Associations of dietary linoleic acid and alpha linolenic acid intake with cardiovascular, cancer and all-cause mortalities in patients with diabetes: NHANES 1999-2008.

Objective: To investigate the association between the dietary intake of linoleic acid (LA) and alpha linolenic acid (ALA) with mortality outcomes in patients with diabetes. Participants: 3,112 U.S. adults aged≥20 years. Setting: Basic information was collected at baseline of the National Health and Nutrition Examination Survey (NHANES). Serum CRP (mg/dL), total protein (g/L), waist circumference (cm), fasting blood glucose (mmol/L), white blood cell count, serum LDL-C, and serum HDL-C were also measured. Daily diets were also recorded using a 24-hour dietary review to produce the individuals' intake of LA and ALA. The association between tertiles of LA and ALA intake with mortality was analyzed by weighted Cox models adjusted for the main confounders. Main outcome measures: The study included 3,112 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. Death outcomes were ascertained by linkage to the database records through 31 December 2015. Results: Subjects with a high intake of LA (T3) had 17% [hazard ratio (HR) 0.83, 95% CI 0.70 to 0.99) and 48% (HR=0.52, 0.35 to 0.80)] reductions in all-cause mortality and cardiovascular mortality, respectively, compared with subjects with lowest intake (T1). Similar results were observed for ALA, HR of cardiovascular mortality was 0.55 (0.38 to 0.81) and for all-cause mortality was 0.85 (0.69 to 1.04) comparing the highest to lowest intake tertiles. Conclusion: Higher intakes of LA and ALA were inversely associated with CVD and all-cause deaths in patients with diabetes. Proper dietary intakes of LA and ALA could contribute to the cardiovascular health and the long-term survival of patients with diabetes.

Microalgae polyphosphate nanoparticles deliver bioavailable calcium against phytate antagonism: Ex vivo and in vivo studies.

Biogenic nanoparticles are promising carriers to deliver essential minerals. Here, calcium-enriched polyphosphate nanoparticles (CaPNPs) with a Ca/P molar ratio > 0.5 were produced by Synechococcus sp. PCC 7002 in the growth medium containing 1.08 g/L CaCl2, and had nearly spherical morphologies with a wide size distribution of 5-75 nm and strongly anionic surface properties with an average ζ-potential of -39 mV, according to dynamic light-scattering analysis, transmission and scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The ex-vivo ligated mouse ileal loop assays found that calcium in CaPNPs was readily available to intestinal absorption via both ion channel-mediated and endocytic pathways, specifically invoking macropinocytic internalization, lysosomal degradation, and transcytosis. Rat oral pharmacokinetics revealed that CaPNPs had a calcium bioavailability approximately 100 % relative to that of CaCl2 and more than 1.6 times of that of CaCO3. CaPNPs corrected the retinoic acid-induced increase in serum calcium, phosphorus, and bone-specific alkaline phosphatase, and decrease in serum osteocalcin, bone mineral content/density, and femoral geometric parameters with an efficacy equivalent to CaCl2 and markedly greater than CaCO3. In contrast to CaCl2, CaPNPs possessed desirable resistance against phytate's antagonistic action on calcium absorption in these ex vivo and in vivo studies. Overall, CaPNPs are attractive as a candidate agent for calcium supplementation, especially to populations on high-phytate diets.

Rational design of peptide-based fluorescent probe for sequential recognitions of Cu(II) ions and glyphosate: Smartphone, test strip, real sample and living cells applications.

A new peptide-based fluorescent probe named DMDH with easy-to-synthesize, excellent stability, good water solubility and large Stokes shift (225 nm) was synthesized for highly selective sequential detections of copper ions (Cu2+) and glyphosate (Glyp). DMDH demonstrated great detection performance towards Cu2+via strong fluorescence quenching, and forming non-fluorescence DMDH-Cu2+ ensemble. As a new promising cascade probe, the fluorescence of DMDH-Cu2+ ensemble was significantly recovered based on displacement approach after glyphosate was added. Interestingly, the limit of detections (LODs) for Cu2+ and glyphosate were 40.6 nM and 10.6 nM, respectively, which were far lower than those recommended by the WHO guidelines for drinking water. More importantly, DMDH was utilized to evaluate Cu2+ and glyphosate content in three real water samples, demonstrating that its effectiveness in water quality monitoring. Additionally, it is worth noting that DMDH was also applied to analyze Cu2+ and glyphosate in living cells in view of significant cells permeability and low cytotoxicity. Moreover, DMDH soaked in filter paper was used to create qualitative test strips and visually identify Cu2+ and glyphosate through significant color changes. Furthermore, smartphone RGB color recognition provided a new method for semi-quantitative testing of Cu2+ and glyphosate in the absence of expensive instruments.

