Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

[Optimization of production-living-ecology spatial pattern in Dongting Lake Ecological Economic Zone based on comprehensive benefits of development and protection]. / 基于开发保护综合效益的洞庭湖生态经济区"三生空间"æ ¼å±€ä¼˜åŒ–.

The optimization of production-living-ecology (PLE) space is an important basis for promoting regional high-quality development. Taking the Dongting Lake Eco-economic Zone as an example, from the perspective of improving the comprehensive benefits of the development and protection of the PLE space, we coupled the GMOP-FLUS model, and proposed an optimization method combining the scenario configuration and the bottom line protection of the PLE space. We compared the three optimization scenarios (economic optimization scenario, ecological optimization scenario, and multi-objective optimization scenario), and coordinated the conflict areas of two lines to clarify the comprehensive optimization scheme of the PLE space in the Dongting Lake Eco-economic Zone. The results showed the characteristics of increasing production space and living space and decreasing ecological space from 2010 to 2020, resulting in the partial loss of land ecological and environmental benefits. Under the economic optimization scenario, the ecological optimization scenario promoted the rapid growth of regional economy but damaged regional ecological security. The ecological optimization scenario inhibited regional economic development. The multi-objective optimization scenario led to improvement of economic and ecological benefits of the PLE space, which increased by 2.0% and 1.3%, respectively. The multi-objective optimization scenario was the best optimization scenario among the three scenarios. By superimposing the best scenario and the two-line conflict regional coordination results, we obtained the comprehensive optimization scheme for 2030. The production space, living space, and ecological space areas of the scheme were 25777.18, 2062.94, and 32552.68 km2, respectively. Based on the natural and social conditions, combining the comprehensive optimization scheme, we put forward different control suggestions for each type of PLE space. Our results could provide reference for the rational formulation of territorial spatial planning and the formulation of policies for the coordinated development of ecological environment and social economy in the Dongting Lake Eco-economic Zone.

Case report: Tall cell carcinoma with reversed polarity of the breast: an additional case and review of the literature.

Objective: The aim of this report was to comprehensively investigate the clinicopathological features, histological characteristics, and differential diagnosis of tall cell carcinoma with reversed polarity of the breast (TCCRP) to enhance the understanding of this tumour for precise therapeutic interventions. Methods: The clinicopathological characteristics and differential diagnosis of a patient with TCCRP were retrospectively analysed, and a systematic literature review was extracted from relevant published studies on PubMed. Results: All patients included in the study were female, with a median age of 51 years. Microscopically, the tumour cells exhibited a solid papillary growth pattern with tall columnar morphology and reversed nuclear polarity. Immunohistochemistry revealed that the tumours were triple-negative breast cancer (negative for ER, PR, and HER-2), with a low Ki-67 proliferation index. Different degrees of expression were observed for CK7, Calretinin, and S-100 markers; however, CK5/6 showed high expression levels. Conclusions: TCCRP is an uncommon invasive carcinoma subtype found in the breast. Its histological morphology resembles that of tall cell subtype papillary thyroid carcinoma. Accurate diagnosis requires the integration of histomorphological assessment along with immunohistochemistry and molecular genetics analysis.

Regulation of I1-imidazoline receptors on the sedation effect of dexmedetomidine in mice.

Dexmedetomidine has been used as a sedative drug in the clinic for a long time. Many studies demonstrated that the sedative mechanism of dexmedetomidine might be related to the activation of α2-adrenoceptor (α2AR). In addition, it was reported that dexmedetomidine had some affinity for the I1-imidazoline receptor (I1R); however, the role of I1R in dexmedetomidine-induced sedative effects and its possible mechanism are poorly studied. In the present study, we found that agmatine, an I1R agonist, was able to enhance the sedative effect of dexmedetomidine in mice. Efaroxan, an α2AR and I1R antagonist, could prevent and rescue the sedative action of dexmedetomidine in mice, and its preventive effect was better than atipamezole, the specific α2AR antagonist. Knockout of imidazoline receptor antisera-selected (IRAS), the functional I1R candidate protein, suppressed the dexmedetomidine-induced sedation. Moreover, IRAS knockout led to the inhibition of agmatine and efaroxan in regulating dexmedetomidine-induced sedative effects in mice, but not of atipamezole. We then used CHO cell lines that stably expressed α2AR and IRAS to investigate the possible molecular mechanism of IRAS in regulating the dexmedetomidine-induced sedative effect. The results showed that IRAS expression significantly up-regulated dexmedetomidine-induced ERK phosphorylation, which was enhanced by agmatine and inhibited by efaroxan at low concentrations. Therefore, by taking advantage of pharmacological and genetic approaches, our finding revealed the evidence that IRAS plays an important role in the sedative effects of dexmedetomidine, and the ERK signal pathway may be involved in the mechanism of IRAS in regulating dexmedetomidine-induced sedation. This study may offer valuable insights for the advancement of novel anesthetic adjuvants.

