Iron deficiency at birth and risk of hidden hearing loss in infants modification by socioeconomic status: mother-newborn cohort in Shenyang, China.

OBJECTIVE: The diagnosis of hidden hearing loss (HHL) in calm state has not yet been determined, while the nutritional status is not involved in its pathogenic risk factors. In utero iron deficiency (ID) may delay auditory neural maturation in infants. We evaluated the association between ID and HHL as well as the modification effect of socioeconomic status (SES) on this association in newborns. STUDY DESIGN: We included 859 mother-newborns from the baseline of this observational northeast cohort. Data on exposure assessment included iron status [maternal hemoglobin (Hb) and neonatal heel prick serum ferritin (SF)] and SES (occupation, education and income). Auditory neural maturation was reflected by auditory brainstem response (ABR) testing and electrocochleography (ECochG). RESULTS: Iron status and SES were independently and jointly associated with the prediction of neonatal HHL by logistic and linear regression model. The mediation effects were performed by Process. ID increased absolute latency wave V, interpeak latency (IPL) III-V, and summting potentials (SP) /action potentials (AP), which were combined as HHL. Low SES showed the highest risk of HHL and the highest levels of related parameters in ID newborns. Moreover, after Corona Virus Disease 2019 (COVID-19) were positive, preschool children who experience ID in neonatal period were more likely to suffer from otitis media with effusion (OME). High SES also showed similar risk effects. CONCLUSION: Both low and high SES may strengthen the risk of ID on neonatal HHL in Northeast China.

Curcumin simultaneously improves mitochondrial dynamics and myocardial cell bioenergy after sepsis via the SIRT1-DRP1/PGC-1α pathway.

Septic cardiomyopathy (SCM) is associated with an imbalance in mitochondrial quality and high mortality rates, with no effective treatment developed to date. Curcumin provides antioxidant, anti-inflammatory, cardiovascular, and mitochondrial protection. However, curcumin has not been confirmed to improve cardiac dysfunction in sepsis. We hypothesized that curcumin can reduce abnormal inflammatory responses by improving mitochondrial function as a novel mechanism to improve SCM. To explore this hypothesis, we used an in vivo male C57BL/6 mouse sepsis model and an in vitro model of lipopolysaccharide-stimulated HL-1 cells. The effects of curcumin on sepsis-induced cardiac dysfunction, inflammatory responses, and mitochondrial quality of cardiac cells were observed using quantitative polymerase chain reaction, western blotting, echocardiography, and transmission electron microscopy. Curcumin activated sirtuin 1 (SIRT1); increased expression of the mitochondrial biogenesis-related genes Pgc1α, Tfam, and Nrf2; reduced dynamin-related protein 1 translocation from the cytoplasm to mitochondria; and restored the mitochondrial morphology and function in cardiac cells. Accordingly, curcumin protected heart function after septic shock and alleviated the effects of SCM. SIRT1 knockdown reversed the protective effects of curcumin on mitochondria. Therefore, curcumin promotes mitochondrial biogenesis and inhibits mitochondrial fragmentation by activating SIRT1, thereby improving the mitochondrial quality and reducing oxidative stress in cardiomyocytes and sepsis-induced cardiac dysfunction. These findings provide new evidence supporting the use of curcumin to treat SCM.

Development of hybrid electrospun alginate-pulverized moringa composites.

