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Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H 2 O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mg Ni -1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites., (© 2024 Wiley-VCH GmbH.)

Genome integration enables host organisms to stably carry heterologous DNA messages, introducing new genotypes and phenotypes for expanded applications. While several genome integration approaches have been reported, a scalable tool for DNA message storage within site-specific genome landing pads is still lacking. Here, we introduce an iterative genome integration method utilizing orthogonal serine integrases, enabling the stable storage of multiple heterologous genes in the chromosome of Escherichia coli MG1655. By leveraging serine integrases TP901-1, Bxb1, and PhiC31, along with engineered integration vectors, we demonstrate high-efficiency, marker-free integration of DNA fragments up to 13 kb in length. To further simplify the procedure, we then develop a streamlined integration method and showcase the system's versatility by constructing an engineered E. coli strain capable of storing and expressing multiple genes from diverse species. Additionally, we illustrate the potential utility of these engineered strains for synthetic biology applications, including in vivo and in vitro protein expression. Our work extends the application scope of serine integrases for scalable gene integration cascades, with implications for genome manipulation and gene storage applications in synthetic biology.

This study investigated the use of endophyte-assisted Tillandsia brachycaulos to enhance formaldehyde removal in indoor environments. A formaldehyde-degrading endophyte from the root of Epipremnum aureum, Pseudomonas plecoglossicida, was identified and used for inoculation. Among the inoculation methods, spraying proved to be the most effective, resulting in a significant 35 % increase in formaldehyde removal after 36 hours. The results of the light exposure experiment (3000 Lux) demonstrate that an increase in light intensity reduces the efficiency of the Tillandsia brachycaulos-microbial system in degrading formaldehyde. In a 15-day formaldehyde fumigation experiment at 2 ppm in a normal indoor environment, the inoculated Tillandsia brachycaulos exhibited removal efficiency ranging from 42.53 % to 66.13 %, while the uninoculated declined from 31.62 % to 3.17 %. The Pseudomonas plecoglossicida (referred to as PP-1) became the predominant bacteria within the Tillandsia brachycaulos after fumigation. Moreover, the endophytic inoculation effectively increased the resistance and tolerance of Tillandsia brachycaulos to formaldehyde, as evidenced by lower levels of hydroxyl radical, malondialdehyde (MDA), free protein, and peroxidase activity (POD), as well as higher chlorophyll content compared to uninoculated Tillandsia brachycaulos. These findings indicate that the combination of endophytic bacteria and Tillandsia brachycaulos has significant potential for improving indoor air quality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The thermoelectric properties and infrared emissivity of materials may seem unrelated, but both are influenced by electrical conductivity and thermal conductivity. The photothermal effect of SrTiO 3 can establish a connection between the Seebeck coefficient and infrared absorption in the 8-14 μm range. However, there is currently limited research on the relationship between thermoelectric performance and infrared emissivity. In this study, ZnO/SrTiO 3 composites were prepared using a hydrothermal method combined with spark plasma sintering. The intrinsic relationship between the thermoelectric and infrared emission performance of the composites was investigated by varying the ZnO content. As the ZnO content increased, the grain boundary barrier of the samples changed, affecting both electrical and thermal conductivities. The infrared emissivity initially decreased and then increased with increasing ZnO content, which contrasted with the trend observed in electrical conductivity, in accordance with the Hagen-Rubens relationship. The ZT value and infrared emissivity exhibited opposite trends, with the ZnO-5 sample having the highest thermoelectric performance and the lowest infrared emissivity, making it the most representative sample. The relationship between the thermoelectric performance and infrared emissivity of SrTiO 3 is of significant importance for developing multifunctional materials with both thermoelectric and infrared properties.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored., (Copyright © 2024 American Society of Hematology.)

Sodium-glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i) is a novel class of anti-diabetic drug, which has displayed a promising benefit for non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of SGLT2i against NAFLD and the underlying mechanisms. The db/db mice and western diet-induced NAFLD mice were treated with dapagliflozin (1 mg·kg -1 ·d -1 , i.g.) or canagliflozin (10 mg·kg -1 ·d -1 , i.g.) for 8 weeks. We showed that the SGLT2i significantly improved NAFLD-associated metabolic indexes, and attenuated hepatic steatosis and fibrosis. Notably, SGLT2i reduced the levels of pro-inflammatory cytokines and chemokines, downregulated M1 macrophage marker expression and upregulated M2 macrophage marker expression in liver tissues. In cultured mouse bone marrow-derived macrophages and human peripheral blood mononuclear cell-derived macrophages, the SGLT2i (10, 20 and 40 μmol/L) significantly promoted macrophage polarization from M1 to M2 phenotype. RNA sequencing, Seahorse analysis and liquid chromatography-tandem mass spectrometry analysis revealed that the SGLT2i suppressed glycolysis and triggered metabolic reprogramming in macrophages. By using genetic manipulation and pharmacological inhibition, we identified that the SGLT2i targeted PFKFB3, a key enzyme of glycolysis, to modulate the macrophage polarization of M1 to M2 phenotype. Using a co-culture of macrophages with hepatocytes, we demonstrated that the SGLT2i inhibited lipogenesis in hepatocytes via crosstalk with macrophages. In conclusion, this study highlights a potential therapeutic application for repurposing SGLT2i and identifying a potential target PFKFB3 for NAFLD treatment., (© 2024. The Author(s).)

