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Medium entropy alloys (MEAs) have a high potential in industrial applications due to their excellent mechanical properties. Here we report a strategy to improve the ductility of the Ni40Co30Cr20Al5Ti5 MEAs by rapid solidification (RS). The as-cast alloy is composed of dendritic structure and L12 nano-precipitates. After RS, the lattice misfit of precipitate and matrix is reduced from 0.251 % to 0.167 %, and the size of the precipitate decreases from 85 nm to 28 nm. Meanwhile, RS also reduces the grain size of matrix. Gliding dislocation can cut through precipitates with low lattice misfit and smaller size, which can avoid strain accumulation and prevent crack initiation at the precipitate-matrix interfaces. Compared with the as-cast alloy, the ductility of the RS alloy is increased by 17 %–42 % without a decrease in strength. Our results can provide a guidance for other experiments using the RS technology (laser cladding, magnetron sputtering, etc.) to achieve the strength-ductility balance in the MEAs.

In the summer of 2020, multiple efforts were undertaken to establish safe and effective vaccines to combat the spread of the coronavirus disease (COVID-19). In the United States (U.S.), Operation Warp Speed (OWS) was the program designated to coordinate such efforts. OWS was a partnership between the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector, that aimed to help accelerate control of the COVID-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. The U.S. Department of Veterans Affairs’ (VA) was identified as a potential collaborator in several large-scale OWS Phase III clinical trial efforts designed to evaluate the safety and efficacy of various vaccines that were in development. Given the global importance of these trials, it was recognized that there would be a need for a coordinated, centralized effort within VA to ensure that its medical centers (sites) would be ready and able to efficiently initiate, recruit, and enroll into these trials.The manuscript outlines the partnership and start-up activities led by two key divisions of the VA's Office of Research and Development's clinical research enterprise. These efforts focused on site and enterprise-level requirements for multiple trials, with one trial serving as the most prominently featured of these studies within the VA. As a result, several best practices arose that included designating clinical trial facilitators to study sites to support study initiation activities and successful study enrollment at these locations in an efficient and timely fashion.

Summary: Mouse models are key tools for investigating host-microbiome interactions. However, shotgun metagenomics can only profile a limited fraction of the mouse gut microbiome. Here, we employ a metagenomic profiling method, MetaPhlAn 4, which exploits a large catalog of metagenome-assembled genomes (including 22,718 metagenome-assembled genomes from mice) to improve the profiling of the mouse gut microbiome. We combine 622 samples from eight public datasets and an additional cohort of 97 mouse microbiomes, and we assess the potential of MetaPhlAn 4 to better identify diet-related changes in the host microbiome using a meta-analysis approach. We find multiple, strong, and reproducible diet-related microbial biomarkers, largely increasing those identifiable by other available methods relying only on reference information. The strongest drivers of the diet-induced changes are uncharacterized and previously undetected taxa, confirming the importance of adopting metagenomic methods integrating metagenomic assemblies for comprehensive profiling.

Study objective: Oral anticoagulants (direct oral anticoagulants [DOACs] or warfarin) prevent stroke in patients with atrial fibrillation (AF), but their use may be associated with acute kidney injury (AKI). We aimed to compare AKI risk across individual oral anticoagulants in patients with AF. Design: Systematic review and network meta-analysis. Setting: Randomized trials and population-based studies. Participants: Patients with AF. Interventions: Oral anticoagulants. Main outcome measures: AKI. Results: A systematic literature search in Medline and Embase databases performed on December 17, 2021 identified ten randomized trials and eight population-based longitudinal studies based on prespecified inclusion criteria for systematic review. Clinical trials had short follow-ups and reported only low event rates of serious AKI. Retrospective longitudinal studies were assessed to be at higher risk for bias from confounding and outcome ascertainment, but follow-up was longer (1.5 to 8 years), with AKI incidence ranging from 2 to 29/100 person-years. Eight longitudinal studies that met transitivity assumption were included in a random-effects network meta-analysis within a Bayesian framework. All DOACs were associated with significantly lower risk of AKI compared to warfarin. Dabigatran was associated with lower risk of AKI compared to apixaban (hazard ratio [HR] = 0.82; 95% confidence interval [CI]: 0.68–0.99), rivaroxaban (HR = 0.84; 95%CI: 0.72–0.98), and warfarin (HR = 0.68; 95%CI: 0.59–0.77). Effect size estimates varied by chronic kidney disease status and study geographic locations. Conclusion: Apixaban, rivaroxaban, and dabigatran were associated with lower long-term risk of AKI compared to warfarin among patients with AF, with dabigatran potentially associated with the lowest risk.

Sudden cardiac death in young athletes is a rare, but devastating complication of several clinically silent conditions which can become unmasked during periods of intense physical activity. Prevention of sudden cardiac death starts with robust screening to allow the early identification of at risk individuals and the implementation of preventive strategies. The specific approach to screening (history and physical, with or without pre-participation electrocardiograms) varies across the globe with some notable differences between that used in Europe and the United States. The rationale for this variation is complex, but can be linked to the differences in risk factor prevalence, the healthcare infrastructure, and the capacity to identify and triage at risk individuals in a cost-effective manner. Beyond knowing the differences in the approaches to screening, establishing strategies that work (including novel techniques) and those that can be implemented in a successful and sustainable manner are key.

