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Importance: Adjuvant therapy is an important and effective treatment for retinoblastoma. However, there is a lack of head-to-head clinical trials comparing 3 vs 6 cycles of CEV chemotherapy (carboplatin, etoposide, and vincristine) for enucleated unilateral retinoblastoma with high-risk pathological features., Objective: To assess whether 3 cycles of CEV chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features., Design, Setting, and Participants: This double-center, randomized, open-label, noninferiority trial was conducted at 2 premier eye centers in China and included 187 patients who had undergone enucleation for unilateral retinoblastoma with high-risk pathological features (massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration) between August 2013 and March 2024. The final date of follow-up was March 21, 2024., Interventions: Patients were randomly assigned to receive either 3 (n = 94) or 6 (n = 93) cycles of CEV chemotherapy regimen after enucleation., Main Outcomes and Measures: The primary end point was disease-free survival, with a noninferiority margin of 12%. Secondary end points encompassed overall survival, safety, economic burden, and the quality of life of children., Results: All 187 patients (median [IQR] age, 25.0 [20.0-37.0] months; 83 [44.4%] female) completed the trial. Median (IQR) follow-up was 79.0 (65.5-102.5) months. Five-year disease-free survival was 90.4% for the 3-cycle group vs 89.2% for the 6-cycle group (difference, 1.2% [95% CI, -7.5% to 9.8%]), which met the noninferiority criterion (P = .003 for noninferiority). The 6-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the 3-cycle group., Conclusions and Relevance: Among patients with unilateral pathologic high-risk retinoblastoma, 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy., Trial Registration: ClinicalTrials.gov Identifier: NCT01906814.

In this work, electrical and optical performances for 250 nm AlGaN-based flip-chip deep ultraviolet light emitting diodes (DUV LEDs) with different chip sizes are studied. Reduced chip size helps increase the light extraction efficiency (LEE) with the cost of increased surface nonradiative recombination. Nevertheless, a thin p-Al 0.67-0 Ga 0.33-1 N layer of 10 nm can manage current distribution while suppressing surface recombination and reducing light absorption simultaneously, which results in the increased optical power density. Thanks to the better current management and reduced optical self-absorption effect, the reduced Joule heating effect suppresses the thermal droop of the optical power density for a small DUV LED chip. We also find that the p-Al 0.67-0 Ga 0.33-1 N layer thickness shows very significant impact on device resistance especially for the small DUV LED chip, such that the device resistance has a remarkable increase when the p-Al 0.67-0 Ga 0.33-1 N layer is thickened to 100 nm.

Reduning injection (RDN) is a traditional chinese medicine injection widely used in clinical practice. In this study, qualitative and quantitative analysis of RDN were conducted by UPLC-Orbitrap MS/MS simultaneously. Totally 118 compounds were identified and 34 compounds were quantified in RDN. The method with completed method validation proved the high sensitivity and efficiency of the method and it was applied to quantify compounds in RDN. Multivariate statistical analysis method selected 11 key variables that affect the content consistency of RDN. 20 batches with high biological potency were screened by cox-2 enzyme activity assay. Spectrum-effect relationship analysis and multivariate statistical analysis showed that 7 batches were high-quality selected after comprehensive quality evaluation and 9 compounds were key indicators for screening it. This strategy including fingerprint, qualitative analysis and multiple-component quantification could be well applied to modern quality evaluation of RDN, which could be valuable for the further quality control of more other traditional Chinese medicines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, Wei xiao,mengyu qian, liang cao, xialin chen, jingqiu gu,zhenzhong wang has patent pending to wei xiao，mengyu qian, liang cao, xialin chen, jingqiu gu, zhenzhong wang. If there are other authors, they 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.)

Cities are treated as global methane (CH 4 ) emission hotspots and the monitoring of atmospheric CH 4 concentration in cities is necessary to evaluate anthropogenic CH 4 emissions. However, the continuous and in-situ observation sites within cities are still sparsely distributed in the largest CH 4 emitter as of China, and although obvious seasonal variations of atmospheric CH 4 concentrations have been observed in cities worldwide, questions regarding the drivers for their temporal variations still have not been well addressed. Therefore, to quantify the contributions to seasonal variations of atmospheric CH 4 concentrations, year-round CH 4 concentration observations from 1st December 2020 to 30th November 2021 were conducted in Hangzhou megacity, China, and three models were chosen to simulate urban atmospheric CH 4 concentration and partition its drivers including machine learning based Random Forest (RF) model, atmospheric transport processes based numerical model (WRF-STILT), and regression analysis based Multiple Linear Regression (MLR) model. The findings are as follows: (1) the atmospheric CH 4 concentration showed obvious seasonal variations and were different with previous observations in other cities, the seasonality were 5.8 ppb, 21.1 ppb, and 50.1 ppb between spring-winter, summer-winter and autumn-winter, respectively, where the CH 4 background contributed by -8.1 ppb, -44.6 ppb, and -1.0 ppb, respectively, and the CH 4 enhancements contributed by 13.9 ppb, 65.7 ppb, and 51.1 ppb. (2) The RF model showed the highest accuracy in simulating CH 4 concentrations, followed by MLR model and WRF-STILT model. (3) We further partition contributions from different factors, results showed the largest contribution was from temperature-induced increase in microbial process based CH 4 emissions including waste treatment and wetland, which ranged from 38.1 to 76.3 ppb when comparing different seasons with winter. The second largest contribution was from seasonal boundary layer height (BLH) variations, which ranged from -13.4 to -6.3 ppb. And the temperature induced seasonal CH 4 emission and enhancement variations were overwhelming BLH changes and other meteorological parameters., 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.)

Orthosiphon wulfenioides is a medicinal plant to treat arthritis, vascular inflammation, edema, and dyspepsia. To explore the anti-inflammatory components and their mechanism of action, 12 previously undescribed highly oxidized diterpenes, wulfenioidones L-W (1-12), were isolated from O. wulfenioides by bioactivity orientation. Their structures were elucidated using HRESIMS, NMR, specific rotation, single-crystal X-ray diffraction, and ECD spectra analysis. Compounds 1-4 exhibited significant inhibition on LDH release by preventing macrophage J774A.1 pyroptosis. Compound 1 showed the most potent inhibitory effect with an IC 50 value of 5.81 μM. It was revealed in the western blot experiment that compound 1 not only significantly and dose-dependently decreased the activation of CASP1 and IL-1β, but also prevented GSDMD-FL from splitting into GSDMD-NT, the membrane pore-forming protein to release inflammatory factors, thus blocking the extracellular release of IL-1β. More interestingly, compound 1 not only blocked the activation of NLRP3 inflammasome, but also strikingly enhanced the orange fluorescence of JC-1 aggregates, thus showing the activity of maintaining mitochondrial membrane potential and reversing mitochondria damage., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Ethnopharmacological Relevance: According to the theory of traditional Chinese medicine,Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient., Aim of the Study: To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial., Materials and Methods: A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT 3 ) and free thyroxine (FT 4 ) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint., Results: 150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT 3 levels (group A, p=0.0027; group B, p<0.0001; group C, p=0.0028) and FT 4 levels (group A, p<0.0001; group B, p<0.0001; group C, p<0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p=0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p<0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p<0.0001), eye (p=0.0490), tiredness (p<0.0001), cognition (p<0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety., Conclusions: Pingkang granules significantly reduced serum FT 3 , FT 4 and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism., Competing Interests: Declaration of Competing Interest This study was supported by the Project of Clinical Center (Traditional Chinese Medicine) of Endocrinology and Metabolism Disease of Shenyang (Grant Number SKF201875), the Traditional Chinese Medicine Clinical Discipline and Specialty Capacity Construction Project of Liaoning Province (Grant Number LNZYXZK201902). All the authors declare no conflicts of interest associated with this research and the study received no financial support that could have influenced its outcomes., (Copyright © 2024. Published by Elsevier B.V.)

