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Background: We aimed to explore the variation in blood pressure (BP) control in primary care hypertensive patients with or without diabetes, and investigate potential factors associated with inadequate BP control during follow-up., Methods: Primary care hypertensive patients with and without diabetes were recruited in 2020 from Jianye District of Nanjing and prospectively followed up until 2023. Effective BP control was measured in terms of consistent normal readings of systolic BP <140 mmHg and of diastolic BP <90 mmHg based on the most recent assessment during the follow-up period. We used the negative binomial model with total person-years as an offset to evaluate whether the study population would achieve BP control after the 3-y follow-up period in terms of rate ratio (RR) and 95% CI. We further conducted subgroup analysis based on the absence or presence of clinically confirmed diabetes and BP stability at baseline., Results: Of a total of 32 701 patients with hypertension, compared with those without comorbid diabetes and stable BP at baseline, patients with comorbid diabetes and unstable BP at baseline were less likely to have effective BP control at follow-up (adjusted RR=2.01, 95% CI 1.89 to 2.15). We observed an elevated risk of ineffective BP control at follow-up in those aged 60-70 y (1.69; 95% CI 1.56 to 1.83) or ≥70 y (1.73; 95% CI 1.59 to 1.88), females (1.09; 95% CI 1.03 to 1.16), those with a higher waist-to-height ratio (1.25; 95% CI 1.17 to 1.34), overweight/obese in terms of body mass index (1.16; 95% CI 1.09 to 1.23) or regularly consuming alcohol (1.26; 95% CI 1.16 to 1.37). Higher educational attainment indicated a reduced risk of ineffective BP control at follow-up (0.68; 95% CI 0.63 to 0.75)., Conclusions: Achieving effective BP control remains a persistent challenge, especially for patients with comorbid hypertension and diabetes. In the absence of any novel strategies for hypertension care, the existing multidisciplinary care approaches could be repurposed and integrated for effective management of the aforementioned comorbid conditions in primary care settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Monitoring mercury (Hg) is critical for environmental and public health. Metal-organic framework (MOF)-based sensors demonstrate the advantage of high sensitivity and rapid response. We summarize the advances of MOF sensors for Hg2+ detection from the perspective of MOF type and role in the sensors. First, we introduce three MOFs used in Hg sensors-UIO, ZIF, and MIL-that have demonstrated superior performance. Then, we discuss the specifics of MOF-based sensors for Hg2+ detection in terms of the recognition and signal elements. Currently, the recognition elements include T-rich aptamers, noble metal nanoparticles, central metal ions, and organic functional groups inherent to MOFs. Sensors with fluorescence and colorimetric signals are the two main types of optical MOF sensors used for Hg detection. Electrochemical sensors have also been fabricated, but these are less frequently reported, potentially due to the limited conductivity and cycling stability of MOFs. Notably, dual-signal sensors mitigate background signals interference and enhance the accuracy of Hg2+ detection. Furthermore, to facilitate portability and user-friendliness, portable devices such as microfluidics, paper-based devices, and smartphones have been developed for Hg2+ detection, showcasing potential applications. We also address the challenges related to MOF-based sensors for Hg2+ and future outlook., (© 2024 Wiley‐VCH GmbH.)

Germanium (Ge), as a viable candidate anode material for future sodium-ion batteries, has attracted much attention. However, such material is usually troubled by huge volume changes during charge/discharge process, leading to the rapid degradation of electrochemical performance. Notably, construction of carbon coating layers is a practical strategy to alleviate the volumetric effect of Ge. Moreover, rational design of nanosized Ge with amorphous structure can also significantly enhance its sodium-ion storage performance. Herein, amorphous Ge (a-Ge) encapsulated by nitrogen-doped carbon nanofiber (Ge@NC) was successfully prepared by facile electrostatic spinning technique and annealing treatment. Impressively, the a-Ge nanoparticles are effectively protected by the flexible nitrogen-doped carbon nanofiber (NC), contributing to faster reaction kinetics and improved cycling stability since the high electrical conductivity and buffering effect of the NC layers. In addition, the nanosized Ge with amorphous structure can offer more open framework and higher structural stability. Therefore, the integrated Ge@NC electrode displays a high capacity of 404 mAh g -1 after 300 cycles at 0.1 A g -1 . More excited, the synergistic effect of amorphous structure of Ge and nitrogen-doped carbon layers endow Ge@NC with remarkable long cycle life up to 15,000 cycles at 5 A g -1 ., 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.)

Background: The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions., Methods: Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7-65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed., Results: Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA., Limitations: The sample size is small., Conclusion: MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity., Competing Interests: Declaration of competing interest 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. The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

N mineralization and immobilization are important N cycling pathways. While they are widely studied in individual coastal habitats, they are rarely compared across different habitats along the river-estuary-sea continuum. We addressed this gap by investigating gross nitrogen mineralization (GNM) and gross ammonium immobilization (GAI) in urban rivers, estuary, and adjacent sea of the Yangtze River-Estuary-East China Sea system. We sampled 30 stations during winter and summer, quantifying GNM and GAI rates using enriched 15 N stable isotopes. We observed a 65 % decrease in total organic C concentrations and a three-fold increase in fungi/bacteria ratios from river to sea. Along the gradient, GNM decreased from 5.41 to 2.41 μg N g -1 d -1 and GAI decreased from 6.08 to 3.27, with their ratios generally >1, indicating nitrogen limitation. Redundant analyses identified temperature and Fe as significant environmental variables. This study highlights the importance of cross-habitat comparisons to N cycling studies in coastal systems., 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.)

Despite the excellent properties of single-crystalline ordered macro-microporous MOFs (SOM-MOFs) compared to conventional MOFs, their further development has been hindered by the lack of versatile and high-yielding preparation protocols. This study introduces an innovative universal fabrication method that can easily solve the two major challenges of precursor stabilization and crystallization modulation, enabling the efficient synthesis of various SOM-MOFs with high yields. Notably, our approach has successfully yielded SOM-MIL-88A, a novel MOF showcasing exceptional stability in both water and acidic solutions, a remarkable achievement unprecedented in prior SOM-MOF research. SOM-MIL-88A has demonstrated exponentially improved performance over conventional MIL-88A in adsorption, catalysis, immobilized enzymes, and composite biosensing. Furthermore, our versatile protocol has been successfully applied to synthesize SOM-HKUST-1 and SOM-ZIF-8, resulting in significantly improved yields (increase by about 10-fold and 2-fold, respectively, compared to the previously reported protocol). This groundbreaking achievement marks a pivotal advancement in the preparation of diverse SOM-MOFs with tailored properties, presenting exciting prospects for future research on MOFs.

The calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis, and small-molecule and peptide positive allosteric modulators (PAMs) of CaSR, so-called calcimimetics, are used in the treatment of hyperparathyroidism and hypocalcemic disorders. In this study, four monovalent nanobodies - representing four distinct nanobody families with CaSR PAM activity - were subjected to elaborate pharmacological profiling at the receptor. While Nb5 displayed negligible PAM activity at CaSR in all assays, Nb4, Nb10 and Nb45 all potently potentiated Ca 2+ -evoked signalling through a myc epitope-tagged CaSR expressed in HEK293 or HEK293T cells in Gα q and Gα i1 protein activation assays and in a Ca 2+ /Fluo-4 assay. Nb4 and Nb10 also displayed comparable PAM properties at a stable CaSR-HEK293 cell line in a Ca 2+ /Fura-2 imaging assay, but surprisingly Nb45 was completely inactive at this cell line in both the Ca 2+ /Fura-2 and Ca 2+ /Fluo-4 assays. Investigations into this binary difference in Nb45 activity revealed that the nanobody only possesses modulatory activity at CaSRs tagged N-terminally with various epitopes (myc, HA, Flag-SNAP), whereas it is inactive at the untagged wild-type receptor. In conclusion, overall each of the nanobodies exhibit similar CaSR PAM properties in a range of assays, and thus none of them display pathway bias as modulators. However, of the four nanobodies Nb4 and Nb10 would be applicable as pharmacological tools for the wild-type CaSR, and the complete inactivity of Nb45 at the untagged CaSR serves as an reminder that epitope-tagging of a receptor, even if deemed functionally silent, can have profound implications for ligand discovery efforts., 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.)

Cancer-associated extracellular vesicles (EVs) are crucial biomarkers for cancer diagnosis as they contain abundant tumor cell information. To efficiently and accurately detect cancer-associated EVs, an electrochemical hydrogen peroxide reduction reaction (HPRR)-based biosensor was developed, utilizing enzyme-linked immunosorbent and diatomic catalyst strategies for catalytic HPRR current amplification for specific identification and highly sensitive detection. The anti-CXCR4 antibody was immobilized on a Au-plated electrode to selectively capture EVs from the sample. Subsequently, Fe/Cu diatomic catalysts, modified with an anti-CD63 antibody, were bound to the CD63 on the EVs. Quantitative detection of EVs was achieved by measuring the electrical signals from the HPRR catalyzed by the labeled Fe/Cu diatomic catalysts. Under optimized conditions, the electrochemical signals exhibited a linear relationship with EV concentration in the range of 500 to 1 × 10 7 particles mL -1 , with a detection limit of 117 particles mL -1 , maintaining accuracy even in FBS. With its affordability, high sensitivity, and ease of use, this sensor holds significant potential for medication guidance and postoperative evaluation.

The transition-metal-catalyzed alkenylation strategy of propargylic alcohol derivatives provides an efficient protocol to access multifunctional products in a double-nucleophilic attack pattern. While limited relevant asymmetric examples have been reported via palladium catalysis, here we first demonstrate that a nonprecious Ni(0)-based chiral complex can efficiently promote the tandem substitution process between propargylic carbonates and N -trifluoroethyl ketimines via consecutive aza-vinylogous activations, finally accomplishing a (3 + 2) annulation reaction to afford products embedding a 4-methylene-3,4-dihydro-2 H -pyrrole framework with high regio-, diastereo-, and enantiocontrol. Their assemblies with a few all-carbon-based vinylogous precursors are also successful, and enantioenriched adducts containing a 3-methylenecyclopentene scaffold are furnished effectively. The substitution patterns for both types of substrates are substantial, and an array of synthetic elaborations is conducted to deliver more versatile architectures with high application potential. In addition, density functional theory calculations and control experiments have been conducted to rationalize the catalytic pathways and regio- and enantioselectivity control.

The ion interfacial transport driven by ion-surface interactions in calcareous soil has a profound impact on the nutrient storage and environmental buffer capacity of the main agricultural soils in dry and semi-arid areas. The roles that carbonate plays in preserving the soil's inorganic carbon pool and soil structure stability have been widely investigated, but its significance in the aforementioned microscopic processes, especially the influence of carbonate on the interfacial reaction kinetics of nutrient elements, is yet to be determined. In this study, potassium (K) was used as an indicator ion to investigate its affinity in carbonate-removed (CREM) and carbonate-reserved (CRES) calcareous soil using the general theory of ion diffusion in an external electric field. We discovered that (1) at a given initial K concentration, the carbonate in CRES soil retards the adsorption rate and diminishes the adsorption amount of K in calcareous soil, reducing the interfacial transport properties of nutrient ions at the solid-liquid interface of calcareous soils compared with CREM soil; and (2) this weakening of the interfacial transport effect on nutrient K originates from the soil carbonate, which prefers to weaken the electrostatic interaction intensity between K and the calcareous soil surface. Furthermore, this is due to the carbonate shielding effect on the surface adsorption sites of other soil components and the competitive relationship between K + and cations released by carbonate dissolution. The influence of carbonate on the nutrient ion transport at the solid-liquid interface of calcareous soil has been investigated by soil electrochemistry theory-based ion adsorption kinetics, and the links between kinetic features and ion-surface binding energy have been clarified., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aliphatic amines are widely distributed in the environment and food sources, posing potential health risks through skin and mucosal irritation. Consequently, their quantitative detection is crucial for assessing environmental health. Despite high reactivity and fluorescence properties of succinimidyl ester-based derivatization reagents, their application in the aliphatic amines detection is hampered by challenges such as limited detection sensitivity and fluorescence interference. We established an innovative synthetic approach to produce a series of succinimidyl esters with the desirable substituents. This advancement enabled the creation of efficient and highly sensitive reagents for the detection of aliphatic amines. Among them, 2-methyl-6-methoxy-4-quinolinecarboxylic acid N-hydroxysuccinimide ester (MMQC-OSu) exhibited the best detection performance. MMQC-OSu reacted with aliphatic amines at 40 °C in pH 8.0 buffer for 20 min, which was subsequently separated in a C18 chromatographic column with the fluorescence detection wavelength of 336/432 nm. This detection approach featured a rapid and mild reaction process, minimal interference from corresponding hydrolysis products, and impressive sensitivity (0.05 nM). These characteristics indicate that MMQC-OSu significantly surpassing commercial aliphatic amines detection reagents. Finally, the detection strategy of MMQC-OSu was successfully applied in environmental sample analysis, with recovery rate of 93 %-108 % and RSDs between 1.4 % and 6.5 %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity., Methods: A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model., Results: A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64-0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation., Conclusion: In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth., (© 2024. The Author(s).)

