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Sunitinib, N-desmethyl imatinib, dasatinib, imatinib, and bosutinib are tyrosine kinase inhibitors (TKIs) that are commonly employed in the treatment of a multitude of cancers. However, the inappropriate concentrations of TKIs can result in ineffective treatment or the emergence of multiple adverse effects. Consequently, the development of a rapid and sensitive analytical method for TKIs is of paramount importance for the safe administration of drugs. In this work, solid-phase microextraction (SPME) probe combined with an electrospray ionization mass spectrometry (ESI-MS) coupling platform was constructed for rapid and sensitive determination of TKIs. The covalent organic frameworks (COFs) coated SPME probe was made of 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and 2,5-dibutoxyterephthalaldehyde (DBTA) by in-situ layer-by-layer chemical bonding synthesis strategy. The TAPT-DBTA-SPME probe exhibited several advantageous properties which rendered it suitable for the enrichment of TKIs. Under the optimal conditions, the developed analytical method demonstrated a broad linear range (0.05-500.00 µg/L), a low limit of detection (0.02 µg/L) and a high enrichment factor (51-203) for TKIs. The developed analytical method was successfully applied to a pharmacokinetic study of TKIs in mouse plasma and tissue matrix, demonstrating that the proposed analytical method has promise for clinical applications and metabolic monitoring., 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.)

In the current battle against antibiotic resistance, the resilience of Gram-negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self-assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1-2.8 µg mL -1 ), which is at least ten times lower than the reported data for NO donors (≥200 µg mL -1 ). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self-assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next-generation antimicrobial agents., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Currently, the field of neurobiology of language is based on data from only a few Indo-European languages. The majority of this data comes from younger adults neglecting other age groups. Here we present a multimodal database which consists of task-based and resting state fMRI, structural MRI, and EEG data while participants over 65 years old listened to sections of the story The Little Prince in Cantonese. We also provide data on participants' language history, lifetime experiences, linguistic and cognitive skills. Audio and text annotations, including time-aligned speech segmentation and prosodic information, as well as word-by-word predictors such as frequency and part-of-speech tagging derived from natural language processing (NLP) tools are included in this database. Both MRI and EEG data diagnostics revealed that the data has good quality. This multimodal database could advance our understanding of spatiotemporal dynamics of language comprehension in the older population and help us study the effects of healthy aging on the relationship between brain and behaviour., (© 2024. The Author(s).)

Using current water treatment systems, significant amounts of microplastics (MPs) are passing through and being released into the aquatic environment. However, we do not clearly know what effects disinfection processes have had on these particles. In this study, we applied inductively coupled plasma-mass spectrometry (ICP-MS) operating in time-resolved analysis (TRA) mode for quantifying changes in the chlorine (Cl) content of MPs under a variety of water treatment scenarios. Our results illustrated that time-resolved ICP-MS offers a potential method for sensitive and direct analysis of Cl content, including Cl mass and chlorine association (%Cl/C), of discrete particles in the MP suspension by the fast sequential measurements of signals from 35 Cl 1 H 2 and 12 C 1 H. Our research, across various water treatment scenarios, also showed that polystyrene (PS) MPs exhibited greater reactivity to Cl disinfectant after being pre-disinfected with UV light and in mildly acidic to neutral pH environments. It is noteworthy that about half of the particles in MP suspension exposed to 10 mg Cl 2 /L, a typical Cl dose applied in water treatment, were chlorinated, and had a Cl content comparable to that of particles subjected to extreme conditions. Of even greater concern is the fact that our cell viability tests revealed that chlorinated MPs induced considerably higher rates of cell death in both human A549 and Caco-2 cells, and that the effects were Cl dose- and polymer type-dependent. Overall, this study demonstrates the potential of time-resolved ICP-MS as a valuable technique for quantifying the Cl content of MP particles, which is crucial to assessing the fate and transformation of MPs in our water supply and treatment systems., (Copyright © 2024. Published by Elsevier B.V.)

Microplastics (MPs) are pervasive environmental contaminants that have infiltrated even the most remote ecosystems. Despite their widespread distribution, the transfer patterns and impacts of MPs in remote lakes remain poorly understood. This study aimed to address the knowledge gap regarding the pathways and consequences of MP pollution in these isolated environments. Focusing on Kyêbxang Co, a remote salt lake in Tibet, this study investigated the transfer patterns, sources and ecological impacts of MPs, providing insights into their mobility and fate in pristine ecosystems. Water, sediment and biota (brine shrimp) samples from Kyêbxang Co, collected during the summer of 2020, were analyzed using µ-Raman spectroscopy to determine MP abundances, polymer types and potential sources. Findings indicated significant MP contamination in all examined media, with concentrations highlighting the role of runoff in transporting MPs to remote locations. The majority of detected MPs were small fragments (<0.5 mm), constituting over 93 %, with polypropylene being the predominant polymer type. The presence of a halocline may slow the descent of MPs, potentially increasing the exposure and ingestion risk to brine shrimp. Despite the currently low ecological risk estimated for MPs, this study underscores the need for long-term monitoring and development of a comprehensive ecological risk assessment model for MPs., 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 electrochemical nitric oxide reduction reaction (NORR), which utilizes water as the sole hydrogen source, has the potential to facilitate ammonia production while concurrently mitigating pollutants. However, limited research has been dedicated to characterizing the structure of interfacial water due to the challenges associated with probing this intricate system, impeding the development of more efficient catalysts for the NORR process. Herein, the Cu 2 O microcrystals with distinct exposed facets, including {100}, {110}, and {111}, are employed for the model catalysts to investigate interfacial water structure and intermediate species in the NORR process. The results from shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) indicated that the NORR performance in 0.1 M Na 2 SO 4 (with heavy water as the solvent) was positively correlated to the proportion of hydrated Na + ion water. In addition, a sequence of intermediates from the NORR, including *NOH, *NH, *NH 2 , and *NH 3 , was detected by employing a combination of multiple in situ characterization methods. Furthermore, in conjunction with experimental results and theoretical calculations, we revealed the potential reaction pathway of NORR. This study offers novel insights into the NORR mechanism and valuable guidance for the design of high-performance catalysts for ammonia production.