Unlike traditional multi-step synthetic approaches, we developed a single-step synthesis of versatile π-conjugated building blocks bearing post-functionalizable C-H and C-Br bonds. Direct C-H arylation of 3-bromothiophene with various iodo(hetero)aryls was successfully carried out with good regio- and chemo-selectivity. Under optimized reaction conditions, 20 new compounds were facilely prepared in yields up to 91%. One of the obtained compounds was demonstrated to further extend its conjugation length using a succinct synthetic plan to create two symmetrical oligo(hetero)aryls (MLC01 and MLC02) that were fabricated as effective hole-transporting materials (HTM) for perovskite solar cells (PSC). PSC devices utilizing MLC01 as hole-transport layer displayed promising power conversion efficiencies of up to 17.01%., (© 2024 Wiley‐VCH GmbH.)

The thermal properties of interfaces in nanomaterials are critical for various technological applications, including thermal management in electronic and photonic devices, thermoelectric conversion and thermal insulation. Recent advancements in numerical simulation tools (the non-equilibrium Green's approach, the Boltzmann transport equation and the Monte Carlo method, molecular dynamics simulations) have significantly enhanced our understanding of phonon transport and scattering processes in nanomaterials. These advances have led to the discovery of new thermal interfacial materials and enabled precise modulation of phonon thermal conductance to achieve desired thermal performance. This review summarizes recent research progress in interface thermal transport, focusing on intriguing heat phenomena such as finite size effect and phonon coherent property. Additionally, it discusses strategies for modulating thermal conductance through disorder and roughness. Finally, the review proposes the opportunities and challenges associated with modulating interface thermal transport., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Managing the redox reactions of polysulfides is crucial for improving the performance of lithium-sulfur batteries (LSBs). Herein, we introduce a progressive theoretical framework: the balanced d-band model, which is based on classical d-band center theory. Specifically, by optimizing the position of the d-band center in the middle between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of each sulfur species, balanced and fast oxidation and reduction reactions of the sulfur species can be achieved simultaneously. To validate this theory, we synthesized a catalyst featuring an in situ phosphorized heterostructure (NOP) based on nickel oxide (NiO), which effectively optimizes the d-band center at the middle between the HOMO and LUMO of each sulfur species. Aided by the balanced oxidation and reduction kinetics of the sulfur species, the NOP-based cell achieved a high reversible capacity, superior cycling stability, and prolonged cycle life. This study extends the conventional d-band center theory and introduces an innovative theoretical model to expand our understanding of the internal reaction mechanisms in LSBs.

Plant-based diets are currently gaining more popularity as a means of reducing the environmental footprint and promoting human health. Herein, plant protein-based acidic high internal phase emulsion gels (HIPE gels) were fabricated via a facile one-pot approach using wheat gluten (WG) solely. Pre-dissolving WG in edible vinegar-water solution was contributed to the fabrication of stable emulsion gels. Factors that affect the structure and performance of plant proteins as HIPE gels stabilizers were investigated. The results indicated that the stable HIPE gels could be formed with a vinegar concentration between 5 % and 20 % and a WG concentration of 1.0 %-7.5 % only. Microscopy images reveal that a collaboration of the soluble protein molecules adsorption and protein aggregate Pickering stabilization at oil-water interface, which was turned to form stable HIPE gels. In addition, the resulted HIPE gels exhibited shear thinning behavior, viscoelastic features, and good thixotropic recovery, which provide a similar perceived texture and sensory property for formulating egg-free mayonnaise. These findings provide a useful approach to construct HIPE-based softs from low-cost wheat gluten for preparing plant-based mayonnaise., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: A prenylated flavonoid, broussoflavonol F (BFF), was isolated from Macaranga genus with cytotoxicities against various cancer cells, though its underlying mechanisms have not been fully elucidated., Hypothesis: This study aimed to investigate the anti-tumor and anti-angiogenesis activities of BFF and its underlying mechanisms in colon cancer., Method: In the in vitro study, the cytotoxic effects of BFF in human colon cancer HCT-116 and LoVo cells were examined using MTT assay, BrdU assay and colony formation assay. The anti-proliferative effects of BFF in these cells were assessed via cell apoptosis and cell cycle analysis using flow cytometry. The anti-angiogenesis effects of BFF in human endothelial HEMC-1 cells were also detected using scratch wound healing assay and tube formation assay. While the in vivo effects of BFF in colon cancer were further examined in zebrafish embryos and HCT116 tumor-bearing mice. The underlying mechanisms of BFF were predicted using network pharmacology analysis, and Western blotting was performed to validate both in vitro and in vivo results., Results: BFF exhibited cytotoxicities on 5 colon cancer cell lines, as well as anti-proliferative activities via inducing apoptosis and cell cycle arrest at the G0/G1 phase in HCT116 and LoVo cells. BFF at 1.25-5 µM also suppressed cell proliferation in these two colon cancer cell lines by downregulating HER2, RAS, p-BRAF, p-MEK and p-Erk protein expressions. In addition, BFF at 2.5-5 µM could significantly decrease the length of subintestinal vessels of zebrafish embryos through decreasing mRNA expressions of NRP1a, PDGFba, PDGFRb, KDR, FLT1 and VEGRaa. Besides, BFF exhibited anti-angiogenesis activity via inhibiting cell proliferation, motility and tube formation in HMEC-1 cells. Furthermore, intraperitoneal administration of BFF (10 mg/kg) suppressed tumor growth and decreased the expression of tumor proliferation marker Ki-67 and angiogenesis marker CD31 in the tumor tissues in HCT116 tumor-bearing mice. BFF treatment could also significantly decrease expressions of RAS, p-BRAF, p-MEK and p-Erk in the tumor section, which are consistent with the in vitro results., Conclusions: This study revealed the anti-tumor and anti-angiogenesis effects of BFF in colon cancer. This is the first report of the in vitro and in vivo anti-proliferative activity of BFF in colon cancer through regulating the HER2-RAS-MEK-ERK pathway. These findings further support the research development of BFF as an anti-cancer agent in colon cancer., 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 GmbH.)

