Complete Genome Sequence of Candida mucifera from an Otitis Media Patient.

We describe for the first time, a high-quality genome for a rare human yeast pathogen Candida mucifera, from a patient with chronic suppurative otitis media. This pathogen exhibited reduced azole susceptibility, similar to its close relatives within the Trichomonascus ciferrii species complex.

Enhancing proton-coupled electron transfer drives efficient methanogenesis in anaerobic digestion.

The enhancement of electron or proton transfer between syntrophic microbes has been widely recognised as a means for improving methane generation. However, the uncoupled supplementation of electrons and protons in multiphase anaerobic environment hinders the balanced uptake of electrons and protons in the cytoplasm of methanogens, limiting methanogenesis efficiency. Herein, the cooperative effect of a proton-conductive material (PM) and an electron-conductive material (EM) in enhancing proton-coupled electron transfer (PCET) and driving efficient methanogenesis in anaerobic digestion was investigated. The cooperation of the PM and EM significantly increased methane production and the maximum methane generation rate by 78.9 % and 103.5 %, respectively, indicating enhanced methanogenesis efficiency. Analysis of the physicochemical properties, biochemical components, and microbial dynamics revealed that the cooperation of the PM and EM improved the metabolism of syntrophic microbes, which was critically dependent on electron and proton transfer. This enhancement was primarily due to the improvement in PCET, as mainly supported by hydrogen/deuterium kinetic isotope effect measurements, multi-omics integration analyses and reaction thermodynamics and kinetics analyses. Our findings suggest that the PCET enhancement stimulated efficient membrane-bound enzymatic reactions related to electron-driven proton translocation and facilitated electron and proton supply for CO2 reduction to realise highly efficient methane generation. These findings are expected to provide a new insight into effective electron and proton coupling transfer for methanogenic metabolism in multiphase anaerobic environments.

Prevalence and clinical characteristics of venous thromboembolism in patients with lung cancer: a systematic review and meta-analysis.

Background: The prevalence of venous thromboembolism (VTE) is high in patients with cancer and can often present as the first symptom of malignancy. Cancer-associated VTE is one of the most important risk factors contributing to cancer mortality, making its prevention and treatment critical for patients with lung cancer. Methods: We systematically searched for observational studies that estimated the prevalence of VTE in patients with lung cancer. A comprehensive search of electronic databases, including PubMed, EMBASE and Cochrane Library, was systematically conducted from database inception through January 21, 2022. The qualities of included studies were assessed in three domains, including patient selection, comparison, and results. Random effects meta-analyses of the prevalence of VTE in lung cancer were conducted using the metaprop procedure. Chi-square test and I 2 value were used to evaluate study heterogeneity. Results: Thirty-five studies involving 742,156 patients were considered eligible for this study. The pooled prevalence of VTE among patients with lung cancer was 5% (95% CI: 0.043-0.056, P = 0.000). The regional prevalence of VTE was 7% (95% CI: 0.06-0.08; I2 = 99.2%) in North America, 8% (95% CI: 0.06-0.10; I2 = 97.6%) in Asia, 6% (95% CI: 0.04-0.09; I2 = 95.9%) in Europe and 11% (95% CI: 0.07-0.15) in Australasia. Conclusions: The prevalence of lung cancer-related VTE is high and region-specific. These results of this review emphasize the importance of understanding the incidence of lung cancer-related VTE and provide argue for VTE screening of patients with lung cancer. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022306400).

Genomic analysis and metabolic characteristics provide insights into inorganic nitrogen metabolism of novel bacterium Acinetobacter pittii J08.

A novel A. pittii J08 with heterotrophic nitrification and aerobic denitrification (HN-AD) isolated from pond sediments could rapidly degrade inorganic nitrogen (N) and total nitrogen (TN-N) with ammonium (NH4+-N) preference. N degradation rate of NH4+-N, nitrite (NO2--N) and nitrate (NO3--N) were 3.9 mgL-1h-1, 3.0 mgL-1h-1 and 2.7 mgL-1h-1, respectively. In addition, strain J08 could effectively utilize most of detected low-molecular-weight carbon (LMWC) sources to degrade inorganic N with a wide adaptability to various culture conditions. Whole genome sequencing (WGS) analysis revealed that assembled genome of stain J08 possessed the crucial genes involved in dissimilatory/assimilatory NO3--N reduction and NH4+-N assimilation. These results indicated that strain J08 could be applied to wastewater treatment in aquaculture.

