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Fragile X mental retardation protein (FMRP), an RNA binding protein (RBP), is aberrantly hyper-expressed in human tumors and plays an essential role in tumor invasion, metastasis and immune evasion. However, there is no small-molecule inhibitor for FMRP so far. In this study, we developed the first FMRP-targeting degrader based on PROteolysis TArgeting Chimera (PROTAC) technology and constructed a heterobifunctional PROTAC through linking a FMRP-targeting G-quadruplex RNA (sc1) to a von Hippel-Lindau (VHL)-targeting ligand peptide (named as sc1-VHLL). Sc1-VHLL specifically degraded endogenous FMRP via ubiquitination pathway in both mouse and human cancer cells. The FMRP degradation significantly changed the secretion pattern of cancer cells, resulting in higher expression of pro-inflammatory cytokine and smaller amounts of immunomodulatory contents. Furthermore, sc1-VHLL, when encapsulated into ionizable liposome nanoparticles (LNP), efficiently targeted tumor site and degraded FMRP in cancer cells. In CT26 tumor-bearing mouse model, FMRP degradation within tumors substantially promoted the infiltration of lymphocytes and CD8 T cells and reduced the proportion of T reg cells, reshaping the proinflammatory tumor microenvironment and accordingly transforming cold tumor into hot tumor. When combined with immune checkpoint blockade (ICB) therapy, sc1-VHLL based treatment remarkably inhibited the tumor growth., (© 2024 Wiley-VCH GmbH.)

Air pollutants have been investigated to be associated with many health issues. Recently, increasing epidemiological studies have suggested the association between air pollution exposure and risk of frailty with inconsistent findings. This systematic review and meta-analysis was to summarize and evaluate effects of exposure to various air pollutants on risk of frailty. PubMed, Embase, Scopus and Web of Science were systematically searched for relevant studies published before May 11, 2024. Studies that explored the potential relationship between exposure to air pollutants (PM 2.5 , PM 10 , O 3 , NO x , solid fuel, secondhand tobacco, and air quality) and risk of frailty were included. The quality of cross-sectional and cohort studies was evaluated using an eight-item assessment instrument for epidemiological studies and Newcastle-Ottawa Scale, respectively. A total of 9,929 papers were retrieved, of which 20 met the inclusion criteria. Meta-analysis indicated that PM 2.5 exposure was significantly associated with frailty assessed by the frailty index [OR (95% CI): 1.24 (1,11-1.38) per 10 μg/m 3 increment]. Moreover, solid fuel exposures were significantly associated with an increased risk of frailty assessed by the frailty phenotype [OR (95% CI): 1.91 (1.09-3.34)] or the frailty index [OR (95% CI): 1.25 (1.11-1.41)]. Exposure to PM 2.5 and solid fuel increases the risk of frailty. Environmental protection policies and public health measures should be developed to reduce PM 2.5 concentrations. Effective measures, such as improving stoves and using clean fuels, should be taken to reduce indoor air pollution levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The interaction between proteins and soluble dietary fibers plays a vital role in the development of animal-derived foods. Herein, the effects of different contents (0-3.0%) of round-bracted psyllium husk powder (PHP) on the gelation behavior, microstructure, and intermolecular interactions of Andrias davidianus myofibrillar protein (MP) were investigated. Rheological and chemical forces suggested that PHP (1.5%-2.0%) enhanced the functional properties of MP at low ionic strength, thereby increasing the viscoelasticity of mixed gels. SDS-PAGE revealed that PHP reinforced the cross-linking and aggregation of protein molecules. Circular dichroism spectroscopy, low-field nuclear magnetic resonance, and scanning electron microscopy demonstrated that PHP induced the transformation of α-helix (decreased by 14.85%) to an ordered β-sheet structure (increased by 81.58%), which was more favorable for the formation of dense network structure and improved (10.53%) the water retention of MP gels. This study provided new insights for PHP to effectively meliorate the heat-induced gelling properties of MP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Adamantinomatous craniopharyngiomas (ACPs), commonly seen in pediatrics and adults often present with large cystic cavities that can compress surrounding tissues, causing severe visual and endocrine symptoms. Complete resection of cystic ACP is challenging, frequently leading to postoperative recurrence. The composition of the cystic fluid is complex, and to date, there has been limited research focusing on exosomes within ACP cyst fluid., Methods: We collected cyst fluid from 12 ACP patients and confirmed the presence of exosomes. Subsequently, we conducted exosomal proteomic analysis using LC-MS/MS. The patients were divided into pediatric and adult groups for the analysis of differential protein enrichment, followed by comprehensive bioinformatics analysis, including GO analysis, KEGG analysis, and PPI network analysis, among other functional pathway and protein interaction analyses. Immunohistochemistry was used to determine the tissue expression distribution of the differential protein APOA1., Results: In our data analysis, 64 significantly differentially expressed proteins were identified, with 37 being overexpressed in the pediatric group and 27 in the adult group. Our results revealed that exosomal proteins in the pediatric group were predominantly enriched in modules and pathways related to high-density lipoprotein particle, apolipoprotein receptor binding, and the PPAR signaling pathway. Additionally, APOA1, as the hub protein with the highest connectivity in the differential protein interaction network, may play a critical role in β-amyloid metabolism pathways in pediatric ACP., Conclusion: This study is the first to construct a proteomic map of ACP cyst fluid exosomes, suggesting significant differences in the tumor microenvironment's lipid metabolism between pediatrics and adults., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Oxidative stress, predominantly from neuronal mitochondrial damage and the resultant cytokine storm, is central to cerebral ischemia-reperfusion injury (CIRI). However, delivering drugs to neuronal mitochondria remains challenging due to the blood-brain barrier (BBB), which impedes drug entry into affected brain tissues. This study introduces an innovative tannic acid (TA) and melanin-modified heteropolyacid nanomedicine (MHT), which highly specifically eliminates the neuronal mitochondrial reactive oxygen radicals burst to efficiently reduce neuronal mitochondrial damage through a strategically designed sequential targeting strategy from affected brain tissue to neuronal mitochondria. TA endows MHT with sequential targeting ability by binding to matrix proteins exposed to the damaged BBB and mitochondrial outer membrane proteins of neurons, while melanin significantly enhances the antioxidant capacity of MHT. Consequently, MHT effectively inhibits neuronal apoptosis by protecting mitochondria and reversing the inflammatory immune environment through the deactivation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. MHT demonstrated a strong therapeutic effect on CIRI, with an ultralow dose (2 mg kg -1 ) proving effective in reversing the condition. This work not only introduces a new avenue to significantly reduce CIRI through sequential targeting therapy but also offers a new paradigm for treating other ischemia-reperfusion injury diseases., (© 2024 Wiley‐VCH GmbH.)

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants. Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury. Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs. This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies., (© 2024. The Author(s).)

