Search

Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although post-transplant cyclophosphamide (PtCy) has improved graft vs. host disease (GvHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. IFN-γ and IL-6 are central in the pathophysiology of GvHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase (JAK)-1. We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy-haplo-HCT to mitigate these complications and improve overall survival. This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GvHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day -3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2-5 CRS. There were no cases of primary graft failure. No patients developed grade 3-4 aGvHD through day +180. The cumulative incidence of grade 2 aGvHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GvHD was 5%. The cumulative incidence of relapse at 2 years was 14%. Overall survival (OS) at 1 year was 80%. The cumulative incidence of nonrelapse mortality at day 180 was 8%. Itacitinib, when added to standard GvHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GvHD, NRM and encouraging rates of GvHD-free relapse-free survival (GRFS) and OS after haplo-HCT. NCT03755414., (Copyright © 2024 American Society of Hematology.)

The ethynylation of formaldehyde catalyzed by Cu-based catalysts is an important synthesis method for 1,4-butynediol relating to high-value-added chemicals. In this work, a series of CuM/SiO 2 (M = Bi, Mg, Mn) catalysts were prepared by a deposition-precipitation method and applied in the ethynylation reaction. The effects of different promoters (Bi, Mg, Mn) on the catalytic activity were investigated. The relationship between the catalyst structure and performance is systematically studied using XRD, TEM, SEM mapping, N 2 low-temperature adsorption/desorption, FT-IR, XPS, and TG-DTA characterization analyses. The results show that 30Cu2Bi/SiO 2 exhibits the highest 1,4-butynediol yield (70%) and selectivity (97%) after the ethynylation reaction for 7 h. Furthermore, compared with the commercial catalyst, 30Cu2Bi/SiO 2 shows similar cyclic stability, 47% yield, and 98% selectivity for 1,4-butynediol after 8 times for about 60 h. It is suggested that small CuO particles are uniformly dispersed in 30Cu2Bi/SiO 2 with the biggest specific surface area (446.37 m 2 g -1 ). Moreover, the Cu-Bi interface existing in 30Cu2Bi/SiO 2 plays an important role in stabilizing cuprous, not excessively reduced to metallic Cu. Therefore, during the ethynylation reaction, 30Cu2Bi/SiO 2 has the most active Cu 2 C 2 and the least polyacetylene by-products. In addition, the richest oxygen vacancies arising in 30Cu2Bi/SiO 2 also contribute to the ethynylation reaction of formaldehyde.

Background: Angioplasty and/or stenting is a rescue therapy for mechanical thrombectomy (MT) in acute intracranial large vessel occlusion. This study was undertaken to determine whether rescue angioplasty and/or stenting improves the outcome after MT and to investigate whether outcomes differ by subgroup of rescue indication., Methods: We performed propensity score matching (PSM) with data from a prospective multicenter registry of patients with acute large vessel occlusion receiving endovascular treatment. Patients were divided into the MT alone group and the MT with rescue therapy group. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. PSM was also performed in the failed MT (modified Thrombolysis In Cerebral Infarction (mTICI) 0-2a) and the residual severe stenosis (mTICI 2b-3) subgroups, respectively., Results: 326 patients of mean±SD age 62.7±12.0 years (90 women, 27.6%) were matched from 1274 patients. In the matched cohort, functional independence at 90 days was higher in the rescue therapy group than in the MT alone group (44.2% vs 29.5%; OR 1.90, 95% CI 1.18 to 3.06, P=0.008). In the failed MT subgroup with 66 matched pairs, more patients had functional independence in the rescue therapy group than in the MT alone group (39.0% vs 17.0%; OR 3.12, 95% CI 1.29 to 7.59, P=0.01). In the residual stenosis subgroup with 63 matched pairs, functional independence rates were similar in the rescue therapy and the MT alone groups (51.6% vs 55.7%; OR 0.85, 95% CI 0.42 to 1.72, P=0.65)., Conclusion: Rescue angioplasty and/or stenting could improve the clinical outcome in patients with acute large vessel occlusion with failed MT, while no benefit was seen in those with residual severe stenosis but substantial reperfusion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A transdermal drug delivery cream, which is non-invasive and painless, containing a liposome-encapsulated Ru(II) complex (LipoRu) is created for the treatment of skin cancer. This formulation capitalizes on the synergistic antitumor effects of two-photon excited photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. LipoRu exhibits effective tumor accumulation, efficient cellular uptake, pH-sensitive and infrared-accelerated release, and dual localization to the nucleus and mitochondria. The released Ru(II) complexes within cells exert multiple antitumor mechanisms, such as DNA topoisomerase and RNA polymerase inhibition, Type I and II PDT, PTT, DNA photodamage, and apoptosis and ferroptosis induction. The biodistribution and therapeutic efficacy of LipoRu in vivo are systematically compared via three distinct administration routes: intratumoral injection, intravenous injection, and transdermal delivery through topical cream application. The positive therapeutic effects of the LipoRu cream fabricated here in subcutaneous tumor-bearing mice offer optimistic potential for the painless and non-invasive treatment of both early-stage and advanced skin cancers, as well as superficially located solid tumors., (© 2024 Wiley‐VCH GmbH.)

Roof breaking is the root cause of rock burst and mine earthquake. However, the classical "thin plate theory" and "thick plate theory" cannot fully reveal the mechanical mechanism of the influence of roof thickness-span ratio on the fracture mode. In this paper, based on the cohesive element technology, the mechanical behavior of cohesive element failure was studied according to the maximum nominal stress criterion and BK fracture criterion, and the fracture mechanical behavior of roofs with different thicknesses fixed on four sides under uniform load was numerically simulated. The fracture pattern and the maximum principal stress evolution laws of roofs with different thicknesses were obtained. The results show that there are three fracture modes of the plates with different thickness: pure tensile fracture mode at the bottom surface, mixed fracture mode around the "X" shape crack, and pure shear fracture mode along the long edge boundary. The crack morphology of thin plate is the transverse "O-X" type, and the crack morphology of thick plate is the "O-❋" type. With the increase of thickness, the tensile-shear mixed failure mode gradually changes from the tensile dominant to the shear dominant., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Advanced smart polymer materials with the ability of reversible deformation under external stimuli hold great potential in robotics, soft machines, and flexible electronics. However, the complexity and low efficiency for fabricating actuators along with their limited functionality hinder further progress. Here an efficient and mild catalyst-free thiol-yne click polymerization was developed to fabricate photosensitive polyimide (PI) films. Then the fluorescent robust photoactuators with single-layered janus structure were directly obtained via UV assisted photo-crosslinking of the films, exhibiting reversible response driven by a pronounced mismatch in expansion between the front and back sides of the films. Achieving selective, non-uniform spatial distribution within the PI films, rapid and reversible complex morphing of the actuators, along with the capabilities for encrypting, reading, and erasing fluorescent information-all through the use of a single UV light source-becomes straightforward. The robust mechanical property and driving ability of these actuators enable the conversion of light energy into obvious motion even under heavy loads and the leaping through the storage and release of energy, ensuring their potential for practical applications that require durability and reliability., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: To delineate the clinical and mutational signatures of patients with CRB1 -associated retinopathies., Methods: This multicentre retrospective cohort study involved 40 patients with CRB1 mutations and 40 age-matched and gender-matched inherited retinal diseases (IRDs). The detailed phenotyping and genotyping characteristics and genotype‒phenotype correlations of the patients were analysed., Results: The mean age of CRB1 cohort was 27.33±14.63 years. Results showed that yellowish geographic macular degeneration (66.67%), small white or yellow dots (65.6%), hyperopia (62.5%), abnormally laminated retina (61.61%), epiretinal membrane (60.6%) and nummular pigment deposits (50%) were the most common signatures in patients with CRB1 mutations. These clinical signatures were notably more prevalent among CRB1 patients than among individuals in other IRD groups (p<0.001). Early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) patients are more likely to present these signatures than retinitis pigmentosa (RP) and macular dystrophy (MD) patients. Furthermore, a significant reduction in central foveal thickness coupled with pronounced thickening of the peripheral retina was observed more distinctly in patients with EOSRD/LCA (p<0.001). The choroidal thickness was not significantly altered compared to the normal controls, but was markedly reduced in the other IRD groups (p<0.001). 55 pathogenic variants were identified, 20 of which were novel. Null mutations were associated with EOSRD/LCA patients, and missense mutations were more prevalent in MD and RP patients., Conclusions: Key clinical and mutational signatures were demonstrated in this study, providing a comprehensive update on CRB1 -associated retinopathies that will aid in diagnosis and lay the foundation for future therapeutic studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Nickel-based hydroxides [Ni(OH) 2 ] have attracted significant attention as effective oxygen evolution reaction (OER) catalysts. In recent years, defect engineering has been extensively utilized in Ni(OH) 2 modification research. Numerous studies have confirmed that the generation of defects can expose more active sites and regulate electronic states, particularly through the introduction of Al cationic vacancies, which enhance conductivity and thereby improve the catalytic performance. The traditional method for producing cationic vacancies is electrochemical etching. However, this method generates a limited number of vacancies in the catalysts and has the complex etching process. Herein, we found that when NiAl layered double hydroxides were treated using a hydrothermal process at 100 °C in a KOH solution, more Al cationic vacancies were generated. Compared to the traditional method with an Al leaching efficiency of 24%, our proposed method achieved an Al leaching efficiency of 44%. Meanwhile, the electrochemical results showed that the overpotential was reduced by 110 mV at 10 A/g. Further experiments showed that the enhanced OER activities resulting from an increased number of cationic defects lead to structural distortions, which broaden the e g * band, significantly affecting the rate of electron transfer between the electrocatalyst and external circuitry, thereby enhancing the OER activity. This work presents a promising approach to creating cationic defects in Ni(OH) 2 for high-performance electrocatalysts.

