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Studies of laminopathy-based progeria offer insights into aging-associated diseases and highlight the role of LMNA in chromatin organization. Mandibuloacral dysplasia type A (MAD) is a largely unexplored form of atypical progeria that lacks lamin A post-translational processing defects. Using iPSCs derived from a male MAD patient carrying homozygous LMNA p.R527C, premature aging phenotypes are recapitulated in multiple mesenchymal lineages, including mesenchymal stem cells (MSCs). Comparison with 26 human aging MSC expression datasets reveals that MAD-MSCs exhibit the highest similarity to senescent primary human MSCs. Lamina-chromatin interaction analysis reveals reorganization of lamina-associating domains (LADs) and repositioning of non-LAD binding peaks may contribute to the observed accelerated senescence. Additionally, 3D genome organization further supports hierarchical chromatin disorganization in MAD stem cells, alongside dysregulation of genes involved in epigenetic modification, stem cell fate maintenance, senescence, and geroprotection. Together, these findings suggest LMNA missense mutation is linked to chromatin alterations in an atypical progeroid syndrome., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Herein, a new strategy is employed to build a controllable thermal-coupled charge ionization (TCCI) device to elucidate the desorption-ionization mechanism of plasma ion sources. Efficient synergistic desorption and ionization are achieved within the TCCI device by independently controlling the desorption temperature and plasma charges. The TCCI device efficiently ionizes samples using abundant free electrons, charges, and active species from arc plasma. The coexistence of free electrons and hydroxide radicals confers redox capability to the TCCI system, implying the presence of a unified redox mechanism even when the arc plasma is transmitted through a metal conductor over a distance. In addition, molecular ions of the analytes facilitate the differentiation between primary and secondary amines during their analysis. Notably, the TCCI device enables a switch between hard and soft ionization by adjusting the thermal desorption temperature. At high temperatures (>400 °C), the TCCI device exhibits hard ionization characteristics, producing fragment ions beneficial for isomer discrimination. The TCCI mass spectrometry exhibits robust performance in terms of sensitivity and accuracy for detecting antibiotics and sterols in saline solutions, achieving linearity with correlation coefficients ≥0.99 and excellent reproducibility. The successful analysis of seven pharmaceuticals and four sterols in complex matrices using the TCCI device demonstrates its excellent salt and matrix tolerance. Overall, the TCCI device, with its independent control over thermal desorption and arc plasma, achieves efficient synergistic desorption and ionization, overcoming limitations in existing ionization technologies and contributing to the study of gas-phase ion dynamics and mechanisms.

Zinc-ion capacitors (ZICs) have attracted great attention due to a series of advantages. However, the cathode materials are still the bottleneck for high-performance ZICs to be achieved. Therefore, ZIF-8-derived porous carbons are one of the most promising candidates but ZIF-8 nanoparticles with different sizes exhibited various electrochemical performances in ZICs. Herein, a series of monodispersed ZIF-8 nanoparticles are first prepared by a temperature-controlled process to fabricate the corresponding ZIF-8-based porous carbon nanoparticles with pre-designed sizes. The as-prepared materials have been tested as cathode materials in ZICs. Thus, their size effect allowed us to disclose its correlation with other factors such as ion transport/storage and capacitance. The results reveal that the optimal-sized porous carbon particles can effectively shorten the ion transport distance and accelerate the ion diffusion rate, resulting in lower electrical resistance, larger ion diffusion coefficients, and faster electron transport. The presented findings can facilitate the design of new advanced cathode materials paving the way for the development of high-performance cathode materials for ZICs in the future., (© 2024 Wiley‐VCH GmbH.)

Studies on the interaction among genetic susceptibility, blue space exposure, and rheumatoid arthritis (RA) risk have been lacking. Therefore, we examined the association between blue space exposure and RA incidence and assess the modifying effect of genetic susceptibility and air pollutants. Form the UK Biobank, 322,783 participants without RA were enrolled in this study. The association between blue space exposure and RA incidence was estimated using a cox proportional hazards model. The combined effect of blue space and genetic factors on the risk of RA was further evaluated. The polygenic risk score (PRS) for RA was calculated to represent individual genetic risk, and the potential modification effect of air pollution on the relationship between blue space, PRS, and RA were explored. During a median follow-up of 12.4 years, 3659 RA cases were identified. A 10 % increase in blue space 300 m was associated with a 22.6 % reduction in RA incidence (HR=0.774, 95 % CI: 0.670, 0.895), exhibiting a consistent downward trend in the exposure-response curve. A high PRS was an independent risk factor for RA (HR=1.393, 95 % CI: 1.347, 1.439). The associations between blue space exposure, PRS, and the risk of RA were dose-dependent, with the lowest risk observed among those with high levels of blue space and lower PRS (HR bluespace300m =0.501, 95 % CI: 0.431, 0.583; HR bluespace1000m =0.476, 95 % CI: 0.408, 0.555). Interaction analysis indicated that increased concentrations of air pollutants strengthened the relationship between PRS and RA. Blue space exposure mitigated the risk of RA development, particularly in individuals with low genetic risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The identification and quantification of melatonin (MT) are crucial for early diagnosis of disorders associated with circadian rhythm disruption. Herein, novel blue-emissive carbon dots (BCDs) were synthesized through an improved hydrothermal treatment using serine and malic acid as reductant and carbon source. The excellent optical properties of the as-obtained BCDs were used for ratiometric sensing by strategically constructing a MT sensing system integrating BCDs with C 3 N 4 nanosheets loaded with platinum/ruthenium nanoparticles (PtRu/CN). In this system, H 2 O 2 activated the peroxidase-like activity of PtRu/CN to generate •OH and 1 O 2 for oxidizing the colorless o-phenylenediamine (OPD) into yellow 2,3-diaminophenazine (DAP) with fluorescence emission at 565 nm. Concurrently, the fluorescence emission of BCDs at 439 nm was quenched by the generated DAP via the static quenching and inner filter effect (IFE) process. However, MT rapidly scavenged the generated free radicals to reverse the ratio fluorescence signal. The developed BCDs/PtRu/CN/OPD/H 2 O 2 sensing platform enabled quantitative analysis of MT at concentrations ranging from 0.06 to 600 μmol/L with a low detection limit of 23.56 nmol/L. Moreover, smartphone-based RGB sensing of MT was successfully developed for rapid visualization and portable processing. More broadly, novel insights into the preparation of carbon dots with sensitive fluorescence sensing properties were presented, promising for future considerations., 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: While measuring meniscal extrusion quantitatively is an early risk factor for knee osteoarthritis (KOA), the biomechanics involved in this process are not well understood. This study aimed to investigate the effects of varying degrees of medial and lateral meniscal extrusion and their material softening on knee osteoarthritis progression., Methods: Finite element analysis (FEA) was utilized to simulate varying degrees of meniscal extrusion (1-5 mm) in 72 knee joint models, representing progressive meniscal degeneration and material softening due to injury. Changes in von Mises stress of the cartilage and menisci and the load distribution on the tibial plateau's meniscus and cartilage were studied under balanced standing posture in both healthy and injured knees, and statistical analysis was performed using Spearman correlation., Results: Compared to healthy knees, peak stress in medial compartment tissues increased by over 40% with 4 mm of medial meniscus extrusion, and in lateral compartment tissues with 2 mm of lateral meniscus extrusion. Meniscus extrusion reduced the contact load between the meniscus and femoral cartilage but increased it between the tibial and femoral cartilages, with a maximum increase up to fivefold. Spearman correlation analysis indicated that meniscal extrusion significantly affected peak stress and contact loads in the respective knee compartment (p < 0.001), with a lesser impact on the opposite compartment. Notably, medial meniscal extrusion also significantly increased peak stress in the lateral tibial cartilage (p < 0.05)., Conclusions: The quantitative analysis revealed that meniscal extrusion significantly affected the biomechanics of soft tissues within the same compartment, with limited impact on the opposite side. Specifically, Medial extrusion beyond 4 mm significantly affected the biomechanics of the medial compartment, while lateral extrusion over 2 mm had a similar impact on the lateral compartment. Meniscal softening, without altering joint contact characteristics, primarily affected the biomechanics of the meniscus itself, with minimal impact on other soft tissues., Competing Interests: Declarations Ethics approval and consent to participate This study was carried out in accordance with relevant guide‑lines and regulations and was approved by the committee of The Fifth Affiliated Hospital of Guangzhou Medical University. All the participants provided written informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Clinically used amino-ester and amino-amide local anesthetics, such as bupivacaine and lidocaine, face two primary challenges: inadequate duration of action and nonselective action on both sensory and motor neurons, resulting in motor function loss alongside pain relief. In this work, we developed capsaicin-loaded melanin nanoparticles (Cap-MNPs) to address these two challenges. Capsaicin selectively acts on sensory neurons without affecting motor neurons, thereby achieving nociceptive-selective nerve blockade. Melanin is known for its exceptional biocompatibility, biodegradability, and abundance in pigmented human tissue. Melanin's inherent chemical structure and hydrophobic nature enable the encapsulation and sustained release of amino-ester and amino-amide local anesthetics with aromatic rings through π-π interactions and hydrophobic interactions. The drug loading efficiency of Cap-MNPs was 82.99 ± 1.55%, the drug loading capacity was 67.47 ± 4.24%, and capsaicin was continuously released for more than 360 h. In rats, a single injection of Cap-MNPs containing 8.04 mg of capsaicin produced a sciatic sensory nerve block lasting for 6 h without causing any local toxicity and capsaicin-related systemic toxicity. Cap-MNPs show promise as clinically useful therapeutics for pain management.

