gene transcription and anti-proliferative effects in tumor cells, showing significant potency improvements in MDA-MB-231 (88-fold) and MDA-MB-468 cells (307-fold) when compared to its precursor compound SR-4835. These findings underscore the potential of dual-site approaches in disrupting CDK12 function and offer a structural insight-based framework for the design of cyclin K molecular glues.Protein-protein interactions (PPIs) stabilization with molecular glues plays a crucial role in drug discovery. Here, the authors propose a dual-site approach for the design of clyclin K molecular glues, targeting the PPI region and its dynamic surroundings, and report a dual-site molecular glue for the cyclin-dependent kinase 12 - DNA damage-binding protein 1 complex, resulting in further cyclin K degradation. [ABSTRACT FROM AUTHOR]

Atmospheric ozone (O3) has long been a threat to human health, however, rational design of dual-function materials for straightforward sensing and removal of trace O3 in the environment (air, water, etc.) remains challenging. Herein, we present a highly stable and hydrophobic two-dimensional Mn(II)-based metal–organic framework (denoted as BUT-82), which shows distinctive color change on exposure to O3 in air or in liquid water due to the oxidation of Mn2+. The O3 concentration could be quantified by analyzing the color changes of BUT-82 using UV/Vis spectroscopy or more facilely using smartphone photography, and the limits of detection for O3 of the two methods were 47 and 274 ppb, respectively. In addition, BUT-82 showed apparently higher capacity for the removal of O3 from dry or highly humid air flows than its starting materials, namely MnCl2·4H2O and a dicarboxylic acid ligand containing a long alkyl chain (3,3′-bis(dodecyloxy)-[1,1′-biphenyl]-4,4′-dicarboxylic acid). Isoreticular expansion of the MOF to tune its performance was also proven feasible. This work offers new insights into the development of new materials for O3 pollution control. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV1 [β = 0.21 (95% CI 0.12, 0.30)] and FVC [β = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40–60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia are all established risk factors for chronic kidney disease (CKD), and their interplay could exacerbate CKD progression. This study aims to evaluate the potential mediation effects of hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia on the association between hyperuricemia (HUA) and chronic kidney disease (CKD). Methods: We collected electronic medical record data from 2055 participants who underwent physical examinations at the Affiliated Hospital of Qingdao University. The data were utilized to investigate the mediating effect of various factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), homocysteine (HCY), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose (Glu), and hemoglobin A1c (HbA1c) on the relationship between HUA and CKD. Results: Upon adjusting for confounding variables, mediation analysis indicated that only HCY acted as a mediator in the HUA–CKD relationship (p value < 0.05), exhibiting a statistically significant mediation effect of 7.04%. However, after adjustment for multiple testing, none of these variables were statistically significant. Conclusions: Considering the observed associations between hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and CKD, none of the factors of interest remained statistically significant after adjusting for multiple testing as potential mediators of hyperuricemia on CKD. [ABSTRACT FROM AUTHOR]

The high cost of ReB2 limits its application as a member of novel high‐hardness materials, which can be alleviated by forming composites with cheap compound(s). In the present study, a dense ReB2–B4C composite was fabricated via in situ reactive sintering by spark plasma sintering with Re and B13C2 (Re:B = 1:20) as raw materials. The phase composition, microstructure, Vickers hardness, and fracture toughness of the obtained composite were characterized, and the reaction mechanism, crack propagation, and toughening mechanism were clarified. XRD, SEM, Raman, and XPS results revealed that the obtained composite is mainly composed of ReB2 and B4C phases, with a small amount of free B and graphite coexisted. Vickers hardness of 33.5 ± 4.4 GPa under 0.49 N load and 24.6 ± 1.5 GPa under 4.9 N load and fracture toughness of 5.02 ± 0.37 MPa·m1/2 were observed for the obtained composite. The toughening mechanism of the obtained ReB2–B4C composite including crack deflection crack and cracking bridging was analyzed in detail. [ABSTRACT FROM AUTHOR]