RNA G-quadruplex structures (rG4s) play important roles in the regulation of biological processes. So far, all the l-RNA aptamers developed to target rG4 of interest contain G4 motif itself, raising the question of whether non-G4-containing l-RNA aptamer can be developed to target rG4. Furthermore, it is unclear whether an l-Aptamer-based tool can be generated for G4 detection in vitro and imaging in cells. Herein, a new strategy is designed using a low GC content template library to develop a novel non-G4-containing l-RNA aptamer with strong binding affinity and improved binding specificity to rG4 of interest. The first non-G4-containing l-Aptamer, l-Apt.1-1, is identified with nanomolar binding affinity to amyloid precursor protein (APP) D-rG4. l-Apt.1-1 is applied to control APP gene expression in cells via targeting APP D-rG4 structure. Moreover, the first l-RNA-based fluorogenic bi-functional aptamer (FLAP) system is developed, and l-Apt.1-1&#95;Pepper is engineered for in vitro detection and cellular imaging of APP D-rG4. This work provides an original approach for developing non-G4-containing l-RNA aptamer for rG4 targeting, and the novel l-Apt.1-1 developed for APP gene regulation, as well as the l-Apt.1-1&#95;Pepper generated for imaging of APP rG4 structure can be further used in other applications in vitro and in cells., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is approved for obesity treatment, but the specific neuronal sites that contribute to its therapeutic effects remain elusive. Here, we show that GLP-1 receptor-positive (GLP-1R-positive) neurons in the lateral septum (LSGLP-1R) play a critical role in mediating the anorectic and weight-loss effects of liraglutide. LSGLP-1R neurons were robustly activated by liraglutide, and chemogenetic activation of these neurons dramatically suppressed feeding. Targeted knockdown of GLP-1 receptors within the LS, but not in the hypothalamus, substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, while synaptic inactivation of LSGLP-1R neurons diminished the anorexic effects triggered by liraglutide. Together, these findings offer critical insights into the functional role of LSGLP-1R neurons in the physiological regulation of energy homeostasis and delineate their instrumental role in mediating the pharmacological efficacy of liraglutide.

Proteome composition is dynamic and influenced by many internal and external cues, including developmental signals, light availability, or environmental stresses. Protein degradation, in synergy with protein biosynthesis, allows cells to respond to various stimuli and adapt by reshaping the proteome. Protein degradation mediates the final and irreversible disassembly of proteins, which is important for protein quality control and to eliminate misfolded or damaged proteins, as well as entire organelles. Consequently, it contributes to cell resilience by buffering against protein or organellar damage caused by stresses. Moreover, protein degradation plays important roles in cell signaling, as well as transcriptional and translational events. The intricate task of recognizing specific proteins for degradation is achieved by specialized systems that are tailored to the substrate's physicochemical properties and subcellular localization. These systems recognize diverse substrate cues collectively referred to as "degrons," which can assume a range of configurations. They are molecular surfaces recognized by E3 ligases of the ubiquitin-proteasome system but can also be considered as general features recognized by other degradation systems, including autophagy or even organellar proteases. Here we provide an overview of the newest developments in the field, delving into the intricate processes of protein recognition and elucidating the pathways through which they are recruited for degradation., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. 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.)

Epilepsy is a noncommunicable chronic neurological disorder affecting people of all ages, with the highest prevalence in low and middle-income countries. Despite the pharmacological armamentarium, the plethora of drugs in the market, and other treatment options, 30%-35% of individuals still show resistance to the current medication, termed intractable epilepsy/drug resistance epilepsy, which contributes to 50% of the mortalities due to epilepsy. Therefore, the development of new drugs and agents is needed to manage this devastating epilepsy. We reviewed the pipeline of drugs in "ClinicalTrials. gov," which is the federal registry of clinical trials to identify drugs and other treatment options in various phases against intractable epilepsy. A total of 31 clinical trials were found regarding intractable epilepsy. Among them, 48.4% (15) are about pharmacological agents, of which 26.6% are in Phase 1, 60% are in Phase 2, and 13.3% are in Phase 3. The mechanism of action or targets of the majority of these agents are different and are more diversified than those of the approved drugs. In this article, we summarized various pharmacological agents in clinical trials, their backgrounds, targets, and mechanisms of action for the treatment of intractable epilepsy. Treatment options other than pharmacological ones, such as devices for brain stimulation, ketogenic diets, gene therapy, and others, are also summarized., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Research about the commercial sex industry rarely examines the women who are the clients purchasing sexual services. Examining how this challenges gender stereotypes through the undoing gender framework reveals how gender norms can be reshaped through contextual changes. Based on 3 years of ethnographic data from a high-end bar in Tianjin, interviews with 27 female clients and 47 MSWs paint a complex picture of how some women adopted ungendered strategies regarding sexuality. As women take control of their own sexual behavior, they free themselves of some traditional societal expectations about their identity. Primarily motivated by pleasure and control, purchasing sex becomes a means for women to experience empowerment and self-confidence by breaking with traditional gender norms and expectations. Undoing gender involves expanding gendered repertoires, with women finding empowerment in adopting a masculine model of sexuality. However, social stigma and personal efficacy indicate that gender deconstruction is a gradual process. The research contributes to understanding complex gender dynamics and sexual behaviors within commercial sex transactions, shedding light on societal norms and individual agency., (© 2024 The Authors. The British Journal of Sociology published by John Wiley & Sons Ltd on behalf of London School of Economics and Political Science.)

Pinkeye is a highly contagious disease of goats with different aetiologies. Surveys in Lao PDR have identified eye lesions typical of pinkeye as a common condition, however, this has not been confirmed diagnostically, and the responsible pathogens have not been identified. A matched case-control study was implemented in 70 goat holdings from Savannakhet province, Lao PDR, to detect agents causing pinkeye and conduct phylogenetic analysis of the identified pathogens. Fifty eye swabs from goats with infected eyes (cases) and 50 paired samples from unaffected cohorts (controls) were collected from 25 holdings. Samples were tested using quantitative PCR assays targeting known pinkeye pathogens at the genus and species levels. The prevalence of pathogens in case and control goats was as follows: Mycoplasma conjunctivae (94% and 74% respectively, P = 0.006, OR = 5.5), Chlamydia pecorum (4%, 10%), Moraxella ovis (30%, 30%), Moraxella bovis (0%, 0%) and Moraxella bovoculi (0%, 0%). M. conjunctivae was present in a high proportion of goats in both groups revealing that Lao goats are carriers of M. conjunctivae. However, the mean log 10 genome copy number/µL of DNA extract was significantly higher in case goats than control goats (P < 0.05). Thus, M. conjunctivae is likely the principal causative agent of pinkeye in Lao goats with carrier status converting to clinical infection following corneal damage or other causative factors. M. conjunctivae detected in samples from different goats and districts showed low genetic diversity. Identifying the causes of pinkeye in Lao goats will assist in designing appropriate treatment and control strategies., 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 B.V. All rights reserved.)

Pollutants often exist as mixtures in environmental settings, creating a challenge in selecting the most effective combination of biomarkers for routine monitoring. This study was conducted seasonally in Victoria Harbour, Hong Kong, to compare the responses of nine biomarkers in the green-lipped mussel Perna viridis with respect to its tissue levels of persistent organic pollutants and heavy metals. Multivariate statistical techniques were utilised to determine the single best predictor and optimal subset of biomarkers in P. viridis for each of the four scenarios: representing overall biomarker responses in the dry season, and wet season, as well as correlating tissue levels of mixed pollutants in the dry season, and wet season. Our findings recommend lysosomal destabilisation, and the nucleic acid ratio of RNA to DNA, as the core biomarkers in P. viridis for marine pollution monitoring. The non-specificity of these biomarkers allows effective identification of pollution hotspots and guides further detailed assessment., 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. Published by Elsevier Ltd.)