Veratrum nigrum L.: A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, toxicity, and incompatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Veratrum nigrum L. (V. nigrum) is a well-known herb with a lengthy history of use in Asian and European countries. V. nigrum has been traditionally used to treat epilepsy, hypertension, malignant sores, and stroke, and it possesses emetic and insecticide properties. AIM OF THE REVIEW: This review summarized the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, and toxicity of V. nigrum as well as its incompatibility with other herbs. Current challenges in the use of V. nigrum and possible future research directions were also discussed. MATERIALS AND METHODS: Information on V. nigrum was collected from electronic databases such as PubMed, Google Scholar, Web of Science, CNKI, and WanFang DATA; Masterpieces of Traditional Chinese Medicine; local Chinese Materia Medica Standards; and relevant documents. RESULTS: In ethnomedical practice, V. nigrum has been used as an emetic and insecticide. Approximately 137 compounds have been isolated from V. nigrum, including alkaloids, stilbenes, flavonoids, organic acids, and esters. Its crude extracts and compounds have shown various effects, including anticancer, hypotensive, insecticidal, and antimicrobial activities as well as the ability to improve hemorheological abnormalities. Pharmacokinetic studies have indicated that veratramine (VAM) and jervine have high bioavailability and possibly enterohepatic circulation. In addition, the sex-related pharmacokinetic differences in V. nigrum alkaloids warrant further attention. Toxicological studies have indicated that cevanine-type alkaloids and VAM may be the main toxic components of V. nigrum, and purine metabolism disorders may be related to V. nigrum toxicity. Furthermore, the neurotoxicity and embryotoxicity of V. nigrum have also been observed. The quality control of V. nigrum and the mechanism underlying its incompatibility with other herbs also deserve further research and refinement. CONCLUSION: This review summarized the existing information on V. nigrum, laying the foundation for further studies on this herb and its safe use. Among the various compounds present in V. nigrum, steroid alkaloids are the most numerous and have high content; furthermore, they are closely related to the pharmacological effects of V. nigrum, but their toxicity can not also be ignored. Given that toxicity is a critical issue limiting the clinical application of V. nigrum, more toxicological studies on V. nigrum and its active ingredients, especially steroid alkaloids, should be conducted in the future to further explore its toxicity targets and the underlying mechanisms and to provide more evidence and recommendations to enhance the safety of its clinical application.

Ratiometric peptide-based fluorescent probe with large Stokes shift for detection of Hg2+ and S2- and its applications in cells imaging and smartphone-assisted recognition.

In this work, a new ratiometric fluorescent probe DKA was synthesized based on the double sides of lysine backbone conjugated with alanine and dansyl groups. DKA exhibited fluorescence ratiometric response for Hg2+ with high sensitivity (13.4 nM), specific selectivity (only Hg2+), strong anti-interference ability (no interference), fast recognition (within 60 s) and wide pH range (5-10). The stoichiometry of binding of DKA and Hg2+ was determined to be 1:1 via Job's plot, ESI-HRMS and 1HNMR titration analysis. Subsequently, the in situ formation of DKA-Hg2+ complex was used for highly selective detection of S2- as a novel fluorescence "on-off" probe, and the lowest detection limit for S2- was 12.9 nM. In addition, DKA possessed excellent cells permeation and low toxicity, and fluorescence imaging of Hg2+ and S2- was performed in living Hacat cells. Most importantly, the digital imaging using a smartphone color recognition APP indicated that DKA could semi-quantitatively and visually detected Hg2+ and S2- without expensive equipment.