The process by which funding organizations select among the myriad number of proposals they receive is a matter of significant concern for researchers and the public alike. Despite an extensive literature on the topic of peer review and publications on criteria by which clinical investigations are reviewed, publications analyzing peer review and other processes leading to government funding decisions on large multi-site clinical trials proposals are sparse. To partially address this gap, we reviewed the outcomes of scientific and programmatic evaluation for all letters of intent (LOIs) received by the Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) between July 4, 2008, and November 28, 2016. If accepted, these LOIs represented initial steps towards later full proposals that also underwent scientific peer review. Twenty-two of 87 LOIs were ultimately funded and executed as CSP projects, for an overall success rate of 25%. Most proposals which received a negative decision did so prior to submission of a full proposal. Common reasons for negative scientific review of LOIs included investigator inexperience, perceived lack of major scientific impact, lack of preliminary data and flawed or confused experimental design, while the most common reasons for negative reviews of final proposals included questions of scientific impact and issues of study design, including outcome measures, randomization, and stratification. Completed projects have been published in high impact clinical journals. Findings highlight several factors leading to successfully obtaining funding support for clinical trials. While our analysis is restricted to trials proposed for CSP, the similarities in review processes with those employed by the National Institutes of Health and the Patient Centered Outcomes Research Institute suggest the possibility that they may also be important in a broader context.

Background: Access to healthcare delivery programs and systems is a primary correlate to the overall health and well-being of Veterans and the general population. Participation in clinical research is a gateway to novel therapies that are intended to address current global health issues. Meeting or exceeding recruitment goals in clinical research is one of the key determinants of the timely and successful completion of a study. The travel and time burdens experienced by study participants are often considered barriers to their enrollment into clinical research. The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) established a consortium of nine VA medical centers (VAMCs) called the Network of Dedicated Enrollment Sites (NODES). The NODES program provides study site-level expertise and innovative approaches that address challenges to clinical research execution. In alignment with our mission, our program developed an approach to increase study participant access to clinical research through implementing “Mobile Recruitment (MoRe)” units. This manuscript describes the utility and challenges associated with employing this strategy to address three common barriers to clinical research participation: 1) research participant travel burden, 2) participant access to study opportunities, and 3) low participant enrollment. Methods: A plan to introduce the Mobile Recruitment (MoRe) unit as a recruitment strategy was piloted for a high-volume, observational cohort study and mega biobank in the VA health care system, the “Million Veteran Program (MVP)”. MoRe is a recruitment strategy for CSP research integrating mobile technology and atypical research recruitment locations. Recruitment locations include primary or main VA hospitals and their assigned VA Community-Based Outpatient Clinics (CBOCs). Each Node site (n = 9) received components of the MoRe unit including a laptop, printer, portable cart with storage space, cooler/ice packs for specimen storage and transport. Each site's usage of these components varied based on its respective needs. Activities focused on both VA main facilities and CBOC facilities for recruitment. Results: Seven of the nine Node sites compared the effectiveness of the MoRe unit on MVP study enrollment outcomes over three-time points: pre-intervention period, intervention period, and post-intervention period. The utilization of MoRe in the intervention period demonstrated a 36.9% increase in enrollment compared to the previous six months (pre-intervention period). There was a 2% enrollment increase at the six-month post-intervention period as compared to the intervention period. When comparing the pre-intervention period to the post-intervention period (duration of eighteen months), enrollment increased by 38.9%. Conclusion: Five of the seven sites experienced an increase in enrollment during the intervention and post-intervention periods. The two sites without an increase in enrollment experienced various extenuating factors. Characteristics of sites using MoRe included the ability to utilize a smaller, unconventional space, i.e. not a traditional clinical research exam space for recruitment. MoRe was utilized in hospital laboratory space, CBOCs, primary care clinics, and other subspecialty clinics that allowed recruitment activities but did not have dedicated space to offer the research teams for that purpose. This initiative successfully demonstrated the benefit of deploying the unit, proving its utility in cases in where there was a lack of space or alternative workstations for research activities. The implementation of MoRe by NODES as a recruitment strategy for MVP may be transferable to other VA clinical research studies, as well as to other healthcare settings executing similar clinical research activities.