The use of combinatorial siRNAs shows great promise for drug discovery, but the identification of safe and effective siRNA combinations remains challenging. Here, we develop a massively multiplexed technology for systematic screening of siRNA-based cocktail therapeutics. We employ composite micro-carriers that are responsive to near infrared light and magnetic field to achieve photoporation-facilitated siRNA transfection to individual cells. Thus, randomized gene silencing by different siRNA formulations can be performed with high-throughput single-cell-based analyses. For screening anti-cancer siRNA cocktails, we test more than 1300 siRNA combinations for knocking down multiple genes related to tumor growth, discovering effective 3-siRNA formulations with an emphasis on the critical role of inhibiting Cyclin D1 and survivin, along with their complementary targets for synergic efficacy. This approach enables orders of magnitude reduction in time and cost associated with largescale siRNA screening, and resolves key insights to siRNA pharmacology that are not permissive to existing methods., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE)., Objective: To develop and test a blood-based assay for EAC and BE., Design: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia ( EMERALD ) was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE. Tissue-based miRNA sequencing and microarray datasets (n=134) were used to identify candidate miRNAs of diagnostic potential, followed by validation using 42 pairs of matched cancer and normal tissues. The usefulness of the candidate miRNAs was initially assessed using 108 sera (44 EAC, 34 EAC precursors and 30 non-disease controls). We finally trained a machine learning model (XGBoost+AdaBoost) on RT-qPCR results from circulating miRNAs from a training cohort (n=160) and independently tested it in an external cohort (n=295)., Results: After a strict process of biomarker discovery and selection, we identified six miRNAs that were overexpressed in all sera of patients compared with non-disease controls from three independent cohorts of different nationalities (miR-106b, miR-146a, miR-15a, miR-18a, miR-21 and miR-93). We established a six-miRNA diagnostic signature using the training cohort (area under the receiver operating characteristic curve (AUROC): 97.6%) and tested it in an independent cohort (AUROC: 91.9%). This assay could also identify patients with BE among patients with gastro-oesophageal reflux disease (AUROC: 94.8%, sensitivity: 92.8%, specificity: 85.1%)., Conclusion: Using a comprehensive approach integrating unbiased genome-wide biomarker discovery and several independent experimental validations, we have developed and validated a novel blood test that might complement screening options for BE/EAC., Trial Registration Number: NCT06381583., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

It remains a challenge to endow a polymeric material with antithrombotic ability by surface grafting without disturbing the bulk properties of the substrate. Heparin-based functional structures of less than 80 nm were fabricated and covalently grafted on a polyethylene terephthalate surface via carbene chemistry (Hep-g-PET). Heparin was oxidized with the minimum antithrombrin sequence retained, creating an aldehyde group on the chain terminus. Oxidized heparin was then covalently attached to a poly(amidoamine) (PAMAM)-grafted PET substrate. The interface between blood and PET was improved by the surface functionality, and the amount of attached platelets decreased to 29 ± 12.1% of its initial value. The bulk properties of the functionalized film were hardly influenced, and the visible light transmittance remained more than 96%. The tethered structures also showed the ability to kill attached S. aureus and E. coli efficiently. The functionalized membrane showed negligible ex vivo cell cytotoxicity and a low hemolysis ratio. Hep-g-PET was implanted in between rat skin and muscle, and showed an outstanding histological response and antimicrobial ability. The influences of the graft thickness and the heparin chain length were explored. The strategies reported in this work may help to improve the design of polymeric implant bio-devices.

Six polypyridyl Ru(II) complexes were designed for single-molecule photodynamic and sonodynamic therapy (PDT/SDT) synergistic multimodal anticancer toward cisplatin-resistant NSCLC. They demonstrated lowest 3ES with distinct intraligand transition nature, which is beneficial for singlet oxygen generation. Remarkable quantum yields of both singlet oxygen and superoxide anion under either 808 nm laser irradiation or ultrasonic treatment and could induce apoptosis and ferroptosis of A549R cells. Cytotoxicity experiments clearly demonstrated a synergistic effect between PDT and SDT. The relationship between the structures of these complexes and their cellular biological mechanisms has been explored in detail. Using a single-molecule sensitizer to achieve synergistic PDT/SDT may provide valuable insights for the treatment of drug-resistant tumors that located deeply and in hypoxic microenvironment., (© 2024 Wiley‐VCH GmbH.)

Human breathing is crucial for studying indoor environments and human health. Computational Fluid Dynamics (CFD) is a key tool for simulating human respiration. To enhance the accuracy of CFD simulations and reduce computation time, a new simulation strategy for human respiration is proposed in this paper. The effects of steady versus unsteady boundary conditions on simulation results were examined. For the unsteady boundary, sinusoidal exhalation velocities and non-inhalation gas were assumed, while the steady boundary involved constant velocities during both exhalation and inhalation phases. The jet center trajectory under different boundary conditions was analyzed and compared with experimental data. Additionally, variations in pollutant dispersion near the mouth under the two boundary conditions were discussed. Furthermore, the paper compared the calculation accuracy, calculation time and memory occupied by a single turbulence model or switching flow character models in human respiration simulation. Differences in exhaled gas vorticity and jet penetration depth across different flow models were identified. Finally, combined with the non-iterative algorithm, the optimal strategy of human respiration simulation was proposed. Results show that under the comprehensive consideration of calculation accuracy, calculation time and memory occupancy, using sinusoidal expiratory boundary conditions combined with the PISO algorithm, with the RNG k-ε model during expiratory phase, and switching into the laminar flow during inspiratory phase, is the optimal strategy of simulating human breathing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Analyze the clinical and ultrasound characteristics of 15 cases of abdominal pregnancy (AP) to improve the ultrasonography-based diagnosis., Methods: A retrospective research of AP patients from 2010 to 2021 with pathology was performed, clinical and ultrasound characteristics were analyzed and summarized., Results: Fifteen cases of AP occurred in early pregnancy. Most cases of AP were implanted in the pelvic cavity, with a few on the greater omentum and diaphragm, etc. Eight cases showed mixed hyperechoic, four cases had gestational sacs, and three cases exhibited mixed hypoechoic., Conclusion: Combined with the characteristics of AP, ultrasound can provide a valuable diagnosis., (© 2024 Wiley Periodicals LLC.)