Achieving anion capture with metal-organic frameworks (MOFs) usually relies on anion exchange reactions. Here, we report the direct visual imaging of the anion binding process within a charge-neutral Bi-based MOF (UU-200) in water at the single-particle level using in situ dark-field optical microscopy. Notably, an unexpected anion-induced structural shrinkage of UU-200 is mapped, and concentration-dependent responses are applied to determine the association constants. The resulting anion affinity is correlated with its basicity, demonstrating that charge-dense anions such as F - , SO 3 2- , and SO 4 2- feature strong binding with the UU-200 framework. Moreover, the unusual anion binding processes are identified as the C-H hydrogen-bonding interactions between electron-deficient hydrogen atoms on the channel wall and negatively charged anions by combining imaging results, nuclear magnetic resonance spectroscopy, and theoretical simulation. These discoveries reshape and strengthen our fundamental understanding of the anion capture within MOFs, favoring the rational design of MOF-based anion receptors.

Astringency, a sensory experience causing mouth dryness, significantly impacts the taste of foods such as wine and tea, and astringent molecules may exhibit antibacterial properties. Traditional methods for predicting astringency are costly, and the connection between astringency and antibacterial activity remains largely unexplored. In this study, we present a pioneering computational approach that includes: (1) the creation of the first comprehensive astringency database comprising 238 molecules; (2) the development of a Ligand-Based Prediction (LBP) framework that combines large language models, deep learning, and traditional machine learning for enhanced molecular and peptide prediction; (3) an astringency predictor achieving 0.95 accuracy and 0.90 AUC, validated through electronic tongue measurements; (4) antibacterial predictors for molecules and peptides with accuracies of 0.92 and 0.88, respectively, revealing that 51 % of astringent molecules possess antibacterial properties; (5) accessibility of these predictors via the AstringentPD and ABPD web servers. This work not only enhances the understanding of taste-related molecules but also elucidates the relationship between astringency and antibacterial properties, setting the stage for future explorations in food science and medicinal applications., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previous studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk., Methods: This retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes., Results: A total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31-30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09-13.92; all-cause mortality, HR 4.56, 95% CI 2.97-7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes., Conclusions: The classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine., (© 2024. The Author(s).)

The recent advances in micromanufacturing have been pushing boundaries of the new generation of semiconductor devices, which, in the meantime, brings new challenges in the material and structural characterization - a key step to ensure the device quality through the micromanufacturing process. An ultrafast laser-enable optoacoustic characterization methodology is developed, targeting in situ calibration and delineation of the three-dimensional (3-D), nanoscopic interior features of opaque semiconductor chips. With the guidance of ultrafast electron-phonon coupling effect and velocity-perturbated optical interference, a femtosecond-laser pump-probe set-up based on Sagnac interferometer is configured to generate and acquire picosecond ultrasonic bulk waves (P-UBWs) traversing the microchips. The interior features of the microchips shift the phase of acquired P-UBW signals, reflected in the perturbed probe laser beam. The phase shifts are calibrated to compute signal correlation of P-UBW signals between different acquiring positions, whereby to delineate the interior features in an intuitive manner. The approach is experimentally validated by characterizing nanoscopic, invisible interior aurum(Au)-gratings with periodically varied depths in typical microchips. Results highlight that the 3-D nanoscopic features of the microchips can be revealed with a microscopic and a nanoscopic spatial resolution, respectively along the transverse and depth directions of the chip, where the Au-gratings become "visible" with a depth variance of a few tens of nanometers only. This proposed approach has provided a fast, nondestructive approach to "see" through an opaque microchip with a nanoscopic resolution., 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.)

There is limited evidence regarding the effects of long-term exposure to PM 2.5 constituents on the risk of arthritis and rheumatoid arthritis, and the interaction between PM 2.5 and green space remains unclear. This study examined the relationship between long-term exposure to PM 2.5 constituents and the risk of arthritis and rheumatoid arthritis, with the exposure period extending from recruitment until self-reported outcomes, death, loss to follow-up, or end of follow-up. Additionally, the study assessed whether there was an interactive effect between PM 2.5 and green space on these risks. We gathered cohort data on 18,649 individuals aged ≥45 years. We applied generalized linear mixed-effects models to estimate the effects of PM 2.5 constituents, NDVI, and their interaction on arthritis and rheumatoid arthritis. The quantile g-computation and weighted quantile sum regression model were applied to estimate the combined effect of PM 2.5 constituents. Our results showed that exposure to single and mixed PM 2.5 constituents adversely affected arthritis and rheumatoid arthritis, and was mainly attributed to the black carbon component. We observed "U" or "J" shaped exposure-response curves for the effects of PM 2.5 , OM, NO 3 - and NH 4 + exposure on the development of arthritis/rheumatoid arthritis. Additionally, the odds ratio of arthritis for per interquartile range (IQR) increase in PM 2.5 was 1.209 (95% CI:1.198, 1.221), per 0.1-unit decrease in NDVI was 1.091 (95% CI:1.033, 1.151), and the interaction term was 1.005 (95% CI:1.002, 1.007). These findings flesh out the existing evidence for PM 2.5 constituents, NDVI and arthritis, rheumatoid arthritis, but the underlying mechanisms still require further exploration., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Author(s). GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