Association of monocyte to HDL cholesterol ratio and a composite risk score with left ventricular aneurysm formation in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. This study aimed to investigate the potential predictive value of the monocyte count to high-density lipoprotein cholesterol ratio (MHR) and a composite risk score in determining the formation of LVA in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. METHODS: We recruited 1005 consecutive patients with STEMI. Multivariable logistic regression analysis was conducted identify the independent risk factors for LVA formation. Predictive power of MHR and composite risk score for LVA formation were assessed using receiver operating characteristic curve analysis. RESULTS: The MHR was significantly higher among patients with LVA compared to those without LVA [6.6 (3.8-10.8) vs. 4.6 (3.3-6.3), P < 0.001]. Univariable logistic regression analysis revealed that MHR (OR = 3.866, 95% CI = 2.677-5.582, P < 0.001) was associated with the risk of LVA formation. The predictive value of MHR remained significant even after multivariate logistic regression analysis [odds ratio (OR) = 4.801, 95% confidence interval (CI) = 2.672-8.629, P < 0.001]. The discriminant power of MHR for LVA is 0.712, which is superior to both monocyte (C statistic = 0.553) and high-density lipoprotein cholesterol (C statistic = 0.654). The composite risk score including MHR, gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel could significantly increase the predictive ability (C statistic = 0.920). CONCLUSION: A higher MHR could effectively identify individuals at high risk of LVA formation, especially when combined with gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel.

The Piezocatalytic Degradation of Sulfadiazine by Lanthanum-Doped Barium Titanate.

Piezocatalysis, a heterogeneous catalytic technique, leverages the periodic electric field changes generated by piezoelectric materials under external forces to drive carriers for the advanced oxidation of organic pollutants. Antibiotics, as emerging trace organic pollutants in water sources, pose a potential threat to animals and drinking water safety. Thus, piezoelectric catalysis can be used to degrade trace organic pollutants in water. In this work, BaTiO3 and La-doped BaTiO3 were synthesized using an improved sol-gel-hydrothermal method and used as piezocatalytic materials to degrade sulfadiazine (SDZ) with ultrasound activation. High-crystallinity products with nano cubic and spherical morphologies were successfully synthesized. An initial concentration of SDZ ranging from 1 to 10 mg/L, a catalysis dosage range from 1 to 2.5 mg/mL, pH, and the background ions in the water were considered as influencing factors and tested. The reaction rate constant was 0.0378 min-1 under the optimum working conditions, and the degradation efficiency achieved was 89.06% in 60 min. La-doped BaTiO3 had a better degradation efficiency, at 14.98% on average, compared to undoped BaTiO3. Further investigations into scavengers revealed a partially piezocatalytic process for the degradation of SDZ. In summary, our work provides an idea for green environmental protection in dealing with new types of environmental pollution.

Co-benefits for net carbon emissions and rice yields through improved management of organic nitrogen and water.

Returning organic nutrient sources (for example, straw and manure) to rice fields is inevitable for coupling crop-livestock production. However, an accurate estimate of net carbon (C) emissions and strategies to mitigate the abundant methane (CH4) emission from rice fields supplied with organic sources remain unclear. Here, using machine learning and a global dataset, we scaled the field findings up to worldwide rice fields to reconcile rice yields and net C emissions. An optimal organic nitrogen (N) management was developed considering total N input, type of organic N source and organic N proportion. A combination of optimal organic N management with intermittent flooding achieved a 21% reduction in net global warming potential and a 9% rise in global rice production compared with the business-as-usual scenario. Our study provides a solution for recycling organic N sources towards a more productive, carbon-neutral and sustainable rice-livestock production system on a global scale.

Caseinophosphopeptides Overcome Calcium Phytate Inhibition on Zinc Bioavailability by Retaining Zinc from Coprecipitation as Zinc/Calcium Phytate Nanocomplexes.

Caseinophosphopeptides have shown great potential to increase zinc bioavailability from phytate-rich diets, but the mechanism of action remains unclear. Here, caseinophosphopeptides from a sodium caseinate hydrolysate dose-dependently retained zinc in solution against calcium phytate coprecipitation under physiologically relevant conditions. The 3 kDa ultrafiltration separation unveiled no added low-molecular-weight chelates of zinc and calcium by caseinophosphopeptides. Tyndall effect, dynamic light scattering measurements, transmission electron microscopy observation, electron diffraction pattern, X-ray diffraction spectrum, and energy-dispersive X-ray analysis demonstrated the caseinophosphopeptides-mediated formation of single-crystal zinc/calcium phytate nanocomplexes (Zn/CaPA-NCs) with a size and ζ-potential of 10-30 nm and -25 mV, respectively. Caseinophosphopeptides-stabilized Zn/CaPA-NCs were found to deliver bioavailable nanoparticulate zinc in mouse jejunal loop ex vivo model and polarized Caco-2 cells, and the treatments with specific inhibitors revealed that intestinal zinc absorption from Zn/CaPA-NCs invoked macropinocytosis, lysosomal release into the cytosol, and transcytosis. Overall, our study proposes a new paradigm for the benefit of caseinophosphopeptides for zinc bioaccessibility and bioavailability in phytate-rich diets.

