LncRNA SNHG3 discriminates rheumatoid arthritis from healthy individuals and regulates inflammatory response and oxidative stress via modulating miR-128-3p.

OBJECTIVES: This study evaluated the expression and significance of SNHG3 in Rheumatoid arthritis (RA) aiming to explore a biomarker and regulator for RA. METHODS: The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using PCR. The RA animal models were induced by the porcine type II collagen with Wistar rats and validated by the foot volume and AI score. The human fibroblast-like synoviocytes (H-FLS) were treated with LPS to mimic the injury during RA onset and the cell growth was assessed by CCK8 assay. RESULTS: SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine type II collagen induced increasing foot volume and AI scores of rats and SNHG3 was downregulated in RA rats. In LPS-induced H-FLS, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation. CONCLUSIONS: Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress via negatively modulating miR-128-3p.

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. METHODS: Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. RESULTS: NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. CONCLUSIONS: There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Milestones in understanding transport, sensing, and signaling of the plant nutrient phosphorus.

As an essential nutrient element, phosphorus (P) is primarily acquired and translocated as inorganic phosphate (Pi) by plant roots. Pi is often sequestered in the soil and becomes limited for plant growth. Plants have developed a sophisticated array of adaptive responses, termed P starvation responses, to cope with P deficiency by improving its external acquisition and internal utilization. Over the past 2 to 3 decades, remarkable progress has been made toward understanding how plants sense and respond to changing environmental P. This review provides an overview of the molecular mechanisms that regulate or coordinate P starvation responses, emphasizing P transport, sensing, and signaling. We present the major players and regulators responsible for Pi uptake and translocation. We then introduce how P is perceived at the root tip, how systemic P signaling is operated, and the mechanisms by which the intracellular P status is sensed and conveyed. Additionally, the recent exciting findings about the influence of P on plant-microbe interactions are highlighted. Finally, the challenges and prospects concerning the interplay between P and other nutrients and strategies to enhance P utilization efficiency are discussed. Insights obtained from this knowledge may guide future research endeavors in sustainable agriculture.

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Differential Responses of Medicago truncatula NLA Homologs to Nutrient Deficiency and Arbuscular Mycorrhizal Symbiosis.

NITROGEN LIMITATION ADAPTATION (NLA), a plasma-membrane-associated ubiquitin E3 ligase, plays a negative role in the control of the phosphate transporter family 1 (PHT1) members in Arabidopsis and rice. There are three NLA homologs in the Medicago truncatula genome, but it has been unclear whether the function of these homologs is conserved in legumes. Here we investigated the subcellular localization and the responses of MtNLAs to external phosphate and nitrate status. Similar to AtNLA1, MtNLA1/MtNLA2 was localized in the plasma membrane and nucleus. MtNLA3 has three alternative splicing variants, and intriguingly, MtNLA3.1, the dominant variant, was not able to target the plasma membrane, whereas MtNLA3.2 and MtNLA3.3 were capable of associating with the plasma membrane. In contrast with AtNLA1, we found that MtNLAs were not affected or even upregulated by low-phosphate treatment. We also found that MtNLA3 was upregulated by arbuscular mycorrhizal (AM) symbiosis, and overexpressing MtNLA3.1 in Medicago roots resulted in a decrease in the transcription levels of STR, an essential gene for arbuscule development. Taken together, our results highlight the difference between MtNLA homologs and AtNLA1. Further characterization will be required to reveal the regulation of these genes and their roles in the responses to external nutrient status and AM symbiosis.

Protocol for a randomized controlled trial exploring the brain mechanism and therapeutic effect of electroacupuncture on cognitive function and sleep quality in chronic insomnia.

