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Resistance to paclitaxel poses a major obstacle in esophageal squamous cell carcinoma (ESCC) treatment. A better understanding of the mechanisms underlying paclitaxel resistance could help identify prognostic biomarkers and improved therapeutic strategies. In this study, we established a patient-derived xenograft model of acquired paclitaxel resistance and used RNA sequencing to identify galectin-1, encoded by LGALS1, as a key mediator of resistance. Integrative analysis of clinical data and physiological studies indicated that serum galectin-1 levels were elevated in resistant patients and correlated with treatment outcomes before and during taxane therapy. Importantly, exposing cells to serum from resistant patients resulted in increased paclitaxel resistance compared to serum from sensitive patients, which was closely associated with galectin-1 concentrations in the serum. The specific clearance of galectin-1 from resistant patient serum significantly restored paclitaxel sensitivity, and inhibiting galectin-1, through knockdown or the pharmacologic inhibitor OTX008, increased sensitivity to paclitaxel. Galectin-1 inhibition reduced the activity of β-catenin, thereby inhibiting stem cell properties induced by the Wnt/β-catenin pathway. Furthermore, galectin-1 regulated MDR1 transcription through increased nuclear accumulation of β-catenin, thus increasing resistance to paclitaxel. Combining OTX008 with clinical taxane formulations effectively reversed paclitaxel resistance in vitro and in vivo. Elevated galectin-1 levels thus serve as an indicator of response to paclitaxel therapy in ESCC, offering a therapeutic intervention strategy to overcome drug resistance. Significance: Galectin-1 is a key mediator of paclitaxel resistance in esophageal squamous cell carcinoma that can be targeted to improve taxane efficacy, suggesting broad therapeutic potential for treating various cancer types., (©2024 American Association for Cancer Research.)

Disulfiram (DSF) metabolites exhibit antitumor properties when bound to Cu 2+ . This combination also promotes the generation of reactive oxygen species (ROS), ultimately leading to tumor cell death. In this study, CuO 2 served as a carrier for DSF, forming a dual-drug delivery system with Cu 2+ and DSF encapsulated in polydopamine (PDA). In the final delivery system, CuO 2 (DSF-CuO 2 @PDA) was hydrolyzed at the tumor site, releasing both Cu 2+ and H 2 O 2 . Cu 2+ reacts with DSF metabolites to form Bis(diethyldithiocarbamate)-Cu (CuET), which triggers a Fenton-like reaction that generates ROS. Chemotherapy and chemodynamic therapy exhibited significant tumor-suppressive capabilities, with an inhibition rate of 61 %. In addition, the DSF-CuO 2 @PDA complex demonstrated superlative tumor-targeting ability and biocompatibility., 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.)

In tomato, sugar content is highly correlated with consumer preferences, with most consumers preferring sweeter fruit 1-4 . However, the sugar content of commercial varieties is generally low, as it is inversely correlated with fruit size, and growers prioritize yield over flavour quality 5-7 . Here we identified two genes, tomato (Solanum lycopersicum) calcium-dependent protein kinase 27 (SlCDPK27; also known as SlCPK27) and its paralogue SlCDPK26, that control fruit sugar content. They act as sugar brakes by phosphorylating a sucrose synthase, which promotes degradation of the sucrose synthase. Gene-edited SlCDPK27 and SlCDPK26 knockouts increased glucose and fructose contents by up to 30%, enhancing perceived sweetness without fruit weight or yield penalty. Although there are fewer, lighter seeds in the mutants, they exhibit normal germination. Together, these findings provide insight into the regulatory mechanisms controlling fruit sugar accumulation in tomato and offer opportunities to increase sugar content in large-fruited cultivars without sacrificing size and yield., Competing Interests: Competing interests A patent on the use of SlCDPK27 and SlCDPK26 to improve fruit sugar content has been filed by S.H., J.Z., H.L., J.C. and G.Z. (CN202211616622.8; PCT/CN2023/138699). The other authors declare no competing interests., (© 2024. The Author(s).)

Hypervigilance involves increased attentional scanning of the environment to facilitate the detection of possible threats. Accordingly, this state is mostly bound to external attention and as a corollary, it might be detrimental to internal attention and further affect attentional balance defined as the ability to switch dynamically between these two domains. In the current study, we aimed to address this question and induced hypervigilance in 49 healthy participants through the presentation of a task-unrelated aversive sound while they performed the switching attention task (SAT), which was previously devised to study attentional balance. The skin conductance response results, as well as subjective sound ratings, confirmed that the hypervigilance manipulation was successful. At the behavioral level, hypervigilance led to a more symmetrical balance between internal and external attention compared to the control and neutral conditions, where it was asymmetrical, replicating previous studies. Moreover, using a drift diffusion model, we found that hypervigilance reduced the drift rate for internal repetition trials, suggesting that hypervigilance possibly caused an impaired shielding of internal attention., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Clonal hematopoiesis (CH) increases inflammasome-linked atherosclerosis but the mechanisms by which CH mutant cells transmit inflammatory signals to non-mutant cells are largely unknown. To address this question we transplanted 1.5% Jak2VF bone marrow (BM) cells with 98.5% WT BM cells into hyperlipidemic Ldlr-/- mice. Low allele burden (LAB) mice showed accelerated atherosclerosis with increased features of plaque instability, decreased levels of macrophage phagocytic receptors MERTK and TREM2, and increased neutrophil extracellular traps (NETs). These changes were reversed when Jak2VF BM was transplanted with Il1r1-/- BM. LAB mice with non-cleavable MERTK in WT BM showed improvements in necrotic core and fibrous cap formation and reduced NETs. An agonistic TREM2 antibody (4D9) markedly increased fibrous caps in both control and LAB mice eliminating the difference between groups. Mechanistically, 4D9 increased TREM2+PDGFB+ macrophages and PDGF receptor-α positive fibroblast-like cells in the cap region. TREM2 and PDGFB mRNA levels were positively correlated in human carotid plaques and co-expressed in macrophages. In summary, low frequency Jak2VF mutations promote atherosclerosis via IL-1 signaling from Jak2VF to WT macrophages and neutrophils promoting cleavage of phagocytic receptors and features of plaque instability. Therapeutic approaches that stabilize MERTK or TREM2 could promote plaque stabilization especially in CH- and inflammasome-driven atherosclerosis.

Combustion-driven deuterium fluoride/hydrogen fluoride (DF/HF) lasers are a crucial type of chemical lasers. Their chemical efficiency mainly depends on the production efficiency of atomic fluorine in the combustion chamber, where NF 3 serves as the fluorine resource, and H 2 acts as the reducing agent. However, due to the complex combustion process, high reaction temperatures, and potent corrosiveness of the products, the combustion mechanism of NF 3 /H 2 in the combustion chamber is still not fully revealed, including the chemical details of F atom generation. In this work, we firstly employed the molecular dynamics (MD) method to simulate the combustion reaction for combustion-driven DF/HF chemical lasers. Additionally, for the first time, a high-accuracy neural network potential (NNP) for the NF 3 /H 2 system was constructed using machine learning methodologies. The simulation results reveal that the combustion process of the NF 3 /H 2 system comprises three stages: the initiation of combustion, the generation of HF, and the formation of N 2 . The fluorine atoms in the system primarily originate from the cleavage of the N-F bond in N 2 F 4 , which is formed via the dimerization of NF 2 . Temperature and molar ratios of reactants are two important factors influencing the F atom formation. Higher temperatures and an excess number of NF 3 favor the generation of F atoms. Besides, we found that the initial HF production stems from H-abstraction reaction between the F radical and H 2 , rather than the previously proposed reaction between NF 3 and H 2 . The NNP-based MD simulations unveil the atomic-scale reaction mechanisms for NF 3 /H 2 combustion in combustion-driven DF/HF chemical lasers, indicating its potential as an effective tool for the studies in the field of chemical lasers. The results also offer theoretical insights for enhancing the performance of the combustion-driven DF/HF chemical lasers.

