Primary spinal epidural abscess: magnetic resonance imaging characteristics and diagnosis.

RATIONALE AND OBJECTIVE: To investigate the MR characteristics of phlegmonous stage and abscess stage primary spinal epidural abscess. MATERIALS AND METHODS: This study retrospectively analyzed the clinical and imaging characteristics of 27 cases of pathologically confirmed primary spinal epidural abscess. Predisposing conditions of all patients were collected. All patients underwent conventional magnetic resonance imaging, while fifteen patients also underwent post-contrast magnetic resonance imaging. RESULTS: The initial symptoms included back pain in 25 patients, fever in 18, motor deficit in five, and sensory changes in 13. Underlying diseases included distant site of infection in seven, injection therapy in five, neoplasm in five, chronic inflammatory disease in five, diabetes mellitus in four, alcoholism in three, metabolic disorder in three, hepatopathy in three, and obesity in two. Abscess location was ventral epidural space in 15 patients (55.6%) and dorsal epidural space in 12 (44.4%). On T1-weighted image, the abscess was hypointense to the spinal cord in 23 patients (85%) and isointense in four (15%). All abscesses were hyperintense to the spinal cord on T2-weighted image. Among the 15 patients who underwent contrast-enhanced imaging, ring enhancement was present in 13 and homogeneous enhancement in two. Adjacent vertebrae body edema was present in four patients. The abscess was purely intraspinal in 25 patients (92.6%). Paraspinal extension was present in two (7.4%). CONCLUSION: Primary spinal epidural abscess patients have one or more predisposing conditions. Phlegmonous stage primary spinal epidural abscess appears isointense on T1WI and hyperintense on T2WI and enhancement is homogeneous. Abscess stage primary spinal epidural abscess hyperintense on T2WI and hypointense on T1WI and ring enhancement. Presence of vertebral body edema is an important sign to help diagnose primary spinal epidural abscess.

Comparison of the quantitative contrast sensitivity function between early keratoconus and normal eyes.

PURPOSE: To compare the characteristics of the quantitative contrast sensitivity function (qCSF) in eyes with early keratoconus (Early-KC) and normal control (NC) eyes and investigate the associated factors. DESIGN: A cross-sectional study. METHODS: This study included 43 eyes of 43 patients with Early-KC (including subclinical keratoconus [SKC] and forme fruste keratoconus [FFKC]) and 77 NC eyes of 77 participants with corrected distance visual acuity (CDVA) all ≥ 20/20. Contrast sensitivity (CS) was assessed using the qCSF tests. Subgroup analysis was performed according to keratoconus type(SKC and FFKC) and astigmatism(cylindrical refraction >-1.0D or ≤-1.0D). RESULTS: Sex ratio, spherical refraction, and spherical equivalent (SE) varied significantly between the two groups (all P < 0.01). The area under log CSF (AULCSF), CSF Acuity, and CS at low (1.0 and 1.5 cycles per degree [cpd]) and high (12.0 and 18.0 cpd) spatial frequencies decreased significantly in the Early-KC group than that in the NC group (all P < 0.05). The subgroup analysis revealed a similar decrease in the SKC group (all P < 0.05). AULCSF, CSF Acuity, and CS at high spatial frequencies of patients with cylindrical refraction ≤-1.0D in the Early-KC group decreased significantly (all P < 0.05) than those in the NC group. The index of vertical asymmetry and index of height decentration correlated negatively with CS at 1.5 cpd (r= -0.321 and -0.306; both P < 0.05). CONCLUSIONS: CS decreased significantly at low and high spatial frequencies in Early-KC, though with normal CDVA. The qCSF test can sensitively reflect visual performance in early keratoconus.

Comparative analysis of hospital-acquired and community-acquired infections at a tertiary hospital in China before and during COVID-19: A 7-year longitudinal study (2017-2023).

