Predictive models for personalized precision medical intervention in spontaneous regression stages of cervical precancerous lesions.

BACKGROUND: During the prolonged period from Human Papillomavirus (HPV) infection to cervical cancer development, Low-Grade Squamous Intraepithelial Lesion (LSIL) stage provides a critical opportunity for cervical cancer prevention, giving the high potential for reversal in this stage. However, there is few research and a lack of clear guidelines on appropriate intervention strategies at this stage, underscoring the need for real-time prognostic predictions and personalized treatments to promote lesion reversal. METHODS: We have established a prospective cohort. Since 2018, we have been collecting clinical data and pathological images of HPV-infected patients, followed by tracking the progression of their cervical lesions. In constructing our predictive models, we applied logistic regression and six machine learning models, evaluating each model's predictive performance using metrics such as the Area Under the Curve (AUC). We also employed the SHAP method for interpretative analysis of the prediction results. Additionally, the model identifies key factors influencing the progression of the lesions. RESULTS: Model comparisons highlighted the superior performance of Random Forests (RF) and Support Vector Machines (SVM), both in clinical parameter and pathological image-based predictions. Notably, the RF model, which integrates pathological images and clinical multi-parameters, achieved the highest AUC of 0.866. Another significant finding was the substantial impact of sleep quality on the spontaneous clearance of HPV and regression of LSIL. CONCLUSIONS: In contrast to current cervical cancer prediction models, our model's prognostic capabilities extend to the spontaneous regression stage of cervical cancer. This model aids clinicians in real-time monitoring of lesions and in developing personalized treatment or follow-up plans by assessing individual risk factors, thus fostering lesion spontaneous reversal and aiding in cervical cancer prevention and reduction.

Functional analysis of tumor-derived immunoglobulin lambda and its interacting proteins in cervical cancer.

BACKGROUND: Immunoglobulin lambda (Igλ) has been reported to be expressed in many normal and tumor tissues and cells. However, the function and clinical significance of tumor-derived Igλ remain unclear. METHODS: The differential expressions of Immunoglobulin Lambda Constants (IGLCs) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) were examined with The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) databases. The effects of IGLCs on patient clinical phenotypes and prognosis were explored via bioinformatics analyses based on the TCGA databases. We used the bioinformatics analyses based on the TCGA and GTEx databases to elucidate the correlations among IGLC expressions, immunomodulator expressions, tumor stemness, and infiltration scores of tumor infiltrating immune cells. Co-immunoprecipitation (Co-IP) and silver staining combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to obtain potential tumor-derived Igλ-interacting proteins. Functional annotation of candidate proteins identified by LC-MS/MS was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The bioinformatics analyses of 7 IGLCs in CESC and normal cervical tissues were performed based on TCGA, GTEx, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Protein-protein interaction (PPI) network was analyzed based on tumor-derived Igλ-interacting proteins in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Immunohistochemistry (IHC) was used to validate the expressions of IGLCs in CESC. RESULTS: We found that the expressions of the majority of IGLCs (IGLC1, IGLC2, IGLC3, IGLC4, IGLC5, IGLC6, and IGLC7) were upregulated in CESC tissues, compared with those in normal cervical tissues. The expressions of IGLC5 and IGLC7 had significant difference in different pathologic metastasis (M), one of tumor, node, and metastasis (TNM) staging system, categories of CESC. Except for disease-free interval (DFI), 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC7) expression levels were positively associated with patient overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) respectively in CESC tissues. 5 IGLC (IGLC1, IGLC2, IGLC3, IGLC6, and IGLC7) expressions were positively correlated with the expressions of a majority of immunomodulators respectively in CESC tissues. Tumor stemness was negatively correlated with the expressions of 4 IGLCs (IGLC1, IGLC2, IGLC3, and IGLC7) respectively in CESC tissues. Except for IGLC4, IGLC5, and IGLC7, 4 IGLC (IGLC1, IGLC2, IGLC3, and IGLC6) expressions were positively correlated with infiltration scores of 6 tumor-infiltrating immune cells (B cell, T cell CD4, T cell CD8, neutrophil, macrophage, and DC). After analyses of the above bioinformatics data of tumor-derived Igλ, Co-IP and LC-MS/MS were used to confirm that 4 proteins (RPL7, RPS3, H1-5, and H1-6) might interact with tumor-derived Igλ in cervical cancer cells. Functional analyses of these candidate proteins showed that they interacted with many proteins and were involved in various cellular biological processes. Finally, IHC was used to further confirm the above bioinformatics results, it was indicated that the expression level of Igλ in cervical adenocarcinoma and cervical squamous cell carcinoma was higher than that in normal cervical tissue. CONCLUSION: This study comprehensively investigated the functions of tumor-derived Igλ and its interacting proteins based on bioinformatics analysis and the potential value of Igλ as a prognostic and therapeutic marker for CESC, providing new direction and evidence for CESC therapy.