Aim: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults., Methods: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs., Results: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs., Conclusion: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients., Competing Interests: Conflicts of Interest: Wan QQ, None; Zhou JQ, None; Fang LJ, None; Wang YX, None; Wang YN, None; Wang Q, None; Yan YN, None; Yang X, None; Wu SL, None; Chen SH, None; Jonas JB, None; Wei WB, None., (International Journal of Ophthalmology Press.)

Objectives: The type of ligamentous tear and the degree of knee laxity have important guiding significance for the diagnosis and management of anterior cruciate ligament (ACL) tears. Instrumental measurement is necessary for ACL tears since physical examination and magnetic resonance imaging (MRI) cannot provide an objective and quantitative assessment of knee laxity. This study aimed to compare the application of a novel knee arthrometer and simultaneous stress radiography in differentiating between complete and partial acute ACL tears, and further assess the correlation between the two measurements., Methods: A total of 106 patients with complete acute ACL tears and 52 patients with partial acute ACL tears were included in the study. Preoperative arthrometry and simultaneous stress radiography were performed using the Ligs arthrometer at 90, 120, and 150 N to assess side-to-side difference (SSD) in anterior knee laxity. The optimal threshold was determined using the receiver operating characteristic (ROC) curve. The area under the ROC curve (AUC) was used to assess the diagnostic value of the measurement. Pearson's correlation coefficient was used to assess the correlation between the two measurements., Results: The optimal differential SSD thresholds in the Ligs arthrometer were 2.7 mm at 90 N, 3.8 mm at 120 N, and 4.6 mm at 150 N. Similarly, the optimal differential SSD thresholds in simultaneous stress radiography were 3.8 mm at 90 N, 5.1 mm at 120 N, and 5.6 mm at 150 N. The AUC analysis revealed that the Ligs arthrometer was fairly informative at 90 N (AUC = 0.851), 120 N (AUC = 0.878), and 150 N (AUC = 0.884), and simultaneous stress radiography was highly informative at 90 N (AUC = 0.910), 120 N (AUC = 0.925), and 150 N (AUC = 0.948). Moreover, the AUC of the combined measurements was 0.914 at 90 N, 0.931 at 120 N, and 0.951 at 150 N. A significantly strong correlation was found between the two measurements at 90 N (r = 0.743, p < 0.001), 120 N (r = 0.802, p < 0.001), and 150 N (r = 0.823, p < 0.001)., Conclusions: The Ligs arthrometer and simultaneous stress radiography proved to be valid diagnostic tools to differentiate between complete and partial acute ACL tears, with a strong correlation between the two measurements in SSD values. Compared with single instrumental measurement, the combination of the two measurements can further improve the diagnostic value in this regard., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Zearalenone (ZEN), a mycotoxin from Fusarium fungi, impairs fertility and milk production in female animals, however, the mechanisms remain poorly understood. Using the bovine mammary epithelial cells (MAC-T) as the model, this study investigated the impacts of ZEN on programmed cell death (PCD) and milk fat synthesis, and explored the underlying mechanism. We found that 10 ng/mL prolactin (PRL) notably enhanced the differentiation of MAC-T cells, promoting the expression of genes related to the synthesis of milk fat, protein, and lactose. Next, the toxic effects of different doses of ZEN on the differentiated MAC-T with PRL treatment were determined. 10 μM and 20 μM ZEN significantly reduced cell viability, induced oxidative stress, and triggered PCD (e.g. apoptosis and necrosis). Notably, ZEN exposure downregulated the mRNA/protein levels of critical factors involving in milk fat synthesis by disrupting the AKT-mTOR-PPARγ-ACSL4 pathway. Interestingly, melatonin (MT), known for its antioxidant properties, protected against the above ZEN-induced effects by enhancing the binding of PPARγ to the promoter regions of ACSL4, which led to the upregulated expression of ACSL4 gene. These results underscored the potential of MT to mitigate the adverse effects of ZEN on mammary cells, highlighting a way for potential therapeutic intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study ( N case = 140, N control = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella , and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation., Importance: This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis., Competing Interests: The authors declare no conflict of interest.

Background: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI)., Methods: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits., Results: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)&#95;N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT&#95;N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT&#95;N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017)., Conclusions: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus., Trial Registration Number: ChiCTR2100053315; Chinese Clinical Trial Registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Endometrial cancer (EC) is one of the most common gynecologic malignancies, which lacking effective drugs for intractable conditions or patients unsuitable for surgeries. Recently, the patient-derived organoids (PDOs) are found feasible for cancer research and drug discoveries. Here, we established a series of PDOs from EC and performed drug repurposing screening and mechanism analysis for cancer treatment. We confirmed that the regulatory β subunit of methionine adenosyltransferase (MAT2B) is highly correlated with malignant progression in endometrial cancer. Through drug screening on PDOs, we identify JX24120, chlorpromazine derivative, as a specific inhibitor for MAT2B, which directly binds to MAT2B (K d = 4.724μM) and inhibits the viability of EC PDOs and canonical cell lines. Correspondingly, gene editing assessment demonstrates that JX24120 suppresses tumor growth depending on the presence of MAT2B in vivo and in vitro. Mechanistically, JX24120 induces inhibition of S-adenosylmethionine (SAMe) synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism and protein synthesis, and eventually apoptosis. Taken together, our study offers a novel approach for drug discovery and efficacy assessment by using the PDOs model. These findings suggested that JX24120 may be a potent MAT2B inhibitor and will hopefully serve as a prospective compound for endometrial cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: We aimed to develop and externally validate a CT-based deep learning radiomics model for predicting overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients, and investigate the association of radiomics with tumor heterogeneity and microenvironment., Methods: The clinicopathological data and contrast-enhanced CT images of 512 ccRCC patients from three institutions were collected. A total of 3566 deep learning radiomics features were extracted from 3D regions of interest. We generated the deep learning radiomics score (DLRS), and validated this score using an external cohort from TCIA. Patients were divided into high and low-score groups by the DLRS. Sequencing data from the corresponding TCGA cohort were used to reveal the differences of tumor heterogeneity and microenvironment between different radiomics score groups. What's more, univariate and multivariate Cox regression were used to identify independent risk factors of poor OS after operation. A combined model was developed by incorporating the DLRS and clinicopathological features. The SHapley Additive exPlanation method was used for interpretation of predictive results., Results: At multivariate Cox regression analysis, the DLRS was identified as an independent risk factor of poor OS. The genomic landscape of different radiomics score groups was investigated. The heterogeneity of tumor cell and tumor microenvironment significantly varied between both groups. In the test cohort, the combined model had a great predictive performance, with AUCs (95%CI) for 1, 3 and 5-year OS of 0.879(0.868-0.931), 0.854(0.819-0.899) and 0.831(0.813-0.868), respectively. There was a significant difference in survival time between different groups stratified by the combined model. This model showed great discrimination and calibration, outperforming the existing prognostic models (all p values < 0.05)., Conclusion: The combined model allowed for the prognostic prediction of ccRCC patients by incorporating the DLRS and significant clinicopathologic features. The radiomics features could reflect the tumor heterogeneity and microenvironment., (© 2024. The Author(s).)

Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced fecundity and gamete quality. Conversely, reduced IIS confers germ cell resilience to HSF-1 depletion-induced protein folding defects and various proteotoxic stresses. Surprisingly, this effect was not mediated by an enhanced stress response, which underlies longevity in low IIS conditions, but by reduced ribosome biogenesis and translation rate. We found that IIS activates the expression of intestinal peptide transporter PEPT-1 by alleviating its repression by FOXO/DAF-16, allowing dietary proteins to be efficiently incorporated into an amino acid pool that fuels germline protein synthesis. Our data suggest this non-cell-autonomous pathway is critical for proteostasis regulation during gametogenesis., (© 2024. The Author(s).)

Background and Aim: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF., Methods: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction., Results: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM., Conclusion: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Pancreatic ductal adenocarcinoma (PDAC) harbors a complex tumor microenvironment, and cross-talk among cells in the tumor microenvironment can contribute to drug resistance and relapse. Vasoactive intestinal peptide (VIP) is overexpressed in PDAC, and VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to immunotherapy. In this study, we showed that pancreatic cancer cells engage in autocrine VIP signaling through VIP receptor 2 (VPAC2). High coexpression of VIP with VPAC2 correlated with reduced relapse-free survival in patients with PDAC. VPAC2 activation in PDAC cells upregulated Piwi-like RNA-mediated gene silencing 2, which stimulated cancer cell clonogenic growth. In addition, VPAC2 signaling increased expression of TGFβ1 to inhibit T-cell function. Loss of VPAC2 on PDAC cells led to reduced tumor growth and increased sensitivity to anti-PD-1 immunotherapy in mouse models of PDAC. Overall, these findings expand our understanding of the role of VIP/VPAC2 signaling in PDAC and provide the rationale for developing potent VPAC2-specific antagonists for treating patients with PDAC. Significance: Autocrine VIP signaling via VPAC2 promotes cancer cell growth and inhibits T-cell function in pancreatic ductal adenocarcinoma, highlighting its potential as a therapeutic target to improve pancreatic cancer treatment., (©2024 American Association for Cancer Research.)

Large amount of polyethylene terephthalate (PET) plastics waster and emerging contaminants in water, including fluoroquinolone antibiotics, pose challenges to human survival. In this work, a green synthesis scheme is proposed in which the defective UiO-66 (d-UiO-66) is fabricated via a solvent-free routine by using PET plastics waster as raw materials for lomefloxacin (LOM) removal. In comparison with defect-free UiO-66, the created defect imparts d-UiO-66 with higher porosity and abundant defective Zr sites, which are beneficial to boost LOM adsorption. As expected, d-UiO-66 exhibited excellent LOM adsorption performances, showcasing a saturation adsorption capacity of 588 mg g -1 and a kinetic rate constant of 0.204 g mg -1  h -1 , which are 3.5 and 2.0 times higher than those of the pristine UiO-66, respectively. Remarkably, the LOM saturation adsorption capacity of d-UiO-66 surpasses that of all reported adsorbents. Mechanism study reveals that this outstanding adsorption performance of d-UiO-66 is mainly ascribed to the abundant defective sites, high porosity, together with the strong hydrogen bonding interaction and π-π stacking interaction between d-UiO-66 and LOM. Therefore, the d-UiO-66 obtained by the solvent-free method can not only effectively upcycle PET plastic waster, but also efficiently remove LOM, demonstrating a potential routine to simultaneous address the solid PET waster and wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition., (© 2024. The Author(s).)

In nature, basic terpene skeletons are produced and subsequently undergo enzymatic or nonenzymatic oxidative transformations, leading to diverse structural variations. To date, thousands of natural products featuring a variety of oxidation patterns have been isolated solely from the labdane family. This work describes a strategy for the comprehensive introduction of oxidation states into the labdane core by employing a combination of enzyme library screening, directed evolution, and sequential chemical oxidation processes. Furthermore, we showcase the functional viability of our chemoenzymatic approach by accomplishing a formal synthesis of nimbolide, highlighting its potential for streamlining the synthesis of complex natural products.