BACKGROUND: The COVID-19 pandemic profoundly influenced the dynamics of hospital-acquired infections (HAIs) and community-acquired infections (CAIs) across global healthcare systems. This 7-year longitudinal survey (2017-2023) assessed the point prevalence of HAIs and CAIs at a first-class tertiary hospital in China, both prior to and during the pandemic. METHODS: Patients were stratified into pre-pandemic and pandemic periods, as well as into stringent and relaxed infection prevention and control (IPC) phases, to compare the point prevalence of HAIs and CAIs. Multivariate logistic regression was employed to identify risk factors associated with HAIs. RESULTS: A total of 15,296 inpatients were assessed between 2017 and 2023. The overall point prevalence of HAIs was 1.50% (95% confidence interval [CI], 1.32%-1.71%), showing a significant downward trend (P = 0.021). Conversely, CAIs had an overall point prevalence of 24.49% (95% CI, 23.81%-25.18%) with a marked upward trend (P < 0.001). Among patients receiving pathogen testing, the point prevalence of HAIs significantly declined during the pandemic (6.26% vs. 9.89%, P < 0.001), particularly for respiratory HAIs (3.83% vs. 6.89%, P < 0.001). The point prevalence of CAIs demonstrated a notable increase in 2023 compared to 2020-2022 among pathogen-tested patients (81.37% vs. 74.18%, P = 0.001). Multivariate analysis identified hospitalization during the pandemic as a protective factor against HAIs (adjusted odds ratio 0.49, 95% CI, 0.36-0.67). CONCLUSIONS: The comprehensive IPC strategy implemented during the COVID-19 pandemic at this tertiary hospital significantly reduced the point prevalence of HAIs. However, CAIs exhibited a rising trend following the relaxation of COVID-19 IPC measures.

RAG-seq: A NSR Primed and Transposase Tagmentation Mediated Strand-specific Total RNA Sequencing in Single Cell.

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular diversity with unprecedented resolution. However, many current methods are limited in capturing full-length transcripts and discerning strand orientation. We present RAG-seq, an innovative strand-specific total RNA sequencing technique that combines not-so-random (NSR) primers with Tn5 transposase-mediated tagmentation. RAG-seq overcomes previous limitations by delivering comprehensive transcript coverage and maintaining strand orientation, which is essential for accurate quantification of overlapping genes and detection of antisense transcripts. Through optimized reverse transcription with oligo dT primers, rRNA depletion via Depletion of Abundant Sequences by Hybridization (DASH), and linear amplification, RAG-seq enhances sensitivity and reproducibility, especially for low-input samples and single cells. Application to mouse oocytes and early embryos highlights RAG-seq's superior performance in identifying stage-specific antisense transcripts, shedding light on their regulatory roles during early development. This advancement represents a significant leap in transcriptome analysis within complex biological contexts.

Machine learning for predicting device-associated infection and 30-day survival outcomes after invasive device procedure in intensive care unit patients.

This study aimed to preliminarily develop machine learning (ML) models capable of predicting the risk of device-associated infection and 30-day outcomes following invasive device procedures in intensive care unit (ICU) patients. The study utilized data from 8574 ICU patients who underwent invasive procedures, sourced from the Medical Information Mart for Intensive Care (MIMIC)-IV version 2.2 database. Patients were allocated into training and validation datasets in a 7:3 ratio. Seven ML models were employed for predicting device-associated infections, while five models were used for predicting 30-day survival outcomes. Model performance was primarily evaluated using the receiver operating characteristic (ROC) curve for infection prediction and the survival model's concordance index (C-index). Top-performing models progressively reduced the number of variables based on their importance, thereby optimizing practical utility. The inclusion of all variables demonstrated that extreme gradient boosting (XGBoost) and extra survival trees (EST) models yielded superior discriminatory performance. Notably, when restricted to the top 10 variables, both models maintained performance levels comparable to when all variables were included. In the validation cohort, the XGBoost model, with the top 10 variables, achieved an area under the curve (AUC) of 0.810 (95% CI 0.808-0.812), an area under the precision-recall curve (AUPRC) of 0.226 (95% CI 0.222-0.230), and a Brier score (BS) of 0.053 (95% CI 0.053-0.054). The EST model, with the top 10 variables, reported a C-index of 0.756 (95% CI 0.754-0.757), a time-dependent AUC of 0.759 (95% CI 0.763-0.775), and an integrated Brier score (IBS) of 0.087 (95% CI 0.087-0.087). Both models are accessible via a web application. The internally evaluated XGBoost and EST models demonstrated exceptional predictive accuracy for device-associated infection risks and 30-day survival outcomes post-invasive procedures in ICU patients. Further validation is required to confirm the clinical utility of these two models in future studies.