This study utilizes radiomics to explore imaging biomarkers for predicting the recurrence of chronic subdural hematoma (CSDH), aiming to improve the prediction of CSDH recurrence risk. Analyzing CT scans from 64 patients with CSDH, we extracted 107 radiomic features and employed recursive feature elimination (RFE) and the XGBoost algorithm for feature selection and model construction. The feature selection process identified six key imaging biomarkers closely associated with CSDH recurrence: flatness, surface area to volume ratio, energy, run entropy, small area emphasis, and maximum axial diameter. The selection of these imaging biomarkers was based on their significance in predicting CSDH recurrence, revealing deep connections between postoperative variables and recurrence. After feature selection, there was a significant improvement in model performance. The XGBoost model demonstrated the best classification performance, with the average accuracy improving from 46.82% (before feature selection) to 80.74% and the AUC value increasing from 0.5864 to 0.7998. These results prove that precise feature selection significantly enhances the model's predictive capability. This study not only reveals imaging biomarkers for CSDH recurrence but also provides valuable insights for future personalized treatment strategies., (© 2024. International Federation for Medical and Biological Engineering.)

Achieving high rate performance without compromising energy density has always been a critical objective for zinc-ion hybrid supercapacitors (ZHSCs). The pore structure and surface properties of carbon cathode materials play a crucial role. We propose utilizing a hybrid particle size (20 and 40 nm) magnesium oxide templates to regulate the pore structure of nitrogen-doped porous carbon derived from the soybean isolate. The multilevel pore structure enhanced ion transport efficiency while also improving the utilization of micropores. Nitrogen doping and oxygen-containing functional groups enhanced the wettability of carbon materials with aqueous electrolytes and facilitated the chemisorption of Zn2+ on the carbon material surface. The nitrogen-doped multilevel porous carbon material (HT-NMPC-1/1) prepared with a 1:1 mass ratio of the two templates exhibited a specific capacity of 146.65 mAh g-1 at 0.2 A g-1. Moreover, the Swagelok cells assembled with HT-NMPC-1/1 and Zn foil achieved a high energy density of 121.5 W h kg-1, high power output of 166 W kg-1, and 93.09% capacity retention after 8000 cycles at 2 A g-1. Therefore, HT-NMPC-1/1 is a highly promising candidate for ZHSCs cathode materials. Furthermore, the novel pore regulation strategy and straightforward preparation method offer valuable reference points for other porous carbon-based functional materials., (© 2024 Wiley‐VCH GmbH.)

Many studies have confirmed that PM 2.5 exposure can cause a variety of diseases. Because people spend most of their time indoors, exposure to PM 2.5 in indoor environments is critical to population health. Large-population, long-term, continuous, and accurate indoor PM 2.5 data are important but scarce because of the difficulties in monitoring the indoor air quality on a large scale. Model simulation provides a new research direction. In this study, an advanced machine learning model was constructed using environmental health big data to predict the daily indoor PM 2.5 concentration data in 22 typical air pollution cities in China from 2013 to 2017. The test R 2 value of this model reached as high as 0.89, and the RMSE of the model was 9.13. The predicted annual indoor PM 2.5 concentrations of the cities ranged from 54.6 μg/m 3 to 82.7 μg/m 3 , and showed a decreasing trend year by year. The pollution level exceeds the recommended AQG level of PM 2.5 and has potential impact on human health. The results could take a breakthrough in obtaining accurate big data of indoor PM 2.5 and contribute to research on the indoor air quality and human health in China. SYNOPSIS: This study established a machine learning model and predicted indoor PM 2.5 big data, which could support the research of indoor PM 2.5 and health., 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 Inc.)

Objective: To explore the sub-regional histogram features of amide proton transfer-weighted (APTw) MRI, compared with those of diffusion-weighted imaging (DWI), in predicting the tumor budding (TB) grade of rectal cancer (RC)., Materials and Methods: This study prospectively enrolled 74 patients with pathologically confirmed RC, who underwent APTw MRI before surgery from July 2022 to March 2023. Hematoxylin-eosin staining was used for TB scoring. K-means clustering (K = 4-6) was applied to obtain multiple sub-regions (n = 3-5), and corresponding histogram features (including mean, standard deviation, minimum, maximum, and 10th, 25th, 50th, 75th, and 90th quantile) of APT and apparent diffusion coefficient (ADC) maps were extracted and filtered using stepwise regression., Results: When K = 5, the K-means clustering is four sub-regions, showing the best prediction for TB grade compared to K = 4 or 6. When K = 5, there were significantly higher histogram features of the APT map in sub-regions 3 and 4 in the high TB grade group compared to the low-intermediate TB grade group. Receiver operating characteristic (ROC) curve and internal validation suggested that the predictive efficiency of the model was highest when K = 5, with AUC, sensitivity, specificity, accuracy, and kappa values of 0.92, 93%, 71%, 87%, and 0.65, respectively. There were no significant differences in the histogram features of each sub-region in the ADC map (p > 0.05)., Conclusion: The sub-regional histogram features of APTw images can help to distinguish the heterogeneous regions of RC, which can be used to predict the TB grade of RC., Key Points: Question Can the sub-regional histogram features of APTw MRI predict the tumor budding (TB) grade of rectal cancer (RC)? Findings Differences exist in histogram features of APT map subregions between high and low-intermediate TB grade groups; subregions of the APT map have different predictive abilities. Clinical relevance APT-weighted imaging might outperform DWI in predicting TB grade in RC., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

The phase state of atmospheric aerosol particles, dictated by composition, intermolecular interaction, size, and pH, profoundly impacts climate, human health, and air quality. Herein, the phase behavior of internally mixed sodium bitartrate (SBT) and ammonium sulfate (AS) aerosols with equal molar ratio was studied using microscopic imaging, confocal Raman and infrared spectroscopy. We observed atypical phase transition during hygrosopic cycles. On dehydration, micro-solids formed at relative humidity (RH) of 80.1 % without further efflorescence, namely limited efflorescence (LE). On hydration, droplets effloresced at 39.8 % RH and deliquesced at 68.8 % RH, referred as efflorescence on hydration (EH). Raman spectra show that Na 2 SO 4 solids form during LE, while both Na 2 SO 4 and (NH 4 ) 2 SO 4 solids form during EH. The phase transition of the SBT/AS (1:1) droplets is size-dependent, where smaller droplets are prone to "EH" while larger droplets are prone to typical efflorescence. Combining AIOMFAC-VISC viscosity predictions with scanning electron microscopy (SEM) images, we attribute the "LE" and "EH" phenomena to the formation of an ion-organic hydrogel network structure within droplets. pH and organic/inorganic mixing ratios can collaboratively affect the stability of hydrogel network by changing the organic/inorganic mixing ratios. Our study shows that gel network formation can cause atypical phase transition in atmospheric aerosols., 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.)