Background: The aim of this study was to explore the association between tea-drinking habits and health-related quality of life (HRQoL) in Chinese adults and the mediating effect of sleep quality in this association., Methods: Data were derived from the 2020 Survey of Social Factors for Chronic Disease Prevention and Control among adults in Lishui District, Nanjing, Jiangsu Province, China. Tea-drinking habits were measured by participants' self-report. The HRQoL was measured using the 12-item Short Form Health Survey. Multiple linear regression modelling and mediating effects modelling were used for analyses., Results: Habitual tea drinking, frequent tea drinking (drinking tea 6-7 days per week), tea concentration and <10 g of tea per day were strongly associated with an increase in HRQoL among Chinese adults (all p<0.05). The association between tea-drinking habits and HRQoL among Chinese adults was more pronounced in the male population and in those ≥45 y of age (all p<0.05). Tea drinking habits may improve HRQoL in Chinese adults by enhancing sleep quality (all p<0.05)., Conclusions: Maintaining the habit of habitual tea drinking (6-7 days per week), in small amounts (<10 g tea per day) was conducive to improving HRQoL of Chinese adults by improving sleep quality., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Red peel color, a desirable trait in pears, is determined by anthocyanin accumulation. While REVEILLE (RVEs) transcription factors regulate anthocyanin biosynthesis in some plant species, their role in pear peel has not been well-studied. This study investigates the function of RVEs in anthocyanin biosynthesis in 'Zaosu' (low anthocyanin content) and its red bud mutant, 'Red Zaosu' (high anthocyanin content) fruit peel. Consistent with higher anthocyanin content, 'Red Zaosu' pears exhibited increased PbRVE6 expression compared to 'Zaosu', while PbRVE3a and PbRVE3b levels remained unchanged. Additionally, PbRVE6 was localized to the nucleus. Overexpression of PbRVE6 in 'Zaosu' pear pericarp significantly increased anthocyanin content and upregulated key anthocyanin pathway genes PbANS and PbUFGT. Conversely, VIGS silencing of PbRVE6 in 'Red Palacer' pears led to decreased expression of PbANS and PbUFGT and a slight reduction in anthocyanin content. Yeast one-hybrid and dual-luciferase assays confirmed that PbRVE6 can bind and activate the promoters of PbANS and PbUFGT. These findings demonstrate that PbRVE6 promotes anthocyanin accumulation in pear peel by directly regulating PbANS and PbUFGT expression. This study provides a valuable foundation for understanding the regulatory network of anthocyanins in pear peels, and offers potential genetic resources for the production of new pear germplasm., (© 2024 Scandinavian Plant Physiology Society.)

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.

Background Aims: Cord blood mononuclear cells (CBMCs) comprise a variety of single-nucleated cells found in the cord blood, mainly consisting of monocytes and lymphocytes. They also include a smaller proportion of other cell types, such as hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). CBMCs are vital for acquiring HSPCs, MSCs, and other immune cells, like natural killer cells. These cells are essential for supporting subsequent research and clinical applications. Although automated equipment for CBMC enrichment has shown promise, the high cost of these machines and the expense of disposable consumables limit their routine use. Furthermore, limited information is available on manual strategies for isolating CBMCs from cryopreserved cord blood. Therefore, we aimed to optimize the dilution buffer and refine the isolation procedure for CBMCs., Methods: We enhanced the CBMC recovery rate from cryopreserved cord blood using an optimized dilution buffer and a modified isolation procedure., Results: We achieved average recovery rates of 42.4 % and 54.3 % for CBMCs and CD34+ cells, respectively. Notably, all reagents used in the isolation procedure were of GMP-grade or pharmaceutical preparations, underscoring the potential clinical benefits of our strategy., Discussion: We devised an optimized protocol suitable for routine research and clinical applications for enhanced recovery of CBMCs from cryopreserved cord blood units using an optimized dilution buffer and a modified isolation procedure., Competing Interests: Declaration of competing interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2024. Published by Elsevier B.V.)

The sluggish kinetics of hydrogen evolution reaction (HER) via water reduction limits the efficiency of alkaline water electrolysis. The HER kinetics is not only intimately related to the catalyst surface structure but also relevant to the cation identity of the electrolyte. The cation dependence also relies on the surface electronic structure and applied potential, but this interrelated effect and its underlying mechanism awaits elucidation. Herein, differently-charged molybdenum sulfide (MoS x ) cluster supports ([Mo 3 S 13 ] 2- and [Mo 3 S 7 ] 4+ ) are utilized to hybridize with the identical metallic Ru centers. The specific electrostatic interaction between MoS x clusters and Ru precursors induces different Ru valences of the hybrids, with a higher valence state for Ru/Mo 3 S 13 endowing a higher activity. The Ru/Mo 3 S 13 and Ru/Mo 3 S 7 exhibited drastically-different cation dependence, in which the charged support determines the local accumulation of cations and resulting water structures. The more negatively-charged Mo 3 S 13 support induces the facile accumulation of cations, especially for less-hydrated K + cations. The water activation capability by Ru valences and cation accumulation from the support effect in-together determine the cation-dependent alkaline HER activity. This work not only enriches the understanding about the cation-dependent HER mechanism but also shines a light on the rational optimization strategy of electrode/electrolyte interfaces., (© 2024 Wiley‐VCH GmbH.)

Organic single crystals possess distinct advantages due to their highly ordered molecular structures, resulting in improved stability, enhanced carrier mobility, and superior optical characteristics. However, their mechanical rigidity and brittleness impede the applications in flexible and wearable optoelectronic devices. Here, photoluminescence (PL) emission from 2,6-diphenylanthracene (DPA) single crystals is studied under tensile strain, which shows PL enhancement by more than two times with a strain of ≈1.42%. Such a tension induced PL enhancement is reversible, exhibiting no clear optical degradations during 100 cycles of bending and recovery processes. Theoretical calculations reveal that the deformation of molecular structure under strain induces a decrease of the dihedral between anthracene and benzene moieties in DPA molecules. Further, the increased molecular conjugation enhances the molecular oscillator strength, leading to the brightened PL emission. Meanwhile, with the decreased dihedral, the molecular vibrations in DPA crystals are suppressed, which can reduce the non-radiative decay rate. In contrast, no tension induced PL enhancement is observed in polycrystalline DPA thin films as the strain can be released via the grain boundaries. This study highlights the superior optical performance of DPA single crystals under strain field, which will provide new possibilities for DPA-based flexible devices., (© 2024 Wiley‐VCH GmbH.)

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1β that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Carbon nanofibers (CFs) have been widely applied as electrodes for energy storage devices owing to the features of increased contact area between electrodes and electrolyte, and shortened transmission route of electrons. However, the poor electrochemical activity and severe waste of space hinder their further application as supercapacitors electrodes. In this work, MnO 2-x nanoflowers restricted and epitaxial growth in/out carbon nanofibers (MnO 2 /MnO@CF) were prepared as excellent electrode materials for supercapacitors. With the synergistic effect of uniquely designed structure and the introduction of MnO and MnO 2 nanoflowers, the prepared interconnected MnO 2 /MnO@CF electrodes demonstrated satisfactory electrochemical performance. Furthermore, the MnO 2 /MnO@CF//activated carbon (AC) asymmetric supercapacitor offered an outstanding long-term cycle stability. Besides, kinetic analysis of MnO 2 /MnO@CF-90 was conducted and the diffusion-dominated storage mechanism was well-revealed. This concept of "internal and external simultaneous decoration" with different valence states of manganese oxides was proven to improve the electrochemical performance of carbon nanofibers, which could be generalized to the preparation and performance improvement of other fiber-based electrodes., 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.)

