Application of Oral Retractor for Lip Injury Protection in Oral and Maxillofacial Surgeries: A Randomized Controlled Trial.

PURPOSE: Iatrogenic lip injury may occur during oral and maxillofacial surgical procedures. This study aimed to evaluate the effect of oral retractors on iatrogenic lip injury prevention during intraoral procedures of oral and maxillofacial surgery. METHODS: We conducted a randomized controlled trial and included patients who underwent intraoral procedures of oral and maxillofacial surgery. Patients were randomly allocated to receive oral retractor (intervention group) or traditional procedure without lip protection (control group). The incidence of lip injury was the outcome variable. Other study variables included surgical time and satisfaction of patients and surgeons with treatment experience evaluated by visual analog scale (VAS). Student t test and χ2 test were used to compare both groups' variables and measure the relationship between the predictor variable and the outcome variable. P<0.05 was considered significant for all analyses. RESULTS: A total of 114 patients were included, with 56 allocated to intervention group and 58 to control group. The results showed that the application of an oral retractor did not significantly increase surgical time (P=0.318). A total of 12 patients had lip injury, with 1 in the intervention group and 11 in the control group (P=0.003). For the assessment of satisfaction with treatment experience, the intervention group had significantly higher VAS scores for doctors and patients (P<0.05). CONCLUSIONS: We found that the oral retractor was a good tool for iatrogenic lip injury prevention in oral and maxillofacial surgical procedures and could be considered in clinical treatment.

Unveiling Shared Immune Responses in Porcine Alveolar Macrophages during ASFV and PRRSV Infection Using Single-Cell RNA-seq.

African swine fever virus (ASFV) and porcine reproductive and respiratory syndrome virus (PRRSV) infections lead to severe respiratory diseases in pigs, resulting in significant economic losses for the global swine industry. While numerous studies have focused on specific gene functions or pathway activities during infection, an investigation of shared immune responses in porcine alveolar macrophages (PAMs) after ASFV and PRRSV infections was lacking. In this study, we conducted a comparison using two single-cell transcriptomic datasets generated from PAMs under ASFV and PRRSV infection. Pattern recognition receptors (PRRs) RIG-I (DDX58), MDA5 (IFIH1), and LGP2 (DHX58) were identified as particularly recognizing ASFV and PRRSV, triggering cellular defense responses, including the upregulation of four cytokine families (CCL, CXCL, IL, and TNF) and the induction of pyroptosis. Through weighted gene co-expression network analysis and protein-protein interaction analysis, we identified thirteen gene and protein interactions shared by both scRNA-seq analyses, suggesting the ability to inhibit both ASFV and PRRSV viral replication. We discovered six proteins (PARP12, PARP14, HERC5, DDX60, RSAD2, and MNDA) in PAMs as inhibitors of ASFV and PRRSV replication. Collectively, our findings showed detailed characterizations of the immune responses in PAMs during ASFV and PRRSV infections, which may facilitate the treatments of these viral diseases.

Genome and Transcriptome Analysis of the Torreya grandis WRKY Gene Family during Seed Development.

Torreya grandis, an economically significant evergreen tree species exclusive to subtropical China, is highly valued for its seeds. However, the seed development process of T. grandis remains relatively unexplored. Given the pivotal role WRKY transcription factors (TFs) play in coordinating diverse cellular and biological activities, as well as crucial signaling pathways essential for plant growth and development, and the lack of comprehensive investigation into their specific functions in T. grandis, our study investigated its genome and successfully isolated 78 WRKY genes and categorized them into three distinct clades. A conserved motif analysis unveiled the presence of the characteristic WRKY domain in each identified TgWRKY protein. The examination of gene structures revealed variable numbers of introns (ranging from zero to eight) and exons (ranging from one to nine) among TgWRKY genes. A chromosomal distribution analysis demonstrated the presence of TgWRKY across eight chromosomes in T. grandis. Tissue-specific expression profiling unveiled distinctive patterns of these 78 TgWRKY genes across various tissues. Remarkably, a co-expression analysis integrating RNA-seq data and morphological assessments pinpointed the pronounced expression of TgWRKY25 during the developmental stages of T. grandis seeds. Moreover, a KEGG enrichment analysis, focusing on genes correlated with TgWRKY25 expression, suggested its potential involvement in processes such as protein processing in the endoplasmic reticulum, starch, and sucrose metabolism, thereby modulating seed development in T. grandis. These findings not only underscore the pivotal role of WRKY genes in T. grandis seed development but also pave the way for innovative breeding strategies.

The association between tea consumption and non-malignant digestive system diseases: A Mendelian randomized study.