Macrophage-specific autophagy-related gene HSPB8 is involved in the macrophage polarization in atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease, as a main cause leading to vascular diseases worldwide. Although increasing studies have focused on macrophages in AS, the exact relating mechanism is still largely unclear. Our study aimed to explore the pathogenic role and diagnostic role of macrophage autophagy related genes (MARGs) in AS. METHODS: All datasets were downloaded from Gene Expression Omnibus database and Human Autophagy Database. The differential expression analysis and cross analysis were performed to identify candidate MARGs. GO and KEGG enrichment analyses were conducted to obtain the functional information. Moreover, we analyzed the correlation between target gene and macrophage polarization in AS. The correlation between target gene and plaque instability, different stages of AS were also analyzed. RESULTS: Compared with normal samples, a total of 575 differentially expressed genes (DEGs) were identified in AS samples. A total of 12 overlapped genes were obtained after cross-analysis of the above 575 DEGs and autophagy related genes (ARGs). Then, 10 MARGs were identified in AS samples, which were significantly enriched in 22 KEGG pathways and 61 GO terms. The expression of HSPB8 was significantly down-regulated in atherosclerotic samples compared with normal samples (with largest fold change). Meanwhile, the proportion of M-CSF in low HSPB8 expression AS group was higher than high expression AS group. Furthermore, the expression of HSPB8 was negatively correlated with most inflammatory factors. CONCLUSION: The downregulation of MARG HSPB8 probably involves in the M2 macrophage polarization in AS samples. HSPB8 is a promising diagnostic marker for AS patients.

Characterization of four mitochondrial genomes of Crambidae (Lepidoptera, Pyraloidea) and phylogenetic implications.

Loxostege turbidalis, Loxostege aeruginalis, Pyrausta despicata, and Crambus perlellus belong to Crambidae, Pyraloidea. Their mitochondrial genomes (mitogenomes) were successfully sequenced. The mitogenomes of L. turbidalis, L. aeruginalis, P. despicata, and C. perlellus are 15 240 bp, 15 339 bp, 15 389 bp, and 15 440 bp. The four mitogenomes all have a typical insect mitochondrial gene order, including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and one A + T rich region (control region). The PCGs are initiated by the typical ATN codons, except CGA for the cox1 gene. Most PCGs terminate with common codon TAA or TAG, the incomplete codon T is found as the stop codon for cox2, nad4, and nad5. Most tRNA genes exhibit typical cloverleaf structure, except trnS1 (AGN) lacking the dihydrouridine (DHU) arm. The secondary structure of rRNA of four mitogenomes were predicted. Poly-T structure and micro-satellite regions are conserved in control regions. The phylogenetic analyses based on 13 PCGs showed the relationships of subfamilies in Pyraloidea. Pyralidae, and Crambidae are monophyletic, respectively. Pyralidae comprises four subfamilies, which form the following topology with high support values: (Galleriinae + ((Pyralinae + Epipaschiinae)+ Phycitinae)). Crambidae includes seven subfamilies and is divided into two lineages. Pyraustinae and Spilomelinae are sister groups of each other, and form the "PS clade." Other five subfamilies (Crambinae, Acentropinae, Scopariinae, Schoenobiinae, and Glaphyriinae) form the "non-PS clade" in the Bayesian inference tree. However, Schoenobiinae is not grouped with the other four subfamilies and located at the base of Crambidae in two maximum likelihood trees.

Exploring the association of dietary patterns with the risk of hypertension using principal balances analysis and principal component analysis.