Self-control - the ability to alter unwanted impulses and behavior to bring them into agreement with goal-driven responses - is key during adolescence. It helps young people navigate through the myriad challenges they encounter while transitioning into adulthood. We review empirical milestones in our understanding of how individual differences in adolescent self-control exist and develop. We show how the use of molecular genetic measures allows us to move beyond nature versus nurture, and actually investigate how both nature and nurture explain individual differences in self-control. By highlighting the role of gene-environment correlations and gene-environment interactions, this paper aims to enthuse fellow researchers, with or without a background in genetics, to apply genetically sensitive designs too., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS., Methods: A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike's information criterion (AIC) and integrated discrimination improvement (IDI)., Results: Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes., Conclusions: Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction., (© 2024. The Author(s).)

Nanozymes, possessing nanomaterial properties and catalytic activities, offer great opportunities to design sensitive analytical detection systems. However, the low interference resistance of nanozymes poses a significant limitation on the precise detection of target substances. Herein, a nanozyme-based microfluidic chip system for pH-regulated pretreatment and sensitive sensing of cysteine (Cys) is reported. The copper metal-organic framework (Cu MOF) exhibits good cysteine oxidase-like activity at pH 7.0, while demonstrating excellent laccase-like activity at pH 8.0. Taking advantage of the pH-regulated enzyme-like activity, the integrated microfluidic device involving the immobilization of Cu MOF eliminates the interference of dopamine (DA) and accurately detects the target Cys. Compared with the untreated reaction system, the developed nanozyme system shows a significantly improved accuracy in detecting Cys, with an R 2 value of 0.9914. This work provides an efficient method to enhance the interference resistance of nanozymes and broadens the application in sample pretreatment.

The active ingredients most commonly employed in sunscreens are compounds containing one or two aromatic rings. Lignin is the most abundant renewable aromatic polymer that has the potential to yield low molecular weight aromatic chemicals when strategically depolymerized. Here, the UV absorbance of a series of monomeric and dimeric lignin model compounds (LMCs) were studied. Specifically, vanillin and ferulic acid demonstrated good absorption in the UVB (280-320 nm) range, while the 5-5 dimer showed efficient absorption in the UVA (320-400 nm) range. Based on this, vanillin, ferulic acid and 5-5 dimer were mixed in pairs and dispersed in the oily isoeugenol to prepare LMC hybrid dispersions. Subsequently, demethylated lignin (DL) was synthesized and used to encapsulate the LMC hybrid dispersions via ultrasonic cavitation to prepare DL-based nano-capsules (DLNCs). The DLNCs were used as the only active ingredient in sunscreens, whose sun protection factor (SPF) value could be up to 55 with a dosage of 10 wt%. Due to anti-photolysis property of DL, the SPF value of DLNCs-based sunscreens increased initially and maintained >8 h under UV irradiation. Additionally, the prepared DLNCs exhibited excellent anti-permeability, antioxidant capacity and biocompatibility, making them a potential substitute for conventional petroleum-based sunscreen agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Amaranthus spp. are a group of strongly invasive and vigorous plants, and heavy metal phytoremediation using alien invasive Amaranthus spp. has been a popular research topic. In this study, the bioconcentration factor (BCF) and translocation factor (TF) of Amaranthus spp. were evaluated, focusing on the accumulation potential of cadmium (Cd) and lead (Pb) by plants from three different zinc mining areas, namely Huayuan (HYX), Yueyang (LYX), and Liuyang (LYX). The HYX area has the most severe Cd contamination, while the LYX area has the most apparent Pb contamination. The results showed that Amaranthus spp. had a strong Cd and Pb enrichment capacity in low-polluted areas. To elucidate the underlying mechanisms, we used high-throughput sequencing of 16S rRNA and internal transcribed spacer (ITS) regions to analyze rhizosphere bacterial and fungal communities in three areas. The results showed significant differences in the structure, function, and composition of microbial communities and complex interactions between plants and their microbes. The correlation analysis revealed that some key microorganisms (e.g., Amycolatopsis, Bryobacterium, Sphingomonas, Flavobacterium, Agaricus, Nigrospora, Humicola) could regulate several soil factors such as soil pH, organic matter (OM), available nitrogen (AN), and available phosphorus (AP) to affect the heavy metal enrichment capacity of plants. Notably, some enzymes (e.g., P-type ATPases, Cysteine synthase, Catalase, Acid phosphatase) and genes (e.g., ZIP gene family, and ArsR, MerR, Fur, NikR transcription regulators) have been found to be involved in promoting Cd and Pb accumulation in Amaranthus spp. This study can provide new ideas for managing heavy metal-contaminated soils and new ways for the ecological resource utilization of invasive plants in phytoremediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The pseudomagnetic field effect may offer unique opportunities for the emergence of intriguing phenomena. To date, investigations into pseudomagnetic field effects on phonons have been limited to sound waves in metamaterials. The revelation of this exotic effect on the atomic vibration of natural materials remains elusive. Our simulations of twisted graphene nanoribbons reveal well-defined Landau spectra and sublattice polarization of phonon states, mimicking the behavior of Dirac Fermions in magnetic fields. Both valley-specified helical edge currents and snake orbits are obtained. Analysis of dynamics indicates that phonon Landau states have extended lifetimes, which are crucial for the realization of Landau-level lasing. Our findings demonstrate the occurrence of the phonon pseudomagnetic field effect in natural materials, which has important implications for the mechanical tuning of phonon quantum states at the atomic scale.

