Clinical efficacy of Fufang Yinhua Jiedu (FFYH) granules in mild COVID-19 and its anti-SARS-CoV-2 mechanism by blocking autophagy through inhibiting the AKT/mTOR signaling pathway.

Background: Fufang Yinhua Jiedu (FFYH) granules are recommended for treating coronavirus pneumonia (COVID-19) in China. However, its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity and clinical efficacy against COVID-19 remain to be confirmed. Aims: Our study aimed to investigate the anti-SARS-CoV-2 effect and potential mechanism of FFYH. Materials and Methods: The activity of FFYH against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated via cell pathogenic effects, immunoblotting, immunofluorescence staining, and qRT-PCR. The potential mechanism of FFYH against SARS-CoV-2 was investigated by immunoblotting. One head-to-head randomized controlled trial was designed to evaluate the clinical efficacy of FFYH in mild COVID-19. Two hundred patients were randomly recruited to receive either FFYH or LHQW (Lianhua Qingwen) granules. Results: The in vitro results indicated that FFYH effectively inhibited SARS-CoV-2 replication by suppressing CPE and decreasing viral RNA and protein expression. A time-of-drug-addition assay confirmed that FFYH mainly targeted the binding and replication stages of the SARS-CoV-2 life cycle. Mechanistic studies revealed that blocking SARS-CoV-2-triggered autophagy may be the primary mechanism by which FFYH protects against SARS-CoV-2 infection by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Clinical results confirmed that FFYH effectively shortened the recovery time of clinical symptoms and viral nucleic acid negativity, improved abnormal hematology parameters, and controlled excessive cytokine responses in mild COVID-19 patients. Subgroup analysis revealed that FFYH improved the recovery time of clinical symptoms, improved hematological parameters, and controlled excessive cytokine storms to a greater extent in the mild COVID-19 male subgroup, abnormal hematology subgroup, and 32-42-year-old subgroup than in the corresponding LHQW subgroup (P < 0.05). No patients progressed to severe or critical cases. Conclusion: Our results indicate that FFYH not only has good anti-viral activity against SARS-CoV-2 but also has significant efficacy against COVID-19, indicating that FFYH may be a novel complementary option for treating COVID-19.

A Roadmap for Ferroelectric-Antiferroelectric Phase Transition.

Antiferroelectric materials have shown great potential in electronic devices benefiting from the reversible phase transition between ferroelectric and antiferroelectric phases. Understanding the dipole arrangements and clear phase transition pathways is crucial for design of antiferroelectric materials-based energy storage and conversion devices. However, the specific phase transition details remain largely unclear and even controversial to date. Here, we have grown a series of PbZrO3 on SrTiO3 substrates and elucidated the fine atom structures and phase transition pathways using atomic-resolution transmission electron microscopy. Specifically, a roadmap for ferroelectric to antiferroelectric phase transitions, here with increasing film thickness, is determined as ferroelectric rhombohedral (R3c)-ferroelectric monoclinic (Pc)-ferrielectric orthorhombic (Ima2)-antiferroelectric orthorhombic (Pbam), where Pc and Ima2 phases act as structural bridges. Moreover, the phase transition pathway is strongly related to the synergistic effect of oxygen octahedral tilting and cation displacement. These findings provide an insightful understanding for the theories and related properties of antiferroelectrics.

Development of a quinic acid-induced CRISPR/Cas9 genome editing system and its application for the activation of ilicicolin H biosynthesis in Trichoderma reesei.

The CRISPR/Cas9 genome editing tool has been extensively utilized in filamentous fungi, including Trichoderma reesei. However, most existing systems employ constitutive promoters for the expression of Cas9 protein within the cells or directly introduce Cas9 protein into the cells, which often leads to continuous expression of Cas9 resulting in undesired phenotypes or increased operational cost. In this study, we identified a quinic acid (QA)-induced qai5 promoter and employed it to express Cas9, thereby establishing an inducible genome editing system in T. reesei. By utilizing this system, we successfully edited the ypr1 gene and the silent gene cluster involved in ilicicolin H synthesis using donor DNA labeling 41-bp homology arm (HA), resulting in an editing efficiency ranging from 29.2 % to 46.7 %. Consequently, biosynthesis of ilicicolin H was achieved in T. reesei. To summarize, this study presents a novel form of CRISPR/Cas9 genome editing system that enables efficient and controllable genetic modifications in T. reesei.