Circulating miR-30c-2-3p has been closely related to vascular diseases, however, its role and underlying mechanisms in ischemic stroke remained unclear. Our study addressed this gap by observing elevated levels of exosomal miR-30c-2-3p in patients with acute ischemic stroke due to large artery atherosclerosis. Further investigation revealed that these exosomal miR-30c-2-3p primarily originated from macrophages within atherosclerotic plaques, exacerbating ischemic stroke by targeting microglia. Exosomes enriched with miR-30c-2-3p increased microglial inflammatory properties in vivo and aggravated neuroinflammation by inhibiting SMAD2. In summary, our findings revealed a novel mechanism whereby macrophage-derived foam cells within atherosclerotic plaques secrete exosomes with high levels of miR-30c-2-3p, thus aggravate brain damage during ischemic stroke, which serves as crucial link between the periphery and brain., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Tianshu capsule (TSC) is a traditional Chinese medicine (TCM) preparation and has significant clinical effect on migraine. The composition characteristics of TSC formula are worth exploring for the treatment of migraine., Aim of the Study: Identify the compounds in vivo after oral administration of TSC, Gastrodin (GAS), ferulic acid, senkyunolide G and senkyunolide I in the blood of healthy and migraine rats were used as representative compounds for time-dependent processes investigation. And we focus on explaining the characteristics of TSC treatment on migraine from a pharmacokinetic perspective., Materials and Methods: In this study, Ultra-high performance liquid chromatography with Orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) system were used to detect the compounds in rat plasma and brain after oral administration of TSC. A sensitive, selective and reliable ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) system method was established for the simultaneous quantitative analysis of multi-components and evaluate the pharmacokinetic behavior of four main compounds., Results: A total of 46 compounds were significantly identified in vivo of rat, including 35 compounds in plasma, 7 compounds only in brain and 4 compounds both in plasma and brain. The quantitative method has been confirmed to be feasible for multi-components content determination, pharmacokinetic parameters indicated that the four compounds absorbed into blood rapidly, and senkyunolide I also cross the blood-brain barrier (BBB) quickly into brain. GAS has relatively high concentrations in plasma, and the parameters AUC 0-t , CL z/F displayed significant differences between the normal and migraine rats. And the AUC 0-t and C max of GAS and ferulic acid exhibited dose-dependent way., Conclusions: we added compounds for the pharmacokinetic study of TSC, providing powerful help for clinical medication in the treatment of migraine., Competing Interests: Declaration of competing interest The authors confirm that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Serum lipids have been associated with an increased risk of various cardiovascular diseases (CVDs) in several observational studies, but the causal inference between the remnant cholesterol (RC) levels and several CVDs risk has not been established. The purpose of this study was to investigate whether there is a causal relationship between RC levels and risk of developing CVDs by a bidirectional two-sample Mendelian randomization (TSMR) analysis. One TSMR analysis was performed using the publicly released large-scale genome-wide association study (GWAS) data. Inverse variance weighted (IVW) method was chosen as the main analysis method, and MR-Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We conducted a series of sensitivity analyses to assess the robustness of the main results, including the Cochran's Q test, MR-Egger intercept test, leave-one-out sensitivity analysis, and funnel plot. The main IVW method revealed that genetically predicted serum level of RC is significantly associated with an increased risk of developing ischemic heart disease (OR = 1.409, 95%CI = 1.284-1.546, P value = 4.753E-13), unstable angina pectoris (OR = 1.621, 95%CI = 1.398-1.880, P value = 1.672E-10), myocardial infarction (OR = 1.526, 95%CI = 1.337-1.741, P value = 3.771E-10), cardiac arrest (OR = 1.595, 95%CI = 1.322-1.924, P value = 1.076E-06), heart failure (OR = 1.086, 95%CI = 1.009-1.169, P value = 0.028), hypertension (OR = 1.089, 95%CI = 1.043-1.136, P value = 9.458E-05), major coronary heart disease (CHD) events (OR = 1.515, 95%CI = 1.376-1.669, P value = 3.217E-17), coronary atherosclerosis (OR = 1.388, 95%CI = 1.231-1.564, P value = 7.739E-08), cardiac arrhythmias (OR = 1.067, 95%CI = 1.008-1.130, P value = 0.025), and atrial fibrillation and flutter (OR = 1.122, 95%CI = 1.039-1.211, P value = 0.003). Additionally, the causal associations between the RC levels and these CVDs remained significant after correcting for the false discovery rate (all P value < 0.05). However, this study did not find any significant association of RC with cardiomyopathy and pericarditis (both P value > 0.05). Heterogeneity existed in the IVs of RC and ischemic heart disease, unstable angina pectoris, myocardial infarction, heart failure, hypertension, major CHD events, cardiomyopathy, coronary atherosclerosis, cardiac arrhythmias and atrial fibrillation and flutter using the Cochran's Q test (all P value < 0.05). Moreover, there was no horizontal pleiotropy in this study (all P value > 0.05). The leave-one-out sensitivity analyses showed that the causal effects between RC level and CVDs (except for heart failure, cardiomyopathy, pericarditis and cardiac arrhythmias) are not driven by a single SNP. The funnel plots showed that there is no obvious potential bias in our study. In the replication analysis, the genetically predicted RC levels were positively associated with a 43.12% higher risk of coronary artery disease. This present study supported the causal link between RC and heightened the risk of CVDs, indicating that RC-lowering treatment might be effective in preventing CVDs., (© 2024. The Author(s).)

Purpose: This study aimed to analyze the clinicopathological characteristics of a rare malignant tumour, primary orbital mesenchymal chondrosarcoma (MCS), and identify the risk factors influencing its prognosis., Methods: A total of 15 patients with histologically confirmed primary orbital MCS were enrolled between April 2013 and October 2022. The relationships between clinicopathological features and outcomes, including recurrence and survival were analyzed., Results: During the follow-up period, 9 patients (60%) experienced disease relapse, and 7 patients (46.7%) succumbed to the disease. Immunohistochemical analysis showed positive rates for SMA, CD-99, S-100, vimentin, and Bcl-2 at 60%, 60%, 53.3%, 100%, and 93.3%, respectively. The Ki67 index was positively associated with the recurrence and mortality rates., Conclusion: Our study suggested that the Ki67 index could be a vital prognostic factor for MCS. Further follow-up studies are required to assess the efficacy of chemotherapy and radiotherapy in improving patient outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

CRISPR-Cas is the only known adaptive immune system of prokaryotes. It is a powerful defense system against mobile genetic elements such as bacteriophages. While CRISPR-Cas systems can be found throughout the prokaryotic tree of life, they are distributed unevenly across taxa and environments. Since adaptive immunity is more useful in environments where pathogens persist or reoccur, the density and/or diversity of the host/pathogen community may drive the uneven distribution of CRISPR systems. We directly tested hypotheses connecting CRISPR incidence with prokaryotic density/diversity by analyzing 16S rRNA and metagenomic data from publicly available environmental sequencing projects. In terms of density, we found that CRISPR systems are significantly favored in lower abundance (less dense) taxa and disfavored in higher abundance taxa, at least in marine environments. When we extended this work to compare taxonomic diversity between samples, we found CRISPR system incidence strongly correlated with diversity in human oral environments. Together, these observations confirm that, at least in certain types of environments, the prokaryotic ecological context indeed plays a key role in selecting for CRISPR immunity., Importance: Microbes must constantly defend themselves against viral pathogens, and a large proportion of prokaryotes do so using the highly effective CRISPR-Cas adaptive immune system. However, many prokaryotes do not. We investigated the ecological factors behind this uneven distribution of CRISPR-Cas immune systems in natural microbial populations. We found strong patterns linking CRISPR-Cas systems to prokaryotic density within ocean environments and to prokaryotic diversity within human oral environments. Our study validates previous within-lab experimental results that suggested these factors might be important and confirms that local environment and ecological context interact to select for CRISPR immunity.

In this work, a post-synthetic modification strategy was attempted to improve the performance of the probe for sulfite detection. The assembled platform UiO-66-NH-DQA, which was acquired by anchoring the sulfite-response fluorescent probe DQA onto the surface of UiO-66-NH 2 via amide covalent bonds, exhibited enhanced fluorescence intensity and practical intracellular imaging capability. In spite of the structural similarity, as verified by characterization tests, the conversion rate of post-synthetic modification was calculated as 35%, equaling an approximate assembly ratio of 1 : 2 between UiO-66-NH 2 and DQA. Most significantly, conversion into UiO-66-NH-DQA led to a 5.6-fold enhancement in the reporting signal with a red shift of 20 nm. For sulfite detection, the linear range was 0-150 μM, with a limit of detection value of 0.025 μM. UiO-66-NH-DQA retained advantages including high stability (within pH 5.0-9.0), rapid response (within 15 min) and high selectivity. Based on low cytotoxicity and relatively rapid cellular uptake, UiO-66-NH-DQA achieved the imaging of both the exogenous and endogenous sulfite levels in living cells. In particular, its rapid cell-permeating capability was guaranteed during the modification. The post-synthetic modification strategy reported herein has potential for improving the practical properties of fluorescent monitoring materials.

Applying the mixed-linker strategy in synthesizing metal-organic frameworks (MOFs) has drawn considerable attention as a heterogeneous catalyst owing to their easy synthesis and different functional ligands in their frameworks. Following this strategy, we have developed a mixed linker Zr(IV)-based MOF, [Zr 6 O 4 (OH) 4 (FUM) n (PZDC-NO 2 ) 6- n ] (PZDC-NO 2 = 4-nitro-3,5-pyrazoledicarboxylic acid, FUM = fumaric acid) denoted as MOF-801(PZDC-NO 2 ) synthesized via this strategy which possess an electron-withdrawing group (-NO 2 ) on secondary linkers. The MOF-801(PZDC-NO 2 ) has been fully characterized via various analyses, such as Fourier transform infrared, powder X-ray diffraction, 13 C/ 1 H nuclear magnetic resonance, XPS, TGA, and N 2 adsorption/desorption, SEM, EDX, etc. By considering the concurrent existence of acid-base active sites and the synergistic role of these sites, this mixed-linker MOF was used as a catalyst for the cycloaddition reaction of CO 2 and epoxides under mild without-solvent conditions. MOF-801(PZDC-NO 2 ) displays significant catalytic performance by producing the highest catalytic conversion of epoxide to cyclic carbonate (93%) with a turnover number of 130.7 in 8 h reaction time and 100 °C temperature under low-pressure CO 2 pressure. The mixed-linker Zr-MOF exhibits exceptional stability and reusability, maintaining its structure and functionality after consecutive cycles of utilization. Finally, the reaction mechanism was further investigated by density functional theory calculations. The total energy of the reactants, intermediates, and products involved in the process.