The redox status is intricately linked to the development and progression of cancer, a process that can be modulated by long non-coding RNAs (lncRNAs). Previous studies have demonstrated that redox regulation can be considered a potential therapeutic approach for cancer. However, the redox-related lncRNA predictive signature specific to bladder cancer (BCa) has yet to be fully elucidated. The purpose of our study is to establish a redox-related lncRNA signature to improve the prognostic prediction for BCa patients. To achieve this, we downloaded transcriptome and clinical data from the Cancer Genome Atlas (TCGA) database. Prognostic redox-related lncRNAs were identified through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis, resulting in the establishment of two risk groups. A comprehensive analysis corresponding to clinical features between high-risk and low-risk groups was conducted. Eight redox-related lncRNAs (AC018653.3, AC090229.1, AL357033.4, AL662844.4, AP003352.1, LINC00649, LINC01138, and MAFG-DT) were selected to construct the risk model. The overall survival (OS) in the high-risk group was worse than that in the low-risk group (p < 0.001). The redox-related lncRNA signature exhibits superior predictive accuracy compared to traditional clinicopathological characteristics. Gene Set Enrichment Analysis (GSEA) showed that the MAPK signaling pathway and Wnt signaling pathway were enriched in the high-risk group. Compared with the low-risk group, patients in the high-risk group demonstrated increased sensitivity to cisplatin, docetaxel, and paclitaxel. Furthermore, IGF2BP2, a potential target gene of MAFG-DT, was found to be overexpressed in tumor tissues and correlated with overall survival (OS). Our study demonstrated that the predictive signature based on eight redox-related lncRNAs can independently and accurately predict the prognosis of BCa patients., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Short-chain fatty acids have been reported to have anti-inflammatory and antioxidant functions; whether isobutyrate, a short-chain fatty acid, is protective against liver injury in a dextran sodium sulfate (DSS)-induced colitis and its molecular mechanism is unknown. In this study, DSS was used to induce a liver injury from a colitis model in piglets, which was expected to prevent and alleviate DSS-induced liver injury by feeding sodium isobutyrate in advance., Results: The results showed that sodium isobutyrate could restore DSS-induced histopathological changes in the liver, inhibit the activation of the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa-B signaling pathway, and then reduce the DSS-induced release of pro-inflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6, reducing inflammatory response. Moreover, we found that sodium isobutyrate could play an antioxidant and apoptosis-reducing role by maintaining reduced mitochondrial function., Conclusion: In conclusion, sodium isobutyrate has a preventive and protective effect on liver injury in a DSS-induced colitis. There is a potential application prospect for it in treating ulcerative-colitis-induced liver injuries. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Neoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence., Methods: Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite of neoantigen prediction algorithms was used to identify and prioritize cancer neoantigens and facilitate vaccine design for manufacture in an academic GMP facility. Neoantigen DNA vaccines were administered via electroporation in the adjuvant setting (i.e., following surgical removal of the primary tumor and completion of standard of care therapy). Vaccines were monitored for safety and immune responses via ELISpot, intracellular cytokine production via flow cytometry, and TCR sequencing., Results: Eighteen subjects received three doses of a neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4-20). The vaccinations were well tolerated with relatively few adverse events. Neoantigen-specific T cell responses were induced in 14/18 patients as measured by ELISpot and flow cytometry. At a median follow-up of 36 months, recurrence-free survival was 87.5% (95% CI: 72.7-100%) in the cohort of vaccinated patients., Conclusion: Our study demonstrates neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses., Clinical Trial Registration Number: NCT02348320., Competing Interests: Declarations Ethics approval and consent to participate The clinical protocol was reviewed and approved by the Institutional Review Board (ID# 201505074) at Washington University School of Medicine. The research conformed to the principles of the Helsinki/Tokyo/Venice Declaration on experimentation in humans. Consent for publication Written consent for publication was obtained from all participating patients. Competing interests K.S., M.G., and O.G. are consultants for the Jaime Leandro Foundation. All other authors declare that they have no competing interests., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Niuhuang Shangqing Pill (NSP) is a renowned Chinese medicine prescription listed in the Chinese Pharmacopoeia (Edition 2020, volume 1) and is utilized in clinical practice for treating headaches and acute pharyngitis (AP) associated with "Shanghuo". Despite its widespread use, the pharmacological mechanism and bioactive components underlying NSP in treating AP remain unclear., Aim of the Study: This study delved into evaluate the alleviation effect of NSP on AP and explore the mechanisms by analyzing multi-omics., Materials and Methods: UHPLC-Q Exactive Orbitrap HRMS was employed for the chemical ingredients of NSP. Multiple compositions, targets and pathways involved in the treatment of AP with NSP were predicted by network pharmacology. Additionally, wistar rat model of AP induced by capsaicin was established to evaluate the anti-AP activity of NSP in vivo. The potential mechanism of NSP to improve AP was investigated by real-time PCR, pharyngeal transcriptome analysis, non-targeted metabolomics, immunofluorescence and western blot., Results: 119 compounds were identified by UHPLC-Q Exactive Orbitrap HRMS. Both clinical data of Gene Expression Omnibus (GEO) and network pharmacology demonstrated that MAPK signaling pathway and TNF signaling pathway were the critical pathway for AP treatment. In rat model of AP induced by capsaicin, NSP demonstrated the ability to reduce the levels of IL-1β, TNF-α, IL-6, CGRP, SP, PGE 2 , COX-2 in serum. Moreover, Transcriptomics analysis comprehensively indicated that NSP regulated the MAPK signaling pathway, TNF signaling pathway, biosynthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism in AP rats. Metabolomics analysis verified that NSP could rebalance arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan and regulate metabolic profiles. Multi-omics Correlation analysis exhibited that the relative expression of Tnfrsf1b was significantly negatively correlated with 12(S)-HPETE. Immunofluorescence, real-time PCR and western blot of pharyngeal tissue revealed that NSP inhibited the TNF/p38-MAPK/NF-κB signaling pathway. Additionally, in vitro study on RAW264.7 cells confirmed that NSP counteract LPS-induced inflammatory by inhibiting the TNF/p38-MAPK/NF-κB signaling pathway. Overall, NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism and TNF/p38-MAPK/NF-κB signaling pathway., Conclusion: NSP effectively ameliorated capsaicin-induced AP by modulating the arachidonic acid metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, as well as the TNF/p38-MAPK/NF-κB signaling pathway., 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 generation of difluorocarbene from difluoromethane bis(sulfonium ylide) 1 through spin-forbidden excitation under irradiation with 450 nm blue light was reported. The formation of difluorocarbene was confirmed by its reaction with styrene derivatives for the generation of difluorocyclopropanation and insertion into RX-H bonds (X = O, S) for the generation of RXCF 2 H. The spin-forbidden excitation mechanism for the formation of difluorocarbene from difluoromethane bis(sulfonium ylide) was supported by spectroscopic and kinetic studies as well as computational chemistry. The homolytic cleavage of two S-C bonds in compound 1 under irradiation was confirmed by time-resolved EPR spectroscopic studies of the precursor's free-radical-capturing reaction, as well as the isolation of the dimer of dimethyl (phenylthiol)malonyl radical. Further studies showed that the homolytic cleavage process occurred asynchronously in the solvent cage based on the isotope-labeled scrambling experiments and DFT calculations.