Constructing a Large Language Model to Generate Impressions from Findings in Radiology Reports.

Background The specialization and complexity of radiology makes the automatic generation of radiologic impressions (ie, a diagnosis with differential diagnosis and management recommendations) challenging. Purpose To develop a large language model (LLM) that generates impressions based on imaging findings and to evaluate its performance in professional and linguistic dimensions. Materials and Methods Six radiologists recorded imaging examination findings from August 2 to 31, 2023, at Shanghai General Hospital and used the developed LLM before routinely writing report impressions for multiple radiologic modalities (CT, MRI, radiography, mammography) and anatomic sites (cranium and face, neck, chest, upper abdomen, lower abdomen, vessels, bone and joint, spine, breast), making necessary corrections and completing the radiologic impression. A subset was defined to investigate cases where the LLM-generated impressions differed from the final radiologist impressions by excluding identical and highly similar cases. An expert panel scored the LLM-generated impressions on a five-point Likert scale (5 = strongly agree) based on scientific terminology, coherence, specific diagnosis, differential diagnosis, management recommendations, correctness, comprehensiveness, harmlessness, and lack of bias. Results In this retrospective study, an LLM was pretrained using 20 GB of medical and general-purpose text data. The fine-tuning data set comprised 1.5 GB of data, including 800 radiology reports with paired instructions (describing the output task in natural language) and outputs. Test set 2 included data from 3988 patients (median age, 56 years [IQR, 40-68 years]; 2159 male). The median recall, precision, and F1 score of LLM-generated impressions were 0.775 (IQR, 0.56-1), 0.84 (IQR, 0.611-1), and 0.772 (IQR, 0.578-0.957), respectively, using the final impressions as the reference standard. In a subset of 1014 patients (median age, 57 years [IQR, 42-69 years]; 528 male), the overall median expert panel score for LLM-generated impressions was 5 (IQR, 5-5), ranging from 4 (IQR, 3-5) to 5 (IQR, 5-5). Conclusion The developed LLM generated radiologic impressions that were professionally and linguistically appropriate for a full spectrum of radiology examinations. © RSNA, 2024 Supplemental material is available for this article.

Allosteric regulation of Keap1 by 8ß-hydroxy-α-cyclocostunolide for the treatment of acute lung injury.

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Conditional ablation of DIS3L2 ribonuclease in pre-meiotic germ cells causes defective spermatogenesis and infertility in male mice.

Rationale: Spermatogenesis is a highly organized cell differentiation process in mammals, involving mitosis, meiosis, and spermiogenesis. DIS3L2, which is primarily expressed in the cytoplasm, is an RNA exosome-independent ribonuclease. In female mice, Dis3l2-deficient oocytes fail to resume meiosis, resulting in arrest at the germinal vesicle stage and complete infertility. However, the role of DIS3L2 in germ cell development in males has remained largely unexplored. Methods: We established a pre-meiotic germ cell conditional knockout mouse model and investigated the biological function of DIS3L2 in spermatogenesis and male fertility through bulk RNA-seq and scRNA-seq analyses. Results: This study unveils that conditional ablation of Dis3l2 in pre-meiotic germ cells with Stra8-Cre mice impairs spermatogonial differentiation and hinders spermatocyte meiotic progression coupled with cell apoptosis. Such conditional ablation leads to defective spermatogenesis and sterility in adults. Bulk RNA-seq analysis revealed that Dis3l2 deficiency significantly disrupted the transcriptional expression pattern of genes related to the cell cycle, spermatogonial differentiation, and meiosis in Dis3l2 conditional knockout testes. Additionally, scRNA-seq analysis indicated that absence of DIS3L2 in pre-meiotic germ cells causes disrupted RNA metabolism, downregulated expression of cell cycle genes, and aberrant expression of spermatogonial differentiation genes, impeding spermatogonial differentiation. In meiotic spermatocytes, loss of DIS3L2 results in disturbed RNA metabolism, abnormal translation, and disrupted meiotic genes that perturb meiotic progression and induce cell apoptosis, leading to subsequent failure of spermatogenesis and male infertility. Conclusions: Collectively, these findings highlight the critical role of DIS3L2 ribonuclease-mediated RNA degradation in safeguarding the correct transcriptome during spermatogonial differentiation and spermatocyte meiotic progression, thus ensuring normal spermatogenesis and male fertility.