Background: Antihistamines alleviate the side effects of antitumor drugs and exert antitumor effects. This study aimed to investigate the potential impact of short-term concomitant use of antihistamines with immune checkpoint inhibitor (ICI) therapy on the efficacy and immune-related adverse events (irAEs) of immunotherapy for patients with advanced lung cancer., Methods: We retrospectively analyzed the medical records of 211 patients diagnosed with advanced primary lung cancer and treated with immunotherapy at Tianjin Medical University Cancer Institute and Hospital between January 1, 2018, and January 1, 2022. Among these patients, 109 who received H1 antihistamine during the infusion of anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies were assigned to the experimental group; meanwhile, the remaining 102 patients who did not receive H1 antihistamines were assigned to the control group. Balancing was achieved through inverse probability of treatment weight (IPTW) estimation. The data were analyzed using Kaplan-Meier curves and Cox regression analyses., Results: The median progression-free survival (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival (mOS) was 32.8 months in the experimental group and 18.1 months in the control group. In the experimental group, patients treated with only H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines. Similarly, in the control group, patients who did not receive antihistamines had a longer mPFS and mOS than those who only received H2 antihistamines. After conducting multivariate analyses, we found that H1 and H2 antihistamines were respectively identified as good and poor independent prognostic factors for both progression-free survival (PFS) and overall survival (OS). The rates of irAEs in the experimental and control groups were 52.4% and 69.2%, respectively, and grade ≥3 irAEs occurred in 4.5% and 25.9% of patients, respectively., Conclusions: Concomitant use of H1 antihistamines can improve immunotherapy efficacy and reduce irAEs. Meanwhile, concomitant use of H2 antihistamines is associated with reduced PFS and OS time., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-795/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Here we report a three-component reaction of 2-formylarylboronic acids, N -sulfonyl amines and 1,3-enynes, proceeding through a cascade imine formation/Pd 0 -catalysed vinylogous addition/intramolecular Suzuki coupling/isomerization process. This protocol exhibited broad substrate scope and good functionality tolerance, and a spectrum of multifunctionalised benzofulvene derivatives were furnished in moderate to good yields and E / Z -selectivity.

γ-Aminobutyric acid (GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABA A receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley (SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant α6β3δ subunit-containing GABA A receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current (sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex (mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin related kinase B (TrkB) and postsynaptic density protein 95 (PSD-95) in mPFC of mice. The above results suggest that LY-02, as a positive modulator of GABA A receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment.

The transition metal-catalyzed asymmetric hydro-functionalization of 1,3-dienes has been well explored, but most reactions focus on electron-neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4-dienyl hydrazones and oximes can be efficiently utilized in the hydro-cyclization reaction under co-catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron-deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α-regioselective protonation of dienyl substrates by acid and concurrent π-Lewis base activation of Pd 0 complex is energetically favoured in the formation of active π-allylpalladium intermediates, and an outer-sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively., (© 2024 Wiley-VCH GmbH.)

Globally, over three billion people rely on traditional solid fuels for cooking and heating, leading to significant household air pollution and critical public health concerns. While transitioning to clean energy carriers faces challenges of accessibility and affordability-especially among low-income, rural populations-alternative strategies like kitchen layout modifications and the use of ventilation fans may effectively reduce exposure to pollutants. Here, we analyze factors influencing the adoption of separated kitchens and mechanical ventilation and evaluate changes in human exposure to PM 2.5 under different kitchen renovation scenarios by conducting a nationwide survey of household kitchen characteristics in rural China. We found that although 82% of rural households have kitchens separated from other rooms, only 34% use mechanical ventilation. The adoption of ventilation fans is significantly influenced by income and education levels. We estimate that widespread implementation of ventilation fans and separated kitchen designs could prevent approximately 67400 premature deaths annually, resulting in a health benefit of about USD 19 billion per year-substantially exceeding the costs involved. These findings suggest that cost-effective kitchen renovations offer enormous potential for substantial health benefits and present a practical solution compared to the challenges of clean energy transitions in rural areas., 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.)

Objectives: This study seeks to investigate the potential correlation between various levels of frailty and suicidal ideation (SI) in older adults from the USA., Methods: Our cross-sectional study extracted data on adults ≥60 years from the NHANES in 2005-2018. Frailty levels were assessed by computing the Frailty Index, classifying individuals into robust, prefrail, and frail categories. SI was evaluated utilizing Item #9 of PHQ-9. Logistic regression and restricted cubic splines were employed for analysis., Results: The analysis comprised 8564 participants, revealing that 3.3% reported experiencing SI. The association between frailty and SI in older adults was statistically significant in crude model (OR: 5.94, 95% CI: 3.46-11.27, P < 0.001). Upon adjusting for baseline characteristics, the association remained robust (AOR: 5.35, 95% CI: 3.09-10.19, P < 0.001). Model II did not substantially alter the association between frailty and SI after further adjustment for lifestyle factors (AOR: 5.23, 95% CI: 3.02-9.98, P < 0.001). In a sensitivity analysis controlling for depression, the association remained statistically significant (AOR:3.62, 95%CI: 1.76-8.75, P = 0.001). Furthermore, the associations between the Frailty Index and SI were pronounced in the restricted cubic spline (RCS) models (P overall < 0.001, P nonlinearity  = 0.771)., Conclusion: Frailty appears to heighten vulnerability to suicidal ideation in older adults. Training healthcare professionals to identify and address mental health issues related to frailty is crucial. Through comprehensive intervention measures, we can better safeguard the mental well-being of older adults and reduce the risk of suicide., 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.)

Objective: We aim to estimate the prevalence of baseline clinically significant distress in Chinese patients with head and neck squamous cell carcinoma (HNSCC) before receiving the first radiotherapy and assess factors predictive of distress., Methods: One hundred and sixty-eight patients were enrolled to complete a set of questionnaires including Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). Of these, 131 questionnaires were available for the final analysis. The accuracy of DT was validated using HADS as the gold standard, and receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff score of DT., Results: Distress was reported in sixty-two patients (47%). Patients who were visited in the last week (p = 0.022) and those with medical-related occupations (p = 0.017) were less likely to suffer from psychological distress. Additionally, religious belief was negatively associated with both the DT and HADS-T scores, indicating that patients with religious beliefs were less likely to report high levels of distress (odds ratio (OR) for DT ≥ 4 = 0.291, p = 0.039; OR for HADS-T ≥ 15 = 0.316, p = 0.047). Factors such as age, gender, marital status, education and residency did not contribute to distress levels. DT was significantly correlated with HADS-T (Correlation coefficient (r) = 0.624, p < 0.001) and the best cutoff score of DT was 4 in screening distress., Conclusions: DT was a brief and effective tool to screen distress among HNSCC patients., (© 2024. The Author(s).)