Background: Psychological health is crucial for the physical and mental well-being of primary and secondary school students, however, the research on the interrelationships among negative emotions is still limited. This study aims to investigate the network structure of depression, anxiety, and stress, and explore their correlation with screen time in these populations., Method: This study was conducted from March to July 2022 in 157 counties across 18 cities in Henan Province. The Depression Anxiety Stress Scale (DASS-21) was used to assess the negative emotions experienced by students. Firstly, "Expected Influence" and "Bridge Expected Influence" were considered as key indicators within the symptom network to depict the structure of depressive, anxiety and stress symptoms. Secondly. a case-dropping bootstrap procedure was applied to assess the stability of the network. Finally, this study identified the central and bridge symptoms in the network, and explored their relationships with screen time., Results: The study included 52,782 students with an average age of 11.23±2.56 years. Network analysis showed that feelings of worthlessness, panic, and agitation are the predominant symptoms in the negative emotional networks. Depression, anxiety, and stress were interconnected through feelings of low mood, overreaction, and trembling. Additionally, lack of initiative and dry mouth exhibited the most significant direct associations with screen time., Conclusion: The central and bridge symptoms identified in the negative emotion networks can serve as potential focal points for future research on negative emotions among primary and secondary school students., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pre-frailty is a window of opportunity for frailty reversal and can be enhanced by multicomponent exercise. The Lifestyle-integrated Functional Exercise (LiFE) program may be a promising alternative to overcome traditional exercise barriers. The latest advancements in mobile health (mHealth) technology have enabled individuals to retain the advantages of supervised exercise training within group settings while providing exercise programs that can be accessed and completed at home. This study aims to assess the feasibility, acceptability, and primary efficacy of the PF-Life program, which is the Lifestyle-Integrated Functional Exercise program for Pre-Frail supported by an mHealth platform., Methods: Sixteen pre-frail adults aged ≥ 65 years were recruited from five community health centers in Fuzhou, China. All participants were prescribed the PF-Life program by geriatricians using the mhealth platform (web-based portal). Participants engaged in the customized exercises program following in-app video instructions and feedback on the mhealth platform (smartphone application). Physical activity (PA) and sedentary behavior (SB) were registered daily through wearable devices. Study endpoints were feasibility (retention rate, compliance rate, adverse events), usability (system usability scale), acceptability (qualitative interviews), changes in physical function (timed up and go (TUG), handgrip strength (HGS), and 30-second chair rise tests), PA and SB., Results: The intervention was feasible, 88% of participants adhered completely to the study protocol, and 95% had completed at least 75% of the prescribed experimental duration. System usability was high (85 out of 100 best imaginable). Changes were observed from baseline to follow-up for total HGS (21.41 ± 6.38 vs. 24.12 ± 6.62 kg, P < 0.05, d = 0.714), TUG (8.23 ± 1.33 vs. 7.48 ± 2.01 s, P < 0.01, d = 1.647) and 30-second chair rise test (17.13 ± 4.3 vs. 20.04 ± 4.54 repetitions, P < 0.01, d = 0.94). In addition, SB decreased by a mean of 33 min/day (P < 0.01), and low physical activity increased by 31 min/day (P < 0.01). No adverse events occurred. The majority of participants found the PF-Life program to be straightforward, adaptable, and easily integrable into their daily routines., Conclusions: Preliminary studies have demonstrated that the PF-life program exhibits good compliance, safety, and usability for the pre-frail elderly population. Large-scale randomized controlled trials are required to ascertain its long-term effectiveness., (© 2024. The Author(s).)

Although thermal hydrolysis pretreatment enhances disposal efficiency of sludge, it inevitably leads to melanoidins formation, which will negatively impact the subsequent wastewater treatment processes. However, their effect on the dewaterability of thermal hydrolyzed sludge (THS) remains poorly understood. This study aimed to uncover the underlying mechanisms of how melanoidins affecting dewaterability of THS. Using resin-adsorption method to reduce melanoidins content by 50% led to 21% and 6% decreases in capillary suction time and specific resistance to filtration, respectively, and a 14% increase in sludge cake solid content. Conversely, accumulating melanoidins to 200% worsened THS dewaterability, altering surface morphology and reducing floc stability, which increased the content of bound water by 9%. Additionally, a higher melanoidins level increased the hydrophilic components in extracellular polymeric substances while reducing hydrophobic sites and structures. These findings indicate that melanoidins impair THS dewaterability by altering flocs spatial properties and increasing hydrophilic structures and components., 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.)

Recently, 3D Gaussian Splatting (3DGS) has attracted widespread attention due to its high-quality rendering, and ultra-fast training and rendering speed. However, due to the unstructured and irregular nature of Gaussian point clouds, it is difficult to guarantee geometric reconstruction accuracy and multi-view consistency simply by relying on image reconstruction loss. Although many studies on surface reconstruction based on 3DGS have emerged recently, the quality of their meshes is generally unsatisfactory. To address this problem, we propose a fast planar-based Gaussian splatting reconstruction representation (PGSR) to achieve high-fidelity surface reconstruction while ensuring high-quality rendering. Specifically, we first introduce an unbiased depth rendering method, which directly renders the distance from the camera origin to the Gaussian plane and the corresponding normal map based on the Gaussian distribution of the point cloud, and divides the two to obtain the unbiased depth. We then introduce single-view geometric, multi-view photometric, and geometric regularization to preserve global geometric accuracy. We also propose a camera exposure compensation model to cope with scenes with large illumination variations. Experiments on indoor and outdoor scenes show that the proposed method achieves fast training and rendering while maintaining high-fidelity rendering and geometric reconstruction, outperforming 3DGS-based and NeRF-based methods. Our code will be made publicly available, and more information can be found on our project page (https://zju3dv.github.io/pgsr/).

Neurons often grow highly branched and cell-type specific dendrite morphologies to receive and integrate information, which is the basis of precise neural circuit formation. Previous studies have identified numerous mechanisms that promote dendrite branching. In contrast, it is much less understood how this process is negatively regulated. Here we show that EAT-17/EVI5 acts together with the dynein adaptor protein BICD-1 and the motor protein dynein in C. elegans epidermal cells to restrict branching of PVD sensory dendrites. Loss-of-function mutants of these genes cause both ectopic branching and accumulation of the dendrite branching ligand SAX-7/L1CAM on epidermal plasma membranes. Mutants of genes regulating endo-lysosomal trafficking, including rab-5/RAB5 and dyn-1/DNM1, show similar defects. Biochemical characterization, genetic analysis, and imaging results support that EAT-17 and BICD-1 directly interact with each other and function in the endocytic degradation pathway to remove ectopically localized dendrite branching ligands to restrict abnormal branching., (© 2024. The Author(s).)

Lithium-ion batteries (LIBs) face increasingly stringent demands as their application expands into new areas, including extreme temperatures and fast charging. To meet these demands, the electrolyte should enable fast lithium-ion transport and form stable interphases on electrodes simultaneously. In practice, however, improving one aspect often compromises another. For instance, the trend toward electrolytes forming anion-derived interphases typically reduces transport efficiency due to weak-solvating solvents. We propose that instead of relying on anions to form the interphase, leveraging both solvents and anions to form interphases can potentially lead to a balancing point between robust interphase formation and effective ion transport. Guided by this design principle, 2,2-difluoroethyl ethyl carbonate (DFDEC) was identified as the promising solvent. With the new electrolyte using DFDEC as the major solvent and lithium bis(fluorosulfonyl) imide (LiFSI) as the salt, graphite||LiNi 0.8 Mn 0.1 Co 0.1 O 2 (NMC811) full cells are capable of fast charging and demonstrate long-term cycling stability with a cutoff voltage of 4.5 V. Notably, the battery shows a capacity retention of 84.3% after 500 cycles with an average Coulombic efficiency (CE) as high as 99.93%. This new electrolyte also enables stable battery cycling across a wide temperature range (-20 to 60 °C), with excellent capacity retention.