This work investigated the effect of ZrB2 content on phase composition, relative density, microstructure, and mechanical performance of Si3N4 ceramics prepared by Si nitridation and hot‐pressing method. Si3N4 ceramics were fabricated using Si powder by nitridation and hot‐pressing process. Results showed that the addition of ZrB2 enhanced the transformation of α‐Si3N4 into β‐Si3N4 phase during nitridation, resulting in a greater fraction of β‐Si3N4 (above 90 wt.%) phase in Si3N4 ceramics with ZrB2 after hot‐pressing. In contrast, ceramics without ZrB2 had a lower ratio of β‐Si3N4 (40.4 wt.%). The use of 2.5 vol.% ZrB2 yielded a significant bimodal microstructure and increased fracture toughness to 5.0 ± 0.2 MPa·m1/2, but decreased Vickers hardness to 16.4 ± 0.5 GPa. However, increasing the ZrB2 content to 5 vol.% and 10 vol.% led to a massive formation of equiaxed coarse β‐Si3N4 grains and a significant decrease in Vickers hardness and fracture toughness. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is a well‐known pathological factor driving neuronal loss and age‐related neurodegenerative diseases. Melatonin, coenzyme Q10 and lecithin are three common nutrients with an antioxidative capacity. Here, we examined the effectiveness of them administrated individually and in combination in protecting against oxidative stress‐induced neuronal death in vitro, and neurodegenerative conditions such as Alzheimer's disease and associated deficits in vivo. Methods: Mouse neuroblastoma Neuro‐2a (N2a) cells were exposed with H2O2 for 6 h, and subsequently treated with melatonin, coenzyme Q10, and lecithin alone or in combination for further 24 h. Cell viability was assessed using the CCK‐8 assay. Eight‐week‐old male mice were intraperitoneally injected with D‐(+)‐galactose for 10 weeks and administrated with melatonin, coenzyme Q10, lecithin, or in combination for 5 weeks starting from the sixth week, followed by behavioral tests to assess the effectiveness in mitigating neurological deficits, and biochemical assays to explore the underlying mechanisms. Results: Exposure to H2O2 significantly reduced the viability of N2a cells and increased oxidative stress and tau phosphorylation, all of which were alleviated by treatment with melatonin, coenzyme Q10, lecithin alone, and, most noticeably, by combined treatment. Administration of mice with D‐(+)‐galactose‐induced oxidative stress and tau phosphorylation, brain aging, impairments in learning and memory, anxiety‐ and depression‐like behaviors, and such detrimental effects were mitigated by melatonin, coenzyme Q10, lecithin alone, and, most consistently, by combined treatment. Conclusions: These results suggest that targeting oxidative stress via supplementation of antioxidant nutrients, particularly in combination, is a better strategy to alleviate oxidative stress‐mediated neuronal loss and brain dysfunction due to age‐related neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

Insulin‐deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi‐closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high‐risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin‐producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin‐deficient diabetes, these inhibitors have resulted in robust glucose‐lowering responses and generation of insulin‐producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials. [ABSTRACT FROM AUTHOR]

Laser surface texturing (LST) with different patterns was performed on silicon nitride (Si3N4) ceramic. Effect of patterns created by LST on coefficient of friction (COF) and surface damage under dry friction was investigated. Results indicated that fluctuation of COF decreased with the increasing loading force for both un-textured and textured samples. Under the same loading force, COF of Si3N4 ceramic with textured patterns was more stable than the samples with smoothly finished surface. The COF of textured samples was not always lower than that of un-textured samples. This may be caused by differences in the distribution of debris and the continuity of surface contact. The worn surface existed damages of plow and crack. However, peeling was observed on un-textured samples only. The surface damage of textured samples was slighter than un-textured samples. Especially under the high loading force, catastrophic damage appeared on the smooth surface. The worn surface of textured samples still maintained the similar state. This could be mainly due to the more complex friction process on the surface of textured sample. The wear rate of the frictional pair was also studied. The mechanisms of friction process for smooth and textured surface were analyzed. [ABSTRACT FROM AUTHOR]

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype–phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3′ truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins. [ABSTRACT FROM AUTHOR]

