[Study of a patient with Myelodysplastic/myeloproliferative neoplasm with co-morbid neutrophilia and a novel NCOR1::GLYR1 fusion gene].

OBJECTIVE: To explore the genetic background for a patient with refractory myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with co-morbid neutrophilia patient. METHODS: A MDS/MPN patient who was admitted to the First Affiliated Hospital of Nanjing Medical University in May 2021 was selected as the study subject. RNA sequencing was carried out to identify fusion genes in his peripheral blood mononuclear cells. Fusion gene sequence was searched through transcriptome-wide analysis with a STAR-fusion procedure. The novel fusion genes were verified by quantitative real-time PCR and Sanger sequencing. RESULTS: The patient, a 67-year-old male, had progressive thrombocytopenia. Based on the morphological and molecular examinations, he was diagnosed as MDS/MPN with co-morbid neutropenia, and was treated with demethylating agents and Bcl-2 inhibitors. Seventeen months after the diagnosis, he had progressed to AML. A novel fusion gene NCOR1::GLYR1 was identified by RNA-sequencing in his peripheral blood sample, which was verified by quantitative real-time PCR and Sanger sequencing. The patient had attained morphological remission after a DCAG regimen (a combinatory chemotherapy of decitabine, cytarabine, aclarubicin and granulocyte colony-stimulating factors) plus Chidamide treatment. A significant decrease in the NCOR1::GLYR1 expression was revealed by quantitative real-time PCR at post-chemotherapy evaluation. CONCLUSION: NCOR1::GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

A Glycosyl Hydrolase 5 Family Protein Is Essential for Virulence of Necrotrophic Fungi and Can Suppress Plant Immunity.

Phytopathogenic fungi normally secrete large amounts of CWDEs to enhance infection of plants. In this study, we identified and characterized a secreted glycosyl hydrolase 5 family member in Sclerotinia sclerotiorum (SsGH5, Sclerotinia sclerotiorum Glycosyl Hydrolase 5). SsGH5 was significantly upregulated during the early stages of infection. Knocking out SsGH5 did not affect the growth and acid production of S. sclerotiorum but resulted in decreased glucan utilization and significantly reduced virulence. In addition, Arabidopsis thaliana expressing SsGH5 became more susceptible to necrotrophic pathogens and basal immune responses were inhibited in these plants. Remarkably, the lost virulence of the ΔSsGH5 mutants was restored after inoculating onto SsGH5 transgenic Arabidopsis. In summary, these results highlight that S. sclerotiorum suppresses the immune responses of Arabidopsis through secreting SsGH5, and thus exerts full virulence for successful infection.

Risk Factors and Patient-Reported Outcomes in Chinese Women with Postpartum Diastasis Recti Abdominis: An Observational Study.

Purpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women. Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann-Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis). Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group. Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.

Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy.

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

pH-Responsive nanoplatform synergistic gas/photothermal therapy to eliminate biofilms in poly(L-lactic acid) scaffolds.

To date, implant-associated infection is still a significant clinical challenge, which cannot be effectively eliminated by single therapies due to the formation of microbial biofilms. Herein, a pH-responsive nanoplatform was constructed via the in situ growth of zinc sulfide (ZnS) nanoparticles on the surface of Ti3C2 MXene nanosheets, which was subsequently introduced in poly(L-lactic acid) (PLLA) to prepare a composite bone scaffold via selective laser sintering technology. In the acidic biofilm microenvironment, the degradation of ZnS released hydrogen sulfide (H2S) gas to eliminate the biofilm extracellular DNA (eDNA), thus destroying the compactness of the biofilm. Then, the bacterial biofilm became sensitive to hyperthermia, which could be further destroyed under near-infrared light irradiation due to the excellent photothermal property of MXene, finally achieving gas/photothermal synergistic antibiofilm and efficient sterilization. The results showed that the synergistic gas/photothermal therapy for the composite scaffold not only evidently inhibited the formation of biofilms, but also effectively eradicated the eDNA of the already-formed biofilms and killed 90.4% of E. coli and 84.2% of S. aureus under near infrared light irradiation compared with single gas or photothermal therapy. In addition, the composite scaffold promoted the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Thus, the designed scaffold with excellent biofilm elimination and osteogenesis ability has great potential as an alternative treatment for implant-associated bone infections.