The consideration of biopolymers with natural products offers promising and effective materials with intrinsic and extrinsic properties that are utilized in several applications. Electrospinning is a method known for its unique and efficient performance in developing polymer-based nanofibers with tunable and diverse properties presented as good surface area, morphology, porosity, and fiber diameters during fabrication. In this work, we have developed an electrospun sodium alginate (SA) incorporated with pulverized Moringa oleifera seed powder (PMO) as a potential natural biosorbent material for water treatment applications. The developed fibers when observed using a scanning electron microscope (SEM), presented pure sodium alginate with smooth fiber (SAF) characteristics of an average diameter of about 515.09 nm (±114.33). Addition of pulverized Moringa oleifera at 0.5%, 2%, 4%, 6%, and 8% (w/w) reduces the fiber diameter to an average of about 240 nm with a few spindle-like pulverized Moringa oleifera particles beads of 300 nm (±77.97) 0.5% particle size and 110 nm (±32.19) with the clear observation of rougher spindle-like pulverized Moringa oleifera particle beads of 680 nm (±131.77) at 8% of alginate/Moringa oleifera fiber (AMF). The results from the rheology presented characteristic shear-thinning or pseudoplastic behaviour with a decline in viscosity, with characteristic behaviour as the shear rate increases, indicative of an ideal polymer solution suitable for the spinning process. Fourier transform infrared spectroscopy (FT-IR) shows the presence of amine and amide functional groups are prevalent on the alginate-impregnated moringa with water stability nanofibers and thermogravimetric analysis (TGA) with change in degradation properties in a clear indication and successful incorporation of the Moringa oleifera in the electrospun fiber. The key findings from this study position nanofibers as sustainable composites fiber for potential applications in water treatment, especifically heavy metal adsorption.

Association between the oxidative balance score and thyroid function: Results from the NHANES 2007-2012 and Mendelian randomization study.

BACKGROUND: Oxidative stress is a significant contributor to the development of various diseases, and the oxidative balance score (OBS) is a valuable tool for assessing the impact of dietary and lifestyle factors on oxidative stress in humans. Nevertheless, the precise relationship between OBS and thyroid function in adults remains elusive. METHODS: This cross-sectional study comprised 6222 adult participants drawn from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012. Employing weighted multivariable linear regression modeling, the study estimated the connection between OBS quartiles and thyroid functions. The causal relationship between OBS components and thyroid function was analyzed by Mendelian randomization (MR). RESULTS: We found a significant negative correlation between OBS and free thyroxine (FT4) and total thyroxine (TT4). Univariate and multivariate MR Analyses showed a causal relationship between BMI and FT4. Copper, smoking, and riboflavin showed a causal relationship with FT4 after moderation. CONCLUSION: We found that a lifestyle high in antioxidant exposure reduced FT4 and TT4 levels in the population. We suggest that BMI, Copper, and Riboflavin are important factors in the regulation of FT4 levels.

Pharmacokinetics, Safety, and Tolerability of Cedirogant in Healthy Japanese and Chinese Adults.

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma, thymus (RORγt) developed for treatment of psoriasis. This study aimed to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of cedirogant following a single oral dose in Japanese participants and multiple oral doses in Japanese and Chinese participants. The single doses evaluated in healthy Japanese participants were 75, 225, and 395 mg. The multiple doses evaluated in both healthy Japanese and Chinese participants was 375 mg once daily for 14 days. Cedirogant plasma exposure increased dose proportionally with administration of single doses. Maximum cedirogant plasma concentration was reached within a median time of 4-5 hours after dosing. The harmonic mean elimination half-life ranged from 19 to 25 hours. Cedirogant pharmacokinetics were similar between Japanese and Chinese participants. Compared with healthy Western participants in a cross-study analysis, steady-state cedirogant plasma exposure was 38%-73% higher in Japanese or Chinese participants. Ex vivo interleukin-17 inhibition increased in a dose-dependent manner and was maximized by 375 mg once-daily doses. The cedirogant regimens tested were generally well tolerated, and no new safety issues were identified. The results supported enrollment of Japanese and Chinese subjects in subsequent clinical trials for cedirogant.

Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance.

CONTEXT: Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection. OBJECTIVE: To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality. MATERIALS AND METHODS: A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1's safe dosage. Groups for each model were: in vivo-a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro-a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 µM for 30 min). NGR1's effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated. RESULTS: Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 µM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis. DISCUSSION AND CONCLUSIONS: Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1's efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Low-dose Olaparib improves septic cardiac function by reducing ferroptosis via accelerated mitophagy flux.