Gum Arabic-Derived Hydroxyproline-Rich Peptides Stimulate Intestinal Nonheme Iron Absorption via HIF2α-Dependent Upregulation of Iron Transport Proteins.

The stimulation of host iron absorption is a promising antianemia strategy adjunctive/alternative to iron intervention. Here, gum arabic (GA) containing 3.14 ± 0.56% hydroxyproline-rich protein with repetitive X-(Pro/Hyp)n motifs was found to increase iron reduction, uptake, and transport to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin, and hephaestin to inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) and to stabilize HIF2α in polarized Caco-2 cell monolayers in a dose-dependent manner, and this was dependent on its protein fraction, rather than the polysaccharide fraction. Three abundant GA-derived hydroxyproline-containing dipeptides of Hyp-Hyp, Pro-Hyp, and Ser-Hyp were detected by liquid chromatography-mass spectrometry in the lysates of polarized Caco-2 cell monolayers at the maximum levels of  0.167 ± 0.021, 0.134 ± 0.017, and 0.089 ± 0.015 µg/mg of protein, respectively, and showed desirable docking affinity energy values of -7.53, - 7.91, and -7.39 kcal/mol, respectively, against human PHD3. GA-derived peptides also acutely increased duodenal HIF2α stability and Dcytb, DMT1, ferroportin, and hephaestin transcription in rats (P < 0.05). Overall, GA-derived hydroxyproline-rich peptides stimulated intestinal iron absorption via PHD inhibition, HIF2α stabilization, and subsequent upregulation of iron transport proteins.

Role of ferroptosis in chronic kidney disease.

Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.

Construction of PDA-PEI/ZIF-L@PE tight ultra-filtration (TUF) membranes on porous polyethylene (PE) substrates for efficient dye/salt separation.

Tight ultra-filtration (TUF) membranes were constructed by in situ growing zinc imidazole frameworks micro-crystalline leaves (ZIF-L) in polyethylene imine (PEI) and polydopamine (PDA) deposit layers on porous polyethylene (PE) substrates. The effects of preparation conditions on the surface physical and chemical structures as well as on the dye/salt separation performance of the formed TUF membranes were systematically investigated. By inserting selective water permeation channels and increasing contacting surface areas, in situ-grown ZIF-L arrays tightly cross-linked in the coating matrix greatly increased water permeation without trading off dye/salt retention selectivity. The morphology of the included ZIF-L particles could be varied by adjusting the ligand/Zn molar ratio (α) in the preparation processes. Optimized PDA-PEI/ZIF-L@PE TUF membranes containing ZIF-L of cross-cross block morphology showed very high pure water permeability of 180 ± 20 L·m-2·h-1·bar-1 (LMHB) and retention selectivity (SCR/Na2SO4 and SMB/Na2SO4) of 267 and 43, respectively, as well as excellent stability and anti-fouling properties.

Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer.

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.

Associations of different isomeric forms of serum lycopene with cardiovascular disease and all-cause mortality.

Background: The effect of serum lycopene on the progression of cardiovascular diseases (CVDs) and their longevity remains a controversial topic. The purpose of this study was to evaluate the associations of different isomeric forms of serum lycopene with CVD and all-cause mortality in the American population. Methods: The National Health and Nutrition Examination Survey (NHANES) is a large population survey to investigate public health in the US. We analyzed data from 2003-2006 linked with mortality data obtained in 2015. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess the risk of CVD and all-cause mortality caused by serum lycopene. Results: Among 7452 participants (aged 20-85 years, 46.7% male), 298 died from CVDs among the total 1213 deaths during a median follow-up of 10.7 years. Serum lycopene is a protective factor for all-cause and CVD mortality. In multivariable-adjusted models, the hazard ratio (with 95% confidence intervals) associated with Q4 compared to Q1 of serum total-lycopene, trans-lycopene and cis-lycopene was 0.49 (0.38,0.63), 0.49 (0.39,0.63) and 0.55 (0.43,0.70) for all-cause mortality (Ptrend<0.05), and was 0.53 (0.32,0.96), 0.48 (0.32,0.72) and 0.63 (0.41,0.97) for CVD mortality (Ptrend<0.05). The subgroup analyses showed that different isomeric forms of lycopene showed varied associations with CVD and all-cause mortality based on age, drinking status, history of hypertension and diabetes. Conclusions: Serum lycopene concentration was significantly associated with the risk of CVD and all-cause mortality. Cis-lycopene had a U-shaped relationship with mortality, while trans-lycopene had an inverse relationship with it.