Advantages of the zebrafish tumor xenograft model: the evaluation of efficacy in cancer therapy and the application to the study of lncRNAs.

In the current preclinical anti-tumor researches, there is a general lack of an in vivo model that can quickly and efficiently screen effective anti-tumor drugs. As a species that is 87% genetically similar to humans, zebrafish have been widely used to model human diseases, and they are considered an alternative economic model for studying cancer development, proliferation, and metastasis. The zebrafish tumor xenograft model has been effectively used for cancer drug development at all levels, including target validation, and high-throughput screening of long non-coding RNAs (lncRNAs) that may be involved in tumor regulation. In this review, we provide a comprehensive overview of zebrafish as an in vivo model for cancer cell growth, migration, anti-tumor immunotherapy, and anti-tumor drug screening. In addition, the regulatory mechanisms of some active lncRNAs have been identified to play a role in the pathogenesis of cancer, but it is still necessary to take advantage of the efficient zebrafish model to screen and learn more about the role of these molecules in tumor development and migration. Current anti-tumor therapies are limited by severe toxicity and multidrug resistance. There is an urgent need for the cost-effective and efficient in vivo research tools to improve our understanding and overcome these problems. This paper reviews the different purposes of anti-tumor research using zebrafish model. We discuss the use of zebrafish in cancer cell proliferation and metastasis, identifying signaling pathways, cancer drug discovery and treatment development, and toxicity studies. Finally, this review highlights the limitations of the field and future directions to effectively utilize zebrafish as a highly efficient model for cancer treatment development.

Delayed Blastocyst Formation Reduces the Quality and Hatching Ability of Porcine Parthenogenetic Blastocysts by Increasing DNA Damage, Decreasing Cell Proliferation, and Altering Transcription Factor Expression Patterns.

The purpose of this study was to investigate the influence of blastocyst formation timing on the quality of porcine embryos derived from parthenogenetic activation. Newly formed blastocysts at days 6, 7, and 8 of culture [termed formation 6, 7, and 8 blastocysts (F6, F7, and F8 blastocysts)] were obtained, and a series of parameters related to the quality of blastocysts, including apoptosis incidents, DNA replication, pluripotent factors, and blastocyst hatching capacity, were assessed. Delayed blastocyst formation (F7 and/or F8 blastocysts) led to increased levels of ROS, DNA damage, and apoptosis while decreasing the mitochondrial membrane potential, DNA replication, Oct4 levels, and numbers of Sox2-positive cells. F7 blastocysts showed a significantly reduced hatching rate compared to F6 blastocysts; however, F8 blastocysts were unable to develop to the hatching stage. Collectively, our findings suggest a negative correlation between delayed blastocyst formation and blastocyst quality.

Computed tomography-based radiomic model for the prediction of neoadjuvant immunochemotherapy response in patients with advanced gastric cancer.

BACKGROUND: Neoadjuvant immunochemotherapy (nICT) has emerged as a popular treatment approach for advanced gastric cancer (AGC) in clinical practice worldwide. However, the response of AGC patients to nICT displays significant heterogeneity, and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes. AIM: To establish a radiomic model to predict the response of AGC patients to nICT. METHODS: Patients with AGC who received nICT (n = 60) were randomly assigned to a training cohort (n = 42) or a test cohort (n = 18). Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT. An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature. The performance of all the models was assessed through receiver operating characteristic curve analysis, decision curve analysis (DCA) and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The radiomic nomogram could accurately predict the response of AGC patients to nICT. In the test cohort, the area under curve was 0.893, with a 95% confidence interval of 0.803-0.991. DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models. CONCLUSION: A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC. This tool can assist clinicians in treatment-related decision-making.

A Multifunctional Exosome with Dual Homeostasis Disruption Augments cGAS-STING-Mediated Tumor Immunotherapy by Boosting Ferroptosis.

