Integrating molecular pathway with genome-wide association data for causality identification in breast cancer.

OBJECTIVE: The study purpose was to explore the causal association between pyruvate metabolism and breast cancer (BC), as well as the molecular role of key metabolic genes, by using bioinformatics and Mendelian randomization (MR) analysis. METHODS: We retrieved and examined diverse datasets from the GEO database to ascertain differentially acting genes (DAGs) in BC via differential expression analysis. Following this, we performed functional and pathway enrichment analyses to ascertain noteworthy molecular functions and metabolic pathways in BC. Employing MR analysis, we established a causal association between pyruvate metabolism and the susceptibility to BC. Additionally, utilizing the DGIdb database, we identified potential targeted medications that act on genes implicated in the pyruvate metabolic pathway and formulated a competing endogenous RNA (ceRNA) regulatory network in BC. RESULTS: We collected the datasets GSE54002, GSE70947, and GSE22820, and identified a total of 1127 DEGs between the BC and NC groups. GO and KEGG enrichment analysis showed that the molecular functions of these DEGs mainly included mitotic nuclear division, extracellular matrix, signaling receptor activator activity, etc. Metabolic pathways were mainly concentrated in PI3K-Akt signaling pathway, Cytokine-cytokine receptor binding and Pyruvate, Tyrosine, Propanoate and Phenylalanine metabolism, etc. In addition, MR analysis demonstrated a causal relationship between pyruvate metabolism and BC risk. Finally, we constructed a regulatory network between pathway genes (ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C) and targeted drugs, as well as a ceRNA (lncRNA-miRNA-mRNA) regulatory network for BC, further revealing their interactions. CONCLUSIONS: Our research revealed a causal association between pyruvate metabolism and BC risk, found that ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C takes place an important part in the development of BC in the molecular mechanisms related to pyruvate metabolism, and identified some potential targeted small molecule drugs.

Chemical Bath Deposited Antimony Oxide Thin Films for Efficient Perovskite Solar Cells.

The metal oxide electron transport layers (ETLs) of n-i-p perovskite solar cells (PSCs) are dominated by TiO2 and SnO2, while the efficacy of the other metal oxide ETLs still lags far behind. Herein, an emerging, economical, and environmentally friendly metal oxide, antimony oxide (Sb2Ox, x = 2.17), prepared by chemical bath deposition is reported as an alternative ETL for PSCs. The deposited Sb2Ox film is amorphous and very thin (∼10 nm) but conformal on rough fluorine-doped tin oxide substrates, showing matched energy levels, efficient electron extraction, and then reduced nonradiative recombination in PSCs. The champion PSC based on the Sb2Ox ETL delivers an impressive power conversion efficiency of 24.7% under one sun illumination, which represents the state-of-the-art performance of all metal oxide ETL-based PSCs. Additionally, the Sb2Ox-based devices show improved operational and thermal stability compared to their SnO2-based counterparts. Armed with these findings, we believe this work offers an optional ETL for perovskites-based optoelectronic devices.

Effect of Continuous Infusion of Different Doses of Esketamine on the Bispectral Index During Sevoflurane Anesthesia: A Randomized Controlled Trial.

Purpose: To investigate and quantify the effect of continuous esketamine infusion at different doses on the bispectral index (BIS) during sevoflurane anesthesia. Methods: A total of 120 patients scheduled for elective laparoscopic renal surgery were randomly divided into three groups. Under steady anesthesia and surgical situations, the patient was started on continuous infusion of the study drug: 0.125 mg/kg/h esketamine (group E1), 0.25 mg/kg/h esketamine (group E2), and the same volume of saline (group C). The primary outcome was changes in BIS value after 15 min (T15), 30 min (T30), 45 min (T45), and 60 min (T60) of drug infusion. The secondary outcomes were 95% spectral edge frequency (SEF95), electromyogram (EMG), heart rate (HR), and mean arterial pressure (MAP) from T0 to T60. Furthermore, postoperative pain, postoperative recovery, and perioperative adverse events were evaluated. Results: Compared with group C, group E1 exhibited significant BIS elevation at T30-T60 and group E2 at T15-T60 (P < 0.001). Compared with group E1, group E2 showed a more significant BIS elevation at T15-T60 (P < 0.001). The area under the curve (AUC) of BIS and SEF95 were significantly higher in group E2 than in groups C and E1 (P < 0.05). BIS value for any of the three groups was significantly correlated with SEF95 (P < 0.001). No significant differences were observed in the AUC of EMG, HR, and MAP among the three groups. Intraoperative remifentanil consumption and postoperative NRS of pain on movement were significantly reduced in group E2 compared with groups C and E1 (P < 0.05). Conclusion: Continuous infusion of both 0.125 and 0.25 mg/kg/h of esketamine increased the BIS value during sevoflurane anesthesia, and the BIS value gradually stabilized with the prolongation of the infusion time.