Serum apolipoprotein B to apolipoprotein A-I ratio predicts mortality in patients with heart failure.

AIMS: Apolipoproteins have been reported to be involved in many cardiovascular diseases. The aim of our study was to investigate the prognostic value of apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) ratio (ApoB/ApoA-I) in patients with heart failure (HF). METHODS AND RESULTS: We randomly assigned 2400 HF patients into the training cohort (n = 1400) and the validation cohort (n = 1000). Using a receiver operating characteristic curve, we identified the optimal cut-off value of the ApoB/ApoA-I in the training cohort as 0.69, which was further validated in the validation cohort. A propensity score matching (PSM) analysis was conducted to eliminate the imbalance in the baseline characteristics of the high and low ApoB/ApoA-I group. A total of 2242 HF patients were generated in the PSM cohort. We also validated our results with an independent cohort (n = 838). Univariate and multivariate analyses were conducted to explore the independent prognostic value of ApoB/ApoA-I in the training cohort (n = 1400), the validation cohort (n = 1000), the PSM cohort (n = 2242), and the independent cohort (n = 838). Patients with high ApoB/ApoA-I ratio had significantly poorer prognosis compared with those with low ApoB/ApoA-I ratio in the training cohort, the validation cohort, the PSM cohort, and the independent cohort (P < 0.05). Multivariate analysis indicated that the ApoB/ApoA-I was an independent prognostic factor for HF in the training cohort [hazard ratio (HR) = 1.637, 95% confidence interval (CI) = 1.201-2.231, P = 0.002], the validation cohort (HR = 1.54, 95% CI = 1.051-2.257, P = 0.027), the PSM cohort (HR = 1.645, 95% CI = 1.273-2.125, P < 0.001), and the independent cohort (HR = 1.987, 95% CI = 1.251-3.155, P = 0.004). CONCLUSIONS: Serum ApoB/ApoA-I ratio is an independent predictor for the prognosis of HF patients.

Microalgae polysaccharides exert antioxidant and anti-inflammatory protective effects on human intestinal epithelial cells in vitro and dextran sodium sulfate-induced mouse colitis in vivo.

Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 were characterized as mainly branched heteropolysaccharides, and were bioavailable to Caco-2 cells based on fluorescein isothiocyanate labeling and flow cytometry analysis. These MAPS were equally effective to scavenge hydroxyl and superoxide radicals in vitro and to attenuate the H2O2-, dextran sodium sulfate-, tumor necrosis factor α-, and interleukin 1ß-induced burst of intracellular reactive oxygen species and mitochondrial superoxide radicals, interleukin-8 production, cyclooxygenase-2 and inducible nitric oxide synthase expression, and/or tight junction disruption in polarized Caco-2 cells. MAPS and a positive drug Mesalazine were intragastrically administered to C57BL/6 mice daily for 7 d during and after 4-d dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed equivalent anti-colitis efficacies of MAPS and Mesalazine, and based on biochemical analysis of colonic tight junction proteins, goblet cells, mucin 2 and trefoil factor 3 transcription, and colonic and peripheral pro-inflammatory cytokines, MAPS alleviated dextran sodium sulfate-induced intestinal epithelial barrier dysfunction, and their activities were even superior than Mesalazine. Overall, MAPS confer direct antioxidant and anti-inflammatory protection to intestinal epithelial barrier function.

Talaromyces marneffei infection with IFNGR1 gene mutation in a patient with negative Anti-Interferon-γ autoantibodies.

BACKGROUND: Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. OBJECTIVE: To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. METHODS: Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. RESULTS: The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). STUDY LIMITATIONS: The mechanism of the IFNGR1 gene has not been further investigated in this study. CONCLUSIONS: The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.

Identification and Validation of the Glycolysis and Immune-related Gene Signature for Prognosis in Colorectal Cancer.