Six C-6 fluorinated d-swainsonine derivatives and their enantiomers have been designed based on initial docking calculations, and synthesized from enantiomeric ribose-derived aldehydes, respectively. Glycosidase inhibition assay of these derivatives with d-swainsonine (1) and l-swainsonine (ent-1) as contrasts found that the C-6 fluorinated d-swainsonine derivatives with C-8 configurations as R (α) showed specific and potent inhibitions of jack bean α-mannosidase (model enzyme of Golgi α-mannosidase II); whereas their enantiomers with C-8 configurations as S (β) were powerful and selective α-l-rhamnosidase inhibitors. Molecular docking calculations found the C-6 fluorinatedd-swainsonine derivatives 21, 24 and 25 with highly coincident binding conformations with d-swainsonine (1) in their interactions with the active site of α-mannosidase (PDB ID: 1HWW). Reliability of the docking results were confirmed by Molecular Dynamics (MD) simulation. Additionally, solid interactions with residues Gln-392 and Tyr-393 in the active site of α-l-rhamnosidase (PDB ID: 3W5N) were proved to be vital for potent α-l-rhamnosidase inhibitions of the l-swainsonine derivatives. The role of C-6 fluorines in swainsonine derivatives well demonstrated the "mimic effect" of fluorine to hydrogen by minimal influence on the binding conformations and effective compensation for any possible lost interactions. This work contributes to a comprehensive understanding of the structure-activity relationship (SAR) of the fluorinated swainsonines and ever reported branched swainsonines, and has laid good foundation for development of more potent α-mannosidase and α-l-rhamnosidase inhibitors., 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 Masson SAS. All rights reserved.)

Due to their good wearability, smart fabrics have gradually developed into one of the important components of multifunctional flexible electronics. Nevertheless, function integration is typically accomplished through the intricate stacking of diverse modules, which inevitably compromises comfort and elevates processing complexities. The integration of these discrete functional modules into a unified design for smart fabrics represents a superior solution. Here, we put forward a rational approach to functional integration for the typical challenges of thermal management, energy supply, and surface contamination in smart fabrics. This sandwich-structured multilayer fabric (MLF) is obtained by continuous electrospinning of two layer P(VDF-HFP) fabric and one layer P(VDF-HFP) fabric functionalized with core-shell SiO 2 /ZnO/ZIF-8 (SZZ) nanoparticles. Specifically, MLFs achieve effective and stable energy harvesting in triboelectric nanogenerators (TENGs) with hydrophobicity and antibacterial properties. Meanwhile, MLFs also have high mid-infrared emissivity and sunlight reflectivity, successfully realizing radiative cooling under different climates, and have been applied in wearing clothing, roof shading, and car covers. This work may contribute to the design and manufacturing of next-generation thermal comfort smart fabrics and wearable electronics, particularly in terms of the rational design of multifunctional devices.

Group 2 innate lymphoid cells (ILC2s) play a crucial role in allergic diseases by coordinating a complex network of various effector cell lineages involved in type 2 inflammation. However, their function in regulating airway neutrophil infiltration, a deleterious symptom of severe asthma, remains unknown. Here, we observed ILC2-dependent neutrophil accumulation in the bronchoalveolar lavage fluid (BALF) of allergic mouse models. Chromatography followed by proteomics analysis identified the alarmin high mobility group box-1 (HMGB1) in the supernatant of lung ILC2s initiated neutrophil chemotaxis. Genetic perturbation of Hmgb1 in ILC2s reduced BALF neutrophil numbers and alleviated airway inflammation. HMGB1 was loaded onto the membrane of lipid droplets (LDs) released from activated lung ILC2s. Genetic inhibition of LD accumulation in ILC2s significantly decreased extracellular HMGB1 abundance and BALF neutrophil infiltration. These findings unveil a previously uncharacterized extracellular LD-mediated immune signaling delivery pathway by which ILC2s regulate airway neutrophil infiltration during allergic inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Polyethylene (PE) is the most abundant plastic waste, and its conversion to hydrogen (H 2 ) offers a promising route for clean energy generation. However, PE decomposition typically requires high temperatures due to its strong chemical bonds, leading to significant carbon emissions and low H 2 selectivity (theoretically less than 75 vol % after accounting for further steam-reforming reactions). Here, we report a mechanocatalytic strategy that upcycles PE into high-purity H 2 (99.4 vol %) with an exceptional H 2 recovery ratio of 98.5 % (versus 15.7 % via thermocatalysis), using manganese as a catalyst at a low temperature of 45 °C. This method achieves a reaction rate 3 orders of magnitude higher than thermocatalysis. The marked improvement in H 2 recovery ratio is mainly due to metal carbides formation induced by the mechanocatalytic process, which does not catalyze hydrocarbons formation. This work is expected to advance studies of the conversion of polyolefins to high-purity H 2 with net-zero carbon emissions., (© 2024 Wiley-VCH GmbH.)