The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Integrative analysis of homologous recombination repair patterns unveils prognostic signatures and immunotherapeutic insights in breast cancer.

Globally, breast cancer (BC) is the leading cause of female death and morbidity. Homologous recombination repair (HRR) is critical in BC. However, the prognostic role and immunotherapy response of HRR in BC remains to be clarified. Firstly, we identified HRR types in BC samples from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset (GSE42568) based on 65 HRR genes (HRRGs). A differentially expressed gene (DEG) list for different HRR types was generated. Then, the influences of gene sets composed of these DEGs on biological pathways and BC prognosis were explored. Next, we identified gene clusters based on gene sets composed of DEGs. Genes associated with prognosis for DEGs were identified using univariate Cox regression. Finally, the HRR score was constructed based on genes associated with prognosis. We analyzed how HRR score correlates with tumor mutation burden (TMB), immune cell infiltration (ICI), and immunotherapy response. Three HRR clusters were discovered. HRR subtype A demonstrated decreased infiltration and a high number of immunosuppressive cells with a poor prognosis. DEGs among various HRR types were predominantly enriched in cell cycle and genomic stability-related pathways. The prognostic model based on sixteen DEGs accurately predicted BC prognosis. The HRRGs were differentially expressed in three DEG clusters. TMB, ICI, and immunotherapy responses differed significantly between the high and low HRR groups (HSG, LSG). The HSG was distinguished by a high degree of ICI and low TMB. LSG had a better response to anti-PD-1 or anti-PD-1 and anti-CTLA4 combination therapy. This work revealed that HRR patterns would contribute to predicting prognosis and immunotherapy response in BC, which may benefit patients.

Proposed Structural Model for Chiral Au40(SC2H4Ph)24 Nanoclusters.

The structural configuration of thiolate-protected gold nanoclusters plays a pivotal role in elucidating the correlation between their structure and properties, comprehending their stability, and guiding experimental synthesis. In this study, utilizing the grand unified model and the ring model, we employed an innovative strategy of fusing triangular Au3 and tetrahedral Au4 elementary blocks by sharing a gold atom to design the gold core, predicting the structure of the Au40(SR)24 nanoclusters. Density functional theory calculations indicate that with the protective ligands simplified to methyl groups the energy of the predicted Au40(SR)24 is 0.45 eV lower than that of the experimentally reported Au40(o-MBT)24 nanoclusters, implying its substantial stability. Furthermore, the calculated UV absorption spectrum and circular dichroism spectrum of predicted Au40(SR)24 are consistent with the experimental results of Au40(SC2H4Ph)24 nanoclusters, suggesting that the predicted structure is a likely candidate for the structure of Au40(SC2H4Ph)24 nanoclusters.

Heterogeneity of diabetic dyslipidemia, data from the NHANES (2011-2016).

