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The assessment of bone marrow iron stores is typically performed on an aspirate smear slide that has been manually stained by a technologist using a commercially available kit. This approach can contribute to inconsistent results and limit the broad use of iron staining in bone marrow specimens, particularly when laboratories have low staffing and/or high specimen volumes. Here, we describe the adaptation and validation of the Ventana Benchmark automated stainer and iron stain kit for routine clinical use of staining iron in bone marrow aspirate smear slides. We assessed accuracy and precision of the Ventana automated iron staining protocol compared to the Perls Prussian blue manual iron staining index method. Hematopathologists assigned Gale scores and enumerated the percentages of erythroid sideroblasts on paired patient bone marrow aspirate smear slides stained by the automated method and the manual iron staining method. We found a similar level of performance of the Ventana automated iron stain relative to the index manual method (as assessed by Pearson correlation and Bland-Altman analyses). In addition, there was low imprecision between replicates performed via the automated iron stain protocol. We also report superior qualitative findings of the automated method in ease of localization of iron storage, visualization of sideroblasts, and counterstain consistency. Automated iron staining of bone marrow aspirate smear slides performed similarly to the manual method and may allow for accurate routine evaluation of bone marrow iron stores as part of bone marrow analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption and metabolism of heavy metals. Gut microbiota plays a crucial role in heavy metal absorption, metabolism, and related processes. Toxic heavy metals (THMs), such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), can cause damage to multiple organs even at low levels of exposure, and it is crucial to emphasize their potential high toxicity. Nevertheless, certain essential trace elements, including iron (Fe), copper (Cu), and manganese (Mn), play vital roles in the biochemical and physiological functions of organisms at low concentrations but can exert toxic effects on the gut microbiota at higher levels. Some potentially essential micronutrients, such as chromium (Cr), silicon (Si), and nickel (Ni), which were considered to be intermediate in terms of their essentiality and toxicity, had different effects on the gut microbiota and their metabolites. Bidirectional relationships between heavy metals and gut microbiota have been found. Heavy metal exposure disrupts gut microbiota and influences its metabolism and physiological functions, potentially contributing to metabolic and other disorders. Furthermore, gut microbiota influences the absorption and metabolism of heavy metals by serving as a physical barrier against heavy metal absorption and modulating the pH, oxidative balance, and concentrations of detoxification enzymes or proteins involved in heavy metal metabolism. The interactions between heavy metals and gut microbiota might be positive or negative according to different valence states, concentrations, and forms of the same heavy metal. This paper reviews the metabolic interactions of 10 common heavy metals with the gut microbiota and their health implications. This collated information could provide novel insights into the disruption of the intestinal microbiota caused by heavy metals as a potential contributing factor to human diseases., 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 Zhu, Chen, Zhang, Zhang, Guo, Pang, Huang and Wang.)

Drawing upon construal level theory and regulatory fit literature, this research examined the effect of fit between humor and regulatory focus on audience engagement with health information on social media. The results of two studies showed that incongruity humor (vs. aggressive humor) induced greater social proximity between the source and the viewer, and humor type interacted with regulatory focus of a message to impact audience engagement. Specifically, incongruity humor paired with a prevention-focused message (vs. a promotion-focused message) resulted in greater content endorsement and health information engagement, whereas aggressive humor combined with a promotion-focused message (vs. a prevention-focused message) led to greater content endorsement. Results further identified processing fluency as a mediator of the fit effect on audience engagement. This research offers important theoretical and practical implications for public health interventions on social media.

Background: Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric disorders with overlapping symptoms, leading to high rates of misdiagnosis due to the lack of biomarkers for differentiation. This study aimed to identify metabolic biomarkers in urine samples for diagnosing MDD and BD, as well as to establish unbiased differential diagnostic models., Methods: We utilized a metabolomics approach employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to analyze the metabolic profiles of urine samples from individuals with MDD (n = 50), BD (n = 12), and healthy controls (n = 50). The identification of urine metabolites was verified using MS data analysis tools and online metabolite databases., Results: Two diagnostic panels consisting of a combination of metabolites and clinical indicators were identified-one for MDD and another for BD. The discriminative capacity of these panels was assessed using the area under the receiver operating characteristic (ROC) curve, yielding an area under the curve (AUC) of 0.9084 for MDD and an AUC value of 0.9017 for BD., Conclusions: High-resolution mass spectrometry-based assays show promise in identifying urinary biomarkers for depressive disorders. The combination of urine metabolites and clinical indicators is effective in differentiating healthy controls from individuals with MDD and BD. The metabolic pathway indicating oxidative stress is seen to significantly contribute to depressive disorders., Competing Interests: Declaration of competing interest The authors have nothing to disclose. The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Small-sized microplastics (MPs) pose greater ecological toxicity due to their larger surface area, which makes them more likely to act as carriers for other pollutants and to be ingested by aquatic organisms. However, traditional visual analysis often neglects small-sized MPs and their associated ecological risk. This study utilized Laser Direct Infrared (LDIR) spectroscopy and traditional visual analysis to examine MPs in 31 sediment samples from Jinzhou Bay, a typical semi-enclosed bay located at the economic center of Dalian, China. The results showed significant heterogeneity in MP distribution, with averages of 1192 and 2361 items/kg dry weight reported by visual analysis and LDIR spectroscopy, respectively. LDIR spectroscopy identified MPs as small as 10 μm, with the majority of MPs (89.21 %) within the 10-250 μm range, and a significant proportion (46.45 %) between 10 and 50 μm among them. However, visual analysis was limited to detecting MPs >50 μm, and significant portions were identified between 50 and 100 μm (49.36 %) and 100-250 μm (31.01 %), missing a substantial fraction of smaller MPs. The predominant polymers identified were polyamide (PA), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). LDIR spectroscopy demonstrated a strong positive correlation between MP abundance and clay content, a relationship not observed with traditional visual analysis. The Potential Ecological Risk Index (PERI) indicated that over 87 % of sites posed an extremely high risk according to LDIR spectroscopy, compared to 51 % by traditional visual analysis. These discrepancy underscores the underestimation of ecological risks by traditional methods, particularly for small-sized MPs. High-risk polymers such as polyvinyl chloride (PVC), ABS, and polyurethane (PUR) significantly influenced PERI values. These findings highlight the critical need for precise identification and thorough risk assessment of small-sized MPs in environmental studies and offer insights for understanding of MP vertical migration in aquatic environments, particularly in the context of co-settlement with sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In emergencies, uncontrolled severe bleeding can result in undesired complications and even death of the injured. Designing advanced hemostatic agents is a potential solution for emergency hemostasis, yet it remains challenging to realize the persistent adhesion in a wet wound environment. In this study, based on dynamic reversible Schiff base bond and photo-initiated double-bond polymerization, a novel injectable hemostatic hydrogel (L-COC) consisting of methacrylated carboxymethyl chitosan (CMCSMA), oxidized konjac glucomannan (OKGM) and (+)-catechin hydrate (CH) was synthesized for emergency hemostasis. To our delight, the incorporated CH imparted enhanced blood procoagulantion to the L-COC hydrogel by intensifying the hydrogel-red blood cell interactions. As a result, the hemostatic effect of the engineered L-COC hydrogel was significantly superior to that of fluid gelatin Surgiflo TM for liver bleeding wounds in rats (Blood loss: 0.62 ± 0.11 g (L-COC), 0.90 ± 0.08 g (Surgiflo TM ); hemostasis time: 69.0 ± 2.9 s (L-COC), 84.0 ± 2.2 s (Surgiflo TM )). With the favorable antioxidant and antibacterial activities, as well as multifunctional properties, the bio-adhesive L-COC hydrogel and the underlying design principles may facilitate further development of practical hemostatic hydrogels., 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.)