Background: Both high-sensitive C-reactive protein (hsCRP) and CYP2C19 genotypes are independent predictors of clinical outcomes after ischemic stroke. We aim to evaluate the association of CYP2C19 loss-of-function alleles (LoFA) carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels using the CHANCE trial., Methods: Subjects with both of CYP2C19 major alleles information (*2, *3, and *17) and hsCRP measurements were enrolled from the prespecified subgroup. CYP2C19 LoFA carriers were defined as patients with either*2 or *3 allele. Cox proportional hazards models were used to assess the interaction of CYP2C19 LoFA carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels. The primary outcome was recurrent stroke within 90 days., Results: Among 2801 patients, 1646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with non-elevated hsCRP, there was a significant interaction effect between CYP2C19 LoFA carrying status and dual/single antiplatelet regimens for prevention of recurrent stroke and combined vascular events (p =0.048, 0.048, respectively), but, not in patients with elevated hsCRP (p =0.502, 0.472, respectively). Only among patients with non-elevated hsCRP and non-carrier of CYP2C19 LoFA, dual antiplatelets significantly reduced the risk of recurrent stroke compared with aspirin alone (hazard ratio= 0.44 [0.26-0.74], p=0.003). No significant differences in bleeding were found., Conclusions: Non-elevated hsCRP and non-carrier of CYP2C19 LoFA may predict a better response to dual antiplatelet therapy in reducing stroke recurrence and composite vascular events for patients with minor stroke and high-risk TIA., Trial Registration: clinicaltrials.gov Identifier: NCT00979589., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Bus stop layout typically requires consideration of urban population distribution, traffic conditions, and passenger flow demand to establish an efficient foundation for the bus system's operation. Based on the above key factors, this paper introduces a strategic method to optimize the bus stop layout from a macro perspective in order to save passengers' travel time and improve the attractiveness of the bus system. This approach accounts for the matching degree between the Origin-Destination (OD) direction of passengers and their walking direction heading to bus stops. Initially, we take into account factors such as the population and area of traffic districts, and urban road conditions. Utilizing the hypernetwork multidimensional data clustering method along with GIS technology, we construct an alternative set of bus stops based on the hypernetwork framework. This set serves as a reference for the positioning of newly built and moved bus stops. Subsequently, we develop a two-stage model for bus stop layout decision-making. The first stage focuses on determining the bus stop layout at the traffic district level, taking into account multi-factors including the passenger flow matching degree. The second stage is designed to mitigate the negative impact of bus stop optimization on the overall service level of the urban bus system. A case study conducted in XT city demonstrates the effectiveness of our approach. Post-optimization, there is a 15.83% increase in the alignment between passenger flow direction and bus stop layout. Additionally, the average travel time for passengers is reduced by 7.55 minutes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Stair climbing test (SCT) and gait speed test (GST) are two physical performance measures, both of which are associated with postoperative outcomes. However, few studies have compared these two tests for the prognostic value., Methods: A prospective study was conducted in patients undergoing radical gastrectomy for gastric cancer. Handgrip strength (HGS) test, 7-steps SCT and 6-m GST were performed before surgery. Body compositions were analyzed using abdominal computed tomography (CT). Sarcopenia was diagnosed by low HGS plus either low muscle mass or quality., Results: A total of 548 patients were included in this study. Time of GST and SCT were both significantly correlated with HGS, skeletal muscle index and skeletal muscle density, but not with subcutaneous or visceral fat area. Low SCT performance (SCT time ≥12.65s) was associated with higher incidence of postoperative complications and longer postoperative length of stay, whereas low GST performance (GST time ≥5.45s) did not. Low performance in SCT and GST were both associated with worse overall survival (OS) and disease-free survival (DFS) after surgery. Low SCT performance was an independent predictor for postoperative complications, OS, and DFS, whereas low GST performance was not significant in multivariate analyses adjusting for the same covariates. The combination of sarcopenia with low SCT performance showed higher accuracy in predicting postoperative complications and mortality compared with sarcopenia combined with low GST performance., Conclusion: SCT outperformed GST in predicting outcomes after radical gastrectomy for gastric cancer, either as a singular indicator or in combination with sarcopenia assessments., 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, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Studying vascular responses to microgravity (MG) poses significant challenges in space medicine due to the limitations of conventional cell culture and animal models. To address these challenges, we have developed an innovative biosensory μvessel-gravity device that integrates organ-on-a-chip technology, 3D printing, and a 3D clinostat. This device enables cell interaction monitoring and flow shear stress modeling, thereby allowing accurate blood vessel cell sensory to changed mechanical environment. Our study reveals that simulated MG induces senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) within mono-cultured μvessels. Interestingly, co-culturing ECs and VSMCs in the μvessel mitigates EC senescence, although VSMC senescence remains unaffected. Furthermore, the application of continuous flow shear stress delays EC senescence and enhances tight junction integrity under MG conditions, underscoring the importance of incorporating mechanical factors into the device. Knocking down the mechanosensor Piezo1 in VSMCs delays senescence in both VSMCs and ECs under MG, highlighting the critical role of mechanosensors in vascular responses to MG. The biosensory μvessel-gravity device presents an innovative in vitro model designed to sense vascular changes induced by gravitational forces, effectively replicating the pro-aging effects of MG on vascular tissues. This holds significant potential for advancing research in aging-related vascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study assessed the equilibrium solubility, oil-water distribution coefficient, and dissociation constant of Isoxanthohumol (IXN), and formulated IXN nanoparticles (IXN-Nps) using a micro media grinding method. The research characterized the particle size, polydispersity index, zeta potential, morphology, and structure of the nanoparticles, and evaluated the optimal cryoprotectant. Additionally, the study examined the toxicity and in vitro and in vivo release of IXN on HT-29 cells. IXN is classified as a Biopharmaceutical Classification System (BCS) II class drug with weak acidity. The average particle size of IXN-Nps is 249.500 nm, with a polydispersity index (PDI) of 0.149 and a zeta potential of -25.210 mV. The research identified 5 % mannitol as the optimal cryoprotectant. Compared to IXN, the half-maximal inhibitory concentration of IXN-Nps decreased to one-third, demonstrating a significant inhibitory effect on HT-29 colon cancer cells. The in vitro cumulative release rate of IXN-Nps within 24 h was 3.5 times higher than that of the IXN solution. In vivo pharmacokinetic results revealed that the oral bioavailability of IXN-Nps increased significantly by 2.8 times compared to the IXN solution. The correlation coefficient (r = 0.9227) exceeded the critical value for significance at the 0.01 (r = 0.834) level, indicating a strong correlation between in vivo and in vitro results. Consequently, the nanosuspension overcame the low solubility limitation of IXN and proved to be an effective method for enhancing the oral bioavailability of IXN., 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: In patients with diabetes mellitus (DM) and monoclonal gammopathy of undetermined significance (MGUS), the impact of GLP-1 receptor agonists (GLP-1RAs) on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1RA use in the progression of MGUS to multiple myeloma (MM) in patients with DM., Methods: This is a population-based cohort study of Veterans diagnosed with MGUS from 2006-2021 with a prior diagnosis of DM. A validated natural language processing-algorithm was used to confirm MGUS and progression to MM. Gray's test was performed to detect the difference in cumulative Incidence functions (CIFs) for progression by GLP-1RA use status. The association between time-varying GLP-1RA use and progression was estimated in the 1 (exposed):2 (unexposed) matched cohort via multivariable-adjusted hazard ratio (aHR) using stratified Fine-Gray distribution hazard model with death as a competing event and stratum for the matched patient triad., Results: Our analytic cohort included 1,097 MGUS patients who ever used GLP-1RAs, and the matched 2,194 patients who never used GLP-1RAs. Overall, 2.55% progressed in the GLP-1RA ever use group, compared to 5.01% in the GLP-1RA never use group. CIFs were significantly different between the exposed and unexposed groups (P = .02). GLP-1RA use, compared to no-use, was associated with decreased progression to MM (aHR 0.45, 95% confidence interval 0.22 to 0.93, P = .03)., Conclusions: For patients with DM and MGUS, GLP-1RA use is associated with a 55% reduction in risk of progression from MGUS to MM, compared to no use., (© The Author(s) 2024. Published by Oxford University Press.)

Background: With a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear., Methods: The mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR., Results: HPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings., Conclusion: HPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs., Competing Interests: Authors XX, NW, and GJ were employed by Aimin Pharmaceutical Group. The remaining 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 Li, Dai, Zhang, Guo, Gao, Cheng, An, Lin, Xiong, Wang, Jiang, Xu and Lei.)

Intestinal injury is often accompanied by epithelial barrier dysfunction, oxidative stress, and apoptosis. Previous research studies have demonstrated that small extracellular vesicles (sEVs) from animal milk play a crucial role in regulating intestinal injury. Nonetheless, there has been limited research on the impact of goat milk sEVs on intestinal damage. This study aims to explore the functional differences between proteins in colostrum-derived sEVs (CME) and mature milk-derived sEVs (MME) from goat and elucidate their effects and mechanisms on lipopolysaccharide (LPS)-induced injury in IEC-6. Proteomic analysis revealed that both CME and MME are rich in various bioactive proteins that have regulatory effects on cell damage. CME and MME significantly improved LPS-induced IEC-6 barrier dysfunction and oxidative stress. Additionally, CME and MME alleviated LPS-induced IEC-6 proliferation inhibition and apoptosis. Notably, CME exhibited a more significant improvement effect. RNA-Seq analysis indicated that CME ameliorates IEC-6 injury by inhibiting multiple genes and signaling pathways associated with cell damage, particularly the MAPK signaling pathway. In summary, goat milk-derived sEVs improve LPS-induced IEC-6 injury by targeting the MAPK signaling pathway, significantly restoring the intestinal epithelial barrier function, reducing oxidative stress, and alleviating apoptosis. These findings offer scientific evidence supporting the potential application of goat milk-derived sEVs as protective agents against intestinal injury.

