SPASCER: spatial transcriptomics annotation at single-cell resolution.

In recent years, the explosive growth of spatial technologies has enabled the characterization of spatial heterogeneity of tissue architectures. Compared to traditional sequencing, spatial transcriptomics reserves the spatial information of each captured location and provides novel insights into diverse spatially related biological contexts. Even though two spatial transcriptomics databases exist, they provide limited analytical information. Information such as spatial heterogeneity of genes and cells, cell-cell communication activities in space, and the cell type compositions in the microenvironment are critical clues to unveil the mechanism of tumorigenesis and embryo differentiation. Therefore, we constructed a new spatial transcriptomics database, named SPASCER (https://ccsm.uth.edu/SPASCER), designed to help understand the heterogeneity of tissue organizations, region-specific microenvironment, and intercellular interactions across tissue architectures at multiple levels. SPASCER contains datasets from 43 studies, including 1082 sub-datasets from 16 organ types across four species. scRNA-seq was integrated to deconvolve/map spatial transcriptomics, and processed with spatial cell-cell interaction, gene pattern and pathway enrichment analysis. Cell-cell interactions and gene regulation network of scRNA-seq from matched spatial transcriptomics were performed as well. The application of SPASCER will provide new insights into tissue architecture and a solid foundation for the mechanistic understanding of many biological processes in healthy and diseased tissues.

lncRNAfunc: a knowledgebase of lncRNA function in human cancer.

The long non-coding RNAs associating with other molecules can coordinate several physiological processes and their dysfunction can impact diverse human diseases. To date, systematic and intensive annotations on diverse interaction regulations of lncRNAs in human cancer were not available. Here, we built lncRNAfunc, a knowledgebase of lncRNA function in human cancer at https://ccsm.uth.edu/lncRNAfunc, aiming to provide a resource and reference for providing therapeutically targetable lncRNAs and intensive interaction regulations. To do this, we collected 15 900 lncRNAs across 33 cancer types from TCGA. For individual lncRNAs, we performed multiple interaction analyses of different biomolecules including DNA, RNA, and protein levels. Our intensive studies of lncRNAs provide diverse potential mechanisms of lncRNAs that regulate gene expression through binding enhancers and 3'-UTRs of genes, competing for miRNA binding sites with mRNAs, recruiting the transcription factors to gene promoters. Furthermore, we investigated lncRNAs that potentially affect the alternative splicing events through interacting with RNA binding Proteins. We also performed multiple functional annotations including cancer stage-associated lncRNAs, RNA A-to-I editing event-associated lncRNAs, and lncRNA expression quantitative trait loci. lncRNAfunc is a unique resource for cancer research communities to help better understand potential lncRNA regulations and therapeutic lncRNA targets.

SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose.

BACKGROUND: Omicron variant (B.1.1.529) is a dominant variant worldwide. However, the risk factors for Omicron variant clearance are yet unknown. The present study aimed to investigate the risk factors for early viral clearance of Omicron variant in patients with a history of inactivated vaccine injection. METHODS: Demographic, clinical, and epidemiological data from 187 patients were collected retrospectively during the Omicron variant wave. RESULTS: 73/187 and 114/187 patients were administered two and three doses of vaccine, respectively. The median duration of SARS-CoV-2 RNA positivity was 9 days, and the difference between patients with two and three vaccine injections was insignificant (P = 0.722). Fever was the most common symptom (125/187), and most patients (98.4%) had a fever for < 7 days. The RNA was undetectable in 65/187 patients on day 7. Univariable logistic analysis showed that baseline glucose, uric acid, lymphocytes count, platelet count, and CD4+ T lymphocyte count were associated with SARS-CoV-2 RNA-positivity on day 7. Multivariable analysis showed that glucose ≥ 6.1 mmol/L and CD4+T lymphocytes count were independent risk factors for RNA positivity on day 7. 163/187 patients had an undetectable RNA test on day 14, and uric acid was the only independent risk factor for RNA positivity. Moreover, baseline glucose was negatively correlated with uric acid and CD4+ and CD8+ T cell count, while uric acid was positively correlated with CD4+ and CD8+ T cell count. CONCLUSIONS: Omicron variant clearance was delayed in breakthrough cases with elevated fasting blood glucose, irrespective of the doses of inactivated vaccine.

Wafer-scale transfer of vertically aligned carbon nanotube arrays.

The first critical step in making vertically aligned carbon nanotube (VACNT)-based thermal interface materials is to transfer the VACNTs on a large scale. Although VACNTs have been transferred by several methods, they were only transferred inadvertently in most cases. Here we report well-controlled weak-oxidation-assisted transfer of VACNTs. Specifically, after a short time of weak oxidation, we found that VACNTs could be easily detached from the native growth substrates, and thus, a freestanding VACNT film was obtained. Then the VACNTs could be assembled onto specific substrates for its real applications. More importantly, the repeated growth-transfer synthesis of VACNT arrays can be realized in one batch by introducing an additional process of weak oxidation in chemical vapor deposition, which makes the strategy more effective. Surprisingly, no degradation in the quality was observed before and after the weak oxidation according to thermogravimetric analysis and Raman spectra of VACNTs. Enhanced thermal and mechanical properties were achieved after reactive ion etching (RIE) and subsequent metallization of the surfaces of the VACNTs, and this might be due to the removal of impurities such as amorphous carbon and entangled CNTs by RIE. These findings provide an efficient approach for transferring VACNTs, which is important for the application of VACNTs in thermal management.