Cellulose and JbKOBITO 1 mediate the resistance of NaHCO3-tolerant chlorella to saline-alkali stress.

Carbonate stress has profound impacts on both agricultural and industrial production. Although a number of salinity-tolerant genes have been reported and applied in plants, there is a lack of research on the role of cell wall-related genes in resistance to carbonate. Likewise, in industry, current strategies have not been able to more effectively address the conflict between stress-induced microalgal biofuel accumulation and microalgal growth inhibition. It is of great significance to study the adaptation mechanism of carbonate-tolerant organisms and to explore related genes for future genetic modification. In this study, the role of the cell wall in the NaHCO3-tolerant chlorella JB17 was investigated. We found that JB17 possesses a relatively thick cell wall with a thickness of 300-600 nm, which is much higher than that of the control chlorella with a thickness of about 100 nm. Determination of the cell wall polysaccharide fractions showed that the cellulose content in the JB17 cell wall increased by 10.48% after NaHCO3 treatment, and the decrease in cellulose levels by cellulase digestion inhibited its resistance to NaHCO3. Moreover, the saccharide metabolome revealed that glucose, rhamnose, and trehalose levels were higher in JB17, especially rhamnose and trehalose, which were almost 40 times higher than in control chlorella. Gene expression detection identified an up-regulated expressed gene after NaHCO3 treatment, JbKOBITO1, overexpression of which could improve the NaHCO3 tolerance of Chlamydomonas reinhardtii. As it encodes a glycosyltransferase-like protein that is involved in cellulose synthesis, the strong tolerance of JB17 to NaHCO3 may be partly due to the up-regulated expression of JbKOBITO 1 and JbKOBITO 1-mediated cellulose accumulation. The above results revealed a critical role of cellulose in the NaHCO3 resistance of JB17, and the identified NaHCO3-tolerance gene will provide genetic resources for crop breeding in saline-alkali soils and for genetic modification of microalgae for biofuel production.

Transcriptome analysis revealed enrichment pathways and regulation of gene expression associated with somatic embryogenesis in Camellia sinensis.

The high frequency, stable somatic embryo system of tea has still not been established due to the limitations of its own characteristics and therefore severely restricts the genetic research and breeding process of tea plants. In this study, the transcriptome was used to illustrate the mechanisms of gene expression regulation in the somatic embryogenesis of tea plants. The number of DEGs for the (IS intermediate stage)_PS (preliminary stage), ES (embryoid stage)_IS and ES_PS stages were 109, 2848 and 1697, respectively. The enrichment analysis showed that carbohydrate metabolic processes were considerably enriched at the ES_IS stage and performed a key role in somatic embryogenesis, while enhanced light capture in photosystem I could provide the material basis for carbohydrates. The pathway analysis showed that the enriched pathways in IS_PS process were far less than those in ES_IS or ES_PS, and the photosynthesis and photosynthetic antenna protein pathway of DEGs in ES_IS or ES_PS stage were notably enriched and up-regulated. The key photosynthesis and photosynthesis antenna protein pathways and the Lhcb1 gene were discovered in tea plants somatic embryogenesis. These results were of great significance to clarify the mechanism of somatic embryogenesis and the breeding research of tea plants.

Can China achieve its 2030 and 2060 CO2 commitments? Scenario analysis based on the integration of LEAP model with LMDI decomposition.

