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BackgroundOesophageal squamous cell carcinoma (SCC) causes the highest number of cancer deaths in some regions of Northern China. Previously, we narrowed down a critical region at 9q33-34, identified to be associated with tumour-suppressive function of deleted in oesophageal cancer 1 (DEC1) in oesophageal SCC.MethodsWe generated DEC1 antibody and constructed tissue microarrays (TMAs) utilising tissue specimens from Henan, a high-risk region for oesophageal SCC, to investigate the importance of DEC1 expression in this cancer.ResultsTissue microarray immunohistochemical staining reveals significant loss of DEC1 from hyperplasia, to tumour, and to lymph node metastasis. In addition, the loss of DEC1 in tumour is age-dependent. Interestingly, there is significant abrogation of DEC1 expression in patients with a family history of oesophageal SCC. Deleted in oesophageal cancer 1 localises to both the cytoplasm and nucleus. The vesicular pattern of DEC1 in the cytoplasm appears to localise at the Golgi and Golgi-endoplasmic reticulum intermediate compartment.ConclusionThis is the first TMA study to suggest a clinical association of DEC1 in lymph node metastatic oesophageal SCC, early onset oesophageal SCC and familial oesophageal SCC development. Subcellular localisation of DEC1 and its expression in oesophageal SCC tissues provide important insight for further deciphering the molecular mechanism of DEC1 in oesophageal SCC development.

Zi Han Zhai,1,2 Jun Hao Ning,1,2 Linda Dong-Ling Wang1,3 1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 2Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research, Yangzhou, 225001, People’s Republic of China; 3Centre for Psycho-Oncology Research & Training, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: Linda Dong-Ling Wang, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China, Tel +86-051487978925, Email lindawdl@yzu.edu.cnPurpose: The Decisional Conflict Scale (DCS) is a well-known scale for measuring personal decisional conflict, particularly when a person feels uninformed about the risks/benefits of choices, is unclear about personal values, and feels unsupported in making a choice. Higher scores of DCS indicate higher decisional conflict. In the present study, we aimed to assess the psychometric properties of the Chinese version of the DCS among Chinese young women making HPV vaccination decisions.Methods: A total of 107 HPV-unvaccinated Chinese women aged 18– 26 completed the survey assessing decisional conflict, knowledge and decision of HPV vaccination. Factorial validity, construct validity, and reliability of the DCS were examined.Results: The mean score of the DCS-16 was 41.5 (SD=20.0). Principal component analysis extracted a 3-factor model of DCS containing 13 items (DCS-13), but both the original DCS-16 and extracted DCS-13 showed poor factorial validity. An alternative DCS-10 revealed a good fit to the data with Cronbach’s alpha 0.86. Some subscales of the three versions of DCS showed inconsistent correlation.Conclusion: The DCS-10 demonstrated good model fit to the data. By using the DCS-10 total score rather than sub-scores to measure Chinese young women’s HPV vaccination decisional conflict a more valid assessment can be obtained.Keywords: decisional conflict, validation, HPV vaccination, decision making

Esophageal cancer has been associated with tobacco smoking, and nitrosamines are possible causative agents for this cancer. The present study investigated the metabolism of the tobacco carcinogens N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosodimethylamine (NDMA), as well as the presence of xenobiotic-metabolizing enzymes in human esophageal tissues from individuals in the United States and Huixian, Henan Province, China (a high-risk area for esophageal cancer). All esophageal microsomal samples activated NNN and the metabolic rate was 2-fold higher in the esophageal samples from China than the USA. All microsomal samples activated NDMA. However, most of the microsomal samples did not activate NNK. Troleandomycin (an inhibitor of cytochrome P450 3A) decreased the formation of NNN-dervived keto acid by 20-26% in the esophageal microsomes. The activities for NADPH: cytochrome c reductase, ethoxycoumarin O-deethylase, NAD(P)H: quinone oxidoreductase and glutathione S-transferase were present in the esophageal samples. Coumarin 7-hydroxylase (a representative activity for P450 2A6) activity was not detected in the esophageal microsomal samples. The activities for nitrosamine metabolism and xenobiotic-metabolizing enzymes were decreased (by 30-50%) in the squamous cell carcinomas compared with their corresponding non-cancerous mucosa. The presence of activation and detoxification enzymes in the esophagus may play an important role in determining the susceptibility of the esophagus to the carcinogenic effect of nitrosamines. Our results suggest that P450s 3A4 and 2E1 are involved in the activation of NNN and NDMA, respectively, in the human esophagus. [ABSTRACT FROM PUBLISHER]