One new monacolin analog, monacolin V (1), together with two new monacolin-like natural products, 6-hydroxyl monacolin P (2) and 3-keto monacolin S (3), were isolated from the ethyl acetate portion of red yeast rice ethanol extract. Their structures were identified by HRESIMS and NMR experiments, and the complete assignments of 1 H and 13 C NMR data for three compounds were obtained by the aid of HSQC, HMBC, 1 H- 1 H COSY, and NOESY data. This is the first time that the NMR data of compounds 2 and 3 have been fully assigned., (© 2024 John Wiley & Sons Ltd.)

Recombinant human thrombopoietin (rhTPO) is commonly used to improve low platelet status in immune thrombocytopenia (ITP), as one protein product, even with a very low rate, there is still the possibility to produce neutralizing antibodies of thrombopoietin (TPO). We described a 7-year-old boy with ITP and normal TPO levels who had previously received rhTPO for 2 weeks but showed persistent thrombocytopenia and was misdiagnosed as acquired amegakaryocytic thrombocytopenia (AATP) and ineffectively treated with cyclosporine A (CsA) in combination with avatrombopag (AVA). As suspicious the TPO neutralizing antibody development as re-test of TPO level is 0, the CD20 + deletion antibody drug rituximab (RTX) was prescribed and received efficacy. rhTPO serves as one bio-protein drug and should be cautious with developing neutralizing antibodies if the drug effect is lost. The tests for antibody and/or TPO level should be done for the diagnosis, and the antibody eradication medication as an anti-CD20 antibody, RTX, should be prescribed to delete thes e neutralizing antibodies to recover the TPO level to reattain the response of ITP treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Grapevine breeding is hindered by a limited understanding of the genetic basis of complex agronomic traits. This study constructs a graph-based pangenome reference (Grapepan v.1.0) from 18 newly generated phased telomere-to-telomere assemblies and 11 published assemblies. Using Grapepan v.1.0, we build a variation map with 9,105,787 short variations and 236,449 structural variations (SVs) from the resequencing data of 466 grapevine cultivars. Integrating SVs into a genome-wide association study, we map 148 quantitative trait loci for 29 agronomic traits (50.7% newly identified), with 12 traits significantly contributed by SVs. The estimated heritability improves by 22.78% on average when including SVs. We discovered quantitative trait locus regions under divergent artificial selection in metabolism and berry development between wine and table grapes, respectively. Moreover, significant genetic correlations were detected among the 29 traits. Under a polygenic model, we conducted genomic predictions for each trait. In general, our study facilitates the breeding of superior cultivars via the genomic selection of multiple traits., (© 2024. The Author(s).)

With technological advancements, the practical application of ethanol oxidation reaction (EOR) is becoming increasingly promising, yet the need for higher ethanol concentrations highlights the growing importance of the deprotonation ability (Ni 2+ to Ni 3+ ) of the catalyst. The deprotonation ability is the key step for nickel-based catalysts in EOR, as it is essential for Ni 2+ to continuously undergo deprotonation to transform into Ni 3+ in order to maintain the continuous EOR. Herein, we developed Mo-doped Ni(OH) 2 nanosheets by a hydrothermal method. The Mo-doped Ni(OH) 2 nanosheets show excellent EOR performance due to the high valence doping of Mo, the onset potential of the oxidation peak (Ni 2+ to Ni 3+ ) appears at a position with a small overpotential,. The in-situ Raman spectroscopy technique further characterized the increase in NiOOH in the process of EOR. The Mo-doped Ni(OH) 2 nanocomposite catalyst facilitates the oxidation of Ni 2+ into Ni 3+ . Based on the above theoretical guidance, Mo-doped Fe/Ni(OH) 2 nanosheets was designed and synthesized. The outstanding EOR performance of the Mo-Fe/Ni(OH) 2 -3 showed a potential of 1.352 V at 10 mA cm -2 . The catalyst was used to design three-electrode reversible zinc-ethanol-air battery (T-RZEAB), which effectively overcomes the opposing kinetic and thermodynamic requirements for EOR and oxygen reduction reaction (ORR) catalysts in the oxygen electrode. The charging voltage of T-RZEAB with Mo-Fe/Ni(OH) 2 -3 is 240 mV lower than that of a traditional zinc-air battery at 25 mA cm -2 ., 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.)

As an emerging non-wood resource, moso bamboo has attracted extensive attention because of its short growth cycle and high holocellulose content. However, the internal structure of moso bamboo is more compact than that of wood, leading to higher chemical consumption during the pulping process, which greatly reduces the quality of the extracted fibers. Herein, an innovative pulping system including enzymes and alkali is proposed to achieve higher-quality extraction of moso bamboo fibers. Benefiting from the synergistic effects of high-temperature and alkali-resistant cellulase, xylanase, and laccase, supplemented with alkaline pulping, adequate retention and softening of moso bamboo fibers were ultimately achieved. The sample treated with an enzyme/alkali system resulted in a relative increase in fiber length of 7.19 % and a 31.26 % increase in beating efficiency over alkaline pulping. In addition, the tensile index and tearing index of the paper treated with the enzyme/alkali system reached 50.17 N·m·g -1 and 9.12 mN·m 2 ·g -1 , which were 22.52 % and 20.53 % higher than those of the alkaline pulping, respectively. This work provides new insights into the production of high-performance moso bamboo fibers and paper with low energy and alkali consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The demand for multifunctional hydrogels, offering high mechanical strength, efficient cooling, and antimicrobial properties, is growing in food preservation. Here, a dual-network (DN) hydrogel PM@Cur, which includes curcumin, is fabricated through chemical crosslinking and hydrogen bonding interactions. The resulting hydrogels can withstand more than five freeze-thaw cycles at -80 °C, and resist brittleness after liquid nitrogen treatment. PM@Cur also exhibits surface hydrophobicity (contact angle >90°) for both water and organic solvents. These properties meet the mechanical, anti-fouling, and recyclable demands for hydrogel coolants. The antimicrobial assays in vitro confirmed that the inclusion of curcumin provided the PM@Cur with photodynamic antimicrobial capacity. Finally, the prepared PM@Cur hydrogel ice cubes have been confirmed to exhibit better anti-melting properties than traditional ice cubes, thus enabling the preservation of strawberries and shrimp. This study presents an innovative solution for producing advanced functional integrated hydrogels, offering a promising and safer option for food coolants.\., 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.)

Obesity is found to be a significant risk factor for type 2 diabetes mellitus (T2DM), attributed to lipotoxicity-induced β-cell dysfunction. However, the specific mechanism involved in the process remains incompletely unclarified. The current study demonstrated lipotoxicity resulted in the activation of ER stress, which increased the protein level of TXNIP, thereby inducing senescence-assiciated dysfunction in MIN6 cells under high fat environment. And we also found sesamol, a natural functional component extracted from sesame, was able to alleviate senescence-associated β-cell dysfunction induced by lipotoxicity by inhibiting ER stress and TXNIP. Our findings provided novel insights into senescence-related T2DM and propose innovative therapeutic approaches for utilizing sesamol in the treatment of T2DM in the obese elderly population., (© 2024 Wiley Periodicals LLC.)