Enhancing Electrochemical Non-Enzymatic Dopamine Sensing Based on Bimetallic Nickel/Cobalt Phosphide Nanosheets.

In this study, the successful synthesis of bimetallic nickel/cobalt phosphide nanosheets (Ni-Co-P NSs) via the hydrothermal method and the subsequent high-temperature phosphorization process were both confirmed. Ni-Co-P NSs exhibited excellent electrocatalytic activity for the electrochemical non-enzymatic DA sensing. The surface morphologies and physicochemical properties of Ni-Co-P NSs were characterized by atomic force microscopy (AFM), field-emission scanning (FESEM), field-emission transmission electron microscopy (FETEM), and X-ray diffraction (XRD). Further, the electrochemical performance was evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The metallic nature of phosphide and the synergistic effect of Ni/Co atoms in Ni-Co-P NSs provided abundant catalytic active sites for the electrochemical redox reaction of DA, which exhibited a remarkable consequence with a wide linear range from 0.3~50 µM, a high sensitivity of 2.033 µA µM-1 cm-2, a low limit of detection of 0.016 µM, and anti-interference ability. As a result, the proposed Ni-Co-P NSs can be considered an ideal electrode material for the electrochemical non-enzymatic DA sensing.

The deficiency of 5-methylcytosine (5mC) and its ramification in the occurrence and prognosis of colon cancer.

The incidence and mortality of colon cancer are increasing, and effective biomarkers for its diagnosis are limited. 5-methylcytosine (5mC), a vital DNA methylation marker, plays important roles in gene expression, genomic imprinting, and transposon inhibition. This study aimed to identify the predictors of colon cancer prognosis and lay the foundation for research on therapeutic targets by detecting the levels of 5mC, 5-hydroxymethylcytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxylcytosine (5caC) in colon cancer and adjacent non-tumor tissues. A tissue microarray including 100 colon cancer tissue samples and 60 adjacent non-tumor tissue samples was used. The expression levels of 5mC and its ramifications were assessed by immunohistochemistry. According to the expression levels, patients were divided into moderately positive and strongly positive groups, and the correlation between clinicopathological characteristics and methylation marks was assessed using 2-sided chi-square tests. The prognostic values of 5mC, 5hmC, 5fC, and 5caC were tested using Kaplan-Meier analyses. Compared with adjacent non-tumor tissues, the overall levels of DNA methylation were lower in colon carcinoma lesions. However, the clinical parameters were not significantly associated with these methylation markers, except for 5hmC, which was associated with the age of cancer patients (P value = .043). Kaplan-Meier analysis disclosed that moderate positive group had a significantly shorter disease specific survival than strong positive group for patients with different levels of 5mC (65.2 vs 95.2 months, P = .014) and 5hmC (71.2 vs 97.5 months, P = .045). 5mC and its ramifications (5hmC, 5fC, and 5caC) can serve as biomarkers for colon cancer. 5mC and 5hmC are stable predictors and therapeutic targets in colon cancer. However, further understanding of its function will help to reveal the complex tumorigenic process and identify new therapeutic strategies.

Screening and Identification of Host Factors Interacting with the Virulence Factor P0 Encoded by Sugarcane Yellow Leaf Virus by Yeast Two-Hybrid Assay.