Ferroptosis has shown great potential in activating antitumor immunity. However, the cunning tumor cells can evade ferroptosis by increasing the efflux of iron and promoting the production of the reductant glutathione to mitigate oxidative stress. Herein, a multifunctional exosome loaded with manganese-doped iron oxide nanoparticles (MnIO), GW4869, and l-buthionine sulfoximine (BSO) is developed to disrupt the iron metabolism homeostasis and redox homeostasis to enhance tumor immunotherapy. The efficient transport of MnIO by exosomes and the inhibition of iron exocytosis by GW4869 led to a high retention of up to 29.57% ID/g for iron in the tumors. Such a high retention of iron, in combination with the BSO-induced disruption of the redox homeostasis, effectively promotes the ferroptosis of tumor cells. Consequently, the multifunctional exosomes that noticeably enhance ferroptosis by dual homeostasis disruption provoke the cGAS-STING-based antitumor immune response and effectively suppress tumor growth and lung metastasis in orthotopic breast cancer.

Genome-Wide Identification of Pentatricopeptide Repeat (PPR) Gene Family and Multi-Omics Analysis Provide New Insights Into the Albinism Mechanism of Kandelia obovata Propagule Leaves.

Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.

Artificial intelligence algorithms permits rapid acute kidney injury risk classification of patients with acute myocardial infarction.

Objective: This study aimed to develop and validate several artificial intelligence (AI) models to identify acute myocardial infarction (AMI) patients at an increased risk of acute kidney injury (AKI) during hospitalization. Methods: Included were patients diagnosed with AMI from the Medical Information Mart for Intensive Care (MIMIC) III and IV databases. Two cohorts of AMI patients from Changzhou Second People's Hospital and Xuzhou Center Hospital were used for external validation of the models. Patients' demographics, vital signs, clinical characteristics, laboratory results, and therapeutic measures were extracted. Totally, 12 AI models were developed. The area under the receiver operating characteristic curve (AUC) were calculated and compared. Results: AKI occurred during hospitalization in 1098 (28.3 %) of the 3882 final enrolled patients, split into training (3105) and test (777) sets randomly. Among them, Random Forest (RF), C5.0 and Bagged CART models outperformed the other models in both the training and test sets. The AUCs for the test set were 0.754, 0.734 and 0.730, respectively. The incidence of AKI was 9.8 % and 9.5 % in 2202 patients in the Changzhou cohort and 807 patients in the Xuzhou cohort with AMI, respectively. The AUCs for patients in the Changzhou cohort were RF, 0.761; C5.0, 0.733; and bagged CART, 0.725, respectively, and Xuzhou cohort were RF, 0.799; C5.0, 0.808; and bagged CART, 0.784, respectively. Conclusion: Several machines learning-based prediction models for AKI after AMI were developed and validated. The RF, C5.0 and Bagged CART model performed robustly in identifying high-risk patients earlier. Clinical trial approval statement: This Trial was registered in the Chinese clinical trials registry: ChiCTR1800014583. Registered January 22, 2018 (http://www.chictr.org.cn/searchproj.aspx).

A genetic investigation in five Chinese families with keratoconus.

Background: This study investigated the genetic characteristics of five Chinese families with keratoconus (KC). Methods: In the five families affected by KC, medical records, clinical observations, and blood samples were collected from all individuals. All KC family members (n = 20) underwent both whole exome sequencing of genomic DNA and Sanger sequencing to confirm the variants. Online software was utilized to analyze all variants, and the online server I-TASSER was employed for in silico predictions of the three-dimensional protein structures of the variants. The newly discovered variants and single nucleotide polymorphisms were further examined in 322 sporadic KC patients. Results: The Pentacam tomographic composite index in those affected first-degree family members of the probands showed a pathological change. Five new variants were detected in the five probands and other affected members in their families: a heterozygous missense variant g.19043832C>T (p.Ser145Asn) in the homer scaffolding protein 3 (HOMER3) gene; a heterozygous missense variant g.99452113G>A (p.Gly483Arg) in the insulin-like growth factor 1 receptor (IGF1R) gene; a heterozygous missense variant g.55118280G>T (p.Trp843Leu) in the echinoderm microtubule-associated protein like 6 (EML6) gene; a heterozygous frameshift variant c. 1226_1227del (p.Gln410Glufs*17) in the DOP1 leucine zipper-like protein B (DOP1B) gene; and a heterozygous splice-site variant c.7776+2T>A in the neurobeachin-like protein 2 (NBEAL2) gene. These variations were predicted to be potentially pathogenic and associated with KC. Conclusion: Five novel variants in HOMER3, IGF1R, EML6, DOP1B, and NBEAL2 genes were identified in this study and may be associated with the pathogenesis of KC. This study provides new information about the gene variants and their protein changes in KC patients. The findings should be explored further and could potentially be applied to the early diagnosis of KC before clinical onset.