Drawing upon person-environment fit perspective, this study examines the joint and interactive influences of personal competence and environmental characteristics on the happiness of ageing adults around the period of COVID-19 pandemic. Data was collected in two rounds, before and during the pandemic, with 2,028 participants aged 55 years and older in Hong Kong. Personal competence encompassed financial status, physical health, and mental capital, while environmental characteristics included experiences of ageism, perceived social conditions, and age-friendly policies. Ordinary least squares regression was used to examine personal and environmental influences on happiness. Results indicated a significant decline in happiness following the onset of COVID-19 pandemic. Mental capital was found to have the strongest positive influence on happiness, followed by physical health, financial status, and social conditions. Mental capital mitigated the negative relationship between experiences of ageism and happiness. Practical interventions are informed to improve the well-being of ageing adults during pandemic., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Explainable artificial intelligence (XAI) has been increasingly investigated to enhance the transparency of black-box artificial intelligence models, promoting better user understanding and trust. Developing an XAI that is faithful to models and plausible to users is both a necessity and a challenge. This work examines whether embedding human attention knowledge into saliency-based XAI methods for computer vision models could enhance their plausibility and faithfulness. Two novel XAI methods for object detection models, namely FullGrad-CAM and FullGrad-CAM++, were first developed to generate object-specific explanations by extending the current gradient-based XAI methods for image classification models. Using human attention as the objective plausibility measure, these methods achieve higher explanation plausibility. Interestingly, all current XAI methods when applied to object detection models generally produce saliency maps that are less faithful to the model than human attention maps from the same object detection task. Accordingly, human attention-guided XAI (HAG-XAI) was proposed to learn from human attention how to best combine explanatory information from the models to enhance explanation plausibility by using trainable activation functions and smoothing kernels to maximize the similarity between XAI saliency map and human attention map. The proposed XAI methods were evaluated on widely used BDD-100K, MS-COCO, and ImageNet datasets and compared with typical gradient-based and perturbation-based XAI methods. Results suggest that HAG-XAI enhanced explanation plausibility and user trust at the expense of faithfulness for image classification models, and it enhanced plausibility, faithfulness, and user trust simultaneously and outperformed existing state-of-the-art XAI methods for object detection models., 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 Ltd.. All rights reserved.)

G-quadruplexes (dG4 and rG4) are nucleic acid secondary structures formed by the self-assembly of certain G-rich sequences, and they have distinctive chemical properties and play crucial roles in fundamental biological processes. Small molecule G4 ligands were shown to be crucial in characterizing G4s and understanding their functions. Nevertheless, concerns regarding the specificity of these synthetic ligands for further investigation of G4s, especially for rG4 isolation purposes, have been raised. In comparison to G4 ligands, we propose a novel magnetic bead-based pulldown assay that enables the selective capture of general rG4s using functionalized l-Apt.4-1c from both simple buffer and complex media, including total RNA and the cell lysate. We found that our l-RNA aptamer can pulldown general rG4s with a higher efficiency and specificity than the G4 small molecule ligand BioTASQ v.1 in the presence of non-target competitors, including dG4 and non-G4 structures. Our findings reveal that biotinylated l-aptamers can serve as effective molecular tools for the affinity-based enrichment of rG4 of interest using this new assay, which was also verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) on endogenous transcripts. This work provides new and important insights into rG4 isolation using a functionalized l-aptamer, which can potentially be applied in a transcript-specific or transcriptome-wide manner in the future., Competing Interests: The authors declare that they have no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

ConspectusMetal oxo (M═O) and nitrido (M≡N) complexes are two important classes of high-valent transition metal complexes. The use of M═O as oxidants in chemical and biological systems has been extensively investigated. Nature makes use of M═O in enzymes such as cytochrome P450 to oxidize a variety of substrates. Highly oxidizing oxo species have also been synthesized and they have been shown to oxidize organic and inorganic substrates via one-electron oxidation, O atom transfer, and H atom abstraction pathways. In contrast, the oxidation chemistry of M≡N is much less investigated. Although a variety of nitrido complexes are known, most of them are inert and do not show appreciable oxidizing properties, which is not unexpected since the N 3- ligand is much more electron-donating than the O 2- ligand. In principle, highly electrophilic/oxidizing nitrido complexes may be designed by using weakly coordinating ancillary ligands and/or by increasing the oxidation state of the metal centers. A number of such species have been generated in solution at low temperatures. However, attempts to isolate them are often hampered by their ease of decomposition via bimolecular N···N coupling to generate N 2 . In some cases, decomposition occurs by intramolecular nitrogenation of the ancillary ligand.In this account, we describe our recent efforts into the design of nitrido complexes that are highly oxidizing but stable enough so they can be isolated and characterized, and their reactivity toward organic substrates can be readily investigated.We have successfully isolated and determined the structure of the first stable manganese(VI) nitrido complex bearing an oxidation-resistant macrocyclic tetraamido TAML ligand, [Mn VI (N)(TAML)] - (H 4 TAML = 3,3,6,6,9,9-hexamethyl-3,4,8,9-tetrahydro-1 H -benzo[e][1,4,7,10] tetraazacyclotridecine-2,5,7,10(6 H ,11 H )-tetraone). This complex readily undergoes direct aziridination of alkenes; it also abstracts hydrides from NADH analogues via a Separated CPET mechanism. Coupling of the nitrido ligands to give dinitrogen is a major decomposition pathway for electrophilic nitrido complexes. In order to shut down this pathway, we made use of a bulky trianionic corrole ligand TTPPC (H 3 TTPPC = 5,10,15-tris(2,4,6-triphenylphenyl)corrole) to prepare manganese nitrido complexes. Remarkably, we were able to isolate and determine the structures of [Mn V (N)(TTPPC)] - and its one- and two-electron ligand-oxidized products, [Mn V (N)(TTPPC + • )] and [Mn V (N)(TTPPC 2+ )] + ("TTPPC" has a 3- charge, 'TTPPC +• ' has an overall 2- charge and 'TTPPC 2+ ' has an overall 1- charge). Although [Mn V (N)(TTPPC 2+ )] + is formally a manganese(V) complex, it was found to be the most electrophilic among isolated metal nitrido complexes. The use of the bulky corrole ligand effectively prevents the decomposition of Mn≡N by N···N coupling.A number of luminescent M═O species that possess highly oxidizing excited states are known. We have also developed a strongly luminescent osmium(VI) nitrido complex, [Os VI (N)(L)(CN) 3 ] - ( OsN , HL = 2-(2-hydroxy-5-nitrophenyl)benzoxazole), that absorbs visible light to generate a highly oxidizing/electrophilic excited state. The excited state readily reacts with a wide variety of organic and inorganic substrates, many of these reactions are unprecedented. Notably, it reacts with cyclohexane to give an osmium(IV) cyclohexyliminato product, and with benzene to give an osmium(IV) p -benzoquinone iminato species.