First report of ISKpn26 element mediating mgrB gene disruption in the ST1 colistin- and carbapenem-resistant Klebsiella pneumoniae cluster isolated from a patient with chest infection.

Colistin is used as a last-line therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP). However, colistin resistance in Klebsiella pneumoniae is increasingly reported worldwide. This study aims to investigate the instrumental role of insertion sequence (IS) elements in colistin resistance through mgrB disruption in K. pneumoniae during treatment. Five clinical isolates of CRKP, designated KPN1~KPN5 were collected from the lower respiratory tract of a patient with chest infection before and after treatment with colistin. Antimicrobial susceptibility testing was performed using the broth microdilution method. Whole genome sequencing and bioinformatics were used to analyze the sequence types (STs), resistance genes, and genetic characteristics of the five isolates of K. pneumoniae. Antimicrobial susceptibility testing indicated that all five K. pneumoniae isolates were resistant to cephalosporins (ceftriaxone, ceftazidime, and cefepime), several carbapenems (imipenem, meropenem), cefoperazone-sulbactam, piperacillin-tazobactam, ciprofloxacin, and fosfomycin, whereas they were sensitive to amikacin and tigecycline. In addition, three of these isolates were resistant to colistin, with minimum inhibitory concentration values of >8 mg/L. Whole genome sequencing revealed that all five K. pneumoniae isolates belonged to sequence type 1 (ST1), which shared an identical blaKPC-2. Notably, disruption of mgrB by the ISKpn26 insertion sequence was shown to be the primary colistin resistance mechanism during the treatment. To our knowledge, this is the first report of ISKpn26 element mediating mgrB disruption in the ST1 colistin and CRKP obtained from a patient with chest infection in mainland China. This study provides new research ideas to explore the clinical drug resistance mechanism of CRKP and the critical need to monitor and understand resistance mechanisms to preserve the efficacy of last-line antibiotics such as colistin. IMPORTANCE: Of note, this chapter gives an update on colistin resistance in sequence type 1 Klebsiella pneumoniae, by focusing on the mgrB disrupted by ISKpn26 element.

Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk.

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

The Circulating CDC42 Expression in Sepsis: Relation to Disease Susceptibility, Inflammation, Multiple Organ Dysfunctions and Mortality Risk.

OBJECTIVE: Cell division cycle 42 (CDC42) modulates inflammation and multiple organ dysfunction by regulating T-cell differentiation and macrophage polarization. This research intended to explore the association of blood CDC42 expression with septic risk, multi-organ dysfunctions, and mortality. METHODS: 145 sepsis patients and 50 health controls were recruited, then CDC42 expression in peripheral blood mononuclear cell (PBMC) from them was measured by RT-qPCR. RESULTS: CDC42 was decreased in sepsis patients versus health controls (P<0.001); meanwhile, the receiver operating characteristic (ROC) curve showed that CDC42 had a certain value to predict sepsis risk with an area under the curve (AUC) (95% confidence interval (CI): 0.797 (0.725-0.869). Furthermore, CDC42 was negatively correlated with C-reactive protein (P<0.001), tumor necrosis factor-alpha (P<0.001) and interleukin-17A (P<0.001) but less with interleukin-6 (P=0.056). Moreover, CDC42 was negatively related to the SOFA score (P<0.001) and its several subscales (respiratory system, liver, cardiovascular, and renal system) (P<0.05). Furthermore, CDC42 was lower in septic deaths versus survivors (P<0.001); meanwhile, the ROC curve exhibited a certain ability of CDC42 in estimating 28-day mortality with an AUC (95%CI) of 0.766 (0.676-0.855). CONCLUSION: Circulating CDC42 exhibits potency to be a prognostic biomarker reflecting multi-organ dysfunctions and higher mortality risk in sepsis.

