iGWAS: Image-based genome-wide association of self-supervised deep phenotyping of retina fundus images.

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes and identified 14 loci with genome-wide significance (p<5×10-8 and intersection of hits from left and right eyes). We also did GWAS on the retina color, the average color of the center region of the retinal fundus photos. The GWAS of retina colors identified 34 loci, 7 are overlapping with GWAS of raw image phenotype. Our results establish the feasibility of this new framework of genomic study based on self-supervised phenotyping of medical images.

Effect of paternal-maternal parenting styles on college students' internet addiction of different genders: The mediating role of life satisfaction.

This study aimed to understand the current situation of paternal-maternal parenting style, life satisfaction, and internet addiction among college students and explored the influence of paternal-maternal parenting styles and life satisfaction on the internet addiction of male and female college students. A questionnaire survey was administered to 967 college students in China. Life satisfaction partially mediated the effect of the paternal-maternal parenting styles on the internet addiction among college students. However, this mediating role completely varied by gender, and the dimensions of parental styles also had different effects. For male college students, life satisfaction mediated the two dimensions of parenting styles (the father's emotional warmth, the father's overprotection) and internet addiction; the mother's emotional warmth directly related to the internet addiction. Among females, life satisfaction played a partial mediating role between two dimensions of parenting styles (the father's emotional warmth, the mother's interference and protection) and internet addiction. the father's punitiveness and over-involvement were directly related to female students' internet addiction. The study reveals that the mediating effect of life satisfaction on parenting styles and internet addiction among college students is influenced by gender, and the relationship between different parenting styles and internet addiction also varies. These findings indicate that paying attention to the role of the family, especially the parenting style of fathers, is crucial for preventing internet addiction in the future. Prevention and intervention should be treated differently for male and female students.

Wh-Words: Existential or Universal Quantifiers in Child Mandarin?

Wh-words have been analysed as existential quantifiers (Chierchia in Logic in grammar: polarity, free choice, and intervention. Oxford University Press, Oxford, 2013; Fox, in Sauerland U, Stateva P (eds) Presupposition and implicature in compositional semantics (Palgrave studies in pragmatics, language and cognition). Palgrave MacMillan, Houndmills, pp 71-120, 2007; Liao in Alternative and exhaustification: non-interrogative uses of Chinese wh-words. Harvard University, 2010) or universal quantifiers (Nishigauchi, in: Theoretical and applied linguistics at Kobe Shoin 2, Kobe Shoin Institute for Linguistic Sciences, 1999). These two accounts have distinct predictions on how children initially interpret wh-words. The universal account predicts that children should initially interpret wh-words as universal quantifiers, whereas the existential account anticipates that children should start out with the existential interpretation. To adjudicate between the two accounts, the present study was designed to explore pre-schoolers' semantic knowledge of wh-quantification. Specifically, it investigated the interpretation of the wh-word shenme 'what' with 4-and 5-year-old Mandarin-speaking children and a control group of adults. Using a Truth Value Judgment Task (Crain and Thornton in Investigations in universal grammar: a guide to experiments on the acquisition of syntax and semantics. MIT Press, Cambridge, 1998), Experiment 1 evaluated whether children interpret the wh-word shenme 'what' as closer in meaning to the polarity sensitive item renhe 'any' or the universal quantifier suoyou 'all' in the antecedent of ruguo 'if' conditionals. Using a Question-Answer Task, Experiments 2 & 3 respectively investigated whether children interpret shenme 'what' as closer in meaning to renhe 'any' or suoyou 'all' in two types of questions: yes-no questions with the particle ma and A-not-A questions. It was found that both children and adults interpret shenme 'what' as closer in meaning to renhe 'any' than suoyou 'all'. The findings suggest that Mandarin-speaking pre-schoolers already have adult-like semantic knowledge of wh-quantification: wh-words are existential quantifiers rather than universal quantifiers. Due to the paucity of primary linguistic input, children's early mastery of the non-interrogative wh-words appear to support the biolinguistic approach to language acquisition (Chomsky in Aspects of the theory of syntax. MIT Press, Cambridge, 1965; Pinker in Language learnability and language development. Harvard University Press, Cambridge, 1984; Crain et al. in Language acquisition from a biolinguistic perspective. Neurosci Biobehav Rev, 2016. https://doi.org/10.1016/j.neubiorev.2016.09.004 ).

Sustainable upcycling of mixed spent cathodes to a high-voltage polyanionic cathode material.

