Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection.

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

[Identification and expression profiling of SAPK gene family members in Dendrobium officinale].

To investigate the potential roles of stress-activated protein kinase (SAPK) gene family members in Dendrobium officinale, we employed multiple bioinformatics methods to identify the members of this family. The physicochemical properties, chromosomal localization, phylogenetic relationship, gene structure, and cis-acting elements of each D. officinale SAPK (DoSAPK) member were analyzed. In addition, their expression profiles in different tissues and under the low-temperature or salt stress treatment were determined by real-time fluorescence quantitative PCR. The results showed that D. officinale carried eight DoSAPK family members, which belonged to three groups (groups Ⅰ, Ⅱ, and Ⅲ). These genes were located on seven chromosomes, and there were two pairs of genes with replication. The DoSAPK members within the same group had similar gene structures, conserved motifs, and secondary structures. The cis-acting elements in the promoter regions of DoSAPK genes included abundant hormone and stress response elements. DoSAPK family members presented tissue-specific expression in D. officinale. Furthermore, they were differentially expressed under the low-temperature or salt stress treatment, which suggested that they might be involved in the responses to low-temperature and salt stress. Intriguingly, DoSAPK1 might play a role in the abiotic stress responses. The results laid a foundation for in-depth study of the members and roles of the DoSAPK gene family.

Mitochondrial deoxyguanosine kinase is required for female fertility in mice.

Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. In this study, we find that Dguok knockout results in female infertility. Mechanistically, DGUOK deficiency hinders ovarian development and oocyte maturation. Moreover, DGUOK deficiency in oocytes causes a significant reduction in mitochondrial DNA copy number and abnormal mitochondrial dynamics and impairs germinal vesicle breakdown. Only few DGUOK-deficient oocytes can extrude their first polar body during in vitro maturation, and these oocytes exhibit irregular chromosome arrangements and different spindle lengths. In addition, DGUOK deficiency elevates reactive oxygen species levels and accelerates oocyte apoptosis. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate DGUOK as a potential marker for the diagnosis of female infertility.

The gut-joint axis: Genetic evidence for a causal association between gut microbiota and seropositive rheumatoid arthritis and seronegative rheumatoid arthritis.

This study aimed to assess the causal relationship between GM and RA (seropositive RA and seronegative RA). A two-sample Mendelian randomization (MR) analysis was performed to assess the causality of GM on seropositive RA and seronegative RA. GM's genome-wide association study (GWAS) was used as the exposure, whereas the GWAS datasets of seropositive RA and seronegative RA were the outcomes. The primary analysis approach was used as inverse-variance weighted (IVW), followed by 3 additional MR methods (MR-Egger, weighted median, and weighted mode). Cochran's Q test was used to identify heterogeneity. The MR-Egger intercept test and leave-one-out analyses were used to assess horizontal pleiotropy. All statistical analyses were performed in R software. We discovered that Alloprevotella (IVW OR 0.84, 95% CI 0.71-0.99, P = .04) and Christensenellaceae R 7 group (IVW OR 0.71, 95% CI 0.52-0.99, P = .04) were negatively correlated with seropositive RA, Ruminococcaceae UCG002 (IVW OR 1.30, 95% CI 1.10-1.54, P = .002) was positively associated with seropositive RA. Actinomyces (IVW OR 0.73, 95% CI 0.54-0.99, P = .04), Christensenellaceae R 7 group (IVW OR 0.62, 95% CI 0.39-0.97, P = .04), Terrisporobacter (IVW OR 0.64, 95% CI 0.44-0.93, P = .02), Lactobacillales (IVW OR 0.65, 95% CI 0.47-0.90, P = .01) were negatively correlated with seronegative RA. The present MR analysis showed a protective effect of Alloprevotella and Christensenellaceae R 7 group and a potentially anti-protective effect of Ruminococcaceae UCG002 on seropositive RA; and a protective effect of Actinomyces, Christensenellaceae R 7 group, Terrisporobacter, and Lactobacillales on seronegative RA. Further experimental studies and randomized controlled trials are needed to validate these findings.

Association between primary Sjögren's syndrome and gut microbiota disruption: a systematic review and meta-analysis.