Sepsis is a dysregulated response to infection that can result in life-threatening organ failure, and septic cardiomyopathy is a serious complication involving ferroptosis. Olaparib, a classic targeted drug used in oncology, has demonstrated potential protective effects against sepsis. However, the exact mechanisms underlying its action remain to be elucidated. In our study, we meticulously screened ferroptosis genes associated with sepsis, and conducted comprehensive functional enrichment analyses to delineate the relationship between ferroptosis and mitochondrial damage. Eight sepsis-characterized ferroptosis genes were identified in sepsis patients, including DPP4, LPIN1, PGD, HP, MAPK14, POR, GCLM, and SLC38A1, which were significantly correlated with mitochondrial quality imbalance. Utilizing DrugBank and molecular docking, we demonstrated a robust interaction of Olaparib with these genes. Lipopolysaccharide (LPS)-stimulated HL-1 cells and monocytes were used to establish an in vitro sepsis model. Additionally, an in vivo model was developed using mice subjected to cecal ligation and perforation (CLP). Intriguingly, low-dose Olaparib (5 mg/kg) effectively targeted and mitigated markers associated with ferroptosis, concurrently improving mitochondrial quality. This led to a marked enhancement in cardiac function and a significant increase in survival rates in septic mice (p < 0.05). The mechanism through which Olaparib ameliorates ferroptosis in cardiac and leukocyte cells post-sepsis is attributed to its facilitation of mitophagy, thus favoring mitochondrial integrity. In conclusion, our findings suggest that low-dose Olaparib can improve mitochondrial quality by accelerating mitophagy flux, consequently inhibiting ferroptosis and preserving cardiac function after sepsis.

Pharmacokinetics, safety, and efficacy of cedirogant from phase I studies in healthy participants and patients with chronic plaque psoriasis.

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt) developed for the treatment of moderate to severe chronic plaque psoriasis. Here, we report the results from two phase I studies in which the pharmacokinetics (PK), safety, and efficacy of cedirogant in healthy participants and patients with moderate to severe chronic plaque psoriasis were evaluated. The studies consisted of single (20-750 mg) and multiple (75-375 mg once-daily [q.d.]) ascending dose designs, with effect of food and itraconazole on cedirogant exposure also evaluated. Safety and PK were evaluated for both healthy participants and psoriasis patients, and efficacy was assessed in psoriasis patients. Following single and multiple doses, cedirogant mean terminal half-life ranged from 16 to 28 h and median time to reach maximum plasma concentration ranged from 2 to 5 h across both populations. Cedirogant plasma exposures were dose-proportional after single doses and less than dose-proportional from 75 to 375 mg q.d. doses. Steady-state concentrations were achieved within 12 days. Accumulation ratios ranged from approximately 1.2 to 1.8 across tested doses. Food had minimal effect and itraconazole had limited impact on cedirogant exposure. No discontinuations or serious adverse events due to cedirogant were recorded. Psoriasis Area and Severity Index (PASI) and Self-Assessment of Psoriasis Symptoms (SAPS) assessments demonstrated numerical improvement with treatment of cedirogant 375 mg q.d. compared with placebo. The PK, safety, and efficacy profiles of cedirogant supported advancing it to phase II clinical trial in psoriasis patients.

Skin-Inspired, Highly Sensitive, Broad-Range-Response and Ultra-Strong Gradient Ionogels Prepared by Electron Beam Irradiation.