Background: Randomized clinical trials are the gold standard for evaluating healthcare interventions and, more generally, add to the medical knowledge related to the treatment, diagnosis and prevention of diseases and conditions. Recent literature continues to identify health informatics methods that can help improve study efficiency throughout the life cycle of a clinical trial. Electronic medical record (EMR) data provides a mechanism to facilitate clinical trial research during the study planning and execution phases, and ultimately, can be utilized to enhance recruitment. The Department of Veterans Affairs (VA) has a strong history of clinical and epidemiological research with over four decades of data collected from Veterans it has served nationwide. The VA Informatics and Computing Infrastructure (VINCI) provides VA research investigators with a nationwide view of high-value VA patient data. Within VA, the Cooperative Studies Program (CSP) Network of Dedicated Enrollment Sites (NODES) is a consortium of nine sites that are part of an embedded clinical research infrastructure intended to provide systematic site-level solutions to issues that arise during the conduct of VA CSP clinical research. This paper describes the collaboration initiated by the Salt Lake City (SLC) node site to bring informatics and clinical trials together to enhance study planning and recruitment within the VA. Methods: The SLC VA Medical Center physically houses both VINCI and a node site and the co-location of these two groups prompted a natural collaboration on both a local and national level. One of the functions of the SLC NODES is to enhance recruitment and promote the success of CSP projects. VINCI supports these efforts by providing VA researchers access to potential population pools. VINCI can provide 1) feasibility data during study planning, and 2) active patient lists during recruitment. The process for CSP study teams to utilize these services involves regulatory documentation, development of queries, revisions to the initial data request, and ongoing communications with several key study personnel including the requesting research team, study statisticians, and VINCI data managers. Results: The early efforts of SLC NODES and VINCI aimed to provide patient lists exclusively to the SLC CSP study teams for the following purposes: 1) increasing recruitment for trials that were struggling to meet their respective enrollment goals, and 2) decreasing the time required by study coordinators to complete chart review activities. This effort was expanded to include multiple CSP sites and studies. To date, SLC NODES has facilitated the delivery of these VINCI services to nine active CSP studies. Conclusion: The ability of clinical trial study teams to successfully plan and execute their respective trials is contingent upon their proficiency in obtaining data that will help them efficiently and effectively recruit and enroll eligible participants. This collaboration demonstrates that the utilization of a model that partners two distinct entities, with similar objectives, was effective in the provision of feasibility and patient lists to clinical trial study teams and facilitation of clinical trial research within a large, integrated healthcare system. Keywords: Clinical trial recruitment, Clinical informatics, Cooperative studies program (CSP), Network of dedicated enrollment sites (NODES), VA informatics and computing infrastructure (VINCI)

This paper presents the quality journey taken by a Federal organization over more than 20 years. These efforts have resulted in the implementation of a Total Integrated Performance Excellence System (TIPES) that combines key principles and practices of established quality systems. The Center has progressively integrated quality system frameworks including the Malcom Baldrige National Quality Award (MBNQA) Framework and Criteria for Performance Excellence, ISO 9001, and the Organizational Project Management Maturity Model (OPM3), as well as supplemental quality systems of ISO 15378 (packaging for medicinal products) and ISO 21500 (guide to project management) to systematically improve all areas of operations. These frameworks were selected for applicability to Center processes and systems, consistency and reinforcement of complimentary approaches, and international acceptance. External validations include the MBNQA, the highest quality award in the US, continued registration and conformance to ISO standards and guidelines, and multiple VA and state awards. With a focus on a holistic approach to quality involving processes, systems and personnel, this paper presents activities and lessons that were critical to building TIPES and establishing the quality environment for conducting clinical research in support of Veterans and national health care.

Background: Recruitment into clinical trials remains a key determinant to study completion and success. While various strategies have been proposed, it is unclear how they apply across different populations, diseases, and/or study goals. The ability to effectively overcome challenges may require different approaches that more broadly focus on addressing obstacles among sites that cannot be overcome by individual studies. Methods: The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) established the Network of Dedicated Enrollment Sites (NODES) as a consortium of sites to generate systematic site-level solutions to more efficiently recruit in CSP studies. Initial activities identified priorities and developed approaches through team-based efforts. Metrics were also developed to assess overall network performance. Results: Network efforts produced several new strategies and best practices for common problems in CSP research. Recruitment strategies included bringing studies to patients and developing data programs using algorithms for finding eligible patients. Efficiency efforts focused on cross-training and standardizing performance reports. Conclusion: NODES addressed site challenges in clinical trial recruitment and management by taking an overall approach that looked at the system rather than individual studies. Practices and operational changes were implemented for CSP research related to recruitment, staff training and research methodology. The network activities suggest that team-based development of tools and insights may help better identify targets and increase efficiencies for clinical trials recruitment.

The development of environmentally responsive biodegradable polymers is a promising solution for balancing the stability and degradability of biodegradable plastics. In this study, a commercial biodegradable polyester, poly(butylene adipate-co-butylene terephthalate) (PBAT), was used as the substrate and was synthetically modified with a small amount of anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) to obtain the ionized random poly(butylene adipate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBATS). The introduction of the sodium sulfonate ionic group enhanced the mechanical and heat-resistant properties of the material, while significantly improving the hydrophilicity and water absorption of the copolyesters of PBATSs and endowing them with special pH-responsive degradation properties. Compared with PBAT, PBATS copolyesters could accelerate degradation in acidic or alkaline buffer solutions and natural seawater, while degradation was inhibited in neutral buffer solutions at pH 7.2. Degradation experiments in simulated gastric, intestinal, and body fluids revealed that the copolyester showed specific and rapid degradation in acidic gastric fluids. This environmentally-responsive degradable material greatly expands the special applications of biodegradable polyesters in the fields of environmental remediation and medical applications., 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.)