Proteins perform their biological functions through motion. Although high throughput prediction of the three-dimensional static structures of proteins has proved feasible using deep-learning-based methods, predicting the conformational motions remains a challenge. Purely data-driven machine learning methods encounter difficulty for addressing such motions because available laboratory data on conformational motions are still limited. In this work, we develop a method for generating protein allosteric motions by integrating physical energy landscape information into deep-learning-based methods. We show that local energetic frustration, which represents a quantification of the local features of the energy landscape governing protein allosteric dynamics, can be utilized to empower AlphaFold2 (AF2) to predict protein conformational motions. Starting from ground state static structures, this integrative method generates alternative structures as well as pathways of protein conformational motions, using a progressive enhancement of the energetic frustration features in the input multiple sequence alignment sequences. For a model protein adenylate kinase, we show that the generated conformational motions are consistent with available experimental and molecular dynamics simulation data. Applying the method to another two proteins KaiB and ribose-binding protein, which involve large-amplitude conformational changes, can also successfully generate the alternative conformations. We also show how to extract overall features of the AF2 energy landscape topography, which has been considered by many to be black box. Incorporating physical knowledge into deep-learning-based structure prediction algorithms provides a useful strategy to address the challenges of dynamic structure prediction of allosteric proteins., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: Obesity is associated with an exacerbated metabolic condition that is mediated through impairing balance in the secretion of some adipo-myokines. Therefore, the objective of the present study was to explore the impact of astaxanthin supplementation in conjunction with a 12-week CrossFit training regimen on some selected adipo-myokines, insulin insensitivity, and serum lipid levels in obese males., Material and Methods: This study is a randomized control trial design; 60 obese males were randomly divided into four groups of 15, including the control group (CG), supplement group (SG), training group (TG), and combined training and supplement group (TSG). The participants were subjected to 12 weeks of astaxanthin (AST) supplementation [20 mg/d capsule, once/d] or CrossFit training or a combination of both interventions. The training regimen comprised 36 sessions of CrossFit, each lasting 60 min, conducted three times per week. The metabolic indices, body composition, anthropometrical, cardio-respiratory, and also some plasma adipo-myokine factors, including decorin (DCN), activin A, myostatin (MST), transforming growth factor (TGF)-β1, and follistatin (FST), were examined 12 and 72 h before the initiation of the main interventional protocols, and then 72 h after the final session of the training protocol., Results: There was no significant difference in the baseline data between the groups ( p > 0.05). There were significant interactions between group x time for DCN (η 2 = 0.82), activin A (η 2 = 0.50), FST (η 2 = 0.92), MST (η 2 = 0.75), and TGFB-1 (η 2 = 0.67) ( p < 0.001 for all the variables). Significantly changes showed for DCN in TSG compared to TG and SG and also TG compared to SG ( p = 0.0001); for activin A in SG compared to TG ( p = 0.01) and TSG ( p = 0.002); for FST in SG compared to TG and TSG ( p = 0.0001), also in TSG compared to TG ( p = 0.0001); for MST in SG, TG, and TSG compared to CG ( p = 0.0001) and also in TSG compared to SG ( p = 0.0001) and TG ( p = 0.001); for TGFB-1 in SG, TG, and TSG compared to CG ( p = 0.0001) and also TSG compared to SG ( p = 0.0001) and TG ( p = 0.001)., Conclusions: The 12-week CrossFit training concurrent with AST supplementation reduced anthropometric and metabolic factors and also serum lipid levels while producing positive changes in body composition and cardiovascular factors. Increased FST and DCN and reduced activin A, MST, and TGF-β1 were other affirmative responses to both interventions.

Fluorescent nanothermometers based on thermal-dependent lifetime have a significant advantage in biological imaging owing to their immunity toward scattering, absorption, and autofluorescence. In this study, we present the first example of a water-soluble europium complex ( [L 1 Eu] - ) that exhibits high sensitivity (1.2% K -1 at 298 K) based on a temperature-dependent lifetime in the millisecond time range. This complex and its analogues show considerable potential for organelle imaging. The mechanism behind this thermal-sensitive behavior has been extensively investigated using transient absorption spectroscopy and variable temperature time-resolved luminescence methods. A highly efficient ligand sensitization process and a thermally activated back energy transfer process have been demonstrated. This study bridges the gap in small molecule thermometers with lifetimes longer than 1 ms and provides guidance in ligand design for metal coordination complex thermometers.

Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Dermatophytic pseudomycetoma (DPM) is a rarely reported invasive fungal infection of humans and animals, especially cats. This study aimed to identify dermatophytes, breed associations, and the frequency of extracutaneous (EC) involvement in feline DPM. Electronic records and formalin-fixed paraffin-embedded tissue (FFPET) from 32 suspected DPM cases in 30 cats were retrieved from a diagnostic laboratory between 2018 and 2024. To confirm DPM and molecular identity, DNA was extracted from FFPET for ITS2 sequencing, and immunohistochemistry was performed on PCR-negative cases. All cases were confirmed as DPM. Microsporum canis was the only dermatophyte identified. The sensitivity and specificity of ITS2 sequencing for M. canis identification in FFPET were 22/32 (68.8%) and 21/22 (95.5%), respectively. Exotic (36.7%) and Persian (23.3%) but not British breeds (26.3%) were over-represented compared to feline admissions at an affiliated veterinary hospital (8.5%, p < 0.001; 3%, p < 0.001; 21.6%, p = 0.817, respectively). Five cases (16.7%) had EC lesions; two had intra-abdominal masses; two had oral cavity masses, including one which extended into the cranial vault; and one had superficial cervical lymph node invasion. Exotic and Persian breeds are over-represented for DPM and M. canis is the primary cause. EC lesions of DPM may occur more commonly than previously thought.

The lateral preoptic area (LPO) is a component of the hypothalamus involved in various physiological functions including sleep-wakefulness transition, thermoregulation, and water-salt balance. In this study, we discovered that distinct LPO excitatory neurons project separately to the aversive processing center lateral habenula (LHb) and the reward processing hub ventral tegmental area (VTA). Following chronic restraint stress (CRS), the LHb-projecting and VTA-projecting LPO neurons exhibited increased and decreased neuronal activities, respectively. Optogenetic activation of LHb-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within LHb evoked aversion and avoidance behaviors, while activation of VTA-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within VTA produced preference and exploratory behaviors in mice. Furthermore, either optogenetic inhibition of LHb-projecting LPO excitatory neurons or activation of VTA-projecting LPO excitatory neurons during CRS effectively prevented the development of depressive-like behaviors. Our study unveils, for the first-time, divergent pathways originating from LPO that regulate opposite affective states in mice and implicates that an imbalance of their activities could lead to depressive-like behaviors. These circuitries represent promising therapeutic targets to relieve emotional dysfunctions in neuropsychiatric disorders., Competing Interests: Authors have no conflicts of interests to report., (© 2024 The Authors. Published by Elsevier Inc.)