Background and Purpose: Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis., Materials and Methods: We retrospectively analyzed patients with symptomatic intracranial atherosclerotic stenosis stent placement in a prospective cohort at a high-volume stroke center. Clinical, radiologic, and periprocedural characteristics and long-term outcomes were reviewed. Periprocedural intracranial hemorrhage was classified as procedure-related hemorrhage (PRH) and non-procedure-related hemorrhage (NPRH). The long-term outcomes were compared between patients with PRH and NPRH, and the predictors of NPRH were explored., Results: Among 1849 patients, 24 (1.3%) had periprocedural intracranial hemorrhage, including PRH (4) and NPRH (20). The postprocedural 30-day mRS was 0-2 in 9 (37.5%) cases, 3-5 in 5 (20.8%) cases, and 6 in 10 (41.7%) cases. For the 14 survivors, the long-term (median of 78 months) mRS were 0-2 in 10 (76.9%) cases and 3-5 in 3 (23.1%) cases. The proportion of poor long-term outcomes (mRS ≥3) in patients with NPRH was significantly higher than those with PRH (68.4% versus 0%, P = .024). Anterior circulation ( P = .002), high preprocedural stenosis rate ( P < .001), and cerebral infarction within 30 days ( P = .006) were independent predictors of NPRH after stent placement., Conclusions: Patients with NPRH had worse outcomes than those with PRH after stent placement for symptomatic ICAS. Anterior circulation, severe preprocedural stenosis, and recent infarction are independent predictors of NPRH., (© 2024 by American Journal of Neuroradiology.)

Typically, organic solar cells (OSCs) and photodetectors (OPDs) comprise an electron donating and accepting material to facilitate efficient charge carrier generation. This approach has proven successful in achieving high-performance devices but has several drawbacks for upscaling and stability. This study presents a fully vacuum-deposited single-component OPD, employing the neat oligothiophene derivative DCV2-5T in the photoactive layer. Free charge carriers are generated with an internal quantum efficiency of 20 % at zero bias. By optimizing the device structure, a very low dark current of 3.4 · 10 -11  A cm -2 at -0.1 V is achieved, comparable to the dark current of state-of-the-art bulk heterojunction OPDs. This optimization results in specific detectivities of 1· 10 13  Jones (based on noise measurements), accompanied by a fast photoresponse (f -3dB = 200 kHz) and a broad linear dynamic range (> 150 dB). Ultrafast transient absorption spectroscopy unveils that charge carriers are already formed at very short time scales (< 1 ps). The surprisingly efficient bulk charge generation mechanism is attributed to a strong electronic coupling of the molecular exciton and charge transfer states. This work demonstrates the very high performance of single-component OPDs and proves that this novel device design is a successful strategy for highly efficient, morphological stable and easily manufacturable devices., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Ba 0.6 Sr 0.4 TiO 3 /polyvinylidene fluoride (BST/PVDF) dielectric functional composites have been widely used in flexible wearable devices, capacitors, and energy storage devices. In addition to the ceramic phase type, polymer matrix type, composition, and interfacial connectivity of BST/PVDF composite materials, their morphology also significantly influences their electrical characteristics. Therefore, herein, sandwich-structured BST/PVDF layered composites were designed and prepared via tape-casting processing using different types of BST fillers [i.e., formless zero-dimensional (0D)-BST, rod-like one-dimensional (1D)-BST, and plate-like two-dimensional (2D)-BST]. The microstructures and electrical characteristics of sandwich-structured BST/PVDF composites were studied in relation to the BST morphology. The effects of the internal mechanisms of different interfacial models on the breakdown strength of BST/PVDF composites were discussed. According to our findings, unlike the 0D-BST and 1D-BST powders, 2D-BST powders form multiscale parallel interfaces in sandwich-structured composites due to their unique lamella-like morphology, which enhances the breakdown strength of sandwich-structured composites. Sandwich-structured BST/PVDF composites containing 2D-BST powders exhibit good electrical characteristics with an energy storage density of 19.71 J/cm 3 , an energy storage efficiency of 85.3%, a dielectric constant of 30.4 (1 kHz), a dielectric loss of 0.036 (1 kHz), and a dielectric tunability of 93.2%. This study provides a method for preparing functional composites with high dielectric tunability and high energy storage characteristics.

The prognostic nutritional index (PNI) is a useful tool for assessing nutritional status using serum albumin and lymphocyte count. This study indicates that a higher preoperative PNI correlates with improved mobility and health-related quality of life during the initial postoperative period in elderly patients with hip fractures., Purpose: To investigate the prognostic value of the prognostic nutritional index (PNI) in predicting mobility and health-related quality of life (HRQoL) in elderly hip fracture patients after surgery., Methods: We prospectively involved patients aged 65 and above, who could walk freely before injury and underwent surgery between 2018 and 2019. Admission PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count (× 10 9 /L). Patients were classified into two groups based on PNI median value. All patients were followed up by telephone for four times (30-day, 120-day, 1-year, and 3-year after surgery). The Fracture Mobility Score (FMS) and EuroQol 5-Dimension 5-Level (EQ-5D 5L) were used to evaluate mobility and HRQoL, respectively., Results: Of 705 eligible patients, 487 completed all assessments. Patients in the higher PNI group had a significantly increased possibility of achieving unrestricted mobility at the 120-day follow-up (OR 1.69, 95% CI 1.10-2.61, P.adj = 0.017), while no significant differences were observed at other follow-ups. Additionally, patients in the higher PNI group had a significantly higher EQ-5D utility value at the 30-day follow-up (P.adj = 0.015). A linear regression model with adjusting for all confounders showed that admission PNI value was positively associated with EQ-5D utility values at 30-day, 120-day, and 1-year follow-up assessments (P.adj = 0.011, P.adj = 0.001, and P.adj = 0.030, respectively). However, this correlation was not observed at the 3-year time point (P.adj = 0.079)., Conclusion: The PNI is a valuable predictor of functional outcomes in elderly patients with hip fractures following surgery., (© 2024. The Author(s).)

This research aims to explore the diagnostic value of computed tomography (CT) indicators in patients with stable chronic obstructive pulmonary disease (COPD) in a plateau of China, and to find out the correlation between CT indexes and lung function and symptoms. This study screened out 53 stable COPD patients and 53 healthy people through inclusion and exclusion criteria in Hongyuan county, Aba Prefecture, Sichuan Province, between July 2020 and December 2020, and then collected their baseline data, conducted lung function tests and chest CT scans, and collected COPD Assessment Test (CAT), modified Medical Research Council Dyspnea Scale (mMRC) scores. The CT indexes of the 2 groups were compared, binary logistic regression was used to analyze the influence of COPD, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of the CT indexes for COPD. The Spearman test was used to understand the correlation analysis between the CT indexes and lung function, symptom score, and the number of acute exacerbations. Multiple linear regression was used to analyze the influencing factors of lung function. The percentage of low-attenuation areas less than -950 Hounsfield units (%LAA-950; t = -4.387,P = 0), percentage of wall area (WA%; t = -4.501, P = 0), and thickness-diameter ratio (TDR; t = -4.779, P = 0) in the COPD group were higher than those in the normal group. ROC shows that: %LAA-950 (P = .047) and TDR (P = .034) were independent influence in COPD in the plateau. %LAA-950 combined with TDR (AUC = 0.757, P < .001) had the value of diagnosis of COPD in the plateau. All 3 indexes are negatively correlated with lung function, and positively correlated with the symptoms and the number of acute exacerbations. Multiple linear regression analysis showed that the main factors for decrease of ratio of measurement to prediction of forced expiratory volume to the first second (FEV1%) included %LAA-950 (OR = -0.449, P < .001) and WA% (OR = -0.516, P < .001). CT indexes have a certain diagnostic value in patients with stable COPD at high altitude., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Second-harmonic (SH) generation is an important way to generate short-wavelength light sources. Thin-film lithium niobate (TFLN) resonators and waveguides featuring tight light confinement are flexible to realize mode- or quasi-phase-matching (MPM or QPM) and thus efficient SH generation. Here, we report an efficient SH with an absolute conversion efficiency of 45% in a reverse-polarized double-layer TFLN waveguide. Such a high conversion efficiency without periodic poling was realized with the pump of 67 mW in the 1550 nm band, benefiting from the employment of the largest nonlinear coefficient d 33 and the significant nonlinear interaction of the fundamental transverse electric (TE) mode and the first-order TE mode in the vertical direction. This work paves the way toward on-chip integrated nonlinear optics in terms of harmonic generation and quantum light sources across the telecom and visible bands.