This study investigates the magneto-optical response of liquid crystals (LCs) with planar anchoring in the presence of γ-Fe 2 O 3 magnetic nanoparticles (MNPs). This research demonstrates the formation of novel magnetic composite chains of LCs wrapped around γ-Fe 2 O 3 MNP chains within the LC matrix under an applied magnetic field. These composite chains exhibit a distinct magneto-optical response, characterized by changes in birefringence and dichroism as the magnetic field direction is altered. Based on experimental findings, a two-subsystem model and an effective volume fraction of composite chains are proposed to describe the magneto-optical behavior of the γ-Fe 2 O 3 MNP-doped LCs. The first subsystem comprises the LC matrix, which retains its inherent anisotropic optical properties and does not respond to the applied magnetic field. The second subsystem consists of the magnetic composite chains, which exhibit a distinct magneto-optical response due to their rotational alignment with the magnetic field. The difference in absorbance, 2 α d d , which corresponds to dichroism, decreases with increasing magnetic field angle Θ , indicating a corresponding change in dichroism. This interplay between the two subsystems leads to the macroscopic magneto-optical response observed in the γ-Fe 2 O 3 MNP-doped LCs. Due to the stability of the composite chains, the magneto-optical response is stable and can be reversed.

Objective: This work aims to explore the effectiveness and safety of doxofylline in asthma treatment., Data Sources: Relevant studies published before March 2023 were retrieved from EMBASE, Cochrane Library, PubMed, and Web of Science databases., Study Selections: Risk of Bias tool (RoB 2) was applied to determine the quality of randomized controlled trials (RCTs). Relative risks (RR, 95% confidence intervals [CI]) and weighted mean differences (WMD, 95% CI) were calculated for dichotomous and continuous outcomes, respectively, under fixed or random-effects models., Results: A total of eight clinical trials comprising 1627 patients were analyzed. The meta-analysis revealed no notable change in forced expiratory volume in 1 second (FEV1) (WMD = 0.48; 95% CI: -2.09 to 3.05), the use of albuterol as a rescue medication (WMD = -0.02; 95% CI: -0.57 to 0.52), forced vital capacity (FVC) (WMD = 0.19; 95% CI: -0.28 to 0.67) and FEV1 predicted value (WMD = 1.53; 95%CI:-0.88 to 3.94) between doxofylline and control groups. However, doxofylline treatment significantly reduced adverse reactions (RR = 0.71; 95% CI: 0.60 to 0.84) and decreased the incidence of asthma events (WMD = -0.18; 95% CI: -0.33 to 0.03). Subgroup analysis results indicated that the improvement in FEV1 with doxofylline combined with budesonide was superior to that of budesonide combined with montelukast or tiotropium but inferior to that of budesonide plus formoterol combination., Conclusion: Doxofylline treatment significantly reduces the risk of asthma events and adverse events (AEs), demonstrating good safety and longer-term benefits.

Combination therapy is increasingly favored by pharmaceutical companies and researchers as an effective way to quickly discover new drugs with excellent efficacy, especially in the treatment of complex diseases. Previously, we successfully developed a computational screening method to identify such combinations, although it fell short in elucidating their synergistic mechanisms. In this work, we have transitioned to a highest single agent (HSA) synergy model for network screening, which streamlines the discovery of promising combinations and facilitates the investigation of their synergistic effects. Through this refined approach, the trimebutine-methoxsalen combination emerged as a promising candidate for heart failure (HF) treatment, exhibiting significant in vitro cardioprotective effects and effectively mitigating isoproterenol (ISO)-induced structural remodeling in the mouse heart. Further mechanistic studies have demonstrated that trimebutine and methoxsalen could synergistically inhibit intracellular calcium overload in myocardial cells and reduce the production of ROS, thus exerting cardioprotective effects. Overall, this study introduces an advanced computational strategy that not only identifies a novel combination therapy against HF but also sheds light on its underlying synergistic mechanisms.

The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid-liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents., (© 2024. The Author(s).)

Background: N6-Methyladenosine (m 6 A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m 6 A methylation in photoaging remains unknown., Objectives: This study aims to investigate the biological role and underlying mechanism of m 6 A methylation in photoaging., Methods: m 6 A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m 6 A level and specific m 6 A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m 6 A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay., Results: m 6 A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m 6 A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m 6 A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m 6 A modification and KIAA1429 might suppress collagen synthesis through an m 6 A-MFAP4-mediated process., Conclusions: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging., (© 2024. The Author(s).)

Traditional diagnostic methods, such as blood tests, are invasive and time-consuming, while sweat biomarkers offer a rapid physiological assessment. Surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in sweat analysis because of its high sensitivity, label-free nature, and nondestructive properties. However, challenges related to substrate reproducibility and interference from the biological matrix persist with SERS. This study developed a novel ratio-based 3D hydrogel SERS chip, providing a noninvasive solution for real-time monitoring of pH and glucose levels in sweat. Encapsulating the probe molecule (4-MBN) in nanoscale gaps to form gold nanoflower-like nanotags with internal standards and integrating them into an agarose hydrogel to create a 3D flexible SERS substrate significantly enhances the reproducibility and stability of sweat analysis. Gap-Au nanopetals modified with probe molecules are uniformly dispersed throughout the porous hydrogel structure, facilitating the effective detection of the pH and glucose in sweat. The 3D hydrogel SERS chip demonstrates a strong linear relationship in pH and glucose detection, with a pH response range of 5.5-8.0 and a glucose detection range of 0.01-5 mM, with R 2 values of 0.9973 and 0.9923, respectively. In actual sweat samples, the maximum error in pH detection accuracy is only 1.13%, with a lower glucose detection limit of 0.25 mM. This study suggests that the ratio-based 3D hydrogel SERS chip provides convenient, reliable, and rapid detection capabilities with substantial application potential for analyzing body fluid pH and glucose.

