Long-term cardiovascular disease outcomes in non-hospitalized medicare beneficiaries diagnosed with COVID-19: Population-based matched cohort study.

BACKGROUND: SARS-CoV2, the virus that causes coronavirus disease 2019 (COVID-19), can affect multiple human organs structurally and functionally, including the cardiovascular system and brain. Many studies focused on the acute effects of COVID-19 on risk of cardiovascular disease (CVD) and stroke especially among hospitalized patients with limited follow-up time. This study examined long-term mortality, hospitalization, CVD and stroke outcomes after non-hospitalized COVID-19 among Medicare fee-for-service (FFS) beneficiaries in the United States. METHODS: This retrospective matched cohort study included 944,371 FFS beneficiaries aged ≥66 years diagnosed with non-hospitalized COVID-19 from April 1, 2020, to April 30, 2021, and followed-up to May 31, 2022, and 944,371 propensity score matched FFS beneficiaries without COVID-19. Primary outcomes were all-cause mortality, hospitalization, and incidence of 15 CVD and stroke. Because most outcomes violated the proportional hazards assumption, we used restricted cubic splines to model non-proportional hazards in Cox models and presented time-varying hazard ratios (HRs) and Bonferroni corrected 95% confidence intervals (CI). RESULTS: The mean age was 75.3 years; 58.0% women and 82.6% non-Hispanic White. The median follow-up was 18.5 months (interquartile range 16.5 to 20.5). COVID-19 showed initial stronger effects on all-cause mortality, hospitalization and 12 incident CVD outcomes with adjusted HRs in 0-3 months ranging from 1.05 (95% CI 1.01-1.09) for mortality to 2.55 (2.26-2.87) for pulmonary embolism. The effects of COVID-19 on outcomes reduced significantly after 3-month follow-up. Risk of mortality, acute myocardial infarction, cardiomyopathy, deep vein thrombosis, and pulmonary embolism returned to baseline after 6-month follow-up. Patterns of initial stronger effects of COVID-19 were largely consistent across age groups, sex, and race/ethnicity. CONCLUSIONS: Our results showed a consistent time-varying effects of COVID-19 on mortality, hospitalization, and incident CVD among non-hospitalized COVID-19 survivors.

Comparison of Pipeline embolization device versus Tubridge embolization device in unruptured intracranial aneurysms: a multicenter, propensity score matched study.

BACKGROUND: Flow diverter devices (FDs) are increasingly used for treating unruptured intracranial aneurysms (UIAs), but limited studies compared different FDs. OBJECTIVE: To conduct a propensity score matched analysis comparing the Pipeline embolization device (PED) and Tubridge embolization device (TED) for UIAs. METHODS: Patients with UIAs treated with either PED or TED between July 2016 and July 2022 were included. Propensity score matching was performed to adjust for age, sex, comorbidities, smoking, drinking, aneurysm size, morphology, neck, location, parent artery diameter, adjunctive coiling, and angiographic follow-up duration. Perioperative complications and clinical and angiographic outcomes were compared after matching. RESULTS: 735 patients treated by PED and 290 patients treated by TED were enrolled. Compared with the PED group, patients in the TED group had a greater number of women and patients with ischemia, a smaller proportion of vertebrobasilar and non-saccular aneurysms, a smaller size and neck, and fewer adjunctive coils and overlapping stents, but a larger parent artery diameter and lumen disparities. After adjusting for these differences, 275 pairs were matched. No differences were found in perioperative complications (4.4% vs 2.5%, P=0.350), in-stent stenosis (16.0% vs 15.6%, P>0.999), or favorable prognosis (98.9% vs 98.5%, P>0.999). However, PED showed a trend towards better complete occlusion over a median 8-month angiographic follow-up (81.8% vs 75.3%, P=0.077). CONCLUSION: Compared with PED, TED provides a comparable rate of perioperative and short-term outcomes. Nevertheless, a better occlusion status in the PED group needs to be further verified over a longer follow-up period.

Corn Silk Polysaccharide Reduces the Risk of Kidney Stone Formation by Reducing Oxidative Stress and Inhibiting COM Crystal Adhesion and Aggregation.