Objective: To verify the equivalence of hawthorn leaves standard decoction and formula granules., Methods: In this experiment, liquid chromatograph mass spectrometer (LC-MS) was used to examine the chemical composition of hawthorn leaves standard decoction and formula granules, separately. In addition, oxidative stress test was used to explore the antioxidant capacity of them., Results: 71 chemical components were identified by LC-MS. Among them, 64 and 56 compounds were identified in the standard decoction and formula granules, respectively. There were a total of 49 common components, with no significant difference in content. Oxidative stress test showed that hawthorn leaves standard decoction and formula granules had no obvious toxicity to human umbilical vein endothelial cells. Compared with the model group, the same dose of hawthorn leaves formula granule and standard decoction could inhibit the secretion of lactate dehydrogenase and malondialdehyde (P < 0.05), and increase the content of superoxide dismutase (P < 0.01), with no statistically significant difference., Conclusions: There is no significant difference in the main active ingredients between the standard decoction and the formula granules, and the antioxidant activity in vitro is equivalent, providing an important theoretical basis for the further development of hawthorn leaves formula granules., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Oxygen evolution reaction (OER) is an indispensable anode reaction for sustainable hydrogen production from water electrolysis, yet overreliance on metal-based catalysts featured with vibrant d-electrons. It still has notable gap between metal-free and metal-based electrocatalysts, due to lacking accurate and efficient p-band regulation methods on non-metal atoms. Herein, a molecular modularization strategy is proposed for fine-tuning the p-orbital states of series metal-free covalent organic frameworks (COFs) for realizing OER performance beyond benchmark precious metal catalysts. Optimized combination of benzodioxazole/benzodiimide-based building blocks achieves an impressive applied potential of 1.670 ± 0.004 V versus reversible hydrogen electrode (RHE) and 1.735 ± 0.006 V versus RHE to deliver enhanced current densities of 0.5 and 1.0 A cm -2 , respectively. Moreover, it holds a notable charge transfer amount (stands for a long service life) within operation period that outperforms all reported metal-free electrocatalysts. Operando differential electrochemical mass spectrometry (DEMS) with isotope labeling identifies the adsorbate evolution mechanism (AEM). A variety of spectroscopic techniques and density functional theory (DFT) calculations reveal that the p-band center of these catalysts can be shifted stepwise to optimize the oxygen intermediate adsorption and lower the reaction energy barrier. This work provides a novel perspective for enhancing the electrocatalytic performance of metal-free COFs., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background : Macrophage-mediated cancer cell phagocytosis has demonstrated considerable therapeutic potential. While the initiation of phagocytosis, facilitated by interactions between cancer cell surface signals and macrophage receptors, has been characterized, the mechanisms underlying its sustentation and attenuation post-initiation remain poorly understood. Methods : Through comprehensive phosphoproteomic profiling, we interrogated the temporal evolution of the phosphorylation profiles within macrophages during cancer cell phagocytosis. Results : Our findings reveal that activation of the mTOR pathway occurs following the initiation of phagocytosis and is crucial in sustaining phagocytosis of cancer cells. mTOR inhibition impaired the phagocytic capacity, but not affinity, of the macrophages toward the cancer cells by delaying phagosome maturation and impeding the transition between non-phagocytic and phagocytic states of macrophages. Conclusions : Our findings delineate the intricate landscape of macrophage phagocytosis and highlight the pivotal role of the mTOR pathway in mediating this process, offering valuable mechanistic insights for therapeutic interventions.

The voltage decay of Li-rich layered oxide cathode materials results in the deterioration of cycling performance and continuous energy loss, which seriously hinders their application in the high-energy-density lithium-ion battery (LIB) market. However, the origin of the voltage decay mechanism remains controversial due to the complex influences of transition metal (TM) migration, oxygen release, indistinguishable surface/bulk reactions and the easy intra/inter-crystalline cracking during cycling. We investigated the direct cause of voltage decay in micrometer-scale single-crystal Li 1.2 Mn 0.54 Ni 0.13 Co 0.13 O 2 (SC-LNCM) cathode materials by regulating the cut-off voltage. The redox of TM and O 2- ions can be precisely controlled by setting different voltage windows, while the cracking can be restrained, and surface/bulk structural evaluation can be monitored because of the large single crystal size. The results show that the voltage decay of SC-LNCM is related to the combined effect of cation rearrangement and oxygen release. Maintaining the discharge cutoff voltage at 3 V or the charging cutoff voltage at 4.5 V effectively mitigates the voltage decay, which provides a solution for suppressing the voltage decay of Li-rich and Mn-based layered oxide cathode materials. Our work provides significant insights into the origin of the voltage decay mechanism and an easily achievable strategy to restrain the voltage decay for Li-rich and Mn-based cathode materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Declaration of interests The authors have no conflicts of interest relevant to the above work. LDW serves on the SAB of Autolomous, Ltd, consults for Gerson Lehrman Group, and has provided expert witness services.

Background: People diagnosed with Inflammatory bowel disease (IBD) often have severe dietary restrictions and avoidance due to the uncertainty of intestinal symptoms. Inadequate dietary intake may increase the risk of malnutrition and result in impaired food-related quality of life (FRQoL). Few studies investigated factors influencing FRQoL in patients with IBD. This study aimed to synthesize the existing evidence regarding FRQoL among patients with IBD, including the current situation, measurement instruments, and related influencing factors., Method: The comprehensive literature search was conducted in databases including PubMed, Embase, CINAHL, PsycInfo, Cochrane Library, as well as the most commonly used Chinese databases (CNKI, Wanfang and CBM). Studies published between January 2015 and December 2023 on FRQoL in patients with IBD were included. The Joanna Briggs Institute (JBI) critical appraisal checklist was utilized to evaluate the methodological quality of the selected studies., Results: Finally, only five studies met the inclusion criteria were reviewed, including three cross-sectional studies and two case-control studies. The Food-related quality of life-29 Scale (FR-QoL-29) with a total core of 145 was the most used instrument measuring FRQoL in patients with IBD. The mean scores of FRQoL ranged from 69.9 to 102.3 in adult patients with IBD and 94.3 in children. A diverse range of factors were associated with FRQoL, including socio-demographic, clinical, psychological, diet-related, and nutrient intake factors., Conclusions: The main influencing factors of FRQoL among patients with IBD included disease activity status, severe symptoms, history of IBD surgery, negative emotion reaction, and restrictive eating behaviour. Clinicians should work in concert with dietitians, keeping an eye on the disease status, nutrition intake, and restrictive eating habits, assessing FRQoL and providing personalized dietary recommendation for the patients with IBD., (© 2024 John Wiley & Sons Ltd.)

Competing Interests: None declared.