Plant viruses exist in a broader ecological community, with key components include non-vector herbivores that can impact vector abundance, behavior, and virus transmission within shared host plants. However, little is known about the effects of non-vector herbivores infestation on the virus transmission by vector insects on the neighboring plants through inter-plant airborne chemicals. In this study, we investigated how volatiles emitted from tomato plants infested with the two-spotted spider mite (Tetranychus urticae) affect the infection of Tomato yellow leaf curl virus (TYLCV) transmitted by the whitefly (Bemisia tabaci) in the neighboring plants. Exposure of neighboring tomato plants to volatiles released from T. urticae-infested tomato plants reduced subsequent herbivory as well as TYLCV transmission and infection, and JA signaling pathway was essential for generation of the inter-plant defense signals. We also demonstrated that (E)-β-Ocimene and MeSA were two volatiles induced by T. urticae that synergistically attenuated TYLCV transmission and infection in tomato. Thus, our findings suggest that plant-plant communication via volatiles likely represents a widespread defensive mechanism that substantially contributes to plant fitness. Understanding such phenomena may help us to predict the occurrence and epidemic of multiple herbivores and viruses in the agroecosystem, ultimately to manage pest and virus outbreaks., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. 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.)

Background: Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism., Method: The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay., Results: By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.

Objective: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC., Methods: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM., Results: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect., Conclusion: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes., (© 2024. The Author(s).)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chen Sheng reports financial support was provided by the Research Grant Council of the Government of Hong Kong SAR. YANG Xuemei reports financial support was provided by the Research Grant Council of the Government of Hong Kong SAR. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

In this work, we report the syntheses of three Pt(II) emitters, namely, Pt4N1, Pt4N2, and Pt4N3, to which their tetradentate chelates were assembled by linking two pyrazolate chelates with a single xylenylamino entity. Functionalization of Pt4N1 was achieved upon addition of electronegative CF3 substituent on pyridinyl groups and switching to more electron deficient pyrazinyl groups in giving Pt4N2 and Pt4N3, respectively. The vertical arranged xylenylamino entity has effectively suppressed the inter-molecular π-π stacking and Pt···Pt interaction, as shown by the single crystal X-ray structural analyses. Upon fabrication of OLED devices, Pt4N2 and Pt4N3 based devices delivered efficient cyan and green emission, with an EQEmax of 15.2% and 11.2%, respectively, affirming the successfulness of the tetradentate chelating strategy., (© 2024 Wiley‐VCH GmbH.)

Extracellular clustering of amyloid-β (Aβ) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aβ 1-42 , Iowa mutation Aβ, Dutch mutation Aβ fibrils and oligomers exhibiting enhanced emission with high affinity. Importantly, F-SLCOOH can readily pass through the blood-brain barrier and shows highly selective binding toward the extracellular Aβ aggregates in real-time in live animal imaging of a 5XFAD mice model. In addition, a high concentration of F-SLCOOH in both brain and plasma of wildtype mice after intraperitoneal administration was found. The ex vivo confocal imaging of hippocampal brain slices indicated excellent colocalization of F-SLCOOH with Aβ positive NU1, 4G8, 6E10 A11 antibodies and THS staining dye, affirming its excellent Aβ specificity and targetability. The molecular docking studies have provided insight into the unique and specific binding of F-SLCOOH with various Aβ species. Importantly, F-SLCOOH exhibits remarkable anti-fibrillation properties against toxic Aβ aggregate formation of Aβ 1-42 , Iowa mutation Aβ, and Dutch mutation Aβ. F-SLCOOH treatment also exerts high neuroprotective functions and promotes autophagy lysosomal biogenesis in neuronal AD cell models. In summary, the present results suggest that F-SLCOOH is a highly promising theranostic agent for diagnosis and therapeutics of AD.

To identify potent inhibitors of the type III secretion system (T3SS) in the foodborne pathogen Pseudomonas aeruginosa , we synthesized 35 thiazole-containing aryl amides by merging salicylic acid with various heterocycles through active splicing. Screening for exoS promoter activity led to the discovery of a highly effective T3SS inhibitor from these 35 compounds. Through subsequent experiments, it was confirmed that compound II-22 specifically targeted the T3SS of P. aeruginosa . Additionally, compound II-22 inhibited the secretion of the effector protein ExoS by modulating the CyaB-cAMP/Vfr-ExsA and ExsCED-ExsA regulatory pathways. Furthermore, compound II-22 suppressed the transcription of genes involved in the needle complex assembly, leading to reduced bacterial virulence. Further validation through inoculation tests using Galleria mellonella larvae demonstrated the strong in vivo efficacy of compound II-22 . The study also revealed that compound II-22 enhanced the bactericidal activity of antibiotics, such as CIP (ciprofloxacin) and TOB (tobramycin). These results could help develop novel antimicrobial drugs to reduce bacterial resistance.

Non-Hermitian physics has emerged as a new paradigm that profoundly changes our understanding of non-equilibrium systems, introducing novel concepts such as exceptional points, spectral topology, and non-Hermitian skin effects (NHSEs). Most existing studies focus on non-Hermitian eigenstates, whereas dynamic properties have been discussed only recently, and the dynamic NHSEs are not yet confirmed in experiments. Here, we report the experimental observation of non-Hermitian skin dynamics using tunable one-dimensional nonreciprocal double-chain mechanical systems with glide-time symmetry. Remarkably, dynamic NHSEs are observed with various behaviors in different dynamic phases, which can be understood via the generalized Brillouin zone and the related concepts. Moreover, the observed dynamic NHSEs, amplifications, bulk unidirectional wave propagation, and boundary wave trapping provide promising ways to manipulate waves in a controllable and robust way. Our findings open a new pathway toward non-Hermitian dynamics, which will fertilize the study of non-equilibrium phases of matter., (© 2024. The Author(s).)

Introduction: Growing concerns regarding the reproductive toxicity associated with daily life exposure to micro-/nano-plastics (abbreviated as MNPs) have become increasingly prevalent. In reality, MNPs exposure involves a heterogeneous mixture of MNPs of different sizes rather than a single size., Methods: In this study, an oral exposure mouse model was used to evaluate the effects of MNPs of four size ranges: 25-30 nm, 1-5 µm, 20-27 µm, and 125-150 µm. Adult male C57BL/6 J mice were administered environmentally relevant concentrations of 0.1 mg MNPs/day for 21 days. After that, open field test and computer assisted sperm assessment (CASA) were conducted. Immunohistochemical analyses of organ and cell type localization of MNPs were evaluated. Testicular transcriptome analysis was carried out to understand the molecular mechanisms., Results: Our result showed that MNPs of different size ranges all impaired sperm motility, with a decrease in progressive sperm motility, linearity and straight-line velocity of sperm movement. Alterations did not manifest in animal locomotion, body weight, or sperm count. Noteworthy effects were most pronounced in the smaller MNPs size ranges (25-30 nm and 1-5 µm). Linear regression analysis substantiated a negative correlation between the size of MNPs and sperm curvilinear activity. Immunohistochemical analysis unveiled the intrusions of 1-5 µm MNPs, but not 20-27 µm and 125-150 µm MNPs, into Leydig cells and testicular macrophages. Further testicular transcriptomic analysis revealed perturbations in pathways related to spermatogenesis, oxidative stress, and inflammation. Particularly within the 1-5 µm MNPs group, a heightened perturbation in pathways linked to spermatogenesis and oxidative stress was observed., Conclusions: Our data support the size-dependent impairment of MNPs on sperm functionality, underscoring the pressing need for apprehensions about and interventions against the escalation of environmental micro-/nano-plastics contamination. This urgency is especially pertinent to small-sized MNPs., 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.)