OBJECTIVE: In the field of nutritional epidemiology, principal component analysis (PCA) has been used extensively in identifying dietary patterns. Recently, compositional data analysis (CoDA) has emerged as an alternative approach for obtaining dietary patterns. We aimed to directly compare and evaluate the ability of PCA and principal balances analysis (PBA), a data-driven method in CoDA, in identifying dietary patterns and their associations with the risk of hypertension. DESIGN: Cohort study. A 24-h dietary recall questionnaire was used to collect dietary data. Multivariate logistic regression analysis was used to analyse the association between dietary patterns and hypertension. SETTING: 2004 and 2009 China Health and Nutrition Survey. PARTICIPANTS: A total of 3892 study participants aged 18-60 years were included as the subjects. RESULTS: PCA and PBA identified five patterns each. PCA patterns comprised a linear combination of all food groups, whereas PBA patterns included several food groups with zero loadings. The coarse cereals pattern identified by PBA was inversely associated with hypertension risk (highest quintile: OR = 0·74 (95 % CI 0·57, 0·95); Pfor trend = 0·037). None of the five PCA patterns was associated with hypertension. Compared with the PCA patterns, the PBA patterns were clearly interpretable and accounted for a higher percentage of variance in food intake. CONCLUSIONS: Findings showed that PBA might be an appropriate and promising approach in dietary pattern analysis. Higher adherence to the coarse cereals dietary pattern was associated with a lower risk of hypertension. Nevertheless, the advantages of PBA over PCA should be confirmed in future studies.

Obesity as a mediator linking sleep-disordered breathing to both impaired fasting glucose and type 2 diabetes.

PURPOSE: To examine whether or not associations between sleep-disordered breathing (SDB) and impaired fasting glucose and type 2 diabetes are mediated by obesity. METHODS: We used cross-sectional data including participants from the Multi-Ethnic Study of Atherosclerosis (MESA). SDB, including obstructive sleep apnea (OSA), hypoxia and sleep fragmentation, was evaluated by polysomnography. Further, five obesity measures related to overall obesity and central obesity were assessed. Mediation analysis was conducted to explore the mediating effect of obesity on these relationships between SDB and impaired fasting glucose and type 2 diabetes. RESULTS: Among 1615 participants, OSA and hypoxia, including apnea hypopnea index (AHI) ≥ 15, percent of total sleep time (TST) with SaO2 < 90% (TST90), oxygen desaturation index (ODI), and lowest oxygen saturation (SaO2), were significantly associated with impaired fasting glucose and type 2 diabetes. In addition, mean SaO2 was also associated with impaired fasting glucose. Mediation analysis showed that these relationships were significantly mediated by all five obesity measures, where central obesity had greater mediating effect than overall obesity. Proportion of mediation of obesity ranged from 21.5 to 62.5% for impaired fasting glucose and 25.85 to 71.6% for type 2 diabetes, with substantial differences found in the subgroup analysis by gender or race/ethnicity. The consistency of the mediating effect was demonstrated across multiple measures of SDB, obesity, and glucose metabolism. CONCLUSION: Obesity, especially central obesity, may play a critical role in the pathway where SDB, including OSA and hypoxia, increases the occurrence of impaired fasting glucose and type 2 diabetes. Weight management is important for patients with SDB to prevent type 2 diabetes.

Association between nutrient patterns and hyperuricemia: mediation analysis involving obesity indicators in the NHANES.

BACKGROUND: Diet has long been hypothesized to play an important role in hyperuricemia, and weight gain is a factor that is strongly associated with the rise in serum urate. We aimed to clarify the mediating role of obesity in the relationship between diet and hyperuricemia and to determine whether a weight-loss diet is an effective way to prevent hyperuricemia. METHODS: This cross-sectional study analysed representative samples of United States (n = 20,081; NHANES 2007-2016) adults. Nutrient patterns were derived with two methods: principal component analysis (PCA) and reduced rank regression (RRR) with obesity. Logistic regression and multivariable linear regression were applied to analyse the association between nutrient patterns in obesity and hyperuricemia. Mediation analyses were used to determine whether four obesity indicators, including body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI) and lipid accumulation product index (LAP), mediated the relationship between nutrient patterns and hyperuricemia. RESULTS: PCA revealed three nutrient patterns (including "Low energy diet", "Lower vitamin A, C, K pattern" and "Vitamin B group"), and only Vitamin B group had a total effect on hyperuricemia. RRR revealed one main nutrient pattern associated with obesity, which was characterized by High fat and low vitamin levels and was significantly associated with hyperuricemia. Mediation analysis showed that obesity mostly or even completely mediated the relationship between nutrient patterns and hyperuricemia, especially traditional obesity indicators, which played a key intermediary effect. The proportions of indirect effects for BMI and WC were as high as 53.34 and 59.69, respectively. CONCLUSIONS: Our findings suggest that the direct effect of diet on hyperuricemia is weak, and obesity plays a critical mediating role in the relationship between diet and hyperuricemia, which confirms that a weight-loss diet such as a "Low fat and high vitamin diet" may be useful in preventing hyperuricemia.