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics.

The ovary is indispensable for female reproduction, and its age-dependent functional decline is the primary cause of infertility. However, the molecular basis of ovarian aging in higher vertebrates remains poorly understood. Herein, we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries. From a global view, somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region, likely constituting a hostile microenvironment that facilitates ovarian aging. Further, we uncovered that inflammation, the senescent-associated secretory phenotype, senescence, and fibrosis are the likely primary contributors to ovarian aging (PCOA). Of note, we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2 (Metallothionein 2) highly expressing spot (MT2high) characterized by high levels of inflammation, potentially serving as an aging hotspot in the primate ovary. Moreover, with advanced age, a subpopulation of MT2high accumulates, likely disseminating and amplifying the senescent signal outward. Our study establishes the first primate spatiotemporal transcriptomic atlas, advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.

Old Age is an Independent Risk Factor for Pneumonia Development in Patients with SARS-CoV-2 Omicron Variant Infection and a History of Inactivated Vaccine Injection.

Objective: Analyzing the risk factors for pneumonia development in breakthrough cases with a history of inactivated vaccine injection is important. The present study aimed to investigate the risk factors for pneumonia development during Omicron variant infection. Design and Methods: The clinical data were retrospectively collected from 187 patients who previously received inactivated vaccine and were infected by the Omicron variant. Results: Among the 187 patients, 73 had 2 doses of inactivated vaccine injection and the remaining 114 had 3 doses; 19 patients had pneumonia at admission. The univariate logistic analysis showed that age, baseline platelet count, D-dimer level, and CD8+ T lymphocyte count were associated with pneumonia development at admission. The multivariate analysis showed that only age was the independent risk factor for pneumonia development (odds ratio = 1.046, 95% confidence interval: 1.003-1.091, P = 0.04). With an optimal cutoff value of 46, 4.4% (4/91) patients in the age <46 years group and 15.63% (15/96) patients in the age ≥46 years group had pneumonia (χ 2 = 6.454, P = 0.01). Moreover, age negatively correlated with CD8+ T cell count, B cell count, and albumin and uric acid levels (all P < 0.01), while age positively correlated with the glucose level (P < 0.01). Conclusion: Old age was the only independent risk factor for pneumonia development in patients with Omicron variant infection and a history of inactivated vaccine injection.

Transactivation of Met signalling by semaphorin4D in human placenta: implications for the pathogenesis of preeclampsia.

OBJECTIVE: The signalling of the receptor tyrosine kinase Met is critical in promoting trophoblast cell invasion, and the deficiency in HGF/Met signalling is associated with preeclampsia. The semaphorin family member semaphorin4D (sema4D) and its receptor Plexin-B1 have been reported to control tumour cell invasion by coupling with Met. We hypothesized that sema4D/Plexin-B1 may promote trophoblast invasion by activating Met, and downregulation of sema4D/Plexin-B1 may account for the deficiency in Met signalling in preeclamptic placenta. METHODS: In this study, Met and Erk activation and the expression of sema4D/Plexin-B1 in normal and preeclamptic placentas were comparably measured. The role of sema4D in trophoblast cell invasion and tubulogenesis was examined in vitro using the Transwell invasion assay and tube formation assay in trophoblast-endothelial cell co-culture model. RESULTS: Met, sema4D and Plexin-B1 co-localized in various subtypes of human trophoblast cells, including villous trophoblasts and extravillous trophoblasts (EVTs). In early-onset preeclampsia (E-PE) placentas, the phosphorylated Met and Erk as well as sema4D and Plexin-B1 were much lower than those in gestational week-matched preterm-labour (PTL) placentas. In human trophoblast HTR8/SVneo cell line, sema4D could promote Met and Erk phosphorylation as well as enhance trophoblast cell invasion and tubulogenesis with endothelial cells. Moreover, the effect of sema4D on HTR8/SVneo could be blocked by knocking down Met with specific siRNA. CONCLUSION: The crosstalk between sema4D and Met could transactivate Met to promote trophoblast cell invasion and differentiation, and decreased expression of sema4D and Plexin-B1 may be responsible for the deficiency in Met signalling and the development of preeclampsia.

miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b and Activating Ras-MAPK Signal.