Advances in mass spectrometry (MS) have enabled high-throughput analysis of proteomes in biological systems. The state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide-spectrum matches (PSMs), which convert mass spectra to peptide sequences. Different database search algorithms use distinct search strategies and thus may identify unique PSMs. However, no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate (FDR). To fill in this gap, we proposed a statistical framework, Aggregation of Peptide Identification Results (APIR), that is universally compatible with all database search algorithms. Notably, under an FDR threshold, APIR is guaranteed to identify at least as many, if not more, peptides as individual database search algorithms do. Evaluation of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the FDR. Real data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search algorithms. The APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis, e.g., differential gene expression analysis on RNA sequencing data. The APIR R package is available at https://github.com/yiling0210/APIR., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

To investigate the mechanism by which Peitu Yifei Granules inhibit idiopathic pulmonary fibrosis(IPF) in rats, fifty specific-pathogen-free(SPF) grade male Wistar rats were randomly divided into blank group and modeling group. IPF was induced in the modeling group rats by tracheal infusion of 5 mg·kg~(-1) bleomycin(BLM) and then randomly divided into model group, pirfenidone group, and high-dose, medium-dose, and low-dose groups treated with Peitu Yifei Granules. After 24 hours of modeling, the treatment groups received intragastric administration of either Peitu Yifei Granules or pirfenidone as a positive control drug; meanwhile, the model group received an equal volume of normal saline. After 21 days of treatment administration, lung tissue samples were collected for analysis. Pathological changes in lung tissues were assessed using hematoxylin-eosin(HE) staining and Masson's trichrome staining. The expression levels of protein kinase B(Akt), mammalian target of rapamycin(mTOR), their phosphorylated forms, and sequestosome 1(p62) were determined through Western blot(WB). Fluorescent quantitative real-time polymerase chain reaction(RT-qPCR) was used to measure messenger ribonucleic acid(mRNA) expression levels of Beclin-1, microtubule-associated proteins 1A/1B light chain 3B(LC3B), and p62. Immunohistochemistry was performed to assess protein expression levels of Beclin-1 and LC3B in lung tissue samples. RESULTS:: demonstrated that lung tissue structure appeared normal without significant collagen deposition in the blank group rats. In contrast, rats from the model group exhibited thickened alveolar septa along with evident inflammatory changes and collagen deposition. Compared to the model group rats, those treated with Peitu Yifei Granules or pirfenidone showed significantly improved lung tissue structure with reduced inflammation and collagen deposition observed histologically. Furthermore, compared with those of the blank group, the expressions of p62 and its mRNA, p-Akt and p-mTOR protein in lung tissues of the model group were significantly increased, while Beclin-1, LC3B and their mRNA levels were significantly decreased. Compared with those of the model group, the expressions of p62 and its mRNA, p-Akt and p-mTOR in lung tissues of the pirfenidone group and Peitu Yifei Granules high-dose and medium-dose groups were significantly decreased, while Beclin-1, LC3B and their mRNA expressions were significantly increased. The above results indicate that Peitu Yifei Granules can improve autophagy levels in lung tissues by inhibiting the phosphoinositide 3-kinase(PI3K)/Akt/mTOR signaling pathway and delay the development of IPF disease.

This study aimed to explore the mediating effects of ADL and depression on the relationship between sleep quality and HRQOL among older people in rural China, while also exploring the moderating impact of loneliness. The study gathered data from a household survey conducted among 1587 Chinese rural older adults (mean age = 73.63 years). The collected data was analyzed using SPSS version 23.0 software (IBM, New York, USA) and the PROCESS macro version 4.0 program. The findings indicated a significant correlation between sleep quality, ADL, depression, loneliness and HRQOL. ADL and depression exhibited a chain mediation effect on the relationship between sleep quality and HRQOL. Notably, the association between sleep quality and HRQOL was entirely mediated by ADL and depression. Additionally, loneliness acted as a moderator in the relationship between ADL and HRQOL. The findings of this study suggest that interventions focusing on sleep quality should prioritize strategies for enhancing older adults' ADL and depression as integral components of promoting older adults' HRQOL., (© 2024. The Author(s).)

Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

Purpose of Review: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH., Recent Findings: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches., (© 2024. The Author(s).)

Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan. Secondary objectives included overall survival, disease response, cytokine dynamics and tumor immune contexture biomarkers. This trial evolved to evaluate three routes of locoregional T cell administration (intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV) and two manufacturing platforms, culminating in arm 5, which utilized dual ICT/ICV delivery and an optimized manufacturing process. Locoregional CAR-T cell administration was feasible and well tolerated, and as there were no dose-limiting toxicities across all arms, a maximum tolerated dose was not determined. Probable treatment-related grade 3+ toxicities were one grade 3 encephalopathy and one grade 3 ataxia. A clinical maximum feasible dose of 200 × 10 6 CAR-T cells per infusion cycle was achieved for arm 5; however, other arms either did not test or achieve this dose due to manufacturing feasibility. A recommended phase 2 dose will be refined in future studies based on data from this trial. Stable disease or better was achieved in 50% (29/58) of patients, with two partial responses, one complete response and a second complete response after additional CAR-T cycles off protocol. For rGBM, median overall survival for all patients was 7.7 months and for arm 5 was 10.2 months. Central nervous system increases in inflammatory cytokines, including IFNγ, CXCL9 and CXCL10, were associated with CAR-T cell administration and bioactivity. Pretreatment intratumoral CD3 T cell levels were positively associated with survival. These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients. ClinicalTrials.gov Identifier: NCT02208362 ., (© 2024. The Author(s).)

