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Androgen receptor (AR) antagonists are widely used for the treatment of prostate cancer (PCa), but their therapeutic efficacy is usually compromised by the rapid emergence of drug resistance. However, the lack of the detailed interaction between AR and its antagonists poses a major obstacle to the design of novel AR antagonists. Here, funnel metadynamics is employed to elucidate the inherent regulation mechanisms of three AR antagonists (hydroxyflutamide, enzalutamide, and darolutamide) on AR. For the first time it is observed that the binding of antagonists significantly disturbed the C‐terminus of AR helix‐11, thereby disrupting the specific internal hydrophobic contacts of AR‐LBD and correspondingly the communication between AR ligand binding pocket (AR‐LBP), activation function 2 (AF2), and binding function 3 (BF3). The subsequent bioassays verified the necessity of the hydrophobic contacts for AR function. Furthermore, it is found that darolutamide, a newly approved AR antagonist capable of fighting almost all reported drug resistant AR mutants, can induce antagonistic binding structure. Subsequently, docking‐based virtual screening toward the dominant binding conformation of AR for darolutamide is conducted, and three novel AR antagonists with favorable binding affinity and strong capability to combat drug resistance are identified by in vitro bioassays. This work provides a novel rational strategy for the development of anti‐resistant AR antagonists. [ABSTRACT FROM AUTHOR]

Aim Design Methods Results Conclusion Implications for clinical practice Patient and Public Contribution To explore the views and preferences for advance care planning from the perspectives of residents, family members and healthcare professionals in long‐term care facilities.A qualitative descriptive design.We conducted semi‐structured interviews with 12 residents of long‐term care facilities, 10 family members and 14 healthcare professionals. Data were analysed using reflexive thematic analysis. The social ecological model was used to develop implementation recommendations.We constructed a conceptual model of barriers and facilitators to advance care planning in long‐term care facilities, drawing upon four dominant themes from the qualitative analysis: (1) The absence of discourse on end‐of‐life care: a lack of cultural climate to talk about death, the unspoken agreement to avoid conversations about death, and poor awareness of palliative care may hinder advance care planning initiation; (2) Relational decision‐making process is a dual factor affecting advance care planning engagement; (3) Low trust and ‘unsafe’ cultures: a lack of honest information sharing, risks of violating social expectations and damaging social relationships, and risks of legal consequences may hinder willingness to engage in advance care planning; (4) Meeting and respecting residents' psychosocial needs: these can be addressed by readiness assessment, initiating advance care planning in an informal and equal manner and involving social workers.Our findings show that residents' voices were not being heard. It is necessary to identify residents' spontaneous conversation triggers, articulate the value of advance care planning in light of the family's values and preferences, and respect residents' psychosocial needs to promote advance care planning in long‐term care facilities. Advance care planning may alleviate the decision‐making burden of offspring in nuclear families.The evidence‐based recommendations in this study will inform the implementation of context‐specific advance care planning in Asia‐Pacific regions.Patients and caregivers contributed to the interview pilot and data collection. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy. Method: We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated. Results: We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06–0.39, I2 = 0.37%), 27% (95% CI 0.03–0.60, I2 = 60.43%) and 65% (95% CI 0.23–0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08–0.99, I2 = 85.20%), 47% (95% CI 0.14–0.81, I2 = 74.17%), 59% (95% CI 0.27–0.89, I2 = 60.23%), and 50% (95% CI 0.13–0.87, I2 = 73.89%), respectively. Conclusion: CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever. Registration: The protocol was registered in prospero, with the registration number CRD42022342647. [ABSTRACT FROM AUTHOR]

Grylloprimevala jilina is a true cave insect living in the dark areas of caves. It has the characteristics of sparse skin pigmentation, degeneration of the compound eyes and monocular eyes, and obvious preference for high‐humidity and low‐temperature environments. Given the highly specialized, rare, and limited distribution, G. jilina is considered an endangered species and also a first‐level national protected insect in China. Cave creatures often undergo dramatic morphological changes in their sensory systems to adapt to the cave environment. Most previous studies mainly focused on morphological adaptive changes in cave insects, and only a few studied the changes at the gene level. In this study, we performed transcriptome analysis of G. jilina and constructed phylogenetic trees of genes that are related to environmental adaptation, including chemosensory, visual‐related, reproduction‐related, temperature adaptation‐related, and winged morph differentiation‐related genes. Besides, the expression levels of environmental adaption‐related genes in different tissues, including antennae, heads, thoraxes, abdomens, legs, and tails, were analyzed. The results showed the loss of chemosensory genes and vision‐related genes, the conservation of reproduction‐related genes and temperature adaptation‐related genes, and the conservation of wing‐related genes despite the loss of wings, and the results were consistent with other cave insects. The identification and expression study of genes possibly related to the environmental adaptability in G. jilina provided basic data for the protection of this endangered species and increased knowledge about insect evolution in general. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy. Method: We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated. Results: We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06–0.39, I2 = 0.37%), 27% (95% CI 0.03–0.60, I2 = 60.43%) and 65% (95% CI 0.23–0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08–0.99, I2 = 85.20%), 47% (95% CI 0.14–0.81, I2 = 74.17%), 59% (95% CI 0.27–0.89, I2 = 60.23%), and 50% (95% CI 0.13–0.87, I2 = 73.89%), respectively. Conclusion: CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever. Registration: The protocol was registered in prospero, with the registration number CRD42022342647. [ABSTRACT FROM AUTHOR]

Paclitaxel, a natural anticancer drug, is widely recognized and extensively utilized in the treatment of breast cancer (BC). However, it may lead to certain side effects or drug resistance. Fortunately, combination therapy with another anti-tumor agent has been explored as an option to improve the efficacy of paclitaxel in the treatment of BC. Herein, we first evaluated the synergistic effects of paclitaxel and flubendazole through combination index (CI) calculations. Secondly, flubendazole was demonstrated to synergize paclitaxel-mediated BC cell killing in vitro and in vivo. Moreover, we discovered that flubendazole could reverse the drug resistance of paclitaxel-resistant BC cells. Mechanistically, flubendazole was demonstrated to enhance the inhibitory effect of paclitaxel via HIF1α/PI3K/AKT signaling pathways. Collectively, our findings demonstrate the effectiveness of flubendazole in combination with paclitaxel for treating BC, providing an insight into exploiting more novel combination therapies for BC in the future. [ABSTRACT FROM AUTHOR]

Understanding the microglial neuro-immune interactions in the primate brain is vital to developing therapeutics for cortical injury, such as stroke or traumatic brain injury. Our previous work showed that mesenchymal-derived extracellular vesicles (MSC-EVs) enhanced motor recovery in aged rhesus monkeys following injury of primary motor cortex (M1), by promoting homeostatic ramified microglia, reducing injury-related neuronal hyperexcitability, and enhancing synaptic plasticity in perilesional cortices. A focal lesion was induced via surgical ablation of pial blood vessels over lying the cortical hand representation of M1 of aged female rhesus monkeys, that received intravenous infusions of either vehicle (veh) or EVs 24 h and again 14 days post-injury. The current study used this same cohort to address how these injury- and recovery-associated changes relate to structural and molecular interactions between microglia and neuronal synapses. Using multi-labeling immunohistochemistry, high-resolution microscopy, and gene expression analysis, we quantified co-expression of synaptic markers (VGLUTs, GLURs, VGAT, GABARs), microglia markers (Iba1, P2RY12), and C1q, a complement pathway protein for microglia-mediated synapse phagocytosis, in perilesional M1 and premotor cortices (PMC). We compared this lesion cohort to age-matched non-lesion controls (ctr). Our findings revealed a lesion-related loss of excitatory synapses in perilesional areas, which was ameliorated by EV treatment. Further, we found region-dependent effects of EVs on microglia and C1q expression. In perilesional M1, EV treatment and enhanced functional recovery were associated with increased expression of C1q + hypertrophic microglia, which are thought to have a role in debris-clearance and anti-inflammatory functions. In PMC, EV treatment was associated with decreased C1q + synaptic tagging and microglia–spine contacts. Our results suggest that EV treatment may enhance synaptic plasticity via clearance of acute damage in perilesional M1, and thereby preventing chronic inflammation and excessive synaptic loss in PMC. These mechanisms may act to preserve synaptic cortical motor networks and a balanced normative M1/PMC synaptic function to support functional recovery after injury. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. Methods: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. Results: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. Conclusions: We developed a DLAT-based model to predict patients' clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy. [ABSTRACT FROM AUTHOR]