Epidemiologic studies have demonstrated that diabetes amplifies the effects of dyslipidemia as a risk factor for cardiovascular disease (CVD). A better understanding of lipid profiles is important for lipid-lowering treatment and reducing cardiovascular risk in populations with diabetes. To describe the dyslipidemia patterns in patient with and without diabetes in the adult US population. Data from National Health and Nutrition Examination Survey (NHANES) 2011 to 2016 was analyzed. Surprisingly, 49.9% of the people with diabetes have both normal triglycerides (TGs) and normal high-density lipoprotein cholesterol (HDL-C). 33.4% of the people with diabetes have elevated TGs and 36.1% of them have low HDL-C. Only 19.3% of them have both elevated TGs and low HDL-C. Among people without diabetes, 67.5% have normal TGs and normal HDL-C, 28.0% have elevated TGs, 23.9% have low HDL-C and 8.8% have both elevated TGs and low HDL-C. The differences in the proportions of individuals with both elevated TGs and low HDL-C between the diabetic group and the nondiabetic group were more obvious in females: 7.7% in women without diabetes and 22.7% in women with diabetes. The proportion of individuals in the TG↑HDL-C↓group in the population with diabetes exhibited a decreasing trend in age groups > 30 years old, and the 30 to 40 years group of individuals with diabetes had the highest proportion of atherogenic dyslipidemia. The low-density lipoprotein cholesterol (LDL-C) to apoB ratio is generally lower in people with diabetes, with the lowest level in the TG↑HDL-C↓group. Dyslipidemia patterns in diabetes patients are highly heterogeneous. Deep phenotyping sub-groups of dyslipidemia is warranted to identify higher-risk patients for evaluation of non-LDL-C therapies. This explained at least partially of the difficult search for novel therapies in the post-LDL-C era.

Integrated ultrastructural, physiological, transcriptomic, and metabolomic analysis uncovers the mechanisms by which nicotinamide alleviates cadmium toxicity in Pistia stratiotes L.

Exogenous nicotinamide (NIC) is a promising solution to relieve heavy metal (HM) toxicity in plants. Nonetheless, the underlying mechanisms involved remain poorly understood. As NIC addition (200 µM) can increase the tolerance of Pistia stratiotes L. to Cd stress (10 mg L-1), this strategy was subjected to integrated ultrastructural, physiological, transcriptomic, and metabolomic analysis to reveal the mechanisms involved. Exogenous NIC initiated a series of physiological, transcriptional, and metabolic responses that alleviated Cd damage. NIC addition improved Cd transfer from roots to leaves and reduced Cd damage in roots. The transported Cd to leaves did not induce further toxicity because it was abundantly compartmentalised in cell walls, which might be mediated by lignin synthesis. Moreover, NIC addition improved the repair of photosystem II in leaves under Cd stress by inducing key genes (e.g., chlorophyll A-B binding protein and PSII repair protein encoding genes), resulting in the restoration of Fv/Fm. In addition, antioxidant enzyme activities (e.g., peroxidase and catalase) and synthesis of antioxidants (e.g., stachydrine and curculigoside) were triggered to overcome oxidative stress. Our work paves the way for a deeper understanding of the mechanisms by which NIC alleviates HM toxicity in plants, providing a basis for improving phytoremediation.

Reduction-Oxidation Cascade Strategy for Reforming a Au13-Kerneled Gold Thiolate Nanocluster.

Gold nanoclusters protected by thiolate ligands are ideal models for investigating the structure-property correlation of nanomaterals. Introducing relatively weak coordinating ligands into gold thiolate nanoclusters and thus reforming their structures is beneficial for further releasing their activities. However, controlling the selectivity of the process is a challenging task. In this work, we report a cascade strategy for deeply and purposefully reforming the structures of gold thiolate nanoclusters, exemplified by a Au13-kerneled Au23 nanocluster. Specifically, weakly coordinated triphenylphosphine was utilized to reduce (activate) the surface of Au23, enabling its further structural reformation by the following oxidation step. A structurally distinctive Au20 nanocluster was obtained based on this reduction-oxidation cascade strategy. Mechanism studies reveal that both the reduction and oxidation steps and their working sequence are critical for the transformation. Theoretical and experimental results all indicate that the deep structural reformation results in the evolution of the electronic and photoluminescent properties of the gold thiolate nanocluster.

Decoding Chemical Formula to Spatial Conformation: A Structural Study Targeting the [Au25(SR)19]0 Nanocluster.