Hemipteran insects transmit viruses when infesting plants, during which vectors activate salicylic acid (SA)-regulated antiviral defenses. How vector-borne plant viruses circumvent these antiviral defenses is largely unexplored. During co-infections of begomoviruses and betasatellites in plants, betasatellite-encoded βC1 proteins interfere with SA signaling and reduce the activation of antiviral resistance. βC1 inhibits SA-induced degradation of NbNPR3 (Nicotiana benthamiana nonexpressor of pathogenesis-related genes 3), a negative regulator of SA signaling. βC1 does not bind directly to NbNPR3, but regulates NbNPR3 degradation via heat shock protein 90s (NbHSP90s). NbHSP90s bind to both NbNPR3 and βC1 and suppress SA signaling. This viral success strategy appears to be conserved as it is also documented for viral proteins encoded by two aphid-borne viruses. Our findings reveal an exquisite mechanism that facilitates the persistence of vector-borne plant viruses and provide important insights into the intricacies of the virus life cycle., (© 2024. The Author(s).)

Background: Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen., is widely used to treat cardiovascular and cerebrovascular diseases in China. Longxuetongluo Capsule (LTC) is a total phenolic compound extracted from Chinese dragon's blood, currently used in treating ischemic stroke. Myocardial injury can be aggravated after reperfusion of ischemic myocardium, which is called myocardial ischemia-reperfusion injury (MIRI), and the mechanism of MIRI is complex. However, the exact effect and mechanism of LTC on MIRI are still unclear. We explore the effect of LTC on alleviating MIRI based on mitochondrial dysfunction and oxidative stress., Aim of the Study: To explore the cardioprotective mechanism of LTC against MIRI., Materials and Methods: A rat MIRI model was constructed through ligation of the left anterior descending coronary artery, and LTC was given continuously for 28 days before surgery. The H9c2 cardiomyocyte injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R), and LTC was given 24 h before OGD. Myocardial ischemia areas were detected with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cardiac histopathological changes were detected with hematoxylin-eosin (HE) staining. And biochemical indexes were detected with serum biochemical kit. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. Fluorescent probes were used to observe reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), Ca 2+ and other indexes. MitoTracker staining and immunofluorescence were used to observe the morphology of mitochondria and translocation of dynamin-related protein 1 (Drp1). Finally, immunohistochemistry and Western blotting were used to examine the expression of proteins related to apoptosis, mitochondrial fission and fusion and oxidative stress., Results: LTC could ameliorate cardiac pathological changes, decrease myocardial infarct area and the content or level of relevant serum cardiac enzymes, indicating that LTC could alleviate MIRI. Meanwhile, LTC could inhibit cardiomyocyte apoptosis via regulating apoptosis-related protein expression, and it could restore mitochondrial morphology, maintain ΔΨm, inhibit mitochondrial ROS generation and Ca 2+ accumulation, increase the expression of mitochondrial fusion protein 2 (Mfn2), decrease the level of phosphorylation dynamin-related protein 1 (p-Drp1), and regulate ATP synthesis, thereby significantly ameliorating mitochondrial dysfunction. Moreover, LTC significantly reduced the expression of NADPH oxidase 2 (NOX2), NADPH oxidase 4 (NOX4) and neutrophil cytosolic factor 2 (NOXA2/p67 phox ), and reduced ROS production., Conclusion: The study demonstrated that LTC could inhibit MIRI induced cardiomyocyte apoptosis by inhibiting ROS generation and mitochondrial dysfunction, and these fundings suggested that LTC can be used to alleviate MIRI, which provides a potential therapeutic approach for future treatment of MIRI., 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 GmbH. All rights reserved.)

Background: The incidence of rectal neuroendocrine tumors (RNETs) has witnessed a significant surge, with a notable proportion being amenable to endoscopic removal. However, the clinical significance of positive resection margin for RNETs patients following endoscopic resection remain unknown, resulting in a lack of consensus regarding the appropriateness of implementing salvage treatment., Methods: In this large, multicenter, retrospective cohort study, we analyzed the medical records of individuals who underwent endoscopic resection for RNETs and classified them into two groups: the positive resection margin and the negative resection margin group. The overall survival (OS) and disease-free survival (DFS) were compared among two group. The independent variables were identified using univariate and multivariate logistic regression analyses to predict positive resection margin. Then, the model was established to predict the patients with positive resection margin using multivariate logistic regression., Results: 181 RNETs patients (34.3 %) represented positive margin after endoscopic resection. Following a median follow-up period of 72 months, tumor recurrence manifested in 12 out of 527 patients (2.2 %) and the presence of positive resection margin was associated with worse DFS. Independent factors correlating with positive resection margin included endoscopic resection method choice, RNETs located in the low rectum, NLR >4.44 and tumor size exceeding 14.89 mm. A prediction model was therefore established with high predictive accuracy and excellent clinical applicability determined by calibration curves and DCA curve. Among RNETs patients with positive margin following endoscopic resection, implementing salvage treatment was beneficial for improving DFS and salvage endoscopic resection offer equal efficiency compared with salvage radical resection., Conclusions: Positive resection margin following endoscopic resection may indicate negative prognosis. Salvage treatment can improve the prognosis of RNETs patients with positive resection margin. Notably, salvage local resection exhibited similar efficacy compared with radical surgery in term of survival benefit., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recently, solar-driven interfacial evaporation (SDIE) has been developed quickly for low-cost and sustainable seawater desalination, but addressing the conflict between a high evaporation rate and salt rejection during SDIE is still challenging. Here, a spatial confinement strategy is proposed to prepare the gel composite solar evaporator (SCE) by loading one thin hydrogel layer onto the skeleton of a carbon aerogel. The SCE retains the hierarchically porous structure of carbon aerogels with an optimized water supply induced by dual-driven forces (capillary effects and osmotic pressure) and takes advantage of both aerogels and hydrogels, which can gain energy from air and reduce water enthalpy. The SCE has a high evaporation rate (up to 4.23 kg m -2  h -1 under one sun) and excellent salt rejection performance and can maintain structural integrity after long-term evaporation even at high salinities. The SDIE behavior, including heat distribution, water transport, and salt ion distribution, is investigated by combining theoretical simulations and experimental results. This work provides new inspiration and a theoretical basis for the development of high-performance interfacial evaporators., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cadmium (Cd) is a heavy metal that pollutes the environment and threatens human and animal health via the food chain. The spleen is one of the target organs affected by Cd toxicity. However, the mechanism of Cd toxicity is not fully understood. In this study, 80 chicks were allocated into 4 groups (n = 20) and exposed to different doses of CdCl 2 (0 mg/kg, 35 mg/kg, 70 mg/kg and 140 mg/kg) for 90 d. The pathological changes in the spleen, mitochondrial dynamics-related factors, cytochrome P450 (CYP450) enzyme system contents, activities, transcription levels, nuclear receptors (NRs) response molecule levels, and mitochondrial unfolded protein-related factors were detected. The findings indicate that exposure to Cd significantly leads to spleen injury. In Cd groups, the total contents of CYP450 and cytochrome b5 (Cyt b5) increased, and the activities of the CYP450 enzyme system (APND, ERND, AH, and NCR) changed. The NRs response was induced, and the gene levels of AHR/CAR and corresponding CYP450 isoforms (CYP1B1, CYP1A5, CYP1A1, CYP2C18, CYP2D6 and CYP3A4) were found altered. The study found that Cd exposure altered the mRNA expression levels of mitochondrial dynamics-related factors, such as OPA1, Fis1, MFF, Mfn1, and Mfn2, breaking mitochondrial fusion and cleavage and ultimately leading to mitochondrial dysfunction. Changes were detected in the gene levels of several mitochondrial unfolded protein response (mtUPR)-related factors, namely (SIRT1, PGC-1α, NRF1, TFAM, SOD2, and HtrA2). Cd also altered the gene levels of mitochondrial function-related factors (VDAC1, Cyt-C, COA6, PRDX3, RAF and SIRT3). It is showed that Cd can initiate the NRs response, influence the homeostasis of the CPY450 enzyme system, trigger the mtUPR, impair mitochondrial function, and ultimately lead to Cd toxicity in the spleen of chickens., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Controversy remains as to whether initiating haemodialysis (HD) with a central venous catheter (CVC) and vascular access conversion are associated with the risk of morbidity and mortality in incident HD patients., Methods: At our dialysis centre, the vascular access strategy is to create an arteriovenous fistula (AVF) early and use the AVF to initiate HD. In emergency situations, HD is initiated with a CVC and subsequent conversion from a CVC to an AVF as soon as possible. The effects of early AVF conversion on hospitalization and mortality were analysed., Results: At HD initiation, 35.42% used AVF, 15.63% used CVC with immature AVF and 48.96% used CVC, and all patients were able to convert from CVC to AVF within approximately 3 months. Compared to starting HD using an AVF, using a CVC was associated with access-related hospitalizations at 2 years, regardless of whether an AVF was created before (incidence rate ratio (IRR) = 3.02, 95% CI 0.89-10.24, p  = 0.03) or after (IRR = 4.10, 95% CI 1.55-10.85, p  < 0.01) HD initiation. The Kaplan-Meier method showed that the 2-year survival probability was not statistically significant between the three groups (log-rank χ 2  = 0.165, p  = 0.921). Multivariate Cox proportional hazards regression showed that starting HD with a CVC was not associated with mortality at 2 years ( p  > 0.05)., Conclusion: In this cohort, initiating HD with a CVC was associated with more access-related hospitalizations. Under the impact of an early AVF conversion strategy, despite initiating HD with a CVC, subsequent conversion from a CVC to an AVF within approximately 3 months had no impact on all-cause mortality in incident HD patients., 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.