Background: There is strong interest in the evaluation of longer-term outcome metrics for congenital heart diseases (CHDs); however, registries focus on postoperative metrics., Methods and Results: Informed by user online discussion forums and scoping of national data, we selected sentinel CHDs and long-term outcome metrics suitable for routine monitoring. We then developed sentinel CHD phenotypes and algorithms for identifying treatment pathway procedures using clinical codes. Finally, we calculated the metrics within a retrospective national cohort analysis. The 9 selected sentinel CHDs had a higher-than-average prevalence, typically involved surgery in infancy, and were associated with an increased risk of late mortality. The selected metrics of survival and reinterventions at 1, 5, and 10 years were both important and feasible. The cohort included 29 319 (41.3% of all operated CHD births) English and Welsh children born with sentinel CHDs in 2000 to 2022. Example metrics at age 10 years included: survival-hypoplastic left heart syndrome: 57.6% (95% CI, 54.9%-60.4%), functionally univentricular heart: 86.7% (95% CI, 84.6%-88.9%), transposition of the great arteries: 93.1% (95% CI, 92.2%-93.9%), pulmonary atresia: 81.0% (95% CI, 79.1%-82.9%), atrioventricular septal defect: 88.5% (95% CI, 87.5%-89.5%), tetralogy of Fallot: 95.1% (95% CI, 94.4%-95.8%), aortic stenosis: 94.4% (95% CI, 93.3%-95.6%), coarctation: 96.7% (95% CI, 96.2%-97.3%), and ventricular septal defect: 96.9% 95% CI, (96.4%-97.3%); and (2) cumulative incidence of reintervention-hypoplastic left heart syndrome : 54.5% (95% CI, 51.5%-57.3%), functionally univentricular heart: 57.3% (95% CI, 53.9%-60.5%), transposition of the great arteries: 20.9% (95% CI, 19.5%-22.3%), pulmonary atresia: 66.8% (95% CI, 64.2%-69.1%), atrioventricular septal defect: 21.6% (20.3%-23.0%), tetralogy of Fallot: 26.6% (95% CI, 25.2%-28.0%), aortic stenosis: 31.2% (95% CI, 28.8%-33.6%), coarctation: 19.8% (95% CI, 18.6%-21.1%), and ventricular septal defect: 6.1% (95% CI, 5.5%-6.8%)., Conclusions: It is feasible to report important long-term outcomes of survival and reintervention for sentinel CHDs using routinely collected procedure records, adding value to national audit.

Two-dimensional transition metal carbides and nitrides (MXenes) and MXene-based membranes hold promise for applications including water purification and seawater desalination; however, their environmental behavior and fate in these matrices remain unknown. In this study, we systematically assessed the reaction efficiencies of Ti 3 C 2 T x at varying important environmental conditions. Our experiments revealed that copper and iron ions accelerated the oxidation rate of Ti 3 C 2 T x 55.4 and 33.4 times, respectively. TiO 2 and amorphous carbon were identified as the primary solid products. Based on in situ water-phase atomic force microscopy, atomic high-angle annular dark-field scanning transmission electron microscopy, and theoretical results, we postulate that metal ions enhance Ti 3 C 2 T x oxidation by spontaneously migrating and anchoring at Ti vacancies, which then become active sites for this reaction. This process increases the adsorption of H 2 O and oxygen, making the Ti vacancy-rich surface convex area the most vulnerable site to attack. The findings in this study provide useful information for a comprehensive understanding of the interaction between MXene structural defects and metal ions as well as for the design and modification of MXene membranes resistant to metal ion impact.

Multiple van der Waals (vdW) gaps invoke abundant opportunities for contriving artificial architectures and tailoring desired properties via the intercalation route beyond the reach of conventional concepts. Intriguingly, the electrochemical intercalation strategy can precisely and reversibly tune the intercalation stage of charged functional species. This study presents a valid structural editing protocol facilitated by electrochemical intercalation to engineer MXene interlayers, ultimately incorporating in situ constructed carbon nanotube (CNT) electric bridges for enhanced ion storage and transport pathways. The method allows for the precise modulation of electrochemical forces to tailor materials for specific applications. Deep intercalation and in situ growth processes establish robust anchoring sites and connectivity hubs between MXenes and CNTs, ensuring structural homogeneity and stability in advanced electrode materials. The results demonstrate the effectiveness of electrochemistry-mediated interlayer nanoengineering in MXenes, offering a versatile approach to design vdW heterostructures with tailored functionalities for energy storage and conversion applications. This work highlights the potential of electrochemical modulation in advancing materials engineering strategies for next-generation energy storage technologies.

The widespread prevalence of microplastics (MPs) in the environment poses concerns as they are vectors of antibiotic resistance genes (ARGs). The relationships between antibiotic resistomes and MPs remain unexplored in soil which was considered as the reservoirs of MPs and ARGs. This study investigated the effects of polyvinyl chloride (PVC) MPs on soil bacterial communities and ARG abundance which soil samples sourced from 20 provinces across China. We found that PVC significantly influences soil bacterial community structure and ARG abundance. Structural equation modeling revealed that PVC alters soil characteristics, ultimately affecting soil bacterial communities, including ARG-containing bacterial hosts, and the relative abundance of ARGs. This study enhances our understanding of how MPs influence the proliferation and hosts of ARGs within diverse soil environments, offering crucial insights for future strategies in plastic management and disposal., 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 this work, by using molecular dynamics simulations, we elucidate the effect of sulfation substitution on the stability of the curdlan triple helix structure. The simulation results indicate that the stability of the triple helix structure is significantly influenced by the sites of sulfation substitution. The substitution at the O 2 site directly disrupts the hydrogen bonding network between the triple helix chains, significantly destroying the triple helix conformation. When substitutions occur at both the O 4 and O 6 sites simultaneously (O 4,6 ), the electrostatic repulsion between numerous sulfate groups introduces considerable energy perturbation to the triple helix, leading to alterations in the glucan chain conformation and consequent destabilization of the triple helix structure. Meanwhile, we find that even if the sulfation substitution is performed at the same substitution sites, the difference in the degree of substitution also has an impact on the triple helix stability. The resistance of the triple helix to sulfation substitution at O 2 is weak, and low degree of substitution can lead to the unwinding of the triple helix. However, it demonstrates higher resistance to substitution at O 4,6 where only higher degree of substitution results in triple helix destabilization., 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: Lamina-implantation is gradually becoming the main surgical method for the treatment of intraspinal tumors. Traditional titanium (Ti) internal fixation not only produces artifacts, which affects the observation of tumors and dural sac closure, but also faces the problem of secondary surgical removal. In this study, absorbable material were used in lamina replantation for the first time and was evaluated for its efficacy and safety., Methods: We retrospectively enrolled patients who underwent short-segment lamina replantation for intraspinal tumors in our center from February 2020 to November 2022. After condition matching of the number of fixation segment and fixation position, the baseline information, complications, neurological function, quality of life, spinal mobility and bone healing rate of the absorbable group and the Ti group were compared. Fisher exact, Chi-square, or rank sum test were used for categorical variables, and t-test was used for continuous variables to distinguish differences between groups., Results: Cerebrospinal fluid leak was the most common complication, with no difference between the two groups (12.9% vs. 19.4%, p = 0.366). The bone healing rates of the two groups at 3 months after surgery were 77.4% and 87.1%, respectively, and there was no significant difference (p = 0.508). At 1 year after surgery, the resorbable group showedlower levels of anxiety/depression (1.20 ± 0.41 vs. 1.61 ± 0.61, p = 0.050), however, it did not affect the overall quality of life of the patients at 1 year., Conclusion: Both titanium and absorbable internal fixation have shown good clinical results in the treatment of intraspinal tumors by laminareplantation. Regardless of cost, absorbable screws and plates are also suitable options for patients undergoing lamina replantation, because it has no stress shielding effect and does not require secondary removal. In addition, there are no artifacts in the image, which is more conducive to observing the recurrence of the tumor and the closure of the dural sac., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Multiple redox-active amphoteric organics with more n-p fused electron transfer is an ongoing pursuit for superior zinc-organic batteries (ZOBs). Here we report multi-heterocycle-site donor-acceptor conjugated amphoteric organic superstructures (AOSs) by integrating three-electron-accepting n-type triazine motifs and dual-electron-donating p-type piperazine units via H-bonding and π-π stacking. AOSs expose flower-shaped N-heteromacrocyclic electron delocalization topologies to promise full accessibility of built-in n-p redox-active motifs with an ultralow activation energy, thus liberating superior capacity (465 mAh g-1) for Zn||AOSs battery. More importantly, the extended multiple donor-acceptor-fused conjugated AOSs feature satisfied discharge voltage and anti-dissolution in electrolytes, pushing both the energy density and cycle life of the ZOBs to a new level (412 Wh kg-1 and 70,000 cycles@10 A g-1). An anion-cation hybrid 18 e- charge storage mechanism is rationalized for heteromacrocyclic modules of AOSs cathode, entailing six tert-N motifs coupling with CF3SO3- ions at high potential and twelve imine sites coordinating with Zn2+ ions at low potential. These findings constitute a major advance of amphoteric multielectron organic materials and stand for a good starting point for advanced ZOBs., (© 2024 Wiley‐VCH GmbH.)