This work presents an innovative approach focusing on fine-tuning the coordination environment of atomically dispersed cobalt catalysts for tandem synthesis of primary benzylamines from oxidized lignin model compounds. By meticulously regulating the Co-N coordination environment, the activity of these catalysts in the hydrogenolysis and reductive amination reactions was effectively controlled. Notably, our study demonstrates that, in contrast to cobalt nanoparticle catalysts, atomically dispersed cobalt catalysts exhibit precise control of the sequence of hydrogenolysis and reductive amination reactions. Particularly, the CoN3 catalyst with a triple Co-N coordination number achieved a remarkable 94% yield in the synthesis of primary benzylamine. To our knowledge, there is no previous documentation of the synthesis of primary benzylamines from lignin dimer model compounds. Our study highlights a promising one-pot route for sustainable production of nitrogen-containing aromatic chemicals from lignin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Osteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify differentially expressed genes (DEGs) in OS and explore their role in the carcinogenesis and progression of OS., Methods: RNA sequencing was performed to identify DEGs in OS. The functions of the DEGs in OS were investigated using bioinformatics analysis, and DEG expression was verified using RT-qPCR and Western blotting. The role of SLC25A4 was evaluated using gene set enrichment analysis (GSEA) and then investigated using functional assays in OS cells., Results: In all, 8353 DEGs were screened. GO and KEGG enrichment analyses indicated these DEGs showed strong enrichment in the calcium signaling pathway and pathways in cancer. Moreover, the Kaplan-Meier survival analysis showed ten hub genes were related to the outcomes of OS patients. Both SLC25A4 transcript and protein expression were significantly reduced in OS, and GSEA suggested that SLC25A4 was associated with cell cycle, apoptosis and inflammation. SLC25A4 -overexpressing OS cells exhibited suppressed proliferation, migration, invasion and enhanced apoptosis., Conclusion: SLC25A4 was found to be significantly downregulated in OS patients, which was associated with poor prognosis. Modulation of SLC25A4 expression levels may be beneficial in OS treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wang, Zhang, Feng, Xing, Wang, Huang, Li and Zhang.)

N 4 -acetylcytidine (ac 4 C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac 4 C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac 4 C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac 4 C level of tRNA Ser-CGA-1-1 . Mutagenesis at the ac 4 C site in tRNA Ser-CGA-1-1 inhibited its ac 4 C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNA Ser-CGA-1-1 ac 4 C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac 4 C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases., (© 2024. The Author(s).)

Background: Given the significant burden of upper digestive diseases, there has been a substantial increase in the utilization of esophagogastroduodenoscopy (EGD) in China from 2012 to 2019. The objective of this study is to investigate the development, practice, and factors influencing the widespread use of EGD during this period., Methods: Two national censuses were conducted among all hospitals in mainland China that perform gastrointestinal endoscopy. These censuses aimed to extract information on the infrastructure, volume, and quality of EGD. The analysis of potential factors influencing EGD practice was based on real-world data from open access sources., Results: From 2012 to 2019, the number of hospitals performing EGD in mainland China increased from 1,518 to 2,265 (1.49-fold) in tertiary hospitals and from 3,633 to 4,097 (1.12-fold) in secondary hospitals, respectively. The national utilization rate of EGD also increased from 1,643.53 to 2,018.06 per 100,000 inhabitants, indicating a 1.23-fold increase. Regions with more endoscopists per 100,000 inhabitants (OR 9.61, P <0.001), more tertiary hospitals performing EGD per million inhabitants (OR 2.43, P <0.001), higher incidence of esophageal and gastric cancer (OR 2.09, P =0 016), and higher number of hospitals performing EGD per million inhabitants (OR 1.77, P =0.01) tended to provided more numerous and qualitied EGD. And hospital grading, regional GDP, incidence of esophageal and gastric cancer and the volume of EGD were observed as the significantly relevant factors of malignant dictation rate (MDR) ( P <0.05), but not the number and educational background of endoscopists., Conclusion: Over the past seven years, China has made significant progress in EGD. However, challenges persist in terms of quality and inequality., 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 Zhou, Chen, Jiao, Cheng, Gao, Wang, Xin, Wan and Wang.)

Women experiencing postpartum depression (PPD) often face the debilitating symptoms of depression as well as the stigmatization associated with having a mental health crisis during motherhood. Accordingly, there have been numerous calls for theoretical-based approaches to reduce the stigma and promote social support for women with PPD. Guided by stigma research, anthropomorphism literature, and attribution theory, this research explored the effect of PPD anthropomorphism (i.e., imbuing humanlike intentions and characteristics to PPD) on perceived controllability, sympathy, anger toward PPD, and willingness to provide social support (WPSS). Results of three studies revealed that humanizing PPD led to decreased perceived controllability attributed to women with PPD, resulting in increased sympathy, more anger toward PPD, and consequently, greater WPSS. This research contributes to the extant health communication literature, particularly in the realm of mental health stigma, by addressing how humanizing risk-bearing entities affects individuals' mental health related perceptions and decisions.

Supercritical CO 2 has wide application in enhancing oil recovery, but the low viscosity of liquid CO 2 can lead to issues such as poor proppant-carrying ability and high filtration loss. Therefore, the addition of thickening agents to CO 2 is vital. Hydrocarbon polymers, as a class of green and sustainable materials, hold tremendous potential for acting as thickeners in supercritical CO 2 systems, and PVAc is one of the best-performing hydrocarbon thickeners. To further improve the viscosity enhancement and solubility of PVAc, here we designed a novel polymer structure, PVAO, by introducing CO 2 -affine functional groups to PVAc. Molecular dynamics simulations were adopted to analyze viscosity and relevant solubility parameters systematically. We found that PVAO exhibits superior performance, with a viscosity enhancement of 1.5 times that of PVAc in supercritical CO 2 . While in the meantime, PVAO maintains better solubility characteristics than PVAc. Our findings offer insights for the future design of other high-performance polymers.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China., Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China., Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita ( P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers., Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (© 2024 Yunfei Jiao, Zhiyuan Cheng, Ye Gao, Tianjiao Wang, Lei Xin, Han Lin, Mengxi Cai, Xudong Ma, Zhaoshen Li, Luowei Wang, published by De Gruyter on behalf of Scholar Media Publishing.)