Background: Clinical epidemiological studies have found that some patients with ulcerative colitis (UC) are prone to mental disorders. DSS-induced acute and chronic UC models are often used to evaluate the efficacy of anti-UC drugs. However, whether DSS has an effect on mouse behavior has not been reported. Methods: Acute and chronic UC models were induced by 3% DSS and 1.5% DSS, respectively. The bloody stool, the changes in the colon length, and histopathological changes in the colon were used to evaluate the success of the animal model. The behavior of mice was evaluated by open field experiment, tail suspension experiment and Sucrose preference test. Results: The weight of mice in 3% DSS group decreased significantly, the DAI score increased significantly, the colon length of mice was significantly shortened, and the structure of colonic crypts was abnormal, which showed inflammatory cell infiltration and shrinkage of crypts. Compared with the control group, the immobility time of 3%DSS group mice in the tail suspension test and forced swimming test had no effect, the number of running and grooming times was significantly reduced, and there was no significant difference in the number of standing times. No abnormality was observed in HE staining of the hippocampus. However, in 1.5% DSS-induced chronic UC model, behavioral and hippocampal abnormalities were observed not only UC symptoms. Conclusions: The acute UC model induced by 3% DSS has certain influence on the behavior of mice, but the mental state of mice is normal, which may be the abnormal behavior caused by UC symptoms; However, the chronic UC model induced by 1.5% DSS has a significant effect on the behavior of mice, and the mice have mental disorders, which are caused by mental disorders. [ABSTRACT FROM AUTHOR]

Undesirable side effects and multidrug tolerance are the main holdbacks to the treatment of cancer in conventional chemotherapy. Fortunately, targeted drug delivery can improve the enrichment of drugs at the target site and reduce toxicity to normal tissues and cells. A targeted drug delivery system is usually composed of a nanocarrier and a targeting component. The targeting component is called a "ligand". Aptamers have high target affinity and specificity, which are identified as attractive and promising ligands. Therefore, aptamers have potential application in the development of smart targeting systems. For instance, aptamers are able to efficiently recognize tumor markers such as nucleolin, mucin, and epidermal growth factor receptor (EGFR). Besides, aptamers can also identify glycoproteins on the surface of tumor cells. Thus, the aptamer-mediated targeted drug delivery system has received extensive attention in the application of cancer therapy. This article reviews the application of aptamers as smart ligands for targeted drug delivery in cancer therapy. Special interest is focused on aptamers as smart ligands, aptamer-conjugated nanocarriers, aptamer targeting strategy for tumor microenvironment (TME), and aptamers that are specified to crucial cancer biomarkers for targeted drug delivery. [ABSTRACT FROM AUTHOR]

As a prevailing solution for visual tracking, Siamese networks manifest high performance via convolution neural networks and weight-sharing schemes. Most existing Siamese networks have adopted various offline training strategies to realize precise tracking by comparing the extracted target features with template features. However, their performances may degrade when dealing with unknown targets. The tracker is unable to learn background information through offline training, and it is susceptible to background interference, which finally leads to tracking failure. In this paper, we propose a twin-branch architecture (dubbed SiamOT) to mitigate the above problem in existing Siamese networks, wherein one branch is a classical Siamese network, and the other branch is an online training branch. Especially, the proposed online branch utilizes feature fusion and attention mechanism, which is able to capture and update both the target and the background information so as to refine the description of the target. Extensive experiments have been carried out on three mainstream benchmarks, along with an ablation study, to validate the effectiveness of SiamOT. It turns out that SiamOT achieves superior performance with stronger target discrimination abilities. [ABSTRACT FROM AUTHOR]

There is a significant potential demand around the world for a flexible product to manage individual longevity risk. However, annuity markets remain thin, driven by factors including lack of pricing transparency, high product loadings, bequest motives, loss aversion, and the difficulty to hedge the risk. This paper proposes an individual retirement product to allow flexible management of longevity risk. The product combines a lifetime income with a flexible death benefit to meet individual bequest needs. It also benefits the issuers by lower mortality risk due to the natural hedging, and thus lower capital cost as a risk margin. We apply actuarial models that provide transparent pricing for interest rate and mortality risk, the construction of immunized bond portfolios, and the determination of a loading and solvency margin for systematic longevity risk. We also quantify the natural hedging benefits arising from the flexible inclusion of both survival benefits and death benefits. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study is the first to investigate the function of TREM-1 in neuroinflammation induced by TBI. • We found that inhibition of TREM-1 reduced brain edema, decreased mNSS and improved neurobehavioral outcomes after TBI. We also determined inhibition of TREM-1 alleviated neuroinflammation, which was associated with SYK/p38MAPK signaling pathway. • It suggest that TREM-1 may be a potential therapeutic target to alleviate neuroinflammation after TBI. Traumatic brain injury (TBI), as a major public health problem, is characterized by high incidence rate, disability rate, and mortality rate. Neuroinflammation plays a crucial role in the pathogenesis of TBI. Triggering receptor expressed on myeloid cells-1 (TREM-1) is recognized as an amplifier of the inflammation in diseases of the central nervous system (CNS). However, the function of TREM-1 remains unclear post-TBI. This study aimed to investigate the function of TREM-1 in neuroinflammation induced by TBI. Brain water content (BWC), modified neurological severity score (mNSS), and Morris Water Maze (MWM) were measured to evaluate the effect of TREM-1 inhibition on nervous system function and outcome after TBI. TREM-1 expression in vivo was evaluated by Western blotting. The cellular localization of TREM-1 in the damaged region was observed via immunofluorescence staining. We also conducted Western blotting to examine expression of SYK, p-SYK and other downstream proteins. We found that inhibition of TREM-1 reduced brain edema, decreased mNSS and improved neurobehavioral outcomes after TBI. It was further determined that TREM-1 was expressed on microglia and modulated subtype transition of microglia. Inhibition of TREM-1 alleviated neuroinflammation, which was associated with SYK/p38MAPK signaling pathway. These findings suggest that TREM-1 can be a potential clinical therapeutic target for alleviating neuroinflammation after TBI. [ABSTRACT FROM AUTHOR]

The microstructure and composition of corrosion film deposited on pure Mg were systematically investigated, and for the first time DFT was used to reveal the adsorption behavior of carboxylates on the surface of corrosion layer rather than the metallic Mg. Presence of carboxylate inhibitor dramatically modified composition of the corrosion film and bonded directly with Mg atoms in the outermost MgO based corrosion layer by means of carboxyl. The bonded Mg atoms were lifted by 0.8 – 1.1 Å from their original position when abundant inhibitors started to act as complexing agent, leading to deteriorated inhibition effect. [Display omitted] • The corrosion film deposited on pure Mg was systematically investigated. • DFT was used for the first time to reveal the adsorption behavior of inhibitor on corrosion layer. • Carboxylate bonded with Mg atoms in the outermost MgO based corrosion layer. • Adsorption energy of inhibitors was found to be associated with its concentration. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of computerized cognitive training on the cognitive functions of stroke patients. Background: With increased publications on computerized cognitive training, a meta‐analysis is essential to determine the effects of computerized cognitive training among stroke patients. Design A systematic review and meta‐analysis of randomized controlled studies. Data Sources: Cochrane Library, Pubmed, EBSCO, Scopus, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were explored to search for research studies from inception to January 2020. Review Methods: Six outcomes indicators were considered to determine the effects of computerized cognitive training. Two reviewers were selected to search and independently appraise the available articles from various databases. Meta‐analysis was performed using the RevMan 5.3 software. Results: A total of 622 patients with 17 studies were included. Computerized cognitive training significantly improves global cognition, working memory, attention and executive function of stroke patients. However, there was inadequate evidence to demonstrate any effects of computerized cognitive training on activities of daily living and depression. Conclusion: Computerized cognitive training improves the cognitive functions of stroke patients. However, further research studies are needed to confirm its efficacy in activities of daily living as well as on alleviating depression. Summary statement: What is already known about this topic? Stroke commonly results in health impairments, particularly on cognitive functions, activities of daily living and depression, which may have a negative impact on a patient's quality of life.Previous studies indicated that computerized cognitive training is a safe and efficacious intervention for improving the cognition of older patients with dementia.Little is known about the efficacy of computerized cognitive training on improving cognitive functions, activities of daily living and depression among stroke patients. What this paper adds? Computerized cognitive training significantly improves global cognition, working memory, attention and executive function among stroke patients compared with control groups.No statistically significant effects were found on activities of daily living and depression.Subgroup analysis indicated that 4 and 12 weeks of medium‐high intensity computerized cognitive training showed significant improvement on global cognition for stroke patients. The implications of this paper: Healthcare providers should recognize the efficacy of computerized cognitive training on the cognitive rehabilitation of stroke patients.Cognitive outcome measurements vary between studies and further appraisal of reliability and validity is essential to avoid reporting bias and to validate research trials with uniform neuropsychological measurements.Further clinical trials are required with large samples and long‐term follow‐up of interventions and reporting adverse events. [ABSTRACT FROM AUTHOR]