Aucklandiae radix targeted PKM2 to alleviate ulcerative colitis: Insights from the photocrosslinking target fishing technique.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease marked by chronic tissue inflammation that alters the integrity and function of the gut, seriously impacting patient health and quality of life. Aucklandiae Radix (AR), known as Mu Xiang in Chinese, is a traditional Chinese medicine documented in Chinese Pharmacopoeia with effects of strengthening the intestine and stopping diarrhea. However, the potential of AR in treating intestinal inflammation and its underlying mechanism have yet to be further elucidated. PURPOSE: The objective of this study was to explore the protective effect and the potential mechanism attributable to AR for treating ulcerative colitis (UC). STUDY DESIGN AND METHODS: A murine model of UC was constructed using dextran sulfate sodium (DSS) to examine the therapeutic potential of AR in alleviating inflammation and modulating the immune response. Advanced techniques such as photocrosslinking target fishing technique, click chemistry, Western blot analysis, real-time quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry were employed to unveil the therapeutic mechanism of AR for treating IBD. RESULTS: AR decreased disease activity index (DAI) score to alleviate the course of IBD through ameliorating intestinal barrier function in DSS-induced mice. Furthermore, AR suppressed NF-κB and NLRP3 pathways to reduce the release of pro-inflammatory factors interleukin-6 and 1ß (IL-6 and IL-1ß) and tumor necrosis factor α (TNF-α), allowing to alleviate the inflammatory response. Flow cytometry revealed that AR could reduce the accumulation of intestinal macrophages and neutrophils, maintaining intestinal immune balance by regulating the ratio of Treg to Th17 cells. It was worth noting that pyruvate kinase isozyme type M2 (PKM2) served as a potential target of AR using the photocrosslinking target fishing technology, which was further supported by cellular thermal shift assay (CETSA), drug affinity target stability (DARTS), and PKM2 knockdown experiments. CONCLUSION: AR targeted PKM2 to inhibit NF-κB and NLRP3 pathways, thereby modulating the inflammatory response and immunity to alleviate DSS-induced UC. These findings suggested the potential of AR in the treatment of UC and AR as a candidate for developing PKM2 regulators.

The mediating and moderating role of nursing information competence between nurses' creative self-efficacy and innovation behavior in a specialized oncology hospital.

OBJECTIVE: This study aims to examine the impact of nurses' nursing information competence on their creative self-efficacy and innovation behavior, and to investigate its role as a mediating factor between these two elements. METHODS: A survey was conducted from July to September 2023 involving 1,200 nurses from two tertiary-level oncology specialty hospitals in Beijing, selected through convenience sampling. Instruments used included the Creative Self-Efficacy Scale, Nursing Information Competence Assessment Scale, and Nurses' Innovative Behavior Scale. Data analysis was conducted using SPSS 25.0 and R 4.1.2; AMOS26 was used to construct structural equation models and Bootstrap method was used to test the mediating hypotheses. RESULTS: Out of the distributed questionnaires, 1,166 were valid, yielding an effective response rate of 97.16%. Pearson correlation analysis revealed significant correlations between innovation self-efficacy, nursing information competence, and nurses' innovative behaviors (P < 0.001). The Bootstrap method indicated that nursing information competence serves as a mediating factor in the relationship between creative self-efficacy and innovative behaviors, contributing to 24.5% of the observed effect. Additionally, regression analysis suggested that nursing information competence moderates the relationship between creative self-efficacy and innovation behavior. CONCLUSION: The findings suggest that nursing information competence not only mediates but also moderates the relationship between creative self-efficacy and innovative behavior. Enhancing nurses' information competence could therefore foster creative self-efficacy, leading to an increase in innovative behavior and, subsequently, improvements in the quality of oncology nursing care.

Induction of Pluripotent Stem Cells from Muscle Cells of Large Yellow Croaker (Larimichthys Crocea) Via Electrotransfection.

Induced pluripotent stem cells (iPSCs) are a new type of pluripotent cells reprogrammed from somatic cells back into an embryonic-like pluripotent state of stem cells to study development, disease and potential gene therapies. The induction and regulation mechanisms of iPSCs in fish are still unclear. By using the transfection technique, we investigated the crucial function of the OSKMNL factor co-expression for somatic reprogramming in the muscle cell line of large yellow croaker (Larimichthys crocea) (LYCMs) and successfully established a stable iPSCs line (Lc-OSNL-iPSCs). Stable culturing of iPSCs with high alkaline phosphatase activity and a stable karyotype was achieved. The qRT-PCR and immunofluorescence labeling results revealed that Lc-OSNL-iPSCs displayed a high expression level of pluripotent marker genes such as Nanog, Oct4, and Sox2. There were significant differences between Lc-OSNL-iPSCs, Lc-OSKMNL-iPSCs, and LYCMs, and the expression of several genes in maintaining cell pluripotency was up-regulated when the pluripotency signal pathway of stem cells was activated. The technical system for inducing iPSCs of Larimichthys crocea was constructed in this study. This system can serve as a basic model to understand germ cell differentiation mechanism, gender control, genetics, and breeding of large yellow croaker and a platform for studying iPSCs in fish. Interestingly, the acquired iPSCs serves as a useful material for the directional induction of muscle stem cells, thereby establishing the groundwork for obtaining "artificial fish" in the future.