T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across North America and Europe. While HLA-A∗02:01 was the most frequent HLA-A∗02 allele, others (A∗02:02, A∗02:03, A∗02:06) considerably increased HLA eligibility in Hispanic, Black, and Asian populations. Overall, MAGE-A4 prevalence based on clinical trial enrollment was 26% (447/1,750) across 10 solid tumor types, and was highest in synovial sarcoma (70%) and lowest in gastric cancer (9%). The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies., Competing Interests: T.W., J.-M.N., S.R., C.K., M.C., R.B., K.H., A.L., A.C., R.W., L.Q., J.P.S., C.M., F.B., E.E., P.B., and D.W. are or were employees of Adaptimmune at the time of the study and may own stock/stock options in Adaptimmune. M.V.K., S.V.R., K.S., and K.A. are employees of CellCarta NV, Antwerp, Belgium, and were involved in the development and validation of the MAGE-A4 IHC assay. G.B.J. received consulting fees from AbbVie, Daiichi Sankyo, Eli Lilly, Genzyme, Gilead, Merck Sharp & Dohme, Novartis, Regeneron; expenses from Regeneron; research funding from AstraZeneca, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Exelixis, Genentech, Incyte, Merck Sharp & Dohme, Novartis, Regeneron. M.O.B. received grant support from Merck, Takara Bio; quality improvement support from Novartis; is on the advisory board of Adaptimmune, Bristol Myers Squibb, GlaxoSmithKline, IDEAYA, Instil Bio, Iovance, La Roche Possey, Medison, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma; oral presentations given for Bristol Myers Squibb, Merck, Novartis, Pfizer, Sanofi. J.M.C. received grant/research support from AbbVie, Adaptimmune, Array, AstraZeneca, Bayer, Bristol Myers Squibb, CBMG, Genentech, GlaxoSmithKline, Grid Therapeutics, Medpacto, Moderna, Spectrum; consultant for Amgen, Corbus, G1 Therapeutics, Novartis, Omega, Sanofi, Turning Point, Vivacitas; speaker’s bureau for AstraZeneca. J.F.G. was compensated consultant or received honoraria from AI Proteins, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Curie Therapeutics, Genentech/Roche, Gilead, iTeos, Jounce, Karyopharm, Loxo/Lilly, Merck, Merus Pharmacueticals, Mirati, Moderna, Novartis, Novocure, Nuvalent, Pfizer, Silverback Therapeutics, Takeda; research support from Genentech/Roche, Novartis, Takeda; institutional research support from Adaptimmune, Alexo, Array Biopharma, Bristol Myers Squibb, Blueprint Medicines, Jounce, Merck, Moderna, Novartis, Palleon, Tesaro; equity in AI Proteins; and has an immediate family member who is an employee with equity at Ironwood Pharmaceuticals. V.M. received consulting fees from Affimed, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Roche, Syneos; was principal investigator – institutional funding from AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BioInvent International AB, Bristol Myers Squibb, Boehringer, Boston, Celgene, Daichii Sankyo, DEBIOPHARM, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GlaxoSmithKline, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. M.J. received research funding (institutional) from AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics; had a consulting/advisory role (institutional) for AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Black Diamond, Boehringer Ingelheim, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, Gilead Sciences, GlaxoSmithKline, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Normunity, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics. D.S.H. received travel, accommodations, expenses from AACR, ASCO, CLCC, Bayer, Genmab, SITC, Telperian; had consulting, speaker, or advisory role with 28Bio, AbbVie, Acuta, Adaptimmune, Alkermes, Alpha Insights, Amgen, Affini-T, Astellas, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, CARSgen, CLCC, COG, COR2ed, Cowen, EcoR1, Erasca, Fate Therapeutics, F. Hoffmann-La Roche, Genentech, Gennao Bio, Gilead, GLG, Group H, Guidepoint, HCW Precision Oncology, Immunogenesis, InduPro, Janssen, Liberium, MedaCorp, Medscape, Numab, Oncologia Brasil, ORI Capital, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, Projects in Knowledge, Quanta, RAIN, Ridgeline, SeaGen, Stanford, STCube, Takeda, Tavistock, Trieza Therapeutics, Turning Point Therapeutics, WebMD, YingLing Pharma, Ziopharm; has other ownership interests in Molecular Match (advisor), OncoResponse (founder, advisor), Telperian (founder, advisor); received institutional research/grant funding from AbbVie, Adaptimmune, Adlai-Nortye, Amgen, AstraZeneca, Bayer, Biomea, Bristol Myers Squibb, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Erasca, F. Hoffmann-La Roche, Fate Therapeutics, Genentech, Genmab, Immunogenesis, Infinity, Kyowa Kirin, Merck, Mirati, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, Revolution Medicine, SeaGen, STCube, Takeda, TCR2, Turning Point Therapeutics, VM Oncology., (© 2024 The Authors.)

Objective: Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence-associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi-omics approach and to establish diagnostic assays for AD., Methods: This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high-resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K-nearest neighbors (KNN) algorithm was utilized to construct a multi-dimensional model for distinguishing AD from CN., Results: Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C-reactive protein (CRP), fibronectin (FN1), and serum amyloid A-1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN-based three-dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD., Interpretation: The multi-omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging-associated pathophysiology., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Ramie bone (RB), an agricultural waste generated in the textile industry, is a vastly productive renewable natural resource with the potential to be used as a source of cellulose. In this study, ramie bone cellulose (RB-CE) was obtained in one step using a simple and ecologically friendly hydrogen peroxide-citric acid (HPCA) treatment procedure that avoided the use of halogenated reagents and strong acids while also streamlining the treatment processes. Various analytical methods were used to investigate the chemical composition and structure, crystallinity, morphology, thermal properties, surface area and hydration properties of cellulose separated at different treatment temperatures. HPCA successfully removed lignin and hemicellulose from RB, according to chemical composition analysis and FTIR. RB-CE had a type I cellulose crystal structure, and the crystallinity improved with increasing treatment temperature, reaching 72.51 % for RB-CE90. The RB-CE showed good thermal stability with degradation temperatures ranging from 294.2 °C to 319.1 °C. Furthermore, RB-CE had a high water/oil binding capacity, with RB-CE90 having WHC and OBC of 9.68 g/g and 7.24 g/g, respectively. The current work serves as a model for the environmentally friendly and convenient extraction of cellulose from biomass, and the cellulose obtained can be employed in the field of food and composite materials., 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma., Methods: Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale., Results: There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05)., Conclusion: In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.)

