Trimatch comparison of the prognosis of hypochloremia, normolchloremia and hyperchloremia in patients with septic shock.

BACKGROUND: Septic shock is a lethal disease, and identifying high-risk patients through noninvasive and widely available biomarkers can help improve global outcomes. While the clinical impact of chloride levels on critically ill patients remains unclear, this study aims to investigate the association between hypochloremia and mortality following ICU admission among septic shock patients. METHODS: This is an analysis of data stored in the databases of Medical Information Mart for Intensive Care IV (MIMIC-IV). The initial chloride levels were classified ashypochloremia, normal chloraemia, and hyperchloraemia. A multivariate logistic regression model was applied, adjusting for age, lactate, pH, PO2, urine volume, RDW, creatinine, and liver disease, to assess the association between the three categories of chloride levels and mortality. RESULTS: Of 3726 patients included in the study, 470 patients (12.6%) had hypochloremia on ICU admission. During the follow-up period, 1120 (33.5%) patients died. Hypochloremia was significantly associated with increased mortality and the incidence of AKI after adjusting for several variables. CONCLUSIONS: Hypochloremia is independently associated with higher hospital mortality, AKI incidence among septic shock patients. However, further high-quality research is necessary to establish the precise relationship between hypochloremia and septic shock prognosis.

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

The Predictive Value of Neutrophil Extracellular Trap-Related Risk Score in Prognosis and Immune Microenvironment of Colorectal Cancer Patients.

Colorectal cancer (CRC) has brought great healthy burden for patients. Neutrophil extracellular traps (NETs) have been explored in several tumors, while it remains largely unclear in CRC. CRC-related data were downloaded from Cancer Genome Atlas and Gene Expression Omnibus databases. Then, a NET risk score was built after univariate Cox and LASSO Cox regression analysis. Prognostic value was evaluated via survival analysis, stratification analysis, and ROC analysis. The functional enrichment analysis was conducted basing on bulk and scRNA-seq data. The immune landscape difference was analyzed using CIBERSORT, XCell, and MCPcounter portals. NET risk score was built for CRC patients, basing on G0S2, HIST1H2BC, CRISPLD2, and IL17A. In TCGA-CRC and validation datasets, regardless of age or gender, high-risk CRC patients had significantly worse prognosis, besides higher NET risk score was mainly found in samples with MSI-H and advanced T, N, and M stages. Employing multiple databases, we noticed that M0 and M2 Macrophages infiltrated the most in high-risk CRC patients, besides M2 Macrophages and neutrophils showed positive correlation with NET risk score. A novel reliable prognostic NET risk score was developed for CRC patients, and high-risk patients had unfavorable prognosis with advanced disease status.

DEVELOPMENT AND INTERNAL-EXTERNAL VALIDATION OF THE ACCI-SOFA MODEL FOR PREDICTING IN-HOSPITAL MORTALITY OF PATIENTS WITH SEPSIS-3 IN THE ICU: A MULTICENTER RETROSPECTIVE COHORT STUDY.

ABSTRACT: Objective: To achieve a better prediction of in-hospital mortality, the Sequential Organ Failure Assessment (SOFA) score needs to be adjusted and combined with comorbidities. This study aims to enhance the prediction of SOFA score for in-hospital mortality in patients with Sepsis-3. Methods: This study adjusted the maximum SOFA score within the first 3 days (Max Day3 SOFA) in relation to in-hospital mortality using logistic regression and incorporated the age-adjusted Charlson Comorbidity Index (aCCI) as a continuous variable to build the age-adjusted Charlson Comorbidity Index-Sequential Organ Failure Assessment (aCCI-SOFA) model. The outcome was in-hospital mortality. We developed, internally validated, and externally validated the aCCI-SOFA model using cohorts of Sepsis-3 patients from the MIMIC-IV, MIMIC-III (CareVue), and the FAHWMU cohort. The predictive performance of the model was assessed through discrimination and calibration, which was assessed using the area under the receiver operating characteristic and calibration curves, respectively. The overall predictive effect was evaluated using the Brier score. Measurements and main results: Compared with the Max Day3 SOFA, the aCCI-SOFA model showed significant improvement in area under the receiver operating characteristic with all cohorts: development cohort (0.81 vs 0.75, P < 0.001), internal validation cohort (0.81 vs 0.76, P < 0.001), MIMIC-III (CareVue) cohort (0.75 vs 0.68, P < 0.001), and FAHWMU cohort (0.72 vs 0.67, P = 0.001). In sensitivity analysis, it was suggested that the application of aCCI-SOFA in early nonseptic shock patients had greater clinical value, with significant differences compared with the original SOFA scores in all cohorts ( P < 0.05). Conclusion: For septic patients in intensive care unit, the aCCI-SOFA model exhibited superior predictive performance. The application of aCCI-SOFA in early nonseptic shock patients had greater clinical value.