Transition metal oxides ion diffusion channels have been developed for ammonium-ion batteries (AIBs). However, the influence of microstructural features of diffusion channels on the storage and diffusion behavior of NH 4 + is not fully unveiled. In this study, by using MnCo 2 O 4 spinel as a model electrode, the asymmetric ion diffusion channels of MnCo 2 O 4 have been regulated through bond length optimization strategy and investigate the effect of channel size on the diffusion process of NH 4 + . In addition, the reducing channel size significantly decreases NH 4 + adsorption energy, thereby accelerating hydrogen bond formation/fracture kinetics and NH 4 + reversible diffusion within 3D asymmetric channels. The optimized MnCo 2 O 4 with oxygen vacancies/carbon nanotubes composite exhibits impressive specific capacity (219.2 mAh g -1 at 0.1 A g -1 ) and long-cycle stability. The full cell with 3,4,9,10-perylenetetracarboxylic diimide anode demonstrates a remarkable energy density of 52.3 Wh kg -1 and maintains 91.9% capacity after 500 cycles. This finding provides a unique approach for the development of cathode materials in AIBs., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cardiovascular disease (CVD) is becoming prevalent among younger people who have dual roles at both work and home. A possible contributor to CVD is conflict between work and home life. Thus, this study investigated the impact of work-to-family conflict (WFC) and family-to-work conflict (FWC) on metabolic risk factors. We used longitudinal data with a 4-yr interval from the Midlife in Japan study. 152 participants who were employed at baseline without missing variables of interest were included. We assessed the associations of baseline WFC and FWC with changes in metabolic risk factors between baseline and follow-up using Generalized Estimating Equations. After adjusting for baseline sociodemographic, work and family-related, and lifestyle factors, the fully adjusted model showed WFC was significantly associated with changes in low-density lipoprotein cholesterol (LDL-C) and Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. However, FWC was not significantly associated with changes in any metabolic risk factors. Our findings indicated a significant impact of WFC on LDL-C and TC/HDL-C ratio but no significant impact of FWC on metabolic health. Since these metabolic risk factors cause CVD, understanding the physiological responses to occupational psychosocial stress could help create primary prevention interventions and assess their effects on workers' metabolic health.

Deep vein thrombosis (DVT) is a serious health issue that often leads to considerable morbidity and mortality. Diagnosis of DVT in a clinical setting, however, presents considerable challenges. The fusion of metabolomics techniques and machine learning methods has led to high diagnostic and prognostic accuracy for various pathological conditions. This study explored the synergistic potential of dual-platform metabolomics (specifically, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) to expand the detection of metabolites and improve the precision of DVT diagnosis. Sixty-one differential metabolites were identified in serum from DVT patients: 22 from GC-MS and 39 from LC-MS. Among these, five key metabolites were highlighted by SHapley Additive exPlanations (SHAP)-guided feature engineering and then used to develop a stacking diagnostic model. Additionally, a user-friendly interface application system was developed to streamline and automate the application of the diagnostic model, enhancing its practicality and accessibility for clinical use. This work showed that the integration of dual-platform metabolomics with a stacking machine learning model enables faster and more accurate diagnosis of DVT in clinical environments.

Human coronaviruses are a group of pathogens that primarily cause respiratory and intestinal diseases. Infection can easily cause respiratory symptoms, as well as a variety of serious complications. There are several types of human coronaviruses, such as SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, and SARS-CoV-2. The prevalence of COVID-19 has led to a growing focus on drug research against human coronaviruses. The main protease (M pro ) from human coronaviruses is a relatively conserved that controls viral replication. X77 was discovered to have extremely high inhibitory activity against SARS-CoV-2 M pro through the use of computer-simulated docking. In this paper, we have resolved the crystal structure of the HCoV-NL63 M pro complexed with X77 and analyzed their interaction in detail. This data provides essential information for solving their binding modes and their structural determinants. Then, we compared the binding modes of X77 with SARS-CoV-2 M pro and HCoV-NL63 M pro in detail. This study illustrates the structural basis of HCoV-NL63 M pro binding to the inhibitor X77. The structural insights derived from this study will inform the development of new drugs with broad-spectrum resistance to human coronaviruses., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The SARS-CoV-2 coronavirus is characterized by high mutation rates and significant infectivity, posing ongoing challenges for therapeutic intervention. To address potential challenges in the future, the continued development of effective drugs targeting SARS-CoV-2 remains an important task for the scientific as well as the pharmaceutical community. The main protease (M pro ) of SARS-CoV-2 is an ideal therapeutic target for COVID-19 drug development, leading to the introduction of various inhibitors, both covalent and non-covalent, each characterized by unique mechanisms of action and possessing inherent strengths and limitations. Natural products, being compounds naturally present in the environment, offer advantages such as low toxicity and diverse activities, presenting a viable source for antiviral drug development. Here, we identified a natural compound, rosmarinic acid, which exhibits significant inhibitory effects on the M pro of the SARS-CoV-2. Through detailed structural biology analysis, we elucidated the precise crystal structure of the complex formed between rosmarinic acid and SARS-CoV-2 M pro , revealing the molecular basis of its inhibitory mechanism. These findings not only enhance our understanding of the antiviral action of rosmarinic acid, but also provide valuable structural information and mechanistic insights for the further development of therapeutic strategies against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research., (© The Author(s) 2024. Published by Oxford University Press.)