Background: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma., Methods: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma (confirmed by cytogenetics) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 10 9 -10·0 × 10 9 T cells) after lymphodepletion. The primary endpoint was overall response rate in cohort 1, assessed by a masked independent review committee using Response Evaluation Criteria in Solid Tumours (version 1.1) in the modified intention-to-treat population (all patients who received afami-cel). Adverse events, including those of special interest (cytokine release syndrome, prolonged cytopenia, and neurotoxicity), were monitored and are reported for the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04044768; recruitment is closed and follow-up is ongoing for cohorts 1 and 2, and recruitment is open for cohort 3., Findings: Between Dec 17, 2019, and July 27, 2021, 52 patients with cytogenetically confirmed synovial sarcoma (n=44) and myxoid round cell liposarcoma (n=8) were enrolled and received afami-cel in cohort 1. Patients were heavily pre-treated (median three [IQR two to four] previous lines of systemic therapy). Median follow-up time was 32·6 months (IQR 29·4-36·1). Overall response rate was 37% (19 of 52; 95% CI 24-51) overall, 39% (17 of 44; 24-55) for patients with synovial sarcoma, and 25% (two of eight; 3-65) for patients with myxoid round cell liposarcoma. Cytokine release syndrome occurred in 37 (71%) of 52 of patients (one grade 3 event). Cytopenias were the most common grade 3 or worse adverse events (lymphopenia in 50 [96%], neutropenia 44 [85%], leukopenia 42 [81%] of 52 patients). No treatment-related deaths occurred., Interpretation: Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies., Funding: Adaptimmune., Competing Interests: Declaration of interests EC reports participation in an advisory board for Adaptimmune; and research support paid to their institution for clinical trial activities from Adaptimmune, Novartis, Tracon, Boehringer Ingelheim, Merck, Bayer, Amgen, and Mirati. J-YB reports grants paid to institution from Netsarc+ and Euracan; and research support and honoraria from Adaptimmune and GSK. FT reports research support paid to institution for clinical trial activities from Adaptimmune, Achilles Therapeutics, T-knife Therapeutics, GSK, Immunocore, and Instil Bio; consulting fees from T-knife Therapeutics; speaker fees from Kite and Royal Marsden Hospital Cell Therapy Preceptorship; travel or meeting support from Kite; advisory board fees from Immatics, Bristol Myers Squibb (BMS), GSK, Janssen, Leucid, and Scenic Biotech; institutional advisory board fees from Pfizer; and is an unpaid panel member with Sarcoma UK, Cancer Research UK New Agents Committee, and the Medical Research Council Developmental pathway funding scheme. MA reports institutional support from Exelixis; consulting fees from Boehringer Ingelheim and Aadi; and honoraria from Regeneron, Deciphera, and Bayer. EF reports honoraria from Novartis, Alexion, Astellas, GSK, Gilead, and Sanofi; and travel or meeting support from Novartis, Alexion, Gilead, Sanofi, MSD, and Neovii. SJS reports consulting fees from Ceridwen Oncology; honoraria from Boehringer Ingelheim; travel or meeting support from Adaptimmune; and participated on advisory or data safety monitoring boards for GSK and Inhibrx. ARAR reports support from Adaptimmune, AbbVie, Amgen, Blueprint Medicines, BMS, Daiichi Sankyo, Deciphera Pharmaceuticals, GSK, Iterion Therapeutics, Karyopharm Therpaeutics, MedImmune, Merck, Neoleuki Therapeutics, Pfizer, Rain Therapeutics, Roche/Genentech, and Symphogen; honoraria from Medison; and participated on advisory or data safety monitoring boards for Adaptimmune, Bayer, GSK, Inhibrx, and Medison. SMS reports institutional support from Adaptimmune, Boehringer Ingelheim, GSK, Rain Oncology, Shanghai Pharma, and TRACON; royalties or licenses from UpToDate; participated on an advisory or data safety monitoring board for Bioatla; and is an unpaid National Comprehensive Cancer Network Soft Tissue Sarcoma committee member. CMVM reports institutional support from Adaptimmune; consulting fees from Deciphera; honoraria from Bayer; travel or meeting support from PharmaMar; and participation on advisory or data safety monitoring boards for PharmaMar, Bayer, and Boehringer Ingelheim. MJW reports consulting fees from Adaptimmune, Deciphera, Aadi, Epizyme, and PharmaEssentia. JG reports support from Adaptimmune for this study. VM reports consulting fees from Roche, Bayer, Pieris, BMS, Janssen, Basilea, Regeneron/Sanofi, and Nanobiotix; and institutional support from AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BioInvent International, BMS, Boehringer Ingelheim, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Therapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millenium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, PharmaMar, Pricipia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, and Upsher-Smith. LH, TW, JB, AS, LF, EVW, EN, DW, RW, J-MN, SR, and EE are employees of, and have stock options in, Adaptimmune. SB, CM, and CL were employees of Adaptimmune at the time of the study. VLK reports institutional support from Adaptimmune, Deciphera, Plexxikon, Advenchen, Boehringer Ingelheim, and TRACON; consulting fees from Epizyme; and honoraria from Deciphera. WDT reports institutional support from Adaptimmune; consulting and travel fees from Eli Lilly; consulting fees from C4 Therapeutics, Daiichi Sankyo, Deciphera, Adcendo, Ayala Pharmaceuticals, Kowa, Servier, Bayer Pharmaceuticals, Epizyme, Cogent, Medpacto, Foghorn Therapeutics, Amgen, AmMax Bio, Boehringer Ingelheim, BioAtla, Inhibrx, PharmaEssentia, Avacta, Ipsen, Sonata, Curadev, Nuvation Bio, and Abbisko; has patents pending for companion diagnostics with Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center (New York, NY, USA); is on advisory boards of Innova Therapeutics and the Osteosarcoma Institute; is on the advisory board and holds stock in Certis Oncology Solutions; and is a co-founder and has stock in Atropos Therapeutics. JAC reports consulting fees from Adaptimmune and Deciphera; and honoraria from Adaptimmune. BAVT reports a research grant from Polaris; royalties or licenses from Accuronix Therapeutics; consulting fees from Bayer, Deciphera, GIST Expert Interview Project, Daiichi Sankyo, EcoR1, Advenchen, Putnam, Salarius Pharmaceuticals, Boxer Capital, Acuta Capital Partners, Aadi, Race Oncology, Hinge Bio, Kronos Bio, and Sonata Therapeutics; honoraria from Total Health Conference and Iterion Therapeutics; travel or meeting support from Adaptimmune, Kronos Bio, Advenchen Laboratories, and Polaris; has a patent with Accuronix Therapeutics; participated in advisory boards for Apexigen, Daiichi Sankyo, Epizyme, Bayer, PTC Therapeutics, Aadi Biosciences, Boehringer Ingelheim, Agenus, Regeneron Pharmaceuticals, Exp, Advenchen, EcoR1 Capital, Curis, and Inhibrx; and is a board member for Polaris. GDD reports institutional support from Adaptimmune, Bayer, Novartis, PharmaMar, and Daiichi-Sankyo; is a co-founder and scientific advisory board member with minor equity holding in IDRx; is a consultant or scientific advisory board member with minor equity holding in G1 Therapeutics, Caris Life Sciences, Erasca Pharmaceuticals, RELAY Therapeutics, Bessor Pharmaceuticals, CellCarta, Ikena Oncology, Kojin Therapeutics, Aadi Biosciences, Acrivon Therapeutics, Blueprint Medicines, Tessellate Bio, and Boundless Bio; and is a scientific consultant for EMD-Serono/Merck KGaA, WCG/Arsenal Capital, Rain Therapeutics, and Minghui Pharmaceuticals. SPD'A reports institutional support from Adaptimmune for this study; grants, contracts, consulting fees, and honoraria from EMD Serono, Amgen, Nektar, Immune Design, GlaxoSmithKline, Incyte, Merck, Adaptimmune, Immunocore, Pfizer, Servier, Rain Therapeutics, GI Innovations, and Aadi Biosciences; travel support from Adaptimmune, EMD Serono, and Nektar; participation on advisory boards for GlaxoSmithKline, Nektar, Adaptimmune, and Merck; and a leadership or fiduciary role at the Connective Tissue Oncology Society in 2023–24. SA reports institutional support from Adaptimmune for this study; and institutional support from TRACON Pharma, Ayala Pharmaceuticals, Cogent Biosciences, InhibRx, Rain Therapeutics, Trillium Therapeutics, Boehringer Ingelheim, Salarius Pharmaceuticals, Theseus Pharmaceuticals, Monopar Therapeutics, C4 Therapeutics, Noxopharm, Jazz Pharmaceuticals, Shanghai Pharma, and PharmaMar. KNG reports participation in advisory boards for Adaptimmune, Daiichi Sankyo, Boehringer Ingelheim, and Deciphera. MD reports consultancy fees and advisory board fees from Deciphera, Aadi Bioscience, and Daiichi Sankyo. BAW reports consultancy fees from Springworks, Deciphera, Epizyme, Adcendo, Polaris, Boehringer Ingelheim, and AADi, research funding from Exelixis, and travel support from Agenus. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ammonia (NH 3 ) is pivotal in modern industry and represents a promising next-generation carbon-free energy carrier. Electrocatalytic nitrate reduction reaction (eNO 3 RR) presents viable solutions for NH 3 production and removal of ambient nitrate pollutants. However, the development of eNO 3 RR is hindered by lacking the efficient electrocatalysts. To address this challenge, we synthesized a series of macrocyclic molecular catalysts for the heterogeneous eNO 3 RR. These materials possess different coordination environments around metal centers by surrounding subunits. Consequently, electronic structures of the active centers can be altered, enabling tunable activity towards eNO 3 RR. Our investigation reveals that metal center with an N 2 (pyrrole)-N 2 (pyridine) configuration demonstrates superior activity over the others and achieves a high NH 3 Faradaic efficiency (FE) of over 90 % within the tested range, where the highest FE of approximately 94 % is obtained. Furthermore, it achieves a production rate of 11.28 mg mg cat -1  h -1 , and a turnover frequency of up to 3.28 s -1 . Further tests disclose that these molecular catalysts with diverse coordination environments showed different magnetic moments. Theoretical calculation results indicate that variated coordination environments can result in a d-band center variation which eventually affects rate-determining step energy and calculated magnetic moments, thus establishing a correlation between electronic structure, experimental activity, and computational parameters., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-N x sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-N x sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry., (© 2024. The Author(s).)

Objective: Accumulating evidence from microbial studies have highlighted the modulatory roles of intestinal microbes in numerous human diseases, however, the shared microbial signatures across different diseases remain relatively unclear., Methods: To consolidate existing knowledge across multiple studies, we performed meta-analyses of 17 disease types, covering 34 case-control datasets of 16S rRNA sequencing data, to identify shared alterations among different diseases. Furthermore, the impact of a microbial species, Lactobacillus salivarius, was established in a dextran sodium sulphate-induced colitis model and a collagen type II-induced arthritis mouse model., Results: Microbial alterations among autoimmune diseases were substantially more consistent compared with that of other diseases (cancer, metabolic disease and nervous system disease), with microbial signatures exhibiting notable discriminative power for disease prediction. Autoimmune diseases were characterized by the enrichment of Enterococcus, Veillonella, Streptococcus and Lactobacillus and the depletion of Ruminococcus, Gemmiger, Oscillibacter, Faecalibacterium, Lachnospiracea incertae sedis, Anaerostipes, Coprococcus, Alistipes, Roseburia, Bilophila, Barnesiella, Dorea, Ruminococcus2, Butyricicoccus, Phascolarctobacterium, Parabacteroides and Odoribacter, among others. Functional investigation of L. salivarius, whose genus was commonly enriched in numerous autoimmune diseases, demonstrated protective roles in two separate inflammatory mouse models., Conclusion: Our study highlights a strong link between autoimmune diseases and the gut microbiota, with notably consistent microbial alterations compared with that of other diseases, indicating that therapeutic strategies that target the gut microbiome may be transferable across different autoimmune diseases. Functional validation of L. salivarius highlighted that bacterial genera associated with disease may not always be antagonistic, but may represent protective or adaptive responses to disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