A newly discovered glycosyltransferase gene UGT88A1 affects growth and polysaccharide synthesis of Grifola frondosa.

Grifola frodosa polysaccharides, especially ß-D-glucans, possess significant anti-tumor, antioxidant and immunostimulatory activities. However, the synthesis mechanism remains to be elucidated. A newly discovered glycosyltransferase UGT88A1 was found to extend glucan chains in vitro. However, the role of UGT88A1 in the growth and polysaccharide synthesis of G. frondosa in vivo remains unclear. In this study, the overexpression of UGT88A1 improved mycelial growth, increased polysaccharide production, and decreased cell wall pressure sensitivity. Biomass and polysaccharide production decreased in the silenced strain, and the pressure sensitivity of the cell wall increased. Overexpression and silencing of UGT88A1 both affected the monosaccharide composition and surface morphology of G. frondosa polysaccharides and influenced the antioxidant activity of polysaccharides from different strains. The messenger RNA expression of glucan synthase (GLS), UTP-glucose-1-phosphate uridylyltransferase (UGP), and UDP-xylose-4-epimerase (UXE) related to polysaccharide synthesis, and genes related to cell wall integrity increased in the overexpression strain. Overall, our study indicates that UGT88A1 plays an important role in the growth, stress, and polysaccharide synthesis of G. frondosa, providing a reference for exploring the pathway of polysaccharide synthesis and metabolic regulation. KEY POINTS: •UGT88A1 plays an important role in the growth, stress response, and polysaccharide synthesis in G. frondosa. •UGT88A1 affected the monosaccharide composition, surface morphology and antioxidant activity of G. frondosa polysaccharides. •UGT88A1 regulated the mRNA expression of genes related to polysaccharide synthesis and cell wall integrity.

The Identification Distinct Antiviral Factors Regulated Influenza Pandemic H1N1 Infection.

Influenza pandemic with H1N1 (H1N1pdms) causes severe lung damage and "cytokine storm," leading to higher mortality and global health emergencies in humans and animals. Explaining host antiviral molecular mechanisms in response to H1N1pdms is important for the development of novel therapies. In this study, we organised and analysed multimicroarray data for mouse lungs infected with different H1N1pdm and nonpandemic H1N1 strains. We found that H1N1pdms infection resulted in a large proportion of differentially expressed genes (DEGs) in the infected lungs compared with normal lungs, and the number of DEGs increased markedly with the time of infection. In addition, we found that different H1N1pdm strains induced similarly innate immune responses and the identified DEGs during H1N1pdms infection were functionally concentrated in defence response to virus, cytokine-mediated signalling pathway, regulation of innate immune response, and response to interferon. Moreover, comparing with nonpandemic H1N1, we identified ten distinct DEGs (AREG, CXCL13, GATM, GPR171, IFI35, IFI47, IFIT3, ORM1, RETNLA, and UBD), which were enriched in immune response and cell surface receptor signalling pathway as well as interacted with immune response-related dysregulated genes during H1N1pdms. Our discoveries will provide comprehensive insights into host responding to pandemic with influenza H1N1 and find broad-spectrum effective treatment.

CPT1A mediates chemoresistance in human hypopharyngeal squamous cell carcinoma via ATG16L1-dependent cellular autophagy.