Effects of fermentation conditions on molecular weight, production, and physicochemical properties of gellan gum.

Gellan gum has been widely used in many industries due to its excellent physical properties. In this study, the effects of different fermentation conditions on molecular weight and production of gellan gum were analyzed, and the optimized fermentation conditions for a high molecular weight gellan gum (H-GG: 6.42 × 105 Da) were obtained, which increased the molecular weight and yield of gellan gum by 201.4 % and 44.9 % respectively. Fourier transform infrared spectroscopy (FT-IR) and x-ray diffraction (XRD) analysis indicated that H-GG has similar characteristic absorption and semi-crystalline structures with the initial gellan gum (I-GG), and it was composed of glucose, rhamnose, and glucuronic acid showing no obvious changes in the molecular structure. Scanning electron microscope (SEM) observation revealed that the filaments of H-GG were slender, longer, and looser with larger pores. Importantly, gel properties analysis showed that the gel strength, viscoelasticity, and water-holding capacity of H-GG were better than those of I-GG, and the rheological results revealed that the H-GG is a pseudoplastic fluid with higher apparent viscosity and stable viscoelasticity at 20-70 °C. Therefore, the molecular weight and yield of gellan gum are significantly affected by fermentation conditions, and the obtained H-GG demonstrates improved gel and rheological properties.

Genetics of posttraumatic stress disorder and cardiovascular conditions using Life's Essential 8, Electronic Health Records, and Heart Imaging.

BACKGROUND: Patients with post-traumatic stress disorder (PTSD) experience higher risk of adverse cardiovascular (CV) outcomes. This study explores shared loci, and genes between PTSD and CV conditions from three major domains: CV diagnoses from electronic health records (CV-EHR), cardiac and aortic imaging, and CV health behaviors defined in Life's Essential 8 (LE8). METHODS: We used genome-wide association study (GWAS) of PTSD (N=1,222,882), 246 CV diagnoses based on EHR data from Million Veteran Program (MVP; N=458,061), UK Biobank (UKBB; N=420,531), 82 cardiac and aortic imaging traits (N=26,893), and GWAS of traits defined in the LE8 (N = 282,271 ~ 1,320,016). Shared loci between PTSD and CV conditions were identified using local genetic correlations (rg), and colocalization (shared causal variants). Overlapping genes between PTSD and CV conditions were identified from genetically regulated proteome expression in brain and blood tissues, and subsequently tested to identify functional pathways and gene-drug targets. Epidemiological replication of EHR-CV diagnoses was performed in AllofUS cohort (AoU; N=249,906). RESULTS: Among the 76 PTSD-susceptibility risk loci, 33 loci exhibited local rg with 45 CV-EHR traits (|rg|≥0.4), four loci with eight heart imaging traits(|rg|≥0.5), and 44 loci with LE8 factors (|rg|≥0.36) in MVP. Among significantly correlated loci, we found shared causal variants (colocalization probability > 80%) between PTSD and 17 CV-EHR (in MVP) at 11 loci in MVP, that also replicated in UKBB and/or other cohorts. Of the 17 traits, the observational analysis in the AoU showed PTSD was associated with 13 CV-EHR traits after accounting for socioeconomic factors and depression diagnosis. PTSD colocalized with eight heart imaging traits on 2 loci and with LE8 factors on 31 loci. Leveraging blood and brain proteome expression, we found 33 and 122 genes, respectively, shared between PTSD and CVD. Blood proteome genes were related to neuronal and immune processes, while the brain proteome genes converged on metabolic and calcium-modulating pathways (FDR p <0.05). Drug repurposing analysis highlighted DRD2, NOS1, GFAP, and POR as common targets of psychiatric and CV drugs. CONCLUSION: PTSD-CV comorbidities exhibit shared risk loci, and genes involved in tissue-specific regulatory mechanisms.