This study aims to assess the role of methotrexate-related gene polymorphisms in children with acute lymphoblastic leukemia (ALL) during high-dose methotrexate (HD-MTX) therapy and to explore their effects on serum metabolites before and after HD-MTX treatment. The MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435C>T, and GSTP1 313A>G genotypes of 189 children with ALL who received chemotherapy with the CCCG-ALL-2020 regimen from January 2020 to April 2023 were analyzed, and toxic effects were reported according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Fasting peripheral blood serum samples were collected from 27 children before and after HD-MTX treatment, and plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The results of univariate and multivariate analyses showed that MTHFR 677C>T and ABCB1 3435 C>T gene polymorphisms were associated with the delayed MTX clearance (P < 0.05) and lower platelet count after treatment in children with MTHFR 677 mutation compared with wild-type ones (P < 0.05), and pure mutations in ABCB1 3435 were associated with higher serum creatinine levels (P < 0.05). No significant association was identified between MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435 C>T, and GSTP1 313A>G genes and hepatotoxicity or nephrotoxicity (P > 0.05). However, the serum metabolomic analysis indicated that the presence of the MTHFR 677C > T gene polymorphism could potentially contribute to delayed MTX clearance by influencing L-phenylalanine metabolism, leading to the occurrence of related toxic side effects., Conclusion: MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene., Trial Registration: This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/ )., What Is Known: • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear., What Is New: • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Localized scleroderma (LoS) is an autoimmune disease in which craniofacial lesions can cause severe facial deformities with brain involvement. Objective evaluation of craniofacial LoS is challenging. Magnetic resonance imaging (MRI) may be used as a damage assessment tool. This study aimed to analyze the tissue involvement of craniofacial LoS based on MRI and evaluate MRI for craniofacial LoS assessment., Methods: This cross-sectional study included patients with craniofacial LoS from September 2021 to August 2022 in Peking Union Medical College Hospital. Patients who were clinically assessed in a stable phase were enrolled; patients with previous surgical treatment or contraindications to MRI were excluded. Participants underwent clinical, MRI, and ultrasound assessments. MRI was compared with ultrasound by correlation analysis and Bland-Altman analysis. The involvement of different tissues and different facial subunits was compared. The accumulated soft tissue atrophy index (ASTAI) was compared with clinical scores by correlation analysis., Results: A total of 28 patients were included (13 female; mean age, 18 years). MRI showed a good correlation and agreement with ultrasound (r=0.916, P<0.001). In different facial subunits, a significant negative correlation between the forehead and chin was found (r=-0.593, P=0.001). The ASTAI correlated well with the facial LoS damage index (r=0.580, P=0.001) and the Peking Union Medical College LoS facial aesthetic index (PUMC LoSFAI) (r=0.921, P<0.001). A total of 38.6% of clinical scores were inaccurate based on MRI. Neurological changes were found in one patient., Conclusions: MRI can reliably quantify damage in craniofacial LoS, and may serve as a useful and objective tool for overall craniofacial LoS evaluation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-980/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: High-intensity interval training (HIIT) has been shown to enhance cardiovascular health. However, there is a lack of research investigating the specific cardiovascular effects of different HIIT training modes. Therefore, this study aimed to compare the acute effects of cycling-type high intensity interval training (C-HIIT) and resistance-type high intensity interval training (R-HIIT) on arterial stiffness, cardiac autonomic modulation, and cardiac biomarkers in healthy young men., Methods: This is a cross-over randomized trial. Eleven healthy active young men took part in both C-HIIT and R-HIIT. Cardio-ankle vascular index (CAVI), heart rate variability (HRV), and systolic blood pressure (SBP) were measured before, immediately and 30 min after the exercise in C-HIIT and R-HIIT. Meanwhile, blood samples for cardiac troponin-T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) were assessed using ELISA before, 5min and 35min after exercise., Results: There was a significant time × group interaction effect (P = 0.019, η p 2  = 0.182) and time main effect for ⊿CAVI (P < 0.001, η p 2  = 0.729), and R-HIIT resulted in a more significant reduction in ⊿CAVI compared to C-HIIT (- 0.60 ± 0.30, P = 0.043, d = 0.924) immediately after exercise. There was a significant time main effect was observed for SBP (P = 0.001, η p 2  = 0.304). A significant time main effect for lnHF (P < 0.001, η p 2  = 0.782), lnRMSSD (P < 0.001, η p 2  = 0.693), and LF/HF (P = 0.001, η p 2  = 0.302) of HRV was observed. A significant time main effect was observed for cTnT (P = 0.023, η p 2  = 0.193) and NT-proBNP (P = 0.001, η p 2  = 0.334) of cardiac biomarkers., Conclusion: R-HIIT and C-HIIT elicited similar acute responses in cardiac autonomic modulation and cardiac biomarkers. However, R-HIIT was more effective in reducing arterial stiffness in healthy young men. Furthermore, the increase in cardiac biomarkers induced by both C-HIIT and R-HIIT was reversible., Trial Registration: The study was prospectively registered on 22 February 2022 at www.chictr.org.cn with identification number ChiCTR2200056897., (© 2024. The Author(s).)

To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI < 13; and Group B, OSDI ≥ 13. The OSDI scores, tear meniscus height (TMH), first non-invasive tear film break-up time (NIBUT-First), and meibomian gland loss (MGL, %) were recorded at postoperative 1 -week and 1-month.113 eyes (57 patients) were enrolled, 70 eyes in Group A, and 43 eyes in Group B. In Group A, the OSDI scores significantly increased at 1-week and 1-month postoperative (all P < 0.001); the TMH, NIBUT-First and lipid layer grade significantly decreased at postoperative 1-week (P = 0.003, 0.005, 0.007, 0.004, respectively), but returned to preoperative level at 1-month postoperative. In Group B, only the lipid layer grade significantly decreased at postoperative 1-week (P < 0.05). Patients with different preoperative OSDI scores may experience different changes early after SMILE surgery. Patients with OSDI scores < 13 may experience more dramatic changes in dry eye symptoms which would resolve, while subjective complains could still exists at 1 month after surgery., (© 2024. The Author(s).)

Hydrogen peroxide combined with acid treatment demonstrates its respective characteristics for the separation of lignocellulosic biomass. Herein, holocellulose was extracted from Cattail leaves (CL) by a two-step treatment with alkali and hydrogen peroxide-acetic acid (HPAA). Then carboxylated nanocellulose was hydrolyzed with a mixed organic/inorganic acid. The chemical composition of the holocellulose and the physicochemical properties of the separated carboxylated nanocellulose were comparable. Carboxyl groups were introduced on the nanocellulose as a result of the esterification process with citric acid (CA), which endows the nanocellulose with high thermal stability (315-318 °C) and good light transmission (>80 %). Furthermore, morphological analyses revealed that nanocellulose had a spider-web-like structure with diameter between 5 and 20 nm., 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The measurement of hemoglobin is a vital index for diagnosing and monitoring diseases in clinical practice. At present, solutions need to be found for the soreness, high risk of infection, and inconvenient operation associated with invasive detection methods. This paper proposes a method for non-invasively detecting hemoglobin levels based on multi-wavelength photoplethysmography (PPG) signals. AFE4490 and TMUX1109 were used to implement the low-cost collection of an eight-LED transmissive PPG signal. We used seven regular LEDs and one broadband LED (Osram SFH4737) as light sources. Additionally, a finger clip integrating multiple sensors was designed and manufactured via 3D printing to simultaneously monitor the LED-sensor distance and the pressure from the tester's finger during PPG signal acquisition. We used a method to extract features from PPG signals using a sliding-window's variance and an evaluation metric for PPG signals based on the AdaCost classification. Data were gathered from 56 participants from the Nephrology department, including 16 anemic patients. Pearson correlation analysis was conducted on the collected data to remove any data with a weak correlation. The advantage of using a broadband LED as a light source was also demonstrated. Several non-invasive hemoglobin regression models were created by applying AdaBoost, BPNN, and Random Forest models. The study's results indicate that the AdaBoost model produced the best performance, with a mean absolute error (MAE) of 2.67 g/L and a correlation coefficient (R 2 ) of 0.91 The study results show that the device we designed and manufactured can achieve effective non-invasive hemoglobin detection and represents a new methodological approach to obtaining measurements that can be applied in a clinical setting.