In the present study, we presented the detailed procedure and experience of endoscope-assisted transoral procedure of accessory parotid gland (APG) tumor resection. The surgical steps and tips were described and summarized clearly in our video. Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

FGFR has been considered a crucial oncogenic driver and promising target for cancer therapy. Herein, we reported the design and synthesis of 3-amino- N -(3,5-dihydroxyphenyl)-6-methylpyrazine-2-carboxamide derivatives as novel FGFR inhibitors. SAR exploration led to the identification of 18i as a pan-FGFR inhibitor with favorable in vitro activity against FGFR1-4. Moreover, 18i blocked the activation of FGFR and downstream signaling pathways at the submicromolar level and exhibited potent antitumor activity in multiple cancer cell lines with FGFR abnormalities. Molecular docking was performed to investigate the possible binding modes of 18i within the binding site of FGFR2. These results suggest that compound 18i is a promising candidate for further drug discovery., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Lammas growth of trees means the additional growth of the shoot after the growth cessation and bud set in late summer. In temperate tree species, lammas growth occurs irregularly and is often regarded as abnormal, disturbed growth. In subtropical tree species, however, lammas growth is a prevalent phenomenon, possibly due to the prolonged occurrence of high temperatures in the autumn. The occurrence of lammas growth extends the growing season of trees, but its influence on subsequent dormancy phenomena and bud burst phenology remains largely unexplored. By comparing seedlings showing lammas growth with others not showing it, we carried out an experimental study of how lammas growth affects the bud burst phenology and the underlying dormancy phenomena under both ambient and controlled chilling, forcing and warming conditions in four subtropical tree species: Carya illinoinensis, Cinnamomum japonicum, Phoebe chekiangensis and Torreya grandis. With the exception of C. illinoinensis, lammas growth delayed bud burst in all the species under ambient conditions. In the chilling experiment, the delayed bud burst appeared to be due to higher minimum forcing requirement, higher dormancy depth, and in T. grandis, also due to lower chilling sensitivity in the lammas-growth seedlings than in the non-lammas-growth ones. However, a spring warming experiment showed that the sensitivity of bud burst to spring temperatures was higher in the lammas-growth seedlings than in the non-lammas-growth ones. Because of this, the difference between the two phenotypes in the timing of bud burst vanished with increasing warming. Our findings elucidate the significant impact of lammas growth on the dormancy dynamics of subtropical tree species, highlighting the necessity to better understand how the physiological phenomena causing lammas growth change the trees' subsequent environmental responses under changing climatic conditions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Cardaminezhangjiajieensis , a new species from Hunan Province, China, is described and illustrated. Cardaminezhangjiajieensis is similar to C.circaeoides . From the latter, C.zhangjiajieensis is readily distinguished by the terminal leaflet of the cauline leaf 4.5-7 cm (vs. 2.5-4.5 cm), mostly round or oblong (vs. oblong-oval to triangular-oval), margin undulating sinuses (vs. crenate or subentire), seed apically narrow wing (vs. wingless)., Competing Interests: The authors have declared that no competing interests exist., (Jia-Lu Li, Cheng Zhang, Yi He, Quan-Ru Liu.)

Oncocytic thyroid tumors are characterized by an elevated mitochondrial density within the cells, distinguishing them from other thyroid tumors, exhibit distinct clinical behaviors, including increased invasiveness and iodine therapy resistance. However, the proteomic alterations in oncocytic thyroid tumors remain inadequately characterized. In this study, we analyzed 156 Asian patients with oncocytic thyroid adenomas (OA) and carcinomas (OCA) to explore their clinical, genetic, and proteomic features. Genetic testing of 73 samples revealed frequent mutations in TERT, NRAS, EIF1AX, EZH1, and HRAS, with TERT promoter mutations being exclusive to OCAs. Proteomic analysis identified 66 mitochondrial-specific proteins significantly highly expressed in oncocytic tumors than in non-oncocytic tumors. This led to the development of a thyroid oncocytic score (TOS) to quantify oncocytic characteristics. Among these proteins, isocitrate dehydrogenase 2 (IDH2) was substantially overexpressed in oncocytic tumors and further confirmed by immunohistochemistry in oncocytic tumor slides (n = 41) and non-oncocytic tumor slides (n = 40). Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Environmental heat and cold exposure (EHCE) remains the principal preventable cause of morbidity and mortality in children and adolescents globally., Objective: To report EHCE-related burden and analyze its temporal trends among children and adolescents from 1990 to 2019., Design, Setting, and Participants: This repeated cross-sectional study used data from the Global Burden of Disease Study 2019, which encompassed 204 countries and territories from 1990 to 2019. Children and adolescents aged 0 to 19 years were included in the study. Data analysis occurred from December 2023 to March 2024., Exposure: EHCE in children and adolescents from January 1990 to December 2019., Main Outcomes and Measures: The primary outcomes were cases and rates of EHCE incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and average annual percentage changes (AAPCs). Global trends in these metrics were also analyzed by sex, age, and sociodemographic index (SDI), which is a comprehensive indicator of the socioeconomic status of a country or region. A linear regression model was used to calculate AAPCs and a joinpoint regression model was used to identify the years in which trends changed significantly., Results: From 1990 to 2019, EHCE-related incidence, prevalence, mortality, and DALYs showed a downward trend globally. However, an upward trend in EHCE incidence and prevalence was detected between 2010 and 2019 (incidence AAPC, 1.46; 95% CI, 1.05-1.87; prevalence AAPC, 1.25; 95% CI, 1.01-1.50). Regionally, although EHCE-related incidence showed a decreasing trend in most regions from 1990 to 2019, there were still some regions with an increasing trend (Southern sub-Saharan Africa AAPC, 0.23; 95% CI, 0.01-0.44). In 2019, the mortality and DALYs of EHCE were higher among children and adolescents in countries with low SDI levels. Additionally, the burden of EHCE among children and adolescents varied according to sex and age., Conclusions and Relevance: In this cross-sectional study, a global increase was observed in EHCE incidence and prevalence since 2010. Furthermore, children and adolescents in low-SDI regions, which bear the brunt of the climate crisis, were disproportionately impacted. This suggests that future responses to climate change crises should emphasize health equity, which implies that vulnerable populations, such as children and adolescents, should be given priority in the allocation of resources to address climate change.

Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape of a cohort of 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic and 5 neoadjuvant GISTs from 105 patients. GISTs have notably low tumor mutation burden but widespread copy number variations. Aggressive GISTs harbor remarkably more genomic aberrations than low-/intermediate-risk GISTs. Complex genomic alterations, chromothripsis and kataegis, occur selectively in aggressive GISTs. Despite the paucity of mutations, recurrent inactivating YLPM1 mutations are identified (10.3%, 7 of 68 patients), enriched in high-risk/metastatic GIST and functional study further demonstrates YLPM1 inactivation promotes GIST proliferation, growth and oxidative phosphorylation. Spatially and temporally separated GISTs from individual patients demonstrate complex tumor heterogeneity in metastatic GISTs. Finally, four prominent subtypes are proposed with different genomic features, expression profiles, immune characteristics, clinical characteristics and subtype-specific treatment strategies. This large-scale analysis depicts the landscape and provides further insights into GIST pathogenesis and precise treatment., (© 2024. The Author(s).)

Mycotoxin contamination poses serious threats to human and animal health. Food and environmental systems are often simultaneously contaminated with multiple mycotoxins, a problem that is further exacerbated by the synergistic toxicological effects of these co-occurring mycotoxins. Consequently, the development of rapid detection methods capable of simultaneously identifying multiple mycotoxins in agricultural products is essential to prevent their entry into the food chain. Compared to standard detection methods, optical and electrochemical (EC) sensing methods have distinct advantages for the rapid detection of mycotoxins. This review comprehensively summarizes the latest advancements in the field of simultaneous detection of multiple mycotoxins using optical and EC sensing methods over the last 6 years (2018-2024). First, the review introduces the classification and relevant principles of optical and EC sensing methods. Thereafter, it emphasizes innovative simultaneous detection strategies within these approaches. Finally, it discusses current challenges and offers a reference for further research. Currently, the main challenge lies in the mutual interference among targets, making the development of an interference-free detection platform essential. Furthermore, the ongoing development of integrated technology is expected to aid regulatory authorities in improving the quality of agricultural products for field applications., (© 2024 Institute of Food Technologists®.)

Harnessing the immunogenic potential of senescent tumor cells provides an opportunity to remodel tumor microenvironment (TME) and boost antitumor immunity. However, this potential needs to be sophisticatedly wielded to avoid additional immunosuppressive capacity of senescent cells. Our study shows that blocking the JAK2/STAT3 pathway enhances immunogenic efficacy of Aurora kinase inhibitor alisertib (Ali)-induced senescence by reducing immunosuppressive senescence-associated secretory phenotype (SASP) while preserving immunogenic SASP. Hypothesizing that SASP reprogramming with Ali and JAK2 inhibitor ruxolitinib (Rux) will benefit cancer immunotherapy, we create nanoparticulate crystals (Ali-Rux) composed of Ali and Rux with a fully active pharmaceutical ingredient. Immunization with Ali-Rux-orchestrated senescent cells promotes stronger activation of antigen-presenting cells, enhancing antitumor immune surveillance. This approach remodels the TME by increasing CD8 + T cell and NK recruitment and activation while decreasing MDSCs. Combined with PD-L1 blockade, Ali-Rux elicits a durable antitumor immune response, suggesting the TME reshaping approach as a potential cancer immunotherapy.

Wheat (Triticum aestivum L.) is a globally staple crop vulnerable to various fungal diseases, significantly impacting its yield. Plant cell surface receptors play a crucial role in recognizing pathogen-associated molecular patterns (PAMPs) and activating PAMP-triggered immunity, boosting resistance against a wide range of plant diseases. Although the role of plant chitin receptor CERK1 in immune recognition and defense has been established in Arabidopsis and rice, its function and potential agricultural applications in enhancing resistance to crop diseases remain largely unexplored. Here, we identify and characterize TaCERK1 in Triticeae crop wheat, uncovering its involvement in chitin recognition, immune regulation, and resistance to fungal diseases. By a comparative analysis of CERK1 homologs in Arabidopsis and monocot crops, we demonstrate that AtCERK1 in Arabidopsis elicits the most robust immune response. Moreover, we show that overexpressing TaCERK1 and AtCERK1 in wheat confers resistance to multiple fungal diseases, including Fusarium head blight, stripe rust, and powdery mildew. Notably, transgenic wheat lines with moderately expressed AtCERK1 display superior disease resistance and heightened immune responses without adversely affecting growth and yield, compared to TaCERK1 overexpression transgenics. Our findings highlight the significance of plant chitin receptors across diverse plant species and suggest potential strategies for bolstering crop resistance against broad-spectrum diseases in agricultural production through the utilization of plant immune receptors., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin-treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH 2 , are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin-induced CoQH 2 depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin-exposed mice. Mitochondrial SIRT3 is reduced in cisplatin-treated mouse kidneys and HK-2 cells. Both in vitro SIRT3 overexpression and in vivo NMN supplementation attenuated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis. By contrast, Sirt3 knockout aggravated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis, which can not be attenuated by NMN. Additional experiments showed that cisplatin caused mitochondrial dysfunction and SIRT3 SUMOylation. Pretreatment with mitochondria-target antioxidant MitoQ alleviated cisplatin-caused mitochondrial dysfunction, SIRT3 SUMOylation, and DHODH acetylation. MitoQ pretreatment protected against cisplatin-caused AKI and renal cell ferroptosis. Taken together, these results suggest that mitochondrial dysfunction-evoked DHODH acetylation partially contributes to renal cell ferroptosis during cisplatin-induced AKI., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus, characterized by complex pathogenesis that involves numerous molecules and signaling pathways. Among these, CD2 glycoprotein and CD44 play pivotal roles in cell adhesion, signal transduction, and inflammatory responses, potentially contributing significantly to the onset and progression of DN. This study aimed to investigate the central features of CD2 glycoprotein and CD44 in preventing diabetic nephropathy. To achieve this, kidney tissue sample data from DN patients were sourced from a public gene expression database. The roles of CD2 glycoprotein and CD44 within the PPI network were then analyzed, focusing on their interactions with other related genes. WGCNA analysis identified several significant gene modules associated with DN, including CD2 glycoprotein and CD44. PPI network analysis showed that these two proteins had a high degree of connectivity in the network, suggesting that they may be central regulatory molecules of DN. Further functional enrichment analysis revealed the potentially important role of CD2 glycoprotein and CD44 in diabetic nephropathy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbe-material hybrid systems which facilitate the solar-driven synthesis of high-value chemicals, harness the unique capabilities of microbes, maintaining the high-selectivity catalytic abilities, while concurrently incorporating exogenous materials to confer novel functionalities. The effective assembly of both components is essential for the overall functionality of microbe-material hybrid systems. Herein, we conducted a critical review of microbe-material hybrid systems for solar energy conversion focusing on the perspective of interface assembly strategies between microbes and materials, which are categorized into five types: cell uptake, intracellular synthesis, extracellular mineralization, electrostatic adsorption, and cell encapsulation. Moreover, this review elucidates the mechanisms by which microbe-material hybrid systems convert elementary substrates, such as carbon dioxide, nitrogen, and water, into high-value chemicals or materials for energy generation., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The intricate nature of pain classification and mechanism constantly affects the recovery of diseases and the well-being of patients. Key medical challenges persist in devising effective pain management strategies. Therefore, a comprehensive review of relevant methods and research advancements in pain management is conducted. This overview covers the main categorization of pain and its developmental mechanism, followed by a review of pertinent research and techniques for managing pain. These techniques include commonly prescribed medications, invasive procedures, and noninvasive physical therapy methods used in rehabilitation medicine. Additionally, for the first time, a systematic summary of the utilization of responsive biomaterials in pain management is provided, encompassing their response to physical stimuli such as ultrasound, magnetic fields, electric fields, light, and temperature, as well as changes in the physiological environment like reactive oxygen species (ROS) and pH. Even though the application of responsive biomaterials in pain management remains limited and at a fundamental level, recent years have seen the examination and debate of relevant research findings. These profound discussions aim to provide trends and directions for future research in pain management., (© 2024 Wiley‐VCH GmbH.)