BACKGROUND: Insomnia is a prevalent sleep disorder that affects up to 15% of the population worldwide and is the second most common mental health issue. There is increasing interest in the effects of long-term insomnia on cognitive function. Electroacupuncture can effectively improve cognitive function and sleep quality, yet the underlying brain network mechanisms remain unclear. This study aims to explore the network regulatory mechanisms associated with enhanced cognitive function and sleep quality, providing theoretical support for the use of electroacupuncture in the clinical treatment of chronic insomnia. METHODS: This study is divided into two parts. Sixteen individuals with chronic insomnia and 16 healthy controls of similar age and gender will be recruited in Study 1 to examine the brain network topology of individuals with chronic insomnia. Study 2 will be a randomized controlled trial with 120 chronic insomnia patients divided into three groups: Group A (electroacupuncture plus placebo drug), Group B (drug plus placebo electroacupuncture), and Group C (placebo electroacupuncture plus placebo drug). Participants will be exposed to 24 treatments over an 8-week period (3 times per week) and monitored for 12 additional weeks. The primary outcome measure will be changes in brainwave data from before to after the treatment. In addition, the Wisconsin Card Sorting Test and the Pittsburgh Sleep Quality Index will be utilized as secondary outcomes to measure from before to after treatment and during the follow-up. A correlation analysis will be conducted to explore links among modifications in brainwave patterns, Wisconsin Card Sorting Test scores, and Pittsburgh Sleep Quality Index scores. Additionally, any adverse events will be strictly monitored. DISCUSSION: Electroacupuncture may represent an alternative treatment for chronic insomnia, and this trial is expected to reveal the brain mechanism by which electroacupuncture improves cognitive function and sleep quality in chronic insomnia patients. TRIAL REGISTRATION: ChiCTR2200060150 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 20 May 2022).

The role of T cells and shared genes in psoriasis and inflammatory bowel disease based on single-cell RNA and comprehensive analysis.

Psoriasis and inflammatory bowel disease (IBD) have a similar etiology, including abnormal activation of T cells. Differentially expressed genes (DEGs) analysis was used to search for shared genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis were then performed. Secondly, single-cell RNA analysis (scRNA-seq) and immune infiltration were employed to explore the immune imbalance of the diseases. By weighted gene co expression network analysis (WGCNA), we obtained hub shared genes. Furthermore, we analyzed the diagnostic performance and immune association with the hub genes. Finally, functional enrichment of miRNAs related to hub shared genes was carried out. Single-cell analysis showed a high proportion of T cells among infiltrated immune cells and immune infiltration showed CD4+ T and γδ T cells were significantly elevated in diseases. Hub shared genes, LCN2, CXCL1 and PI3 had excellent diagnostic properties and were positively correlated with neutrophils, CD4+ T and γδ T cells. IL17 and TNF signaling pathway were the common pathway. In conclusion, CD4+ and γδ T cells and hub shared genes may play a crucial part in common mechanism between psoriasis and IBD. Moreover, hub shared genes may be potential diagnostic markers.

Identification of prognostic genes for breast cancer related to systemic lupus erythematosus by integrated analysis and machine learning.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multi-organ involvement, and some studies have found that SLE has a reduced risk of breast cancer (BRCA). So, we tried to find prognostic genes for BRCA related to SLE by integrated analysis and machine learning. METHOD: First, we downloaded 2 SLE datasets from Gene Expression Omnibus (GEO) and BRCA data from the Cancer Genome Atlas (TCGA). Subsequently, we performed differentially expressed genes (DEGs) and functional enrichment analysis by Metascape in SLE. Genes that were differentially expressed in both datasets were the validated DEGs. And after constructing PPI network, genes with nodes >30 were intersected with survival genes in BRCA to obtain candidate genes. Then, the candidate genes were validated by lasso regression in both training and validation sets to obtain prognostic genes. Afterwards, we investigated the diagnostic potential of prognostic genes for SLE and the predictive efficacy for BRCA prognosis. Moreover, GSEA analysis and immune infiltration were performed for SLE and BRCA. Finally, we constructed a prognostic gene-miRNAs network and did functional enrichment of the shared genes. RESULT: DEGs for SLE were mainly enriched with neutrophil degranulation and IFN pathways. After the lasso model of BRCA was established, IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE and had good predictive ability for the prognosis of BRCA. Prognostic genes had excellent diagnostic potential for SLE, with IFI35 and EIF2AK2 positively associated with SLE activity and IRF7 positively associated with IFI35. GSEA showed that both SLE and BRCA were associated with ubiquitinated degradation. Immune infiltrates suggest that plasma cells, dendritic cells (DC), neutrophils and monocyte were elevated in SLE. DC, NK and CD8+ T cells were elevated in the BRCA low-risk group. Finally, 5 shared miRNAs were confirmed, which were mainly enriched in the IFN pathway. CONCLUSION: IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE. IFN pathway played an important role in the etiology of SLE and the prognosis of BRCA.