Oxidative stress, inflammation, and bacterial infection are critical barriers to wound healing. In this work, a composite wound dressing was designed to promote wound healing and reduce complications. A hydrogel with antibacterial, anti-inflammatory, and antioxidant properties was prepared by crosslinking chitosan (CS) and oxidized konjac glucomannan with Mg 2+ . We named the prepared hydrogel CPO/Mg 2+ . The proposed hydrogel demonstrated a significant capacity for promoting wound healing. Experimental results indicate that the CPO/Mg 2+ composite hydrogel exhibits a bacteriostatic rate of over 95 % against S. aureus and P. aeruginosa. Furthermore, CPO/Mg 2+ reduced oxidative damage to L929 cells in an H 2 O 2 -induced ROS microenvironment and promoted the polarization of macrophage M2. In vivo full-thickness skin defect experiments revealed that the CPO/Mg 2+ composite hydrogel enhances collagen deposition and angiogenesis, achieving a closure rate of over 95 % for infected wounds within 14 days. This novel composite hydrogel offers an effective strategy for the repair of infected wounds., 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.)

Ferroptosis is a unique modality of regulated cell death that is driven by iron-dependent phospholipid peroxidation. N6-methyladenosine (m 6 A) RNA modification participates in varieties of cellular processes. However, it remains elusive whether m 6 A reader Fragile X Mental Retardation Protein (FMRP) are involved in the modulation of ferroptosis in breast cancer (BC). In this study, we found that FMRP expression was elevated and associated with poor prognosis and pathological stage in BC patients. Overexpression of FMRP induced ferroptosis resistance and exerted oncogenic roles by positively regulating a critical ferroptosis defense gene SLC7A11. Mechanistically, upregulated FMRP catalyzes m 6 A modification of SLC7A11 mRNA and further influences the SLC7A11 translation through METTL3-dependent manner. Further studies revealed that FMRP interacts with splicing factor hnRNPM to recognize the splice site and then modulated the exon skip splicing event of SLC7A11 transcript. Interestingly, SLC7A11-S splicing variant can effectively promote FMRP overexpression-induced ferroptosis resistance in BC cells. Moreover, our clinical data suggested that FMRP/hnRNPM/SLC7A11 expression were significantly increased in the tumor tissues, and this signal axis was important evaluation factors closely related to the worse survival and prognosis of BC patients. Overall, our results uncovered a novel regulatory mechanism by which high FMRP expression protects BC cells from undergoing ferroptosis. Targeting the FMRP-SLC7A11 axis has a dual effect of inhibiting ferroptosis resistance and tumor growth, which could be a promising therapeutic target for treating BC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Asymmetric sponge dressings with a hydrophobic surface and a hydrophilic inner layer can prevent bacterial infiltration and ensure efficient absorption of wound exudate. In this work, ε-polylysine/aliphatic polyurethane sponge (EPU) was prepared by prepolymer foaming process, and oxidized hyaluronic acid (OHA) was cross-linked with ε-polylysine (EPL) in EPU through schiff-base reaction to obtain EHPU. Octaisobutyl polyhedral oligomeric silsesquioxane (Oi-POSS) was uniformly sprayed onto the surface of EHPU as the hydrophobic layer, resulting in asymmetric sponge dressings denoted as P-EHPU. These dressings demonstrate capabilities in resisting staining and bacterial invasion, with internal EPL effectively inhibiting bacterial proliferation on the wound surface. The introduction of OHA and EPL leads to a denser and more complete pore structure of the sponge, endowing it with good compression, tensile strength, and hemostatic performance. Wound healing studies indicate that P-EHPU effectively prevents external bacterial infiltration and promotes wound healing., 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.)

α3β4, a vital subtype of neuronal nicotinic acetylcholine receptors (nAChRs), is widely distributed in the brain, ganglia, and adrenal glands, associated with addiction and neurological diseases. However, the lack of specific imaging tools for α3β4 nAChRs has hindered the investigation of their tissue distribution and functions. [D11A]LvIA, a peptide derived from marine cone snails, demonstrates high affinity and potency for α3β4 nAChRs, making it a valuable pharmacological tool for studying this receptor subtype. In this study, three fluorescent conjugates of [D11A]LvIA were synthesized using 6-TAMRA-SE (R), Cy3-NHS-ester (Cy3), and BODIPY-FL NHS ester (BDP) dyes. The electrophysiological activities were assessed in Xenopus laevis oocytes by two-electrodes voltage clamp (TEVC). [D11A]LvIA-Cy3 and [D11A]LvIA-BDP show improved selectivity and affinity, with IC 50 values of 512.70 nM and 343.50 nM, respectively, and [D11A]LvIA-Cy3 exhibits better stability in cerebrospinal fluid (CSF). Utilizing [D11A]LvIA-Cy3, we successfully visualized the distribution of α3β4 nAChRs in rat trigeminal ganglia, retina, adrenal glands, and various brain regions. This novel fluorescent peptide provides a significant pharmacological tool for the exploration and visualization in-situ distribution of α3β4 nAChRs in different tissues and also assists in clarifying the function., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Lymphovascular space invasion (LVSI) is a strong and independent risk factor that increases the probability of endometrial carcinoma (EC) recurrence and reduces the survival rate of patients., Purpose: To investigate the value of amide proton transfer weighted (APTw) and mDixon-Quant techniques in evaluating EC lymphovascular space invasion (LVSI)., Material and Methods: Data of 50 EC patients (18 LVSI+ and 32 LVSI-) confirmed by surgery and pathology were retrospectively analyzed. Preoperative magnetic resonance imaging (MRI) scans included APTw and mDixon-Quant imaging. APT, transverse relaxation rate (R2*), and fat fraction (FF) plots were obtained by postprocessing. The APT, R2*, and FF values of the two groups of cases were measured by two observers., Results: The agreement between the two observers was good. The mean APT, R2*, and FF values of LVSI+ EC were 2.947% ± 0.399%, 20.605 /s (range = 18.525-27.953), and 2.234% ± 1.047%, respectively, while the parameters of LVSI- EC were 2.628% ± 0.307%, 18.968 /s (range = 16.225-20.544), and 2.103% ± 1.070%, respectively. The APT and R2* values of LVSI+ EC were higher than those of LVSI- EC ( P  < 0.05). There was no significant difference in FF value between the two groups. The AUC values of APT, R2*, and APT + R2* for LVSI were 0.751, 0.713, and 0.781, respectively (all P  > 0.05). APT value was moderately correlated with R2* value (r = 0.528, P  < 0.001) and weakly correlated with FF value ( r  = 0.312, P  = 0.027)., Conclusion: APTw and mDixon-Quant techniques could evaluate the LVSI status of EC, and their combined application could improve diagnostic efficiency., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