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H 2 O 2 -treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Context and Objectives: The human calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis, and most identified CASR variants are associated with hypercalcemic and hypocalcemic disorders. Here we characterized the pharmacological implications of five heterozygous CASR variants from individuals with familial hypocalciuric hypercalcemia 1 [FHH1: Y63C, I81T, Q459R, W818stop] or autosomal dominant hypocalcemia 1 [ADH1: R955stop]., Methods: Total and cell surface expression levels of wild-type (WT) and variant CaSRs expressed in human embryonic kidney 293T (HEK293T) cells were determined using ELISA, and the pharmacological properties of the receptors were delineated in two functional assays., Results: The Y63C and I81T variations in the extracellular domain (ECD) of CaSR yielded markedly reduced cell surface expression and Ca2+ responsiveness, while Q459R displayed WT-like expression and functional properties. Truncation of the 7-transmembrane domain (7TMD) in W818stop eliminated cell surface expression, whereas R955stop in the intracellular carboxy-terminal yielded modestly increased surface expression and Ca2+ potency compared with WT CaSR. Interestingly, the effectiveness of positive allosteric modulators (PAMs) at the variants varied. Ca2+-mediated signaling through Y63C and I81T was significantly augmented by 7TMD-binding PAMs (NPS R-568 and Evocalcet) but not by ECD-binding PAMs (Etelcalcetide and Nb4), whereas signaling through Q459R and R955stop were robustly potentiated by all four PAMs., Conclusions: While the molecular phenotypes exhibited by the five CaSR variants concord with the clinical phenotypes in individuals harboring them, CASR variant-induced calcium homeostasis disorders clearly arise from diverse molecular origins, and the effectiveness of calcimimetics in these disorders could differ depending on the specific variants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. 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. See the journal About page for additional terms.)

Peach gummosis, a devastating disease caused by Neofusicoccum parvum , significantly shortens peach tree lifespan and reduces the yield of peach trees. Despite its impact, the molecular mechanism underlying this disease remains largely unexplored. In this study, we used RNA-seq, sugar metabolism measurements, and an integrated transcriptional and metabolomic analysis to uncover the molecular events driving peach gummosis. Our results revealed that N. parvum infection drastically altered the transcripts of cell wall degradation-related genes, the log 2 Fold change in the transcript level of Prupe.1G088900 encoding xyloglucan endotransglycosylase decreased 2.6-fold, while Prupe.6G075100 encoding expansin increased by 2.58-fold at 12 hpi under N. parvum stress. Additionally, sugar content analysis revealed an increase in maltose, sucrose, L-rhamnose, and inositol levels in the early stages of infection, while D-galactose, D-glucose, D-fructose consistently declined as gummosis progressed. Key genes related to cell wall degradation and starch degradation, as well as UDP-sugar biosynthesis, were significantly upregulated in response to N. parvum . These findings suggest that N. parvum manipulates cell wall degradation and UDP-sugar-related genes to invade peach shoot cells, ultimately triggering gum secretion. Furthermore, weighted gene co-expression network analysis (WGCNA) identified two transcription factors, ERF027 and bZIP9 , as central regulators in the downregulated and upregulated modules, respectively. Overall, this study enhances our understanding of the physiological and molecular responses of peach trees to N. parvum infection and provide valuable insights into the mechanisms of peach defense against biotic stresses., 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 Zhang, Liu, Gan, Du, Ai, Zhu, Wang, Wang, Gong and He.)

Limestone calcined clay cement (LC3), enhanced through reactions with volcanic ash and the interaction between limestone and clay, significantly improves the performance of cementitious materials. It has the potential to cut CO 2 emissions by up to 30% and energy consumption in cement manufacture by 15% to 20%, providing a promising prospect for the large-scale production of low-carbon cement with a lower environmental effect. To effectively manufacture LC3 concrete, this study utilized limestone (15%), calcined clay (30%), and gypsum (5%) as supplementary cementitious materials (SCMs), replacing 50% of ordinary Portland cement (OPC). However, in regions abundant in sulfate, sulfate attack can cause interior cracking of concrete, reducing the longevity of the building. To address this issue, microcapsules containing microcrystalline wax, ceresine wax, and nano-CaCO 3 encapsulated in epoxy resin were prepared and successfully incorporated into LC3 concrete. Sulfate resistance tests were conducted through sulfate dry-wet cycles, comparing samples with and without microcapsules. The findings revealed that the initial mechanical and permeability properties of LC3 concrete did not significantly differ from OPC concrete. LC3 concrete with added microcapsules (SP4) exhibited enhanced resistance to sulfate attack, reducing mass loss and compressive strength degradation. SEM images displayed a mesh-like structure of repair products in SP4. After 14 days of self-repair, SP4 exhibited a 44.2% harmful pore ratio, 98.1% compressive strength retention, 88.7% chloride ion diffusion coefficient retention, 91.12 mV maximum amplitude, and 9.14 mV maximum frequency amplitude. The experimental results indicate that the presence of microcapsules enhances the sulfate attack self-healing performance of LC3 concrete.

Two coumarin derivatives SWJT-33 and SWJT-34 were synthesized as probes for the detection of cadaverine (Cad). Among them, SWJT-34 exhibits high selectivity and low detection limits for Cad using fluorescence or UV-vis spectrum. The detection limits for Cad were calculated to be 0.018 μM by fluorescence spectrum and 0.34 μM by UV-vis spectrum, which was much lower than those of most of reported probes. The probe could realize colorimetric and ratiometric detection of Cad because an aza-Michael addition reaction occurred between SWJT-34 and Cad to form the Schiff base compound as a product. In addition, SWJT-34 could be fabricated as portable test strips for the selective detection of Cad in vapor, and the corresponding detection limits were calculated to be 1.88 ppm in the fluorescent mode and 57 ppm in UV-vis mode, respectively. Additionally, these test strips could be used to test the freshness of Rottweiler shrimp and pork at different temperatures., 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: Motile Sperm Domain-Containing Protein 1 (MOSPD1) has been implicated in breast cancer (BC) pathophysiology, but its exact role remains unclear. This study aimed to assess MOSPD1 expression levels in BC versus normal tissues and investigate its diagnostic potential., Methods: MOSPD1 expression was analyzed in BC and normal tissues, with Receiver Operating Characteristic analysis for diagnostic evaluation. Validation was performed using immunohistochemistry. Functional studies included tumor growth assays, MOSPD1 suppression and overexpression experiments, and testing BC cell responses to anti-PD-L1 therapy., Results: MOSPD1 expression was significantly higher in BC samples than normal tissues, correlating with poor clinical outcomes in BC patients. MOSPD1 suppression inhibited tumor growth, while overexpression accelerated it. Silencing MOSPD1 enhanced BC cell sensitivity to anti-PD-L1 therapy and decreased Th2 cell activity. In vivo experiments supported these findings, showing the impact of MOSPD1 on tumor growth and response to therapy., Conclusions: Elevated MOSPD1 levels in BC suggest its potential as a biomarker for adverse outcomes. Targeting MOSPD1, particularly with anti-PD-L1 therapy, may effectively inhibit BC tumor growth and modulate immune responses. This study emphasizes the significance of MOSPD1 in BC pathophysiology and highlights its promise as a therapeutic target., (© 2024. The Author(s).)