Hypopharyngeal squamous cell carcinoma (HSCC) is a highly aggressive malignancy that constitutes approximately 95% of all hypopharyngeal carcinomas, and it carries a poor prognosis. The primary factor influencing the efficacy of anti-cancer drugs for this type of carcinoma is chemoresistance. Carnitine palmitoyltransferase 1A (CPT1A) has been associated with tumor progression in various cancers, including breast, gastric, lung, and prostate cancer. The inhibition or depletion of CPT1A can lead to apoptosis, curbing cancer cell proliferation and chemoresistance. However, the role of CPT1A in HSCC is not yet fully understood. In this study, we discovered that CPT1A is highly expressed in HSCC and is associated with an advanced T-stage and a poor 5-year survival rate among patients. Furthermore, the overexpression of CPT1A contributes to HSCC chemoresistance. Mechanistically, CPT1A can interact with the autophagy-related protein ATG16L1 and stimulate the succinylation of ATG16L1, which in turn drives autophagosome formation and autophagy. We also found that treatment with 3-methyladenine (3-MA) can reduce cisplatin resistance in HSCC cells that overexpress CPT1A. Our findings also showed that a CPT1A inhibitor significantly enhances cisplatin sensitivity both in vitro and in vivo. This study is the first to suggest that CPT1A has a regulatory role in autophagy and is linked to poor prognosis in HSCC patients. It presents novel insights into the roles of CPT1A in tumorigenesis and proposes that CPT1A could be a potential therapeutic target for HSCC treatment.

Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants.

BACKGROUND: There is a research gap between genetic predisposition, socioeconomic factors, and their interactions on thyroid tumorigenesis. METHODS: Individual and genetic data were obtained from UK Biobank. Logistic regression models were used to evaluate the association between genetic risk, socioeconomic factors, and thyroid cancer (TCa). A stratified analysis was conducted to estimate their joint effects. A two-sample Mendelian randomization (MR) analysis was further used to examine the potential causality. RESULTS: A total of 502,394 participants were included in this study. Three index loci (rs4449583, rs7726159, and rs7725218) of telomerase reverse transcriptase (TERT) were found to be significantly related to incident TCa. Association analyses showed that high genetic risk, low household income, and high education level were independent risk factors, while unemployment and frequent social connection were suggestive risk factors for TCa. Interaction analyses showed that in participants with low genetic risk, low household income was significantly associated with TCa (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.00-2.46). In participants with high genetic risk, those with a high education level (OR = 1.32, 95%CI: 1.06-1.65) and frequent social connection (OR = 1.36, 95%CI: 1.02-1.81) had a significantly increased risk of TCa. However, no causal relationship was observed in the MR analysis. CONCLUSION: Interactions exist between genetic risk, household income, education level, and social connection and thyroid cancer.

Clinical efficacy of sufentanil combined with dexmedetomidine in patient-controlled subcutaneous analgesia for advanced cancer pain.

To evaluate the efficacy of sufentanil combined with dexmedetomidine in patient-controlled subcutaneous analgesia (PSCA) for advanced cancer pain, 62 patients with advanced cancer pain treated in Department of Oncology of Hebei PetroChina Central Hospital from January 2017 to May 2020 were recruited and assigned via the random number table method to either the control group or the observation group. The control group (group A) received PSCA with sufentanil and the observation group was divided into group B1 receiving PSCA with sufentanil and dexmedetomidine (20:1) and group B2 given PSCA with sufentanil and dexmedetomidine (10:1). The numeric rating scale (NRS) scores of patients in the three groups decreased significantly after medication (P<0.05), with significantly lower NRS scores in groups B1 and B2 than in group A (P<0.05) and comparable results between groups B1 and B2 (P>0.05). Significantly higher Ramsay sedation scores were observed in groups B1 and B2 than in group A after drug administration (P<0.05), without significant differences between groups B1 and B2 (P>0.05). The incidence of constipation, nausea and vomiting in group B1 and group B2 was significantly lower than that in group A. PSCA with sufentanil and dexmedetomidine is effective in patients with cancer pain.

Efficient Drug Delivery of Ti3C2Tx MXenes for Synergistic Treatment of Human Hypopharyngeal Squamous Cell Carcinoma.