This paper studies properties of the mixed spherical vector p -spin model. At zero temperature, we establish and investigate a Parisi type formula for the ground state energy. At finite temperature, we provide some properties of minimizers of the Crisanti–Sommers formula recently obtained in Ko (2018). In particular, we extend some of the one-dimensional Parisi measure results of Auffinger and Chen (2015) to the vector case. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries will generate a large amount of heat during high-rate charging and discharging. By transferring the heat to the environment in time, the batteries can be kept in a suitable temperature range. This allows them to work normally, prolongs their cycle life, and reduces the risk of thermal runaway. Immersion cooling is a simple and efficient thermal management method. In this paper, a battery thermal management system (BTMS) with immersion cooling was designed by immersing the lithium-ion cells in the non-conductive coolant—dimethyl silicone oil. The electric–thermal coupled model was adopted to obtain the heat production and temperature distribution of the cell during discharging, and the performance of the system was obtained by numerical calculation. It was found that, compared with natural cooling, immersion cooling could significantly reduce both the maximum temperature (MAT) of the cell and the temperature of the tabs during the 3C discharging process. However, the maximum temperature difference (MATD) of the cell was significantly increased. To solve this problem, the effects of the flow rate, viscosity, specific heat capacity, and thermal conductivity of the coolant on the performance of immersion cooling were further investigated and discussed, including the MAT and MATD of the cell, and the pressure drop of the coolant. The method and results could provide references for the design and application of the BTMS with immersion cooling in the future. [ABSTRACT FROM AUTHOR]

The jet fire caused by thermal runaway in lithium-ion batteries can be regarded as typical hazard, severely threatening human life. To study the inhibitory effect of water mist containing additives on thermal runaway-induced jet fire in lithium-ion batteries, an experimental test device employing water mist to suppress fire in lithium-ion batteries was developed. In this work, water mist containing additives was used to extinguish the thermal runaway-induced jet fire. The optimal composition of the additive-containing water mist was as follows by mass: 0.22% FC4430, 0.2% TEOA, 0.32% urea, and 2% KCl. The four-factor and three-level orthogonal methods were employed to explore the inhibitory effect of additive-containing water mist on thermal runaway-induced jet fire in lithium-ion batteries. The optimal composition of mist as determined from these methods was: 0.17% FC-4430, 0.2% TEOA, 0.32% urea, and 2.5% KCl. The results show that the synergistic effects of the physical and chemical additives can significantly improve the ability of water mist to suppress jet fires in lithium-ion batteries. In addition, the additive-containing water mist could be used as a new type of extinguishing agent. [ABSTRACT FROM AUTHOR]

Cancer cells prefers to rely on aerobic glycolysis than pyruvate oxidation to meet the high demand of energy for rapidly proliferation. Peroxisome proliferator-activated receptors (PPARs) are a kind of important ligand-inducible transcription factors and play crucial roles in glucose and lipid metabolism. Careful designing of novel agonists for PPARs, may show improvement with the side effects and also increase the therapeutic value for cancer and other metabolic disorder diseases. Compared with normal human liver cells, lower expression or acitivity of PPARs is observed in hepatocellular carcinoma (HCC). In this study, we show that oroxyloside (OAG) is a new dual agonist of PPARγ/ɑ, and inhibits cell proliferation of HCC based on metabolic switch. Via both PPAR-dependent and PPAR-independent regulations on glycolipid metabolic enzymes, OAG shuts down the catabolism of glucose and promotes fatty acids oxidation to generate acetyl-CoA for TCA cycle and oxidative phosphorylation. The metabolic switch induced by OAG results in a marked increase of reactive oxygen species (ROS) levels, leading to rapid dephosphorylation of RB and cell-cycle arrest in G1 phase. Pyruvate dehydrogenase kinase 4 (PDK4) and β-Oxidation are required for the suppression of cell cycle progression by OAG. Together, our findings provide a new drug candidate and a viable therapeutic strategy for HCC based on metabolic reprogram. [Display omitted] • OAG is a Dual PPARγ/ɑ Agonist and Induces Glycolipid Metabolism Switch in HCC. •OAG Induces Cell Cycle Arrest via a Metabolism Switch Triggered ROS-Dependent Mechanism. •PDK4 and β-Oxidation Are Required for the Anti-HCC Effect of OAG. [ABSTRACT FROM AUTHOR]

Soot formation during very fuel-rich oxidation of ethylene (with equivalence ratio, φ , ranging from 3 to infinity) at relatively low temperatures (1473–1673 K) was studied in a flow reactor, in which temperature was well controlled through an external heater, and φ of the reactants was adjusted by adding different amounts of O 2 (0–6000 ppm) at the inlet of the reactor. Detailed sooting properties including soot volume fraction, number density, particle size distribution (PSD), and morphology were examined. The results show that at a temperature of 1673 K, the total soot yield increases monotonously with φ. However, at 1473 and 1573 K, the soot volume fraction increases first and then decreases as φ increases from 3 to infinity, which means a small amount of oxygen can promote soot formation. The PSD and number density results indicate that this promotion effect is more prominent at the nucleation stage and weakens as soot grows at longer residence times. In addition, soot morphology is affected mostly by temperature rather than φ , and the decrease of temperature leads to larger primary particles and less fractal aggregates. Kinetic modeling results indicate that the concentrations of PAHs and soot increase because a small amount of O 2 addition can enhance the C 3 + C 3 pathways through the generation of reactive oxygenated species. [ABSTRACT FROM AUTHOR]

Halogenated α, β-unsaturated C 4 -dicarbonyl (X-BDA), a novel family of high-toxicity ring cleavage products, is produced during the disinfection of phenolic compounds. The technique of electrocatalytic hydrodehalogenation (ECH) is efficient in rupturing carbon-halogen bonds and generating useful chemicals. This study used first principles to examine the ECH reaction mechanism of X-BDA and the subsequent hydrogenation reaction of the toxic derivative BDA over the 1 T′-MoS 2 /Ti 3 C 2 T 2 (T = O, OH, F) catalysts. The catalytic activity of Ti 3 C 2 T 2 (T = O, OH, F) catalysts decreases gradually with -OH, -F, -O functional group. The loading of 1 T′-MoS 2 onto the Ti 3 C 2 T 2 surface improves the stability and selectivity of Ti 3 C 2 T 2. In particular, 1 T′-MoS 2 /Ti 3 C 2 (OH) 2 is most conducive to the ECH reaction of X-BDA via a direct-indirect continuous reduction process. It exhibits excellent removal capability towards Cl-BDA, with decreasing reactivity in the order of the Cl-, Br-, and I-BDA. The material offers a solution to the challenging dechlorination issue. The dehalogenated product BDA can be hydrogenated to produce 1,4-butanedial, 1,4-butanediol, and 1,4-butenediol. Three valuable chemicals can be obtained by exerting an applied potential of − 0.65 V. This work suggests that the formation of heterojunction catalyst may lead to new strategies to improve ECH for environmental remediation applications. [Display omitted] • 1 T′-MoS2 loading significantly improved the stability and activity of Ti3C2T2 catalyst. • 1 T′-MoS2/Ti3C2(OH)2 is an excellent surface material for X-BDA hydrodechlorination reaction. • 1 T′-MoS2/ Ti3C2(OH)2 has stronger catalytic activity for Cl-BDA than Br-BDA and I-BDA. • BDA continues hydrogenation to generate valuable chemicals. [ABSTRACT FROM AUTHOR]