Anchorene, identified as an endogenous bioactive carotenoid-derived dialdehyde and diapocarotenoid, affects root development by modulating auxin homeostasis. However, the precise interaction between anchorene and auxin, as well as the mechanisms by which anchorene modulates auxin levels, remain largely elusive. In this study, we conducted a comparative analysis of anchorene's bioactivities alongside auxin and observed that anchorene induces multifaceted auxin-like effects. Through genetic and pharmacological examinations, we revealed that anchorene's auxin-like activities depend on the indole-3-pyruvate-dependent auxin biosynthesis pathway, as well as the auxin inactivation pathway mediated by Group II Gretchen Hagen 3 (GH3) proteins that mainly facilitate the conjugation of indole-3-acetic acid (IAA) to amino acids, leading to the formation of inactivated storage forms. Our measurements indicated that anchorene treatment elevates IAA levels while reducing the quantities of inactivated IAA-amino acid conjugates and oxIAA. RNA sequencing further revealed that anchorene triggers the expression of numerous auxin-responsive genes in a manner reliant on Group II GH3s. Additionally, our in vitro enzymatic assays and biolayer interferometry (BLI) assay demonstrated anchorene's robust suppression of GH3.17-mediated IAA conjugation with glutamate. Collectively, our findings highlight the significant role of carotenoid-derived metabolite anchorene in modulating auxin homeostasis, primarily through the repression of GH3-mediated IAA conjugation and inactivation pathways, offering novel insights into the regulatory mechanisms of plant bioactive apocarotenoids., (© 2024 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

The color-changing self-assembly and autonomous disassembly of colloidal gold nanoparticles (AuNPs) is reported by simply mixing negatively charged phosphine ligand-capped AuNPs with partially oxidized polyethylene glycol (PEG). The assembly of AuNPs is initiated by PEG adsorption, which disrupts the hydration layer of AuNPs, leading to depletion attraction and reduction of hydration repulsion among the AuNPs. The oxidative species in PEG subsequently oxidize and remove the charged ligands from the AuNP surface, resulting in a decrease and reversal of the negative surface charge. This causes the PEG to adsorb on AuNPs in a tighter and more direct manner, providing strong steric shielding to the AuNPs, thereby triggering the disassembly of the AuNP assemblies. The self-regulated assembly-disassembly process can be tuned widely by controlling chemical conditions of PEG, nanoparticle concentration, and the environmental conditions, suggesting potential applications as colorimetric time-temperature indicators for food and medicine storage conditions. As a proof of concept, it is demonstrated that the lifetime of the color-changing assembly-disassembly process can be extended from tens of minutes to weeks when subjected to a refrigerated environment, with tunability achievable through varying polymer conditions and storage atmospheres., (© 2024 Wiley‐VCH GmbH.)

Background: Cardiometabolic multimorbidity (CMM) and aging are increasing public health concerns. This prospective study used UK Biobank cohort to investigate the relationship between biological aging and the trajectory of CMM to dementia and mortality., Methods: CMM is the coexistence of at least two cardiometabolic diseases (CMD), including stroke, ischemic heart disease, and diabetes. Biological age was calculated using the KDM-BA and PhenoAge algorithms. Accelerated aging indicated biological age advances more rapidly than chronological age., Results: The study included 415,147 individuals with an average age of 56.5 years. During the average 11-year follow-up period, CMD-free individuals with accelerated aging had a significantly greater risk of CMD (KDM-BA, HR 1.456; PhenoAge, HR 1.404), CMM (KDM-BA, HR 1.952; PhenoAge, HR 1.738), dementia (KDM-BA, HR 1.243; PhenoAge, HR 1.212), and mortality (KDM-BA, HR 1.821; PhenoAge, HR 2.047) in fully-adjusted Cox regression models ( p  < 0.05 for all). Accelerated aging had adjusted HRs of 1.489 (KDM-BA) and 1.488 (PhenoAge) for CMM, 1.434 (KDM-BA) and 1.514 (PhenoAge) for dementia, and 1.943 (KDM-BA) and 2.239 (PhenoAge) for mortality in participants with CMD at baseline ( p  < 0.05 for all). CMM significantly mediated accelerated aging's indirect effects on dementia by 13.7% (KDM-BA, HR) and 21.6% (PhenoAge); those on mortality were 4.7% (KDM-BA) and 5.2% (PhenoAge). The population attributable-risk of Life's Essential 8 score (≥80 vs. <80) were 0.79 and 0.43 for KDM-BA and PhenoAge accelerated aging, respectively., Conclusion: Biological aging involves the entire trajectory of CMM from a CMD-free state to CMD, to CMM, and ultimately to dementia and death. Life's Essential 8 may be a potential target to counter age acceleration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Jia, Li, Wan, Lei, Liao, Zhao and Li.)

Objective: To investigate the efficacy of erector spinal plane block (ESPB) after spinal fusion surgery in this study., Methods: The PubMed, Embase, Cochrane library, and Web of Science databases were searched with a search deadline of March 30, 2024, and Stata 15.0 was used to analyze the data from the included studies., Result: Nine randomized controlled trials involving 663 patients were included. Meta-analysis showed that EPSB could reduce pain scores at 2h (standard mean difference (SMD) = -0.78, 95% CI [-1.38 to -0.19], GRADE: Moderate), 6 h (SMD = -0.81, 95% CI [-1.23 to -0.38], GRADE: Moderate), 12 h (SMD = -0.59, 95% CI [-1.05 to -0.13], GRADE: Moderate), 24 h (SMD = -0.54, 95% CI [-0.86 to -0.21], GRADE: Moderate), 48 h (SMD = -0.40, 95% CI [-0.75 to -0.05], GRADE: Moderate) after spinal fusion surgery, as well as the PCA (analgesia medication use) (SMD = -1.67, 95% CI [-2.67 to -0.67], GRADE: Moderate). However, EPSB had no effect on intraoperative blood loss (SMD = -0.28, 95% CI [-1.03 to 0.47], GRADE: Low) and length of hospital stay (SMD = -0.27, 95% CI [-0.60-0.06], GRADE: Low)., Conclusion: Combined with the current findings, EPSB may reduce pain scores in spinal fusion surgery, possibly reducing the use of postoperative analgesics. However, due to the limitations of the study, we need more high-quality, multi-center, large sample randomized controlled trials to merge., Competing Interests: The authors declare there are no competing interests., (©2024 He et al.)