What Is Already Known About This Topic?: Interventions aimed at modifying lifestyle behaviors can effectively reduce the risk of depression among adolescents. These lifestyle behaviors tend to be interconnected; thus, changes to one behavior can often lead to changes in others, usually occurring simultaneously., What Is Added by This Report?: Adolescents from Jiangsu Province displayed distinct lifestyle patterns, with those engaging in multiple specific behaviors, such as excessive consumption of sugar-sweetened beverages and prolonged screen time, showing increased odds of depression., What Are the Implications for Public Health Practice?: Early implementation of anti-depression interventions in adolescents should be advocated and prioritized, particularly targeting multiple high-risk lifestyles., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

With significant advancements in the study of DNA Damage Response (DDR) and Fanconi Anemia (FA) signaling, we previously introduced the term "FA signaling" to encompass "all signaling transductions involving one or more FA proteins." This network has now evolved into the largest cellular defense network, integrating over 30 key players, including ATM, ATR, BLM, HRR6, RAD18, FANCA, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4, ERCC4, RAD51, BRCA1, UBE2T, XRCC2, MAD2L2, RFWD3, FAAP20, FAAP24, FAAP100, and CENPX. This system responds to both endogenous and exogenous cellular insults. However, the mutational signatures associated with this defense mechanism in non-FA human cancers have not been extensively explored. In this study, we report that different types of human cancers are characterized by distinct somatically mutated genes related to DDR/FA signaling, each accompanied by a unique spectrum of potential driver mutations. For example, in pan-cancer samples, ATM emerges as the most frequently mutated gene (5%) among the 31 genes analyzed, with the highest number of potential driver mutations (1714), followed by BRCA2 (4% with 970 putative driver mutations). However, this pattern is not universal across specific cancer types. For example, FANCT is the most frequently mutated gene in breast (14%) and liver (4%) cancers. In addition, the alteration frequency of DDR/FA signaling due to these mutations exceeds 70% in a subtype of prostate cancer, with each subtype of brain, breast, lung, and prostate cancers displaying distinct patterns of gene alteration frequency. Furthermore, these gene alteration patterns significantly impact patient survival and disease-free periods. Collectively, our findings not only enhance our understanding of cancer development and progression but also have significant implications for cancer patient care and prognosis, particularly in the development of effective therapeutic strategies., 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 Rai, Du, Zhang, Yu, Deng and Fei.)

The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen. In this study, we investigated how the RGR-d exacerbates AMD-like changes under oxidative stress, both in vivo and in vitro. Fundus atrophy became evident, at 12 months old, particularly in the RGR-d + HFD group, and fluorescence angiography revealed narrower retinal vessels and a reduced perfusion area in the peripheral retina. Although rod electroretinography revealed decreasing trends in the a- and b-wave amplitudes in the RGR-d + HFD group at 12 months, the changes were not statistically significant. Mice in the RGR-d + HFD group showed a significantly thinner and more fragile retinal morphology than those in the WT + HFD group, with disordered and discontinuous pigment distribution in the RGR-d + HFD mice. Transmission electron microscopy revealed a thickened Bruch's membrane along the choriocapillaris endothelial cell wall in the RGR-d + HFD mice, and the outer nuclear layer structure appeared disorganized, with reduced nuclear density. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significantly lower levels of 25(OH)-vitamin D3 metabolites in the RGR-d + HFD group. Under oxidative stress, RGR-d localized to the mitochondria and reduced the levels of the PINK1-parkin pathway. RGR-d mice fed an HFD were used as a new animal model of dry AMD. Under high-fat-induced oxidative stress, RGR-d accumulated in the mitochondria, disrupting normal mitophagy and causing cellular damage, thus exacerbating AMD-like changes both in vivo and in vitro., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge., Methods: A study dynamically comparing levels of fifteen lectin-specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan-Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression-free survival (PFS) of the HCC patients., Results: HCC patients presented significantly higher levels of the lectin-specific glycans in preoperative serum than disease-free individuals (p < 0.001 - p = 0.029), except ConA. The glycans in preoperative sera were significantly related to tumor size, pTNM, metastasis, BCLC stage, portal hypertension (PHT), and platelet count (PLT), respectively (p < 0.05). Multivariate logistic analyses indicated that tumor size and pTNM independently impact on glycan-specific lectins either LTL, UEA-I, VVL, NPL, WGA, PNA, MAL-I, SNA, or PHA-L (p = 0.003 - p = 0.044); BCLC stage and PLT were independent factors influencing the serum glycans recognizable DSA (p = 0.024) and SNA (p = 0.050), respectively. Surgical excision of tumor mass significantly reduced glycan levels in sera. Tumor differentiation, albumin, and ABO type significantly revealed independent influence on glycan-specific lectins, such as RCA-I (p = 0.024), VVL (p = 0.024), and Con A (p = 0.026) in the postoperative serum. HCC patients with high levels of VVL-binding glycans significantly benefited from a longer OS time (p = 0.016, HR: 0.460, 95% CI: 0.237-0.892) and a better PFS time (p = 0.004; HR: 0.435, 95% CI: 0.237-0.799), respectively., Conclusion: Serum glycans could reflect surgical outcomes in at-risk patients and become valuable biomarkers in evaluating the progression of HCC patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Animals spend a considerable proportion of their life span at rest. However, resting status has often been overlooked when investigating how species respond to environmental conditions. This may induce a large bias in understanding the local adaptation of species across environmental gradients and their vulnerability to potential environmental change. Here, we conducted an empirical study on montane agamid lizards, combined with mechanistic modeling, to compare elevational variations in body temperature and metabolisms (cumulative digestion and maintenance cost) between resting and active status. Our study on three populations of an agamid lizard along an elevational gradient revealed a trend of decreasing body temperature toward higher elevations, the main contributor of which was resting status of the lizards. Using population-specific reaction norms, we predicted greater elevational variation in hourly and cumulative digestion for resting lizards than for active lizards. Climate-change impacts, estimated as the change in cumulative digestion, also show greater elevational variation when resting status is factored into the analysis. Further, our global analysis of 98 agamid species revealed that in about half of their combined distributional range, the contribution of resting status in determining the elevational variation in cumulative digestion and maintenance cost of lizards was greater than the contribution made by a lizard's active status. Our study highlights the importance of considering resting status when investigating how species respond to environmental conditions, especially for those distributed over tropical and subtropical mountain areas., (© 2024 The Ecological Society of America.)