The influence of ferrocene addition (∼60 ppm on a molar basis) on soot formation in laminar premixed burner-stabilized stagnation ethylene flames (with an equivalence ratio of 2.0) is investigated both experimentally and computationally. The results show that ferrocene addition has a very small effect on both flame temperature and concentrations of small soot precursors from kinetic modeling, but apparently promotes soot inception and particle size growth from particle size distribution measurements, and decreases soot maturity from elemental analysis. Transmission electron microscope (TEM) images and energy dispersive spectrometry (EDS) results show that distinct iron cores are present in large soot aggregates, consistent with the kinetic modeling results that iron predominates over iron oxide in ferrocene-doped flames. Iron in the incipient soot may be too dispersed or form too small cores to be observed by TEM; and as the soot particles coagulate, iron in the soot coalesces into large cores. Since iron is not exposed on the soot surface, and the concentrations of soot precursors are also not significantly increased by ferrocene, ferrocene promotes soot size growth mainly through enhanced coagulation rather than surface growth. • The influence of ferrocene addition at ppm level on soot formation in premixed ethylene flames is investigated. • Ferrocene shows a very small effect on both flame temperature and soot precursors. • Ferrocene apparently promotes both soot inception and size growth, and decreases soot maturity. • Ferrocene promotes soot size growth mainly through enhanced particle coagulation. [ABSTRACT FROM AUTHOR]

Nicotinic acetylcholine receptor (nAChR) is recognized as a significant insecticide target for neonicotinoids and some agonists. In this study, the nAChR α1 subunit from Apis mellifera was first found to be narrowly tuned to different bee toxicity insecticides, namely, sulfoxaflor (SFX) and flupyradifurone (FPF). Hence, novel sulfoximine derivatives 7a-h were rationally designed and synthesized by introducing a benzo[ d ][1,3]dioxole moiety into a unique sulfoximine skeleton based on the binding cavity characteristics of Amelα1/ratβ2. The two electrode voltage clamp responses of 7a-h were obviously lower than that of SFX, indicating their potentially low bee toxicity. Besides, representative compounds 7b and 7g exhibited low bee toxicity (LD 50 > 11.0 μg/bee at 48 h) revealed by acute contact toxicity bioassays. Molecular modelling results indicated that Ile152, Ala151, and Val160 from honeybee subunit Amelα1 and Lys144 and Trp80 from aphid subunit Mpα1 may be crucial for bee toxicity and aphicidal activity, respectively. These results clarify the toxic mechanism of agonist insecticides on nontargeted pollinators and reveal novel scaffold sulfoximine aphicidal candidates with low bee toxicity. These results will provide a new perspective on the rational design and highly effective development of novel eco-friendly insecticides based on the structure of the nAChR subunit. [Display omitted] • nAChR α1 subunit from Apis mellifera was related to bee toxicity of sulfoxaflor. • Novel low bee-toxicity sulfoximine aphicides were discovered by targeting Amelα1/ratβ2 complex. • Some residues were critical for aphicidal activity and bee toxicity, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • The carbon foam with great smoke inhibition was prepared by modified lignin. • The total smoke release of carbon foam decreased by 80.91%∼98.12% at most. • Modified lignin reduced the use of raw material phenol by 30 wt%. In this work, a lignin phenolic carbon foam (LCF) with preferable smoke suppression performance was fabricated by substitute 10 wt.% and 30 wt.% phenol with modified lignin in the traditional process. The result showed that the LCF 600 s (LCFs carbonized at 600℃) with different lignin percentages showed better smoke suppression performance than the traditional phenolic carbon foam (CF 600). The peak smoke production rate (pSPR) and total smoke release (TSR) of LCF 600 s decreased by 6.90%∼48.28% and 80.91%∼96.28%, and the peak CO production rate and CO yield decreased by 41.17%∼70.59% and 53.80%∼77.79%, respectively. Besides, LCF 1-10-600 and LCF 2-30-600 displayed the best smoke suppression performance (0020, 0.0015 m2/s of pSPR and 0.61, 2.76 m2/m2 of TSR, respectively). Since the introduced modified lignin significantly increased the amount of benzene rings in the forms, the degree of graphitization of the resulted carbon foams greatly improved, leading to better smoke suppression performance. Furthermore, the added lignin facilitated the preservation of the carbon layer, resulting in reducing smoke production consequently. [ABSTRACT FROM AUTHOR]

Nicotinic acetylcholine receptor (nAChR) is recognized as a significant insecticide target for neonicotinoids and some agonists. In this study, the nAChR α1 subunit from Apis mellifera was first found to be narrowly tuned to different bee toxicity insecticides, namely, sulfoxaflor (SFX) and flupyradifurone (FPF). Hence, novel sulfoximine derivatives 7a-h were rationally designed and synthesized by introducing a benzo[ d ][1,3]dioxole moiety into a unique sulfoximine skeleton based on the binding cavity characteristics of Amelα1/ratβ2. The two electrode voltage clamp responses of 7a-h were obviously lower than that of SFX, indicating their potentially low bee toxicity. Besides, representative compounds 7b and 7g exhibited low bee toxicity (LD 50 > 11.0 μg/bee at 48 h) revealed by acute contact toxicity bioassays. Molecular modelling results indicated that Ile152, Ala151, and Val160 from honeybee subunit Amelα1 and Lys144 and Trp80 from aphid subunit Mpα1 may be crucial for bee toxicity and aphicidal activity, respectively. These results clarify the toxic mechanism of agonist insecticides on nontargeted pollinators and reveal novel scaffold sulfoximine aphicidal candidates with low bee toxicity. These results will provide a new perspective on the rational design and highly effective development of novel eco-friendly insecticides based on the structure of the nAChR subunit. [Display omitted] • nAChR α1 subunit from Apis mellifera was related to bee toxicity of sulfoxaflor. • Novel low bee-toxicity sulfoximine aphicides were discovered by targeting Amelα1/ratβ2 complex. • Some residues were critical for aphicidal activity and bee toxicity, respectively. [ABSTRACT FROM AUTHOR]

Jisuikang (JSK) is an herbal formula composed of many kinds of traditional Chinese medicine, which has been proved to be effective in promoting the rehabilitation of patients with spinal cord injury (SCI) after more than ten years of clinical application. However, the mechanisms of JSK promoting nerve regeneration are yet to be clarified. The aim of this study was to investigate the effects of JSK protecting neurons, specifically the regulation of NgR/RhoA/ROCK signal pathway. The motor function of rats was evaluated by the BBB score and inclined plate test, Golgi staining and transmission electron microscope were used to observe the microstructure of nerve tissue, and fluorescence double-labeling method was used to detect neuronal apoptosis. In this study, we found that JSK could improve the motor function of rats with SCI, protect the microstructure (mitochondria, endoplasmic reticulum, and dendritic spine) of neurons, and reduce the apoptosis rate of neurons in rats with SCI. In addition, JSK could inhibit the expression of Nogo receptor (NgR) in neurons and the NgR/RhoA/ROCK signal pathway in rats with SCI. These results indicated JSK could improve the motor function of rats with SCI by inhibiting the NgR/RhoA/ROCK signal pathway, which suggests the potential applicability of JSK as a nerve regeneration agent. [ABSTRACT FROM AUTHOR]

Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity. Author summary: Phenamacril is a recently identified myosin I inhibitor that is a potent and highly species-specific and myosin subtype-selective fungicide. We report the high-resolution structure of the phenamacril-bound myosin I motor domain of the major crop pathogen Fusarium graminearum, providing insight into the molecular mechanism of phenamacril action and resistance. These results are of broad significance for understanding the mode of actions of myosin-based fungicides and for designing novel myosin I inhibitors for crop protection and for treatment of human myosin dysfunction diseases. [ABSTRACT FROM AUTHOR]