China is the photovoltaic (PV) leader worldwide and will be confronted with significant challenges stemming from the scrap tide of PV products. Constructing an effective recycling system is essential for retired PV product management. Using the Stackelberg game theory, this study establishes and compares three recycling modes including manufacturer recycling, third-party recycling, and producer responsibility organization (PRO) recycling for decommissioned PV products. Afterward, the effects of module processing costs, echelon utilization rates, and collection subsidies on the transfer prices, collection quantities, supply chain profits, and carbon emissions of the various recycling modes are simulated and analyzed. The results reveal that: (1) The manufacturer recycling realizes optimal supply chain profits; (2) Compared to the PRO recycling mode, the third-party recycling experiences superior performances when retired module processing costs are lower than a specific threshold; (3) Uplifting echelon utilization rates and collection subsidies while reducing module processing costs could supplement the overall economic and environmental benefits within the PV closed-loop supply chain (CLSC); (4) Environmental performances of the different recycling modes are associated with the carbon emission reduction efficiency. Accordingly, valuable insights are provided for manufacturers, recyclers, and governments to develop a sustainable retired PV product recycling system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This investigation aimed to examine the mediating effect of inflammatory biomarkers on the relationship between dust exposure and lung function levels among steelworkers., Methods: The study comprised 2,315 front-line workers employed at an iron and steel company in Tangshan, who underwent occupational health assessments through cluster sampling. Demographic and lifestyle data were collected via a self-administered questionnaire, while physical examinations measured parameters such as height and weight. Lung function was assessed using a portable pulmonary function tester (CHEST). Blood cell counts were uniformly analyzed using a Mindray fully automated biochemistry analyzer (BS-800). Inflammatory biomarkers, including leukocyte count, neutrophil count, lymphocyte count, and platelet count, were assessed, and the neutrophil-to-lymphocyte ratio and systemic immune inflammation index were computed. Generalized linear models and Spearman rank correlation analyses were employed to explore the interplay among dust exposure, inflammatory biomarkers, and alterations in lung function. A mediation analysis model was constructed to elucidate how inflammatory biomarkers mediate the relationship between dust exposure and lung function levels., Results: After adjusting for covariates, dust exposure was significantly associated with reduced lung function levels, with statistically significant differences observed between dust-exposed and non-exposed groups across various lung function indicators (P < 0.001). In the dust-exposed group, inflammatory biomarkers were elevated, showing significant correlations with FVC and FEV 1 (P < 0.05). However, the correlation between FEV 1 /FVC and various inflammatory biomarkers was insignificant (P > 0.05). Mediation analysis revealed that white blood cells and neutrophils partially mediated the association between dust exposure and FVC, with proportions of 1.75% and 1.09%, respectively. Similarly, white blood cells, neutrophils, and the systemic immune inflammation index partially mediated the association between dust exposure and FEV 1 , with proportions of 1.15%, 0.82%, and 0.82%, respectively., Conclusion: In conclusion, dust exposure poses a risk for decreased lung function levels. Inflammatory biomarkers derived from blood cells offer a valuable and easily obtainable means of identifying changes in lungfunction levels. Among these biomarkers, white blood cells, neutrophils, and the systemic immune inflammation index significantly mediate the association between dust exposure and lung function levels, although further exploration is needed to understand their underlying mechanisms., Competing Interests: Declarations Conflict of interest The authors declare no conflict of interest. Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was conducted in accordance with the Helsinki Declaration and approved by the Medical Ethics Review Committee of North China University of Science and Technology (No.16040). Consent to participate Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As the first discovered histone demethylase, LSD1 plays a vital role in maintaining pathological processes such as cancer, infection, and immune diseases. Based on previous researches, LSD1 is highly expressed in sorts of tumor cells such as acute myeloid leukemia, non-small cell lung cancer, prostate cancer, breast cancer and gastric cancer, etc. Therefore, targeting LSD1 is a prospective strategy for tumor treatment. Cancer stem cells could preserve self-renewal, cell proliferation, cell migration and malignant phenotype. So, the reduction of tumor cell stemness can effectively inhibit the growth of tumor cells, which may be a new strategy for the treatment of cancers. Up to now, there exist many researches confirming the significant role of LSD1 in regulating the stemness characteristics such as embryonic stem cells differentiation. Many reports show that inhibition of LSD1 effectively decreases the property of cancer cell stemness. However, there lacks a detailed review about the relationship between LSD1 and cancer cell stemness. Herein, in this review, we summarized the mechanisms how LSD1 regulates cell stemness comprehensively. In addition, some related inhibitors targeting LSD1 to reduce the proliferation characteristics of cancer stem cells are also described., 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.)

The dynamic balance between the self-renewal and differentiation of stem cells in plants is precisely regulated by a series of developmental regulated genes that exhibit spatiotemporal-specific expression patterns. Several studies have demonstrated that the WOX family transcription factors play critical roles in maintaining the identity of stem cells in Arabidopsis thaliana. In this study, we obtained amiR-WOX9 transgenic plants, which displayed terminating prematurely of shoot apical meristem (SAM) development, along with alterations in inflorescence meristem and flower development. The phenotype of amiR-WOX9 plants exhibited similarities to that of wus-101 mutant, characterized by a stop-and-go growth pattern. It was also found that the expression of WUS in amiR-WOX9 lines was decreased significantly, while in UBQ10::WOX9-GFP transgenic plants, the WUS expression was increased significantly despite no substantial alteration in meristem size compared to Col. Therefore, these data substantiated the indispensable role of WOX9 in maintaining the proper expression of WUS. Further investigations unveiled the direct binding of WOX9 to the WUS promoter via the TAAT motif, thereby activating its expression. It was also found that WUS recognized identical the same TAAT motif cis-elements in its own promoter, thereby repress self-expression. Next, we successfully identified a physical interaction between WOX9 and WUS, and verified that it was harmful to the expression of WUS. Finally, our experimental findings demonstrate that WOX9 was responsible for the direct activating of WUS, which however was interfered by the ways of WUS binding its own promoter and the interaction of WUS and WOX9, thereby ensuring the appropriate expression pattern of WUS and then the stem cell stability. This study contributes to an enhanced comprehension of the regulatory network of the WOX9-WUS module in maintaining the equilibrium of the SAM., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