Causal relationship between inflammatory skin diseases and immunoglobulin A nephropathy: A Mendelian randomization and enrichment analysis study.

OBJECTIVE: To investigate the causal relationship between inflammatory skin diseases (atopic dermatitis, and psoriasis) and IgA nephropathy using Mendelian randomization and enrichment analysis. METHODS: The instrumental variables (IVs) in the European Bioinformatics Institute (EBI) database were used for two-sample MR analysis. The results of inverse variance weighting (IVW) were used as the main method, the MR-Egger method was used for pleiotropy analysis and the leave-one-out method was used for sensitivity analysis to verify the reliability of the data. Combined with the human genome database GeneCards database and Metascape enrichment analysis. RESULTS: People with AD had an increased risk of IgA nephropathy (IVW: OR = 1.06, 95% CI [1.0002-1.1248], p = 0.0491). Psoriasis and IgA nephropathy (IVW: OR = 0.97, 95% CI [0.9394-1.0055], p = 0.1002) no statistical significance, therefore cannot prove cause-and-effect relationship between. CONCLUSIONS: This study provides evidence that atopic dermatitis is associated with an increased risk of IgA nephropathy, but does not provide evidence that psoriasis is causologically associated with IgA nephropathy. Enrichment analysis suggested a causal relationship between inflammatory skin diseases and IgA nephropathy at the genetic level.

CRYAB Promotes Colorectal Cancer Progression by Inhibiting Ferroptosis Through Blocking TRIM55-Mediated ß-Catenin Ubiquitination and Degradation.

BACKGROUND: α-Crystallin B (CRYAB) is a chaperone member of the HSPs family that protects proteins with which it interacts from degradation. This study aims to investigate the effect of CRYAB on the progression of colorectal cancer (CRC) and its underlying mechanism. METHODS: CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP). RESULTS: CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from ß-catenin interacting with TRIM55, leading to an increase in ß-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression. CONCLUSIONS: Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.

B Cell Epigenetic Modulation of IgA Response by 5-Azacytidine and IgA Nephropathy.

BACKGROUND: IgA nephropathy is an important global cause of kidney failure. Dysregulation of IgA production is thought to play a key role in IgA nephropathy pathogenesis, however, little is known about the epigenetic mechanisms such as RNA 5- methylcytosine (5mC) modification in regulating IgA synthesis. METHODS: To decipher the role of RNA 5mC in regulation of IgA class switch, the miR-23b-/- and LCWE induced Kawasaki disease mice were treated with 5-azacytidine. Trdmt1-/- and double Trdmt1-/-/ miR-23b-/- mice, Aid-/- mice or Aid-/-/ miR-23b-/- mice were also employed. RESULTS: We showed that miR-23b down regulated expression of Transfer RNA Aspartic Acid Methyltransferase 1 (Trdmt1) and consequently reduced 5-methylcytosine (m5C) RNA modification and IgA synthesis in B cells. Inhibition of m5C RNA modification normalised serum IgA levels and ameliorated progression of the IgA nephropathy-like kidney disease in miR-23b-/- and Kawasaki disease mice while mesangial IgA and C3 deposition failed to develop in Trdmt1-/-miR-23b-/- mice. By contrast, increased m5C RNA modification resulted in an exaggerated IgA nephropathy phenotype. miR-23b regulation of serum IgA levels and the development of an IgA nephropathy-like kidney disease in miR-23b-/- and Kawasaki disease mice is likely mediated through TRDMT1 driven 5-methylcytosine RNA modification in B cells, resulting in impaired activation-induced cytidine deaminase activity and IgA class switch recombination. CONCLUSIONS: This study revealed TRDMT1 induced RNA 5mC methylation regulate IgA class switch and inhibition of RNA 5mC by 5-Azacytidine could ameliorate progression of IgA nephropathy.