Structural global searches employing highly efficient algorithms have been extensively applied for studying molecules and clusters. However, the code-aided spatial conformational determination of thiolated gold nanoclusters (AuNCs) has not been accomplished because of the complex structural architecture of AuNCs, especially when only the chemical formula of the cluster is known. Experiments have shown that the star [Au25(SR)18]-1 cluster can transform into the [Au25(SR)19]0 cluster. However, the crystal structure of the [Au25(SR)19]0 cluster has not been experimentally determined, and theoretical structural predictions for this cluster are challenging because no template cluster presents for [Au25(SR)19]0. Utilizing the grand unified model, this study succeeded in obtaining the structure of the [Au25(SR)19]0 cluster by using minimal computations, which was verified to be reasonable through stability analysis and experimental absorption spectrum confirmation. Although the predicted [Au25(SR)19]0 cluster has the same number of Au atoms as the [Au25(SR)18]-1 cluster, the structure is considerably altered, owing to the presence of a face-centered cubic kernel. This study provides insights for decoding the chemical formulas of AuNCs to determine their spatial conformations.

Association between anemia-related biomarkers and the adequacy of peritoneal dialysis in Chinese patients with chronic kidney disease.

Objectives: The study aimed to examine the association of three anemia-related biomarkers with the adequacy of peritoneal dialysis (PD) in patients with chronic kidney disease (CKD). Methods: This study included 127 PD patients. The total Kt/V urea (Kt/V) was calculated according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. All patients were classified into two groups based on Kt/V, viz., adequate (Kt/V ≥1.7) and inadequate (Kt/V <1.7) groups. Effect sizes are expressed as odds ratios (ORs) and 95% confidence interval (CI). Results: After adjusting for age, gender, hypertension, diabetes, and PD duration, 20 g/L increment in hemoglobin (Hgb) was observed to significantly reduce the risk of inadequate PD by 19% (OR; 95% CI; P: 0.81; 0.70 to 0.95; 0.009), 5 g/L increment in the mean corpuscular hemoglobin concentration (MCHC) by 7% (0.93; 0.88 to 0.98; 0.009), and 5% increment in transferrin saturation (TS) by 23% (0.77; 0.64 to 0.94; 0.012). The gender-specific nomogram model was constructed by incorporating three significant anemia-related biomarkers and convenient influencing factors, and the prediction accuracy was good (concordance index (C-index): 0.686 for men and 0.825 for women). Conclusion: Our findings indicate that the deterioration of three anemia-related biomarkers (Hgb, MCHC, and TS) can precipitate the development of inadequate PD in Chinese patients with CKD.

Deep learning for real-time detection of breast cancer presenting pathological nipple discharge by ductoscopy.

Objective: As a common breast cancer-related complaint, pathological nipple discharge (PND) detected by ductoscopy is often missed diagnosed. Deep learning techniques have enabled great advances in clinical imaging but are rarely applied in breast cancer with PND. This study aimed to design and validate an Intelligent Ductoscopy for Breast Cancer Diagnostic System (IDBCS) for breast cancer diagnosis by analyzing real-time imaging data acquired by ductoscopy. Materials and methods: The present multicenter, case-control trial was carried out in 6 hospitals in China. Images for consecutive patients, aged ≥18 years, with no previous ductoscopy, were obtained from the involved hospitals. All individuals with PND confirmed from breast lesions by ductoscopy were eligible. Images from Beijing Chao-Yang Hospital were randomly assigned (8:2) to the training (IDBCS development) and internal validation (performance evaluation of the IDBCS) datasets. Diagnostic performance was further assessed with internal and prospective validation datasets from Beijing Chao-Yang Hospital; further external validation was carried out with datasets from 5 primary care hospitals. Diagnostic accuracies, sensitivities, specificities, and positive and negative predictive values for IDBCS and endoscopists (expert, competent, or trainee) in the detection of malignant lesions were obtained by the Clopper-Pearson method. Results: Totally 11305 ductoscopy images in 1072 patients were utilized for developing and testing the IDBCS. Area under the curves (AUCs) in breast cancer detection were 0·975 (95%CI 0·899-0·998) and 0·954 (95%CI 0·925-0·975) in the internal validation and prospective datasets, respectively, and ranged between 0·922 (95%CI 0·866-0·960) and 0·965 (95%CI 0·892-0·994) in the 5 external validation datasets. The IDBCS had superior diagnostic accuracy compared with expert (0.912 [95%CI 0.839-0.959] vs 0.726 [0.672-0.775]; p<0.001), competent (0.699 [95%CI 0.645-0.750], p<0.001), and trainee (0.703 [95%CI 0.648-0.753], p<0.001) endoscopists. Conclusions: IDBCS outperforms clinical oncologists, achieving high accuracy in diagnosing breast cancer with PND. The novel system could help endoscopists improve their diagnostic efficacy in breast cancer diagnosis.