By combining dark-field optical microscopy with an in situ thermochemical aqueous solution system, we report a single-particle imaging strategy to investigate the host-guest interactions between covalent organic framework-300 (COF-300) as a representative COF host and a series of linear-chain fatty amines. The thermodynamic parameters, such as dissociation constant, Gibbs free energy changes, enthalpy changes, and entropy changes for the binding events within COF-300 are quantified. Correlation between the hydrophobicity of various amines and other data suggests that the mechanism of the host-guest bindings arises from the entropy-driven noncovalent interactions such as hydrogen bonds and van der Waals forces. These mechanistic insights allow for the rational design and preparation of COF-300-encapsulated n -octylamine with enhanced trapping performance of radioactive 131 I - . This study not only provides thermodynamic insights into the host-guest interactions within the COF framework but also establishes a structure-property relationship between fatty amines and energetic magnitude information.

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression., 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.)

Developing low-Pt oxygen reduction reaction (ORR) catalysts with high efficiency and robustness is critical for practical fuel cells. The most advanced ORR catalysts either feature high percentages of Pt (>70 at.%) or exhibit poor durability when reducing Pt loading. Herein, a multicomponent solid-solution Pt 3 (FeCoNi) honeycomb nano-framework supported by the specially designed high-entropy metallic glass (MG) is reported for efficient ORR. This hybrid catalyst with a low surface Pt loading of 5.79 µg cm -2 displays exceptional mass and specific activities of 7.02 A mg pt -1 and 8.15 mA cm Pt -2 at 0.9 V, respectively, which are ≈15 and 22 times higher compared with commercial Pt/C. The analyses reveal the weakened chemisorption of oxygenated species, which is induced by the strong strain and ligand effects originating from the synergistic multicomponent alloying. This in turn enhances the intrinsic ORR activity. Moreover, benefiting from a unique replenishment behavior, the hybrid catalyst delivers ultra-high durability with negligible activity decay even after 50 000 potential cycles. This mechanism is achieved by sacrificing the interior MG supplementary support to dynamically compensate for the loss of catalytically active surface. The work provides an alternative way to design more efficient and durable low-Pt electrocatalysts for electrochemical devices., (© 2024 Wiley‐VCH GmbH.)

Background: Flavonoids, found in common vegetables and fruits, have health benefits that are often limited by their low bioavailability. Excipient emulsions provide an effective strategy to overcome these obstacles. However, the nature of the emulsifier used to formulate excipient emulsions and the chemical structure of the flavonoids both affect the bioaccessibility of the flavonoids., Results: The purpose of this study was to investigate the impact of the interfacial properties of excipient emulsions on the in vitro gastrointestinal fate of representative structural flavonoids (quercetin, kaempferol, and apigenin) through the INFOGEST method. Tween 80 (TW80) (a nonionic surfactant) was more effective at reducing the oil-water interfacial tension than whey protein isolate (WPI) (a protein-based emulsifier) or octenyl succinic anhydride (OSA)-modified starch (MS) (a polysaccharide-based emulsifier). Moreover, TW80 created excipient emulsions with smaller oil droplets, which were more resistant to oral and gastric conditions. The WPI-emulsions underwent severe flocculation in the gastric phase, leading to an appreciable increase in particle size (from 220 to 3000 nm). The TW80-coated oil droplets were more digestible than WPI- or MS-coated ones. This was attributed to the larger lipid surface area for lipase attachment. The bioaccessibility of quercetin, kaempferol, and apigenin was also affected by emulsifiers: TW 80 (25% to 45%) > WPI (14% to 29%) ≈ MS (15% to 25%). Flavonoid bioaccessibility appeared to be related to their molecular properties., Conclusion: This study provides guidance for the design of effective excipient emulsions to enhance the bioavailability of flavonoids. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This study aimed to investigate the role of ITFG2, a protein highly expressed in cardiac tissues, in myocardial ischemic injury and its potential interactions with NEDD4-2. An in vivo myocardial infarction (MI) model was induced in mice via left anterior descending artery ligation, and ITFG2 expression was modulated using adeno-associated virus AAV9 vectors. Echocardiography was used to assess cardiac function, and primary mouse cardiomyocytes were cultured and subjected to hypoxia. ITFG2 expression was found to be significantly reduced following MI and in hypoxia-treated neonatal cardiomyocytes. Overexpression of ITFG2 improved cardiac contractility, reduced apoptosis, and stabilized calcium levels by inhibiting NEDD4-2-mediated ubiquitination of SERCA2a. Conversely, ITFG2 knockdown exacerbated calcium overload and cardiac dysfunction. Mechanistically, ITFG2 binds to NEDD4-2, decreasing its interaction with SERCA2a and preventing SERCA2a degradation. These findings suggest that ITFG2 acts as a critical inhibitor of NEDD4-2, preserving SERCA2a function and maintaining calcium homeostasis in cardiomyocytes under ischemic conditions. Therefore, ITFG2 may represent a potential therapeutic target for preventing myocardial ischemic injury and improving outcomes in MI patients., 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.)

Grain hardness has important effects on grain quality and the end-use of wheat. In this study, a collection of 103 common wheat germplasms and a DH population of 194 lines were used to identify new quantitative trait loci (QTL) for grain hardness. Two stable genetic loci on chromosome 5D were detected under different locations and years with one of them being the Ha locus on 5DS where the major gene Puroindolines for wheat grain hardness is located. Another locus of qTaHa-5DL also showed a significant impact on grain hardness index (HI) with HI increasing from ~ 20 to ~ 45 and hardness type changing from soft to mixed when Puroindolines are wild type. A kompetitive allele-specific PCR (KASP) marker for qTaHa-5DL was developed and the effectiveness of the QTL was confirmed in 184 breeding lines with the marker K-Ha5DL dividing wheat into two distinct categories. This new QTL can be effectively used to select soft or medium hard wheat., (© 2024. The Author(s).)