The prognosis of patients with high-risk acute myeloid leukemia (AML) is dismal even after allogeneic stem cell transplantation (allo-HSCT), with relapse remaining the leading cause of treatment failure. Here, we investigated whether ruxolitinib and decitabine plus modified busulfan-cyclophosphamide (mBu/Cy) conditioning could reduce relapse in high-risk AML after allo-HSCT. This prospective, single-arm, phase II trial enrolled 37 patients who received allo-HSCT between September 2020 and March 2022 at the First Medical Center of Chinese People's Liberation Army (PLA) General Hospital. Eligible patients (10-62 years) had relapsed/refractory, positive measurable residual disease (MRD) prior to conditioning or adverse genetic abnormalities. Ruxolitinib (35 mg twice daily, days - 15 to - 10) and decitabine (20 mg/m 2 /day, days - 15 to - 10) were administered followed by mBu/Cy conditioning. All patients achieved engraftment. The cumulative incidences (CIs) of acute graft-versus-host disease (GVHD) grades II-IV and III-IV were 35.0% and 10.5%, respectively. The 1-year cumulative incidence of chronic GVHD was 8.1%. The 1-year CI of relapse was 29.7% among all patients, 0% in patients who achieved the first complete remission (CR1) prior to conditioning, and 0% in those with MRD-negative prior to conditioning. The 1-year non-relapse mortality was 5.4%. The 1-year probabilities of overall survival, disease-free survival, and GVHD-free relapse-free survival were 70.3%, 62.2%, and 54.1%, respectively. In conclusion, the novel conditioning showed primary efficacy in terms of a reduction in relapse in high-risk patients with AML after allo-HSCT, especially in those who achieved CR1 and MRD-negative prior to conditioning. Also, the new conditioning regimen may help reduce the incidence of chronic GVHD. ClinicalTrials.gov identifier: NCT04582604., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There are variations in individual eltrombopag concentrations that may impact efficacy and adverse drug reactions (ADRs) in paediatric immune thrombocytopenia (ITP). To solve this problem, we tailored the eltrombopag dosage refer to concentration, then followed up to assess concentration value in paediatric ITP. This is a single-centre, prospective, observational study. The eltrombopag dosage was adjusted, and children were divided into three groups: the maintenance, discontinuation, and increase groups. Concentration and other data were compared to explore concentration value in guiding the individualized treatment of paediatric ITP. Thirty-nine patients were enrolled, including 23 in the maintenance group, 3 in the discontinued group and 13 in the increase group. 3 patients discontinued eltrombopag due to ADRs, which was significantly higher than patients in the maintenance group (t = 3.606, p = 0.001). In all, 13 patients increased their dosage due to poor response, whose concentration and platelet count were significantly lower than patients in the maintenance group (t = 2.461, p = 0.019; t = 4.633, p < 0.001). Two months after the increase, the number of patients reaching CR and R respectively increased by 2 and 3, while the median platelet count was significantly raised (Z = -2.411, p = 0.016). Concentration could be used as a reference index for the individualized treatment of eltrombopag in paediatric ITP., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background and Purpose: The definitive diagnosis of gastroesophageal reflux disease (GERD) often requires invasive investigations like upper gastrointestinal endoscopy or reflux monitoring. We aimed to explore the relationship between salivary pepsin and GERD and its value as a non-invasive diagnostic tool., Methods: Databases (PubMed, Web of Science, Cochran Library, and EMBASE) were searched from their inception to January 22, 2024 to explore the correlation of salivary pepsin with GERD. The meta-analysis data retrieved were summarized, including the salivary pepsin concentration, sensitivity of diagnosis (SEN), specificity of diagnosis (SPE), negative likelihood ratio, positive likelihood ratio, diagnostic odds ratio, and receiver operating characteristic (ROC) curve., Results: The meta-analysis comparing salivary pepsin concentration in two groups (proven GERD and non-GERD) with 18 studies revealed that the proven GERD group had higher salivary pepsin concentration than the non-GERD group (SMD = 1.74 [95% CI 1.14-2.34]). The meta-analysis of salivary pepsin diagnostic value for proven GERD incorporated 23 studies. The results showed pooled SEN (0.73 [95% CI 0.66-0.80]), SPE (0.72 [95% CI 0.65-0.78]), positive likelihood ratio (2.61 [95% CI 2.02-3.39]), negative likelihood ratio (0.37 [95% CI 0.28-0.50]), diagnostic odds ratio (7.03 [95% CI 4.24-11.66]) and area under the SROC curve (0.79 [95% CI 0.75-0.82])., Conclusion: GERD patients presented a higher salivary pepsin concentration. Salivary pepsin is both sensitive and specific in identifying GERD, making it a promising non-invasive marker for diagnosis., (© 2024 John Wiley & Sons Ltd.)

Social exchange- and social identity-based mechanisms have been commonly juxtaposed as two pivotal proxies of the relational approach for studying organizational justice. Despite their distinct theoretical roots, less is known about whether and how these two proximal mechanisms complement one another in accounting for justice effects on key outcomes. Tracing back to their disparate fundamental premises-"reciprocity" underpinning social exchanges and "oneness" underpinning identity construction-we attempt to disentangle the relative mediating effects of these two mechanisms. Our empirical testing hinges on one meta-analytic study with 105 independent samples ( N = 29,868), coupled with one preregistered experience-sampling study with 1,941 cross-day observations over 3 weeks from 147 subordinate-supervisor pairs. Overall, we find that exchange-based mechanisms account for more of the indirect effect of justice on task performance, whereas identity-based mechanisms (particularly interdependent identity) account for more of the indirect effect of justice on counterproductive work behavior. Regarding the indirect effect on organizational citizenship behavior, identity-based mechanisms (particularly positive self-evaluations) and exchange-based mechanisms respectively present great utility between the two studies. By providing nuanced insight into the complementary yet distinct nature of these two prominent mechanisms, our research encourages a more granular theoretical approach for studying organizational justice effects. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose: This case series and literature review evaluated the baseline variables, clinical symptoms, pathological characteristics, and prognosis of patients with orbital oncocytic carcinoma., Methods: This retrospective case series collected the medical histories and other related data from 13 patients pathologically diagnosed with oncocytic carcinoma., Results: The average age of patients with orbital oncocytic carcinoma was 64.8 years, with a significantly higher rate of males than females. Furthermore, unilateral disease was more common than bilateral disease. All patients had surrounding tissue invasion, most commonly to extraocular muscles (69.2%) and bones (53.8%). The clinical manifestations were proptosis (30.8%), swelling of the lesion area (23.1%), vision loss (23.1%), diplopia (23.1%), periocular mass (23.1%), tears (15.4%), eye pain (7.7%), ptosis (7.7%), and visual field loss (7.7%). Microscopic examination revealed many large eosinophilic cells. There were obvious nuclei and abundant mitotic figures. The cancer cells expressed cytokeratin, but not P63 or S-100. The follow-up duration was 2-53 months, and the metastasis rate was 16.7%. The patients exhibited a good prognosis. The main treatment methods included surgical resection, surgery combined with radiotherapy, and the enucleation of ocular contents., Conclusions: Orbital oncocytic carcinoma has the immunohistochemical characteristics of eosinophilic tumor cells, with expression of cytokeratin but not P63 or S-100. The prognosis is favorable. Surgical resection, surgery combined with radiotherapy, and enucleation of intraocular material are effective treatment options. Nevertheless, long-term follow-up and close observation for metastases are required., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Gut microbiota symbiosis faces enormous challenge with increasing exposure to drugs such as environmental poisons and antibiotics. The gut microbiota is an important component of the host microbiota and has been proven to be involved in regulating spermatogenesis, but the molecular mechanism is still unclear. A male mouse model with gut microbiota depletion/dysbiosis was constructed by adding combined antibiotics to free drinking water, and reproductive parameters such as epididymal sperm count, testicular weight and paraffin sections were measured. Testicular transcriptomic and serum metabolomic analyses were performed to reveal the molecular mechanism of reproductive dysfunction induced by gut microbiota dysbiosis in male mice.This study confirms that antibiotic induced depletion of gut microbiota reduces sperm count in the epididymis and reduces germ cells in the seminiferous tubules in male mice. Further study showed that exosomes isolated from microbiota-depleted mice led to abnormally high levels of retinoic acid and decrease in the number of germ cells in the seminiferous tubules and sperm in the epididymis. Finally, abnormally high levels of retinoic acid was confirmed to disrupted meiotic processes, resulting in spermatogenesis disorders. This study proposed the concept of the gut microbiota-exosome-retinoic acid-testicular axis and demonstrated that depletion of the gut microbiota caused changes in the function of exosomes, which led to abnormal retinoic acid metabolism in the testis, thereby impairing meiosis and spermatogenesis processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Emissions of nitrogen oxides (NOx) are a dominant contributor to ambient nitrogen dioxide (NO 2 ) concentrations, but the quantitative relationship between them at an intracity scale remains elusive. The Chengdu 2021 FISU World University Games (July 22 to August 10, 2023) was the first world-class multisport event in China after the COVID-19 pandemic which led to a substantial decline in NOx emissions in Chengdu. This study evaluated the impact of variations in NOx emissions on NO 2 concentrations at a fine spatiotemporal scale by leveraging this event-driven experiment. Based on ground-based and satellite observations, we developed a data-driven approach to estimate full-coverage hourly NO 2 concentrations at 1 km resolution. Then, a random-forest-based meteorological normalization method was applied to decouple the impact of meteorological conditions on NO 2 concentrations for every grid cell, the resulting data were then compared with the timely bottom-up NOx emissions. The SHapley-Additive-exPlanation (SHAP) method was employed to delineate the individual contributions of meteorological factors and various emission sources to the changes in NO 2 concentrations. According to the full-coverage meteorologically normalized NO 2 concentrations, a decrease in NOx emissions and favorable meteorological conditions accounted for 80 % and 20 % of the NO 2 reduction, respectively, across Chengdu city during the control period. Within the strict control zone, a 30 % decrease in the meteorologically normalized NO 2 concentrations was observed during the control period. The normalized NO 2 concentrations demonstrated a strong correlation with NOx emissions (R = 0.96). Based on the SHAP analysis, traffic emissions accounted for 73 % of the reduction in NO 2 concentrations, underscoring the significance of traffic control measures in improving air quality in urban areas. This study provides insights into the relationship between NO 2 concentrations and NOx emissions using real-world data, which implies the substantial benefits of vehicle electrification for sustainable urban development., 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: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients., Methods: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs., Results: Of 497 elderly patients, 157 (31.6 ​%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 ​%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 ​% vs. 72.1 ​%, P ​< ​0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 ​% confidence interval 1.879-6.198, P ​< ​0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy., Conclusion: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology., Competing Interests: Declaration of competing interest We confirm that this work is original and has not previously been published. None of the authors have any financial disclosures or conflict of interest. Approval for this study was obtained from the Ethics Committee of the participating hospitals. All the authors have been involved in the design, performance, and interpretation of data of this study, and in drafting the article and its critical revision. Should the article be accepted, all authors agree to transfer copyright to your journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Grapholita molesta is an important and harmful fruit pest worldwide, with widespread feeding hosts. Trypsin, an indispensable hydrolytic digestive protease in the insect gut, is crucial in digestion, growth and development. We analyzed the characteristics of the trypsin-encoding genes, screened for the optimal dose of RNAi mediated by nanocarriers, and investigated various indices of larval growth and development of G. molesta., Results: Gut content (GC) and RNase A degraded double-stranded RNA (dsRNA), with a faster degradation rate at higher concentrations. Star polycation (SPc) nanomaterials protected dsGFP from degradation by anion-cation binding and did not migrate through agarose gel. The key conserved motifs of the trypsin-encoding genes were similar, exhibiting high homology with those in other lepidopteran insects. An interference efficiency of ≈70% was achieved with SPc nanomaterial-mediated RNA interference with 0.05 μg dsRNA. The efficiency of continuous interference was stable. Trypsin activity, body weight of 8-day-old larvae, pupal weight and emergence rate were significantly reduced, and the larval stage was significantly prolonged., Conclusion: The investigated trypsin gene is a key target gene in the growth and development of G. molesta. We investigated the efficiency and convenience of feeding SPc nanomaterials in a functional study of insects. Our results provide valuable data for the development of efficient trypsin-targeting pesticides. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As a reproducible intermediate for hydrogen (H2) and carbon cycling, methanol mixed with water (H2O) in a ratio of 1:1 can multiply the outcome of green H2 generation via Photocatalytic reforming of methanol-H2O (PRMW). Hitherto, low-energy and mild-condition PRMW remains a serious challenge. Here, the amino acid-derived carbon nitrides (ACN) were synthesized supramolecular precursor strategy for PRMW and achieved excellent performance (H2, 35.6 mmol h-1 g-1; CO2, 11.5 mmol h-1 g-1) under sunlight at 35 °C. We revealed that the surface-terminating carboxyl groups (-COOH) promote the dark dehydrogenation of methanol on MetCNx to form methoxy (⁎OCH3) and methylol (⁎CH2OH) simultaneously, with the hydroxyl (⁎OH) generated by photostimulated H2O oxidation promotes the C-H activation of formaldehyde, then leads the whole reaction into the formation of CO2 and three H2. The extended light absorption, enhanced charge separation and transport, and efficient surface reaction improve photocatalytic efficiency., (© 2024 Wiley‐VCH GmbH.)