Two-dimensional (2D) all-carbon van der Waals (vdW) heterostructures consisting of graphene and graphyne component layers are reported to have enormous application prospects. Understanding the thermal transport properties of such graphene/graphyne (G/GY) heterostructures is critical to control their performance and stability in prospective applications. In this study, using molecular dynamics simulations and a machine learning (ML) method, we investigate the thermal conductivity of pristine G/GY heterostructures and their defective counterparts. Our simulation results show a significant reduction in the thermal conductivity of G/GY heterostructures due to the presence of vacancies, which become more aggressive as the defect concentration increases. Besides the concentration, the distribution of defects is another important factor affecting the thermal conductivity of defective G/GY heterostructures. Moreover, the defect effect on the thermal conductivity of G/GY heterostructures is majorly determined by the defect characteristics of their graphene layer. Such an impact is found to originate from the changes in both phonon scattering and heat flux. Based on the ML method together with a transfer learning strategy, we also develop a convolutional neural network that can be used to quickly and effectively predict the thermal conductivities of massive possible structures of defective G/GY heterostructures.

The reductive amination of 1,6-hexanediol with ammonia is one of the most promising green routes for synthesis of 1,6-hexanediamine. Herein, we developed a phosphorous modified Ni catalyst of Ni-P/Al 2 O 3 . It presented satisfactory improved selectivity to 1,6-hexanediamine in the reductive amination of 1,6-hexanediol compared to the Ni/Al 2 O 3 catalyst. The phosphorous tended to interact with Al 2 O 3 to form AlPO x species, induced Ni nanoparticle to be flatter, and the decrease of strong acid sites, the new-formed Ni-AlPO x -Al 2 O 3 interface and the flatter Ni nanoparticle were the key to switch the dominating product from hexamethyleneimine to 1,6-hexanediamine. This work develops an efficient catalyst for production of 1,6-hexanediamine from the reductive amination of 1,6-hexanediol, and provides a point of view about designing selective non-noble metal catalysts for producing primary diamines via reductive amination of diols., (© 2024 Wiley-VCH GmbH.)

