University-Associated SARS-CoV-2 Omicron BA.2 Infections,Maricopa County,Arizona, USA, 2022

We investigated a university-affiliated cohort of SARS-CoV-2 Omicron BA.2 infections in Arizona, USA. Of 44 cases, 43 were among students; 26 persons were symptomatic, 8 sought medical care, but none were hospitalized. Most (55%) persons had completed a primary vaccine series; 8 received booster vaccines. BA.2 infection was mild in this young cohort.     

Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension

BackgroundAberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.MethodsFresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E₂) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.ResultsMany circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E₂ strongly regulated it. E₂ decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E₂ reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E₂ and miR‐21‐5p antagonist.ConclusionsmiR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E₂ on MCT‐PH through ERβ.     

一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损的疗效分析

目的观察一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损的疗效。方法回顾分析2021年7月—2022年2月符合选择标准的13例采用一次性皮肤拉拢装置治疗的难闭性皮肤软组织缺损患者临床资料。其中男9例，女4例；年龄15～71岁，平均39.8岁。致伤原因：摔伤5例，交通事故伤5例，高处坠落伤3例。皮肤软组织缺损原因：开放骨折4例，伤口感染4例，骨髓炎3例，脱套伤1例，植皮坏死1例。损伤部位：小腿8例，跟骨3例，骨盆1例，足底1例。皮肤软组织缺损范围为5.0 cm×2.0 cm～10.5 cm×6.5 cm。记录伤口情况（包括伤口闭合和伤口愈合）及有无并发症等情况。结果13例患者均获随访，随访时间32～225 d，中位时间164 d。伤口闭合时间5～14 d，平均8.8 d；伤口闭合速度0.7～13.7 cm²/d，平均3.6 cm²/d。所有伤口均甲级愈合，均未发生皮缘损伤、伤口坏死、感染、裂开、水肿等并发症，患者均未诉疼痛不适等，随访时未发现明显瘢痕形成等情况。伤口愈合时间17～28 d，平均21.7 d。其中1例使用该装置后因肺癌病情变化转科，术后17 d随访时伤口未经缝合已直接愈合。 结论一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损疗效确切，伤口闭合时间短，并发症少，操作简便。     

Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies due to structural and dynamic changes of the viral spike glycoprotein (S). The heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains of S drive virus–host membrane fusion by assembly into a six-helix bundle, resulting in delivery of viral RNA into the host cell. We surveyed mutations of currently reported SARS-CoV-2 variants and selected eight mutations, including Q954H, N969K, and L981F from the Omicron variant, in the postfusion HR1HR2 bundle for functional and structural studies. We designed a molecular scaffold to determine cryogenic electron microscopy (cryo-EM) structures of HR1HR2 at 2.2–3.8 Å resolution by linking the trimeric N termini of four HR1 fragments to four trimeric C termini of the Dps4 dodecamer from Nostoc punctiforme. This molecular scaffold enables efficient sample preparation and structure determination of the HR1HR2 bundle and its mutants by single-particle cryo-EM. Our structure of the wild-type HR1HR2 bundle resolves uncertainties in previously determined structures. The mutant structures reveal side-chain positions of the mutations and their primarily local effects on the interactions between HR1 and HR2. These mutations do not alter the global architecture of the postfusion HR1HR2 bundle, suggesting that the interfaces between HR1 and HR2 are good targets for developing antiviral inhibitors that should be efficacious against all known variants of SARS-CoV-2 to date. We also note that this work paves the way for similar studies in more distantly related viruses.