Delayed ventricular septal rupture complicated with ventricular aneurysm in a case of myocardial infarction with non-obstructive coronary arteries.

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. CASE PRESENTATION: We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. CONCLUSIONS: The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

The value of the platelet/high-density lipoprotein cholesterol ratio in predicting depression and its cardiovascular disease mortality: a population-based observational study.

Background: Cardiovascular disease (CVD) and depression have a bidirectional association, with inflammation and metabolic factors being common important triggers for both conditions. However, as a novel inflammatory and metabolic marker, platelet-to-HDL-C ratio (PHR) has not been established in relation to depression and cardiovascular disease. Materials and methods: Participants aged 20 years and older were included in the 2005-2018 NHANES database. PHR was calculated as the ratio of platelet count (1000 cells/µL) to HDL-C (mmol/L). The Patient Health Questionnaire (PHQ-9) was used to diagnose depression, with a cutoff value of 10. Weighted logistic regression analysis and restricted cubic spline (RCS) analysis were employed to examine the association between PHR and depression-related features. Additionally, weighted COX regression and RCS were used to analyze the association of PHR with CVD mortality in patients with depression. Receiver operating characteristic curves were used to assess whether PHR had an advantage over HDL-C in predicting depression. Finally, the mediating role of PHR in the latest cardiovascular health indicator Life's Essential 8 and depression was explored. Results: A total of 26,970 eligible participants were included, including 2,308 individuals with depression, representing approximately 160 million U.S. adults when weighted. After full adjustment, we estimated that the odds ratio (OR) of depression associated with a per standard deviation (SD) increase in PHR was 1.06 (95% CI: 1.01-1.12, P=0.03). The restricted cubic spline (RCS) analysis indicated a linear association (Nonlinear P=0.113). When PHR was divided into four groups based on quartiles and included in the model after full adjustment for depression risk factors, participants in quartile 2, quartile 3, and quartile 4 of PHR showed a trend of increasing risk of depression compared to the lowest quartile group (P trend=0.01). In addition, weighted COX regression and RCS revealed that a per SD increase in PHR was associated with a higher risk of CVD mortality among patients with depression (HR: 1.38, 95% CI: 1.05-1.81, P=0.02, Nonlinear P=0.400). Subgroup analyses showed that current alcohol consumption enhanced the association between PHR and depression (P for interaction=0.017). Furthermore, the areas under the ROC curves (AUC) were 0.556 (95% CI, 0.544-0.568; P < 0.001) for PHR and 0.536 (95% CI, 0.524-0.549; P < 0.001) for HDL-C (PDeLong = 0.025). Finally, mediation analysis indicated that PHR was an intermediate mechanism between LE8 and depression (mediation proportion=5.02%, P=0.02). Conclusion: In U.S. adults, an increase in PHR linearly increases the risk of depression and CVD mortality among individuals with depression. Additionally, PHR has a better predictive advantage for depression compared to HDL-C. Furthermore, PHR significantly mediates the association between LE8 scores and depression.

Bioinspired molecular catalysts with a unique tricopper architecture for highly efficient oxygen reduction reaction.

In situ growth of intertwined trinuclear copper complexes (nCu3) on a cellulose-derived carbon support (CMC) produced a high-performance electrocatalyst (CMC-nCu3) for the oxygen reduction reaction (ORR), which demonstrated superior performance in zinc-air batteries compared to a commercial Pt/C catalyst. This work highlights the importance of copper-based molecular catalysts with rich and intertwined tricopper structures for boosting both ORR activity and stability.

The association of platelet count, high-density lipoprotein cholesterol, and platelet/high-density lipoprotein cholesterol ratio with serum soluble Klotho.