Evidence of gut microbiota disruption for numerous autoimmune diseases has accumulated. Recently, the relationship between the microbiota and primary Sjögren's disease has been increasingly investigated but has yet to be systematically elucidated. Therefore, a meta-analysis of publications dealing on topic was conducted. Case-control studies comparing primary Sjögren's syndrome patients and healthy controls (HCs) were systematically searched in nine databases from inception to March 1, 2023. The primary result quantitatively evaluated in this meta-analysis was the α-diversity. The secondary results qualitatively extracted and analyzed were the ß-diversity and relative abundance. In total, 22 case-control studies covering 915 pSS patients and 2103 HCs were examined. The quantitative analysis revealed a slight reduction in α-diversity in pSS patients compared to HCs, with a lower Shannon-Wiener index (SMD = - 0.46, (- 0.68, - 0.25), p < 0.0001, I2 = 71%), Chao1 richness estimator (SMD = - 0.59, (- 0.86, - 0.32), p < 0.0001, I2 = 81%), and ACE index (SMD = - 0.92, (- 1.64, - 0.19), p = 0.01, I2 = 86%). However, the Simpson index (SMD = 0.01, (- 0.43, 0.46) p = 0.95, I2 = 86%) was similar in the two groups. The ß-diversity significantly differed between pSS patients and HCs. Variations in the abundance of specific microbes and their metabolites and potential functions contribute to the pSS pathogenesis. Notably, the abundance of the phylum Firmicutes decreased, while that of Proteobacteria increased. SCFA-producing microbes including Ruminococcaceae, Lachnospiraceae, Faecalibacterium, Butyricicoccus, and Eubacterium hallii were depleted. In addition to diversity, the abundances of some specific microbes were related to clinical parameters. According to this systematic review and meta-analysis, gut microbiota dysbiosis, including reduced diversity, was associated with proinflammatory bacterium enrichment and anti-inflammatory bacterium depletion in pSS patients. Further research on the relationship between the gut microbiota and pSS is warranted.

Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single-arm meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. SETTING AND DESIGN: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random-effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. PARTICIPANTS: Patients with ABR tests receiving chloral hydrate sedation. MAIN OUTCOME MEASURES: The pooled sedation failure rate and the pooled incidence of adverse events. RESULTS: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p < .01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p < .01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p < .01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p < .01]. CONCLUSIONS: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted.

Identification of Key Genes for Pyroptosis-Induced Salivary Gland Inflammation in Sjogren's Syndrome Based on Microarray Data and Immunohistochemistry Analysis.

Purpose: Sjogren's Syndrome (SS) is a systemic autoimmune disease primarily characterized by dysfunction of the exocrine glands. Research into the etiology and pathogenesis of salivary glands (SG) inflammation of SS is very limited. The aim of this study was to identify potential pyroptosis-related genes in SG inflammation through bioinformatics analysis and validation of the SG in SS. Methods: GSE157159 dataset and GSE159574 dataset were downloaded from Gene Expression Omnibus (GEO). Differentially Expressed Genes (DEGs) analysis was used to screen DEGs from SS and non-SS SG samples. Pyroptosis-related genes were obtained from GeneCards. After intersecting DEGs with pyroptosis-related genes, the pyroptosis-related DEGs in SS were obtained. Subsequently, ClueGO enrichment analysis, Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, Protein-protein Interaction (PPI), and identification and co-expression analysis of hub genes were performed. Subsequently, we collected SG samples from 17 SS patients and 17 non-SS patients and validated the expression of two hub genes (GZMA, GBP1) and characteristic genes (GSDMD) of pyroptosis through immunohistochemistry. The accuracy of hub genes as biomarkers for predicting SS was evaluated by receiver operating characteristic (ROC) curve. Results: 834 DEGs were selected from the GSE157159 dataset, and a total of 39 pyroptosis-related DEGs were obtained. Functional analysis showed that these DEGs were significantly enriched in some inflammatory signaling pathways. Through the intersection of seven algorithms proposed by CytoHubba and validation using the GSE159574 dataset, 11 hub genes were identified, including IL18, AIM2, CCL5, CD274, GBP1, GBP5, GZMA, GZMB, TLR8, TNFS13B, and ICAM1. Finally, the results of immunohistochemistry showed that GSDMD, GZMA and GBP1 were all significantly highly expressed in SG from SS. And ROC analysis showed a high combined diagnostic value of the 3 genes (AUC=0.8858). Conclusion: Our study revealed enhanced levels of pyroptosis in the SS. GZMA and GBP1 were identified as candidate genes for pyroptosis-induced inflammation of the SG in SS, which may be used as biomarkers or potential therapeutic targets for SS.

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren's syndrome.

This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1ß, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1ß), providing experimental evidence for its clinical application in treating SS.