Electrically conductive fiberfibre/fabric composites (ECFCs) are competitive candidates for use in wearable electronics. Therefore, it is essential to develop mechanically robust ECFC strain sensors with sensing performance. In this study, MXene assembly and hot-pressing were combined to prepare strong yet breathable ECFCs for strain and temperature sensing. Hydrogen bonding between MXene and polyurethane (PU) and ultrasonication-induced interfacial sintering were responsible for MXene nanosheets assembly on the PU nanofibers. MXene decoration made PU nanofibers electrically conductive, resulting in a conductive network. Hot-pressing improved interface adhesion among the conductive nanofibers. Thus, the mechanical properties of the nanofiber composites, including tensile strength, toughness and fracture energy, were enhanced. The nanofiber composites exhibited surface stability and durability. When the nanofiber composites were used as strain sensors, they showed breathability with a linear resistance response ranging from 1 % to 100 % and cycling stability. In addition, they produced stable sensing signals over 1000 cycles when a notch was present. They could also monitor temperature variations with a negative temperature coefficient (-0.146 %/°C). This study provides an interfacial regulation method for the preparation of multi-functional nanofiber composites with potential applications in flexible and wearable electronics., 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.)

Melting in the deep rocky parts of planets plays an important role in geological processes such as planet formation, seismicity, magnetic field generation, thermal convection, and crustal evolution. Such processes are the key way to understanding the dynamics of planetary interiors and the history as well as mechanisms of planetary evolution. We herein investigate the melting curves and pressure-temperature ( P - T )-phase diagrams for CaO 3 , a candidate mineral for the lower mantle, by means of the deep learning potential model. Using first-principles, molecular dynamics, and quasi-harmonic approximation, the reliability of the deep learning potential model is verified by calculating the high-temperature and high-pressure equations of state and phase transition pressures for the orthorhombic and tetragonal structures of CaO 3 described by space groups Aea 2 and P 4̅2 1 m , respectively. The melting temperatures of 975, 850, and 755 K at zero pressure are obtained by the single-phase, void, and two-phase methods, respectively, and their melting temperatures are analyzed by the radial distribution function and mean-square displacement to analyze the melting process. Finally, the melting phase diagrams of CaO 3 at 0-135 GPa were obtained by the two-phase method.

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Introduction: Deep vein thrombosis (DVT) is a common complication observed in aneurysmal subarachnoid hemorrhage (aSAH) patients, which significantly increases the survival risks and reduces the patient's quality of life. However, preventive clinical measures for DVT have not been standardized; therefore, the scientific basis and effectiveness of these measures require further validation., Objective: This study aims to employ evidence-based practices to effectively prevent the occurrence of DVT in aSAH patients., Methods: This study was performed from June 2023 to March 2024 in the neurosurgical intensive care unit of a Grade III Class A general hospital in Nanchang, China. Furthermore, it was based on the healthcare model published by the Joanna Briggs Institute Library (JBI) in 2016, which emphasizes the use of previous evidence-based practices while considering appropriateness, feasibility, clinical significance, and validity. In this research study, 15 review indicators were developed, and baseline assessments on 47 nurses and 49 patients were conducted. Furthermore, factors promoting and obstructing implementation were analyzed, and targeted strategies to address these obstacles were formulated. Moreover, a follow-up audit was performed to identify best practices., Results: The baseline review results indicated that the incidence of DVT in aSAH patients was 16.3%. Furthermore, the implementation rates of six review indicators (1, 2, 4, 5, 8, 13) were all < 100.0%, with indicators 2, 5, and 8 indicating < 60.0% implementation rates. After the project implementation, a subsequent audit revealed that the best practice initiative yielded significant improvements compared to the baseline data. Moreover, the incidence of lower limb DVT in aSAH patients decreased from 16.3% before the evidence-based practices to 6.1% after their implementation. At the nursing level, the DVT prevention knowledge and practice questionnaire scores increased from 63.62 ± 11.48 to 74.77 ± 9.98 after the evidence-based practices (t = -5.03, p < .001). In addition, the implementation rates of the six review indicators improved to varying degrees after the implementation of evidence-based practices (p < .050)., Conclusions: This project implemented evidence-based practices and indicated a reduced incidence of lower limb DVT in patients with aSAH. Furthermore, this study improved the knowledge, provided evidence for DVT prevention for the neurosurgical ICU nurses, promoted the implementation rate of review indicators for DVT prevention, standardized the behavior of neurosurgical ICU nurses for preventing DVT in aSAH patients, and ensured the safety of patients., Trial Registration: This study has been registered at the EvidenceBased Nursing Center of Fudan University in China. Clinical trial number ER20230578., (© 2024. The Author(s).)

EfpA, the first major facilitator superfamily (MFS) protein identified in Mycobacterium tuberculosis (Mtb), is an essential efflux pump implicated in resistance to multiple drugs. EfpA-inhibitors have been developed to kill drug-tolerant Mtb. However, the biological function of EfpA has not yet been elucidated. Here, we present the cryo-EM structures of EfpA complexed with lipids or the inhibitor BRD-8000.3 at resolutions of 2.9 Å and 3.4 Å, respectively. Unexpectedly, EfpA forms an antiparallel dimer. Functional studies reveal that EfpA is a lipid transporter and BRD-8000.3 inhibits its lipid transport activity. Intriguingly, the mutation V319F, known to confer resistance to BRD-8000.3, alters the expression level and oligomeric state of EfpA. Based on our results and the observation of other antiparallel dimers in the MFS family, we propose an antiparallel-function model of EfpA. Collectively, our work provides structural and functional insights into EfpA's role in lipid transport and drug resistance, which would accelerate the development of antibiotics against this promising drug target., Competing Interests: Competing interests statement:The authors declare no competing interest.