Skin, characterized by its distinctive gradient structure and interwoven fibers, possesses remarkable mechanical properties and highly sensitive attributes, enabling it to detect an extensive range of stimuli. Inspired by these inherent qualities, a pioneering approach involving the crosslinking of macromolecules through in situ electron beam irradiation (EBI) is proposed to fabricate gradient ionogels. Such a design offers remarkable mechanical properties, including excellent tensile properties (>1000%), exceptional toughness (100 MJ m-3 ), fatigue resistance, a broad temperature range (-65-200°C), and a distinctive gradient modulus change. Moreover, the ionogel sensor exhibits an ultra-fast response time (60 ms) comparable to skin, an incredibly low detection limit (1 kPa), and an exceptionally wide detection range (1 kPa-1 MPa). The exceptional gradient ionogel material holds tremendous promise for applications in the field of smart sensors, presenting a distinct strategy for fabricating flexible gradient materials.

Socioeconomic Status Impacts the Prognosis of Chronic Rhinosinusitis Treated by Endoscopic Sinus Surgery: An Observational Cohort Study in Northeast China.

Objective: To explore the association between socioeconomic status (SES) and postoperative outcomes in patients with chronic sinusitis (CRS) after functional endoscopic sinus surgery (ESS). Methods: We conducted an observational cohort study of 1,047 patients with CRS undergoing ESS. Discharged patients were followed up to 72 weeks for all-cause recurrence events. Baseline SES was established based on occupation, education level, and family income of the patients 1 year before the operation. Kaplan-Meier method was used to calculate the recovery rate after ESS, and Cox proportional hazards regression analysis was used to evaluate the relationship between SES and prognosis. Results: Patients of middle SES had lower unadjusted all-cause recurrence than those of low or high SES; 24-week overall recovery rate was 90.4% [95 % confidence interval ( CI): 89.6%-91.2%] in patients of middle SES, 13.5% (95 % CI: 12.8%-14.2%) in patients of low SES, and 31.7% (95 % CI: 30.7%-32.7%) in patients of high SES (both log-rank P < 0.001). After adjustment for covariates, hazard ratios ( HRs) were 7.69 (95 % CI: 6.17-9.71, P trend < 0.001) for all-cause recurrence for low SES versus middle SES, and 6.19 (95 % CI: 4.78-7.93, P trend < 0.001) for middle SES versus high SES. Conclusion: Low SES and high SES were more associated with the worse prognosis of CRS patients after ESS than middle SES.

Hypothyroidism reduces the risk of lung cancer through oxidative stress response and the PI3K/Akt signaling pathway: An RNA-seq and Mendelian randomization study.

Hypothyroidism has been suggested to play a role in tumor progression. However, the causal association between hypothyroidism and lung cancer remains unknow. To elucidate the potential association between hypothyroidism and lung cancer risk, we employ a Mendelian randomization (MR) approach. MR was performed to analyze pooled data from the International Lung Cancer Consortium (11,348 cases and 15,861 controls; European ancestry) to determine the causal relationship between hypothyroidism and lung cancer. We used 36, 83, and 14 single nucleotide polymorphisms as instrumental variables for hypothyroidism/myxoedema, hypothyroidism, and exercise, respectively. We further investigated the mechanisms involved in transcriptome analysis using data from The Cancer Genome Atlas and Genotype-Tissue Expression database. We conducted an initial validation of intermediary factor using a two-step MR analysis. Genetically predicted hypothyroidism was significantly related to the risk of overall lung cancer, specifically the risk of lung squamous cell cancer (LSCC) but not with the risk of lung adenocarcinoma (LUAD) as assessed using the inverse-variance weighted (IVM) method. A similar causal association was found between hypothyroidism/myxoedema and the risk of lung cancer, LSCC, and LUAD. Transcriptome analysis showed that genes associated with hypothyroidism, lung cancer, and LSCC were enriched in the PI3K/Akt signaling pathway and oxidative stress response. However, genes related to hypothyroidism and LUAD did not exhibit enrichment in these pathways. Hypothyroidism was significantly associated with strenuous sports or other exercises. Moreover, genetically predicted exercise was significantly related to the risk of overall lung cancer, and LSCC, but not LUAD. We detected no horizontal pleiotropy using the MR-PRESSO and MR Egger regression intercept. Hypothyroidism was causally associated with a lower risk of lung cancer, and these effects might be mediated by the oxidative stress response and the PI3K/Akt signaling pathway. Therefore, our study suggests that the potential factors and viable etiologies of hypothyroidism that contributed to lung cancer risk deserve further investigation.