The aim of this study is to explore the inhibition of nanocalcium oxalate monohydrate (nano-COM) crystal adhesion and aggregation on the HK-2 cell surface after the protection of corn silk polysaccharides (CSPs) and the effect of carboxyl group (-COOH) content and polysaccharide concentration. METHOD: HK-2 cells were damaged by 100 nm COM crystals to build an injury model. The cells were protected by CSPs with -COOH contents of 3.92% (CSP0) and 16.38% (CCSP3), respectively. The changes in the biochemical indexes of HK-2 cells and the difference in adhesion amount and aggregation degree of nano-COM on the cell surface before and after CSP protection were detected. RESULTS: CSP0 and CCSP3 protection can obviously inhibit HK-2 cell damage caused by nano-COM crystals, restore cytoskeleton morphology, reduce intracellular ROS level, inhibit phosphoserine eversion, restore the polarity of the mitochondrial membrane potential, normalize the cell cycle process, and reduce the expression of adhesion molecules, OPN, Annexin A1, HSP90, HAS3, and CD44 on the cell surface. Finally, the adhesion and aggregation of nano-COM crystals on the cell surface were effectively inhibited. The carboxymethylated CSP3 exhibited a higher protective effect on cells than the original CSP0, and cell viability was further improved with the increase in polysaccharide concentration. CONCLUSIONS: CSPs can protect HK-2 cells from calcium oxalate crystal damage and effectively reduce the adhesion and aggregation of nano-COM crystals on the cell surface, which is conducive to inhibiting the formation of calcium oxalate kidney stones.

MEMS Oscillators-Network-Based Ising Machine with Grouping Method.

Combinatorial optimization (CO) has a broad range of applications in various fields, including operations research, computer science, and artificial intelligence. However, many of these problems are classified as nondeterministic polynomial-time (NP)-complete or NP-hard problems, which are known for their computational complexity and cannot be solved in polynomial time on traditional digital computers. To address this challenge, continuous-time Ising machine solvers have been developed, utilizing different physical principles to map CO problems to ground state finding. However, most Ising machine prototypes operate at speeds comparable to digital hardware and rely on binarizing node states, resulting in increased system complexity and further limiting operating speed. To tackle these issues, a novel device-algorithm co-design method is proposed for fast sub-optimal solution finding with low hardware complexity. On the device side, a piezoelectric lithium niobate (LiNbO3) microelectromechanical system (MEMS) oscillator network-based Ising machine without second-harmonic injection locking (SHIL) is devised to solve Max-cut and graph coloring problems. The LiNbO3 oscillator operates at speeds greater than 9 GHz, making it one of the fastest oscillatory Ising machines. System-wise, an innovative grouping method is used that achieves a performance guarantee of 0.878 for Max-cut and 0.658 for graph coloring problems, which is comparable to Ising machines that utilize binarization.

Effect of smoking cessation medications on intracranial aneurysm risk: A Mendelian randomization study.

INTRODUCTION: We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level. METHODS: Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested. RESULTS: Cigarettes smoked per day (OR=2.89; 95% CI:1.85-4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64-8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10-2.8) and smoking cessation (OR=6.80; 95% CI: 0.01-4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/day could be a main mediator of HYKK's effect on IA risk. CONCLUSIONS: This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation.

Suppression of hepatic ChREBP⍺-CYP2C50 axis-driven fatty acid oxidation sensitizes mice to diet-induced MASLD/MASH.