Objective: To investigate whether honokiol (HNK) acted as an analgesic in connection with inhibiting the voltage-gated proton channel (Hv1)., Methods: The model of gouty arthritis was induced by injecting monosodium urate (MSU) crystals into the hind ankle joint of mice. HNK was given by intragastric administration. Ankle swelling degree and mechanical allodynia were evaluated using ankle joint circumference measurement and von Frey filaments, respectively. Hv1 current, tail current, and action potential in dorsal root ganglion (DRG) neurons were recorded with patch-clamp techniques., Results: HNK (10, 20, 40 mg/kg) alleviated inflammatory response and mechanical allodynia in a dose-dependent manner. In normal DRG neurons, 50 µM Zn 2+ or 2-GBI significantly inhibited the Hv1 current and the current density of Hv1 increased with increasing pH gradient. The amplitude of Hv1 current significantly increased on the 3rd after MSU treatment, and HNK dose-dependently reversed the upregulation of Hv1 current. Compared with MSU group, 40 mg/kg HNK shifted the activation curve to the direction of more positive voltage and increased reversal potential to the normal level. In addition, 40 mg/kg HNK reversed the down-regulation of tail current deactivation time constant (τ tail ) but did not alter the neuronal excitability of DRG neurons in gouty mice., Conclusion: HNK may be a potential analgesic by inhibiting Hv1 current., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: One of the pathological characteristics of obesity is fat accumulation of skeletal muscles (SKM) and the myocardium, involving mechanisms of insulin resistance and abnormal lipid metabolism. Apolipoprotein A-IV (ApoA-IV) is an essential gene in both glucose and lipid metabolisms., Materials and Methods: Using high-fat diet (HFD) induced obese apoA-IV -knockout mice and subsequent introduction of exogenous recombinant-ApoA-IV protein and adeno-associated virus (AAV)-transformed apoA-IV , we examined lipid metabolism indicators of SKM and the myocardium, which include triglyceride (TG) content, RT-PCR for lipogenic indicators and western blotting for AKT phosphorylation. Similarly, we used high-glucose-fed or palmitate (Pal)-induced C2C12 cells co-cultured with ApoA-IV protein to evaluate glucose uptake, the phosphoinositide 3-kinase (PI3K)-AKT pathway, and lipid metabolisms., Results: In stable obese animal models, we find ApoA-IV-knockout mice show elevated TG content, enhanced expression of lipogenic enzymes and diminished phosphorylated AKT in SKM and the myocardium, but both stable hepatic expression of AAV- apoA-IV and brief ApoA-IV protein administration suppress lipogenesis and promote AKT phosphorylation. In a myoblast cell line C2C12, ApoA-IV protein suppresses Pal-induced lipid accumulation and lipogenesis but enhances AKT activation and glucose uptake, and the effect is abolished by a PI3K inhibitor., Conclusion: We find that ApoA-IV reduces fat accumulation by suppressing lipogenesis and improves glucose uptake in SKM and the myocardium by regulating the PI3K-AKT pathway.

Fluid sensing has been an important but missing part of the massive Internet-of-Things sensor networks due to challenges including excessive manufacturing time/cost, finite wireless interrogation range, limited immunity to ambient clutter, and excessive required power for autonomous microfluidics operability. Here, we proposed an additive manufacturing flexible system as a solution to those challenges while enabling fluid analysis from controlled labs to virtually everywhere. Energy harvesting provides all required power for the actuation of the micro-pump enabling battery-less liquid sample acquisition. Energy sources including ultra-high-frequency radio frequency identification and hand-held devices like two-way talk radio are harvested simultaneously to support energy requirements for periodic monitoring every 6.6 min and on-demand monitoring within 4.63 s. Backscattering topologies are used to significantly extend the reading range while increasing the immunity to interferences and reducing the cost to the reader. A new additive manufacturing process is proposed to reduce fabrication time and cost while enabling massive scalability of flexible microfluidics. The good flexibility makes the system suitable for working toward future wearable applications. Prototypes of a sweat sensing system are demonstrated and successfully interrogated at 3 m with more than 15 dB signal-to-noise ratio using only a 14 dBm transmitter equivalent isotropic radiated power., (© 2024. The Author(s).)

Background and Aims: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This protocol is for a study to test the effectiveness of a self-determination theory-based intervention (quit immediately or progressively) plus instant messaging (WhatsApp or WeChat) to help smokers with cancer to quit smoking., Design: This will be a multi-centre, two-arm (1:1), single-blind, pragmatic, individually randomized controlled trial., Setting: Taking part will be specialist outpatient clinics in five major hospitals in different location-based clusters in Hong Kong., Participants: The sample will include 1448 Chinese smokers living with cancer attending medical follow-ups at outpatient clinics., Interventions: The intervention group will receive brief advice (approximately 5-8 minutes) from research nurses in the outpatient clinics and then be invited to choose their own quit schedules (immediate or progressive). During the first 6-month follow-up period they will receive instant messaging with smoking cessation advice once per week for the first 3 months, and thereafter approximately once per month. They will also receive four videos, and those opting to quit progressively will receive a smoking reduction leaflet. The control group will also receive brief advice but be advised to quit immediately, and instant messaging with general health advice during the first 6-month follow-up period using the same schedule as the intervention group. Participants in both groups will receive smoking cessation leaflets., Measurements: The primary outcome is biochemically validated smoking abstinence at 6 months, as confirmed by saliva cotinine level and carbon monoxide level in expired air. Secondary outcomes include biochemically validated smoking abstinence at 12 months, self-reported 7-day point prevalence of smoking abstinence at 6 and 12 months, self-reported ≥ 50% reduction of cigarette consumption at 6 and 12 months and quality of life at 6 and 12 months. All time-points for outcomes measures are set after randomization., Comments: The results could inform research, policymaking and health-care professionals regarding smoking cessation for patients living with cancer, and therefore have important implications for clinical practice and health enhancement., (© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dysregulation of brain innate immunity involving microglia is implicated in the pathology of neurological disorders including depression. Depression is a prominent medical challenge to global public health systems. Synthetic antidepressant drugs are limited by severe side-effects. The present study aimed to identify the active compounds from the well-documented herbal medicine formula Banxia-Houpo decoction (BHD) and discover the underlying mechanisms for tuning microglia. We initially employed LC-MS profiling and network pharmacology analysis to predict the active compound-target interaction networks. We subsequently validated the potential active compounds and targets in a mouse model of corticosterone (CORT)-induced depression and post-synaptic microglia BV2 cells. As results, 64 compounds were identified in the ethanolic BHD extract and predicted to target 25 depression-related genes. Interestingly, the serotonergic synapse pathway received the highest enrichment score while 5-hydroxytryptamine receptor 1A (HTR1A) was targeted by six compounds (i.e., baicalein, luteolin, N-nornuciferine, roemerine, scutellarin, 6-shogaol). In parallel assays, a six-compound combo (SCC) and BHD markedly ameliorated the depressive-like behaviors in CORT-lesioned mice and well protected highly differentiated (HD) PC12 cells against CORT challenge. Moreover, SCC and BHD effectively induced HTR1A expression in mice and post-synaptic microglia BV2 cells. HTR1A antagonist WAY-100635 at 1mg/kg/d via intraperitoneal injection attenuated the effects of SCC and BHD on the depressive behaviors in mice. These results suggest that SCC might be a potential remedy against depression and other neurological disorders via targeting HTR1A in microglia., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. 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.)