Association between animal source foods consumption and risk of hypertension: a cohort study.

PURPOSE: This study assessed the association between animal source foods (ASF) consumption and hypertension, a recognised risk factor for cardiovascular disease. Adverse effects of red and processed meat (RPM) consumption and beneficial effects of the consumption of dairy products and other ASF have been discovered separately; however, the constrained nature of food intake has been typically ignored. We assessed the effects of substituting RPM and other ASF. METHODS: We followed-up 5394 Chinese adults (age 18-60 years) at baseline using the China Health and Nutrition Survey from 2004 to 2011. Food consumption was assessed using individual-based consecutive 24-h recall and household-based food weighing approaches. Both traditional substitution analysis and substitution analysis based on compositional transformation were used to assess substitution effects. RESULTS: In total, 1267 participants were newly diagnosed with hypertension during the median follow-up time of 6.81 years (range, 2.97-6.99 years). The traditional substitution analysis found that substituting eggs for RPM was associated with a lower risk of hypertension. The compositional transformation substitution analysis revealed that replacing RPM with any other ASF was associated with a lower risk of hypertension; it implemented substitutions of one or many ASF for RPM; it also revealed different substitution effects of RPM and dairy products, and substituting dairy products for RPM was associated with reduced hypertension risks. CONCLUSION: The compositional transformation substitution analysis considers the constrained and relative nature of food consumption. It is a flexible approach to estimating substitution effects using different patterns to obtain personalised estimation effects and provide individualised dietary recommendations.

Anticancer effect evaluation in vitro and in vivo of iridium(III) polypyridyl complexes targeting DNA and mitochondria.

To investigate the antitumor effect of iridium complexes, three iridium (III) complexes [Ir(ppy)2(dcdppz)]PF6 (ppy = 2-phenylpyridine, dcdppz = 11,12-dichlorodipyrido[3,2-a:2',3'-c]phenazine) (Ir1), [Ir(bzq)2(dcdppz)]PF6 (bzq = benzo[h]quinoline) (Ir2) and [Ir(piq)2(dcdppz)]PF6 (piq = 1-phenylisoquinoline) (Ir3) were synthesized and characterized. Geometry optimization, molecular dynamics simulation and docking studies have been performed to further explore the antitumor mechanism. The cytotoxicity of Ir1-3 toward cancer cells was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The localization of complexes Ir1-3 in the mitochondria, intracellular accumulation of reactive oxygen species (ROS) levels, the changes of mitochondrial membrane potential and morphological changes in apoptosis were investigated. Flow cytometry was applied to quantify fluorescence intensity and determine cell cycle distribution. Western blotting was used to detect the expression of apoptosis-related proteins. The anti-tumor effect of Ir1 in vivo was evaluated. The results showed that Ir1-3 had high cytotoxicity to most tumor cells, especially to SGC-7901 cells with a low IC50 value. Ir1-3 can increase the intracellular ROS levels, reduce the mitochondrial membrane potential. Additionally, the complexes induce an increase of apoptosis-related protein expression, enhance the percentage of apoptosis. The complexes inhibit the cell proliferation at G0/G1 phase. The results obtained from antitumor in vivo indicate that Ir1 can significantly inhibit the growth of tumors with an inhibitory rate of 54.08%. The docking studies show that complexes Ir1-3 interact with DNA through minor-groove intercalation, which increases the distance of DNA base pairs, leading to a change of DNA helix structure. These experimental and theoretical findings indicate that complexes Ir1-3 can induce apoptosis in SGC-7901 cells through the mitochondrial dysfunction and DNA damage pathways, and then exerting anti-tumor activity in vitro and vivo.

Fab fragment glycosylated IgG may play a central role in placental immune evasion.