Variation of growth and transcriptome responses to arbuscular mycorrhizal symbiosis in different foxtail millet lines.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) have been applied to promote the growth of different crop species, but knowledge about the impacts of symbiosis on foxtail millet at the physiological and molecular levels have remained limited. In this study, we compared the mycorrhization phenotypes of one cultivar and three different landraces and performed a comprehensive transcriptomic analysis to assess the effects of genetic variation on the responses to symbiosis. RESULTS: Our results showed that colonization by AMF did not enhance biomass accumulation but significantly increased grain production only in three lines. More than 2,000 genes were affected by AMF colonization in all lines. Most AM symbiosis-conserved genes were induced, but the induction levels varied between lines. Gene Ontology (GO) analysis showed that Biological Function terms related to nitrogen transport and assimilation were only enriched in TT8. Similarly, two of phosphate starvation-induced phosphate transporters were only simultaneously downregulated in TT8. In the other two lines, the enrichment of GO terms associated with cell wall reorganization and lignification was observed, though the effects were different. CONCLUSION: This study reveals the impacts of genetic variation of millet lines on the responses to AM symbiosis and provides information regarding AMF application for millet production.

A modified CVD method for the synthesis of monolayer MoS2and photoelectric improvement by HfO2passivation.

Molybdenum disulfide (MoS2) is an emerging class of new materials with a wide range of potential practical applications. However, the uncontrollability of monolayer MoS2synthesized by traditional chemical vapor deposition method and the low responsivity of MoS2photodetectors limit its further development in the field of photoelectric detection. To achieve controlled growth of monolayer MoS2and construct MoS2photodetectors with a high responsivity, we propose a novel single crystal growth strategy of high-quality MoS2by controlling the Mo to S vapor ratio near the substrate, and deposit a layer of hafnium oxide (HfO2) on the surface of MoS2to enhance the performance of the pristine metal-semiconductor-metal structure photodetector. At a reverse bias of 8 V, the HfO2passivated MoS2photodetector features an extremely high responsivity of1201AW-1,a response time of around 0.5 s, and a detectivity of7.7×1011Jones.Meanwhile, we deeply investigate the effect of the HfO2layer on the performance of the fabricated MoS2photodetector and propose a physical mechanism to interpret the obtained experiment results. These results might facilitate a better understanding on the performance modulation of the MoS2photodetectors and accelerate the development of MoS2-based optoelectronic devices.

Genes associated with cellular senescence favor melanoma prognosis by stimulating immune responses in tumor microenvironment.

PURPOSE: Skin cutaneous melanoma (SKCM), a malignant tumor from melanocytes, is the fifth most prevalent tumor. Immune checkpoint inhibitor (ICI) immunotherapy improves prognosis of SKCM, but immune response varies for different populations. Cellular senescence in the tumor microenvironment (TME) promotes antitumor immunity, mediated by dendritic cells (DC) and CD8+ T cells. Therefore, we sought to explore the role of cellular senescence in the TME of SKCM through bioinformatics and machine learning. METHODS: First, we obtained 93 cellular senescence-prognosis genes (CSPGs) by univariate survival analysis. Thereafter, 23 optimal CSPGs were obtained by least absolute shrinkage and selection operator (lasso) analysis. Based on the riskscore obtained by lasso analysis and clinical information from multivariate cox, we obtained the nomogram of SKCM, which was validated in the validation cohort. Based on the riskscore, the patients were split into low- and high-risk groups. Functional differences between the two groups were analyzed using Metascape and GSEA, and immune infiltration differences were achieved by multiple algorithms. We obtained a risk prediction nomogram for the validated SKCM based on the lasso model by univariate and multivariate cox regression analysis. RESULTS: In the low-risk group, immune responses were in an active state. NK, CD8+ T, DC, macrophages, and neutrophils were significantly upregulated, and ICI-relevant genes were notably upregulated. With the differentially expressed genes (DEGs) and optimal CSPGs, we obtained the hub genes: NOX4, NTN4, PROX1, and TRPM8. The hub genes were mainly expressed by cancer-associated fibroblasts (CAFs) and endothelial cells by single cell analysis, which were mainly associated with angiogenesis. CONCLUSION: Genes associated with cellular senescence favor SKCM prognosis by stimulating immune responses in TME. Patients with high expression of cellular senescence associated genes in the TME might have better benefit from ICI immunotherapy. Cellular senescence functions as a pro-tumor agent in mesenchymal cells and needs further study.