Three previously unknown beta-coronaviruses have emerged in the first two decades of this century: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 (1). The most recent outbreak of SARS-CoV-2 that causes coronavirus disease 2019 (COVID-19) has claimed about 6 million lives in 2 y, and several variants of concern have emerged around the globe despite the relatively low mutation rate of coronaviruses (2). Some of these variants pose a challenge to currently available vaccines (3–6), likely due to structural changes of the target of these vaccines (7–11). Hence, there is an urgent need for new antiviral therapeutics (12) that target regions of viruses with conserved structural features that are less likely to be affected by mutations.SARS-CoV, MERS-CoV, and SARS-CoV-2 are enveloped viruses that rely on membrane fusion to deliver RNA to the host cell (13). In each case, the process of viral membrane fusion (14, 15) is mediated by the trimeric viral spike glycoprotein (S) that is cleaved into S1 and S2 subunits by multiple host proteases upon infection (16) (Fig. 1A). S1 recognizes the human angiotensin-converting enzyme 2 (ACE2) receptor and dissociates from S2. Subsequently, S2 undergoes substantial conformational changes that drive membrane remodeling. Similar to other enveloped viruses (14, 15), this process likely proceeds via an intermediate extended state that pulls together the two membranes via the transmembrane domain and fusion peptide of the S2 subunit (17). Two heptad repeat regions, HR1 and HR2, distant from each other in the prefusion S, drive membrane fusion by assembly into a six-helix bundle (18). This HR1HR2 bundle formation is thought to provide the energy for membrane fusion and is therefore a target for therapeutics, as exemplified by peptide inhibitors that disrupt infection by the HIV-1 (19, 20), SARS-CoV (21), MERS-CoV (22), SARS-CoV-2 (23–25), human parainfluenza virus 3 (26), and respiratory syncytial virus (26).Open in a separate windowFig. 1.Mutations of interest in the HR1HR2 bundle of SARS-CoV-2 variants. (A) Schematic diagram of the domain structures of the SARS-CoV-2 spike protein. The N and C termini are labeled on the left and right, respectively. FP, fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; TM, transmembrane region. (B) Locations of the five selected point mutations of SARS-CoV-2 variants (black spheres) and the three mutations of the SARS-CoV-2 Omicron variant (purple spheres) indicated in the crystal structure of the HR1HR2 bundle (PDB ID code 6lxt). Two HR2 residues, R1185 and N1187, that may be affected by the selected mutations are shown as red spheres. The HR1 and HR2 fragments are colored as light blue and light red, respectively. (C) Effects on fusion activity of these mutations. The fusion activity is shown as a percentage (Left)/fold change (Right) relative to that of the wild type (Materials and Methods). The Omicron construct used here for the fusion assay has three mutations—Q954H, N969K, and L981F—in the HR1 portion of the HR1HR2 bundle, but not other mutations from different regions of the spike found in the Omicron variant. *P < 0.05, **P < 0.01, ***P < 0.001, by a Student’s t test.Despite the established value of inhibitors targeting formation of the HR1HR2 bundle, the structural plasticity of this bundle upon mutation is largely unknown. Comparison with distantly related viruses suggests that the overall architecture is maintained despite vast differences in primary sequence (SI Appendix, Fig. S1). To what degree does the structure of the HR1HR2 bundle change upon mutation? To address this question, we surveyed mutations of all currently known variants (including Omicron) of