Wearable, noninvasive sweat sensors enable real-time monitoring of metabolites in human health management. However, the commercial enzyme-based and currently nonenzymatic glucose sensor represents sluggish glucose oxidation kinetics and a narrow sensing range. Rational design of sensitive materials is significant yet faces a huge challenge. Herein, we construct a single-atom Pt supported on NiCo-LDH/Ti 3 C 2 T x heterostructures (Pt 1 -NiCo-LDH/Ti 3 C 2 T x ) as the nonenzymatic electrochemical glucose sensor sensitive materials for selective detection of glucose level in human sweat. The obtained Pt 1 -NiCo-LDH/Ti 3 C 2 T x with improved structural stability and enhanced charge transfer efficiency shows a low oxidation peak potential of 0.49 V, high sensitivity of 506.6 μA mM -1 cm -2 , a low detection limit of 0.035 μM, and long-term stability toward the glucose detection. The wearable sensor, coupled with a wireless transmission module and a signal processing chip, is used for real-time perspiration glucose monitoring during outdoor exercise. The result is comparable to that of high-performance liquid chromatography (HPLC). This research provides a new paradigm for designing a wearable nonenzymatic electrochemical glucose sensor, enabling noninvasive real-time monitoring of glucose concentrations in human sweat.

Antibiotic resistance is a global health concern that is rapidly spreading among human and animal pathogens. Developing novel antibiotics is one of the most significant approaches to surmount antibiotic resistance. Given the difficult in identifying novel targets, cryptic binding sites provide new pockets for compounds design to combat antibiotic resistance. However, there exists a lack of comprehensive analysis and discussion on the successful utilization of cryptic pockets in overcoming antibiotic resistance. Here, we systematically analyze the crucial role of cryptic pockets in neutralizing antibiotic resistance. First, antibiotic resistance development and associated resistance mechanisms are summarized. Then, the advantages and mechanisms of cryptic pockets for overcoming antibiotic resistance were discussed. Specific cryptic pockets in resistant proteins and successful case studies of designed inhibitors are exemplified. This review provides insight into the discovery of cryptic pockets for drug design as an approach to overcome antibiotic resistance., Competing Interests: Declaration of Competing Interest There are no declaration of interest., (Copyright © 2024. Published by Elsevier Ltd.)

When treating perimembranous ventricular septal defect, median sternotomy leads to unsightly scar, right subaxillary thoracotomy requires cardiopulmonary bypass, and transcatheter device closure constrained by vascular condition. Using small left intercostal incision, we employed transthoracic device closure to get around these issues. During this study, right subaxillary thoracotomy was used for surgical repair in 117 patients (Surgical group), whereas small left intercostal incision was used for transthoracic device closure in 131 patients (Device group). Retrospective data collection and analysis were conducted. The success rate was comparable (117/117 vs. 130/131, P = 1.000). The device group experienced notably reduced operating time, mechanical ventilation duration, ICU stay, and postoperative hospital stay (All P < 0.001). Given that the device group's incision was much smaller than the surgical group's (1.1 ± 0.3 vs. 6.8 ± 1.6 cm, P < 0.001), blood transfusion or drainage tube was not needed. The device group observed a lower frequency of complications, with the exception of small residual shunt. It is feasible and safe to perform transthoracic device closure in children with perimembranous ventricular septal defects via small left intercostal incision. It can be a good minimally invasive substitute for surgical closure when utilized properly., (© 2024. The Author(s).)

The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m 2 /day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9-28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML., (© 2024. The Author(s).)

In this study, the chain length distribution (CLD) of amylopectin in eight varieties of corn, the properties of corn flour, and the quality of the corresponding sweet dumplings were analyzed, with commercially available waxy corn (CAWC) and waxy rice (CAWR) as controls. Three test samples (Feng nuo 168, Feng nuo 211, and Feng nuo 10) exhibited significant differences (P < 0.05) in the pasting properties of the whole flours from the other samples, with Feng nuo 10 exhibiting lower viscosity, breakdown, and setback, while Feng nuo 211 exhibited the highest viscosity and breakdown. The quality of sweet dumplings varied markedly: The sweet dumpling of Feng Nuo 211 showed the highest springiness, gumminess, and chewiness. All of the corn sweet dumplings had a water loss rate lower than CAWR. Feng Nuo 211 and Wan Nuo 2000 sweet dumplings displayed the lowest cooking loss rates of 0.61 % and 0.58 %, respectively. Correlation analysis indicated that CLD play a pivotal role in both whole flour characteristics and sweet dumpling quality. The findings of this study enhance our understanding of the relationship between amylopectin structure and both whole flour characteristics and product quality, and provided reference for the development of corn sweet dumplings., 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 B.V.)

Introduction: The main enzymes that hydrolyzes nucleotides at the cell surface are nucleoside triphosphate diphosphohydrolases (NTPDases), ecto-nucleotide pyrophosphatases/phosphodiesterases (ENPPs), alkaline phosphatases (APs) and ecto-5'- nucleotidase (e5'NT, CD73) and by regulating the concentration of nucleotides at the cell surface, these enzymes have the potential to affect various conditions such as fibrosis, cancer metastasis, pruritus, inflammation, and autoimmune diseases. Thus, they represent a prospective therapeutic target., Area Covered: A number of molecules, including nucleoside/nucleotide and non-nucleoside analogues, and bicyclic compounds, have shown strong potential as ectonucleotidase inhibitors. This review covers the chemistry and clinical uses of ectonucleotidase inhibitors patented between 2017 and 2023., Expert Opinion: By binding to their specific P1 and P2 receptors at the cell surface, nucleosides and nucleotides regulate a number of pathophysiological events such as inflammation, fibrosis, cancer, and autoimmune diseases. Interestingly, these nucleotides can be hydrolyzed to nucleosides by several cell surface enzymes called ectonucleotidases. The development of small molecules that modulate ectonucleotidase activity is, therefore, of therapeutic value. This review provides valuable insights into recent advancements, including combination therapy and enhanced selectivity, which are poised to shape the future of ectonucleotidase inhibition through a comprehensive analysis of patents.