Sugarcane yellow leaf virus (SCYLV), a member of the genus Polerovirus in the family Luteoviridae, causes severe damage and represents a great threat to sugarcane cultivation and sugar industry development. In this study, inoculation of Nicotiana benthamiana plants with a potato virus X (PVX)-based vector carrying the SCYLV P0 gene induced typical mosaic, leaf rolling symptoms and was associated with a hypersensitive-like response (HLR) necrosis symptom, which is accompanied with a systemic burst of H2O2 and also leads to higher PVX viral genome accumulation levels. Our results demonstrate that SCYLV P0 is a pathogenicity determinant and plays important roles in disease development. To further explore its function in pathogenic processes, a yeast two-hybrid assay was performed to screen the putative P0-interacting host factors. The recombinant plasmid pGBKT7-P0 was constructed as a bait and transformed into the yeast strain Y2HGold. The ROC22 cultivar (an important parental resource of the main cultivar in China) cDNA prey library was constructed and screened by co-transformation with the P0 bait. We identified 28 potential interacting partners including those involved in the optical signal path, plant growth and development, transcriptional regulation, host defense response, and viral replication. To our knowledge, this is the first time we have reported the host proteins interacting with the P0 virulence factor encoded by sugarcane yellow leaf virus. This study not only provides valuable insights into elucidating the molecular mechanism of the pathogenicity of SCYLV, but also sheds light on revealing the probable new pathogenesis of Polerovirus in the future.

Predicting Malignancy of Thyroid Micronodules: Radiomics Analysis Based on Two Types of Ultrasound Elastography Images.

RATIONALE AND OBJECTIVES: To develop a multimodal ultrasound radiomics nomogram for accurate classification of thyroid micronodules. MATERIALS AND METHODS: A retrospective study including 181 thyroid micronodules within 179 patients was conducted. Radiomics features were extracted from strain elastography (SE), shear wave elastography (SWE) and B-mode ultrasound (BMUS) images. Minimum redundancy maximum relevance and least absolute shrinkage and selection operator algorithms were used to select malignancy-related features. BMUS, SE, and SWE radiomics scores (Rad-scores) were then constructed. Multivariable logistic regression was conducted using radiomics signatures along with clinical data, and a nomogram was ultimately established. The calibration, discriminative, and clinical usefulness were considered to evaluate its performance. A clinical prediction model was also built using independent clinical risk factors for comparison. RESULTS: An aspect ratio ≥ 1, mean elasticity index, BMUS Rad-score, SE Rad-score, and SWE Rad-score were identified as the independent predictors for predicting malignancy of thyroid micronodules by multivariable logistic regression. The radiomics nomogram based on these characteristics showed favorable calibration and discriminative capabilities (AUCs: 0.903 and 0.881 for training and validation cohorts, respectively), all outperforming clinical prediction model (AUCs: 0.791 and 0.626, respectively). The decision curve analysis also confirmed clinical usefulness of the nomogram. The significant improvement of net reclassification index and integrated discriminatory improvement indicated that multimodal ultrasound radiomics signatures might work as new imaging markers for classifying thyroid micronodules. CONCLUSION: The nomogram combining multimodal ultrasound radiomics features and clinical factors has the potential to be used for accurate diagnosis of thyroid micronodules in the clinic.

[Comparison of effect between internal fixation and total hip replacement in the treatment of displaced femoral neck fracture in middle age patients].

OBJECTIVE: To analyze and compare the clinical efficacy of internal fixation and total hip replacement in the treatment of displaced femoral neck fracture from 55 to 65 years. METHODS: From September 2016 to August 2020, 86 patients with Garden type Ⅲ or Ⅳ femoral neck fracture were divided into two groups according to different surgical methods. Among them, 38 patients were treated with lag screws for internal fixation, there were 26 males and 12 females, aged 55 to 64 years old with an average of(60.2±3.1) years;the other 48 patients were treated with total hip replacement, including 28 males and 20 females, aged from 57 to 65 years old with an average of(61.3±3.8) years. The time from injury to operation ranged from 1 to 3 days. The reoperation rate, incidence of deep infection, Harris score of hip joint function, visual analogue scale(VAS) of pain and patients reported outcome scores(European five-dimensional Health Questionnaire, EQ-5D) were compared between two groups. RESULTS: All patients were followed up for 24 to 54 months with an average of (35.8±10.3) months. There was significant difference in reoperation rate between two groups (P<0.05). There was no significant difference on the incidence of deep infection, hip Harris score and VAS between two groups(P>0.05) . The postoperative EQ-5D score of patients with internal fixation was lower than that of total hip replacement, and the difference was statistically significant(P<0.05). CONCLUSION: Both the surgery of internal fixation and total hip replacement have similar effect in short-and medium term among the patients aged 55 to 65 years old. However, for the reoperation rate, the group of internal fixation was higher than that of total hip replacement. For the subjective functional score of patients, the group of internal fixation was lower than that of total hip replacement.