China's ambitious targets of peaking its Carbon dioxide (CO2) emissions on or before 2030 and achieving carbon neutrality by 2060 have been a topic of discussion in the international community. This study innovatively combines the logarithmic mean Divisia index (LMDI) decomposition method and the long-range energy alternatives planning (LEAP) model to quantitatively evaluate the CO2 emissions from energy consumption in China from 2000 to 2060. Using the Shared Socioeconomic Pathways (SSPs) framework, the study designs five scenarios to explore the impact of different development pathways on energy consumption and related carbon emissions. The LEAP model scenarios are based on the result of LMDI decomposition, which identifies the key influencing factors on CO2 emissions. The empirical findings of this study demonstrate that the energy intensity effect is the primary factor of the 14.7 % reduction in CO2 emissions observed in China from 2000 to 2020. Conversely, the economic development level effect has been the driving factor behind the increase of 50.4 % in CO2 emissions. Additionally, the urbanization effect has contributed 24.7 % to the overall change in CO2 emissions during the same period. Furthermore, the study investigates potential future trajectories of CO2 emissions in China up to 2060, based on various scenarios. The results suggest that, under the SSP1 scenarios. China's CO2 emissions would peak in 2023 and achieve carbon neutrality by 2060. However, under the SSP4 scenarios, emissions are expected to peak in 2028, and China would need to eliminate approximately 2000 Mt of additional CO2 emissions to reach carbon neutrality. In other scenarios, China is projected to be unable to meet the carbon peak and carbon neutrality goals. The conclusions drawn from this study offer valuable insights for potential policy adjustments to ensure that China could fulfill its commitment to peak carbon emissions by 2030 and achieve carbon neutrality by 2060.

Neurodegenerative disease and antioxidant biomarkers: A bidirectional Mendelian randomization study.

Objective: Previous observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause-effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD)]. Methods: A bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson's Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer's Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data. Results: Based on the Bonferroni correction p < 0.0015, there was no significant causal evidence for the antioxidant biomarkers on neurodegenerative diseases, however, the reverse analysis found that AD was significantly related to the decrease in retinol (IVW: beta = -0.023, p = 0.0007; WM: beta = -0.025, p = 0.0121), while the same analysis was carried out between the AD validation database and retinol, the results were consistent (IVW: beta = -0.064, p = 0.025). Moreover, AD on Glutathione S-transferase (GST), PD on Glutathione Peroxidase (GPX) as well as PD on uric acid (UA) also indicated potential causal-and-effect associations (IVW: p = 0.025; p = 0.027; p = 0.021, respectively). Conclusions: There was no sufficient evidence that antioxidant imbalance has a significant causal effect on neurodegenerative diseases. However, this study revealed that genetically predicted AD was significantly related to the decrease in retinol, which provides a new insight into previous research and indicates the possibility to regard retinol as potential biomarker for the diagnosis and progress of AD.

Hydroxychloroquine protects against autoimmune premature ovarian insufficiency by modulating the Treg/Th17 cell ratio in BALB/c mice.

AIMS: The role of hydroxychloroquine (HCQ) in premature ovarian insufficiency (POI) remains unclear. The purpose of this study was to evaluate the effect of HCQ on ovarian function in mice with POI and to clarify its potential mechanisms. METHODS: POI was induced in mice by injection with zona pellucida 3 peptide (pZP3), and HCQ was administered intragastrically. Stages of the estrous cycle were determined using vaginal cytology. The ovarian structure was observed under a microscope after hematoxylin-eosin staining. The levels of serum hormones and anti-ZP antibody (aZPAb) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of CD4, CD45, and ZP2, ZP3 were determined using immunofluorescence and immunohistochemistry, respectively. The T regulatory (Treg)/ T helper 17 (Th17) cell ratio was analyzed using flow cytometry analysis. Western blotting was performed to assess the expression levels of proteins, transcription factors and cytokines. RESULTS: Administration of HCQ to mice with POI greatly restored their estrus cycle. In the treatment group compared to the POI group, estradiol (E2 ) levels were higher, and follicle stimulating hormone (FSH) levels were lower. In addition, following pZP3, HCQ treatment increased ZP2 and ZP3 expression. Additionally, by inhibiting the activation of the TLR7 signaling pathway, HCQ attenuated the infiltration of inflammatory cells and prevented the activated naive CD4+ T cells from developing into Th17 cells. CONCLUSION: Our findings showed that HCQ effectively restored ovarian function by altering the Treg/Th17 cell ratio in mice with POI, indicating that HCQ maybe a promising therapeutic method for patients with POI.