This study aims to investigate the effect of the combined method of freeze-thaw and leaching on the removal of cadmium (Cd) in soil and to provide a theoretical basis for the remediation of farmland soil polluted by heavy metals. The removal process and mechanism of Cd were deduced through oscillatory leaching experiments and freeze-thaw leaching simulation experiments, and the influence of the freeze-thaw leaching technology on the soil environment was evaluated. The results of oscillatory leaching showed that a mixture consisting of 0.80 mol/L citric acid and 0.80 mol/L ferric chloride in a 1:19 vol ratio effectively remove 47.75 % of Cd, indicating that the composite leaching agent could effectively remove Cd from the soil. The results of the freeze-thaw leaching simulation experiment showed that although the freeze-thaw leaching treatment increased the total Cd content in the 0-5 cm soil layer, the total Cd content in the 5-10 cm, 10-15 cm, and 15-20 cm soil layers decreased by 5.08 %, 2.39 %, and 5.68 %, respectively. The freeze-thaw leaching increased the content of exchangeable Cd (p<0.05), carbonate bound Cd, but decreased organic bound Cd and residual Cd (p<0.05), thereby increasing the bioavailability of Cd. Freeze-thaw leaching not only increased the competitive adsorption of Cd 2+ by decreasing soil pH, cation exchange capacity, and increasing the content of exchangeable calcium and exchangeable magnesium, thus reducing the adsorption of Cd in soil. And the results of XPS and FTIR similarly showed that the freeze-thaw leaching could promote the chelation between Cd 2+ and hydroxyl, carboxyl and carbonyl functional groups. Although the freeze-thaw leaching destroyed the large particle structure (0.05-2 mm) and large pores in the soil, and increased the clay content (<0.002 mm) and the proportion of small pores in the soil, the XRD results showed that freeze-thaw leaching had no significant effect on the minerals in the soil. In summary, this study shows that freeze-thaw leaching has a significant effect on the removal of soil heavy metals, suggesting that the synergistic effect of freeze-thaw and leaching should be considered in the process of removing soil pollutants in seasonal freeze-thaw zones, and that this method provides a new insight into the remediation of contaminated soils., 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.)

Denitrification, anammox, and DNRA are three important nitrogen (N) reduction pathways in estuarine sediments. Although salinity is an important variables controlling microbial growth and activities, knowledge about the effects of changing salinity on those three processes in estuarine and coastal wetland sediments are not well understood. Herein, we performed a 60-d microcosms experiment with different salinities (0, 5, 15, 25 and 35 ‰) to explore the vital role of salinity in controlling N-loss and N retention in estuarine wetland sediments. The results showed that sediment organic matter, sulfide, and nitrate (NO 3 - ) were profoundly decreased with increasing salinity, while sediment ammonium (NH 4 + ) and ferrous (Fe 2+ ) varied in reverse patterns. Meanwhile, N-loss and N retention rates and associated gene abundances were differentially inhibited with increasing salinity, while the contributions of denitrification, anammox, and DNRA to total nitrate reduction were apparently unaffected. Moreover, denitrification rate was the most sensitive to salinity, and then followed by DNRA, while anammox was the weakest among these three processes. In other words, anammox bacteria showed a wide range of salinity tolerance, while both denitrification and DNRA reflected a relatively limited dynamic range of it. Our findings could provide insights into temporal interactive effects of salinity on sediment physico-chemical properties, N reduction rates and associated gene abundances. Our findings can improve understanding of the effects of saltwater incursion on the N fate and N balance in estuarine and coastal sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening., (© 2024. The Author(s).)

With the wide application of electromagnetic waves in national defense, communication, navigation and home appliances, the electromagnetic pollution problem is becoming more and more prominent. Therefore, high-performance, and low-density composite wave-absorbing materials have attracted much attention. In this paper, three-dimensional (3D) network structures of flower-like 1T/2H Molybdenum disulfide nanosheets anchored to carbon fibers (1T/2H MoS 2 /CNFs) were prepared by electrostatic spinning technique and calcination process. The morphology and electromagnetic wave absorption properties were tuned by changing the content of flower-like MoS 2 . The optimized 1T/2H MoS 2 /CNFs composite exhibits superior electromagnetic wave absorption with minimum reflection (RL min ) of -42.26 dB and effective absorption bandwidth (EAB) of 6.48 GHz at 2.5 mm. Multi-facts contribute to the super performance. First, the uniquely designed nanosheet and 3D interconnected networks leads to multiple reflection and scattering of electromagnetic waves, which promotes the attenuation of electromagnetic waves. Second, the propriate content of CNFs and MoS 2 with different phase regulates its impedance matching characteristic. Third, Numerous heterogeneous interfaces existed between CNFs and MoS 2 , 1T and 2H MoS 2 phase results in interface polarization. Besides, the 1T/2H MoS 2 rich in defects induces defect polarization, improving the dielectric loss. Furthermore, the electromagnetic wave absorption performance was proved via radar reflectance cross section simulation. This work illustrates 1T/2H MoS 2 /CNFs is a promising material for electromagnetic absorption with wide bandwidth, strong absorption, low density, and high thermal stability., 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.)

For every epidemic outbreak, the prevention and treatments in resource-limited areas are always out of reach. Critical to this is that high accuracy, stability, and more comprehensive analytical techniques always rely on expensive and bulky instruments and large laboratories. Here, a fully integrated and high-throughput microfluidic system is proposed for ultra-multiple point-of-care immunoassay, termed Dac system. Specifically, the Dac system only requires a handheld portable device to automatically recycle repetitive multi-step reactions including on-demand liquid releasing, dispensing, metering, collecting, oscillatory mixing, and discharging. The Dac system performs high-precision enzyme-linked immunosorbent assays for up to 17 samples or targets simultaneously on a single chip. Furthermore, reagent consumption is only 2% compared to conventional ELISA, and microbubble-accelerated reactions shorten the assay time by more than half. As a proof of concept, the multiplexed detections are achieved by detecting at least four infection targets for two samples simultaneously on a singular chip. Furthermore, the barcode-based multi-target results can rapidly distinguish between five similar cases, allowing for accurate therapeutic interventions. Compared to bulky clinical instruments, the accuracy of clinical inflammation classification is 92.38% (n = 105), with a quantitative correlation coefficient of R 2 = 0.9838, while the clinical specificity is 100% and the sensitivity is 98.93%., (© 2024 Wiley‐VCH GmbH.)