BACKGROUND AND OBJECTIVE: Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. METHODS: Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. RESULTS: A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (ß: -51.19, 95% CI: -75.41 to -26.97, P < 0.001) and the highest quartile group of PC (ß: -72.34, 95% CI: -93.32 to -51.37, P < 0.0001) were significantly lower than those in their respective lowest quartile groups, and a significant downward trend was presented among the four groups (P for trend < 0.05, respectively). However, high-density lipoprotein cholesterol (HDL-C) concentrations were not significantly associated with S-Klotho concentrations. RCS revealed that the PHR and PC were nonlinearly associated with S-Klotho concentrations; two-piecewise linear regression revealed that the inflection points were 175.269 and 152, respectively, and that these associations slightly weakened after the inflection point. According to the subgroup analysis, liver disease status enhanced the association between the PC and S-Klotho concentrations. CONCLUSIONS: Both the PHR and PC were significantly negatively associated with S-Klotho concentrations, and these associations were nonlinear. There was no significant association between HDL-C and S-Klotho concentrations. Liver disease status enhances the negative association between the PC and S-Klotho concentrations, and the specific mechanism deserves further exploration.

The novel HLA-A*02:1146 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:1146 differs from HLA-A*02:01:01:01 by one nucleotide in exon 1.

The nucleus accumbens in reward and aversion processing: insights and implications.

The nucleus accumbens (NAc), a central component of the brain's reward circuitry, has been implicated in a wide range of behaviors and emotional states. Emerging evidence, primarily drawing from recent rodent studies, suggests that the function of the NAc in reward and aversion processing is multifaceted. Prolonged stress or drug use induces maladaptive neuronal function in the NAc circuitry, which results in pathological conditions. This review aims to provide comprehensive and up-to-date insights on the role of the NAc in motivated behavior regulation and highlights areas that demand further in-depth analysis. It synthesizes the latest findings on how distinct NAc neuronal populations and pathways contribute to the processing of opposite valences. The review examines how a range of neuromodulators, especially monoamines, influence the NAc's control over various motivational states. Furthermore, it delves into the complex underlying mechanisms of psychiatric disorders such as addiction and depression and evaluates prospective interventions to restore NAc functionality.

Comparison and elucidation of the changes in the key odorants of precooked stewed beef during cooking-refrigeration-reheating.

The key odorants contributing to the warmed-over flavor (WOF) of reheated precooked stewed beef were characterized using a sensomics approach. Overall, 36 odorants were identified, and based on flavor dilution factors, odor activity values, aroma recombination, and omission test, 11 compounds mainly derived from lipid oxidation were characterized as the key odorants contributing to the formation of WOF. In particular, 3-(methylthio)propanal, which was positively correlated with meaty aroma, was implicated in an overall increase in WOF. Thus, these odorants were elected as potential markers of WOF in the reheated precooked stewed beef. In summary, the WOF of the precooked stewed beef could be attributed to an overall increase in lipid oxidation products and a decrease in the odorants with desirable aromas. The characterization of WOF in precooked stewed beef will aid in the flavor quality control of precooked stewed beef dishes.

Deciphering the triclosan degradation mechanism in Sphingomonas sp. strain YL-JM2C: Implications for wastewater treatment and marine resources.

Triclosan (TCS), an antimicrobial agent extensively incorporated into pharmaceuticals and personal care products, poses significant environmental risks because of its persistence and ecotoxicity. So far, a few microorganisms were suggested to degrade TCS, but the microbial degradation mechanism remains elusive. Here, a two-component angular dioxygenase (TcsAaAb) responsible for the initial TCS degradation was characterized in Sphingomonas sp. strain YL-JM2C. Whole-cell biotransformation and crude enzyme assays demonstrated that TcsAaAb catalyzed the conversion of TCS to 4-chlorocatechol and 3,5-dichlorocatechol rather than the commonly suggested product 2,4-dichlorophenol. Then two intermediates were catabolized by tcsCDEF cluster via an ortho-cleavage pathway. Critical residues (N262, F279, and F391) for substrate binding were identified via molecular docking and mutagenesis. Further, TcsAaAb showed activity toward methyl triclosan and nitrofen, suggesting its versatile potential for bioremediation. In addition, TCS-degrading genes were also present in diverse bacterial genomes in wastewater, ocean and soil, and a relatively high gene abundance was observed in marine metagenomes, revealing the transformation fate of TCS in environments and the microbial potential in pollutant removal. These findings extend the understanding of the microbe-mediated TCS degradation and contribute to the mining of TCS-degrading strains and enzymes, as well as their application in the bioremediation of contaminated environments.

Histone modifications in hypoxic ischemic encephalopathy: Implications for therapeutic interventions.