The efficacy of haemoperfusion combined with continuous venovenous haemodiafiltration in the treatment of severe viral encephalitis in children.

BACKGROUND: This study investigated the efficacy of the integrated blood purification mode of early haemoperfusion (HP) combined with continuous venovenous haemodiafiltration (CVVHDF) in children with severe viral encephalitis, and evaluated the correlation of cerebrospinal fluid (CSF) neopterin (NPT) levels with prognosis. METHODS: The records of children with viral encephalitis who received blood purification treatment in the authors' hospital from September 2019 to February 2022 were retrospectively analysed. According to the blood purification treatment mode, they were divided into the experimental group (HP + CVVHDF, 18 cases), control group A (CVVHDF only, 14 cases), and control group B (16 children with mild viral encephalitis who did not receive blood purification treatment). The correlation between the clinical features, severity of the disease and the extent of lesions on brain magnetic resonance imaging (MRI) and the CSF NPT levels was analysed. RESULTS: The experimental group and control group A were comparable with respect to age, gender and hospital course (P > 0.05). There was no significant difference in speech and swallowing functions between the two groups after treatment (P > 0.05) and no significant difference in 7 and 14-day mortality (P > 0.05). The CSF NPT levels in the experimental group before treatment were significantly higher compared with control group B (P < 0.05). The extent of brain MRI lesions correlated positively with CSF NPT levels (P < 0.05). In the experimental group (14 cases), the serum NPT levels decreased after treatment, whereas the CSF NPT levels increased after treatment, and the differences were statistically significant (P < 0.05). Dysphagia and motor dysfunction correlated positively with CSF NPT levels (P < 0.05). CONCLUSION: Early HP combined with CVVHDF in the treatment of severe viral encephalitis in children may be a better approach than CVVHDF only for improving prognosis. Higher CSF NPT levels indicated the likelihood of a more severe brain injury and a greater possibility of residual neurological dysfunction.

Correlation between Mycoplasma pneumoniae drug resistance and clinical characteristics in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: To investigate the resistance-gene mutation of Mycoplasma pneumoniae (MP) in the bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia (MPP) and the clinical characteristics of refractory Mycoplasma pneumoniae pneumonia (RMPP) correlation. METHODS: Forty-eight children with MPP were selected and placed in RMPP and non-RMPP groups based on their clinical status - whether they had worsening clinical symptoms, persistent fever and a worsening lung image. They were also separated into drug-resistance gene mutation and non-mutated groups using nucleic acid detection. The participants' data were collected on high-sensitivity C-reactive protein and MP-DNA loads, fever time, hospitalisation time, macrolide antibiotic application time and fever regression time after application. The differences in imaging manifestations were determined by using multivariate logistic regression to analyse the clinical characteristics of RMPP. Additionally, the correlation between drug-resistance gene mutations and the clinical characteristics of RMPP was summarised. RESULTS: Among the 48 MPP children, 31 (64.6%) had A2063G and/or A2064G gene mutation, 31 (64.6%) had RMPP and 23 (74.2%) had drug-resistance gene mutation. The children in the drug-resistance gene mutation group had higher high-sensitivity C-reactive protein and MP-DNA loads, longer fever time, hospitalisation time, macrolide antibiotic application time, fever regression time after application and extrapulmonary complications. There were more symptoms and more severe changes under bronchoscopy. The difference was statistically significant (P < 0.05). Logistic multivariate regression analysis showed that the mutation of drug-resistance genes had no significant correlation with RMPP. CONCLUSION: The mutation rate of drug-resistance genes in children with MPP is high, the inflammatory index and MP-DNA load are high, the course of the disease is long, and the changes under bronchoscopy are severe. The occurrence of RMPP is not only determined by drug-resistance genes but may also be the result of a combination of factors.

[Influence factors of deep venous thromboembolism after knee arthroplasty and significance of changes of serum nets and sVCAM-1 levels].