Ga-Doped Ultrahigh-Nickel Oxide Microspheres with Radially Aligned Primary Grains as a Cathode for Stable Cycling Li-Ion Batteries.

Owing to the high energy density, ultrahigh-nickel (Ni > 0.9) layered oxides are used as promising cathode materials for next-generation Li-ion batteries. Unfortunately, the serious pulverization and rapid capacity fading during cycling limit the commercial viability of an ultrahigh-nickel oxide cathode. Herein, the introduction of Ga into LiNi0.96Co0.04O2 brings a radially aligned microstructural change of oxide microspheres during the lithiation of the Ni0.96Co0.04(OH)2 precursor. As expected, such radially aligned needle-like primary grains on microspheres have a positive influence to reduce the anisotropic volume change and suppress the formation of microcracks of Ga-induced Li(Ni0.96Co0.04)0.99Ga0.01O2 during cycling. Specifically, compared with irregular primary grains of LiNi0.96Co0.04O2, Ga-induced oxide presents a high initial discharge capacity of 227.9 mA h g-1 at 0.1C rate between 2.8 and 4.3 V. Especially, Ga-induced oxide delivers higher initial discharge capacities of 233.9 and 240.3 mA h g-1 with higher cutoff charge voltages of 4.4 and 4.5 V at 0.1C, respectively. Furthermore, a good capacity retention of 74.1% at 1 C rate is obtained after 300 cycles, which is almost 85% higher than that of the pristine sample, mainly due to the generation of microcracks of oxide microspheres during the long-term cycle. Therefore, the introduction of Ga into LiNi0.96Co0.04O2 is a feasible approach for improving the microstructure and cycling stability of the ultrahigh-Ni layered oxides.

Macrophage migration inhibitory factor may contribute to the occurrence of multiple primary lung adenocarcinomas.

BACKGROUND: This study aimed to identify the key genes involved in the development of multiple primary lung cancers. METHODS: Differential expression analysis was performed, followed by comparing the infiltration levels of 22 immune cell types between multiple and single primary lung adenocarcinomas. Marker genes for epithelial cells with different proportions between the two types of lung adenocarcinomas were identified. The common genes between the marker genes and differentially expressed genes were identified. Finally, the effects of the key genes were tested on the in vitro proliferation, migration and morphology. RESULTS: The infiltration levels of helper follicular T cells, resting NK cells, activated NK cells, M2 macrophages and resting mast cells were higher in the patients with multiple than in those with single primary lung adenocarcinomas. A total of 1553 differentially expressed genes and 4414 marker genes of epithelial cells were identified. Logistic regression analysis was performed on the 164 resulting genes. The macrophage migration inhibitory factor expression was positively associated with the occurrence of multiple primary lung adenocarcinomas. Moreover, its signalling pathway was the key pathway among the epithelial cells and multiple and single primary lung adenocarcinoma cells, and it was upregulated in lung adenocarcinoma cells. It also increased the expression of lung cancer markers, including NES and CA125, induced morphological changes in alveolar epithelial type II cells, and promoted their proliferation, migration and invasion. CONCLUSIONS: Multiple and single primary lung adenocarcinomas have different tumour immune microenvironments, and migration inhibitory factor may be a key factor in the occurrence of multiple primary lung adenocarcinomas.

Multifaceted functions of Drp1 in hypoxia/ischemia-induced mitochondrial quality imbalance: from regulatory mechanism to targeted therapeutic strategy.