STUDY QUESTION: How does the placenta protect the fetus from immune rejection by the mother? SUMMARY ANSWER: The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities. WHAT IS KNOWN ALREADY: The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother. aIgG in serum is increased during pregnancy and returns to the normal range after giving birth. aIgG can react to antigens to form immune complexes which do not cause a subsequent immune effector reaction, including fixing complements, inducing cytotoxicity and phagocytosis, and therefore has been called 'blocking antibody'. STUDY DESIGN, SIZE, DURATION: Eighty-eight human placentas, four trophoblast cell lines (TEV-1, JAR, JEG and BeWo), primary culture of human placental trophoblasts and a gene knock-out mouse model were investigated in this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The general approach included the techniques of cell culture, immunohistochemistry, in situ hybridization, immuno-electron microscopy, western blot, quantitative PCR, protein isolation, glycosylation analysis, enzyme digestion, gene sequencing, mass spectrophotometry, laser-guided microdissection, enzyme-linked immunosorbent assay, pulse chase assay, double and multiple staining to analyze protein and DNA and RNA analysis at the cellular and molecular levels. MAIN RESULTS AND THE ROLE OF CHANCE: Three major discoveries were made: (i) placental trophoblasts and endothelial cells are capable of producing IgG, a significant portion of which is aberrantly glycosylated at one of its Fab arms to form aIgG; (ii) the asymmetrically glycosylated IgG produced by trophoblasts and endothelial cells can react to immunoglobulin molecules of human, rat, mouse, goat and rabbit at the Fc portion; (iii) asymmetrically glycosylated IgG can react to certain leukocytes in the membrane and cytoplasm, while symmetric IgG from the placenta does not have this property. LIMITATIONS, REASONS FOR CAUTION: Most of the experiments were performed in vitro. The proposed mechanism calls for verification in normal and abnormal pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: This study identified a number of new phenomena suggesting that aIgG produced by the placenta would be able to react to detrimental antibodies and leukocytes and interfere with their immune reactions against the placenta and the fetus. This opens a new dimension for further studies on pregnancy physiology and immunology. Should the mechanism proposed here be confirmed, it will have a direct impact on our understanding of the physiology and pathology of human reproduction and offer new possibilities for the treatment of many diseases including spontaneous abortion, infertility and pre-eclampsia. It also sheds light on the mechanism of immune evasion in general including that of cancer.

A morphologic and semi-quantitative technique to analyze synthesis and release of specific proteins in cells.

BACKGROUND: With the rapid advancement of cell biology, the evaluation of a given protein's synthesis and release in cells becomes critical. However, up to now there has been no technique available to morphologically visualize and measure a newly synthesized protein in cells, nor can we measure the protein's release from the cells. RESULTS: In this study, we developed a set of assays combining pulse chase amino acid substitution, non-radioactive labeling, and immunofluorescence co-localization to visualize newly synthesized proteins in individual cells and then to detect their release using modified ELISA. We demonstrated the synthesis and release of Bcl-2, MMP-9, and immunoglobulin G (IgG) in a human trophoblast cell line, of which the last finding has not been reported previously. CONCLUSIONS: This new technique offers a powerful tool to evaluate the dynamics of the synthesis and release of target proteins in individual cultured cells with wide applications in genetic and protein analysis.

Heterlimnius luyashanensis sp. n. and Zaitzevia triangularis sp. n. from Shanxi Province, China (Coleoptera: Elmidae).

Two new species, Heterlimnius luyashanensis sp. n. and Zaitzevia triangularis sp. n. are described from Shanxi Province, China. The genus Heterlimnius Hinton, 1935 and Zaitzevia Champion, 1923 are reported from Shanxi Province for the first time. Heterlimnius luyashanensis sp. n. belonging to the Heterlimnius trachys species group has the following characteristics: 1. anterior margin of pronotum strongly produced anteriad; 2. median longitudinal sulcus of pronotum extends from basal 0.3 to 0.8. Zaitzevia triangularis sp. n. has a larger body size and a triangular apex of penis.

The mediating effect of 24-h time-use behaviors on the relationship between depression and mortality: A compositional mediation analysis for survival outcomes.