Preeclampsia is a pregnancy-specific complication defined as newly onset gestational hypertension and proteinuria. Deficiency in placental development is considered as the predominant cause of preeclampsia. Our previous study found that the expression of miR-518b increased significantly in the preeclamptic placentas, indicating the potential participation of this small RNA in the occurrence of preeclampsia. In this study, data analysis using multiple databases predicted Rap1b as a candidate target of miR-518b. An evident decrease in Rap1b expression was observed in preeclamptic placentas when compared with the control placentas, which was negatively correlated with the level of miR-518b. Based on the data of in situ hybridization and immunohistochemistry showing that Rap1b exhibited similar localization with miR-518b in villous cytotrophoblast cells and column trophoblasts, we further explored their function in regulating trophoblast cell proliferation. In HTR8/SVneo cells, exogenous transfection of miR-518b reduced the expression of Rap1b, and dual-luciferase reporter assay validated Rap1b as the direct target of miR-518b. The small RNA could increase the BrdU incorporation and the ratio of cells at S phase, and enhance the phosphorylation of Raf-1 and ERK1/2. Such growth-promoting effect could be efficiently reversed by Rap1b overexpression. The data indicate that miR-518b can promote trophoblast cell proliferation via Rap1b-Ras-MAPK pathway, and the aberrant upregulation of miR-518b in preeclamptic placenta may contribute to the excessive trophoblast proliferation. The study provides new evidence to further understand the etiology of preeclampsia.

Siomycin A Induces Apoptosis in Human Lung Adenocarcinoma A549 Cells by Suppressing the Expression of FoxM1.

Forkhead box M1 (FoxM1), a transcription factor of the Forkhead family, is demonstrated to be critical for proliferation, apoptosis, migration and invasion of lung cancer. In this study, we extensively investigated the anticancer effect of siomycin A, which was identified as an inhibitor of FoxM1 transcriptional activity, on human lung adenocarcinoma A549 cells. Our study indicated that treatment with siomycin A resulted in the suppression of FoxM1 expression, which consequently contributed to its effect of cell growth inhibition and cell apoptosis induction in A549 cells. Then the molecular mechanism of siomycin A's apoptotic action on A549 cells was further investigated. The results revealed that siomycin A induced apoptosis by influencing the downstream events of FoxM1, including inhibiting the expression of Bcl-2 and Mcl-1, as well as leading to caspase-3 cleavage. Taken together, our findings may be useful for understanding the mechanism of action of siomycin A on lung cancer cells and provide new insights into the possible application of such a compound in lung cancer therapy in the future.

Characterization of the complete mitochondrion genome of diurnal Moth Amata emma (Butler) (Lepidoptera: Erebidae) and its phylogenetic implications.

Mitogenomes can provide information for phylogenetic analyses and evolutionary biology. The complete mitochondrial genome of Amata emma (Lepidoptera: Erebidae) was sequenced and analyzed in the study. The circular genome is 15,463 bp in size, with the gene content, orientation and order identical to other ditrysian insects. The genome composition of the major strand shows highly A+T biased and exhibits negative AT-skew and GC-skew. The initial codons are the canonical putative start codons ATN with the exception of cox1 gene which uses CGA instead. Ten genes share complete termination codons TAA, and three genes use incomplete stop codons TA or T. Additionally, the codon distribution and Relative Synonymous Codon Usage of the 13 PCGs in the A. emma mitogenome are consistent with those in other Noctuid mitogenomes. All tRNA genes have typical cloverleaf secondary structures, except for the trnS1 (AGN) gene, in which the dihydrouridine (DHU) arm is simplified down to a loop. The secondary structures of two rRNA genes broadly conform with the models proposed for these genes of other Lepidopteran insects. Except for the A+T-rich region, there are three major intergenic spacers, spanning at least 10 bp and five overlapping regions. There are obvious differences in the A+T-rich region between A. emma and other Lepidopteran insects reported previously except that the A+T-rich region contains an 'ATAGA' -like motif followed by a 19 bp poly-T stretch and a (AT)9 element preceded by the 'ATTTA' motif. It neither has a poly-A (in the α strand) upstream trnM nor potential stem-loop structures and just has some simple structures like (AT)nGTAT. The phylogenetic relationships based on nucleotide sequences of 13 PCGs using Bayesian inference and maximum likelihood methods provided a well-supported a broader outline of Lepidoptera and which agree with the traditional morphological classification and recently working, but with a much higher support.

[Pregnant women hepatitis B markers investigation and analysis of intrauterine infection].

OBJECTIVE: To investigate the relationship between the hepatitis B virus (HBV) infection in pregnant women and intrauterine infection in local region. METHODS: The markers of hepatitis B (HBVM) were determined by time-resolved fluoroimmunoassay and HBV-DNA were determined by FQ-PCR. RESULTS: A total of 1262 pregnant women were examined the HBVM, 2.6%, 38.2%, 0.9%, 22.6%, 23.1% subjects were identified HBsAg, HBsAb, HBeAg, HBeAb, HBcAb positive respectively. In 33 cases of serum HBsAg-positive pregnant women, HBV-DNA were observed in most of 11 cases of pregnant women with HBeAg-positive and intrauterine infection rates were 6/11. In contrast, 22 cases of pregnant women with HBeAg negative, HBV-DNA were detected lowly-loaded and intrauterine infection rates were 2/22 (P < 0.01). Intrauterine infection rates of HBV in pregnant women with HBsAg-positive were 24.2% (8/33). CONCLUSION: HBV infective rates in pregnant women in the local region were low. Pregnant women with serum HBeAg positive and HBV-DNA high-loaded were prone to intrauterine infection.