Hypoxic-ischemic injury is a common pathological dysfunction in clinical settings. Mitochondria are sensitive organelles that are readily damaged following ischemia and hypoxia. Dynamin-related protein 1 (Drp1) regulates mitochondrial quality and cellular functions via its oligomeric changes and multiple modifications, which plays a role in mediating the induction of multiple organ damage during hypoxic-ischemic injury. However, there is active controversy and gaps in knowledge regarding the modification, protein interaction, and functions of Drp1, which both hinder and promote development of Drp1 as a novel therapeutic target. Here, we summarize recent findings on the oligomeric changes, modification types, and protein interactions of Drp1 in various hypoxic-ischemic diseases, as well as the Drp1-mediated regulation of mitochondrial quality and cell functions following ischemia and hypoxia. Additionally, potential clinical translation prospects for targeting Drp1 are discussed. This review provides new ideas and targets for proactive interventions on multiple organ damage induced by various hypoxic-ischemic diseases.

Lithiated Phosphoryl Cellulose Nanocrystals Enhance Cycling Stability and Safety of Quasi-Solid-State Lithium Metal Batteries.

Cycling stability and safety are two of the main challenges facing lithium metal batteries with metallic lithium as anodes. Quasi-solid-state lithium metal batteries based on gel polymer electrolytes are one of the important development directions for lithium metal batteries addressing those challenges. Herein, we prepare lithiated phosphoryl cellulose nanocrystals (PCNC-Li) as a modification material for poly(vinylidene fluoride) (PVDF) gel polymer electrolyte to improve cycling stability and safety of quasi-solid-state lithium metal batteries. The synthesized PCNC-Li tends to form a uniform network structure on the surface of the PVDF membrane, in which the phosphoryl groups grafted regularly on celluloses can regulate the transport of lithium ions. As a result, a more uniform ion flux and more stable lithium anode interface support an obviously improved cycling stability for lithium metal batteries. Moreover, the introduction of the PCNC-Li coating layer makes the modified PVDF membranes have a better thermal stability and an enhanced mechanical strength, which is beneficial for improvement of safety of lithium metal batteries. This work provides a new alternative to fabricating a better composite gel polymer electrolyte for lithium metal batteries.

Identification and validation of a novel mitochondrion-related gene signature for diagnosis and immune infiltration in sepsis.

Background: Owing to the complex pathophysiological features and heterogeneity of sepsis, current diagnostic methods are not sufficiently precise or timely, causing a delay in treatment. It has been suggested that mitochondrial dysfunction plays a critical role in sepsis. However, the role and mechanism of mitochondria-related genes in the diagnostic and immune microenvironment of sepsis have not been sufficiently investigated. Methods: Mitochondria-related differentially expressed genes (DEGs) were identified between human sepsis and normal samples from GSE65682 dataset. Least absolute shrinkage and selection operator (LASSO) regression and the Support Vector Machine (SVM) analyses were carried out to locate potential diagnostic biomarkers. Gene ontology and gene set enrichment analyses were conducted to identify the key signaling pathways associated with these biomarker genes. Furthermore, correlation of these genes with the proportion of infiltrating immune cells was estimated using CIBERSORT. The expression and diagnostic value of the diagnostic genes were evaluated using GSE9960 and GSE134347 datasets and septic patients. Furthermore, we established an in vitro sepsis model using lipopolysaccharide (1 µg/mL)-stimulated CP-M191 cells. Mitochondrial morphology and function were evaluated in PBMCs from septic patients and CP-M191 cells, respectively. Results: In this study, 647 mitochondrion-related DEGs were obtained. Machine learning confirmed six critical mitochondrion-related DEGs, including PID1, CS, CYP1B1, FLVCR1, IFIT2, and MAPK14. We then developed a diagnostic model using the six genes, and receiver operating characteristic (ROC) curves indicated that the novel diagnostic model based on the above six critical genes screened sepsis samples from normal samples with area under the curve (AUC) = 1.000, which was further demonstrated in the GSE9960 and GSE134347 datasets and our cohort. Importantly, we also found that the expression of these genes was associated with different kinds of immune cells. In addition, mitochondrial dysfunction was mainly manifested by the promotion of mitochondrial fragmentation (p<0.05), impaired mitochondrial respiration (p<0.05), decreased mitochondrial membrane potential (p<0.05), and increased reactive oxygen species (ROS) generation (p<0.05) in human sepsis and LPS-simulated in vitro sepsis models. Conclusion: We constructed a novel diagnostic model containing six MRGs, which has the potential to be an innovative tool for the early diagnosis of sepsis.