Comparison of wideband acoustic immittance in Chinese infants under three months of age with normal and abnormal middle ear function.

OBJECTIVES: This study aims to compare the characteristics of Wideband Acoustic Immittance (WAI) in Chinese infants under three months of age, with either normal or abnormal middle ear function. METHODS: We recruited 98 infants with either normal or abnormal middle ear function, and subsequently divided them into four groups based on their middle ear function and chronological age. The absorbances at tympanometric peak pressure (TPP) were collected across 1/3rd octave frequencies ranging from 226 to 8000 Hz. RESULTS: Among infants with normal middle ear function, no significant differences were observed concerning ear laterality. However, significant differences were noted at 3364 Hz and 4000 Hz with respect to age. For infants with either normal or abnormal middle ear function, we found significant differences at the majority of frequencies. Additionally, the receiver operating characteristic (ROC) curves and maxima Youden index indicated that absorbances at 1682 Hz and 1297 Hz could be employed to evaluate the middle ear function of infants at 1 and 2 months of age. CONCLUSION: This study demonstrates that WAI holds promise as a valuable tool for assessing the middle ear condition of infants at 1 and 2 months of age. Infants aged 1 and 2 years, having absorbance values equal to or greater than 0.7470 at 1682 Hz and 0.6775 at 1297 Hz respectively, may indicate normal middle ear function. Furthermore, it underscores the necessity of establishing ethnicity- and age-specific norms for WAI in infants under 3 months of age.

Genome-wide DNA methylation sequencing reveals epigenetic features and potential biomarkers of Sjögren syndrome.

AIM: Sjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease. METHODS: Whole-genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network-based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves. RESULTS: We identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (HLA) class I, ADAR, and OAS2 was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS. CONCLUSION: Clinical sample validation suggested that HLA class I, ADAR, and OAS2 might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.

Single-cell multi-omics sequencing reveals chromosome copy number inconsistency between trophectoderm and inner cell mass in human reconstituted embryos after spindle transfer.

STUDY QUESTION: Is the chromosome copy number of the trophectoderm (TE) of a human reconstituted embryos after spindle transfer (ST) representative of the inner cell mass (ICM)? SUMMARY ANSWER: Single-cell multi-omics sequencing revealed that ST blastocysts have a higher proportion of cell lineages exhibiting intermediate mosaicism than conventional ICSI blastocysts, and that the TE of ST blastocysts does not represent the chromosome copy number of ICM. WHAT IS KNOWN ALREADY: Preimplantation genetic testing for aneuploidy (PGT-A) assumes that TE biopsies are representative of the ICM, but the TE and ICM originate from different cell lineages, and concordance between TE and ICM is not well-studied, especially in ST embryos. STUDY DESIGN, SIZE, DURATION: We recruited 30 infertile women who received treatment at our clinic and obtained 45 usable blastocysts (22 from conventional ICSI and 23 reconstituted embryos after ST). We performed single-cell multi-omics sequencing on all blastocysts to predict and verify copy number variations (CNVs) in each cell. We determined the chromosome copy number of each embryo by analysing the proportion of abnormal cells in each blastocyst. We used the Bland-Altman concordance and the Kappa test to evaluate the concordance between TE and ICM in the both groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public tertiary hospital in China, where all the embryo operations, including oocytes retrieval, ST, and ICSI, were performed in the embryo laboratory. We utilized single-cell multi-omics sequencing technology at the Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, to analyse the blastocysts. Transcriptome sequencing was used to predict the CNV of each cell through bioinformatics analysis, and the results were validated using the DNA methylation library of each cell to confirm chromosomal normalcy. We conducted statistical analysis and graphical plotting using R 4.2.1, SPSS 27, and GraphPad Prism 9.3. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the volunteers, the blastocyst morphology, and the developmental ratewere similar in ST and ICSI groups. The blastocysts in the ST group had some additional chromosomal types that were prone to variations beyond those enriched in the blastocysts of the ICSI group. Finally, both Bland-Altman concordance test and kappa concordancetest showed good chromosomal concordance between TE and ICM in the ICSI blastocysts (kappa = 0.659, P < 0.05), but not in ST blastocysts (P = 1.000), suggesting that the TE in reconstituted embryos is not representative of ICM. Gene functional annotation (GO and KEGG analyses) suggests that there may be new or additional pathways for CNV generation in ST embryos compared to ICSI embryos. LIMITATIONS, REASONS FOR CAUTION: This study was mainly limited by the small sample size and the limitations of single-cell multi-omics sequencing technology. To select eligible single cells, some cells of the embryos were eliminated or not labelled, resulting in a loss of information about them. The findings of this study are innovative and exploratory. A larger sample size of human embryos (especially ST embryos) and more accurate molecular genetics techniques for detecting CNV in single cells are needed to validate our results. WIDER IMPLICATIONS OF THE FINDINGS: Our study justifies the routine clinical use of PGT-A in ICSI blastocysts, as we found that the TE is a good substitute for ICM in predicting chromosomal abnormalities. While PGT-A is not entirely accurate, our data demonstrate good clinical feasibility. This trial was able to provide correct genetic counselling to patients regarding the reliability of PGT-A. Regarding ST blastocysts, the increased mosaicism rate and the inability of the TE to represent the chromosomal copy number of the ICM are both biological characteristics that differentiate them from ICSI blastocysts. Currently, ST is not used clinically on a large scale to produce blastocysts. However, if ST becomes more widely used in the future, our study will be the first to demonstrate that the use of PGT-A in ST blastocysts may not be as accurate as PGT-A for ICSI blastocysts. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key R&D Program of China (2018YFA0107601) and the National Key R&D Program of China (2018YFC1003003). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Identification of key genes in salivary gland in Sjögren's syndrome complicated with Hashimoto thyroiditis: Common pathogenesis and potential diagnostic markers.