SARS-CoV-2 S in the postfusion HR1HR2 bundle, selected eight mutations of potential interest, and investigated their effects on structure and function.Structural characterization of the HR1HR2 bundle has proven surprisingly challenging. To date, two successful approaches for determining structures of the HR1HR2 bundle have been employed. First, several HR1HR2 structures with the HR1 and HR2 domains synthetically linked were determined by X-ray crystallography (2.9 Å, Protein Data Bank [PDB] ID code 6lxt; 1.5 Å, PDB ID code 6m1v) (23, 25). Second, a sample of postfusion S2 was generated from a recombinant source (mammalian HEK-293F cells) expressing full-length S; as such, multiple states of S undergoing spontaneous transition from the prefusion to the postfusion state were present in the sample and the postfusion structure was determined by single-particle cryogenic electron microscopy (cryo-EM) (3.0 Å, PDB ID code 6xra) (18). Although the structures of the postfusion HR1HR2 bundle are similar, there are differences between these structures and the local resolution is quite variable or limited. More importantly, neither approach is particularly suited for efficient structure determination of multiple mutants at high resolution. Therefore, we decided to develop a platform for using single-particle cryo-EM to efficiently determine structures of HR1HR2 bundles at atomic resolution.The postfusion HR1HR2 bundle of SARS-CoV-2 is a 115 × 25 × 25 Å bundle consisting of six helices (PDB ID code 6lxt) (23). Its molecular weight is 40 kDa, close to the theoretical minimum size needed to achieve a reconstruction with near-atomic resolution by cryo-EM (27). To our knowledge, it has not yet been possible to determine structures of individual proteins <50 kDa to high resolution, with exception in the case of multimers (28, 29) or small RNA molecules (30). In addition, efforts extending the resolution limit of cryo-EM have largely focused on globular proteins (28, 29, 31, 32), perhaps because fibrous samples are more flexible, more susceptible to the issue of preferred orientation, and require thicker ice to bury the entire particle—all of which inevitably increase noise in the already extremely low-contrast and hard-to-align images. To overcome the size limit of single-particle cryo-EM, two strategies have been employed to increase the effective mass of the target protein, e.g. using antibodies/nanobodies/legobodies (33, 34) and molecular scaffolds (35–38). Since developing antibodies/nanobodies/legobodies can be time-consuming we resorted to the molecular scaffold approach. We first attempted to use existing scaffolds but were unable to engineer a linkage ensuring proper HR1HR2 bundle formation. We therefore designed a scaffold to efficiently determine structures of the postfusion HR1HR2 bundle and its mutants to near-atomic resolution by single-particle cryo-EM.Our high-resolution wild-type structure of the HR1HR2 bundle resolves uncertainties in some side-chain positions present in prior structures. Our HR1HR2 structures of SARS-CoV-2 variants reveal an overall architecture that is highly conserved, with only side-chain rearrangement for five point mutations and, for the Omicron variant containing three mutations in HR1, a slight shift of the HR2 backbone in a nonhelical region that interacts with HR1. These results suggest that interactions between HR1 and HR2 are excellent targets for disruption by broadly efficacious antiviral inhibitors. Moreover, our approach can be directly used to study the binding of potential HR2-based peptide inhibitors and adapted to study the postfusion bundles of other coronaviruses or other structurally similar viruses.     

Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants

The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein–based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) “unhelped” mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and “helped” CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (β) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell–targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to exert devastating impacts on the human life, with >280 million infections and over 5.4 million deaths to date. Although there are millions of convalescent people with some measure of immunity and 8.8 billion doses of vaccine administered to date, further threats of widespread severe COVID-19 disease looms heavily as immunity induced by infection or the first-generation vaccines may not provide effective and durable protection, either due to waning immunity or due to poor antibody cross-reactivity to new variants (1–5).It is clear that virus-neutralizing antibodies provide the most effective protection to SARS-CoV-2, following vaccination or recovery from infection (6). However, T cell–based protection against SARS-CoV-2 has become a central focus because T cells recognize short amino acid sequences that can be conserved across viral variants (7–9). Indeed, T cells in convalescent COVID-19 patients have shown robust responses that are directed at multiple viral proteins, and depletion of these T cells delayed SARS-CoV-2 control in mice (10–12). These data suggest a protective role for T cells in COVID-19 infection. In effect, what constitutes an effective, an ineffective, or a perilous T cell response to SARS-CoV-2 in lungs remains poorly defined. Controlled studies in laboratory animals are of critical importance to elucidate the role and nature of T cells in lungs during SARS-CoV-2 virus infection and in protective immunity.Based on the differentiation state, anatomical localization and traffic patterns, memory T cells are classified into effector memory (T_EM), central memory (T_CM), and tissue-resident memory (T_RM) (13, 14). There is accumulating evidence that airway/lung-resident T_RMs, and not migratory memory T cells (T_EMs) are critical for protective immunity to respiratory mucosal infections with viruses, such as influenza A virus (IAV) and respiratory syncytial virus (15–21). Development of T_RMs from effector T cells in the respiratory tract requires local antigen recognition and exposure to critical factors, such as transforming growth factor (TGF)-β and interleukin (IL)-15 (15). Therefore, mucosal vaccines are more likely to elicit T_RMs in lungs than parenteral vaccines (22, 23). A subset of effector T cells in airways of COVID-19 patients display T_RM-like features (24), but the development of T_RMs or their importance in protective immunity to reinfection are yet to be determined. Furthermore, all SARS-CoV-2 vaccines in use are administered parenterally and less likely to induce lung T_RMs. While depletion of CD8 T cells compromised protection against COVID-19 in vaccinated rhesus macaques (25), the relative effectiveness of vaccine-induced systemic/migratory CD8 T cell memory vs. lung/airway T_RMs in protective immunity to COVID-19 is yet to be defined.In this study, using the K18-hACE2 transgenic (tg) mouse model of SARS-CoV-2 infection, we have interrogated two key aspects of T cell immunity: 1) the requirements for lung-resident vs. migratory T cell memory in vaccine-induced immunity to SARS-CoV-2; and 2) the role of lung-resident memory CD4 vs. CD8 T cells in protection against viral variants in the presence or absence of virus-neutralizing antibodies. Studies of mucosal versus systemic T cell–based vaccine immunity using a subunit protein-based adjuvant system that elicits neutralizing antibodies and T cell immunity, demonstrated that: 1) both mucosal and parenteral vaccinations provide effective immunity to SARS-CoV-2 variants; 2) CD4 T cell–dependent immune mechanisms exert primacy in protection against homologous SARS-CoV-2 strain; and 3) the development of spike (S) protein-specific “unhelped” memory CD8 T cells in the respiratory mucosa are insufficient to protect against a lethal challenge with the homologous Washington (WA) strain of SARS-CoV-2. Unexpectedly, we found that systemic or mucosal lung-resident memory CD4 and “helped” CD8 T cells engendered effective immunity to the South African B1.351 β-variant in the apparent absence of detectable mucosal or circulating virus-neutralizing antibodies. Taken together, mechanistic insights from this study have advanced our understanding of viral pathogenesis and might drive rational development of next-generation broadly protective SARS-CoV-2 vaccines that induce humoral and T cell memory.     

Impact of natural selection on global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection

Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (angiotensin converting enzyme 2 [ACE2], transmembrane protease serine 2 [TMPRSS2], dipeptidyl peptidase 4 [DPP4], and lymphocyte antigen 6 complex locus E [LY6E]). We analyzed data from 2,012 ethnically diverse Africans and 15,977 individuals of European and African ancestry with electronic health records and integrated with global data from the 1000 Genomes Project. At ACE2, we identified 41 nonsynonymous variants that were rare in most populations, several of which impact protein function. However, three nonsynonymous variants (rs138390800, rs147311723, and rs145437639) were common among central African hunter-gatherers from Cameroon (minor allele frequency 0.083 to 0.164) and are on haplotypes that exhibit signatures of positive selection. We identify signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage compared with the chimpanzee genome. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19. Our study provides insights into global variation at host genes related to SARS-CoV-2 infection, which have been shaped by natural selection in some populations, possibly due to prior viral infections.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses are enveloped, positive-sense, and single-stranded RNA viruses, many of which are zoonotic pathogens that crossed over into humans. Seven coronavirus species, including SARS-CoV-2, have been discovered that, depending on the virus and host physiological condition, may cause mild or lethal respiratory disease. There is considerable variation in disease prevalence and severity across populations and communities. Importantly, minority populations in the United States appear to have been disproportionally affected by COVID-19 (1, 2). For example, in Chicago, more than 50% of COVID-19 cases and nearly 70% of COVID-19 deaths are in African Americans (who make up 30% of the population of Chicago) (1). While social and economic factors are largely responsible for driving COVID-19 health disparities, investigating genetic diversity at host genes related to SARS-CoV-2 infection could help identify functionally important variation, which may play a role in individual risk for severe COVID-19 infection.In this study, we focused on four key genes playing a role in SARS-CoV-2 infection (3). The ACE2 gene, encoding the angiotensin-converting enzyme-2 protein, was reported to be a main binding site for severe acute respiratory syndrome coronavirus (SARS-CoV) during an outbreak in 2003, and evidence showed stronger binding affinity to SARS-CoV-2, which enters the target cells via ACE2 receptors (3, 4). The ACE2 gene is located on the X chromosome (chrX); its expression level varies among populations (5); and it is ubiquitously expressed in the lung, blood vessels, gut, kidney, testis, and brain, all organs that appear to be affected as part of the COVID-19 clinical spectrum (6). SARS-CoV-2 infects cells through a membrane fusion mechanism, which in the case of SARS-CoV, is known to induce down-regulation of ACE2 (7). Such down-regulation has been shown to cause inefficient counteraction of angiotensin II effects, leading to enhanced pulmonary inflammation and intravascular coagulation (7). Additionally, altered expression of ACE2 has been associated with cardiovascular and cerebrovascular disease, which is highly relevant to COVID-19 as several cardiovascular conditions are associated with severe disease. TMPRSS2, located on the outer membrane of host target cells, binds to and cleaves ACE2, resulting in activation of spike proteins on the viral envelope and facilitating membrane fusion and endocytosis (8). Two additional genes, DPP4 and LY6E, have been shown to play an important role in the entry of SARS-CoV-2 virus into host cells. DPP4 is a known functional receptor for the Middle East respiratory syndrome coronavirus (MERS-CoV), causing a severe respiratory illness with high mortality (9, 10). LY6E encodes a glycosylphosphatidylinositol-anchored cell surface protein, which is a critical antiviral immune effector that controls coronavirus infection and pathogenesis (11). Mice lacking LY6E in hematopoietic cells were susceptible to murine coronavirus infection (11).Previous studies of genetic diversity at ACE2 and TMPRSS2 in global human populations did not include an extensive set of African populations (5, 12–14). No common coding variants (defined here as minor allele frequency [MAF] > 0.05) at ACE2 were identified in any prior population studies. However, few studies included diverse indigenous African populations whose genomes harbor the greatest diversity among humans. This leads to a substantial disparity in the representation of African ancestries in human genetic studies of COVID-19, impeding health equity as the transferability of findings based on non-African ancestries to African populations can be low (15). Including more African populations in studying the genetic diversity of genes involved in SARS-CoV-2 infection is extremely necessary. Additionally, the evolutionary forces underlying global patterns of genetic diversity at host genes related to SARS-CoV-2 infection are not well understood. Using methods to detect natural selection signatures at host genes related to viral infections helps identify putatively functional variants that could play a role in disease risk.We characterized genetic variation and studied natural selection signatures at ACE2, TMPRSS2, DPP4, and LY6E in ethnically diverse human populations by analyzing 2,012 genomes from ethnically diverse Africans (referred to as the “African diversity” dataset), 2,504 genomes from the 1000 Genomes Project (1KG), and whole-exome sequencing of 15,977 individuals of European ancestry (EA) and African ancestry from the Penn Medicine BioBank (PMBB) dataset (SI Appendix, Fig. S1). The African diversity dataset includes populations with diverse subsistence patterns (hunter-gatherers, pastoralists, agriculturalists) and speaking languages belonging to the four major language families in Africa (Khoesan; Niger–Congo, of which Bantu is the largest subfamily; Afroasiatic; and Nilo-Saharan). We identify functionally relevant variation, compare the patterns of variation across global populations, and provide insight into the evolutionary forces underlying these patterns of genetic variation. In addition, we perform an association study using the variants identified from whole-exome sequencing at the four genes and clinical traits derived from electronic health record (EHR) data linked to the subjects enrolled in the PMBB. The EHR data include diseases related to organ dysfunctions associated with severe COVID-19, such as respiratory, cardiovascular, liver, and renal complications. Our study of genetic variation in genes involved in SARS-CoV-2 infection provides data to investigate infection susceptibility within and between populations and indicates that variants in these genes may play a role in comorbidities relevant to COVID-19 severity.     