Sustainable battery recycling is essential for achieving resource conservation and alleviating environmental issues. Many open/closed-loop strategies for critical metal recycling or direct recovery aim at a single component, and the reuse of mixed cathode materials is a significant challenge. To address this barrier, here we propose an upcycling strategy for spent LiFePO4 and Mn-rich cathodes by structural design and transition metal replacement, for which uses a green deep eutectic solvent to regenerate a high-voltage polyanionic cathode material. This process ensures the complete recycling of all the elements in mixed cathodes and the deep eutectic solvent can be reused. The regenerated LiFe0.5Mn0.5PO4 has an increased mean voltage (3.68 V versus Li/Li+) and energy density (559 Wh kg-1) compared with a commercial LiFePO4 (3.38 V and 524 Wh kg-1). The proposed upcycling strategy can expand at a gram-grade scale and was also applicable for LiFe0.5Mn0.5PO4 recovery, thus achieving a closed-loop recycling between the mixed spent cathodes and the next generation cathode materials. Techno-economic analysis shows that this strategy has potentially high environmental and economic benefits, while providing a sustainable approach for the value-added utilization of waste battery materials.

p21/Zbtb18 repress the expression of cKit to regulate the self-renewal of hematopoietic stem cells.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.

Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow.

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.

Views of Hong Kong Chinese medicine practitioners on the application of the "Chinese Medicine Anti-epidemic Plans" prepared by the Chinese medicine expert group of central authorities: a focus group study.

BACKGROUND: Drawing on the extensive utilization of traditional Chinese medicine (TCM) to combat COVID-19 in Mainland China, experts designed a series of TCM anti-epidemic strategies. This study aims to understand Hong Kong CM practitioners' application of and opinions on the "Chinese Medicine Anti-epidemic Plans." METHODS: Online focus group interviews were conducted, and purposive sampling was employed to invite 22 CM practitioners to voluntarily participate in three interview sessions. The interviews were audio recorded, then transcribed verbatim. The transcripts were analyzed using template analysis. RESULTS: Three themes were derived: (1) facilitators of the "Chinese Medicine Anti-epidemic Plans," (2) barriers of the "Chinese Medicine Anti-epidemic Plans," and (3) expectations on improving the "Chinese Medicine Anti-epidemic Plans." The participants could obtain relevant information from various sources, which highlights the value of the plans for TCM medicinal cuisine and non-pharmacologic therapies and guiding junior CM practitioners, supplementing Western medicine interventions, and managing Chinese herb reserves in clinics. However, the barriers included the lack of a specialized platform for timely information release, defective plan content, limited reference value to experienced CM practitioners, and lack of applicability to Hong Kong. The expectations of the CM practitioners for improving the plans were identified based on the barriers. CONCLUSIONS: To enhance the implementation of the anti-epidemic plans, CM practitioners in Hong Kong expect to utilize a specific CM platform and refine the plans to ensure that they are realistic, focused, comprehensive, and tailored to the local context.

A novel long non-coding RNA MIR4500HG003 promotes tumor metastasis through miR-483-3p-MMP9 axis in triple-negative breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.

Advanced anaerobic digestion of household food waste pretreated by in situ-produced mixed enzymes via solid-state fermentation: Feasibility and application perspectives.

Enzymatic pretreatment is an effective method which can improve the anaerobic digestion (AD) efficiency of household food waste (HFW). As an alternative to expensive commercial enzymes, mixed enzymes (MEs) produced in situ from HFW by solid-state fermentation (SSF) can greatly promote the hydrolysis rate of HFW and achieve advanced anaerobic digestion (AAD) economically sustainable. In this paper, strategies for improving the efficiency of the enzyme-production process and the abundance of MEs are briefly discussed, including SSF, fungal co-cultivation, and stepwise fermentation. The feasibility of using HFW as an applicable substrate for producing MEs (amylase, protease, and lignocellulose-degrading enzymes) and its potential advantages in HFW anaerobic digestion are comprehensively illustrated. Based on the findings, an integrated AAD process of HFW pretreated with MEs produced in situ was proposed to maximise bioenergy recovery. The mass balance results showed that the total volatile solids removal rate could reach 98.56%. Moreover, the net energy output could reach 2168.62 MJ/t HFW, which is 9.79% higher than that without in situ-produced MEs and pretreatment. Finally, perspectives for further study are presented.

Recent Trends and Innovations in Bead-Based Biosensors for Cancer Detection.