The coexistence of Sjögren's syndrome (SS) and Hashimoto thyroiditis (HT) has been confirmed, but the common mechanism of its co-occurrence remains unknown. This study aims to further explore the underlying mechanism and biomarkers for the co-occurrence of SS and HT. The Gene Expression Omnibus databases were used to obtain gene expression profiles for SS (GSE127952 and GSE23117) and HT (GSE29315 and GSE138198). Following identifying SS and HT's shared differentially expressed genes, functional annotation, protein-protein interaction network creation, and module assembly were performed to discover hub genes. H&E staining and immunohistochemistry were performed to validate the expression of the hub genes in salivary glands. Finally, the receiver operating characteristic (ROC) curve was utilized to assess the discrimination of the hub genes as biomarkers in predicting SS, this study applied CIBERSORTx to analyze the immune infiltration in SS and HT in addition. A total of 48 common differentially expressed genes (48 upregulated genes and 0 downregulated genes) were chosen for further investigation. We analyzed the expression and function of PTPRC, CD69, IKZF1, and lymphocyte cytosolic protein 2 via H&E, immunohistochemistry, and ROC analysis. The 4 hub genes were mainly enriched in the T-cell receptor signaling pathway. We then evaluated and verified the diagnosis value of 4 hub genes in clinical minor labial gland biopsy of SS with HT, SS without HT, and non-SS. ROC analysis revealed that the 4 hub genes had a strong diagnostic value. Our study showed the common pathogenesis of SS and HT. These hub genes and diagnostic models may put forward some new insights for diagnosing and treating SS complicated with HT.

Serum Metabolomics Analysis of Skin-Involved Systemic Lupus Erythematosus: Association of Anti-SSA Antibodies with Photosensitivity.

Purpose: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis. Patients and Methods: The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies. Results: We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody. Conclusion: This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.

The Dynamics of Gene Expression Unraveling the Immune Response of Macrobrachium rosenbergii Infected by Aeromonas veronii.

To further investigate the immune response of Macrobrachium rosenbergii against Aeromonas veronii, comparative transcriptomic analyses of the M. rosenbergii hepatopancreas were conducted on challenge and control groups at 6, 12, and 24 h post-infection (hpi), independently. A total of 51,707 high-quality unigenes were collected from the RNA-seq data, and 8060 differentially expressed genes (DEGs) were discovered through paired comparisons. Among the three comparison groups, a KEGG pathway enrichment analysis showed that 173 immune-related DEGs were considerably clustered into 28 immune-related pathways, including the lysosome, the phagosome, etc. Moreover, the expression levels of the four key immune-related genes (TOLL, PAK1, GSK3ß, and IKKα) were evaluated at various stages following post-infection in the hepatopancreas, hemolymph, and gills. Both PAK1 and GSK3ß genes were highly up-regulated in all three tissues at 6 hpi with A. veronii; TOLL was up-regulated in the hepatopancreas and hemolymph but down-regulated in the gill at 6 hpi, and IKKα was up-regulated in hemolymph and gill, but down-regulated in the hepatopancreas at 6 hpi. These findings lay the groundwork for understanding the immune mechanism of M. rosenbergii after contracting A. veronii.