BACKGROUND: Tea consumption might be closely related to non-malignant digestive diseases. Nevertheless, this correlation remains inadequately comprehended. Therefore, our objective was to elucidate the essence of these connections. METHODS: This study employed a Mendelian randomization approach to investigate the impact of tea consumption on specific digestive disorders. Genetic data associated with tea consumption were obtained from the UK Biobank (UKB), encompassing 447,485 participants. We chose a gene-wide association study with no sample overlap and UKB as our data source for all outcomes. The primary analytical method utilized was inverse variance weighting, and multiple analytical models were employed to enhance the analysis's reliability and ensure robust results. RESULT: Our investigation revealed that tea consumption was linked to an elevated susceptibility to gastroesophageal reflux disease (GERD). However, there was a lack of substantial evidence suggesting an association between tea intake and Crohn's disease (CD), ulcerative colitis (UC), or non-alcoholic fatty liver disease (NAFLD). CONCLUSIONS: Our study suggests that the excessive consumption of tea may heighten the likelihood of GERD. These results hold potential significance in guiding dietary pattern modifications for individuals with GERD. Furthermore, there may be value in implementing GERD monitoring and preventive measures in populations with elevated tea consumption.

Acute Ammonia Causes Pathogenic Dysbiosis of Shrimp Gut Biofilms.

Acute ammonia exposure has detrimental effects on shrimp, but the underlying mechanisms remain to be fully explored. In the present study, we investigated the impact of acute ammonia exposure on the gut microbiota of the white shrimp Litopenaeus vannamei and its association with shrimp mortality. Exposure to a lethal concentration of ammonia for 48 h resulted in increased mortality in L. vannamei, with severe damage to the hepatopancreas. Ammonia exposure led to a significant decrease in gut microbial diversity, along with the loss of beneficial bacterial taxa and the proliferation of pathogenic Vibrio strains. A phenotypic analysis revealed a transition from the dominance of aerobic to facultative anaerobic strains due to ammonia exposure. A functional analysis revealed that ammonia exposure led to an enrichment of genes related to biofilm formation, host colonization, and virulence pathogenicity. A species-level analysis and experiments suggest the key role of a Vibrio harveyi strain in causing shrimp disease and specificity under distinct environments. These findings provide new information on the mechanism of shrimp disease under environmental changes.

Fork coupling directs DNA replication elongation and termination.

DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify more than 2000 fountain-like structures of chromatin contacts in human and mouse genomes, indicative of coupling of DNA replication forks. Replication fork interaction not only occurs between sister forks but also involves forks from two distinct origins to predetermine replication termination. Termination-associated chromatin fountains are sensitive to replication stress and lead to coupled forks-associated genomic deletions in cancers. These findings reveal the spatial organization of DNA replication forks within the chromatin context.

The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study.

Background: While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods: Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn's disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10-8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Results: Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03-1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03-1.11; (p < 0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03-1.25; p=0.01). Conclusions: The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD.

Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC/Nrf2 axis.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers worldwide. Metastasis is the most common cause of death in patients with CRC. Arenobufagin is an active component of bufadienolides, extracted from toad skin and parotid venom. Arenobufagin reportedly inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in various cancers. However, the mechanism through which arenobufagin inhibits CRC metastasis remains unclear. PURPOSE: This study aimed to elucidate the molecular mechanisms by which arenobufagin inhibits CRC metastasis. METHODS: Wound-healing and transwell assays were used to assess the migration and invasion of CRC cells. The expression of nuclear factor erythroid-2-related factor 2 (Nrf2) in the CRC tissues was assessed using immunohistochemistry. The protein expression levels of c-MYC and Nrf2 were detected by immunoblotting. A mouse model of lung metastasis was used to study the effects of arenobufagin on CRC lung metastasis in vivo. RESULTS: Arenobufagin observably inhibited the migration and invasion of CRC cells by downregulating c-MYC and inactivating the Nrf2 signaling pathway. Pretreatment with the Nrf2 inhibitor brusatol markedly enhanced arenobufagin-mediated inhibition of migration and invasion, whereas pretreatment with the Nrf2 agonist tert­butylhydroquinone significantly attenuated arenobufagin-mediated inhibition of migration and invasion of CRC cells. Furthermore, Nrf2 knockdown with short hairpin RNA enhanced the arenobufagin-induced inhibition of the migration and invasion of CRC cells. Importantly, c-MYC acts as an upstream modulator of Nrf2 in CRC cells. c-MYC knockdown markedly enhanced arenobufagin-mediated inhibition of the Nrf2 signaling pathway, cell migration, and invasion. Arenobufagin inhibited CRC lung metastasis in vivo. Together, these findings provide evidence that interruption of the c-MYC/Nrf2 signaling pathway is crucial for arenobufagin-inhibited cell metastasis in CRC. CONCLUSIONS: Collectively, our findings show that arenobufagin could be used as a potential anticancer agent against CRC metastasis. The arenobufagin-targeted c-MYC/Nrf2 signaling pathway may be a novel chemotherapeutic strategy for treating CRC.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

Reconstruction of Extensive Maxillary Defects Using Flow-Through Fibula Free Flap With Anterolateral Thigh Free Flap.