Taxonomic revision of Geotrichum and Magnusiomyces, with the descriptions of five new Geotrichum species from China.

The arthroconidial yeast-like species currently classified in the asexual genera Geotrichum and Saprochaete and the sexual genera Dipodascus, Galactomyces and Magnusiomyces are frequently associated with dairy and cosmetics production, fruit rot and human infection. However, the taxonomic system of these fungi has not been updated to accommodate the new nomenclature code adopting the "one fungus, one name" principle. Here, we performed phylogenetic analyses of these yeast-like species based on the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit of the rRNA gene. Two monophyletic groups were recognised from these species. One group contained Dipodascus, Galactomyces, and Geotrichum species and the other Magnusiomyces and Saprochaete species. We thus assigned the species in each group into one genus and selected the genus name Geotrichum for the first group and Magnusiomyces for the second one based on the principle of priority of publication. Five new Geotrichum species were identified from arthroconidial yeast strains recently isolated from various sources in China. The new species are described as Ge. dehoogii sp. nov., Ge. fujianense sp. nov., Ge. maricola sp. nov., Ge. smithiae sp. nov., and Ge. sinensis sp. nov.

RNA editing in response to COVID-19 vaccines: unveiling dynamic epigenetic regulation of host immunity.

Background: COVID-19 vaccines are crucial for reducing the threat and burden of the pandemic on global public health, yet the epigenetic, especially RNA editing in response to the vaccines remains unelucidated. Results: Our current study performed an epitranscriptomic analysis of RNA-Seq data of 260 blood samples from 102 healthy and SARS-CoV-2 naïve individuals receiving different doses of the COVID-19 vaccine and revealed dynamic, transcriptome-wide adenosine to inosine (A-to-I) RNA editing changes in response to COVID-19 vaccines (RNA editing in response to COVID-19 vaccines). 5592 differential RNA editing (DRE) sites in 1820 genes were identified, with most of them showing up-regulated RNA editing and correlated with increased expression of edited genes. These deferentially edited genes were primarily involved in immune- and virus-related gene functions and pathways. Differential ADAR expression probably contributed to RNA editing in response to COVID-19 vaccines. One of the most significant DRE in RNA editing in response to COVID-19 vaccines was in apolipoprotein L6 (APOL6) 3' UTR, which positively correlated with its up-regulated expression. In addition, recoded key antiviral and immune-related proteins such as IFI30 and GBP1 recoded by missense editing was observed as an essential component of RNA editing in response to COVID-19 vaccines. Furthermore, both RNA editing in response to COVID-19 vaccines and its functions dynamically depended on the number of vaccine doses. Conclusion: Our results thus underscored the potential impact of blood RNA editing in response to COVID-19 vaccines on the host's molecular immune system.

Exploring the relationship between the interleukin family and lung adenocarcinoma through Mendelian randomization and RNA sequencing analysis.