To clarify the impact of the structure and function of soil microbial communities in the stage of abandoned farmland, three different stages of land abandoned in desert oasis areas were selected as the research objects. We used metagenomic sequencing technology to research soil microbial community structure and functional diversity characteristics of different stages of abandoned farmland. The results showed that there were significant differences in the relative abundance of the dominant phyla Actinobacteria, Proteobacteria, and Gemmatimonadetes in the soil of the three stages of returning farmland. Compared with that in the early stage of abandoned farmland, the later stage of abandoned farmland restoration increased the gene proportion involved in Quorum sensing, porphyrin and chlorophyll metabolism, pantothenate and CoA biosynthesis, and styrene degradation, and there was a significant difference in relative abundance ( P <0.05), which indicated that different stages of abandoned farmland had changed the functional potential of the nutrient cycle and energy metabolism in soil microbial communities. The RDA results showed that EC, AK, and TN had a significant impact on the functional composition of soil microbes, and soil EC had the greatest impact on microbial functional composition. The results showed that different stages of abandoned farmland had a significant impact on the soil microbial community structure and functional composition. In the ecological restoration of abandoned farmland in Minqin Oasis, the sensitivity of microbial community structure and functional composition to soil restoration at different stages should be considered using comprehensive relevant indicators.

Mesotrione, which is a kind of herbicide to control broad-leaved weeds, has been increasingly used due to its excellent selectivity, rapid process and low toxicity. However, the excessive application of mesotrione have led to widespread contamination. Herein, a turn-on competitive coordination-based fluorescent probe, 2-hydroxy-1-(9-purin)-methylidenehydrazinenaphthalene (HPM), has been successfully synthesized. HPM could effectively detect Al 3+ in CH 3 OH/HEPES (1/9, v/v) with low limit of detection (LOD) being 0.2 µM via coordination. HPM also exhibited excellent imaging capabilities for Al 3+ in living cells with low cytotoxicity. On the basis of the competitive coordination of HPM with Al 3+ , the [HPM-Al 3+ ] complex could also serve as a potential fluorescence sensor for detecting mesotrione with the LOD of 0.2 µM. Furthermore, [HPM-Al 3+ ] complex was applied for the detection of mesotrione in real samples and test paper. Finally, the mechanism of [HPM-Al 3+ ] for sensing mesotrione was investigated deeply as well. This work designed a new convenient method for on-site detection of mesotrione without the large-scale equipment or complicated pre-treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5-year survival rate., Method: Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely-targeted metabolomics by UPLC-MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel., Results: A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p < 0.05, (VIP) ≥ 1, and FC ≥ 2 or FC ≤ 0.5. Early-stage GCA patients exhibited a more favorable prognosis compared to those in advanced stages. HER2 overexpression was associated with a more positive outcome compared to the negative and low expression groups. Metabolite panel demonstrated a robust diagnostic performance with AUC of 0.869 in discovery set and 0.900 in validation set., Conclusions: A total of 25 common and stable differential metabolites may hold promise as liquid non-invasive indicators for GCA diagnosis. HER2 may function as a tumor suppressor gene in GCA, as its overexpression is associated with improved survival. The downregulation of bile acid metabolism in GCA may offer valuable theoretical insights and innovative approaches for precision-targeted treatments in GCA patients., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Hyperlipidemia is a major risk factor for many diseases. Previous studies have shown that diet is closely associated with hyperlipidemia. However, the relationship between cooking methods and hyperlipidemia remains unclear. The objective of this study was to identify the major cooking patterns existing in the Eastern Chinese population and evaluate their association with the prevalence of hyperlipidemia., Methods: We interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when they prepare food at home or when eating out and regarding the prevalence of hyperlipidemia. Factor analysis, Chi-square tests, analysis of variance, and binary logistic regression analysis were used to identify the cooking patterns and analyze the characteristics of participants' categories of cooking patterns and the relationship between different cooking patterns and prevalence of hyperlipidemia., Results: Three major cooking patterns were identified: Traditional Chinese, Bland (little or no oil is used to process the food), and High-temperature cooking patterns. After controlling for potential confounders, participants in the highest quartile of the Bland cooking pattern had lower odds of hyperlipidemia than those in the lowest quartile. Nevertheless, no significant associations were observed between the Traditional Chinese and High-temperature cooking patterns and the prevalence of hyperlipidemia., Conclusions: This study confirms the association between cooking patterns and the prevalence of hyperlipidemia and indicates that the Bland cooking pattern is associated with a reduced prevalence of hyperlipidemia., (© 2024. The Author(s).)

Background/purpose: With the development of computer-assisted surgery, digital guide plate was widely used in vascularized bone flap grafts for mandibular reconstruction. The purpose of this study was to design and manufacture a digital guide plate with drill-hole sharing for mandibular reconstruction and assess for surgical accuracy., Materials and Methods: 17 patients that required mandibular reconstruction using fibula free flap or iliac crest free flap were included in the study. The computed tomography (CT) data of the patient's mandible and pelvis or fibula were acquired preoperatively. A surgical simulation was then performed using computer-aided surgical simulation (CASS) technology based on above date, which allowed the design of two cutting guide and a repositioning guide for mandibular reconstruction. After surgery, the accuracy of reconstruction was evaluated by superimposing the postoperative image onto the preoperative image of mandible, recording the linear and angular deviation of landmarks, measuring the differences between the planned and actual outcomes., Results: The osteotomy and repositioning of fibula or iliac crest segments were successfully performed as planned using surgical guides. The digital guide plate with drill-hole sharing showed excellent accuracy, When the iliac crest or the fibula free flap were used for mandibular reconstruction, the largest mean differences between the preoperative and postoperative were 1.11 mm and 2.8° or 1.3 mm and 3.87°., Conclusion: The digital guide plate with drill-hole sharing designed preoperatively provides a reliable method of for the mandibular reconstruction. This can assist surgeons in accurately performing osteotomy and repositioning fibula or iliac crest segments during the mandibular reconstruction., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 10 5 A·g -1 and TOF bulk of 27.66 ± 1.59 s -1 at 1.58 V ( vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm -2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies. Here, we describe CAR T cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. CAR T cell-mediated IFNγ production facilitated by IL-12 signaling is required for tumor cell killing, which is recapitulated by engineering an optimized membrane-bound IL-12 (mbIL12) molecule in CAR T cells. These T cells show improved antigen-dependent T cell proliferation and recursive tumor cell killing in vitro, with robust in vivo efficacy in human ovarian cancer xenograft models. Locoregional administration of mbIL12-engineered CAR T cells promotes durable anti-tumor responses against both regional and systemic disease in mice. Safety and efficacy of mbIL12-engineered CAR T cells is demonstrated using an immunocompetent mouse model, with beneficial effects on the immunosuppressive tumor microenvironment. Collectively, our study features a clinically-applicable strategy to improve the efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting regional and systemic disease., (© 2023. Springer Nature Limited.)

Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in age-related cataract (ARC) with severe visual impairment, in which ferroptosis is gradually receiving numerous attention resulting from lipid peroxide accumulation and reactive oxygen species (ROS) overproduction. However, the essential pathogenic factors and the targeted medical strategies still remain skeptical and indistinct. In this work, by transmission electron microscopy (TEM) analysis, the major pathological courses in the LECs of ARC patients have been identified as ferroptosis, which was manifested with remarkable mitochondrial alterations, and similar results were found in aged mice (24-month-old). Furthermore, the primary pathological processes in the NaIO3-induced mice and HLE-B3 cell model have also been verified to be ferroptosis with an irreplaceable function of Nrf2, proved by the increased sensitivity to ferroptosis when Nrf2 was blocked in Nrf2-KO mice and si-Nrf2-treated HLE-B3 cells. Importantly, it has been found that an increased expression of GSK-3β was indicated in low-Nrf2-expressed tissues and cells. Subsequently, the contributions of abnormal GSK-3β expression to NaIO3-induced mice and HLE-B3 cell model were further evaluated, inhibition of GSK-3β utilizing SB216763 significantly alleviated LECs ferroptosis with less iron accumulation and ROS generation, as well as reversed expression alterations of ferroptosis markers, including GPX4, SLC7A11, SLC40A1, FTH1 and TfR1, in vitro and in vivo. Collectively, our findings conclude that targeting GSK-3β/Nrf2 balance might be a promising therapeutic strategy to mitigate LECs ferroptosis and thus probably delay the pathogenesis and development of ARC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of Review: Correlative studies should leverage clinical trial frameworks to conduct biospecimen analyses that provide insight into the bioactivity of the intervention and facilitate iteration toward future trials that further improve patient outcomes. In pediatric cellular immunotherapy trials, correlative studies enable deeper understanding of T cell mobilization, durability of immune activation, patterns of toxicity, and early detection of treatment response. Here, we review the correlative science in adoptive cell therapy (ACT) for childhood central nervous system (CNS) tumors, with a focus on existing chimeric antigen receptor (CAR) and T cell receptor (TCR)-expressing T cell therapies., Recent Findings: We highlight long-standing and more recently understood challenges for effective alignment of correlative data and offer practical considerations for current and future approaches to multi-omic analysis of serial tumor, serum, and cerebrospinal fluid (CSF) biospecimens. We highlight the preliminary success in collecting serial cytokine and proteomics from patients with CNS tumors on ACT clinical trials., (© 2023. The Author(s).)

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6-18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95% CI 3.3-3.5 million) experiencing their first-ever stroke and another 2.3 million (95% CI 2.2-2.4 million) dying as a result. Additionally, approximately 12.5% (95% CI 12.4-12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95% CI 2.1-2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age ± standard error (SE) was (65.700 ± 0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean ± SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6 ± 16.3), ranging from (13,310.1 ± 12.8) in IS to (81,369.8 ± 260.7) in SAH, and out-of-pocket expenses were (5788.9 ± 8.6), ranging from (4449.0 ± 6.6) in IS to (30,778.2 ± 156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95% CI 9.2-9.2%), ranging from 6.4% (95% CI 6.4-6.5%) for IS to 21.8% for ICH (95% CI 21.8-21.9%). From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT + MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95% CI 3.2-3.3%), 7.7% (95% CI 7.5-8.0%), and 12.9% (95% CI 12.3-13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95% CI 8.8-9.0%), 16.5% (95% CI 16.2-16.9%), and 16.8% (95% CI 16.2-17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [% (95% CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95% CI 14.6-15.0%) and 14.0% (95% CI 13.8-14.2%), respectively. The mortality rate [% (95% CI)] of stroke at 3-month and 12-month was 4.2% (95% CI 4.1-4.3%) and 8.5% (95% CI 8.4-8.6%), respectively. The recurrence rate [% (95% CI)] of stroke at 3-month and 12-month was 3.6% (95% CI 3.5-3.7%) and 5.6% (95% CI 5.4-5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China., (© 2023. The Author(s).)