Nonalcoholic steatohepatitis (NASH), a chronic liver disease characterized by the accumulation of fat in the liver, is highly prevalent on a global scale. In this study, we investigated the effects of total glucosides of Picrorhizae Rhizome (TGPR), the primary active ingredients in traditional Chinese herbal medicine derived from Picrorhiza scrophulariiflora Pennell. TGPR is known for its efficiency in attenuating NASH, in mouse models induced by methionine-choline deficient (MCD) diet or high-fat diet (HFD). Our findings indicated that TGPR exhibited efficacy in reducing hepatic steatosis and lowering serum lipid levels, specifically triglyceride and total cholesterol in the NASH model. Meanwhile, TGPR exhibited a suppressive effect on the production of pro-inflammatory cytokines. Mechanistically, we identified acyl-CoA oxidase 1 (Acox1) as a crucial cellular target of TGPR, influencing lipid metabolism and ATP production to treat NASH. Additionally, we found that the major components of TGPR, including Picroside I, Picroside II, and Picroside IV, exhibit significant binding abilities to the target Acox1 at its catalytic C-terminal α-domain, stabilizing its protein expression. TGPR binding to Acox1 facilitated the degradation of fatty acids via the Acox1-mediated MAPK signaling pathways, and consequently plays a role in regulating energy metabolism and reducing liver inflammation. In summary, our study demonstrates that TGPR effectively counteracts NASH by specifically targeting Acox1, thereby providing a significant clinical solution for the treatment of NASH., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Mitochondrial quality regulation plays an important role in affecting the treatment sensitivity of multiple myeloma (MM). We aimed to develop a mitochondrial quality regulation genes (MQRGs)-related prognostic model for MM patients. The Genomic Data Commons-MM of bulk RNA-seq, mutation, and single-cell RNA-seq (scRNA-seq) dataset were downloaded, and the MQRGs gene set was collected previous study. "maftools" and CIBERSORT were used for mutation and immune-infiltration analysis. Subsequently, the "ConsensusClusterPlus" was used to perform the unsupervised clustering analysis, "survminer" and "ssGSEA" R package was used for the Kaplan-Meier survival and enrichment analysis, "limma" R, univariate and Least Absolute Shrinkage and Selection Operator Cox were used for RiskScore model. The "timeROC" R package was used for Receiver Operating Characteristic Curve analysis. Finally, the "Seurat" R package was used for scRNA-seq analysis. These MQRGs are mainly located on chromosome-1,2,3,7, and 22 and had significant expression differences among age, gender, and stage groups, in which PPARGC1A and PPARG are the high mutation genes. Most MQRGs expression are closely associated with the plasma cells infiltration and can divide the patients into 2 different prognostic clusters (C1, C2). Then, 8 risk models were screened from 60 DEGs for RiskScore, which is an independent prognostic factor and effectively divided the patients into high and low risk groups with significant difference of immune checkpoint expression. Nomogram containing RiskScore can accurately predict patient prognosis, and a series of specific transcription factor PRDM1 and IRF1 were identified. We described the based molecular features and developed a high effective MQRGs-related prognostic model in MM., (© 2024 International Union of Biochemistry and Molecular Biology.)

Intrahepatic circulation is essential for the repair of acute liver injury (ALI); however, very limited information is available concerning changes in the circulatory pathways during ALI. Therefore, multi-scale X-ray phase-contrast CT combined with three-dimensional (3D) visualization is used to quantitatively analyze the intrahepatic circulation pathway (including the hepatic vein, portal vein and hepatic sinusoid) in the mouse model via the intraperitoneal injection of carbon tetrachloride (CCl 4 ) from acute injury to recovery. The results demonstrate that the liver still preserves some vessel-like channels accessed to the central vein when the injury causes the severe collapse of the hepatic sinusoids that cannot be observed in two-dimensional pathologic slices. Moreover, angiogenesis is observed in the terminal branches of the hepatic vein and portal vein. Additionally, we extend the two-dimensional primary lobule to a 3D model and find that the sinusoids in zone III have the most severe injury. The sinusoids in different zones also show changes in parameters such as density and mean diameter during the ALI. In conclusion, phase-contrast CT can reveal the intact vascular system within the liver lobes, thus providing critical information for studying the mechanisms involved in the evolution of circulatory structures from damage to repair., (© 2024. The Author(s).)

Wing dimorphism is a distinguishing characteristic of brown planthopper Nilaparvata lugens (Stål) populations, wherein adults exhibit 2 distinct morphs: long-winged and short-winged. The presence of long-winged individuals often heralds the onset of migration, while short-winged morphs signify high reproduction and can be associated with population outbreaks. This phenomenon underscores the adaptability of these insects in response to environmental cues and their impact on agricultural ecosystems. Wing morphs of N. lugens are controlled by genetical and environmental factors. Mate choice between long and short-winged adults affects wing morphs of offspring. In this study, we found that the wild population had no persistent preference for choosing long-winged or short-winged adults to mate. But in 2 multigenerational selected lineages for long and short-winged morphs, the short-winged males preferred to short-winged females to mate and the long-winged males had no preference. In the nearly pure-bred lineages of long-winged and short-winged morphs, both wing morphs of females preferred for short-winged males. Purification of wing morph lineages enhanced mating preference for short-winged partners. When the wing developmental gene InR1 or InR2 was interfered by RNAi, the pure-bred lineage of long-winged morph mainly produced short-winged adults and the short-winged morphs produced long-winged adults, and these adults exhibited preference to mate with short-winged partners. The tendency to mate with short-winged morphs leads to more short-winged offspring which easily causes the rapid growth of populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. 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.)

Agricultural drought (AD) is the main environmental factor affecting vegetation productivity (VP) in the Yellow River Basin (YRB). In recent years, the nonlinear effects of AD on VP in the YRB have attracted much attention. However, it is still unclear whether fluctuating AD will have complex nonlinear effects on VP in the YRB, and there are scant previous studies at large scale on whether there is a threshold for nonlinear effects of AD on VP in the YRB. Therefore, this study used a newly developed agricultural drought index to explore nonlinear effects on VP revealing the nonlinear effects of AD on VP in the YRB. First, we developed a kernel temperature vegetation drought index (kTVDI) based on kernel normalized difference vegetation index (kNDVI) and land surface temperature data to study the spatiotemporal variation of AD in the YRB. Second, we used GPP data from solar-induced chlorophyll fluorescence inversion as an indicator to explore the spatiotemporal variation of VP in the YRB. Finally, we used several statistical indicators and a distributed lag nonlinear model (DLNM) to analyze the nonlinear effect of AD on VP in the YRB. The results showed that AD decreased significantly during 2000-2020, mainly in the southeast of the Loess Plateau, while GPP increased significantly in 80.93 % of the YRB. Meanwhile, moderate and severe AD stress limited VP growth, with the negative effects gradually decreasing, while mild AD had an increasingly positive promoting effect on VP. AD stress resulted in a VP decrease of 69.78 %, and severe AD stress resulted in a VP decrease of 65.52 %, mainly distributed in the northern Loess and Ordos Plateau. AD had significant nonlinear effects on VP. The effects of moderate and severe AD on the sustained nonlinear lag of vegetation were more obvious, and those of moderate and severe AD on the nonlinear lag of VP were the largest when the lag was approximately 1 month and 7 months. The effect of AD on the nonlinear hysteresis of VP in YRB was significantly different under different vegetation types, and forests were more able to withstand longer and more severe droughts than grasslands and croplands. The results of the study provide a theoretical basis for evaluating AD and analyzing the nonlinear impact of AD on VP. This will provide scientific basis for studying the mechanism of drought effect on vegetation in other regions., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Revealing the interaction modes between nanoscale metal-organic frameworks (NMOFs) and food matrix is crucial for functional release but it still remains largely unknown to date. This study specifically focused on the milk protein adsorption mechanism of NMOFs using UiO66/UiO66-NH 2 and β-lactoglobulin (β-LG) as models. UiO66 and UiO66-NH 2 quenched the fluorescence of β-LG via static mechanism. Due to the enhanced electrostatic forces caused by NH 2 , UiO66-NH 2 -β-LG (2.83 × 10 5  mol·L -1 ) exhibited higher binding constant than UiO66-β-LG (2.61 × 10 5  mol·L -1 ), while UiO66 with higher hydrophobicity adsorbed more β-LG. The defects of UiO influenced the binding sites on the β-LG, and the higher the defect degree, the higher the binding energy. For the stability of the system, the H-bonding between UiO66 and SER30/PRO38, and the hydrophobic interaction between UiO66-NH 2 and LYS101 played important roles. Furthermore, the secondary structure content of β-LG changed after interacting with both UiO, resulting in reduced density of β-LG., 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.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) maintains the only promising curative option for patients with refractory/relapsed (R/R) acute myeloid leukemia (AML). However, the long-term survival results are suboptimal. Optimization of the conditioning regimen aims to eradicate leukemia blasts and reduce early relapse. Here we reported of the preliminary result of the prospective multicenter single arm study to evaluate the efficacy and safety of a modified dual alkylator-conditioning regimen, MCBC (regimen including Melphalan, Cladribine, Busulfan and Cyclophosphamide) (ChiCTR Registration ID: ChiCTR2000029936). This trial enrolled 56 patients from July 2020 to January 2022. With a median follow-up of 854 days (range 48 to 1343), the 2-year overall survival (OS) and relapse-free survival (RFS) were 60.7 ± 6.5% (95% CI 47.5-73.9) and 57.1 ± 6.6% (95% CI 43.8-70.5), respectively, the estimated 3-year OS and RFS rates were 58.9 ± 6.6% (95% CI 45.6-72.2) and 55.4 ± 6.6% (95% CI 41.9-68.8), respectively. A total of 19 patients experienced relapse, the 2-year cumulative incidence relapse (CIR) rate was 34.2 ± 6.6% (95% CI 19.5-44.8), the estimated 3-year CIR rate was 36.3 ± 6.7% (95% CI 21.1-46.7). Six patients died of severe infection or graft-versus-host disease (GVHD). The non-relapse mortality (NRM) rate was 11.8 ± 4.5% (95% CI 2.4-19.1). Mucositis was the main reported regimen-related toxicity, and it was well controlled. Subgroup analyses illustrated that blasts count ≥ 20% before HSCT and the absence of maintenance treatment after HSCT were poor predictors. Our study confirmed the excellent anti-leukemia activity and acceptable toxicity of the MCBC conditioning regimen in R/R AML. Opportune maintenance treatment after HSCT led to significantly improved OS and RFS., Competing Interests: None., (AJCR Copyright © 2024.)