Listening to voices from multiple sources: A qualitative text analysis of the emotional experiences of women living with breast cancer in China.

Background: Receiving a breast cancer diagnosis and treatment is both a physical and emotional journey. Previous studies using single-source data have revealed common and culture-specific emotional experiences of patients living with breast cancer. However, few studies have combined such data from multiple sources. Thus, using a variety of data sources, the current study sought to explore the emotional experiences of women in China newly diagnosed, post-operative, or undergoing chemotherapy. We posited that even though women living with breast cancer in China have multiple channels through which they can express these emotional experiences, little variance would be found in their emotional expressivity and the themes they want to express due to cultural inhibitions. Methods: Text data from female patients newly diagnosed, post-operative, or undergoing chemotherapy were collected between June 2021 and January 2022 via a Python web crawler, semi-structured interviews, and an expressive writing intervention. Data were transcribed and subjected to thematic analysis. Reporting followed the consolidated criteria for reporting qualitative studies (COREQ) guidelines. Results: Analyses were based on 5,675 Weibo posts and comments published by 448 posters and 1,842 commenters, transcription texts from 17 semi-structured interviews, and 150 expressive writing texts. From this total collection of 461,348 Chinese characters, three major themes emerged: (i) conflicting emotions after diagnosis; (ii) long-term suffering and treatment concerns; and (iii) benefit finding and cognitive reappraisal. Conclusions: Despite gathering information from various sources, we found that distress from body-image disturbances, gender role loss and conflict, and changes in sexuality and fertility, were consistent among this sample of female Chinese patients with breast cancer. However, when women engaged actively in benefit finding and cognitive reappraisal with strong social support, patients were able to find ways to adapt and reported post-traumatic growth. Strong social support was an important facilitator in this growth. These study findings emphasize that healthcare professionals ought to increase cultural sensitivity, provide multiple channels to encourage patients to express their emotions, and incorporate screening for patients' emotional distress at all diagnostic and treatment phases as part of routine nursing care.

Endoscopic fenestration combined with catheterization in the treatment of a giant colonic fecalith causing bowel obstruction: a case report.

Obstruction of the colon caused by a fecalith is not a rare condition, but endoscopic attempts at removal of the fecalith are often unsuccessful because of the size of the fecalith and its extremely hard stone-like consistency. We report a case of bowel obstruction of over two weeks' duration caused by a giant colonic fecalith. Conservative treatments including insertion of a gastric tube and enemas failed to resolve the obstruction. After an initial unsuccessful attempt at fecalith removal by colonoscopy using a snare, we successfully resolved the bowel obstruction over the course of subsequent colonoscopies with endoscopic fenestration of the fecalith and placement of a transrectal gastric tube for directed instillation of the enema fluid, and we were able to avoid surgical intervention in this case.

The relationship between hemoglobin and triglycerides in moyamoya disease: A cross-sectional study.

Hemoglobin (Hb) and lipid metabolism are critical in the pathophysiology of moyamoya disease (MMD), and Hb and triglycerides (TGs) both play roles in the development of cerebrovascular illness. However, there is little evidence of a link between Hb and TGs in patients with MMD. This study aimed to determine the association between Hb and TGs in patients who had recently been diagnosed with MMD. From March 2013 to December 2018, 337 patients clinically diagnosed with MMD were admitted to our hospital. Among these, 235 were selected for analysis in this retrospective, cross-sectional study. Each patient's clinical features were documented. For analysis, we used univariate analysis, smoothed-curve fitting, and multivariable, piecewise linear regression. Overall, the mean±standard deviation patient age was 48.14 ± 11.24 years, 44.68% were men, and the mean Hb concentration was 135.72 ± 18.99 g/L. After controlling for relevant confounders, smoothed-curve fitting revealed a nonlinear association between the Hb and TG concentrations (P = 0.0448). When the Hb concentration was below 141 g/L, multivariate piecewise linear regression analysis revealed a significant association between the Hb and TG concentrations [ß: 0.01, 95% confidence interval (CI): 0.00, 0.01; P = 0.0182], although the association disappeared above this threshold (ß:-0.00, 95% CI:-0.01, 0.01; P = 0.4429). In individuals newly diagnosed with MMD, there is a significant correlation between Hb and TGs, which may be connected to MMD pathogenesis.