Integrated analysis and clinical correlation analysis of hub genes, immune infiltration, and potential therapeutic agents related to lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). This study aimed to explore biomarkers, mechanisms, and potential novel agents regarding LN through bioinformatic analysis. METHOD: Four expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were acquired. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses of DEGs were performed using the R software. The protein-protein interaction (PPI) network was developed using the STRING database. Additionally, five algorithms were used to screen out the hub genes. Expression of the hub genes were validated using Nephroseq v5. CIBERSORT was used to evaluate the infiltration of immune cells. Finally, The Drug-Gene Interaction Database was used to predict potential targeted drugs. RESULT: FOS and IGF1 were identified as hub genes, with excellent specificity and sensitivity diagnosis of LN. FOS was also related to renal injury. LN patients had lower activated and resting dendritic cells (DCs) and higher M1 macrophages and activated NK cells than healthy control (HC). FOS had a positive correlation with activated mast cells and a negative correlation with resting mast cells. IGF1 had a positive correlation with activated DCs and a negative correlation with monocytes. The targeted drugs were dusigitumab and xentuzumab target for IGF1. CONCLUSION: We analyzed the transcriptomic signature of LN along with the landscape of the immune cell. FOS and IGF1 are promising biomarkers for diagnosing and evaluating the progression of LN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of LN.

[Renaissance of prepectoral implant-based breast reconstruction: theoretical basis and research status].

Objective: To overview the theoretical basis and research status of prepectoral implant-based breast reconstruction. Methods: The domestic and foreign researches on the application of prepectoral implant-based breast reconstruction in breast reconstruction were retrospectively analyzed. The theoretical basis, clinical advantages, and limitations of this technique were summarized and the future development trend in this field was discussed. Results: The recent advances in breast cancer oncology, the development of materials and the concept of oncology reconstruction have provided a theoretical basis for prepectoral implant-based breast reconstruction. The selection of patients and the experience of surgeons are crucial for postoperative outcomes. Ideal thickness and blood flow of flaps are the most important considerations for the selection of prepectoral implant-based breast reconstruction. However, its long-term reconstruction outcomes and clinical benefits and risks in Asian populations still need to be confirmed by more studies. Conclusion: Prepectoral implant-based breast reconstruction has a broad application prospect in breast reconstruction following mastectomy. However, the evidence is limited at present. Randomized study with long-term follow-up is urgently in need to provide sufficient evidence to evaluate the safety and reliability of prepectoral implant-based breast reconstruction.

MtNF-YC6 and MtNF-YC11 are involved in regulating the transcriptional program of arbuscular mycorrhizal symbiosis.

Arbuscular mycorrhizal fungi are obligate symbionts that transfer mineral nutrients to host plants through arbuscules, a fungal structure specialized for exchange for photosynthetic products. MtNF-YC6 and MtNF-YC11, which encode the C subunits of nuclear factor Y (NF-Y) family in Medicago truncatula are induced specifically by arbuscular mycorrhizal symbiosis (AMS). A previous study showed that MtNF-YC6 and MtNF-YC11 are activated in cortical cells of mycorrhizal roots, but the gene functions were unknown. Herein, we identified both MtNF-YB17 and MtNF-YB12 as the interacting partners of MtNF-YC6 and MtNF-YC11 in yeast and plants. MtNF-YB17 was highly induced by AMS and activated in cortical cells only in mycorrhizal roots but MtNF-YB12 was not affected. The formation of B/C heterodimers led the protein complexes to transfer from the cytoplasm to the nucleus. Silencing MtNF-YC6 and C11 by RNA interference (RNAi) resulted in decreased colonization efficiency and arbuscule richness. Coincidently, genes associated with arbuscule development and degeneration in RNAi roots were also downregulated. In silico analysis showed CCAAT-binding motifs in the promoter regions of downregulated genes, further supporting the involvement of NF-Y complexes in transcriptional regulation of symbiosis. Taken together, this study identifies MtNF-YC6- or MtNF-YC11-containing protein complexes as novel transcriptional regulators of symbiotic program and provides a list of potential downstream target genes. These data will help to further dissect the AMS regulatory network.

Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. METHODS: The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. RESULTS: Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155-5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. CONCLUSION: The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.