BACKGROUND: A compositional mediation model of survival outcomes was established to explore whether 24-h time-use behaviors mediate the relationship between depression and mortality. METHODS: 4137 adults from the National Health and Nutrition Examination Survey (NHANES 2005-2006) were followed up to 2019. Cox proportional hazards regression model was used to estimate the total effect of depression on mortality. Compositional data analysis was used to examine the relationship between 24-h time-use compositions and mortality. Furthermore, we constructed a compositional mediation model for survival outcomes to investigate the mediating effect of 24-h time-use behaviors on depression and mortality. RESULTS: Compared with participants without depression, depressive patients had a significantly higher risk of overall mortality (HR = 1.49, 95 % CI: 1.25,1.79), cardiovascular disease -specific mortality (HR =1.89, 95 % CI: (1.37,2.63)) and mortality from causes other than cardiovascular disease or cancer (HR = 1.62, 95 % CI: (1.25,2.08)). Physical activity, especially moderate-to-vigorous physical activity, significantly mediated the relationship between depression and all-cause and CVD-specific mortality. LIMITATIONS: Despite being a cohort study, the exposure and mediatiors were measured at the baseline. Further research is necessary to require a temporal order between the exposure and mediating variables. CONCLUSIONS: Our findings indicate that 24-h time-use behaviors link depression to mortality. In particular, increasing the time spent on physical activity can reduce the risk of death in patients with depression. This finding provides potential interventions for reducing the risk of death in patients with depression.

An Inhibitor-Loaded LDH- and MOF-Based Bilayer Hybrid System for Active Corrosion Protection of Aluminum Alloys.

A novel inhibitor-loaded bilayer hybrid system based on the LDH inner layer and MOF outer layer is designed on an aluminum alloy 2A12 surface to improve corrosion performance. The hybrid film system covers the inherent cavities and intercrystalline defects of the LDH film using the affinity between the LDH and the MOF compounds. The results demonstrate that the LDH-inhI precursor film is entirely covered by new Zn-based MOF microrods. The LDH-inhI precursor film is partially dissolved and recrystallized in favor of MOF crystal growth to strengthen the binding adhesion between LDH and MOF films. The LDH-inhI/MOF-inhII bilayer film shows significantly enhanced corrosion resistance through the synergistic action of LDH and MOF nanocontainers doped with different corrosion inhibitors (vanadates, 2,5-furandicarboxylic acid, and benzotriazoles). Due to the multiple loadings of the MOF film and the sustained-release of the LDH film, this method provides an effective approach to developing new anticorrosion systems and enhancing both the barrier ability and active corrosion protection performance of LDH-based conversion treatments.

Real-world effectiveness of influenza vaccine against medical-attended influenza infection during 2023/24 season in Ili Kazakh Autonomous Prefecture, China: A test-negative, case-control study.

In the post-COVID-19 pandemic era, influenza virus infections continuously lead to a global disease burden. Evaluating vaccine effectiveness against influenza infection is crucial to inform vaccine design and vaccination strategy. In this study, we recruited 1120 patients with influenza-like illness (ILI) who attended fever clinics of 4 sentinel hospitals in the Ili Kazakh Autonomous Prefecture, Xinjiang Uygur Autonomous Region, China, from January 1 to April 7, 2024. Using a test-negative design, we estimated influenza vaccine effectiveness (VE) of 54.7% (95% CrI: 23.7, 73.1) against medical-attended influenza infection, with 62.3% (95% CrI: 29.3, 79.8) against influenza A, and 51.2% (95% CrI: 28.7, 83.0) against influenza B. Despite the moderate VE estimated in this study, influenza vaccination remains the most important approach to prevent influenza at the community level.

The Current Status of Antisense Gene Therapies for Bacteria-caused Diseases Challenges and Opportunities.

Bacteria-caused diseases continue to pose a serious threat to human health. The current situation of overused antibiotics against those diseases further spurs and exacerbates the ever-increasing drug resistance problems, which really leaves us very few options to combat those nasty bugs. Gene therapies based on the antisense oligonucleotide, though developed more than 40 years ago, did not reform the current treatments as originally expected. Along with the advances of new delivery technologies, this old field thrives again. In addition, newly evolving gene-editing tools based on the CRISPR-Cas system shed new light on this old field, bringing a breeze of hope to gene therapies for bacteria-caused diseases. As a fast-growing field, we strive to summarize in this review the recent progress in using gene therapies in those areas, analyze the potential challenges or problems from using antisense or gene-editing tools for targeting bacterial diseases and seek to explore any potential solutions to the current dilemmas. As a short review, we will focus our discussion mainly on antisense oligonucleotide-based gene therapies while briefly touching on the CRISPR-Cas based ones as the latter is just beginning to get more attention for application in the prokaryotic kingdom.