Large artery atherosclerosis (LAA) is a prevalent cause of acute ischemic stroke (AIS). Understanding the mechanisms linking atherosclerosis to stroke is essential for developing appropriate intervention strategies. Here, we found that the exosomal miRNA Novel-3 is selectively upregulated in the plasma of patients with LAA-AIS. Notably, Novel-3 was predominantly expressed in macrophage-derived foam cells, and its expression correlated with atherosclerotic plaque vulnerability in patients undergoing carotid endarterectomy. Exploring the function of Novel-3 in a mouse model of cerebral ischemia, we found that Novel-3 exacerbated ischemic injury and targeted microglia and macrophages expressing ionized calcium-binding adapter molecule 1 in peri-infarct regions. Mechanistically, Novel-3 increased ferroptosis and neuroinflammation by interacting with striatin (STRN) and downregulating the phosphoinositide 3-kinase-AKT-mechanistic target of rapamycin signaling pathway. Blocking Novel-3 activity or overexpressing STRN provided neuroprotection under ischemic conditions. Our findings suggest that exosomal Novel-3, which is primarily derived from macrophage-derived foam cells, targets microglia and macrophages in the brain to induce neuroinflammation and could serve as a potential therapeutic target for patients with stroke who have atherosclerosis., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Emerging high-power piezoelectric applications demand the development of piezoelectric materials featuring both a high mechanical quality factor ( Q m ) and a large piezoelectric coefficient ( d 33 ). However, it is widely accepted that an increase in d 33 is usually accompanied with a decrease in Q m , and vice versa . Herein, a multiscale regulation strategy is proposed to improve Q m and d 33 simultaneously from the perspectives of phase structure, ferroelectric domains, and lattice defects. A well-balanced combination of electromechanical performances with Q m = 726, d 33 = 502 pC N -1 , k p = 0.69, tan  δ = 0.0024, and T C = 267 °C was obtained. Through structural characterization, it was observed that the morphotropic phase boundary and enhanced dispersion behavior lead to a lowered energy barrier, which contributes to polarization rotation and enhances piezoelectric performance. At the same time, the excellent piezoelectric performances also benefit from the highly oriented domain structure and small domain size after high-temperature poling. Furthermore, the segregation of Ba 2+ causes A-site defects in the crystal lattice, accompanied with an increase in oxygen vacancies, which maintains the hardening effect of the ceramics. This study proposes a multiscale regulation strategy, providing insights for the design of high-power piezoelectric ceramics with high d 33 and Q m .

Introduction: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with the worst prognosis. Exploring novel carcinogenic factors and therapeutic drugs for TNBC remains a focus to improve prognosis. Branched-chain amino acid transaminase 1 (BCAT1), a crucial enzyme in branched-chain amino acid (BCAA) metabolism, has been linked to various tumor developments, but its carcinogenic function and mechanism in TNBC remain unclear. Eupalinolide B (EB) is a naturally-derived small-molecule with anti-tumor activity, but its role in TNBC remains unknown., Objectives: By exploring the targets and pharmacological mechanisms of EB in inhibiting TNBC, this study aimed to discover novel therapeutic targets and potential inhibitors for TNBC, and elucidate novel pathogenic mechanisms of TNBC., Methods: The inhibitory effect of EB on TNBC was investigated using mouse models and cellular phenotypic experiments. Activity-based protein profiling (ABPP) technology, pull down-WB, CETSA-WB and MST were utilized to discover and validate the targets of EB. The oncogenic role of BCAT1 was determined through clinical data analysis and biochemical experiments. To elucidate the mechanism by which EB inhibited TNBC, many methods, including but not limited to HPLC and proteomic sequencing were used., Results: We found that EB significantly inhibited TNBC progression. We identified BCAT1 as the direct target of EB and confirmed that BCAT1 was critical for TNBC development. EB inhibited BCAT1-involved BCAA metabolism to reduce the synthesis of BCAAs (including Leu, Ile, and Val), thereby inhibiting SHOC2 (a Leu-rich repeat protein) expression and the downstream SHOC2-participating RAS-ERK signaling pathway, ultimately leading to apoptosis of TNBC cells., Conclusion: Collectively, this study not only elucidates the oncogenic role of BCAT1 and its downstream SHOC2-RAS-ERK signaling axis in TNBC progression but also opens up avenues for potential therapies targeting BCAT1 or BCAA metabolism (using EB alone or in combination with its inhibitor candesartan) for TNBC treatment., 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. Production and hosting by Elsevier B.V.)

Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications., 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 Long, Xiang, Xiao, Min, Qu, Zhang and Zeng.)

The regulation of adipose tissue homeostasis is essential for maintaining energy and metabolism balance in the body. The peripheral nervous system plays a crucial role in this process. Previous related research primarily focused on the sympathetic nervous system and its release of norepinephrine, while recent attention has shifted to the field of adipose sensory nerves. Studies demonstrate that external stimuli can activate adipose sensory nerves through pathways involving transient receptor potential vanilloid-1 (TRPV1), adipokines, and fatty acids, thereby transmitting signals to the brain. Emerging techniques, such as adipose nerve imaging and denervation of tissues, have revealed the critical role of sensory nerves in the glucose and lipid metabolism, thermogenic function, and vascular regulation of adipose tissue. This article comprehensively reviews the latest research on the regulation and function of sensory nerves in adipose tissue, with a focus on the impact of metabolic diseases on adipose sensory nerves. This review discusses current issues and prospects on the mechanisms behind neural regulation in adipose tissue, hoping to contribute to a comprehensive understanding and providing directions for future research.

Sulfur dioxide (SO 2 ) and viscosity play important roles in living organisms, and abnormal levels of them are associated with many diseases. Hence, a bifunctional fluorescence probe (E)-3-(2-(4-(4-(4-(6-fluoro-3-hydroxy-4-oxo-4H-chromen-2-yl)benzoyl)piperazin-1-yl)styryl)benzo-[d]thiazol-3-ium-3-yl)propane-1-sulfonate (HFBT) with fluorescence resonance energy transfer (FRET) properties was successfully constructed by using 3-hydroxyflavonol as the energy donor and benzothiazole sulphonate derivatives as the energy acceptor, and it can be used for the detection of SO 2 derivatives (HSO 3 - /HSO 3 2- ) and viscosity. HFBT exhibits a large Stokes shift (245 nm), high resonance energy transfer efficiency (95.56 %), and excellent selectivity, anti-interference and low limit of detection (LOD = 0.057 μM) for HSO 3 - . The fluorescence intensity of HFBT at 596 nm gradually increases with the increase of viscosity. Interestingly, a visual HSO 3 - detection platform was successfully constructed and applied to the quantitative detection of HSO 3 - in food. Additionally, HFBT was successfully applied to imaging endogenous and exogenous HSO 3 - in cells. The successful development of HFBT provides an effective tool for the detection and imaging of HSO 3 - in food and cells., 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 order to reveal adsorption-regulation micromechanism and debonding micromechanism between wall surface and magnetorheological (MR) wall-climbing robot legs, an interparticle normal magnetic attraction (NMA) mechanics model was constructed based upon the magnetic-dipole theory. According to analysis of NMA mechanics, it was confirmed that the interparticle NMA could be intensified with enhancing magnetic-particle diameter but was weakened with ratio of adjacent magnetic-particles distance to magnetic-particle radius. It means that the adhesive capacity between MR wall-climbing robot legs and wall surface could be strengthened by increasing magnetic-particle size and decreasing interparticle distance. Furthermore, it was found that the NMA of the first particle in the magnetic chain was positively related to magnetic-particles number until the magnetic-particles number reached a critical value. Consequently, the adsorption ability between MR wall-climbing robot legs and wall surface could be effectively controlled by changing magnetic-particles number. Besides, the strongest NMA appeared at the middle of the magnetic chain. However, the weakest NMA locates at both ends of the magnetic chain. Thus, it could be concluded that the end of the magnetic chain would be separated from wall surface rather than fracture occurred in the middle of the magnetic chain when the MR wall-climbing robot legs divorced from wall surface., (© 2024. The Author(s).)