Several studies have evaluated the effects of resveratrol supplementation on lipid profile parameters in humans and have demonstrated varying results. We systematically evaluated the literature and performed an umbrella meta-analysis of the effects of resveratrol supplementation on lipid profile. A comprehensive literature search was conducted in the following databases; PubMed, Embase, Scopus, and Web of Science for studies published up to November 2023. According to the standardized mean difference (SMD) analysis, resveratrol supplementation was effective in reducing serum triglyceride (TG) (SMD = -0.14 mg/dl, 95 % CI: -0.24, -0.03; p = 0.001), total cholesterol (TC) (SMD = -0.20, 95 % CI: -0.31, -0.08; p= 0.001), but not high-density lipoprotein cholesterol (HDL-c) (SMD = 0.00, 95 % CI: -0.04, 0.05; p =0.92), and low-density lipoprotein-cholesterol (LDL-c) (SMD = -0.16 mg/dl, 95 % CI: -0.40, 0.07; p =0.17). In the weighted mean difference analysis, resveratrol did not significantly decrease lipid profile parameters. Resveratrol supplementation reduces TC and TG (based on SMD analysis), but it does not significantly affect other indices. However, these significant decreases are not clinically important. Therefore, resveratrol only can be considered as an adjunctive therapeutic approach in managing dyslipidemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Estuaries are one of the most important ecosystems in the world, which are economically developed and densely populated. However, the intricate hydrodynamic environment and frequent human activities within estuaries have left the spatiotemporal variability of water properties in these areas inadequately understood. Recently, based on in situ observations and numerical simulations, we found significant spring-neap variability of water mass properties in the Yangtze River Estuary, which exhibited a bi-layered vertical structure. In the Yangtze River Estuary, salinity could decrease (increase) over 4 psu during spring (neap) tides in the upper layer, and satellite observations confirmed that both sea surface chlorophyll-a concentration and particulate organic carbon concentration also showed significant spring-neap variabilities. Decreasing salinity in the upper layer induced a shoreward pressure gradient force in the lower layer, which caused shoreward advection of high salinity water from the deep ocean and resulted in salinity increasing up to 2 psu in the lower layer of the Yangtze River Estuary. Dynamical diagnoses proved that spring-neap variability of water mass properties were caused by the asymmetry of tidal currents via modulating the ratio of freshwater to seawater. Similar situations also occurred in the Mississippi River Estuary. Furthermore, constructions of dams and other hydraulic projects in the watershed could greatly alter the locations with significant spring-neap water masses variability through reducing the riverine sediment flux and thus, leading to the erosion of the tidal flats in estuaries. The above results highlight the important roles of tidal asymmetry and human activities in affecting spring-neap variabilities of water mass properties in estuaries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ferroptosis is a new type of programmed cell death. Although ferroptosis has been studied in various aspects, there has been no visual analysis of ferroptosis in coronavirus disease 2019 (COVID-19) to date. It is still a global health concern of the COVID-19 pandemic worldwide, three years after its outbreak. Yet the emergence of the mutant strain Omicron has caused a fourth wave of infections in many countries. The pathogenesis of COVID-19 is still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics., Methods: For this study, CiteSpace 6.2 R4 software was used for bibliometric and visual atlas analysis of ferroptosis-related research, and the Genecards database was used to mine ferroptosis and COVID-19-related genes., Results: We found increasing studies about ferroptosis. China and the United States have demonstrated robust scientific innovation over recent years, with extensive collaboration between their institutions and authors. Ferroptosis and COVID-19 were seen to have 13 shared genes, which may be new targets for the treatment of COVID-19 in the future. Most of the shared genes are enriched in tumor necrosis factor (TNF) pathways. The majority of those genes are up-regulated under the cellular response to oxidative stress. Genes including Tumour necrosis factor (TNF), RELA proto-oncogene (RELA), Activating transcription factor 4 (ATF4), Cytochrome b -245 beta chain (CYBB), Jun proto-oncogene (JUN), Mitogen-activated protein kinase 1 (MAPK1) and Heme oxygenase 1 (HMOX1), maybe a breakthrough for ferroptosis and COVID-19. Whilst previous research has shown there to be a relationship between ferroptosis and COVID-19, the specific role of ferroptosis remained unclear. Our study aimed to analyze the research status of ferroptosis and its relationship with COVID-19, to provide a useful reference for further prevention and treatment of COVID-19. Overall, uncovering the role of ferroptosis in SARS-CoV-2 infection is important for the development of new treatment strategies for COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Continuous renal replacement therapy (CRRT) used in cardiac surgery-associated acute kidney injury (CSA-AKI) may have different characteristics from other diseases. We reviewed the medical records of patients with CSA-AKI requiring CRRT who underwent cardiac surgery from January 2020 to September 2021. Patients with AKI caused by other reasons who received CRRT during the same period were also evaluated. A total of 28 patients with CSA-AKI and 12 patients with AKI caused by other reasons were enrolled in this study. Compared with AKI patients caused by other reasons, patients with CSA-AKI were found to have lower mean arterial pressure, higher level of bilirubin, higher vasoactive-inotropic score, and larger daily diuretic dosage. The patients with CSA-AKI were prescribed CRRT earlier than the patients with AKI caused by other reasons. There was a significant difference in the CRRT anticoagulation method between patients with CSA-AKI and patients with AKI caused by other reasons. Six patients with CSA-AKI were treated with regional citrate anticoagulation (RCA), and the other 22 patients were treated with low molecular weight heparin or without anticoagulants. The timing of CRRT initiation in patients with CSA-AKI is earlier than that in patients with AKI caused by other reasons. Although RCA is recommended as the preferred anticoagulant for patients without contraindications, patients with CSA-AKI often have circulatory dysfunction and severe liver damage, so the risk of citrate accumulation is greater, whether to use RCA should be determined according to the individual condition of the patient., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Due to frequent and high-risk sports activities, the elbow joint is susceptible to injury, especially to cartilage tissue, which can cause pain, limited movement and even loss of joint function., Aim: To evaluate magnetic resonance imaging (MRI) multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury., Methods: A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study. We analyzed the accuracy of conventional MRI sequences (T1-weighted imaging, T2-weighted imaging, proton density weighted imaging, and T2 star weighted image) and Three-Dimensional Coronary Imaging by Spiral Scanning (3D-CISS) in the diagnosis of elbow cartilage injury. Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy., Results: The diagnostic accuracy of 3D-CISS sequence was 89.34% ± 4.98%, the sensitivity was 90%, and the specificity was 88.33%, which showed the best performance among all sequences ( P < 0.05). The combined application of the whole sequence had the highest accuracy in all sequence combinations, the accuracy of mild injury was 91.30%, the accuracy of moderate injury was 96.15%, and the accuracy of severe injury was 93.33% ( P < 0.05). Compared with arthroscopy, the combination of all MRI sequences had the highest consistency of 91.67%, and the kappa value reached 0.890 ( P < 0.001)., Conclusion: Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults. Multisequence MRI is recommended to ensure the best diagnosis and treatment., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (M pro ) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 M pro , demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the M pro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the M pro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 M pro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to M pro s from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the M pro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Visceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer., Methods: We identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models., Results: In total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer., Conclusion: Patients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dynamic tracking of spinal instrumentation could facilitate real-time evaluation of hardware integrity and in so doing alert patients/clinicians of potential failure(s). Critically, no method yet exists to continually monitor the integrity of spinal hardware and by proxy the process of spinal arthrodesis; as such hardware failures are often not appreciated until clinical symptoms manifest. Accordingly, herein, we report on the development and engineering of a bio-adhesive metal detector array (BioMDA), a potential wearable solution for real-time, non-invasive positional analyses of osseous implants within the spine. The electromagnetic coupling mechanism and intimate interfacial adhesion enable the precise sensing of the metallic implants position without the use of radiation. The customized decoupling models developed facilitate the precise determination of the horizontal and vertical positions of the implants with incredible levels of accuracy (e.g., <0.5 mm). These data support the potential use of BioMDA in real-time/dynamic postoperative monitoring of spinal implants., (© 2024. The Author(s).)

Here, we report the development and application of a novel class of spirosilacycle-based diphosphine ligands (SPOSiPs). This type of diphosphine ligand could be readily prepared in two steps with high efficiency starting from enantiopure spirobiphenoxasilin-diol (SPOSiOL). According to the structural analysis of SPOSiP and its PdCl 2 complex, SPOSiPs possess a flexible chiral pocket and feature a rigid configuration, a large dihedral angle, a long P-P distance, and a large P-M-P bite angle in their metal complexes. The potentials of SPOSiPs in asymmetric catalysis have also been preliminarily disclosed.