Background: This study seeks to assess the utility of T1 and T2 mapping in distinguishing metastatic lymph nodes from reactive lymphadenopathy in patients with head and neck squamous cell carcinoma (HNSCC), using diffusion-weighted imaging (DWI) as a comparison., Methods: Between July 2017 and November 2019, 46 HNSCC patients underwent neck MRI inclusive of T1 and T2 mapping and DWI. Quantitative measurements derived from preoperative T1 and T2 mapping and DWI of metastatic and non-metastatic lymph nodes were compared using independent samples t-test or Mann-Whitney U test. Receiver operating characteristic curves and the DeLong test were employed to determine the most effective diagnostic methodology., Results: We examined a total of 122 lymph nodes, 45 (36.9%) of which were metastatic proven by pathology. Mean T2 values for metastatic lymph nodes were significantly lower than those for benign lymph nodes (p < 0.001). Conversely, metastatic lymph nodes exhibited significantly higher apparent diffusion coefficient (ADC) and standard deviation of T1 values (T1 SD ) (p < 0.001). T2 generated a significantly higher area under the curve (AUC) of 0.890 (0.826-0.954) compared to T1 SD (0.711 [0.613-0.809]) and ADC (0.660 [0.562-0.758]) (p = 0.007 and p < 0.001). Combining T2, T1 SD , ADC, and lymph node size achieved an AUC of 0.929 (0.875-0.983), which did not significantly enhance diagnostic performance over using T2 alone (p = 0.089)., Conclusions: The application of T1 and T2 mapping is feasible in differentiating metastatic from non-metastatic lymph nodes in HNSCC and can improve diagnostic efficacy compared to DWI., (© 2023. The Author(s).)

Purpose: This study aimed to compare the effects on muscle hypertrophy and muscular performance of two resistance training (RT) programs that differed only in set structure: traditional set structure (TS) vs. rest redistribution set structure (RR). Methods: Thirty untrained young men were pair-matched and randomly assigned to a TS ( n = 15) or an RR ( n = 15) protocol based on individual baseline measures. Participants trained for 8 weeks using the same total body RT routines performed twice weekly. The TS protocol comprised four sets of 10 repetitions per exercise with 120-s interset rest, and the RR involved eight sets of five repetitions per exercise with 51-s interset rest. Participants were tested pre- and post-intervention for body composition, regional muscle thickness, upper- and lower-body muscle maximal strength [1-repetition maximum (1RM)], mean power output and velocity at 75% 1RM and muscular endurance (repetitions to failure at 70% 1RM). Results: Compared to baseline, both groups exhibited equally significantly decreased body fat mass ( p < 0.05), increased fat-free mass ( p < 0.001), muscle thickness ( p < 0.05), upper and lower-body muscular maximal strength ( p < 0.001) and endurance performance ( p < 0.001). However, both groups only increase the lower-body power output ( p < 0.001) but not the upper-body ( p > 0.05). No significant differences existed between groups for all measurements ( p > 0.05). Conclusion: These results suggest that RR and TS groups have similar effects for improving muscle hypertrophy and performance in untrained young men., 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 © 2023 Mao, Wang, Wang and Kuan.)

Droplet boiling on the heating surface is a representative phenomenon in two-phase spray cooling under low volumetric fluxes. In particular, droplet boiling in the transition boiling regime holds the advantages of avoiding heat transfer deterioration in a film boiling regime and achieving comparable high heat transfer capacity in a nucleate boiling regime. While it is known to consist of intermittent liquid contact with the surface and surface dryout, quantifying the ensuing transient heat transfer performance and droplet behavior is very illusive. In this study, droplet boiling in the transition boiling regime on a micropillar array surface is investigated systematically, using the lattice Boltzmann model built up in the lab. The major contents discussed include the transient behaviors of the droplet, motion of the liquid bridge, and pinning/depinning of the three-phase contact line (TPCL), as well as the corresponding heat transfer performance. The evolution of a vapor film pierced by micropillars is analyzed from the views of morphological change and pressure distribution. The thickness of the vapor film is determined by the vapor generation rate dominated by the contact area and effective thermal conductivity, and the vapor escape rate by the permeability. The low permeability under a large pillar side length is responsible for the pressure buildup below the droplet, thus facilitating droplet rebound. The competition between capillary pressure and vapor film pressure dominates the trigger mode of the droplet rebound, i.e., fracture of the liquid bridge or filament and depinning of TPCL. The micropillar array surface is optimized to pursue the best cooling performance by assessing the impact from micropillar geometric dimensions on droplet contact time and area.

(1) Background: Preservatives may pose a potential threat to human health. To ensure food safety, this study has devised a method that concurrently detects a dozen preservatives (acetic acid, propionic acid, dehydroacetic acid, benzoic acid, sorbic acid, dimethyl fumarate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, and isobutyl parahydroxybenzoate) in pastry, utilizing gas chromatography-mass spectrometry. (2) Methods: The pastry samples were acidified with hydrochloric acid, extracted with acetonitrile via vortexing, purified by hexane and saturated with sodium chloride solution to remove lipids and impurities, and then concentrated via nitrogen blowing. The method was then quantitatively analyzed using GC-MS with the internal standard method after methanol re-dissolution. (3) Results: The results showed that the content of the 12 preservatives had good linearity within the range of 1.0-50 μg/mL, with correlation coefficients all greater than 0.99. The method detection limit was 0.04-2.00 mg/kg and the quantification limit was 0.12-6.67 mg/kg. The average recovery rates of the samples at three different spiked concentrations of low, medium, and high were 70.18-109.22%, and the relative standard deviations were 1.82-9.79% (n = 6). (4) Conclusions: This method requires a small amount of sample, has high sensitivity, and is simple and fast to operate, making it suitable for the simultaneous determination of 12 preservatives in pastry. This approach contributes to the effective surveillance and regulation of preservative usage in pastries, thereby safeguarding public well-being.

Background & Aim: Reproductive carrier screening seeks to identify couples at a high risk of having offspring affected by autosomal recessive and X-linked (XL) conditions. The aim of this paper is to provide a comprehensive overview of existing carrier screening panels by examining their gene content and characteristics, identifying the most common genes/conditions included in these panels, and analyzing their listed prices., Methods: A comprehensive evaluation of existing carrier screening panels was conducted by searching for web-based content, reviewing information brochures, and establishing direct contact with the providers via email or phone., Results: Twenty-two panels and their providers were identified with a cumulative total of 2205 unique genes. The number of genes included in these panels varied from 44 to 2054. Only 15 genes (0.7%) were included in all the panels. The carrier frequency of these 15 common genes and their associated conditions varied greatly, but the conditions associated with the genes are "severe". The price of these 22 panels ranged from $349 to $4320 per couple (USD in 2023). The correlation between the listed price and the number of selected genes among these panels was small and not statistically significant (r = 0.1023, p = 0.6959)., Conclusion: Considerable discrepancies exist among carrier screening panels. Ongoing research and monitoring are necessary to capture the dynamic nature of the carrier screening landscape, providing up-to-date information for clinical practice and informed decision-making., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