Objective: Maternal environmental metal exposure is common, but long-term prospective epidemiological evidence of its impact on children's intellectual development is still insufficient., Methods: Data on maternal plasma metal levels and child intelligence were obtained for 211 3-6-year-old children from Guangxi Zhuang Birth Cohort. ICP-MS was employed to detect 17 metals, including 7 essential metals (Mn, Fe, Co, Ni, Cu, Zn, Mo) and 10 non-essential metals (As, Rb, Sr, Cd, Sb, Cs, Ba, W, Pb, U), in maternal plasma samples obtained before 13 weeks of gestation during the initial maternity checkup. Child intelligence was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. The GLM, RCS and mixture models were used to assess the associations of maternal plasma metal levels with child intelligence quotient (IQ) scores., Results: The GLM analysis revealed that U had a significant adverse effect on child IQ scores in high-dose exposure groups (-9.236 [-18.644, -4.936], p = 0.006) after adjusting for covariates, while Sb showed a linear adverse effect on children's intelligence in the adjusted model (-4.028 [-7.432, -0.626], p = 0.021). BKMR modeling indicated that overall IQ scores decreased as concentrations of non-essential metals mixtures increased after adjusting for essential metal mixtures, consistent with findings from the WQS (β [95% CI], -8.463 [-14.449, -2.476], p = 0.007) and Qgcomp models (-7.003 [-12.928, -1.078], p = 0.022). Among the non-essential metals, U had the highest negative weight at 37.96%, followed by Pb (23.35%) and Sb (16.91%). Furthermore, potential interactions were observed between metals (Pb and U) and Sb in the study findings., Conclusion: Reducing exposure to non-essential metal mixtures, especially U, Sb and Pb, during early pregnancy and ensuring adequate intake of specific essential metal elements could be a critical intervention in addressing childhood intellectual impairment., 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.)

Reactive oxygen species (ROS) play crucial roles in element cycling and pollutant dynamics, but their variations and mechanisms in the rhizosphere of submerged macrophytes are poorly investigated. This study investigated the light-dark cycle fluctuations and periodic variations in ROS, redox-active substances, and microbial communities in the rhizosphere of Vallisneria natans. The results showed sustained production and significant diurnal fluctuations in the O 2 •- and •OH from 27.6 ± 3.7 to 61.7 ± 3.0 μmol/kg FW and 131.0 ± 6.8 to 195.4 ± 8.7 μmol/kg FW, respectively, which simultaneously fluctuated with the redox-active substances. The ROS contents in the rhizosphere were higher than those observed in non-rhizosphere sediments over the V. natans growth period, exhibiting increasing-decreasing trends. According to the redundancy analysis results, water-soluble phenols, fungi, and bacteria were the main factors influencing ROS production in the rhizosphere, showing contribution rates of 74.0, 17.3, and 4.4 %, respectively. The results of partial least squares path modeling highlighted the coupled effects of redox-active substances and microbial metabolism. Our findings also demonstrated the degradation effect of ROS in rhizosphere sediments of submerged macrophytes. This study provides experimental evidence of ROS-related rhizosphere effects and further insights into submerged macrophytes-based ecological restoration., 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.)

Upon entering the environment, plastics would undergo photoaging and forming microplastics (MPs). However, information on the photoaging behavior of colored MPs and how the color characteristics (wavelength, lightness, and saturation) influence their photoaging process is still lacking. Thus, attention was paid to comparing the photoaging process of transparent and five-colored MPs. To reveal the degree of photodegradation and photooxidation, physicochemical changes (e.g., surface morphology, functional groups, and the leaching of intermediates) of transparent and five-colored MPs were explored. Photodegradation rates and photooxidation degrees ranked transparent > yellow > red ≈ orange > green > blue. However, transparent and five-colored MPs exhibited a different photoaging sequence and eluted different photodegradation products from each other. Pearson correlation analysis was used to describe the relationships between color characteristics (wavelength, lightness, and saturation) and their photoaging properties, and the results indicated that MPs (yellow, red, and orange) with longer color wavelength, higher lightness, and lower saturation are more susceptible to UV light than MPs with shorter color wavelength, lower lightness and higher saturation (green and blue). The findings demonstrate that the photoaging process of colored MPs is correlated to their color characteristics, highlighting the important role of color in MPs' environmental fate., 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.)