Memory is thought to be encoded by sparsely distributed neuronal ensembles in memory‐related regions. However, it is unclear how memory‐eligible neurons react during learning to encode trace fear memory and how they retrieve a memory. We implemented a fiber‐optic confocal fluorescence endomicroscope to directly visualize calcium dynamics of hippocampal CA1 neurons in freely behaving mice subjected to trace fear conditioning. Here we report that the overall activity levels of CA1 neurons showed a right‐skewed lognormal distribution, with a small portion of highly active neurons (termed Primed Neurons) filling the long‐tail. Repetitive training induced Primed Neurons to shift from random activity to well‐tuned synchronization. The emergence of activity synchronization coincided with the appearance of mouse freezing behaviors. In recall, a partial synchronization among the same subset of Primed Neurons was induced from random dynamics, which also coincided with mouse freezing behaviors. Additionally, training‐induced synchronization facilitated robust calcium entry into Primed Neurons. In contrast, most CA1 neurons did not respond to tone and foot shock throughout the training and recall cycles. In conclusion, Primed Neurons are preferably recruited to encode trace fear memory and induction of activity synchronization among Primed Neurons out of random dynamics is critical for trace memory formation and retrieval. [ABSTRACT FROM AUTHOR]

• Defective UiO-66-NH 2 -supported ion imprinted polymers were developed. • The G-IIP-3 exhibits excellent adsorption capacity and selectivity for Gd(III). • 2-hydroxyphosphonoacetic acid was used as the functional monomer and defective linker. • The phosphate groups and Zr-O clusters contribution to the Gd(III) adsorption on G-IIP-3. Developing a high-performance adsorbent for the recovery of Gd(III) from wastewater is of great environmental and economic significance. Metal organic frameworks (MOFs) functionalized with mixed-linker defect strategy hold huge potential for use as adsorbents for removing heavy metal ions from wastewater. However, the defective MOFs still show a relative low selectivity to target metal ions. Herein, we propose the combination of surface-imprinting and defect engineering strategies to synthesize Gd(III) ion-imprinted polymers (G-IIPs) based on mixed-linker Zr-MOFs, and apply them for capturing Gd(III) ions from wastewater. It is worth noting that 2-hydroxyphosphonoacetic acid not only served as monodentate ligand to in-situ induce ligand vacancies and form hierarchical pores on UiO-66-NH 2 , but also as high-efficient functional monomer in imprinted layer to provide the strong coordination ability towards Gd(III). Benefiting from its abundant binding sites and hierarchical pore structure, the as-prepared G-IIP-3 with rich defects displays a high adsorption capacity of 181.75 mg·g−1 and a short equilibration time of 30 min for Gd(III). In addition, G-IIP-3 presents highly selective capture of Gd(III) over interfering ions. Furthermore, density functional theory calculation demonstrates that both phosphate group and Zr-O cluster play key roles in the Gd(III) adsorption process. Thus, this work provides an effective method to develop high-performance materials for Gd(III) recovery by organically combining the advantages of surface-imprinting and defect engineering strategies. [ABSTRACT FROM AUTHOR]

Degradation of Chlorine-containing disinfection by-products(Cl-DBPs) on surface by electrocatalytic hydrodechlorination (EHDC) is considered a promising advanced water treatment method. Cl-DBPs have ecological toxicity and health risks so that it is urgent to degrade DBPs. We designed and verified the degradation performance of the EHDC of 18 kinds of DBPs (TAAs, TANs, TALs, TNMs, TAcAms, THMs) with different substituents led by the Ti 3 C 2 X 2 (X = O/OH) system by the first-principles. On the surface of Ti 3 C 2 (OH) 2 , DBPs react with atomic hydrogen (*H) by a direct-indirect continuous reduction mechanism to eliminate the Cl atom in turn. Dissociative adsorption of DBPs on the surface of Ti 3 C 2 (OH) 2 simultaneously realizes the first electron transfer step and forms H vacancy, which makes its electrocatalytic activity superior to that of Ti 3 C 2 O 2. Removing the six types of DBPs only needs to add −0.1 V of applied potential. In addition, we investigated the impact of substituents and chlorination degree on the reactivity of DBPs removal. The strong electron-withdrawing group is more conducive to the dechlorination reaction. Dehalogenation is much favorable in thermodynamics as the increase in chlorination degree. This study provides important insights and efficient catalysts for the degradation of DBPs and shows the potential of MXenes in eliminating chloride in water. [Display omitted] • The degradation performance of Ti 3 C 2 (OH) 2 is superior to Ti 3 C 2 O 2. • Cl atom was removed in Ti 3 C 2 (OH) 2 by direct-indirect continuous reaction. • The high activity results from H vacancy formation and synchronous first electron transfer. • Substituents effect and chlorination degree affect the reaction activity. [ABSTRACT FROM AUTHOR]

Highlights • Tunable and switchable C- and L-band single-, dual- and triple-wavelength EDFL. • Tuning range for triple-wavelength regimes covers from 1558.71 to 1580.07 nm. • Tuning ranges for single- and dual-wavelength regimes are 11 nm and 6.23 nm. • The SMSR and tuning step for all laser regimes are up to 55 dB and 0.02 nm. Abstract In this paper, we propose and experimentally demonstrate a C- and L-band erbium-doped fiber laser (EDFL) with tunable single-, dual- and triple-wavelength lasing emissions. A tapered structure large-core fiber filter (LCFF) is inserted to serve as tuning component and wavelength selector for tunable and stable multi-wavelength oscillations. Based on the axial strain response of LCFF, two tunable triple-wavelength regimes within the range from 1558.71 to 1579.81 nm are obtained with side mode suppression ratio (SMSR) as high as 55 dB. Moreover, tunable single- and dual-wavelength regimes are also achieved with total tuning range of 11 nm and 6.23 nm, respectively. The tuning step for overall laser regimes is 0.02 nm, and the maximum wavelength sensitivity reaches to 1.87 pm/με. In addition, this proposed versatile EDFL is proved to be very stable since the lasing wavelength shifts and power fluctuations are less than 0.02 nm and 0.78 dB during an hour. [ABSTRACT FROM AUTHOR]

Highlights • A new four-dimensional model was factorially derived based on the data of chinese adults with OCD: Obsessions, Symmetry/Ritual, Contamination/Cleaning and Hoarding/Religion. • In the Yale-Brown Obsessive-Compulsive Scale, 11 of 17 miscellaneous symptoms were associated with one or more of the symptom dimensions. • The obsessions dimension was significantly associated with seven miscellaneous symptoms. The Symmetry/Ritual dimension and Contamination/Cleaning dimension was significantly associated with one miscellaneous symptom. The Hoarding/Religion dimension was related to two miscellaneous symptoms. Abstract Obsessive compulsive-disorder (OCD) is a common mental illness characterized by the presence of obsessions and/or compulsions. Symptom presence and severity is typically evaluated through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). However, miscellaneous symptoms embedded within the Y-BOCS Symptom Checklist have often been overlooked despite being associated with certain dimensions. In this study, we used exploratory factor analysis and logistic regression to explore the relationship between various miscellaneous symptoms and OCD symptom dimensions among 123 Chinese adults with OCD. A four-dimensional model was factorially derived: Obsessions, Symmetry/Ritual, Contamination/Cleaning and Contamination/Cleaning. In general, 11 out of 17 miscellaneous symptoms were associated with one or more of the symptom dimensions. Among them, the Obsessions dimension was significantly associated with seven miscellaneous symptoms: "Fear of not saying just the right thing," "Intrusive (non-violent) images," "Intrusive nonsense sounds, words", etc. The Symmetry/Ritual dimension was significantly associated with "Need to tell, ask, or confess." The Contamination/Cleaning dimension was related to "Need to know or remember". The Hoarding/Religion dimension was related to "Fear of losing things," and "Superstitious fears". Results contribute to the clinical assessment, diagnosis and treatment of Chinese patients with OCD by understanding the extent to which certain miscellaneous symptoms are associated with primary symptom dimensions. [ABSTRACT FROM AUTHOR]