BACKGROUND: The maxillary defects left unreconstructed or inadequately reconstructed often result in significant functional and esthetic impairments. Adequate reconstruction of extensive maxillary defects requires a sufficient volume of hard and soft tissues. METHODS: A 48-year-old male presenting bilateral extensive maxillary defects underwent secondary reconstruction with a flow-through fibula free flap in combination with an anterolateral thigh free flap. RESULTS: The use of flow-through technique allowed minimizing the problem of limited recipient vessels and the length of free flap vascular pedicle usually encountered in secondary reconstruction. The bilateral maxillary defects were successfully reconstructed, and the postoperative outcomes were uneventful. The patient was satisfied with the treatment outcomes. He is being followed up and was referred to the implantology department for the placement of osseointegrated dental implants. CONCLUSIONS: The flow-through fibula free flap, in combination with the anterolateral thigh free flap, was found reliable and feasible for this case of secondary reconstruction of bilateral maxillary defects. This technique has provided satisfactory functional and esthetic outcomes and effectively improved the patient's self-esteem.

A machine learning algorithm-based predictive model for pressure injury risk in emergency patients: A prospective cohort study.

OBJECTIVES: To construct pressure injury risk prediction models for emergency patients based on different machine learning algorithms, to optimize the best model, and to provide a suitable assessment tool for preventing the occurrence of pressure injuries in emergency patients. METHODS: A convenience sampling was used to select 312 patients admitted to the emergency department of a tertiary care hospital in Tianjin, China, from May 2022 to March 2023, and the patients were divided into a modeling group (n = 218) and a validation group (n = 94) in a 7:3 ratio. Based on the results of one-factor logistic regression analysis in the modeling group, three machine learning models, namely, logistic regression, decision tree, and neural network, were used to establish a prediction model for pressure injury in emergency patients and compare their prediction effects. The optimal model was selected for external validation of the model. RESULTS: The incidence of pressure injuries in emergency patients was 8.97 %, 64.52 % of pressure injuries occurred in the sacrococcygeal region, and 64.52 % were staged as stage 1. Serum albumin level, incontinence, perception, and mobility were independent risk factors for pressure injuries in emergency patients (P < 0.05), and the area under the ROC curve of the three models was 0.944-0.959, sensitivity was 91.8-95.5 %, specificity was 72.2-90.9 %, and the Yoden index was 0.677-0.802; the decision tree was the best model that The area under the ROC curve for the validation group was 0.866 (95 % CI: 0.688-1.000), with a sensitivity of 89.8 %, a specificity of 83.3 %, and a Yoden index of 0.731. CONCLUSIONS: The decision tree model has the best predictive efficacy and is suitable for individualized risk prediction of pressure injuries in emergency medicine specialties, which provides a reference for the prevention and early intervention of pressure injuries in emergency patients.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Parental histone transfer caught at the replication fork.

In eukaryotes, DNA compacts into chromatin through nucleosomes1,2. Replication of the eukaryotic genome must be coupled to the transmission of the epigenome encoded in the chromatin3,4. Here we report cryo-electron microscopy structures of yeast (Saccharomyces cerevisiae) replisomes associated with the FACT (facilitates chromatin transactions) complex (comprising Spt16 and Pob3) and an evicted histone hexamer. In these structures, FACT is positioned at the front end of the replisome by engaging with the parental DNA duplex to capture the histones through the middle domain and the acidic carboxyl-terminal domain of Spt16. The H2A-H2B dimer chaperoned by the carboxyl-terminal domain of Spt16 is stably tethered to the H3-H4 tetramer, while the vacant H2A-H2B site is occupied by the histone-binding domain of Mcm2. The Mcm2 histone-binding domain wraps around the DNA-binding surface of one H3-H4 dimer and extends across the tetramerization interface of the H3-H4 tetramer to the binding site of Spt16 middle domain before becoming disordered. This arrangement leaves the remaining DNA-binding surface of the other H3-H4 dimer exposed to additional interactions for further processing. The Mcm2 histone-binding domain and its downstream linker region are nested on top of Tof1, relocating the parental histones to the replisome front for transfer to the newly synthesized lagging-strand DNA. Our findings offer crucial structural insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance.