The complete mitochondrial genome of the butterfly Apatura metis (Lepidoptera: Nymphalidae).

As an important pest in the Slender Leaved Willow (Salix alba), Apatura metis is called Freyer's purple emperor, and its mitochondrial genome is 15,236 bp long. The encoded genes for 22 tRNA genes, two ribosomal RNA (rrnL and rrnS) genes, and 13 protein-coding genes (PCGs), and a control region in the A. metis mitochondria are highly homologous to other lepidopteran species. The mitochondrial genome of A. metis is biased toward a high A + T content (A + T = 80.5%). All protein-coding genes, except for COI begins with the CGA codon as observed in other lepidopterans, start with a typical ATN initiation codon. All tRNAs show the classic clover-leaf structure, except that the dihydrouridine (DHU) arm of tRNA(Ser(AGN)) forms a simple loop. The A. metis A + T-rich region contains some conserved structures including a structure combining the motif 'ATAGA' and 19 bp poly (T) stretch, which is similar to those found in other lepidopteran mitogenomes. The phylogenetic analyses of lepidopterans based on mitogenomes sequences demonstrate that each of the six superfamilies is monophyletic, and the relationship among them is (((Noctuoidea + (Geometroidea + Bombycoidea)) + Pyraloidea) + Papilionoidea) + Tortricoidea. In Papilionoidea group, our conclusion argues that ((Lycaenidae + Pieridae) + Nymphalidae) + Papilionidae.

Identification of m6A-Related lncRNA to Predict the Prognosis of Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In the past decades, HCC treatment has achieved great progress; however, the overall prognosis remains poor. Therefore, it is the need of the hour to identify new prognostic biomarkers which can advance our understanding related to the underlying molecular mechanism of adverse prognosis and apply them to clinical work in prognosis prediction. In the present study, data of 576 HCC patients and 292 normal control cases from TCGA and ICGC databases were enrolled to our bioinformatic analysis. SNHG1 and SNHG3 were identified as overlapping genes in TCGA and ICGC databases using Pearson correlation analysis and univariate Cox regression analysis. Further, we used the median of the SNHG1 and SNHG3 expression values as the cutoff values to define the HCC patient groups with high or low expression level. The subsequent analysis revealed that abnormal high expression of SNHG1 or SNHG3 affected the immune infiltration patterns and the crosstalk among immune cells. Moreover, high expression of SNHG1 or SNHG3 resulted in drug resistant to AKT inhibitor VII, bexarotene, bicalutamide, dasatinib, erlotinib, and gefitinib. In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Further, we found significant relation between the aberrant upregulation of SNHG1 and SNHG3 in tumor grade and stage. We established a nomogram to systematically predict the 5- and 8-year overall survival of liver cancer patients with good accuracy. Finally, the in vitro assays suggest that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells.

The role of lipid traits in mediating the effect of body mass index on serum urate.

Objective: To explore whether total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride (TG) are mediators in the pathway of body mass index (BMI) on serum urate and determine the proportion of the mediation effect. Methods: This study used observational and two-sample Mendelian randomization (MR) analyses to explore the mediation effects of TC, HDL, LDL, and TG in the pathway of BMI on serum urate. We determined the size and the extent to which these lipids mediate any effect of BMI on serum urate. Results: Observational analysis results showed that HDL and TG can partially explain the association of BMI on serum urate, and the proportion of mediation effect was 10.2% and 8.9%, respectively. MR results demonstrated that TG has a causal effect on serum urate (ß = 0.22, 95% CI: 0.15, 0.29; p = 2.28×10-10.) and its proportion of mediation effect was 14.1%. TC, HDL, and LDL are not the mediators in the pathway of BMI on serum urate in MR estimates. Conclusion: To a certain extent, TG mediates the effect of BMI on serum urate, and the risk of gout may be reduced by controlling both BMI and TG.

Corrigendum: PHLDA1 Suppresses TLR4-Triggered Proinflammatory Cytokine Production by Interaction With Tollip.

[This corrects the article DOI: 10.3389/fimmu.2022.731500.].