BACKGROUND: Lung adenocarcinoma (LUAD) is still one of the most prevalent malignancies. Interleukin factors are closely associated with the initiation and progression of cancer. However, the relationship between interleukin factors and LUAD has not been fully elucidated. This study aimed to use Mendelian randomization (MR) and RNA sequencing (RNA-seq) analyses to identify the interleukin factors associated with the onset and progression of LUAD. METHODS: Exposure-related instrumental variables were selected from interleukin factor summary datasets. The LUAD summary dataset from FINGENE served as the outcome. MR and sensitivity analyses were conducted to screen for interleukin factors associated with LUAD occurrence. Transcriptome analyses revealed the role of interleukin factors in lung tissues. The results were validated through Western blotting and further confirmed with driver gene-negative patients from multiple centers. Potential mechanisms influencing LUAD occurrence and development were explored using bulk RNA-seq and single-cell RNA-seq data. RESULTS: MR analysis indicated that elevated plasma levels of IL6RB, IL27RA, IL22RA1, and IL16 are causally associated with increased LUAD risk, while IL18R1 and IL11RA exhibit the opposite effect. Transcriptome analyses revealed that IL11RA, IL18R1, and IL16 were downregulated in tumor tissues compared with normal lung tissue, but only higher expression of IL11RA correlated with improved prognosis in patients with LUAD from different centers and persisted even in driver-gene negative patients. The IL11RA protein level was lower in various LUAD cell lines than in human bronchial epithelial cells. The genes co-expressed with IL11RA were enriched in the Ras signaling pathway and glycosylation processes. Fibroblasts were the primary IL11RA-expressing cell population, with IL11RA+fibroblasts exhibiting a more immature state. The genes differentially expressed between IL11RA+and IL11RA- fibroblasts were involved in the PI3K-Akt/TNF signaling pathway. CONCLUSION: According to the MR and transcriptome analyses, the downregulation of IL11RA was closely related to the occurrence and development of LUAD.

[Corrigendum] (­)­Epigallocatechingallate induces apoptosis in B lymphoma cells via caspase­dependent pathway and Bcl­2 family protein modulation.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 3 on p. 1510, the western blot images selected to portray the caspase 7 and PARP/cleaved PARP experiments were remarkably similar. After having referred to their original data, the authors realized that the PARP/cleaved PARP blots had been inadvertently duplicated in the figure. The revised version of Fig. 3, showing the correct data for the caspase­7 experiment, is shown below. The authors confirm that the errors made during the assembly of Fig. 3 did not adversely affect the major conclusions presented in this paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 1507­1515, 2015; DOI: 10.3892/ijo.2015.2869].

Spencermartinsiella nicolii sp. nov., a potential opportunistic pathogenic yeast species isolated from rotting wood in Brazil.

Nineteen isolates representing a candidate for a novel yeast species belonging to the genus Spencermartinsiella were recovered from rotting wood samples collected at different sites in Atlantic Rainforest and Amazonian Forest ecosystems in Brazil. Similarity search of the nucleotide sequence of the intergenic spacer (ITS)-5.8S and large subunit D1/D2 regions of the ribosomal gene cluster showed that this novel yeast is closely related to Spencermartinsiella cellulosicola. The isolates differ by four nucleotide substitutions in the D1/D2 domain and six substitutions and 31 indels in the ITS region from the holotype of S. cellulosicola. Phylogenomic analysis based on 1474 single-copy orthologues for a set of Spencermartinsiella species whose whole genome sequences are available confirmed that the novel species is phylogenetically close to S. cellulosicola. The low average nucleotide identity value of 83% observed between S. cellulosicola and the candidate species confirms that they are distinct. The novel species produced asci with hemispherical ascospores. The name Spencermartinsiella nicolii sp. nov. is proposed. The holotype is CBS 14238T. The MycoBank number is MB855027. Interestingly, the D1/D2 sequence of the S. nicolii was identical to that of an uncultured strain of Spencermartinsiella causing systemic infection in a male adult crocodile (Crocodylus niloticus). The characterization of some virulence factors and antifungal susceptibility of S. nicolii isolates suggest that this yeast may be an opportunistic pathogen for animals, including humans; the isolates grow at 37 °C.

Telomeres and telomerase in Sarcoma disease and therapy.

Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.

Bulk and single-cell RNA-seq analyses reveals canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy.

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

Higher triglyceride­glucose index is associated with increased risk of stroke among middle-aged and elderly Chinese: a national longitudinal study.

Stroke is a severe cerebrovascular disease. This study aimed to determine the association between triglyceride­glucose (TyG) index and stroke among middle-aged and elderly Chinese. Data was extracted from China Health and Retirement Longitudinal Study survey 2015 and survey 2018. Logistic regression, trend test and subgroup analysis were conducted to assess the association. Possible nonlinear relationships were explored with restricted cubic spline (RCS). Propensity score matching (PSM) was conducted to attenuate the effect of confounding factors. ORs of stroke was positively associated with TyG index. The ORs in RCS analysis also increased with the rising TyG, though p for non-linearity was bigger than 0.05. After PSM, the ORs in the full adjusted models were 1.28 (1.01, 1.62). TyG was suggested as an independent risk factor for stroke in the middle aged and elderly Chinese.