Hypoxic-ischemic encephalopathy (HIE) is a brain injury induced by many causes of cerebral tissue ischemia and hypoxia. Although HIE may occur at many ages, its impact on the neonatal brain is greater because it occurs during the formative stage. Recent research suggests that histone modifications may occur in the human brain in response to acute stress events, resulting in transcriptional changes and HIE development. Because there are no safe and effective therapies for HIE, researchers have focused on HIE treatments that target histone modifications. In this review, four main histone modifications are explored, histone methylation, acetylation, phosphorylation, and crotonylation, as well as their relevance to HIE. The efficacy of histone deacetylase inhibitors in the treatment of HIE is also explored. In conclusion, targeting histone modifications may be a novel strategy for elucidating the mechanism of HIE, as well as a novel approach to HIE treatment.

Effect of AMF Inoculation on Reducing Excessive Fertilizer Use.

Excessive use of chemical fertilizer is a global concern. Arbuscular mycorrhizal fungi (AMF) are considered a potential solution due to their symbiotic association with crops. This study assessed AMF's effects on maize yield, fertilizer efficiency, plant traits, and soil nutrients under different reduced-fertilizer regimes in medium-low fertility fields. We found that phosphorus supplementation after a 30% fertilizer reduction enhanced AMF's positive impact on grain yield, increasing it by 3.47% with pure chemical fertilizers and 6.65% with mixed fertilizers. The AMF inoculation did not significantly affect the nitrogen and phosphorus fertilizer use efficiency, but significantly increased root colonization and soil mycelium density. Mixed fertilizer treatments with phosphorus supplementation after fertilizer reduction showed greater mycorrhizal effects on plant traits and soil nutrient contents compared to chemical fertilizer treatments. This study highlights that AMF inoculation, closely linked to fertilization regimes, can effectively reduce fertilizer use while sustaining or enhancing maize yields.

Size and shape control of microgel-encapsulating tumor spheroid via a user-friendly solenoid valve-based sorter and its application on precise drug testing.

The precision of previous cancer research based on tumor spheroids, especially the microgel-encapsulating tumor spheroids, was limited by the high heterogeneity in the tumor spheroid size and shape. Here, we reported a user-friendly solenoid valve-based sorter to reduce this heterogeneity. The artificial intelligence algorithm was employed to detect and segmentate the tumor spheroids in real-time for the size and shape calculation. A simple off-chip solenoid valve-based sorting actuation module was proposed to sort out target tumor spheroids with the desired size and shape. Utilizing the developed sorter, we successfully uncovered the drug response variations on cisplatin of lung tumor spheroids in the same population but with different sizes and shapes. Moreover, with this sorter, the precision of drug testing on the spheroid population level was improved to a level comparable to the precise but complex single spheroid analysis. The developed sorter also exhibits significant potential for organoid morphology and sorting for precision medicine research.

ResNeXt-CC: a novel network based on cross-layer deep-feature fusion for white blood cell classification.

Accurate diagnosis of white blood cells from cytopathological images is a crucial step in evaluating leukaemia. In recent years, image classification methods based on fully convolutional networks have drawn extensive attention and achieved competitive performance in medical image classification. In this paper, we propose a white blood cell classification network called ResNeXt-CC for cytopathological images. First, we transform cytopathological images from the RGB color space to the HSV color space so as to precisely extract the texture features, color changes and other details of white blood cells. Second, since cell classification primarily relies on distinguishing local characteristics, we design a cross-layer deep-feature fusion module to enhance our ability to extract discriminative information. Third, the efficient attention mechanism based on the ECANet module is used to promote the feature extraction capability of cell details. Finally, we combine the modified softmax loss function and the central loss function to train the network, thereby effectively addressing the problem of class imbalance and improving the network performance. The experimental results on the C-NMC 2019 dataset show that our proposed method manifests obvious advantages over the existing classification methods, including ResNet-50, Inception-V3, Densenet121, VGG16, Cross ViT, Token-to-Token ViT, Deep ViT, and simple ViT about 5.5-20.43% accuracy, 3.6-23.56% F1-score, 3.5-25.71% AUROC and 8.1-36.98% specificity, respectively.