Ascertaining sensitive exposure biomarkers of various metal(loid)s to embryo implantation.

Close relationships exist between metal(loid)s exposure and embryo implantation failure (EIF) from animal and epidemiological studies. However, there are still inconsistent results and lacking of sensitive metal(loid) exposure biomarkers associated with EIF risk. We aimed to ascertain sensitive metal(loid) biomarkers to EIF and provide potential biological explanations. Candidate metal(loid) biomarkers were measured in the female hair (FH), female serum (FS), and follicular fluid (FF) with various exposure time periods. An analytical framework was established by integrating epidemiological association results, comprehensive literature searching, and knowledge-based adverse outcome pathway (AOP) networks. The sensitive biomarkers of metal(loid)s along with potential biological pathways to EIF were identified in this framework. Among the concerned 272 candidates, 45 metal(loid)s biomarkers across six time periods and three biomatrix were initially identified by single-metal(loid) analyses. Two biomarkers with counterfactual results according to literature summary results were excluded, and a total of five biomarkers were further determined from 43 remained candidates in mixture models. Finally, four sensitive metal(loid) biomarkers were eventually assessed by overlapping AOP networks information, including Se and Co in FH, and Fe and Zn in FS. AOP networks also identified key GO pathways and proteins involved in regulation of oxygen species biosynthetic, cell proliferation, and inflammatory response. Partial dependence results revealed Fe in FS and Co in FH at their low levels might be potential sensitive exposure levels for EIF. Our study provided a typical framework to screen the crucial metal(loid) biomarkers and ascertain that Se and Co in FH, and Fe and Zn in FS played an important role in embryo implantation.

Association between COVID 19 exposure and expression of malignant pathological features in oral squamous cell carcinoma: A retrospective cohort study.

OBJECTIVES: To analyze the relationship between the clinical and pathological characters of OSCC and COVID 19 exposure. MATERIALS AND METHODS: A retrospective cohort study in patients with OSCC with or without COVID 19 was performed. A total of 200 OSCC patients treated with surgery from 2019 to 2023 were included. Clinical and pathological features were analysed between two groups. Characters with statistical difference were further analysed by performing univariate analysis and logistic regression analysis. RESULTS: The expression of Ki67 (n = 57, 71.3 %, P < 0.001) and CyclinD1 (n = 64, 80 %, P < 0.001) in OSCC with the exposure history of COVID 19 is higher than that in patients never exposed to COVID 19. COVID 19 exposure history is an independent influencing factor for higher expression of Ki67 (OR = 4.04, 95 % CI: 1.87-8.72, P < 0.001) and CyclinD1 (OR = 5.45, 95 % CI: 2.56-11.60, P < 0.001). CONCLUSION: COVID 19 may suggest more invasive malignant biological behavior of cancer cells in OSCC.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Rice responds to Spodoptera frugiperda infestation via epigenetic regulation of H3K9ac in the jasmonic acid signaling and phenylpropanoid biosynthesis pathways.

KEY MESSAGE: This study provided important insights into the complex epigenetic regulatory of H3K9ac-modified genes involved in the jasmonic acid signaling and phenylpropanoid biosynthesis pathways of rice in response to Spodoptera frugiperda infestation. Physiological and molecular mechanisms underlying plant responses to insect herbivores have been well studied, while epigenetic modifications such as histone acetylation and their potential regulation at the genomic level of hidden genes remain largely unknown. Histone 3 lysine 9 acetylation (H3K9ac) is an epigenetic marker widely distributed in plants that can activate gene transcription. In this study, we provided the genome-wide profiles of H3K9ac in rice (Oryza sativa) infested by fall armyworm (Spodoptera frugiperda, FAW) using CUT&Tag-seq and RNA-seq. There were 3269 and 4609 up-regulated genes identified in plants infested by FAW larvae for 3 h and 12 h, respectively, which were mainly enriched in alpha-linolenic acid and phenylpropanoid pathways according to transcriptomic analysis. In addition, CUT&Tag-seq analysis revealed increased H3K9ac in FAW-infested plants, and there were 422 and 543 up-regulated genes enriched with H3K9ac observed at 3 h and 12 h after FAW feeding, respectively. Genes with increased H3K9ac were mainly enriched in the transcription start site (TSS), suggesting that H3K9ac is related to gene transcription. Integrative analysis of both RNA-seq and CUT&Tag-seq data showed that up-expressed genes with H3K9ac enrichment were mainly involved in the jasmonic acid (JA) and phenylpropanoid pathways. Particularly, two spermidine hydroxycinnamoyl transferase genes SHT1 and SHT2 involved in phenolamide biosynthesis were highly modified by H3K9ac in FAW-infested plants. Furthermore, the Ossht1 and Ossht2 transgenic lines exhibited decreased resistance against FAW larvae. Our findings suggest that rice responds to insect herbivory via H3K9ac epigenetic regulation in the JA signaling and phenolamide biosynthesis pathways.