Selective dehydrogenative C-H silylation is one of the most powerful tools to synthesize silacycles. Herein, we developed Ru-catalyzed sequential hydrosilylation/C-H silylation of allyl-indoles and dehydrogenative O-H/C-H silylation of pyrrole phenols. Both six-membered indole silacycles and pyrrole silyl ether cycles were successfully synthesized with good functional group tolerance. Furthermore, the RuHCl(CO)(PPh 3 ) 3 catalyst exhibited high reaction compatibility in hydrosilylation of alkene, dehydrogenative O-H silylation, and C-H silylation.

DNAzyme-based assays have found extensive utility in pathogenic bacteria detection but often suffer from limited sensitivity and specificity. The integration of a signal amplification strategy could address this challenge, while the existing combination methods require extensive modification to accommodate various DNAzymes, limiting the wide-spectrum bacteria detection. We introduced a novel hook-like DNAzyme-activated autocatalytic nucleic acid circuit for universal pathogenic bacteria detection. The hook-like connector DNA was employed to seamlessly integrate the recognition element DNAzyme with the isothermal enzyme-free autocatalytic hybridization chain reaction and catalytic hairpin assembly for robust exponential signal amplification. This innovative autocatalytic circuit substantially amplifies the output signals from the DNAzyme recognition module, effectively overcoming DNAzyme's inherent sensitivity constraints in pathogen identification. The biosensor exhibits a strong linear response within a range of 1.5 × 10 3 to 3.7 × 10 7 CFU/mL, achieving a detection limit of 1.3 × 10 3 CFU/mL. Noted that the sensor's adaptability as a universal detection platform is established by simply modifying the hook-like connector module, enabling the detection of various pathogenic bacteria of considerable public health importance reported by the World Health Organization, including Escherichia coli , Staphylococcus aureus , Klebsiella pneumoniae , and Salmonella typhimurium . Additionally, the specificity of DNAzyme in bacterial detection is markedly improved due to the signal amplification process of the autocatalytic circuit. This hook-like DNAzyme-activated autocatalytic platform presents a versatile, sensitive, and specific approach for pathogenic bacteria detection, promising to significantly expand the applications of DNAzyme in bacteria detection.

Pseudaminic acid (Pse) is found in the polysaccharide structures of the cell surface of various Gram-negative pathogenic bacteria including Acinetobacter baumannii and considered as an important component of cell surface glycans including oligosaccharides and glycoproteins. However, the glycosyltransferase that is responsible for the Pse glycosylation in A. baumannii remains unknown yet. In this study, through comparative genomics analysis of Pse-positive and negative A. baumannii clinical isolates, we identified a potential glycosyltransferase, KpsS1, located right downstream of the Pse biosynthesis genetic locus. Deletion of this gene in an Pse-positive A. baumannii strain, Ab8, impaired the glycosylation of Pse to the surface CPS and proteins, while the gene knockout strain, Ab8ΔkpsS1, could still produce Pse with 2.86 folds higher amount than that of Ab8. Furthermore, impairment of Pse glycosylation affected the morphology and virulence potential of A. baumannii, suggesting the important role of this protein. This study will provide insights into the further understanding of Pse in bacterial physiology and pathogenesis., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Mental health problems disproportionately affect young people in developing countries. However, there is limited research on help-seeking behaviours and the social support systems that improve mental wellbeing among vulnerable youth populations., Objective: This mixed-methods study aimed to examine the relationship between social support reciprocity and mental health among young informal construction workers in Nigeria, a population at high-risk for occupational and socioeconomic stressors., Methods: A cross-sectional survey was administered to 686 informal workers to measure reciprocity, mental health-related quality of life, and covariates. In-depth interviews with 32 participants provided qualitative context., Results: Quantitative analyses showed 25% of participants reported poor mental health. Reciprocity positively predicted mental health after controlling for covariates. Qualitative findings revealed reciprocity occurs directly between individuals as well as indirectly through trade unions and religious groups. Indirect exchanges through groups helped address limitations of direct support due to limited resources., Conclusions: This study fills important gaps in understanding how social relationships impact mental health in developing country contexts. Findings emphasize the role of collective action and community-based support systems in promoting mental wellbeing among vulnerable populations. Insights can inform culturally relevant, systems-level mental health interventions., (© 2024. The Author(s).)

Carrier-free nanomedicines offer advantages of extremely high drug loading capacity (>80%), minimal non-drug constituent burden, and facile preparation processes. Numerous studies have proved that multimodal cancer therapy can enhance chemotherapy efficiency and mitigate multi-drug resistance (MDR) through synergistic therapeutic effects. Upon penetration into the tumor matrix, nanoparticles (NPs) are anticipated to be uptaken by cancer cells, primarily through clathrin-meditated endocytosis pathways, leading to their accumulation in endosomes/lysosomes within cells. However, endo/lysosomes exhibit a highly degradative environment for organic NPs and drug molecules, often resulting in treatment failure. Hence, this study designed a lysosomal escape mechanism with carrier-free nanomedicine, combining the chemotherapeutic drug, curcumin (Cur), and the photothermal/photodynamic therapeutic drug, indocyanine green (ICG), for synergistic cancer treatment (ICG-Cur NPs) via a facile preparation process. To facilitate endo/lysosomal escape, ICG-Cur NPs were modified with metal-phenolic networks (MPNs) of different thickness. The results indicate that a thick MPN coating promotes rapid endo/lysosomal escape of ICG-Cur NPs within 4 h and enhances the photothermal conversion efficiency of ICG-Cur NPs by 55.8%, significantly improving anticancer efficacy in both chemo- and photo-therapies within 3D solid tumor models. This finding underscores the critical role of endo/lysosomal escape capacity in carrier-free drug NPs for therapeutic outcomes and offers a facile solution to achieve it.