Endocytosis plays a complex role in pathogen-host interactions. It serves as a pathway for pathogens to enter the host cell and acts as a part of the immune defense mechanism. Endocytosis involves the formation of lipid membrane vesicles and the reshaping of the cell membrane, a task predominantly managed by proteins containing BAR (Bin1/Amphiphysin/yeast RVS167) domains. Insights into how BAR domains can remodel and reshape cell membranes provide crucial information on infections and can aid the development of treatment. Aiming at deciphering the roles of the BAR dimers in lipid membrane bending and remodeling, we conducted extensive all-atom molecular dynamics simulations and discovered that the presence of helix kinks divides the BAR monomer into two segments-the "arm segment" and the "core segment"-which exhibit distinct movement patterns. Contrary to the prior hypothesis of BAR domains working as a rigid scaffold, we found that it functions in an "Arms-Hands" mode. These findings enhance the understanding of endocytosis, potentially advancing research on pathogen-host interactions and aiding in the identification of new treatment strategies targeting BAR domains.

Cadmium (Cd) is a common environmental metal. Previous studies indicated that long-term respiratory Cd exposure caused lung injury and airway inflammation. The purpose of this study was to evaluate whether short-term respiratory Cd exposure induces pulmonary ferroptosis and NLRP3 inflammasome activation. Adult C57BL/6J mice were exposed to Cd by inhaling CdCl 2 aerosol (0, 10, or 100 ppm) for 5 days. Serum and lung Fe 2+ contents were elevated in Cd-exposed mice. Oxidized AA metabolites, the major oxidized lipids during ferroptosis, were upregulated in Cd-exposed mouse lungs. Pulmonary MDA content and 4-HNE-positive cells were increased in Cd-exposed mice. ACSL4 and COX-2, two lipoxygenases, were upregulated in Cd-exposed mouse lungs. Further analyses found that phosphorylated NF-kB p65 was elevated in Cd-exposed mouse lungs. Innate immune receptor protein NLRP3 and adapter protein ASC were upregulated in Cd-exposed mouse lungs. Caspase-1 was activated and IL-1β and IL-18 were upregulated in Cd-exposed mouse lungs. Fer-1, a specific inhibitor of ferroptosis, attenuated Cd-induced elevation of pulmonary NLRP3 and ASC, caspase-1 activation, and IL-1β and IL-18 upregulation. Finally, mitoquinone (MitoQ), a mitochondria-target antioxidant, suppressed Cd-caused ferroptosis and NLRP3 inflammasome activation. Our results demonstrate that ferroptosis might partially mediate Cd-evoked activation of NLRP3 inflammasome in the lungs., 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.)

Monascus species are functional fermentation fungi with great potential for selenium (Se) supplementation. This study investigated the effects of Se bio-fortification on the growth, morphology, and biosynthesis of Monascus ruber M7. The results demonstrated a significant increase in the yield of orange and red Monascus pigments (MPs) in red yeast rice (RYR) by 38.52% and 36.57%, respectively, under 20 μg/mL of selenite pressure. Meanwhile, the production of citrinin (CIT), a mycotoxin, decreased from 244.47 μg/g to 175.01 μg/g. Transcriptome analysis revealed significant upregulation of twelve genes involved in MPs biosynthesis, specifically MpigE, MpigF, and MpigN, and downregulation of four genes (mrr3, mrr4, mrr7, and mrr8) associated with CIT biosynthesis. Additionally, three genes encoding cysteine synthase cysK (Log 2 FC = 1.6), methionine synthase metH (Log 2 FC = 2.2), and methionyl-tRNA synthetase metG (Log 2 FC = 1.8) in selenocompound metabolism showed significantly upregulated. These findings provide insights into Se biotransformation and metabolism in filamentous fungi., 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.)

Molecularly imprinted polymers (MIP) have been widely owing to their specificity, however, their singular structure imposes limitations on their performance. Current enhancement methods, such as doping with inorganic nanomaterials or introducing various functional monomers, are limited and single, indicating that MIP performances require further advancement. In this work, a dual-modification approach that integrates both conductive inorganic nanomaterials and diverse bifunctional monomers was proposed to develop a multifunctional MIP-based electrochemical (MMIP-EC) sensor for diuron (DU) detection. The MMIP was synthesized through a one-step electrochemical copolymerization of silver nanowires (AgNWs), o-phenylenediamine (O-PD), and 3,4-ethylenedioxythiophene (EDOT). DU molecules could conduct fluent electron transfer within the MMIP layer through the interaction between anchored AgNWs and bifunctional monomers, and the abundant recognition sites and complementary cavity shapes ensured that the imprinted cavities exhibit high specificity. The current intensity amplified by the two modification strategies of MMIP (3.7 times) was significantly higher than the sum of their individual values (3.2 times), exerting a synergistic effect. Furthermore, the adsorption performance of the MMIP was characterized by examining the kinetics and isotherms of the adsorption process. Under optimal conditions, the MMIP-EC sensor exhibits a wide linear range (0.2 ng/mL to 10 μg/mL) for DU detection, with a low detection limit of 89 pg/mL and excellent selectivity (an imprinted factor of 10.4). In summary, the present study affords innovative perspectives for the fabrication of MIP-EC sensor with superior analytical performance., Competing Interests: Declaration of competing interest We declare that we 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.)