A High-Resolution Imaging Method for Multiple-Input Multiple-Output Sonar Based on Deterministic Compressed Sensing.

Differences between conventional sonar and Multiple-Input Multiple-Output (MIMO) sonar systems arise in achieving high angular and range resolution. MIMO sonar uses Matched Filtering (MF) with well-correlated transmitted signals to enhance spatial resolution by obtaining virtual arrays. However, imperfect correlation characteristics yield high sidelobe values, which hinder accurate target localization in underwater imagery. To address this, a Compressed Sensing (CS) method is proposed by reconstructing echo signals to suppress correlation noise between orthogonal waveforms. A shifted dictionary matrix and a deterministic Discrete Fourier Transform (DFT) measurement matrix are used to multiply received echo signals to yield compressed measurements. A sparse recovery algorithm is applied to optimize signal reconstruction before joint transmit-receive beamforming forms a 2D sonar image in the angle-range domain. Numerical simulations and lake experimental results confirm the effectiveness of the proposed method, by obtaining a lower sidelobe sonar image under sub-Nyquist sampling rates as compared with other approaches.

Bosentan in the treatment of persistent pulmonary hypertension in newborns: a systematic review and meta-analysis.

BACKGROUND: Persistent pulmonary hypertension of the newborn is a life-threatening condition that affects about 1-2 per 1,000 live births worldwide. Bosentan is an oral dual endothelin receptor antagonist that may have a beneficial effect on persistent pulmonary hypertension of the newborn by reducing pulmonary vascular resistance and improving oxygenation. However, its role in persistent pulmonary hypertension of the newborn remains unclear. OBJECTIVES: To systematically evaluate the efficacy and safety of bosentan as an adjuvant therapy for persistent pulmonary hypertension of the newborn in newborns. METHODS: We searched six English and two Chinese databases from their inception to 1 January 2023 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomised controlled trials and retrospective studies that compared bosentan with placebo or other drugs for persistent pulmonary hypertension of the newborn in newborns. We performed a meta-analysis using random-effects models and assessed the risk of bias and heterogeneity in the included studies. RESULTS: We included 10 studies with a total of 550 participants. Bosentan significantly reduced the treatment failure rate (relative risk = 0.25, P < 0.001), pulmonary artery pressure (mean difference = -11.79, P < 0.001), and length of hospital stay (mean difference = -1.04, P = 0.003), and increased the partial pressure of oxygen (mean difference = 10.02, P < 0.001) and blood oxygen saturation (SpO2) (mean difference = 8.24, P < 0.001) compared with a placebo or other drugs. The occurrence of adverse reactions was not significantly different between bosentan and a placebo or other drugs. CONCLUSIONS: Bosentan is effective in the treatment of persistent pulmonary hypertension of the newborn but adverse reactions such as abnormal liver function should be observed when using it.

Predicting the Metal Mixture Toxicity with a Toxicokinetic-Toxicodynamic Model Considering the Time-Dependent Adverse Outcome Pathways.

Chemicals mainly exist in ecosystems as mixtures, and understanding and predicting their effects are major challenges in ecotoxicology. While the adverse outcome pathway (AOP) and toxicokinetic-toxicodynamic (TK-TD) models show promise as mechanistic approaches in chemical risk assessment, there is still a lack of methodology to incorporate the AOP into a TK-TD model. Here, we describe a novel approach that integrates the AOP and TK-TD models to predict mixture toxicity using metal mixtures (specifically Cd-Cu) as a case study. We preliminarily constructed an AOP of the metal mixture through temporal transcriptome analysis together with confirmatory bioassays. The AOP revealed that prolonged exposure time activated more key events and adverse outcomes, indicating different modes of action over time. We selected a potential key event as a proxy for damage and used it as a measurable parameter to replace the theoretical parameter (scaled damage) in the TK-TD model. This refined model, which connects molecular responses to organism outcomes, effectively predicts Cd-Cu mixture toxicity over time and can be extended to other metal mixtures and even multicomponent mixtures. Overall, our results contribute to a better understanding of metal mixture toxicity and provide insights for integrating the AOP and TK-TD models to improve risk assessment for chemical mixtures.