The aim of this work is to analyze the clinicopathological characteristics and prognostic factors of patients with nuclear pedigree of esophageal cancer. The clinicopathological data and follow-up information of 3,260 patients from different nuclear pedigree of esophageal cancer who underwent radical resection of esophageal cancer were collected, and the clinicopathological characteristics and prognostic factors of the patients were analyzed. The male to female ratio of 3,260 patients with esophageal cancer was 1.7:1. The diagnosis age was ranged from 32 to 85 (60.2 ± 8.1) years old. About 53.8% of the patients were ≥ 60 years old; About 88.8% of the patients came from the high incidence area of esophageal cancer; About 82.5% of the tumors were located in the middle and lower segments of esophagus; Poor, moderate and well differentiation accounted for 26.6%, 61.9% and 11.5% respectively; The surgical margin accounted for 94.3%; 47.6% of the tumors were shorter than 4 cm in length; Clinicopathological TNM stage (0+I) accounted for 15.2%, and stage II, III and IV accounted for 54.5%, 29.9% and 0.4%, respectively. Cox analysis showed that male, diagnosed age ≥ 60 years, tumor located in neck and upper esophageal segments, poor differentiation, tumor length ≥ 4 cm, and advanced TNM were independent risk factors for the prognosis of patients in nuclear pedigree with esophageal cancer. Gender, diagnosis age, tumor location, degree of differentiation, tumor length and TNM stage are the influencing factors for the prognosis of patients with nuclear pedigree of esophageal cancer, which will provide important data for the future study of esophageal cancer family aggregation., Competing Interests: Author JL was employed by Zhengzhou White Gown Translation Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Song, Zhao, Han, Bao, Han, Xu, Li, Fan, Wang, Li, Hu, Li, Li, Tan, Gao, Zhou and Wang.)

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.

Purpose: Some studies indicated that gender is associated with prognostic of cancer, However, currently the prognostic value of gender for gastric cardia adenocarcinoma (GCA) survival is unclear. The aim of our study is to reveal the influence of gender on the prognosis of patients with GCA., Patients and Methods: A total of 42,345 cases Chinese GCA patients were enrolled from our previously established GCA and esophageal cancer databases. The clinicopathological characteristics were retrieved from medical records in hospital. The follow-up was performed through letter, telephone or home interview. Among GCA patients, there were 32,544 (76.9%) male patients with the median age 62 years (range 17-97) and 9,801 (23.1%) female patients with the median age 61 years (range 17-95 years). The Chi-square test and Kaplan-Meier method were used to compare the continuous variables and survival. Cox proportional hazards model was used for competing risk analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated., Results: Men had shorter GCA-specific survival than women by multivariate analysis (HR 1.114; 95% CI 1.061 to 1.169; P < 0.001). Whether premenopausal, perimenopausal or postmenopausal, the survival of women was better than that of men (premenopausal vs. male, P < 0.001; perimenopausal vs. male, P < 0.001; postmenopausal vs. male, P = 0.035). It was worth noting that in patients with stages I, II, III, and IV, female patients survive longer than male patients (P = 0.049; P = 0.011; P < 0.001; P = 0.044, respectively)., Conclusion: Gender is an independent prognostic factor for patients with GCA. In comparison with men, women have a significantly better outcome. Smoking and drinking may be protective factors for male GCA patients., (© 2022. The Author(s).)

The stretching breakup of a conical liquid bridge is the core process of micro-dispensing. To precisely control the droplet loading and improve the dispensing resolution, a detailed study of bridge breakup with a moving contact line is required. A conical liquid bridge is established by an electric field and stretching breakup is investigated here. The effect of contact line state is investigated by examining the pressure at the symmetry axis. Compared to the pinned case, the moving contact line causes a shift of the pressure maximum from the bridge neck to top, and it facilitates the evacuation of the bridge top. For the moving case, factors affecting the contact line motion are then considered. The results show that the increase of the stretching velocity U and the decrease of the initial top radius R top accelerate the contact line motion. And the amount of contact line movement is basically constant. To analyze the influence of the moving contact line on bridge breakup, neck evolution is tracked under different U . An increase of U decreases the breakup time and increases the breakup position. Based on the breakup position and the remnant radius, the influences of U and R top on remnant volume V d are examined. It is found that V d decreases with an increase of U and increases with an increase of R top . Accordingly, different sizes of remnant volume can be obtained by adjusting U and R top . This is helpful for the optimization of liquid loading for transfer printing., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) in patients with B cell malignancies treated with chimeric antigen receptor (CAR) T cell therapy. We have observed a toxicity syndrome, distinct from CRS and ICANS, in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). Encompassing the concept of 'pseudoprogression,' but broader than inflammation-induced edema alone, TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of this entity, with the goal of standardizing both reporting and management., (© 2023. Springer Nature America, Inc.)

Inadequate hand-washing among chefs is a major contributor to outbreaks of foodborne illnesses originating in restaurants. Previous studies have found that mental health influences hygiene behaviors among food handlers, who have a high rate of job burnout. However, it is still unclear whether job burnout leads to restaurant kitchen chefs' poor hand washing behaviors (HWBs). In this study, we interviewed 453 restaurant kitchen chefs in Jiangsu Province, China regarding job burnout and HWBs during the summer (July-August) of 2020. The aims were to investigate job burnout (an individual internal motivation factor), identify determinants of job burnout, and examine the association between job burnout and HWBs. Variance analysis, post hoc multiple comparisons, linear regression models, and structural equation modeling were used to analyze the response data. This study revealed that chef age and the scale of the restaurant were significantly and negatively associated with reduced professional efficacy. Combined cuisine and pastry chefs had a more positive perception of their own professional efficacy than the other kitchen chefs, whereas the incidence of exhaustion was significantly higher in pastry chefs than in cuisine chefs and kitchen hands. Reduced professional efficacy was significantly and negatively associated with HWBs for all chefs. To improve the level of hand hygiene among chefs, measures should be taken to enhance chefs' professional efficacy. Furthermore, close attention should be paid to chefs in small-scale restaurants, younger chefs, cuisine chefs, pastry chefs, and kitchen hands.