Objective: This study aimed to investigate the EEG microstate characteristics in patients with persistent Omicron-related Psychiatric Symptoms (ORPS) as well as their correlations with the severity of ORPS., Methods: This study included 31 patients with ORPS, and they were divided into remission group (n=19) and non-remission group (n=12) according to the decrease of Brief Psychiatric Rating Scale (BPRS) at discharge. Multivariate logistic models were applied to analyze the risk features associated with non-remission of ORPS at discharge, and the Spearman rank correlation was adopted to analyze the correlation between the occurrence of microstate class B and BPRS score at admission., Results: The analysis revealed that an increased occurrence of EEG microstate class B was significantly associated with a higher likelihood of non-remission of ORPS at discharge (p < 0.05). Furthermore, a moderate positive correlation was observed between the occurrence of microstate class B and BPRS scores at admission (r = 0.390, p = 0.030), indicating that patients with more frequent microstate class B tended to exhibit more severe psychiatric symptoms at onset., Conclusions: The findings suggest that an increased occurrence of EEG microstate class B is an independent risk factor for non-remission of ORPS at discharge. Additionally, the positive correlation between microstate class B and BPRS scores underscores the potential of microstate class B as a biomarker for the severity of psychiatric symptoms in ORPS patients., Significance: Identifying the increased occurrence of microstate class B at admission could serve as a novel marker for early assessment of ORPS severity and prognostic evaluation., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024. Published by Elsevier Inc.)

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier Inc.)

Rhizobia are common symbiotic microorganisms in the root system of leguminous plants that can usually provide nitrogen to the host through nitrogen fixation. Studies have shown that rhizobium-preinoculated soybean plants usually exhibit improved salt tolerance, but the underlying mechanism is not fully understood. In this paper, transcriptome sequencing (RNA-seq) revealed that preinoculation with rhizobia affected polyamine (PA) metabolism in soybean roots. The assay of PA contents showed that preinoculation with rhizobia significantly increased the putrescine (Put) content in roots and leaves during short-term salt treatment (0-5 d). Long-term salt treatment (5-7 d) resulted in a high Put content and significantly increased Spm and Spd contents, resulting in a rapid increase in the Put/(Spd + Spm) ratio (0-5 d) and subsequent decrease. Moreover, rhizobium preinoculation of soybean plants resulted in increased contents of conjugated and bound PAs under salt stress. Further transcriptome sequencing, PA contents, PA synthase expression and activity analysis revealed that GmADC may be a key gene related to salt tolerance in rhizobium-preinoculated soybean plants, and the GmADC-overexpressing soybean hairy-root composite plants exhibited less ROS damage, lower Cl - /NO 3 - ratios and Na + /K + ratios, and stabilized ion homeostasis. Taken together, preinoculation with rhizobia increased the expression level and enzyme activity of arginine decarboxylase (ADC) in soybean roots, increased the content of Put in roots and leaves, and increased the content of conjugated and bound PAs in soybean plants, thereby alleviating the oxidative and ionic injuries of soybean plants and enhancing the salt tolerance., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Macrophage polarization facilitates the inflammatory response and intensified fibrosis in the silicosis microenvironment by a mechanism related to macrophage pyroptosis, although the upstream target remains poorly defined. Currently, there are few reports on the development of drugs that alleviate macrophage polarization by dampening pyroptosis. The present study aims to explore the mechanics of silica mediating macrophage polarization and to investigate whether quercetin (Que) can depolarize macrophages with this mechanism. Silica processing led to prominent M1 polarization of macrophages. Additionally, significant macrophage polarization could be detected in the lung tissue of mice with airway-perfused silica. Further investigation turned out that pronounced mitochondria damage, mtDNA cytoplasmic ectomy, and pyroptosis occurred in response to silica. Nevertheless, Que treatment could effectively attenuate silica-induced mitochondria damage and pyroptosis as demonstrated in vitro and in vivo. Further exploration presented Que could bind to TOM70 and restore silica-induced mitochondrial damage. More importantly, the M1 polarization of macrophage was depressed with the co-treatment of Que and silica, wherein the inflammatory response and pulmonary fibrosis were also mitigated without obvious damage to vital organs. In conclusion, these findings proved that silica leads to mitochondrial damage, thereby evoking pyroptosis and promoting macrophage M1 polarization. Que could bind to TOM70 and restore its function, suppressing mitochondrial damage and pyroptosis, and depolarizing macrophages to reduce fibrosis, which provides a promising strategy for silicosis treatment in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Despite the exceptional biocompatibility and degradability of Poly ( L -lactic acid) (PLLA), its brittleness, low melting strength, and poor bone induction makes it challenging to utilize for bone repair. This study used a simple, efficient solid hot drawing (SHD) method to produce high-strength PLLA, using supercritical CO 2 (SC-CO 2 ) foaming technology to give PLLA a bionic microporous structure to enhance its toughness, while precisely controlling micropore homogeneity and improving the melt strength by using Polydimethylsiloxane (PDMS). This PDMS-regulated oriented microporous structure resembled that of natural bone, displaying a maximum tensile strength of 165.9 MPa and a maximum elongation at break of 164.2 %. Furthermore, this bionic structure promoted the polarization of mouse bone marrow macrophages (iBMDM), exhibiting a simultaneous pro- and anti-inflammatory effect. This structure also contributed to the adhesion and growth of mouse embryonic fibroblasts (NIH-3 T3), promoting osteogenic differentiation, which paved the way for developing degradable PLLA bone-repair load-bearing materials., 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.)

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height 2 (Ht 2 ) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht 2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer (CRC) is a major threat to human health, as it is one of the most common malignancies with a high incidence and mortality rate. The cancer cell membrane (CCM) has significant potential in targeted tumor drug delivery due to its membrane antigen-mediated homologous targeting ability. The endoplasmic reticulum (ER) in cancer cells plays a crucial role in apoptosis and ferroptosis. In this study, we developed an ER-targeted peptide-modified CCM-biomimetic nanoparticle-delivered lovastatin (LOV) nanomedicine delivery system (EMPP-LOV) for cancer treatment. Both in vitro and in vivo experiments demonstrated that EMPP could effectively target cancer cells and localize within the ER. EMPP-LOV modulated ER function to promote apoptosis and ferroptosis in tumor cells. Furthermore, synergistic antitumor efficacy was observed in both in vitro and in vivo models. EMPP-LOV induced apoptosis in CRC cells by over-activating endoplasmic reticulum stress and promoted ferroptosis by inhibiting the mevalonate pathway, leading to synergistic tumor growth inhibition with minimal toxicity to major organs. Overall, the EMPP-LOV delivery system, with its subcellular targeting capability within tumor cells, presents a promising therapeutic platform for CRC treatment., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to utilize blueberry pectin and calcium chloride to design a gel network structure for loading nut oils (peanut and walnut oil, respectively). The optimization of emulsion gel preparation was conducted through orthogonal experiments, utilizing the oil-holding ratio and gel strength as critical indicators. The emulsion gel was applied to the ice cream production. It was revealed that the peroxide value of the nut oil emulsion gels was significantly lower than that of nut oils. Both nut oil emulsion gel ice creams exhibited higher expansion rates, lower melting rates, and decreased hardness than the nut oil ice creams. Notably, walnut oil emulsion gel ice cream demonstrated a melting rate similar to traditional butter-based ice cream. Emulsion gel ice cream has higher fat globule instability and viscosity. Overall, the comprehensive emulsion gel ice cream indicators were comparable to conventional butter ice cream and notably superior to peanut and walnut oil ice cream. Using emulsion gel as a fat substitute in ice cream was feasible. The implications of these results were significant for advancing the utilization of nut oil emulsion gel within the ice cream industry., 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.)