High structural stability, dual organic-inorganic nature, and tunability in chemical functionality are promising characteristics of zirconium-based metal-organic frameworks (Zr-MOFs). These properties assist Zr-MOFs in extending their applications in various fields, especially adsorptive removal of pollutants. In this work, two well-known Zr-MOFs (UiO-66(Zr) and MIL-140(Zr) with the formula Zr 6 O 4 (OH) 4 (BDC) 6 , H 2 BDC is benzene 1,4-dicarboxylic acid) were synthesized and decorated with a dihydrotetrazine functional group through postsynthesis linker exchange (PSLE). Two dihydrotetrazine (DHTZ)-functionalized frameworks, UiO-66(Zr)-DHTZ and MIL-140(Zr)-DHTZ, were applied for the removal of quinoline (Qui) and indole (Ind) from the model oil. The results of adsorption experiments at room temperature display that these functionalized Zr-MOFs have significantly improved removal capacities for Qui (875% for UiO-66(Zr)-DHTZ and 303% for MIL-140(Zr)-DHTZ) and Ind (722% for UiO-66(Zr)-DHTZ and 257% for MIL-140(Zr)-DHTZ). Mechanistic studies based on X-ray photoelectron (XPS) and Fourier-transform infrared (FT-IR) spectroscopies reveal that there is a specific kind of host-guest interaction between dihydrotetrazine and nitrogen-containing compounds (NCCs). UiO-66(Zr)-DHTZ adsorbs 1426 mg·g -1 Qui and 1176 mg·g -1 Ind, while MIL-140(Zr)-DHTZ adsorbs 619 mg·g -1 Qui and 511 mg·g -1 Ind. The lower adsorption capacities of MIL-140(Zr)-DHTZ compared to UiO-66(Zr)-DHTZ are related to its lower surface area (783 m 2 ·g -1 versus 330 m 2 ·g -1 ). The recyclability of the frameworks goes up to five cycles without any significant decrease in the removal capacity. These results indicate that dihydrotetrazine-functionalized Zr-MOFs are highly stable platforms with superior adsorption capacity compared to basic and neutral NCCs.

For graphene/copper (Gr/Cu) composites, achieving high-quality interfaces between Gr and Cu (strong interfacial bonding strength and excellent electron transport performance) is crucial for enabling their widespread applications in electronic devices. This study employs first-principles calculations and the nonequilibrium Green's function method to systematically investigate the mechanical and electrical conductivity properties of Cu(111)/Gr/Cu(111) interfaces with various stacking sequences and different forms of Gr. For these interface systems, the binding energy, separation work, charge transfer, and electrical conductivity across the interface were obtained. The results show that the top-fcc interface exhibits superior interfacial properties, characterized by relatively high binding energy (-3.00 eV/C atom) and separation work (≥0.78 J/m 2 ), a small interfacial distance (2.85 Å), and enhanced electron transport capacity (2.12 G 0 /nm 2 ). A bilayer form of Gr significantly reduces electronic conductance across the Gr/Cu interface by nearly 2.46 orders of magnitude. Furthermore, point defects in Gr, especially single-vacancy defects, disrupt the traditional trade-offs between mechanical and electrical performance, simultaneously enhancing mechanical performance by 7.50-124.36% and electrical performance by 33.02%. Additionally, stress mechanisms have been proposed to further enhance the interfacial electrical conductivity of Gr/Cu composites. The present study provides a theoretical basis for exploring the engineering applications of Gr/Cu composite materials.

While metal halide light-emitting diodes (PeLEDs) with unique optoelectronic properties are promising emitters for next-generation displays, their performance degrades rapidly due to severe ion migration during continuous operation, especially at high voltages. Here, we realize highly stable PeLEDs by designing inorganic dielectric/perovskite semiconductor emitter/organic dielectric sandwiched nanostructures to mitigate ion migration via regulating the electric field distribution. The bilateral cesium carbonate (Cs 2 CO 3 ) and tetraoctylammonium bromide (TOAB) thin interlayers can not only largely reduce the voltage imposed on the perovskite layer by serving as series resistors and, thus, mitigate the ion migration but also regulate the charge carrier transfer to improve the radiative recombination efficiency. In addition, the underneath inorganic Cs 2 CO 3 film also provides more heterogeneous nucleation sites for growing high-crystallinity perovskite crystals, while the atop TOAB with bifunctional groups (organic amino and Br - ions) refines the morphology and enhances the optical properties of the perovskite film. As a result, efficient and stable green PeLEDs based on such an optoelectric-tunable nanostructure exhibit extremely slow efficiency decay as the applied voltage increases, and the external quantum efficiencies were maintained over 10% at a high bias up to 20 V.

T cells function not only as an essential component of host cancer immunosurveillance but also as a regulator of colonic inflammation, a process that promotes colorectal cancer. Programmed death-ligand 1 (PD-L1) is a T cell-negative regulator, but its role in regulation of T cell functions in the context of colorectal cancer is unknown. We report that global deletion of Cd274 results in increased colonic inflammation, PD-1 + T cells, and inflammation-driven colorectal tumorigenesis in mice. Single-cell RNA sequencing (scRNA-seq) analysis revealed that PD-L1 suppresses subpopulations of programmed cell death protein 1 (PD-1) + Nrp1 lo regulatory T (Treg) cells and interleukin (IL) 6 + neutrophils in colorectal tumor. Treg cells produce transforming growth factor (TGF) β to recruit IL6 + neutrophils. Neutrophils produce IL6 to inhibit activation of tumor-specific cytotoxic T lymphocytes (CTLs) and primary CTLs. Accordingly, IL6 blockade immunotherapy increases CTL activation and suppresses colon tumor growth in vivo. Our findings determine that PD-L1 restrains PD-1 + Nrp1 lo TGFβ + Treg cells to suppress IL6 + neutrophil tumor recruitment to sustain CTL activation to control inflammation-driven colorectal tumorigenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Natural products are a treasure trove for drug discovery, especially in the areas of infection, inflammation and cancer, due to their diverse bioactivities and complex, and varied structures. Chronic inflammation is closely related to many diseases, including complex diseases such as cancer and neurodegeneration. Improving target identification for natural products contributes to elucidating their mechanism of action and clinical progress. It also facilitates the discovery of novel druggable targets and the elimination of undesirable ones, thereby significantly enhancing the productivity of drug discovery and development. Moreover, the rise of polypharmacological strategies, considered promising for the treatment of complex diseases, will further increase the demand for target deconvolution. This review underscores strategies for identifying natural product targets (NPs) in the context of chronic inflammation over the past 5 years. These strategies encompass computational methodologies for early target discovery and the anticipation of compound binding sites, proteomics-driven approaches for target delineation and experimental biology techniques for target validation and comprehensive mechanistic exploration., (© 2024 British Pharmacological Society.)

Quantum walks provide a speed-up in computational power for various quantum algorithms and serve as inspiration for the construction of complex graph representations. Many pioneering works have been dedicated to expanding the experimental state space and the complexity of graphs. However, these experiments are mostly limited to small experimental scale, which do not reach a many-body level and fail to reflect the multi-particle quantum interference effects among non-adjacent modes. Here, we present a quantum walk with three photons on a two-dimensional triangular lattice, which is mapped to a 19 × 19 × 19 high-dimensional state space and constructs a complex graph with 6859 nodes and 45,486 edges. By utilizing the statistical signatures of the output combinations and incorporating machine learning techniques, we successfully validate the nonclassical properties of the experiment. Our implementation provides a paradigm for exponentially expanding the state space and graph complexity of quantum walks, paving the way for surmounting the classical regime in large-scale quantum simulations., (© 2024. The Author(s).)