Demand is strong for sensitive, reliable, and cost-effective diagnostic tools for cancer detection. Accordingly, bead-based biosensors have emerged in recent years as promising diagnostic platforms based on wide-ranging cancer biomarkers owing to the versatility, high sensitivity, and flexibility to perform the multiplexing of beads. This comprehensive review highlights recent trends and innovations in the development of bead-based biosensors for cancer-biomarker detection. We introduce various types of bead-based biosensors such as optical, electrochemical, and magnetic biosensors, along with their respective advantages and limitations. Moreover, the review summarizes the latest advancements, including fabrication techniques, signal-amplification strategies, and integration with microfluidics and nanotechnology. Additionally, the challenges and future perspectives in the field of bead-based biosensors for cancer-biomarker detection are discussed. Understanding these innovations in bead-based biosensors can greatly contribute to improvements in cancer diagnostics, thereby facilitating early detection and personalized treatments.

Immunogenic Material Vaccine for Cancer Immunotherapy by Structure-Dependent Immune Cell Trafficking and Modulation.

Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination is reported. The immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod-like bacteria) is precisely manipulated. The results reveal that innate immune cells accurately sense and respond to the architectures, of which two outperformed material candidates (151 nm hollow spheres and hollow microrods with an aspect ratio of 4.5) show higher competence in creating local proinflammatory environment with promoted innate immune cell influx and stimulation on dendritic cells (DCs). In combination with viral peptides, model proteins, or cell lysate antigens, the outperformed microrod material remarkably primes antigen-specific CD8 cytolytic T cells. In prophylactic and therapeutic regimens, the microrod adjuvanted vaccines display optimal aptitude in tumor suppression in four aggressive murine tumor models, by promoting the infiltration of heterogeneous cytolytic effector cells while decreasing suppressive immunoregulatory populations in tumors. This study demonstrates that a rationally selected architecture of immunogenic materials potentially advances the clinical reality of cancer vaccination.

The ATF4-RPS19BP1 axis modulates ribosome biogenesis to promote erythropoiesis.

Hematopoietic differentiation is controlled by intrinsic regulators and the extrinsic hematopoietic niche. Activating transcription factor 4 (ATF4) plays a crucial role in the function of fetal and adult hematopoietic stem cell maintenance; however, the precise function of ATF4 in the bone marrow niche and the mechanism by which ATF4 regulates adult hematopoiesis remain largely unknown. Here, we employ four cell-type-specific mouse Cre lines to achieve conditional knockout of Atf4 in Cdh5+ endothelial cells, Prx1+ bone marrow stromal cells, Osx+ osteo-progenitor cells, and Mx1+ hematopoietic cells, and uncover the role of Atf4 in niche cells and hematopoiesis. Intriguingly, depletion of Atf4 in niche cells does not affect hematopoiesis; however, Atf4-deficient hematopoietic cells exhibit erythroid differentiation defects, leading to hypoplastic anemia. Mechanistically, ATF4 mediates direct regulation of Rps19bp1 transcription, which is, in turn, involved in 40S ribosomal subunit assembly to coordinate ribosome biogenesis and promote erythropoiesis. Finally, we demonstrate that under conditions of 5-fluorouracil-induced stress, Atf4 depletion impedes the recovery of hematopoietic lineages, which requires efficient ribosome biogenesis. Taken together, our findings highlight the indispensable role of the ATF4-RPS19BP1 axis in the regulation of erythropoiesis.

The FGFR2 Variant rs13387042 is Associated With Breast Cancer Risk: A Meta-Analysis and Systematic Review.

OBJECTIVE: The association of FGFR2-rs13387042 polymorphism with breast cancer (BC) susceptibility in women remains inconclusive due to varying reports. In this study, we conducted a meta-analysis to explore the relationship between FGFR2-rs13387042 polymorphism and susceptibility to BC. METHODS: Relevant literature were acquired through searches across multiple databases. Odds ratio (OR) values were pooled to assess the risk of BC for different alleles and genotypes. The heterogeneity among the included literature was evaluated. Sensitivity analysis was used to verify the stability of the results. Egger's linear regression test was used to assess the significance of publication bias of the included literature. RESULTS: A total of 17 publications were included, encompassing 122,607 cases and 175,966 controls. There was significantly increased risk of BC for allele A compared with G (OR = 1.15, 95% CI = 1.14-1.67, P < .001), genotype AA compared with GG (OR = 1.34, 95% CI = 1.29-1.38, P < .001), and genotype GA compared with GG (OR = 1.19, 95% CI = 1.12-1.26, P < .001). Both Egger's test and funnel plot indicated the presence of publication bias. After adjusting potential publication bias by the trim-and-fill method, the comparison of allele A versus G (OR = 1.15, 95% CI = 1.13-1.17, P < .001), genotype AA versus GG (OR = 1.32, 95% CI = 1.28-1.37, P < .001), and genotype GA versus GG (OR = 1.15, 95% CI = 1.09-1.22, P < .001) remained statistically significant. In various subgroups, the allele A showed significantly higher risk of BC upon allele G in estrogen receptor (ER) positive BC, ER negative BC, progesterone receptor (PR) positive BC, PR negative BC, triple-negative BC, pathological grade I BC, grade II BC, and grade III breast cancer. The subsequent sensitivity analysis suggested the above findings stable and reliable. CONCLUSION: In this study, we found that the allele A of the FGFR2-rs13387042 polymorphism is associated with increased risk of developing breast cancer. This study underscores its potential as a genetic marker for personalized risk assessment and targeted interventions.