Compromised hepatic fatty acid oxidation (FAO) has been observed in human MASH patients and animal models of MASLD/MASH. It remains poorly understood how and when the hepatic FAO pathway is suppressed during the progression of MASLD towards MASH. Hepatic ChREBP⍺ is a classical lipogenic transcription factor that responds to the intake of dietary sugars. We examined its role in regulating hepatocyte fatty acid oxidation (FAO) and the impact of hepatic Chrebpa deficiency on sensitivity to diet-induced MASLD/MASH in mice. We discovered that hepatocyte ChREBP⍺ is both necessary and sufficient to maintain FAO in a cell-autonomous manner independently of its DNA-binding activity. Supplementation of synthetic PPAR⍺/δ agonist is sufficient to restore FAO in Chrebp-/- primary murine hepatocytes. Hepatic ChREBP⍺ was decreased in mouse models of diet-induced MAFSLD/MASH and in patients with MASH. Hepatocyte-specific Chrebp⍺ knockout impaired FAO, aggravated liver steatosis and inflammation, leading to early-onset fibrosis in response to diet-induced MASH. Conversely, liver overexpression of ChREBP⍺-WT or its non-lipogenic mutant enhanced FAO, reduced lipid deposition, and alleviated liver injury, inflammation, and fibrosis. RNA-seq analysis identified the CYP450 epoxygenase (CYP2C50) pathway of arachidonic acid metabolism as a novel target of ChREBP⍺. Over-expression of CYP2C50 partially restores hepatic FAO in primary hepatocytes with Chrebp⍺ deficiency and attenuates preexisting MASH in the livers of hepatocyte-specific Chrebp⍺-deleted mice. Thus, our findings support the protective role of hepatocyte ChREBPa against diet-induced MASLD/MASH in mouse models in part via promoting CYP2C50-driven FAO.

Distinguishing nitroimidazoles from nitrofurans via luminescence sensing.

Similarity of nitroimidazole and nitrofuran antibiotics in molecular structure and photophysical properties makes them difficult to distinguish via luminescence sensing technology. Herein, this is solved by a dye-encapsulated lanthanide metal-organic framework luminescent sensor.

A glycolytic metabolite bypasses "two-hit" tumor suppression by BRCA2.

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes. An analogous SBS signature, again without biallelic BRCA2 inactivation, accompanies MGO accumulation and DNA damage in Kras-driven, Brca2-mutant murine pancreatic cancers and human breast cancers. MGO triggers BRCA2 proteolysis, temporarily disabling BRCA2's tumor suppressive functions in DNA repair and replication, causing functional haploinsufficiency. Intermittent MGO exposure incites episodic SBS mutations without permanent BRCA2 inactivation. Thus, a metabolic mechanism wherein MGO-induced BRCA2 haploinsufficiency transiently bypasses Knudson's two-hit requirement could link glycolysis activation by oncogenes, metabolic disorders, or dietary challenges to mutational signatures implicated in cancer evolution.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis.

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Cr(VI) Reduction and Sequestration by FeS Nanoparticles Formed in situ as Aquifer Material Coating to Create a Regenerable Reactive Zone.

Remediation of large and dilute plumes of groundwater contaminated by oxidized pollutants such as chromate is a common and difficult challenge. Herein, we show that in situ formation of FeS nanoparticles (using dissolved Fe(II), S(-II), and natural organic matter as a nucleating template) results in uniform coating of aquifer material to create a regenerable reactive zone that mitigates Cr(VI) migration. Flow-through columns packed with quartz sand are amended first with an Fe2+ solution and then with a HS- solution to form a nano-FeS coating on the sand, which does not hinder permeability. This nano-FeS coating effectively reduces and immobilizes Cr(VI), forming Fe(III)-Cr(III) coprecipitates with negligible detachment from the sand grains. Preconditioning the sand with humic or fulvic acid (used as model natural organic matter (NOM)) further enhances Cr(VI) sequestration, as NOM provides additional binding sites of Fe2+ and mediates both nucleation and growth of FeS nanoparticles, as verified with spectroscopic and microscopic evidence. Reactivity can be easily replenished by repeating the procedures used to form the reactive coating. These findings demonstrate that such enhancement of attenuation capacity can be an effective option to mitigate Cr(VI) plume migration and exposure, particularly when tackling contaminant rebound post source remediation.

A metabolomics study on carcinogenesis of ground-glass nodules.