Remodeling the active surface through fabricating heterostructures can substantially enhance alkaline water electrolysis driven by renewable electrical energy. However, there are still great challenges in the synthesis of highly reactive and robust heterostructures to achieve both ampere-level current density hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, we report a new Co/CeO 2 heterojunction self-supported electrode for sustainable overall water splitting. The self-supporting Co/CeO 2 heterostructures required only low overpotentials of 31.9 ± 2.2, 253.3 ± 2.7, and 316.7 ± 3 mV for HER and 214.1 ± 1.4, 362.3 ± 1.9, and 400.3 ± 3.7 mV for OER at 0.01, 0.5, and 1.0 A·cm -2 , respectively, being one of the best Co-based bifunctional electrodes. Electrolyzer constructed from this electrode acting as an anode and cathode merely required cell voltages of 1.92 ± 0.02 V at 1.0 A·cm -2 for overall water splitting. Multiple characterization techniques combined with density functional theory calculations disclosed the different active sites on the anode and cathode, and the charge redistributions on the heterointerfaces that can optimize the adsorption of H and oxygen-containing intermediates, respectively. This study presents the tremendous prospective of self-supporting heterostructures for effective and economical overall water splitting.

Background: The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I-III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China., Aim: To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China., Methods: The date of 158,618 patients with ESCC were collected from a database (1973-2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X 2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality., Results: In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients., Conclusion: Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year., Core Tip: Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery., 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 Lei, Song, Zhao, Xu, Wei, Sun, Wang, Yang, Hu, Zhong, Han, Han, Fan, Wang, Li, Zhou, Wang, Zhang, Bao, Qin, Chang, Ku, Yang, Yuan, Ren, Li and Wang.)

Background: This study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma., Methods: A total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What's more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis., Results: The patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable ( P <0.001). A clinical-pathological nomogram was constructed by combining clinical and pathological characteristics to predict the overall survival. In comparison with TNM stage, the concordance index and time-dependent receiver operating characteristic of the clinical-pathological nomogram showed better predictive value ( P <0.001). High quality of calibration plots in overall survival was noticed. As demonstrated by the decision curve analysis, the nomogram has better value than the TNM stage., Conclusions: As evidently revealed by the research findings, tumor-stroma ratio is an independent prognostic factor in patients with esophageal squamous cell carcinoma. The clinical-pathological nomogram has an incremental value compared TNM stage in predicting overall survival., 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 Hu, Song, Zhong, Zhao, Zhou, Xu, Li, Wang, Li, Wang, Lei, Wei, Wang, Fan, Han, Chen, Li, Ji, Yang, Li, Yang, Yang, Chang, Ren, Zhou and Wang.)

Chimeric antigen receptor (CAR) T cell immunotherapy is emerging as a powerful strategy for cancer therapy; however, an important safety consideration is the potential for off-tumor recognition of normal tissue. This is particularly important as ligand-based CARs are optimized for clinical translation. Our group has developed and clinically translated an IL13(E12Y) ligand-based CAR targeting the cancer antigen IL13Rα2 for treatment of glioblastoma (GBM). There remains limited understanding of how IL13-ligand CAR design impacts the activity and selectivity for the intended tumor-associated target IL13Rα2 versus the more ubiquitous unintended target IL13Rα1. In this study, we functionally compared IL13(E12Y)-CARs incorporating different intracellular signaling domains, including first-generation CD3ζ-containing CARs (IL13ζ), second-generation 4-1BB (CD137)-containing or CD28-containing CARs (IL13-BBζ or IL13-28ζ), and third-generation CARs containing both 4-1BB and CD28 (IL13-28BBζ). In vitro coculture assays at high tumor burden establish that second-generation IL13-BBζ or IL13-28ζ outperform first-generation IL13ζ and third-generation IL13-28BBζ CAR designs, with IL13-BBζ providing superior CAR proliferation and in vivo antitumor potency in human xenograft mouse models. IL13-28ζ displayed a lower threshold for antigen recognition, resulting in higher off-target IL13Rα1 reactivity both in vitro and in vivo . Syngeneic mouse models of GBM also demonstrate safety and antitumor potency of murine IL13-BBζ CAR T cells delivered systemically after lymphodepletion. These findings support the use of IL13-BBζ CARs for greater selective recognition of IL13Rα2 over IL13Rα1, higher proliferative potential, and superior antitumor responsiveness. This study exemplifies the potential of modulating factors outside the antigen targeting domain of a CAR to improve selective tumor recognition., Significance: This study reveals how modulating CAR design outside the antigen targeting domain improves selective tumor recognition. Specifically, this work shows improved specificity, persistence, and efficacy of 4-1BB-based IL13-ligand CARs. Human clinical trials evaluating IL13-41BB-CAR T cells are ongoing, supporting the clinical significance of these findings., Competing Interests: B. Badie reports grants from NIH during the conduct of the study; in addition, B. Badie has a patent to CAR T Cell delivery pending. C.E. Brown reports personal fees and other research support from Mustang Bio during the conduct of the study; personal fees from Chimeric Therapeutics outside the submitted work; in addition, C.E. Brown has a patent to US9914909B2 issued, licensed, and with royalties paid. No disclosures were reported by the other authors., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: Stroke has been the leading cause of death in China for decades. The extremely low intravenous thrombolysis rate is largely due to the prehospital delays that make patients ineligible for the time-sensitive therapy. Limited studies evaluated prehospital delays across China. We investigated prehospital delays in the stroke population across China and the associated age, rurality, and geographic disparities., Methods: A cross-sectional study design was employed using the Bigdata Observatory platform for Stroke of China in 2020, the nationwide, prospective, multicentre registry of patients with acute ischaemic stroke (AIS). Mixed-effect regression models were used to account for the clustered data., Findings: The sample contained 78,389 AIS patients. The median onset-to-door (OTD) time was 24 h, with only 11.79% (95% confidence interval [CI]: 11.56-12.02%) patients arriving at hospitals within 3 h. About 12.43% (95% CI: 12.11-12.74%) of patients 65 years or older arrived at hospitals within 3 h, which was significantly higher than the young and middle-aged patients (11.03%; 95% CI: 10.71-11.36%). After controlling for potential confounders, young and middle-aged patients were less likely to present to hospitals within 3 h (adjusted odds ratio: 0.95; 95% CI: 0.90-0.99) compared to patients 65 years or older. The 3-h hospital arrival rate was the highest in Beijing (18.40%, 95% CI: 16.01-20.79%), which was almost 5 times higher than that in Gansu (3.45%, 95% CI: 2.69-4.20%). The arrival rate in urban areas was almost 2 times higher than that in rural areas (13.35% versus. 7.66%)., Interpretation: We found that the low rates of timely arrival at hospitals after a stroke is more salient in the younger population, rural settings, or those residing in less developed geographic regions. This study calls for more tailored interventions focusing on younger people, rural areas, and less developed geographic regions., Funding: The National Natural Science Foundation of China; CIHR, Grant/Award Number: 81973157, PI: JZ. Natural Science Foundation of Shanghai; CIHR, Grant/Award Number: 17dz2308400, PI: JZ. Funding from the University of Pennsylvania; Grant/Award Number: CREF-030, PI: RL., Competing Interests: There are no financial conflicts of interest to disclose., (© 2023 The Author(s).)