Hyaluronan-Induced CD44-iASPP Interaction Affects Fibroblast Migration and Survival.

In the present study, we show that the inhibitor of the apoptosis-stimulating protein of p53 (iASPP) physically interacts with the hyaluronan receptor CD44 in normal and transformed cells. We noticed that the CD44 standard isoform (CD44s), but not the variant isoform (CD44v), bound to iASPP via the ankyrin-binding domain in CD44s. The formation of iASPP-CD44s complexes was promoted by hyaluronan stimulation in fibroblasts but not in epithelial cells. The cellular level of p53 affected the amount of the iASPP-CD44 complex. iASPP was required for hyaluronan-induced CD44-dependent migration and adhesion of fibroblasts. Of note, CD44 altered the sub-cellular localization of the iASPP-p53 complex; thus, ablation of CD44 promoted translocation of iASPP from the nucleus to the cytoplasm, resulting in increased formation of a cytoplasmic iASPP-p53 complex in fibroblasts. Overexpression of iASPP decreased, but CD44 increased the level of intracellular reactive oxygen species (ROS). Knock-down of CD44s, in the presence of p53, led to increased cell growth and cell density of fibroblasts by suppression of p27 and p53. Our observations suggest that the balance of iASPP-CD44 and iASPP-p53 complexes affect the survival and migration of fibroblasts.

Circ_0110498 facilitates the cisplatin resistance of non-small cell lung cancer by mediating the miR-1287-5p/RBBP4 axis.

BACKGROUND: Circular RNAs (circRNAs) play vital roles in non-small cell lung cancer (NSCLC) progression. Our research analyzed the role of circ_0110498 on the cisplatin (DDP) resistance of NSCLC. METHODS: Cell glycolysis was analyzed by measuring glucose consumption and lactate production. Protein expression was determined by western blot analysis. The expression of circ_0110498, microRNA (miR)-1287-5p and RBBP4 was detected by RT-qPCR assay. Cell counting kit-8, colony formation and transwell assays, together with flow cytometry were conducted to analyze cell DDP resistance, proliferation, metastasis and apoptosis. RESULTS: Circ_0110498 expression was elevated in DDP-resistant NSCLC tissues and cells. Circ_0110498 silencing not only suppressed the DDP resistance of NSCLC cells by inhibiting cell growth, metastasis and glycolysis, but also enhanced the DDP sensitivity of NSCLC tumors. MiR-1287-5p was sponged by circ_0110498, and its inhibitor also reversed the effect of circ_0110498 silencing on the DDP resistance of NSCLC cells. MiR-1287-5p interacted with RBBP4, and RBBP4 overexpression partly reversed the inhibitory effect of miR-1287-5p on the DDP resistance of NSCLC cells. CONCLUSION: Circ_0110498 facilitated DDP resistance partly through mediating the miR-1287-5p/RBBP4 signaling in NSCLC.

Comparison of ultrasound-guided erector spinae plane block and thoracic paravertebral block for postoperative analgesia after laparoscopic nephrectomy: a randomized controlled non-inferiority clinical trial.