OBJECTIVE: To investigate the relationship between the changes of serum neutrophil extracellular traps (NETs), soluble vascular cell adhesion molecule-1(sVCAM-1) and deep venous thromboembolism after knee arthroplasty. METHODS: From May 2017 to April 2020, 30 patients with deep venous thromboembolism after knee arthroplasty were retrospectively selected as the observation group, and 60 patients without deep venous thromboembolism after knee arthroplasty in the same period were randomly selected as the control group. The clinical data, serum levels of nets and sVCAM-1 before and 1, 3 and 5 days after operation were compared between the two groups. Logistic regression model was used to analyze the influencing factors of deep venous thromboembolism after knee arthroplasty; Pearson correlation was used to analyze the relationship between serum nets and sVCAM-1 levels;Draw the receiver operating characteristic curve(ROC) to obtain the area under the curve(AUC), and analyze the diagnostic value of serum nets and sVCAM-1 levels for deep vein thromboembolism after knee arthroplasty. RESULTS: There were statistically significant differences between two groups in age, body mass index, and postoperative knee elevation and flexion ratio(P<0.05). The level of serum NETs and sVCAM-1 on the 1st and 3rd day after surgery of the observation group were higher than the control group(P<0.05). Logistic regression analysis showed that age, body mass index, knee flexion position, serum nets and sVCAM-1 levels at 1 and 3 days after operation were all the influencing factors of DVT after knee arthroplasty (P<0.05);Pearson correlation analysis showed that there was a positive correlation between the levels of serum NETs and sVCAM-1 in patients with deep venous thromboembolism after knee arthroplasty 1 and 3 days after operation(P<0.05). The ROC curve of predicting deep venous thromboembolism after knee arthroplasty by serum nets and sVCAM-1 levels at 1 and 3 days after operation was drawn, the results showed that the AUC of serum nets and sVCAM-1 levels at 1 day after operation was higher than that at 3 days after operation, which had a good predictive effect. CONCLUSION: The influencing factors of deep vein thromboembolism after knee arthroplasty are age, body mass index, postoperative knee elevation and flexion, postoperative serum NETs and sVCAM-1 levels, especially postoperative serum NETs and sVCAM-1 levels. Changes can be used as potential biomarkers for predicting postoperative deep vein thromboembolism, and clinical attention should be paid to it.

Effects of Gas Dissolution on Gas Migration during Gas Invasion in Drilling.

Sour gas reservoirs (including CO2 and H2S) are vulnerable to gas invasion when drilling into reservoir sections. The high solubility of the invaded gas in drilling fluid makes the gas invasion monitoring "hidden" and "sudden" for later expansion, and the blowout risk increases. Accurate prediction of gas dissolution is highly significant for monitoring gas invasion. In this study, the gas-liquid flow control equations considering gas dissolution were established. Focusing on the gas dissolution effect, a solubility experiment for CO2 and CH4 in an aqueous solution was performed using a phase equilibrium device. The experimental and simulation results revealed that the addition of CO2 can significantly increase gas dissolution, and the presence of salts decreases it. For solubility prediction of pure CH4 and CO2, the fugacity-activity solubility model, calculated using the Peng-Robinson equation of state, was more accurate than the Soave-Redlich-Kwong equation of state. The Soave-Redlich-Kwong equation of state has higher accuracy for the CO2 and CH4 gas mixture. If the gas dissolution effect is considered for wellbore gas-liquid flow, the time required for the mud pit gain to reach the early warning value increases. When the contents of CO2 and H2S in intrusive gases are higher, the time for mud pit gain change monitored on the ground increases, the concealment increases, and the risk of blowout increases.

IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain.