Association between schizophrenia and prostate cancer risk: Results from a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Observational studies analyzing the risk of prostate cancer in schizophrenia patients have generated mixed results. We performed a meta-analysis and a Mendelian randomization (MR) analysis to evaluate the relationship and causality between schizophrenia and the risk of prostate cancer. METHODS: A comprehensive and systematic search of cohort studies was conducted, and a random-effects model meta-analysis was performed to calculate the standardized incidence ratios (SIRs) for prostate cancer incidence among schizophrenia patients versus the general population. To investigate the correlation between genetically-predicted schizophrenia and prostate cancer risk, we used summary statistics from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (61,106 controls and 79,148 cases), and 75 schizophrenia-associated single nucleotide polymorphisms (SNP) from European descent as the instrumental variable. RESULTS: In the meta-analysis of 13 cohort studies with 218,076 men involved, a decreased risk of prostate cancer was observed among schizophrenia patients [SIR 0.610; 95% confidence interval (CI) 0.500-0.740; p < 0.001] with significant heterogeneity (I2 = 83.3%; p < 0.001). However, MR analysis did not sustain the link between genetically-predicted schizophrenia and prostate cancer [odds ratio (OR) 1.033; 95% CI 0.998-1.069; p = 0.065]. The result was robust against extensive sensitivity analyses. CONCLUSIONS: Our study indicated a decreased risk of prostate cancer in schizophrenia patients through meta-analysis, while MR analysis did not support the connection between schizophrenia and prostate cancer. Due to the interaction of genetic variants between binary exposures, we need to be cautious in interpreting and presenting causal associations. Moreover, further research is needed to investigate underlying factors that might link schizophrenia to the risk of prostate cancer.

Epitaxial growth of wafer-scale molybdenum disulfide semiconductor single crystals on sapphire.

Two-dimensional (2D) semiconductors, in particular transition metal dichalcogenides (TMDCs), have attracted great interest in extending Moore's law beyond silicon1-3. However, despite extensive efforts4-25, the growth of wafer-scale TMDC single crystals on scalable and industry-compatible substrates has not been well demonstrated. Here we demonstrate the epitaxial growth of 2 inch (~50 mm) monolayer molybdenum disulfide (MoS2) single crystals on a C-plane sapphire. We designed the miscut orientation towards the A axis (C/A) of sapphire, which is perpendicular to the standard substrates. Although the change of miscut orientation does not affect the epitaxial relationship, the resulting step edges break the degeneracy of nucleation energy for the antiparallel MoS2 domains and lead to more than a 99% unidirectional alignment. A set of microscopies, spectroscopies and electrical measurements consistently showed that the MoS2 is single crystalline and has an excellent wafer-scale uniformity. We fabricated field-effect transistors and obtained a mobility of 102.6 cm2 V-1 s-1 and a saturation current of 450 µA µm-1, which are among the highest for monolayer MoS2. A statistical analysis of 160 field-effect transistors over a centimetre scale showed a >94% device yield and a 15% variation in mobility. We further demonstrated the single-crystalline MoSe2 on C/A sapphire. Our method offers a general and scalable route to produce TMDC single crystals towards future electronics.

Spontaneous ventilation video-assisted thoracic surgery for mediastinal tumor resection in patients with pulmonary function deficiency.

BACKGROUND: Whether non-intubated spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) is a safe procedure remains controversial for mediastinal tumor patients with impaired lung function. Herein, we assessed feasibility of SV-VATS in lung function deficiency patients underwent mediastinal tumor resection. METHODS: From December 2015 to February 2020, 32 mediastinal tumor patients with impaired lung function (preoperative forced expiratory volume in 1 second <70% of the predicted value) were retrospectively collected. Patients were divided into two groups: SV-VATS group and mechanical ventilation VATS (MV-VATS) group. Intraoperative and postoperative variables were compared between two cohorts. RESULTS: Fifteen patients (46.88%) underwent SV-VATS and 17 patients (53.12%) were performed with MV-VATS. The most common causes of lung function deficiency were smoking (81.25%) and COPD (71.88%). Patients in the SV-VATS group had similar blood loss (20.63 vs. 18.76 mL, P=0.417) with MV-VATS group. The anesthesia time (217.51 vs. 197.76 min; P=0.343) and surgery time (141.23 vs. 132.36 min; P=0.209) were also similar between groups. Five people suffered postoperative complications in each group, in which 1 patient underwent MV-VATS was transferred to intensive care unit (ICU) because of prolonged extubation owing to hypoxia. There was no difference on chest tube removal time (2.6 vs. 2.3 days; P=0.172) or hospital duration (5.03 vs. 4.74 days; P=0.297) in patients underwent SV-VATS and MV-VATS. CONCLUSIONS: SV-VATS is safe and provides similar short-term results to MV-VATS for mediastinal tumor resection in patients with limited pulmonary function.