BACKGROUND: Thoracic paravertebral block offers effective analgesia after laparoscopic nephrectomy but has potential severe complication risks. Erector spinae plane block has been described for analgesia after abdominal surgery. However, there are no prospective randomized trials determining if ultrasound-guided erector spinae plane block is non-inferior to thoracic paravertebral block in terms of analgesia after abdominal surgeries including laparoscopic nephrectomy. METHODS: Sixty-six patients scheduled for laparoscopic nephrectomy were randomized in a 1:1 ratio to receive ultrasound-guided erector spinae plane block (erector spinae plane block group) or thoracic paravertebral block (thoracic paravertebral block group) with 25 mL 0.5% ropivacaine. The primary outcome of this non-inferiority study was the average numerical rating scale score at rest within the first 24 hours following surgery. Secondary outcomes included numerical rating scale scores at rest and while coughing at one, six, 12, 24 and 48 hours postoperatively, total press times of patient-controlled analgesia, time to first press of patient-controlled analgesia, pain rescue, puncture time, the first-attempt success rate to puncture, worst numerical rating scale score during block, dermatomal distribution of sensory blockade, postoperative nausea and vomiting scores, quality of recovery score and time to flatus. RESULTS: Sixty-one subjects, 30 from the erector spinae plane block group and 31 from the thoracic paravertebral block group, completed the study. The median difference (erector spinae plane block minus thoracic paravertebral block) in the primary outcome was 0 (95% CI: 0 to 1). The 95% CI upper limit did not exceed the non-inferiority margin of 1. Numerical rating scale scores at rest at 12 hours and while coughing at six and 12 hours postoperatively were statistically lower in the thoracic paravertebral block group (P=0.04, 0.04 and P<0.05, respectively). There was a shorter puncture time (42.1 s vs. 56.8 s), higher success rate of the first attempt to puncture (83% vs. 58%) and lower pain score during block (2 vs. 3) in the erector spinae plane block group. Other secondary outcomes were similar between groups. CONCLUSIONS: This study demonstrates that erector spinae plane block provides non-inferior analgesia for pain at rest within 24 postoperative hours in comparison to thoracic paravertebral block for laparoscopic nephrectomy.

Bioinformatic Analysis Identifies of Potential miRNA-mRNA Regulatory Networks Involved in the Pathogenesis of Lung Cancer.

Objective: The purpose of the present study was to explore the biomarkers related to lung cancer based on the bioinformatics method, which might be new targets for lung cancer treatment. Methods: GSE17681 and GSE18842 were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs (DEMs) and genes (DEGs) in lung cancer samples were screened via the GEO2R online tool. DEMs were submitted to the mirDIP website to predict target genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted via uploading DEGs to the DAVID database. The protein-protein interaction network (PPI) of the DEGs was analyzed by STRING's online tool. Then, the PPI network was visualized using Cytoscape 3.8.0. Results: 46 DEMs were identified in GSE17681, and the website predicted that there were 873 target genes of these DEMs. 1029 DEGs were identified in the GSE18842 chip. GO analysis suggested that the co-DEGs participated in the canonical Wnt signaling pathway, regulation of the Wnt signaling pathway, a serine/threonine kinase signaling pathway, the Wnt signaling pathway, and cell-cell signaling by Wnt. KEGG analysis results showed the co-DEGs of GSE17681 and GSE18842 were related to the Hippo signaling pathway and adhesion molecules. In addition, six hub genes that were related to lung cancer were identified as hub genes, including mTOR, NF1, CHD7, ETS1, IL-6, and COL1A1. Conclusions: The present study identified six hub genes that were related to lung cancer, including mTOR, NF1, CHD7, ETS1, IL-6, and COL1A1, which might be a potential target for lung cancer.

Directed exfoliating and ordered stacking of transition-metal-dichalcogenides.

Two-dimensional van der Waals crystals provide a limitless scope for designing novel combinations of physical properties by controlling the stacking order or twist angle of individual layers. Lattice orientation between stacked monolayers is significant not only for breaking the engineering symmetry but also for the study of many-body quantum phases and band topology. Thus far the state-of-the-art exfoliation approaches focus on the achievements of quality, size, yield, and scalability, while lacking sufficient information on lattice orientation. Consequently, interlayer alignment is usually determined by later experiments, such as the second harmonic generation spectroscopy, which increase the number of trials and errors for a designed artificial ordering and hampered the efficiency of systematic study. Herein, we report a lattice orientation distinguishable exfoliation method via gold favor epitaxy along the specific atomic step edges, meanwhile, fulfilling the requirements of high-quality, large-size, and high-yield monolayers. Hexagonal- and rhombohedral-stacking configurations of bilayer transition metal dichalcogenides are built directly at once as a result of foreseeing the lattice orientation. Optical spectroscopy, electron diffraction, and angle-resolved photoemission spectroscopy are used to study crystal quality, symmetric breaking, and band tuning, which support the exfoliating mechanism we proposed. This strategy shows the ability to facilitate the development of ordering stacking especially for multilayers assembling in the future.