Background: Quinoa is a good gluten-free resource for food processing, especially bread making, and can improve and prevent the development of complications associated with celiac disease (CD). However, lack of gluten affects quinoa bread quality. Previous research showed that soy protein isolate (SPI) could improve gluten-free bread quality to some extent. Therefore, this study investigated the effects of SPI on the physical properties of quinoa dough and gluten-free bread quality characteristics., Results: Results showed that, with appropriate SPI substitution, the farinograph properties of quinoa flour significantly improved (P < 0.05). The sample with 8% SPI substitution showed a better development time (DT, 3.30 ± 0.20 min), stability time (ST, 8.80 ± 0.10 min) and softening degree (SD, 8.80 ± 0.10 FU), which were close to those of wheat flour, although more water absorption (WA, 76.40 ± 2.10%) was needed than for wheat flour (66.30 ± 3.10%). The extensograph properties of quinoa flour also significantly improved after 8% SPI substitution (P < 0.05). Furthermore, SPI substitution increased G' moduli of quinoa dough and decreased tan δ to some extent, providing better rheological properties closer to those of wheat dough. SPI substitution also improved the quality and texture of quinoa bread and reduced the gap with wheat bread. When SPI substitution was 8%, the specific volume, hardness and springiness of quinoa bread were 2.29 ± 0.05 mL g -1 , 1496.47 ± 85.21 g and 0.71 ± 0.03%, respectively., Conclusion: These results suggested that SPI substitution would be an effective way to develop higher-quality gluten-free bread. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies, which are being harnessed to improve solid tumor CAR T cell therapies. Here, we describe fully optimized CAR T cells targeting tumor-associated glycoprotein-72 (TAG72) for the treatment of solid tumors, identifying the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. These findings have culminated into a phase 1 trial evaluating safety, feasibility, and bioactivity of TAG72-CAR T cells for the treatment of patients with advanced ovarian cancer ( NCT05225363 ). Preclinically, we found that CAR T cell-mediated IFNγ production facilitated by IL-12 signaling was required for tumor cell killing, which was recapitulated by expressing an optimized membrane-bound IL-12 (mbIL12) molecule on CAR T cells. Critically, mbIL12 cell surface expression and downstream signaling was induced and sustained only following CAR T cell activation. CAR T cells with mbIL12 demonstrated improved antigen-dependent T cell proliferation and potent cytotoxicity in recursive tumor cell killing assays in vitro and showed robust in vivo anti-tumor efficacy in human xenograft models of ovarian cancer peritoneal metastasis. Further, locoregional administration of TAG72-CAR T cells with antigen-dependent IL-12 signaling promoted durable anti-tumor responses against both regional and systemic disease in mice and was associated with improved systemic T cell persistence. Our study features a clinically-applicable strategy to improve the overall efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting both regional and systemic disease.

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P <0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P <0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m 2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P <0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P <0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P <0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P <0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P <0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P <0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P =0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P >0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P >0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Keratin pearls (KP) is an important indicator of the degree of tumor cell differentiation of esophageal squamous cell carcinomas (ESCC). However, the independent prognostic value of KP in ESCC patients remains unclear. The hematoxylin-eosin (H&E) stained tissue microarrays (TMAs) or whole slides of the patients were prepared to identify the existence of KP. Kaplan-Meier (KM) survival analysis as well as univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of KP. A nomogram based on KP and other clinicopathologic characteristics was constructed. The C-index, calibration curve, Receiver Operating Characteristic (ROC) curve, and Decision Curve Analysis (DCA) were used to evaluate the nomogram. The results indicated KP is a protective factor against lymph node metastasis and is closely associated with the differentiation degree in ESCC patients. KM survival analysis showed that the overall survival (OS) of patients with KP was significantly better than for patients without KP. In addition, multivariate Cox regression analysis revealed that KP was an independent predictor of OS. Furthermore, ROC curve demonstrated that KP combined with differentiation degree could more accurately predict the 5-year survival rate than differentiation degree alone. Importantly, the nomogram showed good discrimination and calibration abilities in both training and validation groups, which could more accurately predict the 3-, 5-, and 10-year survival rates of ESCC patients and adds to the predictive value of TNM stage alone. In conclusion, KP is an independent predictor of prognosis in patients with ESCC and provides incremental prognostic value to degree of differentiation., Competing Interests: None., (AJTR Copyright © 2022.)