There is no currently approved adoptive cellular therapy for solid tumors. Pre-clinical and clinical studies have demonstrated that low-dose radiotherapy (LDRT) can enhance intratumoral T cell infiltration and efficacy. This case report describes a 71-year-old female patient with rectal mucosal melanoma that had developed metastases to liver, lung, mediastinum, axillary nodes, and brain. After systemic therapies had failed, she enrolled in the radiation sub-study of our phase-I clinical trial exploring the safety and efficacy of afamitresgene autoleucel (afami-cel), genetically engineered T cells with a T cell receptor (TCR) targeting the MAGE-A4 tumor antigen in patients with advanced malignancies (NCT03132922). Prior to the infusion of afami-cel, she received concurrent lymphodepleting chemotherapy and LDRT at 5.6 Gy/4 fractions to the liver. Time to partial response was 10 weeks, and duration of overall response was 18.4 weeks. Although the patient progressed at 28 weeks, the disease was well controlled after high-dose radiotherapy to liver metastases and checkpoint inhibitors. As of the last follow-up, she remains alive over two years after LDRT and afami-cel therapy. This report suggests that afami-cel in combination with LDRT safely enhanced clinical benefit. This provides evidence for further exploring the benefit of LDRT in TCR-T cell therapy., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Shape memory polymers (SMPs) are currently one of the most attractive smart materials expected to replace traditional shape memory alloys and ceramics (SMAs and SMCs, respectively) in some fields because of their unique properties of high deformability, low density, easy processing, and low cost. As one of the most popular SMPs, shape memory polyurethane (SMPU) has received extensive attention in the fields of biomedicine and smart textiles due to its biocompatibility and adjustable thermal transition temperature. However, its laborious synthesis, limitation to thermal response, poor conductivity, and low modulus limit its wider application. In this work, biocompatible poly(ε-caprolactone) diol (PCL-2OH) is used as the soft segment, isophorone diisocyanate (IPDI) is used as the hard segment, and glycerol (GL) is used as the crosslinking agent to prepare thermoset SMPU with a thermal transition temperature close to body temperature for convenient medical applications. The effects of different soft-chain molecular weights and crosslinking densities on the SMPU's properties are studied. It is determined that the SMPU has the best comprehensive performance when the molar ratio of IPDI:PCL-2OH:GL is 2:1.5:0.33, which can trigger shape memory recovery at body temperature and maintain 450% recoverable strain. Such materials are excellent candidates for medical devices and can make great contributions to human health.

This study examined how humor (incongruity humor vs. no humor) interacts with individual differences in perceived efficacy to influence health attitudes and behavioral intentions. Results of a controlled experiment ( N  = 294) revealed that among individuals with lower levels of perceived efficacy, incongruity humor, relative to no humor condition, resulted in greater source liking, which in turn, enhanced their attitudes and intentions to perform preventive health behaviors. However, for individuals higher in perceived efficacy, incongruity humor (vs. no humor) had an indirect negative effect on intentions via decreased attitudes. Theoretical and practical implications of these findings are discussed.

Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.

Purpose: To assess the effect of combination therapy with 3% diquafosol tetrasodium (DQS) and sodium hyaluronate (HA) for dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK)., Design: Prospective nonrandomized comparative trial., Methods: The prospective study included 80 eyes of 40 patients who underwent FS-LASIK with or without preoperative dry eye. Patients were divided into a combination group and a HA group according to their willingness and the doctor's advice. The combination group was treated with DQS six times a day and HA four times a day, and the HA group was treated with HA four times a day after FS-LASIK. Ocular surface disease index (OSDI), ocular symptom score, vision-related score, environmental score, tear meniscus height (TMH), first non-invasive tear breakup time (NIBUT-First), average non-invasive tear breakup time (NIBUT-Ave), tear breakup time (TBUT), Schirmer I test (SIT), corneal fluorescein staining score (CFS), bulbar redness score, limbal redness score, lipid layer grade (LLG), meiboscore, lid margin abnormality, corneal sensitivity, and corneal nerve parameters were examined before surgery and at 1 week and 1 month after surgery. Surface regularity index (SRI) was also examined before surgery and at 1 month postoperatively., Results: OSDI score ( p  = 0.024) and vision-related score ( p  = 0.026) were significantly lower in the combination group than in the HA group at 1 month after FS-LASIK, especially in patients with preoperative dry eye symptoms. The increasements of CFS ( p  = 0.018), bulbar redness score ( p  = 0.021), and limbal redness score ( p  = 0.009) were significantly lower in the combination group than in the HA group at 1 week after FS-LASIK. But other ocular surface parameters showed no difference between both groups at 1 week and 1 month after FS-LASIK. LLG was significantly higher in the combination group than in the HA group at 1 week ( p  = 0.004) and 1 month ( p  < 0.001) after surgery, especially in patients with high meiboscore. Additional DQS significantly improved corneal sensitivity in patients without preoperative dry eye symptoms at 1 month after FS-LASIK ( p  = 0.041)., Conclusion: The combination therapy with DQS and HA significantly relieved subjective symptoms, improved ocular surface status, and had the potential to promote corneal nerve growth in patients after FS-LASIK., 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 © 2023 Wang, Di and Li.)

Patients with multiple myeloma (MM) who are treated with lenalidomide rarely develop a secondary B-cell acute lymphoblastic leukemia (B-ALL). The clonal and biological relationship between these sequential malignancies is not yet clear. We identified 17 patients with MM treated with lenalidomide, who subsequently developed B-ALL. Patient samples were evaluated through sequencing, cytogenetics/fluorescence in situ hybridization (FISH), immunohistochemical (IHC) staining, and immunoglobulin heavy chain (IgH) clonality assessment. Samples were assessed for shared mutations and recurrently mutated genes. Through whole exome sequencing and cytogenetics/FISH analysis of 7 paired samples (MM vs matched B-ALL), no mutational overlap between samples was observed. Unique dominant IgH clonotypes between the tumors were observed in 5 paired MM/B-ALL samples. Across all 17 B-ALL samples, 14 (83%) had a TP53 variant detected. Three MM samples with sufficient sequencing depth (>500×) revealed rare cells (average of 0.6% variant allele frequency, or 1.2% of cells) with the same TP53 variant identified in the subsequent B-ALL sample. A lack of mutational overlap between MM and B-ALL samples shows that B-ALL developed as a second malignancy arising from a founding population of cells that likely represented unrelated clonal hematopoiesis caused by a TP53 mutation. The recurrent variants in TP53 in the B-ALL samples suggest a common path for malignant transformation that may be similar to that of TP53-mutant, treatment-related acute myeloid leukemia. The presence of rare cells containing TP53 variants in bone marrow at the initiation of lenalidomide treatment suggests that cellular populations containing TP53 variants expand in the presence of lenalidomide to increase the likelihood of B-ALL development., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In this work, we studied the evolution of vacancy-like defects and the formation of brittle precipitates in a reduced-activation V-Cr-Mn medium-entropy alloy. The evolution of local electronic circumstances around Cr and Mn enrichments, the vacancy defects, and the CrMn 3 precipitates were characterized by using scanning electron microscopy with energy-dispersive spectroscopy, X-ray diffraction, and positron annihilation spectroscopy. The microstructure measurements showed that the Mn and Cr enrichments in the as-cast sample significantly evolved with temperature, i.e., from 400 °C, the Cr/Mn-segregated regions gradually dissolved into the matrix and then disappeared, and from 900 °C to 1000 °C, they existed as CrMn 3 precipitates. The crystallite size of the phase corresponding to CrMn 3 precipitates was about 29.4 nm at 900 °C and 43.7 nm at 1000 °C. The positron annihilation lifetime results demonstrated that the vacancies mediated the migration of Cr and Mn, and Cr and Mn segregation finally led to the formation of CrMn 3 precipitates. The coincidence Doppler broadening results showed that the characteristic peak moved to the low-momentum direction, due to an increase in the size of the vacancy defects at the interface and the formation of CrMn 3 precipitates., Competing Interests: The authors declare no conflicts of interest.