A novel oncogenic enhancer of estrogen receptor-positive breast cancer.

Estrogen receptor-positive (ER+) breast cancer accounts for the majority of breast cancers diagnosed, and nearly 20% of patients do not respond to endocrine therapy. The pathogenesis of ER+ breast cancer has not been well elucidated. The enhancer is a cis-regulatory element that promotes gene transcription and plays an important role in the spatiotemporal expression of cellular genes. Nevertheless, the oncogenic enhancer and its role in the occurrence and progression of cancer remain unclear. Here, we report a novel oncogenic enhancer (named αE myc ) for c-Myc and reveal its activation mechanism in ER+ breast cancer. The results demonstrated that αE myc enhanced the transcription of downstream genes more than 20-fold. The deletion of the 7-bp region (GGTTGCA) in αE myc significantly downregulated the expression of c-Myc, resulting in cell nuclear changes, cell-cycle arrest, cell apoptosis, and finally, remarkable inhibition of cell proliferation. In conclusion, the present study discovers a novel oncogenic enhancer αE myc (801 base pairs [bp], at Chr8: 127668529-127669329) and offers a remarkable core enhancer target (GGTTGCA) of αE myc for gene therapy of ER+ breast cancer.

Pan-cancer analysis of prognostic and immunological role of DTYMK in human tumors.

Background: Deoxythymidylate kinase (DTYMK) has been reported to correlate with the progression of hepatocellular carcinoma. However, the role of DTYMK in human cancers is not studied. In this study, we studied the prognostic value, functional states, and correlations with immune infiltration of DTYMK in human cancers. Methods: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), the search tool for the retrieval of interacting genes (STRING), GeneMANIA, cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource (TIMER) databases were utilized to analyze DTYMK in cancers. Results: In general, DTYMK is abnormally expressed between most human cancer and normal tissues from a pan-cancer perspective. DTYMK can be used as a diagnostic biomarker to differentiate tumor tissues from normal tissues in most tumors. Upregulation of DTYMK predicted poor survival status in most cancer types in TCGA. Moreover, DTYMK expression was correlated with the T stage in ACC, BRCA, KIRC, LIHC, and LUAD, with the N stage in BLCA, HNSC, KICH, KIRC, LUAD, LUSC, and THCA, with the M stage in ACC, KIRC, KIRP, and LUAD, with TNM stage in ACC, KIRC, LIHC, LUAD, and LUSC. In addition, based on single-cell sequencing data, we concluded that the expression of DTYMK was correlated with the functional status of the cell cycle, DNA damage, DNA repair, invasion, EMT, and proliferation. Finally, DTYMK expression was correlated with six infiltrating immune cells, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells by investigating TIMER. Conclusion: Our findings suggested that abnormally expressed DTYMK was correlated with poor survival, malignant functional status, and immune infiltrates. DTYMK might be served as a potential biomarker for diagnosis and poor prognosis in various cancer types. DTYMK might act as a potential target for immune therapy.

Coronary computed tomography angiography as a screening tool for moderate-high risk asymptomatic type 2 diabetes mellitus patients.