BACKGROUND/AIM: Glycolysis has a role in regulating the tumor immune microenvironment. However, the functions and clinical role for facilitating the prognosis prediction of colorectal cancer (CRC) based on glycolysis and immune-related genes remain to be identified. MATERIALS AND METHODS: Genes associated with glycolysis and immunity (GI) were identified from established databases (MSigDB and ImmPort). The TCGA (training cohort) and GSE39582 (validation cohort) datasets were used. Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were applied for model construction. The prognostic power of the GI signature was examined by multivariate Cox regression analysis. The correlations between the GI signature, immune cell infiltration and immune checkpoint blockade (ICB) genes were analyzed. To further validate the identified gene signature, quantitative RT-PCR was performed. Cell proliferation assays were conducted for CCK8 detection. RESULTS: A new GI model was constructed, and this signature may serve as an independent prognostic biomarker in CRC. The GI signature remained an effective tool for predicting prognosis among each clinical subgroup. This signature was related to immune cell infiltration of myeloid dendritic cells, cancer-associated fibroblasts (CAFs), CD4+ and CD8+ T cells and response to the ICB immunotherapy-related genes IDO1, BTLA, PD-L1 and PD-L2. In addition, our findings showed that PMM2, IL20RB, and NTF4 exhibited high expression levels in CRC. The upregulation of these genes resulted in the promotion of the proliferation of CRC cells. CONCLUSION: This novel prognostic signature contributed to CRC risk stratification and survival prediction based on glycolysis and immune status.

Favorable factors for the survival of ST-segment elevation myocardial infarction patients with medium- and high-risk thrombolysis in myocardial infarction scores.

OBJECTIVE: ST-segment myocardial infarction (STEMI) is a time-sensitive emergency. This study screened the favorable factors for the survival of STEMI patients with medium- and high-risk thrombolysis in myocardial infarction (TIMI) scores. METHODS: According to the TIMI scores at admission, 433 STEMI patients were retrospectively and consecutively selected and allocated into low-/medium-/high-risk groups, with their general information/blood routine/biochemical indicators/coagulation indicators documented. The factors influencing the in-hospital survival of STEMI patients were analyzed using univariate and multivariate logistic regression analyses. Moreover, the predictive value of favorable factors was analyzed by receiver operating characteristics (ROC) curve, and patients were assigned into high/low level groups based on the cut-off value of these factors, with their in-hospital survival rates compared. RESULTS: The in-hospital survival rate of the medium-/high-risk groups was lower than that of the low-risk group. Emergency percutaneous coronary intervention (PCI), lymphocyte (LYM), total protein (TP), albumin (ALB), and sodium (Na) were independent favorable factors for in-hospital survival in the medium-/high-risk groups. Besides, LYM > 1.275 × 109/L, TP > 60.25 g/L, ALB > 34.55 g/L, and Na > 137.9 mmo1/L had auxiliary predictive value for the survival of STEMI patients with medium-/high-risk TIMI scores. Patients with high levels of LYM, TP, ALB, and Na exhibited higher in-hospital survival rates than patients with low levels. CONCLUSION: For STEMI patients with medium- and high-risk TIMI scores, accepting emergency PCI and normal levels of LYM, TP, ALB, and Na were more conducive to in-hospital survival.

Lactobacillus-derived indole-3-lactic acid ameliorates colitis in cesarean-born offspring via activation of aryl hydrocarbon receptor.

Cesarean section (CS) delivery is known to disrupt the transmission of maternal microbiota to offspring, leading to an increased risk of inflammatory bowel disease (IBD). However, the underlying mechanisms remain poorly characterized. Here, we demonstrate that CS birth renders mice susceptible to dextran sulfate sodium (DSS)-induced colitis and impairs group 3 innate lymphoid cell (ILC3) development. Additionally, CS induces a sustained decrease in Lactobacillus abundance, which subsequently contributes to the colitis progression and ILC3 deficiency. Supplementation with a probiotic strain, L. acidophilus, or its metabolite, indole-3-lactic acid (ILA), can attenuate intestinal inflammation and restore ILC3 frequency and interleukin (IL)-22 level in CS offspring. Mechanistically, we indicate that ILA activates ILC3 through the aryl hydrocarbon receptor (AhR) signaling. Overall, our findings uncover a detrimental role of CS-induced gut dysbiosis in the pathogenesis of colitis and suggest L. acidophilus and ILA as potential targets to re-establish intestinal homeostasis in CS offspring.