Objective: This study aimed to analyze uterine artery and spiral artery hemodynamics in patients with unexplained recurrent pregnancy loss (URPL) with varying pregnancy outcomes., Methods: 174 pregnant women with URPL and 144 pregnant women without adverse pregnancy histories were enrolled in this retrospective study. Based on pregnancy outcomes, these patients were divided into two groups: normal pregnancy outcomes (URPL-N, n=138) and adverse pregnancy outcomes (URPL-A, n=36). Control group participants were categorized into normal pregnancy outcomes (CON-N, n=129) and adverse pregnancy outcomes (CON-A, n=15). We compared uterine artery and spiral artery hemodynamics during different stages of gestation and the predictive value of these parameters for pregnancy outcomes., Results: URPL-N group had fewer pregnancy losses and lower BMI compared to URPL-A group (P< 0.05). Spiral artery hemodynamics in URPL-N and CON-N groups were lower than those in URPL-A and CON-A groups during the mid-luteal phase, 11-13 weeks, 15-17 weeks, and 19-21 weeks of gestation, respectively. Uterine artery hemodynamics ((Pulsatility index (mPI), resistive index (mRI), and systolic-to-diastolic ratio (mS/D)) in the mid-luteal period were lower in URPL-N group than URPL-A group. Similarly, in CON-N group were lower than CON-A group. The URPL-A and CON-A groups had higher uterine artery and spiral artery hemodynamics when compared to the URPL-N and CON-N groups. Spiral artery hemodynamics exhibited larger areas under the ROC curve compared to uterine artery parameters., Conclusion: Abnormal hemodynamics in these arteries may contribute to URPL and adverse pregnancy outcomes. Spiral artery hemodynamics are more reliable predictors of pregnancy outcomes than uterine artery parameters., Competing Interests: The authors wish to disclose that they have no known competing financial interests or personal relationships that might have influenced or biased the work presented in this paper., (© 2024 Zhong et al.)

Rationale: Anemarrhenae Rhizoma (AR) has been a frequently utilized traditional Chinese medicine (TCM) for an extended period, with its salt-processed variant being a prevalent application form. Contemporary pharmacological investigations have demonstrated that the salt-processed iteration exhibits a multitude of markedly augmented pharmacological properties. However, whether the pharmacodynamic material basis of this change is related to volatile substances remains unclear. The aim of this study was to develop a strategy to screen volatile pharmacodynamic substances in AR and salt-processed AR (SAR)., Methods: A comprehensive approach was developed to identify volatile pharmacodynamic compounds by integrating plant metabolomics, target network pharmacology, and molecular docking technology. Plant metabolomics using GC-MS analysis was conducted to identify volatile chemical markers distinguishing between AR and SAR. Subsequently, network pharmacology was utilized to investigate the correlation between chemical markers and associated diseases. Following this, molecular docking technology was utilized to explore the correlation between chemical markers and disease targets, resulting in the discovery of potential quality control markers., Results: Fifty volatile compounds were isolated and identified in the salt of AR and SAR. The findings from plant metabolomics analysis demonstrated a distinct differentiation, revealing 13 volatile chemical markers that distinguish between AR and SAR. A target (PPARG) associated with diabetes was identified through target network pharmacology analysis. Thirteen volatile components were subsequently chosen as potential quality markers, taking into account their hypoglycemic activity., Conclusions: The method developed provides a novel strategy for the identification of pharmacophores in AR and SAR, as well as establishing a foundation for the exploration of the volatile differential components and pharmacodynamics in various processed products of TCMs. Additionally, the findings of this study can serve as a theoretical framework for the development and utilization of volatile components in AR and its processed derivatives., (© 2024 John Wiley & Sons Ltd.)