Background: There are few data on the clinical significance of coronary computed tomography angiography (CCTA) in asymptomatic type 2 diabetes mellitus (T2DM) patients. We performed a retrospective study to evaluate coronary heart disease (CHD) screening in asymptomatic patients with T2DM using CCTA and CHD risk stratification prediction. Materials and methods: Data from 141 T2DM patients (58 ± 8 years, 57% males) without known symptoms suggestive of CHD who underwent CCTA were retrospectively analyzed. The patients were classified into three subgroups based on United Kingdom prospective diabetes study (UKPDS) CHD risk stratification prediction. Seventy-four patients without diabetes mellitus and CHD who underwent CCTA successively were chosen as the control group. The segment involvement score (SIS), segment stenosis score (SSS), stenosis coefficient (SC), severe proximal plaque (SPP) positive ratio and CCTA-adapted Leaman score (CT-LeSc) based on CCTA data were evaluated and compared among the groups. Results: Compared with the patients in the control group, patients in the moderate-high risk DM groups had higher scores on the SIS, SSS, SC, CT-LeSc, and a higher SPP positive ratio (all p-values < 0.001), and no difference was observed between the low-risk group and the control group (p = 0.136, p = 0.088, p = 0.0.067, p = 0.225, p = 1.000, respectively). Compared with patients in the control group, the patients in the moderate-high risk DM groups had increased odds of SIS > 3 [odds ratio (OR) = 6.557, p < 0.001; OR = 4.455, p < 0.001, respectively], SSS > 5 (OR = 5.727, p < 0.001; OR = 5.144, p < 0.001, respectively), CT-LeSc > 8.7 (OR = 3.780, p = 0.001; OR = 2.804, p = 0.007, respectively), and obstructive stenosis (OR = 7.233, p < 0.001; OR = 5.787, p < 0.001, respectively). Conclusion: The moderate-high CHD risk patients had increased odds of obstructive coronary artery stenosis, and the distribution of coronary artery stenosis was more extensive and more severe in that group compared to the patients without diabetes mellitus and CHD. CHD can be effectively screened in moderate-high risk asymptomatic T2DM patients using CCTA.

The Classification and Prediction of Ferroptosis-Related Genes in ALS: A Pilot Study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscle paralysis, which is followed by degeneration of motor neurons in the motor cortex of the brainstem and spinal cord. The etiology of sporadic ALS (sALS) is still unknown, limiting the exploration of potential treatments. Ferroptosis is a new form of cell death and is reported to be closely associated with Alzheimer's disease (AD), Parkinson's disease (PD), and ALS. In this study, we used datasets (autopsy data and blood data) from Gene Expression Omnibus (GEO) to explore the role of ferroptosis and ferroptosis-related gene (FRG) alterations in ALS. Gene set enrichment analysis (GSEA) found that the activated ferroptosis pathway displayed a higher enrichment score, and the expression of 26 ferroptosis genes showed obvious group differences between ALS and controls. Using weighted gene correlation network analysis (WGCNA), we identified FRGs associated with ALS, of which the Gene Ontology (GO) analysis displayed that the biological process of oxidative stress was the most to be involved in. KEGG pathway analysis revealed that the FRGs were enriched not only in ferroptosis pathways but also in autophagy, FoxO, and mTOR signaling pathways. Twenty-one FRGs (NR4A1, CYBB, DRD4, SETD1B, LAMP2, ACSL4, MYB, PROM2, CHMP5, ULK1, AKR1C2, TGFBR1, TMBIM4, MLLT1, PSAT1, HIF1A, LINC00336, AMN, SLC38A1, CISD1, and GABARAPL2) in the autopsy data and 16 FRGs (NR4A1, DRD4, SETD1B, MYB, PROM2, CHMP5, ULK1, AKR1C2, TGFBR1, TMBIM4, MLLT1, HIF1A, LINC00336, IL33, SLC38A1, and CISD1) in the blood data were identified as target genes by least absolute shrinkage and selection operator analysis (LASSO), in which gene signature could differentiate ALS patients from controls. Finally, the higher the expression of CHMP5 and SLC38A1 in whole blood, the shorter the lifespan of ALS patients will be. In summary, our study presents potential biomarkers for the diagnosis and prognosis of ALS.

Genome-wide identification of resistance genes and transcriptome regulation in yeast to accommodate ammonium toxicity.