Objective: To elucidate the efficacy of Ginsenoside Rg3 on the reproduction and immigration of HCT-116 cells and its molecular mechanism., Methods: Analysis of the cell cycle along with the colony formation assay, and MTT test were performed to detect the effect of Ginsenoside Rg3 (GRg3) on proliferation of HCT-116 cells. Transwell assay and Cell scratch wound method were carried out to determine the impact on the immigration. The differential expressed genes obtained by RNA-sequencing were intersected with the predicted target genes of GRg3, and PPI was constructed to analyze hub genes. The key target gene expression and its downstream genes were evaluated by western blot assay., Results: The GRg3 can inhibit the reproduction and immigrating ability of colonic carcinoma cells, decrease the ability of colony formation in HCT-116 cells, and arrest the G2 phase. JAK3 was identified as a key target gene. Western blot assay revealed decreased levels of p-STAT5 and JAK3 post-treatment with RG3, while STAT5a and STAT5b did not change significantly., Conclusion: The GRg3 inhibits the phosphorylation of STAT5 but not the expression of total protein by inhibiting the expression of JAK3, and then inhibits the proliferation and migration of HCT-116 cells., (© 2024. The Author(s).)

Transferrin (TF) is a prototypical biological macromolecule protein known for its iron-binding properties. TF proteins play a crucial role in modulating host iron homeostasis and defending against pathogen invasion. In this study, we utilized common carp (Cyprinus carpio) tissues and Epithelioma papulosum cyprinid (EPC) cells to establish experimental models of iron overload with FeCl 3 or ferric amine citrate (FAC), and to establish experimental models of bacterial infection with Aeromonas hydrophila. The current research has successfully identified the CcTF-b gene in common carp, revealing an ORF of 2001 bp with N-terminal and C-terminal structures. CcTF-b exhibited inhibitory effects on the growth of LPS and LTA in vitro. In the experimental models, the upregulations of PTGS2a and PTGS2a-like mRNA and protein levels were observed. Overexpression or interference with CcTF-b levels can modulate the expression of ferroptosis-related genes, inflammatory cytokines, lipid reactive oxygen species, GSH/GSSH levels, and Fe 2+ concentration. Significantly, the expression levels of Nrf2 and GPX4 mRNA and protein, as well as the bacterial load of A. hydrophila, could be also modulated either by upregulating or downregulating CcTF-b factors. In conclusion, in this study, these findings suggest that CcTF-b plays a critical role in the innate immune response of common carp., 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.)

Positively charged nanofiltration membranes have attracted much attention in the field of lithium extraction from salt lakes due to their excellent ability to separate mono- and multi-valent cations. However, the thicker selective layer and the lower affinity for Li + result in lower separation efficiency of the membranes. Here, PEI-P membranes with highly efficient Li + /Mg 2+ separation performance are prepared by introducing highly lithophilic 4,7,10-Trioxygen-1,13-tridecanediamine (DCA) on the surface of PEI-TMC membranes using a post-modification method. Characterization and experimental results show that the utilization of the DCA-TMC crosslinked structure as a space-confined layer to inhibit the diffusion of the monomer not only increases the positive charge density of the membrane but also reduces its thickness by ≈35% and presents a unique coffee-ring structure, which ensures excellent water permeability and rejection of Mg 2+ . The ion-dipole interaction of the ether chains with Li + facilitates Li + transport and improves the Li + /Mg 2+ selectivity (S Li,Mg  = 23.3). In a three-stage nanofiltration process for treating simulated salt lake water, the PEI-P membrane can reduce the Mg 2+ /Li + ratio of the salt lake by 400-fold and produce Li 2 CO 3 with a purity of more than 99.5%, demonstrating its potential application in lithium extraction from salt lakes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Hybrid rice, widely planted in Asia, is pathogen resistant and has superior yields, making it a major contributor to global food security. The two-line hybrid rice system, which utilizes mutants exhibiting photo-/thermo-sensitive genic male sterility (P/TGMS), is the leading hybrid rice breeding technology. Mutations in THERMO-SENSITIVE GENIC MALE STERILE 5 (TMS5) accounts for over 95% of current TGMS lines. We previously found that tms5 carries a mutation in ribonuclease Z S1 . Despite its importance for breeding robust rice lines, the mechanism underlying tms5-mediated TGMS remains elusive. Here, we demonstrate that TMS5 is a tRNA 2',3'-cyclic phosphatase. The tms5 mutation leads to accumulation of 2',3'-cyclic phosphate (cP)-ΔCCA-tRNAs (tRNAs without 3' CCA ended with cP), which is exacerbated by high temperatures, and reduction in the abundance of mature tRNAs, particularly alanine tRNAs (tRNA-Alas). Overexpression of tRNA-Alas in the tms5 mutant restores male fertility to 70%. Remarkably, male fertility of tms5 mutant is completely restored at high temperatures by knocking out OsVms1 which encodes the enzyme for cP-ΔCCA-tRNA generation. Our study reveals the mechanism underlying tms5-mediated TGMS in rice and provides mechanistic insight into the further improvement of TGMS in hybrid crop development., (© 2024. The Author(s) under exclusive licence to Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences.)

Artificial ion diodes, inspired by biological ion channels, have made significant contributions to the fields of physics, chemistry, and biology. However, constructing asymmetric sub-nanofluidic membranes that simultaneously meet the requirements of easy fabrication, high ion transport efficiency, and tunable ion transport remains a challenge. Here, a direct and flexible in situ staged host-guest self-assembly strategy is employed to fabricate ion diode membranes capable of achieving zonal regulation. Coupling the interfacial polymerization process with a host-guest assembly strategy, it is possible to easily manipulate the type, order, thickness, and charge density of each module by introducing two oppositely charged modules in stages. This method enables the tuning of ion transport behavior over a wide range salinity, as well as responsive to varying pH levels. To verify the potential of controllable diode membranes for application, two ion diode membranes with different ion selectivity and high charge density are coupled in a reverse electrodialysis device. This resulted in an output power density of 63.7 W m -2 at 50-fold NaCl concentration gradient, which is 12 times higher than commercial standards. This approach shows potential for expanding the variety of materials that are appropriate for microelectronic power generation devices, desalination, and biosensing., (© 2024 Wiley‐VCH GmbH.)