The I1 imidazoline receptor and its candidate protein imidazoline receptor antisera-selected (IRAS)/Nischarin are linked to µ opioid receptor (MOR) functions associated with MOR trafficking. We previously demonstrated that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo. However, the effects of IRAS on morphine psychological dependence are not fully understood. To extend these studies, we investigated the impact of IRAS on morphine dependence in conditioned place preference (CPP) experiments and explored the underlying mechanisms. Knockout of IRAS enhanced the acquisition and reinstatement of morphine-induced CPP. Conditional-knockout of IRAS in the nucleus accumbens (NAc) reproduced higher CPP, and overexpression of IRAS in the NAc rescued the increased morphine-induced CPP in IRAS-/- mice. IRAS-/- mice showed dramatic cAMP-dependent protein kinase (PKA) activation, upregulation of the phosphorylation of the AMPA receptor GluR1-S845 and NMDA receptor NR1-S897 in the NAc after CPP experiment. Moreover, knockout of IRAS induced an increase in spontaneous excitatory postsynaptic current (sEPSC) frequency and a decrease in the AMPA/NMDA ratio in the NAc after chronic morphine treatment. The selective AMPA receptor antagonist NBQX could inhibit morphine CPP in WT mice, while its effect was significantly reduced in IRAS-/- mice. Together, our results demonstrate that IRAS contributes to the regulation of morphine dependence and that the alteration of glutamatergic transmission in the NAc may participate in the effect of IRAS.

Clinical sequencing uncovers the genomic characteristics and mutation spectrum of the 2018 African swine fever virus in Guangdong, China.

African swine fever (ASF) outbreak have caused tremendous economic loss to the pig industry in China since its emergence in August 2018. Previous studies revealed that many published sequences are not suitable for detailed analyses due to the lack of data regarding quality parameters and methodology, and outdated annotations. Thus, high-quality genomes of highly pathogenic strains that can be used as references for early Chinese ASF outbreaks are still lacking, and little is known about the features of intra-host variants of ASF virus (ASFV). In this study, a full genome sequencing of clinical samples from the first ASF outbreak in Guangdong in 2018 was performed using MGI (MGI Tech Co., Ltd., Shenzhen, China) and Nanopore sequencing platforms, followed by Sanger sequencing to verify the variations. With 22 sequencing corrections, we obtained a high-quality genome of one of the earliest virulent isolates, GZ201801_2. After proofreading, we improved (add or modify) the annotations of this isolate using the whole genome alignment with Georgia 2007/1. Based on the complete genome sequence, we constructed the methylation profiles of early ASFV strains in China and predicted the potential 5mC and 6mA methylation sites, which are likely involved in metabolism, transcription, and replication. Additionally, the intra-host single nucleotide variant distribution and mutant allele frequency in the clinical samples of early strain were determined for the first time and found a strong preference for A and T substitution mutation, non-synonymous mutations, and mutations that resulted in amino acid substitutions into Lysine. In conclusion, this study provides a high-quality genome sequence, updated genome annotation, methylation profile, and mutation spectrum of early ASFV strains in China, thereby providing a reference basis for further studies on the evolution, transmission, and virulence of ASFV.

Case Report: Clinicopathological Analysis of Minute Pulmonary Meningothelial-Like Nodules: Report of 7 Cases.

Objective: To investigate the clinical manifestations, radiologic features, pathological features, and immunophenotype of minute pulmonary meningothelial-like nodules (MPMNs). Method: This is a retrospective observational study. We collected the clinical data of 7 cases of MPMNs, and performed comprehensive characterization using a combination of clinical, morphological, radiologic and immunohistochemical assessments. Results: Of the 7 cases of MPMNs, 6 were female and 1 was male. The median age was 55 years. All MPMNs were multiple in lung with the size from 0,01 to 0,5cm. Chest CT examination showed ground-glass attenuation or solid nodules. Four cases were concomitant with carcinoma and/or pneumonia, and 3 cases occurred alone. Four of the 7 patients had no obvious symptoms; 3 patients had chest pain or cough or shortness of breath or hemoptysis. Multiple white nodules were found macroscopically, and the diseased cells grew along the alveolar septum, with relatively normal morphology, rich cytoplasm, unclear cell boundary, and uniform nucleus with delicate chromatin and without atypia; and the diseased cells showed nest or whorls distribution. EMA, PR, CD56 and vimentin were positive in all cases by immunohistochemistry. Conclusions: MPMNs are rare benign lesions in the lung, often multiple, usually less than 0.5cm in diameter, most of which have no obvious clinical symptoms. MPMNs are often found by chest CT, and occur independently or concomitant with other lesions. The positive immunohistochemical staining of EMA, PR, CD56, vimentin supports the diagnosis.