Abstract The plant-pathogenic fungus Ustilaginoidea virens (Cooke) Takah causes rice false smut (RFS), which is responsible for significant quantitative and qualitative losses in rice industry. Propiconazole is a triazole fungicide which belongs to Demethylation inhibitors (DMIs). It is used to control RFS in China. We previously screened 158 isolates of U. virens collected in the fields in 2015 in Jiangsu province of China, and found two of them were highly resistant to propiconazole (named 82 and 88, respectively). In this study, we have analyzed the physiological and biochemical characters of six field-sensitive isolates and the two field-resistant isolates, including mycelial growth and cell wall integrity. We found there was cross-resistance between different DMIs fungicides, but was no cross-resistance between DMIs and QoIs fungicides. We also analyzed the fitness, and found the pathogenicity in 88 was stronger than the field-sensitive isolates, but was completely lost in 82. Sequence analyses of CYP51 and the 1000-bp upstream of CYP51 coding region showed no mutation in 82 compared to the field-sensitive strains, but two more bases CC were identified at 154-bp upstream of the coding region in the field-resistant isolate 88. Moreover, the expression of CYP51 gene in all tested isolates was significantly induced by propiconazole. However, the up-regulation expression level in both 82 and 88 was much higher than that in the field-sensitive isolates. We also found propiconazole could inhibit the ergosterol biosynthesis in the field-sensitive isolates, but stimulated it in both field-resistant isolates 82 and 88. Given the high level of U. virens developing propiconazole resistance and the good fitness of the field-resistant isolate 88, the resistance of U. virens to DMIs must be monitored and managed in rice fields. Graphical abstract Unlabelled Image Highlights • Two propiconazole -resistant isolates were screened in the field. • Propiconazole has no cross-resistance with QoIs fungicides. • The field-resistant isolate 88 did not reduced fitness and virulence. • The resistance to propiconazole of U. • Virens was associated with increased expression of CYP51 gene. [ABSTRACT FROM AUTHOR]

Highlights • Tunable single-wavelength EDFL using a large-core fiber. • Tuning range covers from 1552.4 nm to 1563.2 nm. • The SMSR for all laser regimes is up to 55 dB. • The proposed laser is proved with good stability. Abstract In this paper, a tunable single-wavelength erbium-doped fiber ring laser is proposed. A novel fiber filter based on a large-core fiber is developed for suppressing the mode competition in erbium-doped fiber lasers (EDFLs). Under the pump power of 250 mW, single-wavelength lasing output is implemented with a side mode suppression ratio (SMSR) higher than 55 dB. By adjusting the curvature applied on the large-core fiber, stably tunable single-wavelength lasing output within the wavelength range from 1552.4 nm to 1563.2 nm is obtained with a 3 dB linewidth of 0.2 nm. Furthermore, the wavelength shift and peak power fluctuation are controlled within 0.02 nm and 0.5 dB by monitoring the lasing output with an interval of 6 min in one hour, respectively. A contrast experiment of a laser without tapering LCF is carried out to examine the importance of the taper in LCF-based filter. Experimental results demonstrate that the side modes of the lasing output can be effectively suppressed and thus SMSR can be improved from 41 dB to 58 dB by using a taper. [ABSTRACT FROM AUTHOR]

The thermal runaway (TR) propagation of lithium-ion batteries (LIBs) is characterized by fast spread and violent reaction, which can cause a massive fire and even explosion. Blocking TR propagation of LIBs and cooling batteries are crucial to avoid the exacerbation of hazards. In this study, three porous materials (nickel foam, glass wool and nanoporous aerogel) were selected as barriers for LIBs and the corresponding blocking mechanism on TR propagation of LIBs were investigated. Based on this, water mist is released at the moment of thermal runaway of the lithium-ion battery and used to cool the battery. In this work, further research on the inhibition of thermal runaway and its propagation in lithium-ion batteries by porous materials and water mist is carried out. The results show that a good suppression effect can be obtained by a synergistic mechanism of pre-insulation and subsequent heat dissipation with the synergistic action of porous materials and water mist. This study also used the failure mode effects analysis (FMEA) method to evaluate the reliability of the inhibition methods and reveal the application effect of FMEA in the field of LIBs. • Glass wool is more suitable for inhibiting thermal runaway propagation. • Fine water mist and porous material have an excellent synergistic inhibition effect. • Porous materials are more suitable for blocking the vertically-arranged batteries. • FMEA can be used to assess the reliability and safety of battery management systems. [ABSTRACT FROM AUTHOR]

Background: The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) (NHHR) serves as a reliable lipid indicator associated with atherogenic characteristics. Studies have indicated a potential connection between suicidality and lipid metabolism. This research aims to investigate any possible association between the NHHR and the emergence of suicidal ideation within the confines of the study. Methods: This study examined the association between NHHR levels and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES), conducted in the United States spanning 2005 and 2016. Calculation of the NHHR corresponds to the proportion of HDL-C to Non-HDL-C. The Patient Health Questionnaire-9's ninth question was implemented for assessing suicidal ideation. Using subgroup analysis, smooth curve fitting, and multivariate logistic regression analysis, the research was conducted. Results: Encompassing a cohort of 29,288 participants, the analysis identified that 3.82% of individuals reported suicidal ideation. After using multivariable logistic regression and thorough adjustments, elevated NHHR levels were significantly and positively associated with a heightened likelihood of suicidal ideation, according to the findings (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.02–1.11; P = 0.0048). Despite extensive adjustment for various confounding factors, this relationship remained consistent. An inverted U-shaped curve was utilized to illustrate the link between NHHR and suicidal ideation among nonsmokers; the curve's inflection point was situated at 7.80. Subgroup analysis and interaction tests (all P for interaction > 0.05) demonstrated that there was no significant influence of the following variables on this positive relationship: age, sex, race, body mass index, education level, married status, hypertension, diabetes, and smoking status. Conclusion: Significantly higher NHHR levels were associated with an elevated likelihood of suicidal ideation. Based on these results, it is probable that NHHR may serve as a predictive indicator of suicidal ideation, emphasizing its potential utility in risk assessment and preventive strategies. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a clinical conundrum with distinct clinical and pathologic features, which is characterized by high aggression, poor prognosis, and lack of targeted therapies. In this study, based on the structural features of type II kinase inhibitors, we designed and synthesized a focused library of 41 pyrimidine derivatives possessing potent anti-proliferation activity, Y29 showed the most potent activity against MDA-MB-231 cells. Subsequently, we carried out target prediction, homology modeling, molecular docking, dynamics simulation and determination of enzymatic activity. The results suggested that PDGFR-β was its potential target. In vitro experiments revealed that Y29 attenuated metastasis by PDGFR-β inhibition-induced autophagy and could enhance autophagy-related cell death through AKT-MAPK feedback loop in MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • TM-Ti 3 C 2 O 2 has thermal and chemical stability. • TM-Ti 3 C 2 O 2 is selective to the products produced by CO 2 reduction hydrogenation reaction. • Co-Ti 3 C 2 O 2 has the best catalytic performance for CH 4 production. • Linear relationship between the dependence of U L affinity on *CO, *HCOOH and *OH in the basic steps of CO 2 RR mechanism. Electrocatalytic CO 2 reduction reaction (CO 2 RR) can transform CO 2 into high-value-added chemicals, which is a key step toward alleviating greenhouse gas emissions and achieving carbon neutrality. Therefore, we constructed a transition metal single-atom catalyst anchored on Ti 3 C 2 O 2 (TM-Ti 3 C 2 O 2) through theoretical calculation. The results show that TMs are stable and capable of activating CO 2. The embedding of TM breaks the symmetry of Ti 3 C 2 O 2 , causing different degrees of charge distribution of TM and distinct selectivity to CH 4 products. Co-Ti 3 C 2 O 2 is the optimum candidate for producing CH 4 with limiting potential of −0.21 V. We established a linear relationship between the activity descriptor and the limiting potential of the product, which provided a method for screening efficient TMs. With applied potential, Co, Sc, and V-Ti 3 C 2 O 2 exhibited great advantages in the CO 2 RR to CH 4. This research serves as a point of reference for industrial production and helps to achieve the objective of carbon peaking more efficiently. [ABSTRACT FROM AUTHOR]