A thermosensitive and injectable hydrogel composed of chitosan (CS), chitosan biguanide hydrochloride (CSG) and collagen (CO) could embed umbilical cord mesenchymal stem cells (UC-MSCs), then was applied for the type 2 diabetes mellitus (T2DM) treatment in vivo. UC-MSCs could adhere well on CS/CSG/CO hydrogel surface and cell division could be clearly observed. Especially, UC-MSCs maintained alive till they grew in CS/CSG/CO hydrogel for 8 days, while the amount of UC-MSCs was limited due to the steric hindrance in hydrogel. To T2DM mice contrastive treatment by intraperitoneal injection for thirteen weeks, UC-MSCs + Hydrogel group could improve the impaired glucose tolerance, maintain glucose homeostasis in vivo, and restore islet morphology for T2DM mice. The immunofluorescence staining and western blot experiments further displayed that both the nuclear antigen Ki67 for cell proliferation and pancreatic duodenal homeobox-1 (Pdx1) expression in UC-MSCs + Hydrogel group were significantly higher than the expressions in untreated T2DM group and treated UC-MSCs + PBS group, which indicated that UC-MSCs + Hydrogel elevated β cell transcriptional activity. Moreover, the positivity rates of iNOS and CD163 in UC-MSCs + Hydrogel group were generally decreased and increased, respectively, compared to those in untreated T2DM group and treated UC-MSCs + PBS group. It displayed that UC-MSCs + Hydrogel could reduce M1 macrophage expression and increase M2 macrophage polarization in T2DM mice., 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.)

Low-temperature cooking causes flavor weakness while improving the texture and digestive properties of meat. To enhance the flavor of low-temperature cooked Tibetan pork, samples were cooked at low-temperature with or without ultrasound-assisted (UBTP, BTP) for different times (30 min, 90 min) and then analyzed using GC-MS and LC-MS. The results showed that ultrasound-assisted cooking caused a significant increase in lipid oxidation by 9.10% in the early stage of the treatment. Additionally, at the later stage of ultrasound-assisted processing, proteins were oxidized and degraded, which resulted in a remarkable rise in the protein carbonyl content by 6.84%. With prolonged effects of ultrasound and low-temperature cooking, the formation of phenylacetaldehyde in UBTP-90 sample originated from the degradation of phenylalanine through multivariate statistics and correlation analysis. Meanwhile, trans, cis-2,6-nonadienal and 1-octen-3-one originated from the degradation of linolenic acid and arachidonic acid. This study clarified the mechanism of ultrasound-assisted treatment improving the flavor of low-temperature-cooked Tibetan pork based on the perspective of lipids and proteins oxidation, providing theoretical supports for flavor enhancement in Tibetan pork-related products., 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.)

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α., (© 2024. The Author(s).)

Purpose: Tibetan patients undergoing total knee arthroplasty (TKA) have greater fluctuations in perioperative haemoglobin levels and blood hypercoagulability. This study was to investigate whether ethnicity and altitude affect perioperative blood loss and the risk of complications after TKA., Methods: We retrospectively enrolled 1,116 patients undergoing TKA for knee osteoarthritis at our hospital between January 2016 and September 2021. We divided patients into four groups according to whether they were of Tibetan or Han ethnicity and whether they lived above or below 2500 m above sea level. Primary outcomes were total, intraoperative, and hidden blood losses, while secondary outcomes were complications and homologous transfusion. Factors associated with increased blood loss were analyzed by multivariate regression., Results: Total blood loss was higher among patients residing at high altitude compared with lower altitude, whether they were of Han (794.6 mL vs. 667.2 mL, P = 0.020) or Tibetan (904.4 mL vs. 663.8 mL, P < 0.001). Total blood loss was similar between the two ethnic groups at the same altitude. Altitude, but not Tibetan ethnicity, remained associated with increased blood loss after being analyzed by multivariate regression. Complications among the four groups were generally similar, although the frequency of calf muscular venous thrombosis was higher among Tibetan patients, while the frequency of blood transfusion was higher among Han subjects., Conclusions: Our findings indicate that residence at high altitude, but not ethnicity, may contribute to increased total blood loss during TKA. Thrombotic complications were more frequent among Tibetan than Han patients., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Background: Pulmonary embolism (PE) is a common and potentially fatal disease, with differences in mortality rates among PE patients of different sexes. This study aims to investigate the disparities in clinical manifestations and in-hospital mortality rates between sexes in PE patients, as well as the association of clinical symptoms with in-hospital mortality., Methods: We analyzed data from the China pUlmonary thromboembolism REgistry Study (CURES), a nationwide, multicenter, prospective registry focusing on patients with acute PE. Using propensity score matching (PSM) to pair male and female patients with PE, we explored the correlation between clinical symptoms and in-hospital mortality through multivariable regression analysis., Results: A total of 15,203 patients with acute PE were enrolled, and 380 died during hospitalization. The incidence of chest pain, hemoptysis, and palpitations was significantly higher in males compared to females. The incidence of dyspnea, fever, and syncope was higher in females. Hemoptysis and dyspnea were associated with increased in-hospital mortality in males, whereas dyspnea, fever, and palpitations were linked to higher mortality in females. Overall, males exhibited a higher in-hospital mortality than females (2.9 % vs. 2.1 %, p = 0.002). After matching 13,130 patients using the PSM method, the mortality rate of males remained higher than that of females (2.7 % vs. 2.1 %, p = 0.020)., Conclusions: Our study demonstrates that male patients with PE have a higher risk of in-hospital mortality than females. Significant differences in clinical symptoms between sexes are associated with increased mortality risk, emphasizing the need for clinical awareness., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Wound infection resulting in delayed wound healing and wound deterioration remains a clinical challenge. Recently, multifunctional hydrogel dressing was a promising strategy which has attracted wide attention in preventing wound infection and promoting wound healing. In this study, a hybrid hydrogel made of gelatin (GL), tannic acid (TA), oxidized sodium alginate (OSA), and zinc oxide nanoparticles (ZnO NPs) was prepared mainly by double network cross-linking approach, named tannic acid-gelatin/oxidized sodium alginate/zinc oxide (TA-GL/OSA/ZnO). The composite hydrogels exhibited improved mechanical properties, which provided by TA modified the structure of GL network, Schiff base reaction between GL and OSA, and the strengthening effect of ZnO NPs. Meanwhile, the composite hydrogel showed high antibacterial activity against Staphylococcus aureus (S. aureus) (97.8 % ± 0.9 %) and Escherichia coli (E. coli) (96.6 % ± 1.2 %), attributed to the synergistic effect of TA and ZnO NPs. Furthermore, benefiting from the good antioxidative properties of TA, the sustain-released Zn 2+ with the good capability to kill bacteria, and promoting the regeneration of skin epithelial tissues in BALB/c mice constantly, the multifunctional hydrogel had a significant therapeutic effect on wound healing and broad application prospects., 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.)