Diabetic Ketoacidosis and Long-term Insulin Requirements in Youths with Newly Diagnosed Type 2 Diabetes During the SARS-CoV-2 Pandemic.

OBJECTIVE: SARS-CoV-2 infection increases the risk of diabetes and diabetic ketoacidosis (DKA) in both adults and children. We investigated the clinical course of new-onset type 2 diabetes in youth presenting with DKA during the COVID-19 pandemic. METHODS: This single-center retrospective cohort study included 148 subjects with obesity aged 10 to 21 years, admitted with DKA from January 2018 to January 2022. Groups were defined by the presence of DKA precipitant: any infection (n = 38, 26%), which included the SARS-CoV-2 (n = 10, 7%) and other infection (n = 28, 19%) groups, and no infection (n = 110, 74%). The primary outcome was insulin discontinuation within a 12-month follow-up. RESULTS: The mean age was 14.9 years (IQR, 13.8-16.5), and age-adjusted body mass index (%) was 99.1 (IQR, 98.0-99.5) with 85.8% identifying as Black or Hispanic. There were no differences in DKA severity among groups. The incidence of DKA was higher during the pandemic (March 2020-January 2022, n = 117) than in the prepandemic period (January 2018-February 2020, n = 31). Within the first year after the acute DKA episode, 46 patients discontinued all insulin within 9 months (IQR, 4-14). Sixteen subjects restarted insulin 10 months (IQR, 6.5-11.0) after insulin discontinuation. Infection with SARS-CoV-2 at diagnosis was not associated with the likelihood (P =.57) or timing (P =.27) of discontinuing all insulin within 1 year, nor was having any infection. CONCLUSION: The incidence of DKA at the onset of type 2 diabetes was higher during the SARS-CoV-2 pandemic than in the prepandemic period. SARS-CoV-2 infection was not associated with DKA severity or insulin discontinuation within the first year of diagnosis in youth with new-onset type 2 diabetes and DKA.

Catalytic reactions of oxalic acid degradation with Pt/SiO2 as a catalyst in nitric acid solutions.

Large quantities of solutions containing oxalic acid and nitric acid are produced from nuclear fuel reprocessing, but oxalic acid must be removed before nitric acid and plutonium ions can be recovered in these solutions. The degradation of oxalic acid with Pt/SiO2 as a catalyst in nitric acid solutions has the characteristics of a fast and stable reaction, recyclable catalyst, and no introduction of impurity ions into the system. This method is one of the preferred alternatives to the currently used reaction of KMnO4 with oxalic acid but lacks theoretical support. Therefore, this study attempts to clarify the reaction mechanism of the method. First, there was no induction period for this catalytic reaction, and no evidence was found that the nitrous acid produced in the solution could have an effect on oxalic acid degradation. Furthermore, oxidation intermediates (structures of Pt-O) were formed through this reaction between NO3- adsorbed on the active sites and Pt on the catalyst surface, but H+ greatly promoted the reaction. Additionally, oxalic acid degradation through the oxidative dehydrogenation reaction occurred between oxalic acid molecules (HOOC-COOH) and Pt-O, with ·OOC-COOH, which is easily self-decomposable especially in acidic solution, generated simultaneously, and finally CO2 was produced.

A pyroptosis-related gene signature that predicts immune infiltration and prognosis in colon cancer.