BACKGROUND: Ammonium is an important raw material for biomolecules and life activities, and the toxicity of ammonium is also an important ecological and agricultural issue. Ammonium toxicity in yeast has only recently been discovered, and information on its mechanism is limited. In recent years, environmental pollution caused by nitrogen-containing wastewater has been increasing. In addition, the use of yeast in bioreactors to produce nitrogen-containing compounds has been developed. Therefore, research on resistance mechanisms that allow yeast to grow under conditions of high concentrations of ammonium has become more and more important. RESULTS: To further understand the resistance mechanism of yeast to grow under high concentration of ammonium, we used NH4Cl to screen a yeast non-essential gene-deletion library. We identified 61 NH4Cl-sensitive deletion mutants from approximately 4200 mutants in the library, then 34 of them were confirmed by drop test analysis. Enrichment analysis of these 34 genes showed that biosynthesis metabolism, mitophagy, MAPK signaling, and other pathways may play important roles in NH4Cl resistance. Transcriptome analysis under NH4Cl stress revealed 451 significantly upregulated genes and 835 significantly downregulated genes. The genes are mainly enriched in: nitrogen compound metabolic process, cell wall, MAPK signaling pathway, mitophagy, and glycine, serine and threonine metabolism. CONCLUSIONS: Our results present a broad view of biological pathways involved in the response to NH4Cl stress, and thereby advance our understanding of the resistance genes and cellular transcriptional regulation under high concentration of ammonium.

Oxygen-rich ligands tailored for novel metal-organic gel electrocatalyst to promote two-electron selectivity electrocatalysis.

More extensive attention has been garnered about the H2O2 electroproduction via two-electron oxygen reduction reaction (2e- ORR). Aiming to develop a more active, more selective and more stable catalyst, herein we reported an unconventional raw metal-organic gels (MOGs) toward this process. This pioneering work, by ingeniously designing and altering the precursor ligands, achieving precisely controlling the number of oxygen groups (OGs). By elaborately comparing more than 70 samples, uncovered the significance that OGs could sufficiently promote the selectivity for H2O2 electrochemical synthesis through the two-electron pathway (realizing enhancement more than 20% in this work). The most potential Fe0.1Co0.9 MOG (H6L), performing an onset potential of 0.76 V (low overpotential), a high selectivity up to 93% ranging 0.15 V to 0.65 V (large voltage window) and 2.1 electron transfer number (implying the 2e- process dominate). This study, unlike other oxidation treatment, through the precise regulation of precursors, further confirmed the feasibility of oxygen-containing functional groups (OGs) tailoring strategy, providing a possibility for low-cost and efficient potential candidate of 2e- ORR.

Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma.

Background: Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) is involved in many human cancers. However, its clinical significance and function in lung adenocarcinoma remain unclear. Here, we examined the prognostic and immunological role of PSMD2 in lung adenocarcinoma. Methods: The Cancer Genome Atlas (TCGA) was conducted to analyze PSMD2 expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of PSMD2 on survival. cBioPortal database was conducted to identify the mutation characteristics of PSMD2. Functional enrichment was performed to determine PSMD2-related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of PSMD2 at single-cell resolution. PSMD2-related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between PSMD2 expression and tumor-infiltrating lymphocytes (TILs). Results: Both mRNA and protein expression of PSMD2 were significantly elevated in lung adenocarcinoma. High expression of PSMD2 was significantly correlated with high T stage (p = 0.014), lymph node metastases (p < 0.001), and TNM stage p = 0.005). Kaplan-Meier curves indicated that high expression of PSMD2 was correlated with poor overall survival (38.2 vs. 59.7 months, p < 0.001) and disease-specific survival (59.9 months vs. not available, p = 0.004). Multivariate analysis suggested that PSMD2 was an independent biomarker for poor overall survival (HR 1.471, 95%CI, 1.024-2.114, p = 0.037). PSMD2 had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of PSMD2 was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma. Functional enrichment suggested PSMD2 expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated PSMD2 expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that PSMD2 expression was correlated with immune cell infiltration levels and abundance of TILs. Conclusion: The upregulation of PSMD2 is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma. Our findings suggest that PSMD2 is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.