This study aims to investigate the clinical characteristics of infections following induction chemotherapy for acute myeloid leukemia (AML) in children and identify risk factors associated with severe infections. Newly diagnosed children with AML treated at the Hematology Oncology Center of Beijing Children's Hospital affiliated to Capital Medical University (referred to as the "Beijing ward") and Baoding Hospital of Beijing Children's Hospital (referred to as the "Baoding ward") between November 2019 and August 2022 were enrolled. The diagnosis and treatment of the patients were carried out in accordance with the CCLG-AML 2019 protocol. Their essential information and infection-related indicators were collected. The various indicators between the two centers were compared. The incidence of infection in children with AML was 100%, with a severe infection rate of 15.3% and an infection-related mortality rate of 2.4%. Respiratory infections accounted for 39.7% of all infections events, and unspecified site infection for 32.2%. Bacterial infections were predominant at 51.2%. The bed unit area (BUA) varied significantly with 4.1 m 2 in the Beijing ward and 10 m 2 in the Baoding ward. Significant differences were observed in gastrointestinal infections (P < 0.001) and severe infections (P = 0.014) between the two wards. Several factors were identified as risk factors for severe infections, including BUA difference (OR = 4.353, 95% CI: 1.078-17.578), time of entering neutropenia phase after chemotherapy (OR = 6.369, 95% CI: 1.713-23.675) and bloodstream infection (OR = 7.466, 95% CI: 1.889-29.507). Respiratory tract infections and infections of unspecified site are most common during induction phase for pediatric AML. Bacteria, especially G - bacteria, are the leading pathogens. Risk factors for severe infections include a small BUA, entering neutropenia phase ≤ 5.5 days after chemotherapy, and bloodstream infection. Recognizing these risk factors can aid in the early identification and intervention of severe infections., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR)., Methods: CD4 + T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4 + T cells. An AR mouse model was established using the ovalbumin-alum protocol., Results: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4 + T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4 + T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4 + T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4 + T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4 + T cells effectively attenuated experimental AR in mice., Conclusions: Elevated amounts of telomerase in CD4 + T cells were found in CD4 + T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The regulatory mechanisms underlying bone metastasis in lung adenocarcinoma (LUAD) are not yet fully understood despite the frequent occurrence of bone involvement. This study aimed to examine the involvement and mechanism of integrin subunit beta 3 (ITGB3) in the process of LUAD bone metastasis. Our findings indicate that ITGB3 facilitates the migration and invasion of LUAD cells in vitro and metastasis to the bone in vivo. Furthermore, ITGB3 stimulates osteoclast production and activation, thereby expediting osteolytic lesion progression. Extracellular vesicles (EVs) isolated from the conditioned medium (CM) of LUAD cells overexpressing ITGB3 determined that ITGB3 facilitates osteoclastogenesis and enhances osteoclast activity by utilizing EVs-mediated transport to RAW264.7 cells. Our in vivo findings demonstrated that ITGB3-EVs augmented the population of osteoclasts, thereby establishing an osteoclastic pre-metastatic niche (PMN) conducive to the colonization and subsequent growth of LUAD cells in the bone. ITGB3 is enriched in serum EVs of patients diagnosed with LUAD bone metastasis, potentially facilitating osteoclast differentiation and activation in vitro. Our research illustrates that ITGB3-EVs derived from LUAD cells facilitate osteoclast differentiation and activation by modulating the phosphorylation level of p38 MAPK. This process ultimately leads to the generation of osteolytic PMN and accelerates the progression of bone metastasis., (© 2024 Wiley Periodicals LLC.)

Temporal Knowledge Graphs (TKGs) enable effective modeling of knowledge dynamics and event evolution, facilitating deeper insights and analysis into temporal information. Recently, extrapolation of TKG reasoning has attracted great significance due to its remarkable ability to capture historical correlations and predict future events. Existing studies of extrapolation aim mainly at encoding the structural and temporal semantics based on snapshot sequences, which contain graph aggregators for the association within snapshots and recurrent units for the evolution. However, these methods are limited to modeling long-distance history, as they primarily focus on capturing temporal correlations over shorter periods. Besides, a few approaches rely on compiling historical repetitive statistics of TKGs for predicting future facts. But they often overlook explicit interactions in the graph structure among concurrent events. To address these issues, we propose a PotentiaL concurrEnt Aggregation and contraStive learnING (PLEASING) method for TKG extrapolation. PLEASING is a two-step reasoning framework that effectively leverages the historical and potential features of TKGs. It includes two encoders for historical and global events with an adaptive gated mechanism, acquiring predictions with appropriate weight of the two aspects. Specifically, PLEASING constructs two auxiliary graphs to capture temporal interaction among timestamps and correlations among potential concurrent events, respectively, enabling a holistic investigation of temporal characteristics and future potential possibilities in TKGs. Furthermore, PLEASING incorporates contrastive learning to strengthen its capacity to identify whether queries are related to history. Extensive experiments on seven benchmark datasets demonstrate the state-of-the-art performances of PLEASING and its comprehensive ability to model TKG semantics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a representative gas of food spoilage, the development of rapid hydrogen sulfide (H 2 S) analysis strategies for food safety control is in great demand. Despite traditional methods for H 2 S detection possessing great achievements, they are still incapable of meeting the requirement of portability and quantitative detection at the same time. Herein, a nanozyme catalysis pressure-powered sensing platform that enables visual quantification with the naked eye is proposed. In this methodology, Pt nanozyme inherits the catalase-like activity to facilitate the decomposition of H 2 O 2 to O 2 , which can significantly improve the pressure in the closed container, further pushing the movement of indicator dye. Furthermore, H 2 S was found to effectively inhibit the catalytic activity of Pt nanozyme, indicating that the catalase-like activity of PtNPs may be regulated by varying concentrations of H 2 S. Therefore, by utilizing a self-designed pressure-powered microchannel device, the concentration of H 2 S was successfully converted into a distinct signal variation in distance. The effectiveness of the as-designed sensor in assessing the spoilage of red wine by H 2 S determination has been demonstrated. It exhibits a strong correlation between the change in dye distance and H 2 S concentration within the range of 1-250 μM, with a detection limit of 0.17 μM. This method is advantageous as it enhances the quantitative detection of H 2 S with the naked eye based on the portable pressure-powered sensing platform, as compared to traditional H 2 S biosensors. Such a pressure-powered distance variation platform would greatly broaden the application of H 2 S-based detection in food spoilage management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The degenerative process of follicular atresia in hens naturally commences in granulosa cells, significantly impacting laying hens' reproductive performance. Past studies suggested that granulosa cell autophagy and apoptosis work together to cause follicular atresia. Recent research indicates that miRNA regulates granulosa autophagy and apoptosis, which contributes to the development of follicular atresia. However, the role of miR-302c-3p in follicular atresia and development remains unclear. In this study with the RNA-seq approach, we found that miR-302c-3p expression was significantly decreased in atrophic follicles, suggesting its involvement in the follicular atresia process. Following this, we performed in vitro studies to confirm that miR-302c-3p inhibits autophagy and apoptosis in chicken granulosa cells. Mechanistically, LATS2 is considered as the putative target gene of miR-302c-3p, and it has been demonstrated that LATS2 exerts a positive regulatory role in the modulation of autophagy and apoptosis in chicken granulosa cells. Furthermore, we verified the regulatory function of miR-302c-3p in chicken granulosa cells via the LATS2-YAP signaling pathway. Our results collectively demonstrates that miR-302c-3p targets LATS2 to modulate the YAP signaling pathway, impacting autophagy and apoptosis in granulosa cells leading to follicular atresia., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartially of the research reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Generating polar map (PM) from [ 68 Ga]Ga-DOTA-FAPI-04 PET images is challenging and inaccurate using existing automatic methods that rely on the myocardial anatomical integrity in PET images. This study aims to enhance the accuracy of PM generated from [ 68 Ga]Ga-DOTA-FAPI-04 PET images and explore the potential value of PM in detecting reactive fibrosis after myocardial infarction and assessing its relationship with cardiac function., Methods: We proposed a deep-learning-based method that fuses multi-modality images to compensate for the cardiac structural information lost in [ 68 Ga]Ga-DOTA-FAPI-04 PET images and accurately generated PMs. We collected 133 pairs of [ 68 Ga]Ga-DOTA-FAPI-04 PET/MR images from 87 ST-segment elevated myocardial infarction patients for training and evaluation purposes. Twenty-six patients were selected for longitudinal analysis, further examining the clinical value of PM-related imaging parameters., Results: The quantitative comparison demonstrated that our method was comparable with the manual method and surpassed the commercially available software-PMOD in terms of accuracy in generating PMs for [ 68 Ga]Ga-DOTA-FAPI-04 PET images. Clinical analysis revealed the effectiveness of [ 68 Ga]Ga-DOTA-FAPI-04 PET PM in detecting reactive myocardial fibrosis. Significant correlations were demonstrated between the difference of baseline PM FAPI% and PM LGE%, and the change in cardiac function parameters (all p < 0.001), including LVESV% (r = 0.697), LVEDV% (r = 0.621) and LVEF% (r = -0.607)., Conclusion: The [ 68 Ga]Ga-DOTA-FAPI-04 PET PMs generated by our method are comparable to manually generated and sufficient for clinical use. The PMs generated by our method have potential value in detecting reactive fibrosis after myocardial infarction and were associated with cardiac function, suggesting the possibility of enhancing clinical diagnostic practices., Trial Registration: ClinicalTrials.gov (NCT04723953). Registered 26 January 2021., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