[Display omitted] • Micro-nano structure of hollow LDH covering with MXenes veil (MX@H-LDH) is designed. • Evident suppressions on heat and smoke releases are observed by using MX@H-LDH. • Marked inhibitions on toxic CO, NO and HCN emissions are found by adding MX@H-LDH. • Comparison with reported works indicates its prominence in reducing fire hazard. The using of epoxy resin (EP) has been compromised by its high fire hazard. In this context, MXenes nanoflakes have been preferred as flame retardant, considering its merits in suppressing heat as well as toxic gases emission. Nevertheless, it is difficult to achieve the desired flame retardancy efficiency when the MXenes dosage is low. Thus far, the development of nanostructure based on MXenes with high flame retardant capacity has been seldom investigated. In this contribution, we have designed a strongly-coupled micro-nano structure based on hollow LDH covering with ultra-thin MXenes veil (MX@H-LDH) via assembly strategy. When loading 5.0 wt% MX@H-LDH, peak heat release rate, total heat release, peak CO production rate and total CO production can be reduced by 54.6%, 37.5%, 47.4%, 63.6%, accordingly. Meanwhile, the prominence of MX@H-LDH in inhibiting the release of heat is confirmed via the comparison with previous works. The curbed toxic CO, NO and HCN releases are also discerned in gases phase analysis. Moreover, it is satisfactory to find that the using of MX@H-LDH strengthens the mechanical capability, assigned to the mechanical interlocking action. Briefly, this work can be instructive for the design of novel MXenes-based nanostructure, mining its potentials in polymer composites with high performance. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper was to systematically evaluate the application value of artificial intelligence in predicting mortality among COVID-19 patients. Methods: The PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature, and VIP databases were systematically searched from inception to October 2022 to identify studies that evaluated the predictive effects of artificial intelligence on mortality among COVID-19 patients. The retrieved literature was screened according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the QUADAS-2 tools. Statistical analysis of the included studies was performed using Review Manager 5.3, Stata 16.0, and Meta-DiSc 1.4 statistical software. This meta-analysis was registered in PROSPERO (CRD42022315158). Findings: Of 2193 studies, 23 studies involving a total of 25 AI models met the inclusion criteria. Among them, 18 studies explicitly mentioned training and test sets, and 5 studies did not explicitly mention grouping. In the training set, the pooled sensitivity was 0.93 [0.87, 0.96], the pooled specificity was 0.94 [0.87, 0.97], and the area under the ROC curve was 0.98 [0.96, 0.99]. In the validation set, the pooled sensitivity was 0.84 [0.78, 0.88], the pooled specificity was 0.89 [0.85, 0.92], and the area under the ROC curve was 0.93 [1.00, 0.00]. In the subgroup analysis, the areas under the summary receiver operating characteristic (SROC) curves of the artificial intelligence models KNN, SVM, ANN, RF and XGBoost were 0.98, 0.98, 0.94, 0.92, and 0.91, respectively. The Deeks funnel plot indicated that there was no significant publication bias in this study (P > 0.05). Interpretation: Artificial intelligence models have high accuracy in predicting mortality among COVID-19 patients and have high prognostic value. Among them, the KNN, SVM, ANN, RF, XGBoost, and other models have the highest levels of accuracy. [ABSTRACT FROM AUTHOR]

The effect of various amounts of 5-sulfosalicylic acid (SSA) on the corrosion and discharge property of pure magnesium (Mg) is studied systematically. It was found that SSA plays a vital role in regulating the dissolution kinetics of the substrate and re-deposition rate of discharge product at the metal/electrolyte interface. Low concentration of SSA can be used as corrosion inhibitor for active Mg surface as it chelates with impurity element (Fe3+), while high concentration of SSA increases dissolution rate of Mg since large amount of SSA also acts as complexing agent for the dissolved Mg2+. In terms of discharge performance, addition of 0.1 M SSA improves the utilization efficiency and lowers the discharge potential in the meanwhile under different current densities. The anode demonstrates low and stable discharge potential (-1.83 V) for 10 h at 2.5 mA cm−2 in SSA containing electrolyte. Localized corrosion of the substrate has been significantly facilitated during discharge test. "Thorn-like effect" has been observed for the first time for Mg with addition of complexing agent. Schematic diagram of degradation mechanism at the metal/electrolyte interface (Left: SSA as corrosion inhibitor, Middle: discharge test with addition of 0.01 M SSA, Right: discharge test with addition of 0.1 M SSA). [Display omitted] [ABSTRACT FROM AUTHOR]

• Hierarchical Co@Ni(OH) 2 -A structure is designed via interfacial engineering strategy. • Co@Ni(OH) 2 -A holds strong interfacial catalytic charring and oxidation activities. • Simultaneously enhanced fire safety and mechanical property of polymer are obtained. • Flame retardation contrast with reported works proves the meliority of Co@Ni(OH) 2 -A. The extended usage of epoxy resin (EP) has suffered from the notorious issue of high fire hazard, including the release of considerable heat and emission of abundant toxicants (smoke and toxic gasses). Hence, a prussian blue analogue (PBA) based hierarchical structure (Co@Ni(OH) 2 -A) with Ni(OH) 2 nanocatalyst, is proposed via interfacial-engineering strategy, towards reducing the fire hazard of EP. As revealed, Co@Ni(OH) 2 -A shows strong interfacial catalytic strengths both in charring of decomposed volatiles and oxidizing of toxic gasses. By using 4.0 wt% Co@Ni(OH) 2 -A, the peak heat release rate, peak smoke production rate, total smoke production and peak CO production rate are reduced by 45.5%, 55.0%, 44.3% and 65.3%, respectively. Fire resistance comparison with previous works confirms the advantage of Co@Ni(OH) 2 -A in toxicants elimination. Owing to the well-generated hierarchical structure-polymer interfaces, the greatly enhanced mechanical property is obtained. Generally speaking, Co@Ni(OH) 2 -A holds exceptional efficacy in promoting the polymer fire safety and mechanical performance. This investigation may offer useful enlightenments for acquiring high-performance EP composites via designing PBA based flame retardants with hierarchically tailored structure. [Display omitted] [ABSTRACT FROM AUTHOR]

Older people in long-term care facilities face clinical uncertainty and unpredictable decline. Advance care planning enables older people to identify preferences and wishes for future treatment and care before any loss of capacity. However, it is unclear how, why and under what circumstances the implementation of advance care planning for older people can be normalised into routine practice within long-term care facilities. To identify and explain mechanisms and contextual factors that underpin the implementation of advance care planning for older people in long-term care facilities. Realist review. Long-term care facilities. Consistent with realist review methodology, we developed the initial programme theory by scoping reviews, engaging UK and China stakeholders and utilising the Normalisation Process Theory. MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and Scopus were subsequently searched from 01/01/1990 to 11/06/2021. Inductive and deductive coding was used to generate context-mechanism-outcome configurations, which were iteratively tested to refine the programme theory. 5459 records were identified, and 48 were retained for final synthesis. Seven context-mechanism-outcome configurations were identified: (1) carry out sensitive conversation gradually in a nonthreatening way; (2) identify 'a window of opportunity'; (3) deliver sustainable and available training; (4) build a collaborative and multidisciplinary network; (5) conduct collaborative negotiation to achieve shared decision-making; (6) secure active leadership buy-in; (7) keep conversation and documentation on track. A logic model was developed to conceptualise the causal pathways between the contexts, mechanisms, and outcomes. Normalising conversations about death is paramount to mainstreaming advance care planning implementation in long-term care facilities. The key to achieving this is older people, family members and staff have a shared understanding of the aims, values, and potential benefits of advance care planning. Advance care planning should be introduced at a time that is important to older people and families, rather than being process-driven. Nurse facilitators play a vital role in ensuring older people's voices are heard and in building bridges between participants in advance care planning. The findings of this study inform the appropriate development and evaluation of advance care planning interventions for older people in long-term care facilities. Further research is needed to explore mechanisms that underpin the implementation of advance care planning in Asian countries. This review is registered with the International Prospective Register of Systematic Reviews (CRD42021214317). [ABSTRACT FROM AUTHOR]

Advanced oxidation process (AOPs) is one of the most effective technologies for organic pollutants removal. In this study, diverse reactive species generation and enhanced sulfamethoxazole (SMX) degradation were investigated based on persulfate (PDS) activated by Fe2+&dithionite (DTN). When involving Fe2+&dithionite in PDS, SMX degradation efficiency reached 84 % within 30 min following a pseudo-first-order kinetic, which was higher than those in Fe2+/PDS (50.4 %) and Fe2+/O 2 /DTN (41.3 %). SO 4 •− and •OH were identified as dominant reactive species with a crucial role of FeSO 3 + based on quenching experiment and electron spin resonance (ESR). The contributions of SO 4 ·− , · OH, and other species to SMX degradation were 60.1 %, 33.9 %, and 6 %, respectively. In Fe2+/DTN/PDS system, SMX was effectively degraded under nearly neutral pH (5.0–9.0), with activation energy of 96.04 kJ·mol−1. The experiments and density functional theory (DFT) calculation demonstrated that three functional groups (benzenesulfonamido, benzene ring, and oxazole ring) were attacked for SMX degradation. Moreover, acute toxicity to Vibrio fischeri has enhanced in the earlier degradation process due to the intermediates and weaken with the continuous reaction. This work not only provides a high-activity SO 4 ·− -AOP for refractory pollutant treatment with possible dual radical generation resources, but elucidated diverse reactive species formation with Fe2+&dithionite. [Display omitted] • Fe2+&dithionite for PDS activation can enhance SMX removal remarkably. • Diverse reactive species are producing in three stages with crucial role of FeSO 3 +. • SMX degradation pathways were proposed and verified by MS and DFT. • Acute toxicity reduction has been confirmed with SMX degradation simultaneously. [ABSTRACT FROM AUTHOR]