Alkylphenols (APs) may cause gestational diabetes mellitus (GDM) in pregnant women by impairing glucose metabolism through endocrine disruption. However, the current literature has limited epidemiological evidence on the association between APs exposure and the risk of GDM, especially the lack of evidence on joint exposure. Thus, we evaluated the effect of exposure to APs during early pregnancy on the risk of GDM. The study involved 2035 pregnant women from Guangxi Zhuang Birth Cohort (GZBC) in China. Poisson regression model, restricted cubic spline (RCS), Bayesian kernel machine regression (BKMR), and quantile g-computation (Qgcomp) were conducted to evaluate the effects of serum APs levels on the risk of GDM in pregnant women. For each Ln-unit increase in the serum nonylphenol (NP) of pregnant women, the adjusted relative risk (RR) for GDM risk was 1.12 (95 % CI: 1.00, 1.24). After sex stratification, the effect was more pronounced among pregnant women carrying female fetuses（RR=1.22; 95 % CI: 1.09, 1.38). The serum 4-t-octylphenol (4-T-OP) of the medium-exposure (adjusted RR = 3.25: 95 % CI: 1.30, 8.12) and high-exposure groups (adjusted RR = 2.90: 95 % CI: 1.15, 7.31) were related to a significantly increased risk of GDM in pregnant women carrying female fetuses only when compared to the low-exposure group. A reverse U-shaped nonlinear association was found between 4-n-octylphenol (4-N-OP) and 4-n-nonylphenol (4-N-NP) concentrations and GDM risk, and it was more susceptible in pregnant women carrying female fetuses. The Qgcomp and BKMR models showed that exposure to APs mixtures was correlated with an elevated risk of GDM in pregnant women carrying female fetuses (adjusted OR = 1.90: 95 % CI: 1.07, 3.38). Exposure to APs during early pregnancy may have potential fetal sex-specific effects on the risk of GDM, with pregnant women carrying female fetuses being more susceptible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Circulating tumor DNA (ctDNA) has emerged as a useful biomarker for cancer detection and prognosis. In this study, we developed a strategy for developing a highly specific multiplex qPCR assay to detect methylated ctDNA in the blood of colorectal cancer (CRC) patients and investigated the potential use for the detection and prognosis of CRC., Methods: Bisulfite conversion and amplicon sequencing were used to confirm potential CRC-specific DNA methylation markers. The selected DNA methylation candidates were validated by qMSP. The six best-performing markers were used to develop a new single-tube multiplex quantitative methylation-specific PCR assay (mqMSP). The mqMSP assay was applied to analyze plasma samples from 114 CRC patients, 47 patients with advanced adenoma, 45 patients with benign polyps, and 57 healthy controls. The clinical performance of the assay and associations with clinical outcomes were assessed., Results: Six DNA methylation biomarkers were confirmed to be specifically hypermethylated in CRC tumor tissues. The newly developed mqMSP assay detected CRC with extremely high specificity (specificity of 98.2 %, with sensitivity of 67.5 %). The detection rate of ctDNA was significantly correlated with tumor size and clinical stage, with ctDNA methylation levels in the blood markedly increased with larger tumor size, poor differentiation, and advanced stage. Moreover, high preoperative methylated ctDNA level was associated with worse recurrence-free survival and overall survival., Conclusion: We provided a strategy for identification of multiple highly-specific DNA methylation markers for designing multiplex DNA methylation assays for liquid biopsies of CRC. The newly developed assay has potential for CRC early detection, and prognosis., Competing Interests: Declaration of competing interest DZ, JL, CD, and SJ have filed a patent for the relevant markers and assays., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Renal fibrosis is a common pathway involved in the progression of various chronic kidney to end-stage diseases, posing a substantial global public health challenge in the search for effective and safe treatments. This study investigated the effects and mechanisms of sacha inchi shell polysaccharide (SISP) on renal fibrosis induced by a high-salt diet (HSD) in mice. By analysing kidney-related protein pathways and the structure of gut microbiota, we found that SISP significantly reduced urinary protein levels induced by a HSD from 41.08 to 22.95 μg/mL and increased urinary creatinine from 787.43 to 1294.50 μmol/L. It reduced renal interstitial collagen fibres by 11.30 %, thereby improving the kidney function. SISP lowered the mRNA expression of TGF-B1, fibronectin, α-SMA, Smad2/3, and TGFBRII, leading to decreased protein levels of TGF-β1, p-Smad2/3, p-TGFβRII, fibronectin, α-SMA, p-Smad2/3/Smad2/3, and p-TGFβRII/TGFβRII. These changes blocked downstream transcription in the TGF-β1/Smad signalling pathway, thereby attenuating renal fibrosis in HSD mice. In addition, SISP altered the intestinal flora imbalance in HSD mice by reducing the relative abundance of the genera, Akkermansia, Faecalibaculum, and unidentified_Ruminococcaceae, and reversing the decline in the levels of the genera, Lactobacillus and Bacteroides. In conclusion, SISP is a promising nutraceutical for renal fibrosis management., 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.)