ELISA has become the gold standard for detecting harmful substances due to its specific antibody recognition and sensitive enzyme-catalyzed reactions. In this study, multifunctional magnetic Prussian blue nanolabels (MPBNs) were synthesized using a simple gentle two-step method to achieve a dual-readout mode. The MPBNs provide a sensitive colorimetric signal by efficiently catalyzing the oxidation of TMB and exhibit prominent photocatalytic degradation activity towards Rhodamine B (RhB). Supplemented by the quenching effect of oxTMB, the fluorescence was enabled to serve as a sensitive second signal. The magnetic property of the labels facilitates the separation and enrichment of the target, thereby improving sensitivity. Utilizing the versatile MPBNs, the visual limit of detection (vLOD) for Staphylococcus aureus is as low as 100 CFU/mL, with a quantitative analysis range of 10 2 -10 8  CFU/mL. The introduction of photocatalytic reactions into immunoassay has opened up a new signal response system with strong momentum for development and application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Increasing the perceived need for CRC screening can facilitate undertaking CRC screening. This study aims to identify factors associated with the need for CRC screening in rural populations., Design: A cross-sectional online survey., Setting: The survey was conducted in June - September 2022 in the rural areas of Alaska, Idaho, Oregon, and Washington, US., Subjects: The subjects of this study were 250 adults (completion rate: 65%) aged 45-75 residing in rural Alaska, Idaho, Oregon, and Washington., Measures: Perceived need for CRC screening, internet usage for health purposes, demographics, and intrapersonal, interpersonal, community, and environmental characteristics., Results: Perceived need for CRC screening were negatively associated with patient-provider miscommunication ( β = -.23, P < .001) and perceived discrimination ( β = -.21, P < .001), cancer fatalism (β = -.16, P < .05), individualism ( β = -.15, P < .05), and dependence on community ( β = -.11, P < .05), but positively with compliance with social norms ( β = .16, P < .05), trust in health care providers ( β = .16, P < .05), knowledge about colorectal cancer ( β = .12, P < .05)., Conclusions: Our study showed potential individual and situational characteristics that might help increase colorectal cancer screening. Future efforts might consider addressing discrimination in health care settings, improving patient-provider communication, and tailoring messaging to reflect the rural culture., 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.

Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease that affects degenerative joints. Currently, there is no treatment available to modify the progression of OA. The pathogenesis of OA is significantly linked with oxidative stress and pyroptosis. Astaxanthin (Ast) is a natural ketocarotenoid pigment with potent antioxidant activity and is shown to effectively alleviate cartilage damage in OA. However, its bioavailability is greatly limited due to poor water solubility, high sensitivity to light, temperature, and pH. In this study, Ast-loaded tetrahedral framework nucleic acids (tFNAs) or tFNA/Ast complexes (TAC) for Ast delivery are developed. Compared with free Ast and tFNA alone, TAC exhibits improved drug stability and cellular uptake. Most importantly, TAC effectively protects chondrocytes against oxidative stress-induced pyroptosis while promoting extracellular matrix anabolism by chondrocytes, and ultimately alleviates cartilage damage in a mouse destabilization of the medial meniscus (DMM) model. Thus, TAC holds great promise for the treatment of OA patients., (© 2024 Wiley‐VCH GmbH.)

Fluoride pollution and water scarcity are urgent issues. Reducing fluoride concentration in water is crucial. Kaolinite has been used to study adsorption and fluoride removal in water and to characterize material properties. The experimental results showed that the adsorption capacity of kaolinite decreased with increasing pH. The highest adsorption of fluoride occurred at pH 2, with a capacity of 11.1 mg/g. The fluoride removal efficiency remained high after four regeneration cycles. The fitting results with the Freundlich isotherm model and the external diffusion model showed that the non-homogeneous adsorption of kaolinite fit the adsorption behavior better. Finally, the adsorption mechanism was analyzed by FT-IR and XPS. The binding energies of various adsorption sites and the chemical adsorption properties of atomic states were discussed in relation to DFT calculations. The results showed that Al and H sites were the main binding sites, and the bonding stability for different forms of fluoride varies, with the size of Al-F (-7.498 eV) > H-F (-6.04 eV) > H-HF (-3.439 eV) > Al-HF (-3.283 eV). Furthermore, the density of states and Mulliken charge distribution revealed that the 2p orbital of F was found to be active in the adsorption process and was the main orbital for charge transfer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes (homologs) together for their faithful segregation, while promoting genetic diversity of the progeny. The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes. Environmental factors, especially temperature, also play an important role in modulating crossovers. However, it is unclear how temperature affects crossovers. Here, we examined the distribution of budding yeast axis components (Red1, Hop1, and Rec8) and the crossover-associated Zip3 foci in detail at different temperatures, and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers. Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci. Most importantly, temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils. These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization. These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic recombination and chromosome organization, with important implications for evolution and breeding., (© 2024. Science China Press.)