Transcriptomic responses of the zearalenone (ZEN)-detoxifying yeast Apiotrichum mycotoxinivorans to ZEN exposure.

Zearalenone (ZEN) is a potent oestrogenic mycotoxin that is mainly produced by Fusarium species and is a serious environmental pollutant in animal feeds. Apiotrichum mycotoxinivorans has been widely used as a feed additive to detoxify ZEN. However, the effects of ZEN on A. mycotoxinivorans and its detoxification mechanisms remain unclear. In this study, transcriptomic and bioinformatic analyses were used to investigate the molecular responses of A. mycotoxinivorans to ZEN exposure and the genetic basis of ZEN detoxification. We detected 1424 significantly differentially expressed genes (DEGs), of which 446 were upregulated and 978 were downregulated. Functional and enrichment analyses showed that ZEN-induced genes were significantly associated with xenobiotic metabolism, oxidative stress response, and active transport systems. However, ZEN-inhibited genes were mainly related to cell division, cell cycle, and fungal development. Subsequently, bioinformatic analysis identified candidate ZEN-detoxification enzymes. The Baeyer-Villiger monooxygenases and carboxylesterases, which are responsible for the formation and subsequent hydrolysis of a new ZEN lactone, respectively, were significantly upregulated. In addition, the expression levels of genes related to conjugation and transport involved in the xenobiotic detoxification pathway were significantly upregulated. Moreover, the expression levels of genes encoding enzymatic antioxidants and those related to growth and apoptosis were significantly upregulated and downregulated, respectively, which made it possible for A. mycotoxinivorans to survive in a highly toxic environment and efficiently detoxify ZEN. This is the first systematic report of ZEN tolerance and detoxification in A. mycotoxinivorans. We identified the metabolic enzymes that were potentially involved in detoxifying ZEN in the GMU1709 strain and found that ZEN-induced transcriptional regulation of genes is key to withstanding highly toxic environments. Hence, our results provide valuable information for developing enzymatic detoxification systems or engineering this detoxification pathway in other species.

Mediating CO2 Electroreduction Activity and Selectivity over Atomically Precise Copper Clusters.

Atomically precise copper clusters are highly desirable catalysts for electrocatalytic CO2 reduction reaction (CO2 RR) and provide an ideal platform for elaborating structure-activity relationships. However, systematic comparative studies of Cu cluster isomers for electrocatalytic CO2 RR are lacking because they are challenging to synthesize. A group of structurally precise Cu8 cluster isomers with different core structures (cube- and ditetrahedron-shaped) were developed and investigated for highly active and selective CO2 reduction. Electrocatalytic measurements showed that the ditetrahedron-shaped Cu8 cluster exhibited a higher FEHCOOH (≈92 %) at -1.0 V and higher selectivity than the cube-shaped cluster. Theoretical investigations revealed different levels of competitiveness with the hydrogen evolution reaction on the respective core-shaped Cu8 clusters and decreased free energies for the adsorbed HCOO* intermediates on the ditetrahedron-shaped Cu8 clusters.

High-Performance All-Polymer Photodetectors Enabled by New Random Terpolymer Acceptor with Fine-Tuned Molecular Weight.

Reducing the dark current density and enhancing the overall performance of the device is the focal point in research for organic photodetectors. Two novel random terpolymers (P3 and P4) with different molecular weights are synthesized and evaluated as acceptors in bulk heterojunction (BHJ) polymer photodetectors. Compared with known acceptor materials, such as N2200 (P1) and F-N2200 (P2), polymer P4 has a lower lowest unoccupied molecular orbital (LUMO) energy level, favorable morphology, and good miscibility with a donor material J71, which leads to proper phase separation of the blend film and better dissociation of excitons and transport of carriers. Therefore, a considerably low dark current density (Jd) of 1.9 × 10-10 A/cm2 and a high specific detectivity (D*) of 1.8 × 1013 cm Hz1/2/W (also "Jones") at 580 nm under a -0.1 V bias are realized for the P4-based photodetector. More importantly, the device also exhibits a fast response speed (τr/τf = 1.24/1.87 µs) and a wide linear dynamic range (LDR) of 109.2 dB. This work demonstrates that high-performance all-polymer photodetectors with ideal morphology can be realized by random polymer acceptors with a fine-tuned molecular weight.