Background: Colon cancer (CC) is a highly heterogeneous malignancy associated with high morbidity and mortality. Pyroptosis is a type of programmed cell death characterized by an inflammatory response that can affect the tumor immune microenvironment and has potential prognostic and therapeutic value. The aim of this study was to evaluate the association between pyroptosis-related gene (PRG) expression and CC. Methods: Based on the expression profiles of PRGs, we classified CC samples from The Cancer Gene Atlas and Gene Expression Omnibus databases into different clusters by unsupervised clustering analysis. The best prognostic signature was screened and established using least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. Subsequently, a nomogram was established based on multivariate COX regression analysis. Next, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential molecular mechanisms between the high- and low-risk groups and to explore the differences in clinicopathological characteristics, gene mutation characteristics, abundance of infiltrating immune cells, and immune microenvironment between the two groups. We also evaluated the association between common immune checkpoints and drug sensitivity using risk scores. The immunohistochemistry staining was utilized to confirm the expression of the selected genes in the prognostic model in CC. Results: The 1163 CC samples were divided into two clusters (clusters A and B) based on the expression profiles of the 33 PRGs. Genes with prognostic value were screened from the DEGs between the two clusters, and an eight PRGs prognostic model was constructed. GSEA and GSVA of the high- and low-risk groups revealed that they were mainly enriched in inflammatory response-related pathways. Compared to those in the low-risk group, patients in the high-risk group had worse overall survival, an immunosuppressive microenvironment, and worse sensitivity to immunotherapy and drug treatment. Conclusion: Our findings provide a foundation for future research targeting pyroptosis and new insights into prognosis and immunotherapy from the perspective of pyroptosis in CC.

Prognostic impact of deep learning-based quantification in clinical stage 0-I lung adenocarcinoma.

OBJECTIVES: To evaluate the performance of automatic deep learning (DL) algorithm for size, mass, and volume measurements in predicting prognosis of lung adenocarcinoma (LUAD) and compared with manual measurements. METHODS: A total of 542 patients with clinical stage 0-I peripheral LUAD and with preoperative CT data of 1-mm slice thickness were included. Maximal solid size on axial image (MSSA) was evaluated by two chest radiologists. MSSA, volume of solid component (SV), and mass of solid component (SM) were evaluated by DL. Consolidation-to-tumor ratios (CTRs) were calculated. For ground glass nodules (GGNs), solid parts were extracted with different density level thresholds. The prognosis prediction efficacy of DL was compared with that of manual measurements. Multivariate Cox proportional hazards model was used to find independent risk factors. RESULTS: The prognosis prediction efficacy of T-staging (TS) measured by radiologists was inferior to that of DL. For GGNs, MSSA-based CTR measured by radiologists (RMSSA%) could not stratify RFS and OS risk, whereas measured by DL using 0HU (2D-AIMSSA0HU%) could by using different cutoffs. SM and SV measured by DL using 0 HU (AISM0HU% and AISV0HU%) could effectively stratify the survival risk regardless of different cutoffs and were superior to 2D-AIMSSA0HU%. AISM0HU% and AISV0HU% were independent risk factors. CONCLUSION: DL algorithm can replace human for more accurate T-staging of LUAD. For GGNs, 2D-AIMSSA0HU% could predict prognosis rather than RMSSA%. The prediction efficacy of AISM0HU% and AISV0HU% was more accurate than of 2D-AIMSSA0HU% and both were independent risk factors. CLINICAL RELEVANCE STATEMENT: Deep learning algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma. KEY POINTS: • Deep learning (DL) algorithm could replace human for size measurements and could better stratify prognosis than manual measurements in patients with lung adenocarcinoma (LUAD). • For GGNs, maximal solid size on axial image (MSSA)-based consolidation-to-tumor ratio (CTR) measured by DL using 0 HU could stratify survival risk than that measured by radiologists. • The prediction efficacy of mass- and volume-based CTRs measured by DL using 0 HU was more accurate than of MSSA-based CTR and both were independent risk factors.