Ti3C2Tx MXene is a versatile two-dimensional material that exhibits exceptional properties, such as an abundance of surface functional groups that facilitate modifications. Additionally, Ti3C2Tx MXene possesses remarkable photothermal effects. In this study, ultrathin Ti3C2Tx nanosheets with dimensions (∼200 nm) suitable for biological applications were prepared by ultrasonication of larger pieces of Ti3C2Tx MXene with a cell pulverizer operating at a specific power. The ultrathin nanosheets exhibited a significant photothermal conversion efficiency (47.1%) under an 808 nm infrared laser irradiation. In addition, they showed an excellent mass extinction coefficient of 15.7 L g-1 cm-1. By exploiting the intermolecular force between these ultrathin nanosheets and doxorubicin (DOX), a drug loading efficiency of 72.8% was achieved. Through layer-by-layer surface modification of a sulfhydryl-modified polymethacrylic acid (PMAsh) shell and a transferrin (Tf) layer with targeting function, a multifunctional nanomedicine platform (Ti3C2Tx-DOX-PMAsh-Tf) was constructed. Experiments executed in vitro with cells and in vivo to inhibit tumors manifested that Ti3C2Tx is biocompatible. Furthermore, the results showed that the drug release behavior of Ti3C2Tx-DOX-PMAsh-Tf is responsive to glutathione (GSH) stimulation. The synergistic treatment of photothermal therapy and the anticancer drug DOX effectively achieved the inhibition of human hypopharyngeal squamous cell carcinoma.

The complete chloroplast genome sequence of Phyllostachys incarnata Wen, 1982.

Phyllostachys incarnata Wen, 1982 is one of the important material and edible bamboo specie of high quality in China. We reported the complete chloroplast(cp) genome of P. incarnata in this study. The cp genome of P. incarnata (GenBank accession number: OL457160) was a typical tetrad structure with a full length of 139,689 bp, comprising a pair of inverted repeated (IR) regions (21,798 bp) separated by a large single-copy (LSC) region (83,221 bp) and a small single-copy (SSC) region (12,872 bp). And the cp genome contained 136 genes, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on 19 cp genomes suggested that P. incarnata was relatively close to P. glauca among the species analyzed.

Host factor TNK2 is required for influenza virus infection.

BACKGROUND: Host factors are required for Influenza virus infection and have great potential to become antiviral target. OBJECTIVE: Here we demonstrate the role of TNK2 in influenza virus infection. CRISPR/Cas9 induced TNK2 deletion in A549 cells. METHODS: CRISPR/Cas9-mediated deletion of TNK2. Western blotting and qPCR was used to measure the expression of TNK2 and other proteins. RESULTS: CRISPR/Cas9-mediated deletion of TNK2 decreased the replication of influenza virus and significantly inhibited the ex-pression of viral proteins and TNK2 inhibitors (XMD8-87 and AIM-100) reduced the expression of influenza M2, while over-expression of TNK2 weakened the resistance of TNK2-knockout cells to influenza virus infection. Furthermore, a decrease of nuclear import of IAV in the infected TNK2 mutant cells was observed in 3 h post-infection. Interestingly, TNK2 deletion enhanced the colocalization of LC3 with autophagic receptor p62 and led to the attenuation of influenza virus-caused accumulation of autophagosomes in TNK2 mutant cells. Further, confocal microscopy visualization result showed that influenza viral matrix 2 (M2) was colocalized with Lamp1 in the infected TNK2 mutant cells in early infection, while almost no colocalization between M2 and Lamp1 was observed in IAV-infected wild-type cells. Moreover, TNK2 depletion also affected the trafficking of early endosome and the movement of influenza viral NP and M2. CONCLUSION: Our results identified TNK2 as a critical host factor for influenza viral M2 protein trafficking, suggesting that TNK2 will be an attractive target for the development of antivirals therapeutics.

Leaf spot disease on Juglans regia caused by Ragnhildiana diffusa in China.