Hypertension is a major global health issue, contributing to significant cardiovascular morbidity and mortality. Mitochondrial dysfunction, particularly through dysregulated mitophagy, has been implicated in the pathogenesis of hypertension. We wanted to find out the relationship between mitochondrial autophagy and changes in arterial smooth muscle cell tension and the molecular mechanism. Using RNA-seq analysis, we identified significant upregulation of autophagy-related genes, including Pink1, in the aortas of spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. Further in vivo and in vitro studies revealed enhanced mitophagy, characterized by increased expression of Pink1 protein. Our experiments showed that knockdown of Pink1 expression by shRNA attenuated KPSS-induced vascular smooth muscle cells (VSMCs) contraction, suggesting that excessive mitophagy contributes to vascular dysfunction in hypertension. These findings highlight Pink1-mediated mitophagy as a crucial player in hypertensive vascular remodeling and present a potential therapeutic target for managing hypertension., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although immune checkpoint inhibitors (ICIs) have demonstrated significant survival benefits in some patients diagnosed with gastric cancer (GC), existing prognostic markers are not universally applicable to all patients with advanced GC., Aim: To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models., Methods: Data from 273 patients diagnosed with GC and distant metastasis, who un-derwent ≥ 1 cycle(s) of ICIs therapy were included in this study. Patients were randomly divided into training and test sets at a ratio of 7:3. Training set data were used to develop the machine learning models, and the test set was used to validate their predictive ability. Shapley additive explanations were used to provide insights into the best model., Results: Among the 273 patients with GC treated with ICIs in this study, 112 died within 1 year, and 129 progressed within the same timeframe. Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting (XGBoost), logistic regression, and decision tree. After comprehensive evaluation, XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival., Conclusion: The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy. Patient nutritional status may, to some extent, reflect prognosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the clinical effect of limited open reduction treatment of proximal phalangeal fracture with miniature external fixator combined with small incision., Methods: Between January 2020 and December 2022, 29 patients with proximal phalangeal fracture were treated with micro external fixator combined with small incision in fracture plane, including 23 males and 6 females, aged from 19 to 62 years old with an average of (36.2±21.0) years old. Five patients with open phalangeal fracture were treated with stageⅠsurgery, 24 cases of closed phalangeal fracture were treated with elective surgery. At the 6 month follow-up, the curative effect was evaluated according to the total active flexion scale (TAFS) of the American Hand Surgery Association. The fracture healing, nail path, local soft tissue healing, and complications were observed., Results: All the 29 patients were followed up for 6 to 10 months with an average of(8.3±2.1) months, 3 patients had delayed fracture healing, 1 patient had distal skin numbness, symptoms were relieved after nutritional nerve treatment, no external fixator broken nails, no infection, the nail path and small incision healing was good, bone healing was achieved at the end of follow-up. Fracture healing time ranged from 10 to 24 with an average of (13.7±3.1) weeks. Six months after operation, according to the TAFS standard, 19 cases (227.68±4.23) were excellent, 7 cases (203.86±14.32) were good, and 3 cases (170.33±7.32) were poor., Conclusion: The micro-combined external fixator combined with limited incision with small incision can be used in the treatment of proximal phalangeal fracture. The operation is simple and beneficial to early functional exercise, small extensor tendon irritation, convenient second-stage removal, and high rate of excellent and good functional score in recovery period.

Ferroptosis is involved in neurodegenerative disorders including diabetes-associated cognitive impairment (DACI). As central immune cells, microglia have strong siderophilic properties. However, the role of iron deposition in microglia and the underlying regulatory mechanism remains unclear in DACI. Here, we established high glucose (HG) model in BV2/HMC3 cells and diabetes model in C57BL/6 J mice with HFD and STZ. Transmission Electron Microscopy, Western blot, assay kits of Fe 2+ , GSH/GSSG, MDA and ROS were carried out in vitro. Prussian blue staining, Western blot and immunofluorescence were implemented in vivo. Y-maze and novel object recognition were performed to assess cognitive performance. LP17 was used to inhibit TREM1 (triggering receptor expressed on myeloid cells 1) specifically in vivo and vitro. We found excessively deposited iron and significant reduction in antioxidants in hippocampal microglia of mice with DACI, concomitant with increased TREM1 (a microglia-specific inflammatory amplifier). Furthermore, LP17 (TREM1 specific inhibitor) ameliorated cognitive impairment caused by HFD/STZ through relieving iron accumulation and antioxidant inactivation. In vitro, ferroptosis was induced by HG in mice microglia-BV2 and human microglia-HMC3 cells, which could be blocked by a ferroptosis inhibitor-Fer-1 and LP17. Moreover, PERK pathway of endoplasmic reticulum stress was activated by HG, and then reversed by PERK inhibitor GSK2606414 and LP17 followed by improved ferroptosis in HG-cultured BV2. In summary, our results indicated that TREM1 effectively aggravates T2DM-associated microglial iron accumulation through the PERK pathway of ERS, which contributes to antioxidant inactivation and lipid peroxidation, eventually, massively boosted ROS result in microglial ferroptosis. The mechanism elucidation in our study may shed light on targeted therapy of DACI., 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., (Copyright © 2024. Published by Elsevier Inc.)

Esophageal cancer is one of the most common cancers in the world, ranking sixth in cancer-related mortality. Doxorubicin (DOX), as a classic broad-spectrum, non-specific small-molecular anti-tumor drug, has achieved widespread use, including in the treatment of esophageal cancer. However, due to its strong cardiotoxicity, poor tumor-targeting ability, and short half-life, the clinical application of DOX has been greatly limited. In this research, we designed and successfully synthesized a peptide sequence IEIIIK (IEK for short) with excellent pH responsiveness. Under physiological conditions (pH 7.4), the peptide can encapsulate DOX and self-assemble into a stable hydrogel (DOX-IEK) through hydrophobic and electrostatic interactions. After being injected into the acidic tumor microenvironment, the protonation degree of alkaline amino acid lysine increased and the negative charge of glutamate decreased, directly leading to enhanced electrostatic repulsion and subsequent hydrogel dissociation. Released DOX can accumulate in tumor tissue and achieve anti-tumor efficacy. More importantly, the hydrogel can act as a drug reservoir for sustained drug release, improving the drug targeting ability, prolonging the duration of drug administration to compensate for the short half-life of DOX, and reducing systemic toxicity. Ideal anti-tumor efficacy has been achieved in both the in vitro and in vivo experiments., 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 Ye, Luo, Zafar, Ge, Liu, Wang, Jin, Wang, Chen and Ye.)

Largemouth bass virus (LMBV) is an infectious pathogen that causes high mortality rates in largemouth bass, and outbreaks of this virus can significantly harm the aquaculture industry. Currently, no vaccine has been developed that can effectively prevent the transmission of LMBV. In this study, we constructed a recombinant Lactobacillus plantarum (L. plantarum) strain capable of expressing the MCP gene of LMBV and displaying this protein on its surface; then, we evaluated the immunoprotective effect of this recombinant bacterium on largemouth bass. Western blotting, immunofluorescence, and flow cytometry confirmed that MCP was successfully expressed and anchored on the surfaces of NC8 cells. Immunization of largemouth bass with NC8-pSIP409-pgsA'-MCP via the oral feeding route induced CD4, CD8, IL-1β, and IL-6 gene expression. In addition, NC8-pSIP409-pgsA'-MCP at different CFUs increased the survival of largemouth bass after LMBV infection; in particular, NC8-pSIP409-pgsA'-MCP (10 9  CFU) resulted in approximately 30 % survival. NC8-pSIP409-pgsA'-MCP immunization alleviated the pathological changes in the liver and spleen, exerting a more advantageous protective effect. These data suggest that the recombinant L. plantarum strain NC8-pSIP409-pgsA'-MCP can increase the resistance of largemouth bass to LMBV infection and that this strain is a promising candidate oral vaccine for the prevention of LMBV infection., Competing Interests: Declaration of competing interest No conflict of interest exists with this paper submission, and all authors have approved the publication of this manuscript. All or any part of the study was not published and was not considered for publication elsewhere., (Copyright © 2024 Elsevier Ltd. All rights reserved.)