Uveal melanoma (UM), the predominant primary ocular malignancy, often progresses to liver metastasis with limited therapeutic options. The interplay of the tumor microenvironment, encompassing secreted soluble factors, plays a crucial role in facilitating liver metastasis. In this study, the role is elucidated of the neural growth factor-inducible gene (VGF), a secreted neuropeptide precursor, in Gαq mutant UM. Employing a multiomics approach, encompassing transcriptomic and secretomic analyses, the intricate involvement of VGF in UM progression is unveiled. VGF is upregulated in Gαq mutant UM cells and associated with poor prognosis of UM patients. Targeting VGF significantly suppressed the growth of UM in vitro and in vivo. Further evidence shows that VGF is regulated by Gαq through MAPK/CREB pathway. Mechanistically, CREB modulates VGF expression by directly binding to consensus DNA response elements in the promoters of the VGF gene. Combined inhibition of Gαq and MEK remarkably reduces tumor burden in the UM xenograft model. Notably, VGF triggers liver metastatic colonization of UM and activates the fibrosis of hepatic stellate cells (HSCs), creating a favorable microenvironment, through an autocrine and paracrine loop. Furthermore, VGF directly binds to TGFBR2 and regulates TGF-β-SMAD signaling pathway, thereby regulating genes associated with endothelial-mesenchymal transition (EMT) to promote metastasis. Taken together, these findings identify VGF as a pivotal driver in the progression and metastasis of Gαq mutant UM and confers a promising therapeutic target and strategy for UM patients., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

A new hard superconducting phase of RhB 4 with the space group Cmca is predicted, and the phase transition and mechanical and superconducting properties of RhB 4 under 300 GPa are studied using first principles. We predict a new high-pressure phase of RhB 4 by substituting the most stable Cmca structure of OsB 4 , known for its excellent mechanical properties. The calculated enthalpy shows that above 112.6 GPa, Cmca is superior to Pmmn as was previously predicted by particle swarm optimization. The stability of the predicted phase is checked using formation enthalpy, elastic constant and phonon dispersion. Additionally, the convex hull of the Rh-B system confirms that the phase is expected to be synthesized experimentally. The Cmca phase is an incompressible hard material with a hardness of 23.75 GPa at 300 GPa attributed to strong intralayer covalent B-B bonds. Furthermore, the phase is a relatively pressure-insensitive superconductor, with a T c of 8.6 K at 112.6 GPa and a pressure-dependent coefficient of -0.03 K GPa -1 . The finding reveals a superconducting hard material that is well-suited for extreme high-pressure environments.

Background: Fine motor impairment is common in Parkinson's disease (PD), which reduces patients' quality of life. There are few suitable targeted treatments. We conducted a clinical trial to determine whether Baduanjin Qigong exercise would increase fine motor skills in PD patients., Methods: Sixty PD patients (Hoehn-Yahr stage 1-4) with hand fine motor impairment were randomly assigned to the Baduanjin group and the physical activity group. Baduanjin group practiced Baduanjin exercise five times weekly for 40 min (warm-up 5 min, Baduanjin 30 min, cool-down 5 min). The usual physical activity groups maintained their habit of usual physical activities. The participants underwent assessments in the "ON" medication state at baseline and 4-week follow-up time points. The Purdue Pegboard Test (PPT) was used as the primary outcome to assess manual dexterity. The secondary outcomes included the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), and the Parkinson's disease questionnaire (PDQ-39)., Results: The results of PPT revealed the Baduanjin group showed statistically significant improvement in the "non-dominant hand" and "assembly" scores compared to the usual physical activity group (P < 0.05), but with no significant difference in "dominant hand" and "both hands" (P > 0.05). Additionally, the Baduanjin group showed better performance in the PDQ-39 (P < 0.05)., Conclusion: Our study concludes that a 4-week Baduanjin exercise is effective in improving fine motor function and quality of life in patients with mild and moderate PD. The results suggest a promising intervention to be implemented in community or home settings for managing fine motor impairment in PD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: As a less invasive technique, peroral endoscopic myotomy (POEM) has recently been widely accepted for treating achalasia with an excellent safety profile, durability, and efficacy in adults. In pediatric and geriatric patients, the treatment is more difficult., Aim: To discuss the clinical outcomes of POEM in pediatric and geriatric patients with achalasia., Methods: We conducted a comprehensive search of PubMed, Embase and Cochrane Library databases from inception to July 2024. The primary outcomes were technical and clinical success. Secondary outcomes of interest included adverse events and gastroesophageal reflux disease (GERD). The pooled event rates were calculated by comprehensive meta-analysis software., Results: A total of 32 studies with 547 pediatric patients and 810 geriatric patients were included in this study. The pooled event rates of technical success, clinical success, GERD and adverse events of POEM for treating achalasia in pediatric patients were 97.1% [95% confidence interval (CI): 95.0%-98.3%; I ² = 0%; P < 0.000], 93.2% (95%CI: 90.5%-95.2%; I ² = 0%; P < 0.000), 22.3% (95%CI: 18.4%-26.7%; I ² = 43.874%; P < 0.000) and 20.4% (95%CI: 16.6%-24.8%; I ² = 67.217%; P < 0.000), respectively. Furthermore, in geriatric patients, the pooled event rates were 97.7% (95%CI: 95.8%-98.7%; I ² = 15.200%; P < 0.000), 93.2% (95%CI: 90.3%-95.2%; I ² = 0%; P < 0.000), 23.9% (95%CI: 19.4%-29.1%; I ² = 75.697%; P < 0.000) and 10.8% (95%CI: 8.3%-14.0%; I ² = 62.938%; P < 0.000], respectively., Conclusion: Our findings demonstrated that POEM was an effective and safe technique for pediatric and geriatric patients with achalasia., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is a major health challenge with high incidence and poor survival rates in China. Systemic therapies, particularly tyrosine kinase inhibitors (TKIs), are the first-line treatment for advanced HCC, but resistance is common. The Rho GTPase family member Rho GTPase activating protein 12 (ARHGAP12), which regulates cell adhesion and invasion, is a potential therapeutic target for overcoming TKI resistance in HCC. However, no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported., Aim: To unveil the expression of ARHGAP12 in HCC, its role in TKI resistance and its potential associated pathways., Methods: This study used single-cell RNA sequencing (scRNA-seq) to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis. CellChat was used to investigate focal adhesion (FA) pathway regulation. We integrated bulk RNA data (RNA-seq and microarray), immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels, correlating with clinical outcomes. We assessed ARHGAP12 expression in TKI-resistant HCC, integrated conventional HCC to explore its mechanism, identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy., Results: ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA. In malignant hepatocytes in high-score FA groups, MDK-[integrin alpha 6 (ITGA6) + integrin β-1 (ITGB1)] showed specificity in ligand-receptor interactions. ARHGAP12 mRNA and protein were upregulated in bulk RNA, immunohistochemistry and proteomics, and higher expression was associated with a worse prognosis. ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway. ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA. High expression of ARHGAP12 was associated with adverse reactions to sorafenib, cabozantinib and regorafenib, but not to immunotherapy., Conclusion: ARHGAP12 expression is elevated in HCC and TKI-resistant HCC, and its regulatory role in FA may underlie the TKI-resistant phenotype., 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.)

The alkaline solid-state electrolytes have received widespread attention for their good safety and electrochemical stability. However, they still suffer from low conductivity and poor mechanical properties. Herein, we report the synthesis of double-network featured hydroxide-conductive membranes fabricated by polyvinyl alcohol (PVA) and chitosan (CS) as the double-skeletons. Then, we implanted quaternary ammonium salt guar hydroxypropyltrimonium chloride (GG) as the OH - conductor for high-performance electrochemical devices. By virtue of the unique stripe-like structure shared from the double skeleton with a high degree of compatibility and stronger hydrogen bond interactions, the polyvinyl alcohol/chitosan-guar hydroxypropyltrimonium chloride (PCG) solid-state electrolytes achieved optimal thermal stability (> 300 °C), mechanical property (∼ 34.15 MPa), dimensional stability (at any bending angle), and high ionic conductivity (13 mS cm -1 ) and ion mobility number (t ion  ∼ 0.90) compared with chitosan-guar hydroxypropyltrimonium chloride (CG) and polyvinyl alcohol-guar hydroxypropyltrimonium chloride (PG) electrolyte membrane. As a proof-of-concept application, the "sandwich"-type zinc-air battery (ZAB) assembled using PCG membrane as the electrolyte realized a high open-circuit voltage (1.39 V) and an excellent power density (128 mW cm -2 ). Notably, in addition to its long-term cycle life (30 h, 2 mA cm -2 ) and stable discharge plateau (12 h, 5 mA cm -2 ), it could even enable a flexible ZAB (F-ZAB) to readily power light-emitting diodes (LED) at any bending angle. These merits afford the PCG membrane a promising electrolyte for improving the performance of solid-state batteries., 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.)