Juglans regia L. is commercially important for its edible nuts, which is a major species of walnut trees in Sichuan Province (Luo et al. 2020). In September 2021, brown leaf spot symptoms were observed on roughly 75% of 60 J. regia trees surveyed in an orchard of Chongzhou city (30°40'6''N, 103°40'18''E). Initially, the lesions measuring 2-10 mm were reddish to brown with a yellowish halo, then increased in size and coalesced to cover the whole leaf, eventually resulting in severe defoliation. Six symptomatic leaves from different trees were collected, and a single fungal isolate was obtained from each of the sampled leaves using single-spore isolation (Chomnunti et al. 2014). The isolates were incubated on potato dextrose agar (PDA) with a 12h photoperiod at 25 ℃, and deposited at the Culture Collection of Sichuan Agricultural University. Colonies were identical with black center and reddish-brown periphery, and the diameter reached 2 cm after 7 days. On the host, conidiophores were mostly reduced to conidiogenous cells, with prominent and thickened conidiogenous loci. Conidia were light green to light brown, and curved with a thickened and darked hilum at the base, 0-17 septate, tapering toward the distal end, and measuring 20-120 × 3-5 µm ((x ) ̅= 56 × 4, n = 30). Morphological characteristics fit the description of Ragnhildiana diffusa (Heald & F.A. Wolf) Videira & Crous (Synonym: Sirosporium diffusum (Heald & F. A. Wolf) Deighton) (Poletto et al. 2017). The internal transcribed spacer (ITS) region, the large subunit of the nrDNA (LSU), and RNA polymerase II second largest subunit (rpb2) were amplified by polymerase chain reaction and sequenced with primers ITS5/ITS4 (White et al. 1990), LR0R/LR5 (Vilgalys & Hester 1990), fRPB2-5F/Rpb2-R3 (Liu et al. 1999, Videira et al. 2017), respectively. The nucleotide blast of the two isolates (SICAUCC 22-0077, SICAUCC 22-0078) showed 99.7% and 99.5% (ITS, 472/473 bp, 471/473 bp), 100% (LSU, 725/725 bp, 725/725 bp), 99.8% (rpb2, 866/867 bp, 866/867 bp) identities with the ex-type strain of Ragnhildiana diffusa (CBS 106.14). The phylogenetic tree combined with ITS, LSU, and rpb2 genes and morphological characteristics confirmed the identification as R. diffusa. These sequences of the three gene regions of two isolates were deposited in GenBank with accession numbers ON409525 and ON409526 (ITS), ON409559 and ON409560 (LSU), ON417473 and ON417474 (rpb2), respectively. The isolate SICAUCC 22-0077 was used for pathogenicity test to fulfill Koch's postulates. Three leaves of each walnut seedlings (2-year-old seedlings) were inoculated by placing a mycelium plug onto fresh wounds on the upper leaf surface punctured via a fine needle (0.7 mm in diameter), and three replicate seedlings were inoculated. For the control, a sterile PDA plug was placed on the same number of replicate leaves on the plants. The inoculated and control plants were placed in a growth chamber at 25°C with relative humidity >80% and a 12-h photoperiod. Irregular light to dark brown spots developed on inoculated leaves after twenty days, and no symptoms were observed on controls. The re-isolation and examination of the fungus showed it to be morphologically and phylogenetically identical to the originally isolated pathogen. R. diffusa has been described on J. regia in Mexico (Farr & Rossman 2022). To our knowledge, this is the first report of R. diffusa causing brown leaf spot on J. regia in China. The identification of the pathogen will provide a basis for disease management in walnut planting areas.

Complete mitochondrial genome of the longicorn Anoplophora horsfieldi Hope (Coleoptera: Cerambycidae).

The chinaberry yellow-banded longhorn beetle, Anoplophora horsfieldi Hope 1842 (Coleoptera: Cerambycidae) is an important pest on many economic tree species. In this study, the complete mitochondrial genome of A. horsfieldi was determined, which was 15,837 bp in length and contained 37 genes, including 13 protein-coding genes (PCGs), two rRNA, 22 tRNA genes, and a non-coding A + T-rich region. The phylogenetic analysis based on mitochondrial genomes showed that A. horsfieldi is sister to a clade formed by A. chinensis and A. glabripennis.

Four polysaccharides isolated from Poria cocos mycelium and fermentation broth supernatant possess different activities on regulating immune response.