Rhizobacterial diversity, community composition, and the influence of keystone taxa on O'Neal blueberry (Vaccinium corymbosum).

Rhizosphere microbiotas play vital roles in resisting environmental stress, transforming soil nutrients, and promoting plant health, growth, and productivity. The effects of rhizosphere microbial community shaping and the characteristics and functions of keystone taxa on blueberries were comprehensively studied by examining the rhizobacteria of healthy old trees (O), young seedlings (OG), and poorly growing seedlings (OB) of O'Neal blueberries. Our results showed that rhizobacterial diversity followed the order OB > > OG > O, and the microbial community of OG was similar to that of O, while that of OB was distinctly different. The predominant rhizobacteria identified included Actinobacteria, Proteobacteria, Firmicutes, Chloroflexi, and Acidobacteria. Firmicutes were highly enriched in healthy blueberries, with Bacillus identified as a key genus that significantly enhanced blueberry growth when inoculated. Bradyrhizobium and Gaiellales were common core bacteria in the blueberry rhizosphere. In contrast, Acidobacteria were the predominant phylum in poorly growing OB, with the specific Vicinamibacterales-related and Latescibacterota-related genera acting as keystone taxa that shaped the microbial community. In addition, bacterial species in Vicinamibacterales might act as a potential pathogen predicted by BugBase. Taken together, these findings provide fundamental insights into the development of the blueberry rhizosphere microbial community and highlight the role of beneficial rhizobacteria, such as Bacillus, in enhancing blueberry growth. This knowledge could contribute to the exploitation of beneficial rhizobacteria and the prevention of pathogens in modern agriculture.

Effects of Wickerhamomyces anomalus Co-Fermented with Saccharomyces cerevisiae on Volatile Flavor Profiles during Steamed Bread Making Using Electronic Nose and HS-SPME-GC-MS.

Steamed bread is a traditional staple food in China, and it has gradually become loved by people all over the world because of its healthy production methods. With the improvement in people's living standards, the light flavor of steamed bread fermented by single yeast cannot meet people's needs. Multi-strain co-fermentation is a feasible way to improve the flavor of steamed bread. Here, the dynamic change profiles of volatile substances in steamed bread co-fermented by Saccharomyces cerevisiae SQJ20 and Wickerhamomyces anomalus GZJ2 were analyzed using the electronic nose (E-nose) and headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The five detectors of the E-nose rapidly detected the changes in volatile substances in different dough or steamed bread with the highest response value in co-fermented dough. A total of 236 volatile substances were detected in all the samples using HS-SPME-GC-MS, and alcohols were the most variable component, especially Phenylethyl alcohol. Significantly, more alcohols and esters were upregulated in co-fermented dough, and the addition of W. anomalus GZJ2 improved the key volatile aroma compounds of steamed bread using the relative odor activity value method (ROAV), especially the aldehydes and alcohols. Moreover, these key volatile aroma compounds can be quickly distinguished using the W2S detector of the E-nose, which can be used for the rapid detection of aroma components in steamed bread.

Dysregulated Airway Host Defense in Hyper IgE Syndrome due to STAT3 Mutations.