Our brain constantly processes multisensory inputs to make decisions and guide behaviors, but how goal-relevant processes are influenced by irrelevant information is unclear. Here, we investigated the effects of intermodal and intramodal task-irrelevant information on visual and auditory categorical decision-making. In both visual and auditory tasks, we manipulated the modality of irrelevant inputs (visual vs. auditory vs. none) and used linear discrimination analysis of EEG and hierarchical drift-diffusion modeling (HDDM) to identify when and how task-irrelevant information affected decision-relevant processing. The results revealed modality-specific impacts of irrelevant inputs on visual and auditory categorical decision-making. The distinct effects on the visual task were shown on the neural components, with auditory distractors amplifying the sensory processing whereas visual distractors amplifying the post-sensory process. Conversely, the distinct effects on the auditory task were shown in behavioral performance and underlying cognitive processes. Visual distractors facilitate behavioral performance and affect both stages, but auditory distractors interfere with behavioral performance and impact on the sensory processing rather than the post-sensory decision stage. Overall, these findings suggested that auditory distractors affect the sensory processing stage of both tasks while visual distractors affect the post-sensory decision stage of visual categorical decision-making and both stages of auditory categorical decisionmaking. This study provides insights into how humans process information from multiple sensory modalities during decision-making by leveraging modalityspecific impacts. [ABSTRACT FROM AUTHOR]

Solar activity, such as sunspots and flares, has a great impact on humans, living beings, and technologies in the whole world. Changes in sunspots will influence high-frequency and space-navigation radio communications. Based on the full-disk, southern and northern hemispheres sunspot areas (SAs) data in 1874–2023 from the Royal Observatory, Greenwich (RGO) USAF/NOAA, extreme value theory (EVT) is applied to predict the trend of the 25th and 26th solar cycles (SCs) in this work. Two methods with EVT, the block maxima (BM) approach and the peaks-over-threshold (POT) approach, are employed to research solar extreme events. The former method focuses on each block's maximum sunspot areas value and is applied for the generalized extreme value (GEV) distribution. The latter method aims to select the extreme values exceeding a threshold value and is used to obtain the generalized Pareto (GP) distribution. It is the first time that the EVT is applied on the sunspot areas data from the Royal Observatory, Greenwich (RGO) USAF/NOAA. The analysis indicates that the estimated 8-year return levels for sunspot areas are 5701 and 6258 using the two methods, while the estimated 19-year return levels are all 7165. This suggests that the trends of the 25th and 26th solar cycles will be stronger than that of the 24th solar cycle. [ABSTRACT FROM AUTHOR]

Physical properties and irradiation damage in four transition metal diborides (TM-diborides) are investigated: one high-entropy diboride (Hf0.2Nb0.2Ta0.2Ti0.2Zr0.2)B2 and three subsets of quaternary diborides. Surprisingly, instead of being generally classified as ceramic materials, the predominant mechanism for heat conduction is through electrons. The irradiation response of these TM-diborides under ion irradiation at room temperature has been investigated using 10 MeV Au ions to fluences up to 6 × 1015 Au cm−2. Black dot dislocation loops are visible at low doses, whereas dislocation networks are observed with increasing fluence. While up to ~ 4% volume expansion has been determined in these diborides, the crystalline structure remains stable under room-temperature irradiation, preserving the hexagonal AlB2 phase. Perspectives of chemical disorder resulting from various TMs in high-entropy materials, along with their associated physical properties and influence on irradiation damage, are discussed in terms of the number of valence electrons, atomic mass, and volume. [ABSTRACT FROM AUTHOR]

Currently, previous studies of low‐temperature sintering of high‐entropy carbide ceramics (HECCs) have followed the traditional approach to use the low‐melting‐point metals, such as Co, Ni, and so forth, as sintering additives. However, metallic binders can cause adverse impacts on hardness of HECCs. This study reported an innovation processing method for low‐temperature sintering of HECCs, which involved the use of various contents of CrN as sintering additive and spark plasma sintering at 1600°C to obtain dense HECCs. In comparison to the grain size of pure (Ti, Zr, Nb, Ta, Mo)C bulk sintered at 2000°C (3.29 ± 1.02 μm), the grain size of samples with the addition of 5–15 wt.% CrN sintered at 1600°C was significantly smaller, ranging from 0.32 to 0.48 μm. By using only 5 wt.% CrN, dense (Ti, Zr, Nb, Ta, Mo)C ceramics with a high hardness value of 26.73 ± 0.43 GPa could be obtained. Furthermore, increasing the amount of CrN to 15 wt.% resulted in a fracture toughness of 3.78 ± 0.10 MPa·m1/2. It is anticipated that the (Ti, Zr, Nb, Ta, Mo)C ceramic with an ideally combined hardness and toughness can be achieved at low sintering temperatures by the proper control of CrN content. [ABSTRACT FROM AUTHOR]