Sonodynamic therapy has attracted much attention as a noninvasive treatment for deep infections. However, it is challenging to achieve high antibacterial activity for hydrogels under ultrasonic irradiation due to the relatively weak sono-catalysis capability of sonosensitizers. Herein, an ultrasound-responsive antibacterial hydrogel (Fe 3 O 4 /HA/Ber-LA) composed of Fe 3 O 4 -grafted-Berberine, chitosan molecules modified with L-arginine and poly (vinyl alcohol) is prepared for enhanced sonodynamic therapy and immunoregulation. The formation of heterojunction between berberine and Fe 3 O 4 with different work function promotes the charge separation and electron flow and disrupts the conjugated structure of berberine, causing a significant decrease in the band gap, eventually enhancing the sonocatalytic activity. The combination of berberine with Fe 3 O 4 also significantly improves the oxygen adsorption energy, enabling more O 2 molecules to react with the electron-rich regions on the surface of Fe 3 O 4 to generate more reactive oxygen species (ROS). L-arginine grafted in the hydrogel is catalyzed by the ROS to release nitric oxide, which not only possesses antibacterial activity, but also positively affects macrophage M1 polarization to display potent phagocytosis to Staphylococcus aureus, thus achieving immuno-sonodynamic therapy. Hence, Fe 3 O 4 /HA/Ber-LA hydrogel under ultrasound irradiation shows excellent antibacterial activity. Furthermore, the antioxidative activity and anti-inflammatory effect of berberine released from the hybrid hydrogel induces macrophages to polarize towards the anti-inflammatory M2 status as infection comes under control, thus accelerating the wound healing. The hybrid hydrogel based on the immuno-sonodynamic therapy may be an extraordinary candidate for the treatment of deep infections., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Ultrasound-Driven Radical Chain Reaction and Immunoregulation of Piezoelectric-Based Hybrid Coating for Treating Implant Infection”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n) and those carrying only p53 deletion (p53n). In culture, the BB-p53n OPCs display growth characteristics more similar to glioma cells than p53n OPCs. When injected in mouse brains, BB-p53n OPC form tumors, while the p53n OPCs do not. Unbiased histone proteomics and transcriptomic analysis on these OPC populations identified higher levels of the histone H3K27me3 mark and lower levels of the histone H4K20me3. The transcriptome of the BB-p53n OPCs was characterized by higher levels of transcripts related to proliferation and cell adhesion compared to p53n OPCs. Pharmacological inhibition of the enzyme responsible for histone H3K27 trimethylation (EZH2i) in BB-p53n OPCs, reduced cell cycle transcripts and increased the expression of differentiation markers, but was not sufficient to restore their growth characteristics. This suggests that PDGF-BB overexpression in p53n OPCs favors the early stages of transformation, by promoting proliferation and halting differentiation in a H3K27me3-dependent pathway, and favoring growth characteristics in a H3K27me3 independent manner., 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.)

Uncontrolled bleeding from incompressible or irregularly shaped wounds is a major factor in the death of people in the battlefield or surgery process. Ideal rapid hemostatic materials should have the performance of rapid hemostasis and at the same time can be applied to a variety of complex wound trauma types, in addition, excellent antimicrobial properties, adhesion, biocompatibility, degradation, and the non-toxicity of degradation products are also necessary, but there are fewer hemostatic materials that meet these requirements. Herein, we prepared an injectable hemostatic hydrogel based on the natural products sodium alginate (SA) and carboxymethyl chitosan (CMC). Oxidized sodium alginate (OSA) was prepared by the oxidation reaction of NaIO 4 with SA, and OSA with aldehyde group was mixed with CMC with amino group to rapidly form an in situ injectable hemostatic hydrogel (OSA/CMC) by the Schiff base reaction. OSA/CMC hydrogel exhibited excellent antimicrobial and adhesion properties by the Schiff base reaction. In addition, OSA/CMC hydrogel directly activate the endogenous coagulation pathway through the synergistic effect of OSA, CMC to enhance the hemostatic effect. The results of in vivo hemostasis study showed that OSA/CMC hydrogel significantly accelerated hemostasis and reduced blood loss in liver hemorrhage model and tail amputation model. Therefore, OSA/CMC hydrogel is expected to be a potential material in the direction of rapid clinical hemostasis due to its good adhesion properties, antimicrobial properties, biocompatibility, blood compatibility, and efficient rapid hemostasis., 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.)

Zinc (Zn) and selenium (Se) are beneficial elements for crops, enhancing crop quality and alleviating heavy metal toxicity. However, there is limited research on the role of foliar Zn and Se in the mechanism of reducing cadmium (Cd) uptake in crops. A field experiment was conducted to investigate the effect on subcellular distribution, leaf antioxidant enzyme activities, and the transcriptional regulation in the process of Cd accumulation of rice grains after foliar applications of Zn, Se, and their mixed solutions (ZnSe). The results show that Zn and ZnSe reduced Cd content in the grains of three different rice (13.9 %-21.8 %/11.9 %-29.5 %) by enhancing the fixation capacity of Cd in the flag leaf by improving the binding efficiency between pectin and Cd in the cell wall. Increased flag leaf antioxidant enzyme activities further mitigated the toxic effects of Cd on rice, while Zn and ZnSe treatments upregulated genes related to metal-binding proteins and antioxidant enzymes and downregulated metal transport genes. This study systematically elucidates the mechanisms by which foliar application of ZnSe alleviates Cd toxicity through the regulation of gene expression and physiological functions, providing a theoretical basis for reducing Cd accumulation in rice and ensuring the safe production of food., 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.)

A series of supramolecular deep eutectic solvents (SURPADESs) consisting of β-cyclodextrin (β-CDs) (β-CD, HP-β-CD, M-β-CD) and l-lactic acid were synthesized and employed as chiral selector to investigate their chiral selectivity in capillary electrophoresis. Key elements influencing the separation efficiency, such as the ratio of HBA/HBD of SUPRADESs, the concentration of SUPRADESs, and buffer pH were thoroughly examined and deliberated upon. Under the optimum enantioseparation conditions, three SUPRADESs systems showed markedly enhanced chiral separation of model chiral drugs, in comparison with single CDs and dual chiral selectors composed by adding its two constituents CDs and l-lactic acid separately. Additionally, the Benesi-Hildebrand plot was employed to determine the binding constant for the inclusion complexes, and molecular modeling was used to explore the mechanisms behind the increased chiral separations in SUPRADESs. Results demonstrated that SUPRADESs exhibit significantly improved chiral selectivity efficiency by enhancing the host-guest encapsulation of the constituent β-CDs, which is attributed to the increased hydrogen bonding and hydrophobic interactions between chiral analytes and β-CDs and HBD of SUPRADESs. This work provides a possibility for SUPRADESs to be used as chiral selection in CE., 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.)