Rationale: Hyper IgE syndrome (STAT3-HIES), also known as Job's syndrome, is a rare immunodeficiency disease typically caused by dominant-negative STAT3 mutations. STAT3-HIES syndrome is characterized by chronic pulmonary infection and inflammation, suggesting impairment of pulmonary innate host defense. Objectives: To identify airway epithelial host defense defects consequent to STAT3 mutations that, in addition to reported mutant STAT3 immunologic abnormalities, produce pulmonary infection. Methods: STAT3-HIES sputum was evaluated for biochemical/biophysical properties. STAT3-HIES excised lungs were harvested for histology; bronchial brush samples were collected for RNA sequencing and in vitro culture. A STAT3-HIES-specific mutation (R382W), expressed by lentiviruses, and a STAT3 knockout, generated by CRISPR/Cas9, were maintained in normal human bronchial epithelia under basal or inflammatory (IL1ß) conditions. Effects of STAT3 deficiency on transcriptomics, and epithelial ion channel, secretory, antimicrobial, and ciliary functions were assessed. Measurements and Main Results: Mucus concentrations and viscoelasticity were increased in STAT3-HIES sputum. STAT3-HIES excised lungs exhibited mucus obstruction and elevated IL1ß expression. STAT3 deficiency impaired CFTR-dependent fluid and mucin secretion, inhibited expression of antimicrobial peptides, cytokines, and chemokines, and acidified airway surface liquid at baseline and post-IL1ß exposure in vitro. Notably, mutant STAT3 suppressed IL1R1 expression. STAT3 mutations also inhibited ciliogenesis in vivo and impaired mucociliary transport in vitro, a process mediated via HES6 suppression. Administration of a γ-secretase inhibitor increased HES6 expression and improved ciliogenesis in STAT3 R382W mutant cells. Conclusions: STAT3 dysfunction leads to multi-component defects in airway epithelial innate defense, which, in conjunction with STAT3-HIES immune deficiency, contributes to chronic pulmonary infection.

Effects of ganciclovir combined with recombinant human interferon-α on clinical efficacy and immune function in children with infectious mononucleosis.

Objective: To evaluate the effects of ganciclovir combined with recombinant human interferon on clinical efficacy and immune function of children with infectious mononucleosis(IM). Methods: This was a retrospective study. Children (n=120) with IM hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from January 2020 to January 2022 were selected and randomly divided into study group and control group((n=60). Patients in the control group were treated with ganciclovir by intravenous infusion, and patients in the study group were given ganciclovir+recombinant human interferon-α1b. The time for eliminating clinical symptoms, the levels of inflammatory cytokines, immune function condition and T-lymphocyte subsets between the two groups were compared and analyzed. Results: After treatment, the time for body temperature returned to normal, time for recovery from cervical lymphadenopathy, time for recovery from hepatosplenomegaly and time for disappearance of angina and oral mucosal congestion in the study group were significantly shorter than those in the control group(p= 0.00); after treatment, the levels of TNF-a and IL-6 in the study group were significantly lower than those in the control group; the indexes of CD3+ and CD8+ in the study group were significantly lower than those in the control group; after treatment, the levels of CD4+ and CD4+/CD8+ in the study group were significantly higher than those in the control group. Conclusion: Ranciclovir combined with recombinant human interferon-α1b, rapid improvements of clinical symptoms, significantly decreased inflammatory cytokines, improved T-lymphocyte function and no significant increase in adverse drug reactions were found in children with IM.

Lysophosphatidic acid improves development of porcine somatic cell nuclear transfer embryos.

This study was conducted to investigate whether lysophosphatidic acid (LPA) could improve the development of porcine somatic cell nuclear transfer (SCNT) embryos. Porcine SCNT-derived embryos were cultured in chemically defined polyvinyl alcohol (PVA)-based porcine zygote medium (PZM)-4 without or with LPA, and the development, cell proliferation potential, apoptosis, and expression levels of pluripotent markers were evaluated. LPA significantly increased the rates of cleavage and blastocyst formation compared to those seen in the LPA un-treatment (control) group. The expression levels of embryonic development-related genes (IGF2R, PCNA and CDH1) were higher (p < 0.05) in the LPA treatment group than in the control group. LPA significantly increased the numbers of total, inner cell mass and EdU (5-ethynyl-2'-deoxyuridine)-positive cells in porcine SCNT blastocysts compared to those seen in the control group. TUNEL assay showed that LPA significantly reduced the apoptosis rate in porcine SCNT-derived embryos; this was confirmed by decreases (p < 0.05) in the expression levels of pro-apoptotic genes, BAX and CASP3, and an increase (p < 0.05) in the expression level of the anti-apoptotic gene, BCL2L1. In addition, LPA significantly increased Oct4 expression at the gene and protein levels. Together, our data suggest that LPA improves the quality and development of porcine SCNT-derived embryos by reducing apoptosis and enhancing cell proliferation and pluripotency.