Objective: It is critical to accurately determine the level of obesity and health status since overweight/obesity has become a main global public health problem. This systematic review attempted to evaluate the consistency and correlation between body composition measurement indicators and body mass index (BMI) in childhood and adolescence., Methods: Seven electronic databases (Web of Science, PubMed, Cochrane Library, Embase, CNKI, WANFANG DATA, SinoMed) were searched to collect the literature published since 1999 with the focus on the relationship between body composition measurement indicators and BMI to measure obesity in childhood and adolescence., Results: Among the 28 articles included, 13 articles reported a moderate to very strong correlation between %BF and BMI in obesity measurement (range: 0.49-0.907), while two articles reported a strong to very strong correlation between FM and BMI (range: 0.60-0.86). Six articles reported good to excellent obesity measurement consistency between %BF and BMI (range: 0.441-0.876), one article reported WC (0.58) and WHtR (0.46) in the moderate consistency with BMI, and one article reported a relatively poor to fair consistency between FM and BMI (range: 0.167-0.409). WC, WHtR, and BMI showed the moderate consistency in pre-adolescent children. In pre-adolescence and adolescence, the measurement consistency between %BF and BMI was higher than that between FM and BMI. Gender difference existed in the consistency between %BF and BMI during adolescence., Conclusion: A range of body composition indicators such as %BF, WC, WHtR, and FM could provide valuable body composition measurements, complement BMI for obesity assessment in children and adolescents, and facilitate efficient and comprehensive surveillance of childhood obesity., Registration: PROSPERO CRD42024506932., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The acute levodopa challenge test (ALCT) is a universal method for evaluating levodopa response (LR). Assessment of Movement Disorder Society's Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) is a key step in ALCT, which is some extent subjective and inconvenience., Methods: This study developed a machine learning method based on instrumented Timed Up and Go (iTUG) test to evaluate the patients' response to levodopa and compared it with classic ALCT. Forty-two patients with parkinsonism were recruited and administered with levodopa. MDS-UPDRS III and the iTUG were conducted in both OFF-and ON-medication state. Kinematic parameters, signal time and frequency domain features were extracted from sensor data. Two XGBoost models, levodopa response regression (LRR) model and motor symptom evaluation (MSE) model, were trained to predict the levodopa response (LR) of the patients using leave-one-subject-out cross-validation., Results: The LR predicted by the LRR model agreed with that calculated by the classic ALCT (ICC = 0.95). When the LRR model was used to detect patients with a positive LR, the positive predictive value was 0.94., Conclusions: Machine learning based on wearable sensor data and the iTUG test may be effective and comprehensive for evaluating LR and predicting the benefit of dopaminergic therapy., (© 2024. The Author(s).)

Metformin (MET) is currently the first-line treatment for type 2 diabetes mellitus (T2DM). However, overdose and long-term use of MET may induce a serious liver injury. What's worse, diagnosis of MET-induced liver injury remains challenging in clinic. Although several probes have been reported for imaging MET-induced liver injury utilizing upregulated hepatic H 2 S as a biomarker, they are still at risk of nonspecific activation in complex physiological environments and rely on light excitation with limited imaging depth. Herein, we rationally designed and developed a dual-locked probe, DPA-H 2 S, for precise imaging of MET-induced liver injury by H 2 S-activated sonoafterglow luminescence. DPA-H 2 S is a small molecule consisting of a sonosensitizer protoporphyrin IX (PpIX) and an afterglow substrate that is dual-locked with a H 2 S-responsive 2,4-dinitrobenzene group and a 1 O 2 -responsive electron-rich double bond. When employing DPA-H 2 S for imaging of MET-induced liver injury in vivo , since the PpIX moiety can produce 1 O 2 in situ at the liver site under focused ultrasound (US) irradiation, the two locks of DPA-H 2 S can be specifically activated by the highly upregulated H 2 S at the liver injury sites and the in situ generated 1 O 2 , respectively. Thus, the sonoafterglow signal of DPA-H 2 S is significantly turned on, enabling precise imaging of the MET-induced liver injury. In vitro results showed that, through H 2 S-activated sonoafterglow luminescence, DPA-H 2 S was capable of imaging H 2 S with good sensitivity and high selectivity and realized deep tissue imaging (∼20 mm, signal-to-background ratio (SBR) = 3.4). Furthermore, we successfully applied DPA-H 2 S for precise in vivo imaging of MET-induced liver injury. We anticipate that our dual-locked probe, DPA-H 2 S, may serve as a promising tool in assisting the diagnosis of MET-induced liver injury in clinics and informing the clinical utilization of MET in the near future.

We investigate the temperature tunable dual quasi-bound states in the continuum (qBICs) in a silicon/vanadium dioxide (Si/VO 2 ) hybrid metasurface with Q-factor being as large as 9.3 × 10 6 and 2.8 × 10 7 by breaking the in-plane C 2 symmetry. The far-field scattering of multipoles and near-field distributions confirm that the toroidal dipole and magnetic quadrupole dominate the dual qBICs resonance. The high performance of slow light with ultralarge group index exceeding 5.6 × 10 5 and the inverse quadratic law between the group index and asymmetric parameter are achieved. By temperature tuning of the VO 2 thin film at the sub-10 K scale, a modulation depth of 90% and the ON/OFF ratio exceeding 12.8 dB are obtained. The proposed temperature tunable dual qBICs have potential applications in the fields of tunable slow light, temperature switches, and sensors.

To explore the characteristics and evaluate the risk of heavy metals in groundwater at a typical smelter-contaminated site, this study focuses on a representative a historical arsenic smelting plant in Southwest China, where the primary historical products were metallic arsenic (∼1000 tons/year) and arsenic trioxide (∼2000 ton/year). The results demonstrated As and Pb as the main pollutants in soil, and As and Cd as main pollutants in groundwater through soil profiling and quarterly groundwater analysis. The maximum As and Pb in the surface soil were 76800 and 2290 mg/kg, respectively, with As vertically infiltrating the deep gravel-sand layer (18-20 m). The groundwater pollution distribution progressively increased along flow direction, influenced by seasonal surface runoff and infiltration fluctuations. The groundwater pollutant concentrations during the dry season notably surpassed those during the wet season, with maximum As and Cd concentrations of 111.64 mg/L and 19.85 μg/L during the dry season, respectively. Furthermore, the analytic hierarchy process (AHP) was applied to evaluate the comprehensive risk of contaminated-site across pollution source load, regional groundwater intrinsic vulnerability, and evaluation of nearby sensitive receptors. The results revealed that the carcinogenic risk of lead in surface soil was moderate to high, while arsenic posed a high carcinogenic risk, contributing to an overall carcinogenic risk proportion of 89.6% in surface soil. Exposure through groundwater intake was identified as the primary pathway, with carcinogenic and noncarcinogenic risks exceeding those through skin contact. The final weights result demonstrated that the principal risk factors are the intrinsic arsenic load and protective target characteristics of regional groundwater at this site. This study provides a reference for comprehensive assessments of similarly contaminated industrial and smelting sites., 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.)

Despite biological wastewater treatment processes (e.g., sequencing batch reactors (SBR)) being able to reduce the dissemination of antibiotic resistance genes (ARGs), the variation of ARGs under exogenous pollutant stress is an open question. This work investigated the impacts of para-chloro-meta-xylenol (PCMX, typical antibacterial contaminants) on ARGs spread in long-term SBR operation. Although the SBR process inherently decreased ARGs abundance, the presence of PCMX substantially amplified both the prevalence (mainly multidrug) and abundance of total ARGs (1.17-fold of the control). Further analysis demonstrated that PCMX disintegrated sludge structures as well as increased membrane permeability, facilitating the release of mobile genetic elements and subsequent horizontal transfer of ARGs. In addition, PCMX selectively enriched potential ARG hosts, notably Nitrospira and Candidatus Accumulibacter, which predominantly served as multidrug ARG hosts. Concurrently, the self-adaptive functions of ARGs hosts in the PCMX-exposed SBR system were activated via quorum sensing, two-component regulatory system, ATP-binding cassette transporters, and bacterial secretion system. The upregulation of these metabolic pathways also contributed to the dissemination of ARGs., 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.)