Hemostatic powders are widely used in incompressible or irregularly shaped bleeding wounds, but traditional hemostatic powders exhibit low adhesion, unsatisfactory hemostatic effect, limited infection control, and are not suitable for clinical or emergency situations. This study developed a novel self-gelling hemostatic powder (QTPM) consisting of quaternized cellulose (QC)/ tannic acid (TA)/ polyethylene glycol (PEG)/ montmorillonite (MMT). QTPM could absorb interfacial liquid hydrating to a stable hydrogel which form a switchable adhesion to tissues. Moreover, QTPM exhibits excellent antibacterial property by the synergistic effect of QC and TA. Furthermore, QTPM directly activate intrinsic and extrinsic coagulation hemostatic pathways to enhance hemostasis, and it concentrate coagulation factors. In vivo hemostasis study results show that QTPM significantly accelerated hemostasis and reduced blood loss compared with the blank group (>75 % reduction in hemostatic time, >85 % reduction in blood loss) in liver bleeding model (hemostasis time of 71.67 ± 7.09 s, blood loss of 19.23 ± 2.60 mg) and tail amputation model (hemostasis time of 91.03 ± 12.05 s, blood loss of 15.24 ± 1.77 mg). Therefore, the advantages of QTPM including rapid and effective hemostasis, easy usage, easy storability and adaptability make it a potential biomaterial for rapid hemostasis direction in the clinical setting., 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.)

Hawthorn is rich in pectin, which is much higher than most cultivated fruits, but conventional extraction methods do not meet the requirements of low energy consumption and green production. Pectin in hawthorn is divided into soluble and insoluble parts, and with the ripening of hawthorn, the original pectin is converted into soluble pectin and pectic acid under the action of enzymes. Therefore, based on the characteristics of hawthorn pectin, this study sequentially extracted hawthorn pectin using water-soluble pectin (WSP) and hot acid-soluble pectin (HAP) method, verifying the feasibility of extracting hawthorn pectin with pure water at room temperature, and systematically analyzing and comparing the physicochemical properties and functional characteristics of the two methods. The combination of texture analysis and gel rheology revealed that WSP formed a more uniform and dense network structure during the gelation process. Additionally, microscopic observations and emulsification index results indicated that the emulsion prepared with WSP (WSE) had a smaller particle size and better stability. This indicates that hawthorn pectin is suitable for extraction with pure water at room temperature, which can maintain its good physical properties while reducing energy consumption, providing a new approach for the large-scale extraction of pectin in the food industry., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Actinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT)., Objective: This study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis., Methods: A total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group(LN-PDT)and control PDT group(C-PDT)with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups., Results: 3 months after the final treatment, the clearance rates for total AK lesions were 97.4%(449/461) in the LN-PDT group and 93.4%(456/488)in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2% (234/237) for the LN-PDT group and 98.3% (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5% (156/160) for the LN-PDT group and 91.9% (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5% (58/64) and 78.7% (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference., Conclusion: Liquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes., (Copyright © 2024. Published by Elsevier B.V.)

Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 μm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. Figures were created with biorender.com., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Periapical lesions (PLs) are common inflammatory diseases primarily caused by microbial infections within root canals. These infections trigger complex immune responses in periapical tissues, with B lymphocytes playing dual roles: defending against pathogens while also contributing to tissue damage. This highlights the crucial role of B cells in the immunological processes of PLs., Method: A comprehensive review of the literature on B cells in PLs was conducted using PubMed, Web of Science, Scopus, and ScienceDirect databases., Results: The review included 123 studies that examined the distribution and subtypes of B cells, their dual functions in PLs, and the potential applications of B-cell-related therapies in treating apical periodontitis., Conclusion: This review enhances our understanding of the complex immune mechanisms in PLs and aids in the development of new therapeutic approaches from a B-cell perspective., (Copyright © 2024. Published by Elsevier Inc.)