Cancer Risks in Solid Organ Transplant Recipients: Results from a Comprehensive Analysis of 72 Cohort Studies.

Understanding the cancer risks in different transplant recipients helps early detection, evaluation, and treatment of post-transplant malignancies. Therefore, we performed a meta-analysis to determine the cancer risks at multiple sites for solid organ transplant recipients and their associations with tumor mutation burden (TMB), which reflects the immunogenicity. A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted. Random effects models were used to calculate the standardized incidence ratios (SIRs) versus the general population and determine the risks of different cancers. Linear regression (LR) was used to analyze the association between the SIRs and TMBs. Finally, seventy-two articles met our criteria, involving 2,105,122 solid organ transplant recipients. Compared with the general population, solid organ transplant recipients displayed a 2.68-fold cancer risk (SIR 2.68; 2.48-2.89; P <.001), renal transplant recipients displayed a 2.56-fold cancer risk (SIR 2.56; 2.31-2.84; P <.001), liver transplant recipients displayed a 2.45-fold cancer risk (SIR 2.45; 2.22-2.70; P <.001), heart and/or lung transplant recipients displayed a 3.72-fold cancer risk (SIR 3.72; 3.04-4.54; P <.001). The correlation coefficients between SIRs and TMBs were 0.68, 0.64, 0.59, 0.79 in solid organ recipients, renal recipients, liver recipients, heart and/or lung recipients, respectively. In conclusion, our study demonstrated that solid organ transplant recipients displayed a higher risk of some site-specific cancers, providing individualized guidance for clinicians to early detect, evaluate, and treat cancer among solid organ transplantation recipients. In addition, the increased cancer risk of solid organ transplant recipients is associated with TMB, suggesting that iatrogenic immunosuppression may contribute to the increased cancer risk in transplant recipients. (PROSPERO ID CRD42020160409).

Optimized stratification of risk factors in and beyond the CHA2DS2-VASc score to differentiate the real thromboembolic risk in mainland China: a systematic review and meta-analysis.

Recent studies have demonstrated the limitations of the CHA2DS2-VASc score [congestive heart failure, hypertension, age (>65 years =1 point; >75 years =2 points), diabetes, and previous stroke/ transient ischemic attack (2 points), vascular disease] which lacks many of less common risk factors for stroke. Moreover, only two risk factors, gender and age, are assigned with different points according to the stratification in the CHA2DS2-VASc score. Thus, this meta-analysis was aimed to optimize the stratification of risk factors in and beyond the CHA2DS2-VASc score for patients in mainland China. PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Journal Database (VIP) were searched from their inception to January 2020 for articles assessing risk factors of nonvalvular atrial fibrillation (NVAF) with ischemic stroke in mainland China. Odd risks (ORs) with 95% confidence intervals (CIs) were applied for dichotomous variable, and the weighed mean differences (WMDs) with standard deviations (SDs) were used for continuous variables. The meta-analysis included 20 eligible studies involving 14,675 patients. Compared with the non-stroke group [systolic blood pressure (SBP): 132.99 mmHg, 95% CI: 131.86-134.12; diastolic blood pressure (DBP): 80.08 mmHg, 95% CI: 78.63-81.53], the ischemic stroke group (SBP:144.07 mmHg, 95% CI: 140.74- 147.40; DBP: 84.41 mmHg, 95% CI: 82.39-86.43) showed increased levels of SBP (WMD 10.98 mmHg, 95% CI: 7.80-14.17, P<0.00001) and DBP (WMD 4.46 mmHg, 95% CI: 2.57-6.35, P<0.00001). In addition, the ischemic stroke group demonstrated significantly lower levels of left ventricular ejection fractions (LVEFs) (WMD 3.05% 95% CI: -5.96 to -0.14, P=0.04), and significantly higher levels of total cholesterol (TC) (WMD 0.32 mmol/L, 95% CI: 0.04-0.61, P=0.02) and low density lipoprotein cholesterol (LDL-C) (WMD 0.14 mmol/L, 95% CI: 0.02-0.26, P=0.02), as compared with the non-stroke group. The optimized stratification and the addition of risk factors in and beyond the CHA2DS2-VASc score may improve the predictive performance, thus helping to differentiate patients with the real thromboembolic risk.