Giant moiré trapping of excitons in twisted hBN.

Excitons in van der Waals (vdW) stacking interfaces can be trapped in ordered moiré potential arrays giving rise to the attractive phenomena of quantum optics and bosonic many-body effects. Compared to the prevalent transition metal dichalcogenides (TMDs) systems, due to the wide bandgap and low dielectric constant, excitons in twist-stacked hexagonal boron nitride (hBN) are anticipated trapped in deeper moiré potential, which enhances the strength of interactions. However, constrained by the common low detectivity of weak light-emitting in the deep-ultraviolet (DUV) bands, the moiré excitons in twist-hBN remain elusive. Here, we report that a remarkable DUV emitting band (peak located at ∼260 nm) only emerges at the twisted stacking area of hBN, which is performed by a high collection efficiency and spatially-resolved cathodoluminescence (CL) at room temperature. Significant peak red shifting contrast to defect-bound excitons of bulk hBN indicates the giant trapping effects of moiré potential for excitons. The observation of deeply trapped excitons motivates further studies of bosonic strongly correlation physics based on the twist-hBN system.

High nitrite-nitrogen stress intensity drives nitrite anaerobic oxidation to nitrate and inhibits methanogenesis.

Nitrite is an important intermediate in nitrogen metabolism. We explored the effect of nitrite-nitrogen stress intensity (NNSI) on nitrite metabolism and methanogenesis in anaerobic digestion. The results showed that the NNSI regulated microbial diversity, composition, and functions, and microbial community assembly was primarily shaped by stochastic processes. Moreover, the NNSI was negatively correlated with α-diversity and positively correlated with non-metric multi-dimensional scaling distance. Denitrification gradually increased with increasing NNSI; however, methanogenesis was gradually inhibited, which was primarily due to the inhibition of the aceticlastic methanogenesis pathway (i.e., Methanosaeta) and methylotrophic methanogenesis pathway (i.e., Candidatus_Methanofastidiosum). High NNSI (1882 ± 98.99 mg/L NO2--N) promoted nitrite anaerobic oxidation to nitrate and was favorable for dissimilatory nitrate reduction to ammonia (DNRA). We present evidence for the microbial transformation of nitrite under anaerobic conditions, with potential geochemical and evolutionary importance. As nitrogen oxides were already present on early Earth, our finding presents the possibility of a nitrogen cycle before the evolution of oxygenic photosynthesis.

Association of blood cobalt concentrations with dyslipidemia, hypertension, and diabetes in a US population: A cross-sectional study.

ABSTRACT: Various heavy metal elements in the human body have been reported to be associated with dyslipidemia, hypertension, and diabetes. The role of cobalt in these conditions is unclear. The current study aimed to investigate the association of blood cobalt concentrations with dyslipidemia, hypertension, and diabetes.Using the data collected from the National Health and Nutrition Examination Survey (2015-2018), we performed logistic regression to explore the association of blood cobalt concentrations with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, hypertension, and diabetes.A total of 6866 adults were included in this study. Participants with higher blood cobalt levels appeared to be older and have a lower body mass index and, were more likely to be female (P for trend < .05). After fully adjusting for demographic characteristics (Model 2), compared with the lowest quartile, the highest quartile of blood cobalt concentrations had lower odds ratios (ORs) for elevated TC [OR: 0.62, 95% confidential interval (CI): 0.53 to 0.72, P < .001], elevated LDL-C (OR: 0.65, 95% CI: 0.53-0.80, P < .001) and low HDL-C (OR: 0.81, 95% CI: 0.69-0.96, P = .013). The adjusted ORs for elevated TC, elevated LDL-C and low HDL-C were negatively correlated with increased blood cobalt concentrations (P for trend < .05). The adjusted ORs for hypertension and diabetes were not associated with blood cobalt concentrations (P > .05 and P for trend > .05).In conclusion, higher blood cobalt concentrations were associated with a lower risk of dyslipidemia. However, blood cobalt concentrations were not associated with the risk of hypertension or diabetes.