Cranial sutures function as growth centers for calvarial bones. Abnormal suture closure will cause permanent cranium deformities. MMP9 is a member of the gelatinases that degrades components of the extracellular matrix. MMP9 has been reported to regulate bone development and remodeling. However, the function of MMP9 in cranial suture development is still unknown. Here, we identified that the expression of Mmp9 was specifically elevated during fusion of posterior frontal (PF) suture compared with other patent sutures in mice. Interestingly, inhibition of MMP9 ex vivo or knockout of Mmp9 in mice (Mmp9 -/- ) disturbed the fusion of PF suture. Histological analysis showed that knockout of Mmp9 resulted in wider distance between osteogenic fronts, suppressed cell condensation and endocranial bone formation in PF suture. Proliferation, chondrogenesis and osteogenesis of suture cells were decreased in Mmp9 -/- mice, leading to the PF suture defects. Moreover, transcriptome analysis of PF suture revealed upregulated ribosome biogenesis and downregulated IGF signaling associated with abnormal closure of PF suture in Mmp9 -/- mice. Inhibition of the ribosome biogenesis partially rescued PF suture defects caused by Mmp9 knockout. Altogether, these results indicate that MMP9 is critical for the fusion of cranial sutures, thus suggesting MMP9 as a potential therapeutic target for cranial suture diseases., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024. Published by Elsevier B.V.)

Osteoarthritis (OA) is a joint disease involving all joint components, including cartilage, calcified cartilage, and subchondral bone. The repair of osteochondral defects remains a significant challenge in orthopedics. Development of new strategies is essential for effective osteochondral injury repair. In this study, gelatin (Gel), polyethylene glycol diglycidyl ether (PEGDGE), hydroxyethyl cellulose (HEC) and chitosan (CS) were used to prepare semi-IPNs and IPNs hydrogels. Mechanical properties of Gel based hydrogels significantly improved with the semi-IPN and IPN structures. Tensile strength ranges from 238.7 KPa to 479.5 KPa, and its compressive strength ranges from 35.6 KPa to 112.7 KPa. Additionally, the stress relaxation rate increased with higher CS concentrations, ranging from 25 % to 35 %. The network structure of Gel-based hydrogels was a key factor in regulating stress relaxation. Viscoelasticity was adjusted by its network structures. Swelling and degradation behaviors of Gel based hydrogels were systematically investigated. Gel based hydrogels had good cytocompatibility. Both semi-IPN and IPN structures Gel based hydrogels could promote cell spreading and osteogenic differentiation. G10HEC1 and G10CS1 hydrogels show promise as candidates for osteochondral tissue regeneration, offering a new strategy for osteochondral tissue engineering., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The synthesis of novel water-soluble polymers with biodegradability is an effective way to mitigate their negative environmental impacts. In this study, semi-aromatic copolyester poly(butylene succinate-co-butylene terephthalate) (PBST) with exceptional biodegradability is used as the resin matrix. Anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) is introduced as a fourth monomer to prepare random poly(butylene succinate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBSTS) copolyesters by melt copolymerization. The incorporation of ionic groups enhances the hydrophilicity and water absorption of the copolyesters, resulting in water-soluble materials that exhibit ionic and temperature responsivity. Furthermore, the ionized biodegradable copolyesters demonstrate distinct pH-dependent degradation, which is accelerated at pH = 5.5 and 8.5 but inhibited at pH = 7.2. Degradation assessments in simulated body fluids reveal that the PBSTS copolyesters exhibit significant degradation in gastric fluids at pH = 1.5 with minimal degradation in intestinal fluids at pH = 6.8 and in body fluids at pH = 7.0. This unique degradation performance highlights the potential of these materials for addressing the challenges associated with selective drug delivery and localized controlled release in the human body., 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.)

Peroxisome proliferator-activated receptor gamma coactivators 1β (PGC1β) is essential in mitochondrial oxidative phosphorylation and alternative macrophages activation. To determine the contribution of PGC1β in obesity induced inflammation, Ppargc1b (PGC1β coding gene) myeloid conditional knockout mice (cKO) were fed with high fat diet (HFD) to examine the following effects. We found that HFD-fed cKO mice gained more fat with increased serum triglyceride (TG), low density lipoprotein (LDL), adiponectin, and leptin. Adipogenesis was stimulated while lipolysis was retarded in HFD-fed cKO mice adipose. Gluconeogenesis, lipogenesis, and fatty acid uptake were provoked while lipolysis was inhibited in HFD-fed cKO liver. Serum alanine transaminase (ALT) level, indicating fatty liver, also increased. Inflammatory cytokine including tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 was elevated in cKO mice, accompanied with glucose intolerant and insulin resistance. Energy expenditure was decreased in HFD-fed cKO mice. Further evidence showed that cKO macrophages were prone to repolarize into M1 inflammatory type in vitro. In addition to mitochondrial biogenesis and oxidative respiration, PGC1β also modulated mitochondrial fission and cytosolic mitochondrial DNA (mtDNA) release, contributing to NLR family pyrin domain containing 3 (Nlrp3) inflammasome priming and activation. Treatment of mitochondrial fission inhibitor abolished the increased mRNA levels of Nlrp3 and IL-1β induced by PGC1β depletion. Nlrp3 knockdown restored the induced IL-1β mRNA expression by PGC1β deficiency. Myeloid PGC1β regulated adipocyte adipogenesis and lipolysis. PGC1β loss-of-function and mtDNA abundance correlated with obesity and diabetes. These observations uncovered the protective role of PGC1β against obesity induced systemic inflammation. Enhancing myeloid PGC1β function may be a potential strategy for the intervention of obesity and related diseases., Competing Interests: Declaration of competing interest All authors state that they have no conflicts of interest, and no AI was used in the writing., (Copyright © 2024. Published by Elsevier B.V.)