Unique Hierarchically Structured High-Entropy Alloys with Multiple Adsorption Sites for Rechargeable Li-CO2 Batteries with High Capacity.

Lithium-carbon dioxide (Li-CO2) batteries offer the possibility of synchronous implementation of carbon neutrality and the development of advanced energy storage devices. The exploration of low-cost and efficient cathode catalysts is key to the improvement of Li-CO2 batteries. Herein, high-entropy alloys (HEAs)@C hierarchical nanosheet is synthesized from the simulation of the recycling solution of waste batteries to construct a cathode for the first time. Owing to the excellent electrical conductivity of the carbon material, the unique high-entropy effect of the HEAs, and the large number of catalytically active sites exposed by the hierarchical structure, the FeCoNiMnCuAl@C-based battery exhibits a superior discharge capability of 27664 mAh g-1 and outstanding durability of 134 cycles as well as low overpotential with 1.05 V at a discharge/recharge rate of 100 mA g-1. The adsorption capacity of different sites on the HEAs is deeply understood through density functional theory calculations combined with experiments. This work opens up the application of HEAs in Li-CO2 batteries catalytic cathodes and provides unique insights into the study of adsorption active sites in HEAs.

Development of a Risk Assessment Model for Predicting Red Blood Cell Transfusion in Neonatal Patients.

BACKGROUND: The goal was to develop a risk assessment model for predicting red blood cell (RBC) transfusion in neonatal patients to assist hospital blood supply departments in providing small portions of RBCs to those requiring RBC transfusion on time. METHODS: Clinical information was collected from 1,201 children admitted to the neonatal unit. Clinical factors associated with predicting RBC transfusion were screened, and prediction models were developed using stepwise and multifactorial logistic regression analyses, followed by the evaluation of prediction models using receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Overall, 81 neonatal patients were transfused with RBCs, and the variables of gestational age at birth, age < 1 month, receipt of mechanical ventilation, and infant anemia were included in the final prediction model. The area under the curve of the prediction model was 0.936 (0.921 - 0.949), which was significantly higher than that of the individual indicators of gestational age at birth, age at admission < 1 month, receipt of mechanical ventilation, and infant anemia (p < 0.001). DCA showed a standardized net benefit for the possible risk of infant RBC transfusion at 0.1 - 1.0. CONCLUSIONS: We developed a risk assessment model to predict the risk of RBC transfusion in neonatal patients that can effectively assess the risk of RBC transfusion in children.

Constructing Bipolar Dual-Active Sites through High-Entropy-Induced Electric Dipole Transition for Decoupling Oxygen Redox.

It remains a significant challenge to construct active sites to break the trade-off between oxidation and reduction processes occurring in battery cathodes with conversion mechanism, especially for the oxygen reduction and evolution reactions (ORR/OER) involved in the zinc-air batteries (ZABs). Here, using a high-entropy-driven electric dipole transition strategy to activate and stabilize the tetrahedral sites is proposed, while enhancing the activity of octahedral sites through orbital hybridization in a FeCoNiMnCrO spinel oxide, thus constructing bipolar dual-active sites with high-low valence states, which can effectively decouple ORR/OER. The FeCoNiMnCrO high-entropy spinel oxide with severe lattice distortion, exhibits a strong 1s→4s electric dipole transition and intense t2g(Co)/eg(Ni)-2p(OL) orbital hybridization that regulates the electronic descriptors, eg and t2g, which leads to the formation of low-valence Co tetrahedral sites (Coth) and high-valence Ni octahedral sites (Nioh), resulting in a higher half-wave potential of 0.87 V on Coth sites and a lower overpotential of 0.26 V at 10 mA cm-2 on Nioh sites as well as a superior performance of ZABs compared to low/mild entropy spinel oxides. Therefore, entropy engineering presents a distinctive approach for designing catalytic sites by inducing novel electromagnetic properties in materials across various electrocatalytic reactions, particularly for decoupling systems.

Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Metabolic score for insulin resistance (METS-IR) and new-onset type 2 diabetes in a middle-aged and elderly population: a nationwide prospective cohort study and implications for primary care.

BACKGROUND: The metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of IR, yet longitudinal evidence supporting the utility of METS-IR in primary prevention of type 2 diabetes mellitus (T2DM) remains limited. OBJECTIVE: We aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles and anthropometrics that can be routinely obtained in resource-limited primary care settings, and incidence of new-onset T2DM. METHODS: We conducted a closed-cohort analysis of a nationwide, prospective cohort of 7,583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of subjects stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in subjects overall, and in subjects stratified by baseline BP. We also applied net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to examine the incremental value of METS-IR. RESULTS: During a mean follow-up period of 6.3 years, T2DM occurred in 527 subjects, among which, two-thirds (63.0%, 95% confidence interval [CI]: 58.7% to 67.1%) had baseline FPG <110 mg/dL. A standard deviation unit increase in baseline METS-IR was associated with the first incidence of T2DM (adjusted hazard ratio [aHR]=1.33, 1.22 to 1.45, P<.001) in all participants. Similar results were obtained in subjects with normal baseline BP (aHR=1.41, 1.22 to 1.62, P<.001) and elevated baseline BP (aHR=1.29, 1.16 to 1.44, P<.001). The predictive capability for incident T2DM improved by adding METS-IR to FPG. In study subjects with new-onset T2DM whose baseline FPG <126 mg/dL and <110 mg/dL, 63.0% (95%CI, 60.0% to 65.9%) and 58.1% (95%CI, 54.3% to 61.9%) of subjects had baseline METS-IR above the cut-off values, respectively. CONCLUSIONS: METS-IR was significantly associated with new-onset T2DM regardless of baseline BP level. Regular monitoring of METS-IR on top of routine blood glucose in clinical practice may add to the ability to enhance the early identification of primary care population at risk for T2DM.

Preoperative localization for pulmonary nodules: a meta-analysis of coil and liquid materials.

PURPOSE: This study was designed to conduct pooled comparisons of the relative clinical efficacy and safety of computed tomography (CT)-guided localization for pulmonary nodules (PNs) using either coil- or liquid material-based approaches. MATERIAL AND METHODS: Relevant articles published as of July 2023 were identified in the Web of Science, PubMed, and Wanfang databases, and pooled analyses of relevant endpoints were then conducted. RESULTS: Six articles that enrolled 287 patients (341 PNs) and 247 patients (301 PNs) that had respectively undergone CT-guided localization procedures using coil- and liquid material-based approaches prior to video-assisted thoracic surgery (VATS) were included in this meta-analysis. The liquid material group exhibited a significantly higher pooled successful localization rate as compared to the coil group (p = 0.01), together with significantly lower pooled total complication rates (p = 0.0008) and pneumothorax rates (p = 0.01). Both groups exhibited similar rates of pulmonary hemorrhage (p = 0.44) and successful wedge resection (p = 0.26). Liquid-based localization was also associated with significant reductions in pooled localization and VATS procedure durations (p = 0.004 and 0.007). CONCLUSIONS: These data are consistent with CT-guided localization procedures performed using liquid materials being safer and more efficacious than coil-based localization in patients with PNs prior to VATS resection.

Insufficient secretion of pancreatic FGF21 is the toxicological mechanism and therapeutic target of asparaginase-associated pancreatitis.

Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute lymphoblastic leukemia among children and adolescents. The toxicological mechanism of AAP is not yet clear, and there are no effective preventive and treatment measures available clinically. Fibroblast growth factor 21 (FGF21) is a secretory hormone that regulates lipid, glucose, and energy metabolism balance. Acinar tissue is the main source of pancreatic FGF21 protein and plays an important role in maintaining pancreatic metabolic balance. In this study, we found that the decrease of FGF21 in pancreas is closely related to AAP. Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. The specific expression of FGF21 in the acinar tissue of AAP rats was significantly downregulated. Asparaginase caused dysregulation of the ATF4/ATF3/FGF21 axis in acinar tissue or cells, and thus mediated the decrease of FGF21. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.