Objective: This study aimed to identify differential metabolites and key metabolic pathways between lung adenocarcinoma (LUAD) tissues and normal lung (NL) tissues using metabolomics techniques, to discover potential biomarkers for the early diagnosis of lung cancer. Material and Methods: Forty-five patients with primary ground-glass nodules (GGN) identified on computed tomography imaging and who were willing to undergo surgery at Shanghai General Hospital from December 2021 to December 2022 were recruited to the study. All participants underwent video thoracoscopy surgery with segmental or wedge resection of the lung. Tissue samples for pathological examination were collected from the site of ground-glass nodules (GGN) lesion and 3 cm away from the lesion (NL). The pathology results were 35 lung adenocarcinoma (LUAD) cases (13 invasive adenocarcinoma, 14 minimally invasive adenocarcinoma, and eight adenocarcinoma in situ), 10 benign samples, and 45 NL tissues. For the untargeted metabolomics technique, 25 LUAD samples were assigned as the case group and 30 NL tissues as the control group. For the targeted metabolomics technique, ten LUAD samples were assigned as the case group and 15 NL tissues as the control group. Samples were analyzed by untargeted and targeted metabolomics, with liquid chromatography-tandem mass spectrometry detection used as part of the experimental procedure. Results: Untargeted metabolomics revealed 164 differential metabolites between the case and control groups, comprising 110 up regulations and 54 down regulations. The main metabolic differences found by the untargeted method were organic acids and their derivatives. Targeted metabolomics revealed 77 differential metabolites between the case and control groups, comprising 69 up regulations and eight down regulations. The main metabolic changes found by the targeted method were fatty acids, amino acids, and organic acids. The levels of organic acids such as lactic acid, fumaric acid, and malic acid were significantly increased in LUAD tissue compared to NL. Specifically, an increased level of L-lactic acid was found by both untargeted (variable importance in projection [VIP] = 1.332, fold-change [FC] = 1.678, q = 0.000) and targeted metabolomics (VIP = 1.240, FC = 1.451, q = 0.043). Targeted metabolomics also revealed increased levels of fumaric acid (VIP = 1.481, FC = 1.764, q = 0.106) and L-malic acid (VIP = 1.376, FC = 1.562, q = 0.012). Most of the 20 differential fatty acids identified were downregulated, including dodecanoic acid (VIP = 1.416, FC = 0.378, q = 0.043) and tridecane acid (VIP = 0.880, FC = 0.780, q = 0.106). Furthermore, increased levels of differential amino acids were found in LUAD samples. Conclusion: Lung cancer is a complex and heterogeneous disease with diverse genetic alterations. The study of metabolic profiles is a promising research field in this cancer type. Targeted and untargeted metabolomics revealed significant differences in metabolites between LUAD and NL tissues, including elevated levels of organic acids, decreased levels of fatty acids, and increased levels of amino acids. These metabolic features provide valuable insights into LUAD pathogenesis and can potentially serve as biomarkers for prognosis and therapy response.

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses.

Background: The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear. Methods: Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination. Results: IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration. Conclusions: These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza.

Consistent signatures in the human gut microbiome of old- and young-onset colorectal cancer.

The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

Effects of micro-nano plastics on the environmental biogeochemical cycle of nitrogen: A comprehensive review.

Micro-nano plastics (MNPs; size <5 mm), ubiquitous and emerging pollutants, accumulated in the natural environment through various sources, and are likely to interact with nutrients, thereby influencing their biogeochemical cycle. Increasing scientific evidences reveal that MNPs can affect nitrogen (N) cycle processes by affecting biotopes and organisms in the environmental matrix and MNPs biofilms, thus plays a crucial role in nitrous oxide (N2O) and ammonia (NH3) emission. Yet, the mechanism and key processes behind this have not been systematically reviewed in natural environments. In this review, we systematically summarize the effects of MNPs on N transformation in terrestrial, aquatic, and atmospheric ecosystems. The effects of MNPs properties on N content, composition, and function of the microbial community, enzyme activity, gene abundance and plant N uptake in different environmental conditions has been briefly discussed. The review highlights the significant potential of MNPs to alter the properties of the environmental matrix, microbes and plant or animal physiology, resulting in changes in N uptake and metabolic efficiency in plants, thereby inhibiting organic nitrogen (ON) formation and reducing N bioavailability, or altering NH3 emissions from animal sources. The faster the decomposition of plastics, the more intense the perturbation of MNPs to organisms in the natural ecosystem. Findings of this provide a more comprehensive analysis and research directions to the environmentalists, policy makers, water resources planners & managers, biologists, and biotechnologists to do integrate approaches to reach the practical engineering solutions which will further diminish the long-term ecological and climatic risks.