Excessive extracellular matrix deposition and increased intrahepatic angiogenesis are prominent features of cirrhosis. β-arrestin2 is thought to be involved in the pathological processes of various fibrotic diseases. This study aimed to investigate the role and possible mechanism of β-arrestin2 in the angiogenesis of cirrhosis. Firstly, β-arrestin2 expression in liver tissues of cirrhotic patients was detected, and the correlation between β-arrestin2 and α-SMA, CD-31, PDGF, and VEGF indexes was analyzed. Then, after liver cirrhosis induced by CCL 4 in Arrb2-KO mice (β-arrestin2 coding gene), liver histopathological changes were observed, and the expressions of α-SMA, CD-31, PDGF, VEGF, and VEGFR2 were detected. Finally, VEGF-A was used to treat human liver sinusoidal endothelial cells (LSECs) to simulate pathological conditions. After transfection with si-ARRB2, the cell activity, MDA and GSH-PX activities, cell invasion, angiogenesis, and the expressions of α-SMA, CD-31, and VEGF/VEGFR2 pathway were detected. Results showed that β-arrestin2 expression in the liver increased significantly during cirrhosis and was positively correlated with angiogenesis. In vivo, Arrb2-KO significantly inhibited fibrosis and angiogenesis in cirrhotic mice, and decreased the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2. Studies using LSECs in vitro showed that after intervention of ARRB2, the activity of LSECs and the number of invasions and tubule formations were significantly reduced. Similarly, after transfection with si-ARRB2, the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2 in LSECs were significantly decreased. Collectively, β-arrestin2 aggravated cirrhosis by promoting the angiogenesis of LSECs. Blocking β-arrestin2 may be an important target against angiogenesis and fibrosis in cirrhosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is a promising cancer treatment, but limited oxygen supply in tumors (hypoxia) can hinder its effectiveness. This is because traditional PDT relies on Type-II reactions that require oxygen. Type-I photosensitizers (PSs) offer a promising approach to overcome the limitations of tumor photodynamic therapy (PDT) in hypoxic environments. To leverage the advantages of Type-I PDT, the design and evaluation of a series of Type-I PSs for developing pure Type-1 PSs, by incorporating benzene, thiophene, or bithiophene into the donor-acceptor molecular skeleton are reported. Among them, CTTI (with bithiophene) shows the best performance, generating the most superoxide radical (O 2 •- ) upon light irradiation. Importantly, CTTI exclusively produced superoxide radicals, avoiding the less effective Type-II pathway. This efficiency is due to CTTI's energy gap and low reduction potential, which favor electron transfer to oxygen for O 2 •- generation. Finally, CTTI NPs are successfully fabricated by encapsulating CTTI into liposomes, and validated to be effective in killing tumor cells, even under hypoxic conditions, making them promising hypoxia-tolerant tumor phototheranostic agents in both in vitro and in vivo applications., (© 2024 Wiley‐VCH GmbH.)

Anode materials for sodium ion batteries (SIBs) are confronted with severe volume expansion and poor electrical conductivity. Construction of assembled structures featuring hollow interior and carbon material modification is considered as an efficient strategy to address the issues. Herein, a novel template-assisted epitaxial growth method, ingeniously exploiting lattice matching nature, is developed to fabricate hollow ordered architectures assembled by SnO 2 nanorods. SnO 2 nanorods growing along [100] direction can achieve lattice-matched epitaxial growth on (110) plane of α-Fe 2 O 3 . Driven by the lattice matching, different α-Fe 2 O 3 templates possessing different crystal plane orientations enable distinct assembly modes of SnO 2 , and four kinds of hollow ordered SnO 2 @C nanorods arrays (HONAs) with different morphologies including disc, hexahedron, dodecahedron and tetrakaidecahedron (denoted as Di-, He-, Do-, and Te-SnO 2 @C) are achieved. Benefiting from the synergy of hollow structure, carbon coating and ordered assembly structure, good structural integrity and stability and enhanced electrical conductivity are realized, resulting in impressive sodium storage performances when utilized as SIB anodes. Specifically, Te-SnO 2 @C HONAs exhibit excellent rate capability (385.6 mAh·g -1 at 2.0 A·g -1 ) and remarkable cycling stability (355.4 mAh·g -1 after 2000 cycles at 1.0 A·g -1 ). This work provides a promising route for constructing advanced SIB anode materials through epitaxial growth for rational structural design., (© 2024 Wiley‐VCH GmbH.)

Estrogen receptor α (ERα) promotes the growth and survival of ER-positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin-bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER-associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER-positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3β pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC., (© 2024 Wiley Periodicals LLC.)

Objective: The prognostic nutritional index (PNI) has been reported as a significant predictor in various diseases. However, the prognostic value of the PNI in geriatric hip fracture patients has not been thoroughly evaluated. This study aimed to investigate the association between admission PNI and 3-year mortality in those patients., Methods: In this post hoc analysis, we included patients aged ≥65 years who underwent surgery for hip fracture between 2018 and 2019. The admission PNI was calculated as serum albumin (g/L) +5 × total lymphocyte count (×10 9 /L). Patients were categorized into four groups based on PNI quartiles (≤ 43.55, 43.55-46.55, 46.55-49.20, and >49.20, respectively). The median follow-up duration was 3.1 years. Cox proportional hazards models were used to calculate the hazard ratio (HR). Receiver operating characteristic curve (ROC) was conducted for using PNI to predict mortality., Results: Of the 942 eligible patients, 190 (20.2%) patients died during the follow-up. Compared to patients in the first quartile (Q1), those in the second (Q2), third (Q3), and fourth (Q4) quartiles had significantly lower mortality risks (HRs 0.50, 95% CI 0.35-0.74; 0.41, 95% CI 0.26-0.64; and 0.26, 95% CI 0.15-0.45, respectively). The optimal cutoff of PNI for predicting mortality was set as 45.275 (sensitivity, 0.674; specificity, 0.692; area under the curve (AUC), 0.727). Patients with higher PNI (>45.275) had a significant lower mortality risk (HR 0.39, 95% CI 0.28-0.55) compared to those with lower PNI (≤ 45.275)., Conclusion: PNI is a reliable and independent predictor of 3-year mortality after hip fracture surgery in the elderly., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm., Methods: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models., Results: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort., Conclusions: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice., (© 2024. The Author(s).)

This paper aims to clarify the effect of Undercarboxylated osteocalcin (ucOC) on cognitive function in rats with type 2 diabetes mellitus (T2DM). This research reviewed the cognitive function of 35 diabetic patients, 33 non-diabetic patients and the serum levels of Undercarboxylated osteocalcin (ucOC) in patients. What's more, we analyzed the correlation between serum ucOC levels and cognitive function. Diabetic rats were treated with high (30 μg·kg -1 ·d -1 ) and low (10 μg·kg -1 ·d -1 ) doses of ucOC to investigate its effects in regulating ucOC on blood lipid, blood glucose and cognitive function. We systematically detected the phosphorylation levels of cognitive level-related proteins (PI3K, AKT, and GSK/3β) in the hippocampus by Western Blot. Finally, PI3K-Akt pathway involved in regulating cognitive function in diabetic rats by ucOC was verified with AKT pathway inhibitor LY294002. MoCA score and serum ucOC levels were significantly reduced in patients with diabetes mellitus. ucOC could concentration-dose-dependently decrease the blood glucose and lipid levels, and improve glucose metabolism and weaken insulin resistance in diabetic rats ( P  < 0.001). In addition, escape latency in diabetic rats was significantly higher than that of normal rats in the Morris maze test, and ucOC dose-dependently shortened the escape latency in diabetic rats (all with P  < 0.05). After using AKT pathway inhibitor, ucOC failed to shorten the escape latency in diabetic rats. In conclusion, this study explored the relevant mechanisms in inducing cognitive dysfunction of T2DM, suggesting the potential value of ucOC as a drug to improve cognitive dysfunction in patients with T2DM in clinical.

Efficient sodium ion storage in graphite is as yet unattainable, because of the thermodynamic instability of sodium ion intercalates-graphite compounds. In this work, sodium fluorozirconate (Na 3 ZrF 7 , SFZ) functionalized graphite (SFZ-G) is designed and prepared by the in situ mechanochemical silicon (Si) replacement of sodium fluorosilicate (Na 2 SiF 6 , SFS) and functionalization of graphite at the same time. During the mechanochemical process, the atomic Si in SFS is directly replaced by atomic zirconium (Zr) from the zirconium oxide (ZrO 2 ) balls and container in the presence of graphite, forming SFZ-G. The resulting SFZ-G, working as an anode material for sodium ion storage, shows a significantly enhanced capacity of 418.7 mAh g -1 at 0.1 C-rate, compared to pristine graphite (35 mAh g -1 ) and simply ball-milled graphite (BM-G, 200 mAh g -1 ). In addition, the SFZ-G exhibits stable sodium-ion storage performance with 86% of its initial capacity retention after 1000 cycles at 2.0 C-rate., (© 2024 Wiley‐VCH GmbH.)