New‐onset pemphigus foliaceus following SARS‐CoV‐2 infection and unmasking multiple sclerosis: A case report

Development of pemphigus foliaceus (PF) following SARS‐CoV‐2 infection has only been reported in one patient who had received Bamlanivimab and thus might be considered as a drug‐induced case of PF. Here, we reported the first case of PF arising solely after COVID infection without taking any culprit drug.     

LncRNA SNHG1 promotes renal cell carcinoma progression through regulation of HMGA2 via sponging miR‐103a

BackgroundLong noncoding RNAs (LncRNAs) plays a vital role in tumorigenesis and development. The molecular mechanism of SNHG1 in renal cell carcinoma (RCC) has not been illustrated. The aim of this research was to explore the expression and function of LncRNA SNHG1 in RCC.Material and MethodsThe expression of SNHG1 in clinical tissues and RCC cell lines was detected. Luciferase reporter assay was performed to verify the correlation between SNHG1, miR‐103a, and HMGA2. CCK‐8 assay was performed to examine cell viability. Cell apoptosis was analyzed using flow cytometry. Cell invasion capacity was determined by Transwell assays. The protein level of HMGA2 was analyzed by Western blotting.ResultsThe expression of SNHG1 markedly increased in RCC tissues and cell lines. Subsequent studies identified SNHG1 as a miRNA sponge for miR‐103a. In addition, SNHG1 knockdown and miR‐103a overexpression significantly inhibited progression of RCC. miR‐103a also regulated HMGA2 levels.ConclusionOur findings showed that SNHG1 was upregulated in RCC cells and tissues. SNHG1 promoted the malignant characteristics of RCC cells. Its regulatory effect may be regulation of HMGA2 by sponging miR‐103a. Therefore, Our study facilitates the understanding of SNHG1 function in RCC.     

SLC2A3 variants in familial and sporadic congenital heart diseases in a Chinese Yunnan population

BackgroundSolute carrier family 2 member 3 (SLC2A3), is a member of a superfamily of transport protein genes. SLC2A3 played an important role in embryonic development. Previous research reported SLC2A3 duplication was reportedly associated with congenital syndromic heart defects. However, it is not clear whether the gene is associated with non‐syndromic congenital heart disease. Our study aimed to elucidate the relationship between its variation and congenital heart disease.MethodsGenomic DNA extracted from the peripheral blood leukocytes of two families with CHD were sequenced with whole‐exome sequencing to identify variations, used Sanger sequencing to investigate SLC2A3 variants in 494 Chinese patients with CHD and 576 healthy unrelated individuals.ResultsIn members from the two families, three with CHD had the SLC2A3 (rs3931701) C > T variant. Of the 494 patients with CHD, 394 had gene variants (86 had the TT type and 308 had the CT type). Of the 576 healthy controls, 272 participants had gene variants (36 had the TT type and 236 had the CT type). The TT type [p < 0.0001, odds ratio (OR) =7.262, 95% confidence interval (CI) =4.631–11.388] and CT type (p < 0.0001, OR =3.967, 95% CI =2.991–5.263) of SLC2A3 (rs3931701) significantly increased the risk of sporadic ASD in a Chinese Yunnan population.ConclusionsSingle nucleotide variations of SLC2A3, particularly, the SLC2A3 (rs3931701) C > T variant increased the risk of CHD among the studied population.