Introduction: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and regarded as one of the most frequent genetic causes of infant mortality. The aim of this study is to develop a cost-effectiveness analysis of AVXS-101 (Onasemnogene Abeparvovec/Zolgensma ® ) and nusinersen (Spinraza ® ) for SMA to inform decision-making on reimbursement policies in Australia., Methods: A Markov model was developed with five health states to evaluate the costs and effects for patients with SMA Type I from a healthcare system perspective over a time-horizon of 100 years. The model parameters were based on clinical trials, parametric distributions, published literature, and Australian registries. One-way and probabilistic sensitivity analysis were performed to appraise the uncertainties of the parameters in the model. A threshold analysis was conducted to estimate the cost of AVXS-101 of being cost-effective., Results: The incremental cost-effectiveness ratio (ICER) of AVXS-101 was $1,808,471 per quality-adjusted life year (QALY) and that of nusinersen was $2,772,798 per QALY, compared to standard of care, respectively. The ICER of AVXS-101 was $1,238,288 per QALY compared to nusinersen. The key drivers influencing on ICERs were costs of using treatments and utility values of sitting and walking independently., Conclusion: Both nusinersen and AVXS-101 resulted in health benefits, but they were not cost-effective with a commonly used willingness-to-pay (WTP) threshold of $50,000 per QALY. Developing high-quality clinical data and exploring appropriate WTP thresholds are critical for decision-making on reimbursement policies in the treatment of rare diseases., (© 2022. The Author(s).)

Triple negative breast cancer (TNBC) is an immunosuppressive "cold" tumor that lacks immune cell infiltration and activation, resulting in a poor response to immune checkpoint blockade (ICB) therapies. In addition, TNBC is poorly responsive to targeted therapies due to the absence of efficient molecular targets. A strategy that can block molecular signal transduction, stimulate immunogenicity, and activate the immune response is a promising approach to achieve ideal clinical benefit. Herein, we designed and synthesized an aggregation-induced emission luminogen (AIEgen)-conjugated self-assembling peptide that targets epidermal growth factor receptor (EGFR), named TPA-FFG-LA. TPA-FFG-LA peptides form nanoassemblies on the surface of EGFR-positive TNBC cells and are internalized into cells through endocytosis, which inhibit EGFR signaling transduction and provoke lysosomal membrane permeabilization (LMP). Upon light irradiation, the aggregated AIEgens produce massive reactive oxygen species (ROS) to exacerbate LMP and trigger immunogenic cell death (ICD), resulting in elimination of residual EGFR-negative tumor cells and exerting long-term antitumor effects. The in vitro and in vivo experiments verified that TPA-FFG-LA nanoassemblies suppress tumor growth, provoke immune cell activation and infiltration, and cause EGFR degradation and LMP. These results suggest that the combination of supramolecular assembly induced molecular targeting effects and lysosome dysfunction with ICD-stimulated immune activation is a plausible strategy for the efficient therapy of immunosuppressive TNBC., Competing Interests: Declaration of Competing Interest All authors declare no competing interest., (Copyright © 2022. Published by Elsevier B.V.)

Nematodes are one of the largest groups of animals on the planet. Many of them are major pathogens of humans, animals and plants, and cause destructive diseases and socioeconomic losses worldwide. Despite their adverse impacts on human health and agriculture, nematodes can be challenging to control, because anthelmintic treatments do not prevent re-infection, and excessive treatment has led to widespread drug resistance in nematode populations. Indeed, many nematode species of livestock animals have become resistant to almost all classes of anthelmintics used. Most efforts to develop commercial anti-nematode vaccines (native or recombinant) for use in animals and humans have not succeeded, although one effective (dead) vaccine (Barbervax) has been developed to protect animals against one of the most pathogenic parasites of livestock animals - Haemonchus contortus (the barber's pole worm). This vaccine contains native molecules, called H11 and H-Gal-GP, derived from the intestine of this blood-feeding worm. In its native form, H11 alone consistently induces high levels (75-95%) of immunoprotection in animals against disease (haemonchosis), but recombinant forms thereof do not. Here, to test the hypothesis that post-translational modification (glycosylation) of H11 plays a crucial role in achieving such high immunoprotection, we explored the N-glycoproteome and N-glycome of H11 using the high-resolution mass spectrometry and assessed the roles of N-glycosylation in protective immunity against H. contortus . Our results showed conclusively that N-glycan moieties on H11 are the dominant immunogens, which induce high IgG serum antibody levels in immunised animals, and that anti-H11 IgG antibodies can confer specific, passive immunity in naïve animals. This work provides the first detailed account of the relevance and role of protein glycosylation in protective immunity against a parasitic nematode, with important implications for the design of vaccines against metazoan parasites., 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 © 2022 Wang, Liu, Wang, Liu, Peng, Srivastav, Zhu, Gupta, Gasser and Hu.)

Given the challenges facing companies in communicating corporate social responsibility (CSR) initiatives amid the pandemic, this study focuses on the effects of CSR appeals in COVID-19 advertising. Using the Ordered Protection Motivation model and CSR literature as the foundation, this study examined the interaction effect between CSR appeal (altruistic CSR vs. strategic CSR) and threat intensity (low vs. high) of the crisis depiction featured in the ad on consumers' responses. Results revealed the moderating role of threat intensity on the relationships between CSR appeal and consumers' responses, such that altruistic CSR appeal outperformed strategic CSR appeal when consumers were exposed to an ad featuring a high-threat crisis depiction, whereas the two appeals yielded similar effects when the ad featured a low-threat crisis depiction. In particular, altruistic CSR appeal (vs. strategic CSR appeal) generated greater message credibility, stronger feelings of warmth, and lower CSR skepticism, resulting in more favorable ad and brand attitudes and stronger purchase intentions, but only in the high threat condition., 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., (© 2022 Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) with prostate-specific membrane antigen (PSMA)-specific high expression is well suited for molecularly targeted theranostics. PSMA expression correlates with the malignancy of PCa, and its dimeric form can promote tumor progression by exerting enzymatic activity to activate downstream signal transduction. However, almost no studies have shown that arresting the procancer signaling of the PSMA receptors themselves can cause tumor cell death. Meanwhile, supramolecular self-assembling peptides are widely used to design anticancer agents due to their unique and excellent properties. Here, a PSMA-targeting supramolecular self-assembling nanotheranostic agent, DBT-2FFGACUPA, which actively targets PSMA receptors on PCa cell membranes and induces them to enter the cell and form large aggregates, is developed. This process not only selectively images PSMA-positive tumor cells but also suppresses the downstream procancer signals of PSMA, causing tumor cell death. This work provides an alternative approach and an advanced agent for molecularly targeted theranostics options in PCa that can induce tumor cell death without relying on any reported anticancer drugs., (© 2022 Wiley-VCH GmbH.)

Background: Worldwide, the volume and availability of digestive endoscopy have undergone dramatic development in recent years, with increasing attention on quality assurance. We investigated the utilization and quality of digestive endoscopy in China from 2015 to 2019 and developed a quantitative quality evaluation tool for medical institutions., Methods: We invited all tertiary/secondary hospitals in Chinese mainland to participate in the survey annually. The questionnaires included the personnel, annual volume, and quality indicators of endoscopy. An endoscopy quality index (EQI) was developed based on recorded quality indicators using principal component analysis to determine the relative weight., Results: From 2015 to 2019, 806, 1412, 2644, 2468, and 2541 hospitals were respectively enrolled in this study. The average annual volume of endoscopy increased from 12,445 to 16,206 (1.30-fold) and from 2938 to 4255 (1.45-fold) in tertiary and secondary hospitals, respectively. The most obvious growth was observed in diagnostic colonoscopy (1.44-fold for all hospitals after standardization). The proportion of early cancer among all esophageal and gastric cancers during diagnostic esophagogastroduodenoscopy increased from 12.3% (55,210/448,861) to 17.7% (85,429/482,647) and from 11.4% (69,411/608,866) to 16.9% (107,192/634,235), respectively. The adenoma detection rate of diagnostic colonoscopy increased from 14.9% (2,118,123/14,215,592) to 19.3% (3,943,203/20,431,104). The EQI model included 12 quality indicators, incorporating 64.9% (7.792/12) of the total variance into one comprehensive index. According to the EQI measurements, the quality of endoscopy was higher in tertiary hospitals and hospitals in developed areas with higher volume or more endoscopists than that in other hospitals., Conclusions: Digestive endoscopy in China has developed considerably in recent years in terms of both volume and quality. The EQI is a promising tool to quantify the quality of endoscopy at different hospitals., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)