Four polysaccharide fractions were isolated and purified from the culture supernatant and mycelium of Poria cocos, and differences in their immunomodulatory activity were investigated. The average molecular weights of EPS-0M, EPS-0.1M, IPS-0M, and IPS-0.1M were 1.77 × 103, 2.01 × 103, 0.03 × 103 and 4.97 × 103 kDa, respectively. They all mainly consisted of 5 monosaccharides, including glucose, mannose, galactose, fucose and rhamnose, but with different molar ratios. At a dose of 50 µg/mL, EPS-0M, EPS-0.1M, and IPS-0.1M significantly increased the production of nitric oxide (NO), as well as the mRNA and protein levels of pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in RAW264.7 cells, suggesting that they enhanced macrophage-mediated innate immunity. Moreover, based on the in vitro inflammation model of lipopolysaccharide (LPS)-stimulated RAW264.7 cells, EPS-0M, EPS-0.1M and IPS-0M but not IPS-0.1M could inhibit the LPS-induced excessive inflammatory response, including NO, IL-6, TNF-α, IL-1ß production and gene transcription. Interestingly, IPS-0M showed a relatively poor immunostimulatory effect, but had the strongest inhibitory effect against the LPS-induced RAW264.7 inflammatory response. Furthermore, our results indicate that the nuclear factor-kappa B (NF-κB) pathway is associated with the immunomodulatory effects of the polysaccharide samples on RAW264.7 cells. This study can provide a reference for the more targeted application of different polysaccharide components from Poria cocos for human health.

Construction of Polyaromatic Hydrocarbons Containing Sulfur and Nitrogen via Controllable Domino Reactions and DFT Studies.

Polyaromatic hydrocarbons (PHAs) containing heteroatoms have attracted considerable attention due to their potential utility in electronic devices. This work reported a novel domino reaction between an aryne precursor and azadiene bearing a benzothiophene moiety to produce a series of PHAs containing sulfur and nitrogen atoms. Further transformation of the product enabled concise synthesis of a new AIEgen, whose photophysical properties were characterized. Density functional calculations on the reaction mechanism revealed that the in situ generated aryne could trigger either a [4 + 2] or [3 + 2] process with azadiene, in which the regioselectivity was mainly a result of the heteroatom effect and may be understood by means of Houk's distortion-interaction model.

Assessing the impact of transfusion thresholds in patients with septic acute kidney injury: a retrospective study.

Background: Sepsis is a severe condition that often leads to complications such as acute kidney injury, which significantly increases morbidity and mortality rates. Septic AKI (S-AKI) is common in ICU patients and is associated with poor outcomes. However, there is no consensus on the optimal transfusion threshold for achieving the best clinical results. This retrospective study aims to investigate the relationship between different transfusion thresholds during hospitalization and the prognosis of septic AKI. Methods: Data from patients with S-AKI was extracted from MIMIC-IV. Based on the lowest hemoglobin level 24 h before transfusion, patients were divided into high-threshold (≥7 g/L) and low-threshold (<7 g/L) groups. We compared the outcomes between these two groups, including hospital and ICU mortality rates as primary outcomes, and 30 days, 60 days, and 90 days mortality rates, as well as duration of stay in ICU and hospital as secondary outcomes. Results: A total of 5,654 patients were included in our study. Baseline characteristics differed significantly between the two groups, with patients in the low-threshold group generally being younger and having higher SOFA scores. After performing propensity score matching, no significant differences in survival rates were found between the groups. However, patients in the low-threshold group had a longer overall hospital stay. Conclusion: A lower transfusion threshold does not impact the mortality rate in S-AKI patients, but it may lead to a longer hospital stay.

Morphology and phylogeny of ascomycetes associated with walnut trees (Juglans regia) in Sichuan province, China.

In Sichuan province, walnuts, consisting of Juglans regia, Juglans sigillata, and the hybrid J. regia × J. sigillata, are commercially important edible nuts, and J. regia is the most widespread plant. To date, the diversity and distribution of fungi inhabiting on Juglans have not received enough attention, although there have been studies focusing on pathogens from fruit and stem. In order to update the checklist of fungi associated with Sichuan walnuts, a survey on fungi associated with the three Juglans species from 15 representative regions in Sichuan was conducted. In this article, ten fungi distributed in two classes of Ascomycota (Dothideomycetes and Sordariomycetes) were described based on morpho-molecular analyses, and two novel species, Neofusicoccum sichuanense and Sphaerulina juglandina, a known species of Ophiognomonia leptostyla, and seven new hosts or geographical records of Cladosporium tenuissimum, Diatrypella vulgaris, Helminthosporium juglandinum, Helminthosporium velutinum, Loculosulcatispora hongheensis, Periconia byssoides, and Rhytidhysteron subrufulum were included. Morphological descriptions and illustrations of these fungi are provided.

Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN.

Peripheral nerve injury (PNI) is often resulting from trauma, which leads to severe and permanently disability. Schwann cells are critical for facilitating the regeneration process after PNI. Adipose-derived mesenchymal stem cells (ADSCs) exosomes have been used as a novel treatment for peripheral nerve injury. However, the underlying mechanism remains unclear. In this study, we isolated ADSCs and extracted exosomes, which were verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot (WB). Cocultured with Dorsal Root Ganglion (DRG) and Schwann cells (SCs) to evaluate the effect of exosomes on the growth of DRG axons by immunofluorescence, and the proliferation and migration of SCs by CCK8 and Transwell assays, respectively. Through exosomal miRNA sequencing and bioinformatic analysis, the related miRNAs and target gene were predicted and identified by dual luciferase assay. Related miRNAs were overexpressed and inhibited, respectively, to clarify their effects; the downstream pathway through the target gene was determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and WB. Results found that ADSC-exosomes could promote the proliferation and migration of SCs and the growth of DRG axons, respectively. Exosomal miRNA-22-3p from ADSCs directly inhibited the expression of Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), activated phosphorylation of the AKT/mTOR axis, and enhanced SCs proliferation and migration. In conclusion, our findings suggest that ADSC-exosomes could promote SCs function through exosomal miRNA-22-3p, which could be used as a therapeutic target for peripheral nerve injury.

Inhibition of cell survival and invasion by Tanshinone IIA via FTH1: A key therapeutic target and biomarker in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a worldwide public health problem; its incidence is increasing and it is now the sixth most common cancer type worldwide. As indicated by existing studies, ferroptosis contributes to HNSCC progression and Tanshinone IIA (TanIIA) may exert therapeutic effects via affecting ferroptosis. However, the underlying mechanisms have remained to be clarified. Therefore, the main aim of the present study was to screen and investigate the key genes in regulating ferroptosis of the human hypopharynx squamous carcinoma cell line FaDu and further elucidate the mechanism of action of TanIIA. A list of ferroptosis-related genes was obtained from the FerrDb database. RNA-sequencing expression (level 3) profiles and corresponding clinical information (cases, n=502; normal controls, n=44) were downloaded from The Cancer Genome Atlas dataset for HNSCC (https://portal.gdc.com). The limma package in R software was used to study the differentially expressed mRNAs. Adjusted P<0.05 and Log2(fold change) >1 or <-1 were defined as the threshold for the differential expression of mRNAs. The ClusterProfiler package (version 3.18.0) in R was employed to analyze the Gene Ontology functional terms associated with potential targets and perform a Kyoto Encyclopedia of Genes and Genomes pathway analysis. The R package ggplot2 was used to draw the boxplot and the pheatmap package was used to draw the heatmap. The DEG-related protein-protein interaction network was built with the Search Tool for the Retrieval of Interacting Genes and proteins database and then the visualization was performed using Cytoscape. Ferritin heavy chain 1 (FTH1), transferrin (TF) and TF receptor were screened out using a Wayne diagram, which was drawn by the Venn Diagram package in R. Kaplan-Meier survival analysis and the log-rank test were used to compare differences in survival between the groups. The receiver operating characteristic (v 0.4) (ROC) curve analysis was used to compare the predictive accuracy of mRNAs. FTH1 was screened out and the expression results were verified using The Human Protein Atlas data. Immunohistochemistry and immunofluorescence were used to localize FTH1 expression in FaDu cells. Furthermore, Cell Counting Kit-8 and Transwell assays were used to detect the cell survival and invasion ability, respectively. Furthermore, western blot analysis was performed to analyze protein expression. The results of the present study indicated that three validated ferroptosis marker genes were differentially expressed in HNSCC, among which FTH1 was significantly associated with poorer survival. TanIIA was demonstrated to significantly affect FaDu cell survival and invasiveness and markedly attenuate FTH1 expression. To conclude, the ferroptosis gene FTH1 is highly expressed in HNSCC and TanIIA significantly inhibited HNSCC, partially by suppressing FTH1.