Electrochemical CO 2 reduction has garnered significant interest in the conversion of sustainable energy to valuable fuels and chemicals. Cu-based bimetallic catalysts play a crucial role in enhancing * CO concentration on Cu sites for efficient C─C coupling reactions, particularly for C 2 product generation. To enhance Cu's electronic structure and direct its selectivity toward C 2 products, a novel strategy is proposed involving the in situ electropolymerization of a nano-thickness cobalt porphyrin polymeric network (EP-CoP) onto a copper electrode, resulting in the creation of a highly effective EP-CoP/Cu tandem catalyst. The even distribution of EP-CoP facilitates the initial reduction of CO 2 to * CO intermediates, which then transition to Cu sites for efficient C─C coupling. DFT calculations confirm that the * CO enrichment from Co sites boosts * CO coverage on Cu sites, promoting C─C coupling for C 2+ product formation. The EP-CoP/Cu gas diffusion electrode achieves an impressive current density of 726 mA cm -2 at -0.9 V versus reversible hydrogen electrode (RHE), with a 76.8% Faraday efficiency for total C 2+ conversion and 43% for ethylene, demonstrating exceptional long-term stability in flow cells. These findings mark a significant step forward in developing a tandem catalyst system for the effective electrochemical production of ethylene., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Leptospirosis is a bacterial zoonotic disease of major One Health significance and public health impact globally, with a wide host range including mammals, cetaceans and herpetofauna. This study aimed to determine Leptospira seroprevalence, risk factors for seroreactivity and prevalence of urinary Leptospira shedding among domestic cats in Hong Kong. Microagglutination testing of 22 Leptospira serovars from 20 serogroups was performed on 738 sera from outdoor free-roaming "community" cats ( n  = 391) and privately-owned ( n  = 347) cats. Urine from 268 community cats was tested for pathogenic Leptospira DNA by qPCR targeting lipL32 . Potential risk factors associated with exposure were assessed using logistic regression. Overall Leptospira seroprevalence was 9.35%. Of 14 serogroups detected, Javanica (4.3%), Djasiman (2.3%) and Australis (1.5%) were most common. Seroreactivity was significantly higher among community (13.3%) than privately-owned cats (4.9%; OR 2.98 [95% CI 1.68-5.25], P  < 0.001), especially to Javanica (7.65% of community cats versus 0.58% of privately-owned cats ( P  < 0.001). Antibody titres to all serogroups ranged from 1:100 to 1:6400 (median 1:200) and were highest for Javanica (median 1:800). Leptospira DNA was detected in urine from 12/268 community cats (4.48%; median load 6.42 × 10 2 copies/mL urine; range 1.40 × 10 1 -9.63 × 10 4 ). One in three seroreactive community cats with paired urine and blood samples had leptospiruria. After adjusting for source, none of breed, sex, neuter status, age, district rodent infestation rate, serum alanine transaminase or creatinine values were associated with seroreactivity. Cats in Hong Kong are exposed to a diversity of Leptospira serogroups and can shed Leptospira silently in urine. The higher seroprevalence among outdoor free-roaming community cats highlights the importance of environmental drivers in leptospirosis transmission and risks of exposure for sympatric human populations. Gloves should be worn when handling feline urine to minimise the risk of zoonotic transmission from subclinically infected cats., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article. Internal funding from City University of Hong Kong had no influence on the study design, results, interpretation or publication of findings. Generative AI tools were not used in the writing of our manuscript., (© 2024 The Author(s).)

The intricate relationship between prestimulus alpha oscillations and visual contrast detection variability has been the focus of numerous studies. However, the causal impact of prestimulus alpha traveling waves on visual contrast detection remains largely unexplored. In our research, we sought to discern the causal link between prestimulus alpha traveling waves and visual contrast detection across different levels of mental fatigue. Using electroencephalography alongside a visual detection task with 30 healthy adults (13 females; 17 males), we identified a robust negative correlation between prestimulus alpha forward traveling waves (FTWs) and visual contrast threshold (VCT). Inspired by this correlation, we utilized 45/-45° phase-shifted transcranial alternating current stimulation (tACS) in a sham-controlled, double-blind, within-subject experiment with 33 healthy adults (23 females; 10 males) to directly modulate these alpha traveling waves. After the application of 45° phase-shifted tACS, we observed a substantial decrease in FTW and an increase in backward traveling waves, along with a concurrent increase in VCT, compared with the sham condition. These changes were particularly pronounced under a low fatigue state. The findings of state-dependent tACS effects reveal the potential causal role of prestimulus alpha traveling waves in visual contrast detection. Moreover, our study highlights the potential of 45/-45° phase-shifted tACS in cognitive modulation and therapeutic applications., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS., (© 2024. The Author(s).)

Objectives: Previous studies showed that nightmares are prevalent and are associated with negative health outcomes. However, no empirical data is available demonstrating the extent to which nightmare disorder persists over time. Current literature provides a limited understanding of the trajectory and wider mental health outcomes of nightmare disorder. This longitudinal study examined the persistence and mental health outcomes of nightmare disorder., Methods: A total of 230 Hong Kong Chinese adults completed standardized assessments twice with an interval of about 6 months., Results: Over half (66.7%) of the participants with probable nightmare disorder at baseline remained to meet the DSM-5 criteria for the disorder at follow-up. Participants with probable nightmare disorder at baseline were significantly more likely to screen positive for PTSD (82.1% vs 18.3%) ( p < .001) ( p  < .001), and they reported higher rates of mental health service usage at both timepoints ( p  = .001 to .003). Baseline nightmare disorder severity was negatively associated with subsequent self-rated mental health (β = -.151, p  = .010) and self-esteem (β = -.141, p  = .009) and it also predicted subsequent PTSD symptoms (β = .122, p  = .012)., Conclusions: This study provides first empirical data showing that nightmare disorder could be persistent over time. Nightmare disorder symptoms are associated not only with PTSD symptoms but also with a broader range of mental health issues. This study points to the public health importance of identifying and managing nightmare disorder symptoms in the community. Additionally, the presence of nightmare disorder symptoms may be a helpful indicator for identifying post-traumatic stress.

Background: DNA repair allows the survival of cancer cells. Therefore, the development of DNA repair inhibitors is a critical need for sensitizing cancers to chemoradiation. Sae2 CtIP has specific functions in initiating DNA end resection, as well as coordinating cell cycle checkpoints, and it also greatly interacts with the DDR at different levels., Results: In this study, we demonstrated that corylin, a potential sensitizer, causes deficiencies in DNA repair and DNA damage checkpoints in yeast cells. More specifically, corylin increases DNA damage sensitivity through the Sae2-dependent pathway and impairs the activation of Mec1-Ddc2, Rad53-p and γ-H2A. In breast cancer cells, corylin increases apoptosis and reduces proliferation following Dox treatment by inhibiting CtIP. Xenograft assays showed that treatment with corylin combined with Dox significantly reduced tumor growth in vivo., Conclusions: Our findings herein delineate the mechanisms of action of corylin in regulating DNA repair and indicate that corylin has potential long-term clinical utility as a DDR inhibitor., 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 Masson SAS.. All rights reserved.)