This research investigated the effect of Bi4Ti3O12 (BiT) template particles size on the structure and piezoelectric properties of 〈001〉‐textured (Bi0.5Na0.5)TiO3 (BNT)‐based lead‐free piezoelectric ceramics. Results of X‐ray diffractometer analyses and scanning electron microscopy observations showed that high purity BiT template particles could be obtained with the KCl as the molten salt system. Highly 〈001〉‐textured (~87%) BNT‐based ceramics prepared with large size BiT templates (7.75 µm) exhibited a high inverse piezoelectric constant d33* (1100 pm/N), which was ∼3.38‐fold larger than that with 1.91 µm (325 pm/N). In addition, we have found that too small the template size can make it difficult to align the orientation of the template during the casting process, whereas too large the size can create problems such as too much hysteresis (∆S/Smax = 67%). This study has demonstrated that the use of high purity large size BiT template particles could provide a feasible route to fabricate BNT‐based textured ceramics with desired electro‐strain properties. [ABSTRACT FROM AUTHOR]

Severe ozone (O3) pollution has been recorded in China in recent years. The key precursor, volatile organic compounds (VOCs), is still not well understood in Nanning, which is a less developed city compared to other megacities in China. In this study, a year-long measurement of VOCs was conducted from 1 October 2020 to 30 September 2021, to characterize the ambient variations and apportion the source contributions of VOCs. The daily-averaged concentration of VOCs was measured to be 26.4 ppb, ranging from 3.2 ppb to 136.2 ppb across the whole year. Alkanes and oxygenated VOCs (OVOCs) were major species, contributing 46.9% and 25.2% of total VOC concentrations, respectively. Propane, ethane, and ethanol were the most abundant in Nanning, which differed from the other significant species, such as toluene (3.7 ppb) in Guangzhou, ethylene (3.8 ppb) in Nanjing, and isopentane (5.5 ppb), in Chengdu. The positive matrix factorization (PMF) model resolved six source factors, including vehicular emission (contributing 33% of total VOCs), NG and LPG combustion (19%), fuel burning (17%), solvent use (16%), industry emission (10%), and biogenic emission (5%). This indicated that Nanning was less affected by industrial emission compared with other megacities of China, with industry contributing 12–50%. Ethylene, m/p-xylene, butane, propylene, and isoprene were key species determined by ozone formation potential (OFP) analysis, which should be priority-controlled. The variations in estimated OFP and observed O3 concentrations were significantly different, suggesting that VOC reactivity-based strategies as well as meteorological and NOx effects should be considered collectively in controlling O3 pollution. This study presents a year-long dataset of VOC measurements in Nanning, which gives valuable implications for VOC control in terms of key sources and reactive species and is also beneficial to the formulation of effective ozone control strategies in other less developed regions of China. [ABSTRACT FROM AUTHOR]

Methylene blue (MB) was regarded as a highly toxic and hazardous substance owing to its irreparable hazard and deplorable damage on the ecosystem and the human body. The treatment of this colorant wastewater appeared to be one of the towering challenges in wastewater treatment. In this study, a microbial fuel cell coupled with constructed wetland (CW-MFC) with effective MB elimination and its energy recuperation concurrently based on the incorporation of carbide lime as a substrate in a new copper oxide-loaded on carbon cloth (CuO/CC) cathode system was studied. The crucial influencing parameters were also delved, and the MB degradation and chemical oxygen demand (COD) removal efficiencies were correspondingly incremented by 97.3% and 89.1% with maximum power output up to 74.1 mW m−2 at optimal conditions (0.2 g L−1 carbide lime loading and 500 Ω external resistance). The carbide lime with high calcium ion content was greatly conducive for the enrichment of critical microorganism and metabolic activities. The relative abundances of functional bacteria including Proteobacteria and Actinobacteriota were vividly increased. Moreover, the impressive results obtained in printed ink wastewater treatment with a COD removal efficiency of 81.3% and a maximum power density of 58.2 mW m−2, which showcased the potential application of CW-MFC. [ABSTRACT FROM AUTHOR]

Purpose: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar–indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). Methods: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. Conclusion: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221). [ABSTRACT FROM AUTHOR]