Whole-genome bisulfite sequencing identified the key role of the Src family tyrosine kinases and related genes in systemic lupus erythematosus.

BACKGROUND: As a multisystemic autoimmune illness, the basic mechanisms behind the pathophysiology of systemic lupus erythematosus (SLE) remain poorly understood. OBJECTIVE: We aimed to investigate the possible significance of SLE's DNA methylation and gain further insight into potential SLE-related biomarkers and therapeutic targets. METHODS: We used whole genome bisulfite sequencing (WGBS) method to analyze DNA methylation in 4 SLE patients and 4 healthy people. RESULTS: 702 differentially methylated regions (DMRs) were identified, and 480 DMR-associated genes were annotated. We found the majority of the DMR-associated elements were enriched in repeat and gene bodies. The top 10 hub genes identified were LCK, FYB, PTK2B, LYN, CTNNB1, MAPK1, GNAQ, PRKCA, ABL1, and CD247. Compared to the control group, LCK and PTK2B had considerably decreased levels of mRNA expression in the SLE group. Receiver operating characteristic (ROC) curve suggested that LCK and PTK2B may be potential candidate biomarkers to predict SLE. CONCLUSIONS: Our study improved comprehension of the DNA methylation patterns of SLE and identified potential biomarkers and therapeutic targets for SLE.

MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort.

BACKGROUND: Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms. METHODS: A case-control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining. RESULTS: The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000-1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017-1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018-1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele. CONCLUSION: The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3'UTR of IKBA and activating NF-κB inflammatory pathways.

Integrated Transcriptomic and Metabolomic Analyses Reveal Low-Temperature Tolerance Mechanism in Giant Freshwater Prawn Macrobrachium rosenbergii.

Water temperature, as an important environmental factor, affects the growth and metabolism of aquatic animals and even their survival. The giant freshwater prawn (GFP) Macrobrachium rosenbergii is a kind of warm-water species, and its survival temperature ranges from 18 °C to 34 °C. In this study, we performed transcriptomic and metabolomic analyses to clarify the potential molecular mechanism of responding to low-temperature stress in adult GFP. The treatments with low-temperature stress showed that the lowest lethal temperature of the GFP was 12.3 °C. KEGG enrichment analyses revealed that the differentially expressed genes and metabolites were both enriched in lipid and energy metabolism pathways. Some key genes, such as phosphoenolpyruvate carboxykinase and fatty acid synthase, as well as the content of the metabolites dodecanoic acid and alpha-linolenic acid, were altered under low-temperature stress. Importantly, the levels of unsaturated fatty acids were decreased in LS (low-temperature sensitive group) vs. Con (control group). In LT (low-temperature tolerant group) vs. Con, the genes related to fatty acid synthesis and degradation were upregulated to cope with low-temperature stress. It suggested that the genes and metabolites associated with lipid metabolism and energy metabolism play vital roles in responding to low-temperature stress. This study provided a molecular basis for the selection of a low-temperature tolerant strain.

Allocation of emergency medical resources for epidemic diseases considering the heterogeneity of epidemic areas.

Background: The resources available to fight an epidemic are typically limited, and the time and effort required to control it grow as the start date of the containment effort are delayed. When the population is afflicted in various regions, scheduling a fair and acceptable distribution of limited available resources stored in multiple emergency resource centers to each epidemic area has become a serious problem that requires immediate resolution. Methods: This study presents an emergency medical logistics model for rapid response to public health emergencies. The proposed methodology consists of two recursive mechanisms: (1) time-varying forecasting of medical resources and (2) emergency medical resource allocation. Considering the epidemic's features and the heterogeneity of existing medical treatment capabilities in different epidemic areas, we provide the modified susceptible-exposed-infected-recovered (SEIR) model to predict the early stage emergency medical resource demand for epidemics. Then we define emergency indicators for each epidemic area based on this. By maximizing the weighted demand satisfaction rate and minimizing the total vehicle travel distance, we develop a bi-objective optimization model to determine the optimal medical resource allocation plan. Results: Decision-makers should assign appropriate values to parameters at various stages of the emergency process based on the actual situation, to ensure that the results obtained are feasible and effective. It is necessary to set up an appropriate number of supply points in the epidemic emergency medical logistics supply to effectively reduce rescue costs and improve the level of emergency services. Conclusions: Overall, this work provides managerial insights to improve decisions made on medical distribution as per demand forecasting for quick response to public health emergencies.