Introduction: p53 plays important roles in regulating the metabolic reprogramming of cancer, such as aerobic glycolysis. Oroxylin A is a natural active flavonoid with strong anticancer effects both in vitro and in vivo. Methods: wt-p53 (MCF-7 and HCT116 cells) cancer cells and p53-null H1299 cancer cells were used. The glucose uptake and lactate production were analyzed using Lactic Acid production Detection kit and the Amplex Red Glucose Assay Kit. Then, the protein levels and RNA levels of p53, mouse double minute 2 (MDM2), and p53-targeted glycolytic enzymes were quantified using Western blotting and quantitative polymerase chain reaction (PCR), respectively. Immunoprecipitation were performed to assess the binding between p53, MDM2, and sirtuin-3 (SIRT3), and the deacetylation of phosphatase and tensin homolog (PTEN). Reporter assays were performed to assess the transcriptional activity of PTEN. In vivo, effects of oroxylin A was investigated in nude mice xenograft tumor-inoculated MCF-7 or HCT116 cells. Results: Here, we analyzed the underlying mechanisms that oroxylin A regulated p53 level and glycolytic metabolism in wt-p53 cancer cells, and found that oroxylin A inhibited glycolysis through upregulating p53 level. Oroxylin A did not directly affect the transcription of wt-p53, but suppressed the MDM2-mediated degradation of p53 via downregulating MDM2 transcription in wt-p53 cancer cells. In further studies, we found that oroxylin A induced a reduction in MDM2 transcription by promoting the lipid phosphatase activity of phosphatase and tensin homolog, which was upregulated via sirtuin3-mediated deacetylation. In vivo, oroxylin A inhibited the tumor growth of nude mice-inoculated MCF-7 or HCT116 cells. The expression of MDM2 protein in tumor tissue was downregulated by oroxylin A as well. Conclusions: These results provide a p53-independent mechanism of MDM2 transcription and reveal the potential of oroxylin A on glycolytic regulation in both wt-p53 and mut-p53 cancer cells. The studies have important implications for the investigation on anticancer effects of oroxylin A, and provide the academic basis for the clinical trial of oroxylin A in cancer patients. [ABSTRACT FROM AUTHOR]

When lithium-ion batteries (LIBs) are subjected to thermal, electrical, or mechanical abuse during use or transport, thermal runaway may occur, which can result in fire and explosion. Fine water mist has attracted considerable attention as an efficient, environmentally friendly fire extinguishing medium. We used fine water mist containing a compound additive to suppress the TR of LIBs and studied the effect of different types of additives at various concentrations on TR. The compound additive consisted of urea, fatty alcohol polyoxyethylene ether (AEO-9), nonionic fluorine surfactant (FC-4430), and dimethyl methylphosphonate (DMMP). The optimal concentration of each component was obtained. An orthogonal experiment based on these optimal concentrations was conducted to determine the additive with the strongest inhibition effect. Fine water mist with this low conductivity compound additive can inhibit TR effectively and reduce the short-circuit damage of batteries without TR caused by water immersion. [ABSTRACT FROM AUTHOR]

Abstract: HQS-3 is a newly baicalein derivative with a benzene substitution. We investigated the anticancer effect of HQS-3 in vivo and in vitro. HQS-3 significantly decreased tumor growth in mice inoculated with Heps and HepG2 cells; and had little influence on the state and weight of animals. After treatment with 20mg/kg HQS-3, the inhibitory rate of tumor weight in mice inoculated with Heps and HepG2 cells were 63.62% and 68.03%, respectively. Meanwhile, HQS-3 inhibited the viability of various kinds of tumor cells with IC50 values in the range of 22.98–54.32μM after 48h treatment measured by MTT-assay. HQS-3 remarkably inhibited viability of hepatoma cells in a concentration- and time-dependent manner and induced apoptosis in HepG2 cells by DAPI staining and Annexin V/PI double staining. The apoptosis-induction effect of HQS-3 was attributed to its ability to modulate the activity of caspase-9, caspase-3 and PARP. Moreover, the expression of bax protein was increased while the bcl-2 protein was decreased, leading to an increase in Bax/Bcl-2 ratio. The accumulation of ROS induced by HQS-3 in HepG2 cells was also observed. The further results suggested that HQS-3 induced mitochondrial-mediated apoptosis by increasing ROS level and inhibiting the expression of anti-oxidative protein SOD2. HQS-3 exerted anti-tumor activity both in vitro and in vivo via inducing tumor cells apoptosis, and these results suggested that it deserves further investigation as a novel chemotherapy for human tumors. [Copyright &y& Elsevier]

The original article [1] contains several errors. [ABSTRACT FROM AUTHOR]

• We reconstruct iceberg discharge for the past 135,000 yrs near Newfoundland. • Iceberg flux increased during each Heinrich event in the western North Atlantic. • Compared to the eastern North Atlantic, the western iceberg flux is higher. • Heinrich layers 3 and 6 cannot solely be the result of foraminifera dissolution. A series of catastrophic iceberg and meltwater discharges to the North Atlantic, termed Heinrich events, punctuated the last ice age. During Heinrich events, coarse terrigenous debris released from the drifting icebergs was preserved in deep-sea sediments, serving as an indicator of iceberg passage. Quantifying the vertical flux of ice-rafted debris (IRD) in open-ocean settings can resolve questions regarding the timing and spatial variation in ice sheet calving intensity. In this study, 230Th xs -based IRD flux throughout the last glacial period was measured in a deep-sea sediment core from the western North Atlantic, and complemented by data spanning 0-32 ka from a sediment core in the Labrador Sea. The cores were recovered from sites downstream from Hudson Strait, a likely conduit for icebergs calving from the Laurentide ice sheet (LIS). We compare our results with equivalent existing data from the eastern North Atlantic and show that the two cores in our study have higher IRD fluxes during all Heinrich events, notably including events H3 (∼31 ka) and H6 (∼60 ka). This study demonstrates that the LIS played a role in all Heinrich events, and raises the likelihood that a single mechanism can account for the genesis of these events. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a syndrome with a decreased ability to a different classification. Alzheimer's disease (AD), memory, and learning affect the classification domain as cognitive-motor or executive function, which is the most common dementia. Death and expensive detection is high treatment and between the result of the count rate of patient care. Early detection of AD is considered very important to improve patients' quality of life and their families. The purpose of this article is to reduce the cost of accelerating related to the diagnosis. The o allow complete access is possible to introduce a new non-invasive early diagnosis method. The new AD screening tests' interaction is based on introducing new technology in the business system, and an immersive and advanced human-computer has been introduced to the Internet system. Four experiments, based on the large-scale screening, damage to the mechanism of classification domain, shows that can be used in the network design of the thing system. In the proposed test, mainly common goal, focusing on evaluating the recent related memory loss in the conversation and events, human and between the virtual world and the real machine; abnormal the ability to recognize, express, and understand diagnostic differences in language problems terms. IOT (IOT) has integrated hundreds of millions of smart devices that can communicate with a minimum of human intervention. It should be strengthened to secure methods to ensure the ecosystem of useful IOT. Machine Learning (ML) is proceeding significantly over the past few years; in some critical applications, machine intelligence is actually of the machine to the laboratory curiosity conversion. The ability to monitor the IOT devices and intelligence will provide an essential solution for new or zero-day attacks. Components and apparatus of the ML Hano IOT are, based on whether learning the IOT in the environment is an effective way to explore the "normal," "abnormal" behavior data. [ABSTRACT FROM AUTHOR]