TRIM22 is involved in tumorigenesis and development, but its mechanism is not clear. In this study, we investigated the expression and biological role of TRIM22 in gastric cancer. We found that TRIM22 mRNA and protein expression was abnormally low in gastric cancer tissues and cells and correlated with tumor size and depth of invasion. Overexpression of TRIM22 significantly inhibited the proliferation, colony formation, and migration of gastric cancer cells and downregulated the expression of HSPA6. However, the HSPA6-siRNA complementation test showed that TRIM22 did not regulate cell proliferation through HSPA6. Furthermore, overexpression of TRIM22 downregulated the phosphorylation of Smad2 and Smad3. In addition, TRIM22 directly binds to Smad2, and overexpression of Smad2 can reverse the inhibition of cell proliferation and migration induced by TRIM22. In vivo, overexpression of TRIM22 significantly inhibited the growth of subcutaneous xenografts in nude mice. Our study indicates that TRIM22 has an important role in the development of gastric cancer and may inhibit the proliferation of gastric cancer cells through Smad2.

The copper ion content in the body maintains homeostasis, and when dysregulated, it can produce cytotoxicity and induce cell death through a variety of pathways. Cuproptosis refers to copper ions combining directly with acylated molecules, leading to the accumulation of oligomerization of lipoylated protein and subsequent downregulation of iron-sulfur cluster proteins; this induces proteotoxic stress and cell death. This study on the relationship between cuproptosis-related lncRNAs (CRLns) and the prognosis of primary hepatic carcinoma (PHC) has important clinical guiding significance for the diagnosis and treatment of PHC. Prognosis-related CRLRs were identified via rank-sum tests, correlational analyses, and univariate Cox regression, and a CRLR risk-scoring model (CRLRSM) was constructed using LASSO Cox regression. Patients were divided into high-risk and low-risk groups based on the median CRLRSM scores. Variance analysis for cuproptosis-related genes, gene set enrichment analysis, and correlational analysis for risk and immunity were performed using boxplots. Quantitative polymerase chain reactions were used to verify the CRLR levels in PHC cell lines. The study results showed that patients in the CRLRSM high-risk group had worse survival rates than those in the low-risk group. The PHC stage and risk score were independent prognostic factors for hepatocellular carcinoma. There were 7 CRLRs (MIR210HG, AC099850.3, AL031985.3, AC012073.1, MKLN1-AS, KDM4A-AS1, and PLBD1-AS1) associated with PHC prognosis, primarily through cellular metabolism, growth, proliferation, apoptosis, and immunity. In conclusion, the overexpression of 7 CRLRs in patients with PHC indicates a poor prognosis.

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

Due to the lack of known therapeutic targets for triple-negative breast cancer (TNBC), chemotherapy is the only available pharmacological treatment. Pirarubicin (tetrahydropyranyl Adriamycin, THP) is the most commonly used anthracycline chemotherapy agent. However, TNBC has a high recurrence rate after chemotherapy, and the mechanisms of chemoresistance and recurrence are not entirely understood. To study the chemoresistance mechanisms, we first screened compounds on a pirarubicin-resistant cell line (MDA-MB-231R) derived from MDA-MB-231. The drug resistance index of MDA-MB-231R cells was approximately five times higher than that of MDA-MB-231 cells. MDA-MB-231R cells have higher GRP78 and lower miR-495-3p expression levels than MDA-MB-231 cells. Transfecting MDA-MB-231R cells with a siGRP78 plasmid reduced GRP78 expression, which restored pirarubicin sensitivity. Besides, transfecting MDA-MB-231R cells with miR-495-3p mimics increased miR-495-3p expression, which also reversed pirarubicin chemoresistance. Cell counting kit-8 (CCK-8), EdU, wound healing, and Transwell assays showed that the miR-495-3p mimics also inhibited cell proliferation and migration. Based on our results, miR-495-3p mimics could down-regulate GRP78 expression via the p-AKT/mTOR signaling pathway in TNBC cells. Remarkably, chemo-resistant and chemo-sensitive TNBC tissues had opposite trends in GRP78 and miR-495-3p expressions. The lower the GRP78 and the higher the miR-495-3p expression, the better prognosis in TNBC patients. Therefore, the mechanism of pirarubicin resistance might involve the miR-495-3p/GRP78/Akt axis, which would provide a possible strategy for treating TNBC.

Potent systemic immunity is important for recalled mucosal immune responses, but in the defense against mucosal viral infections, it usually remains low at mucosal sites. Based on our previous findings that enhanced immune responses can be achieved by immunization with an immunogen in combination with a molecular adjuvant, here we designed chemokine-antigen (Ag) fusion constructs (CCL19- or CCL28-herpes simplex virus 2 glycoprotein D [HSV-2 gD]). After intramuscular (i.m.) immunization with different DNA vaccines in a prime and boost strategy, BALB/c mice were challenged with a lethal dose of HSV-2 through the genital tract. Ag-specific immune responses and chemokine receptor-specific lymphocytes were analyzed to determine the effects of CCL19 and CCL28 in strengthening humoral and cellular immunity. Both CCL19 and CCL28 were efficient in inducing long-lasting HSV-2 gD-specific systemic immunity. Compared to CCL19, less CCL28 was required to elicit HSV-2 gD-specific serum IgA responses, Th1- and Th2-like responses of immunoglobulin (Ig) subclasses and cytokines, and CCR3+ T cell enrichment (>8.5-fold) in spleens. These findings together demonstrate that CCL28 tends to assist an immunogen to induce more potently protective immunity than CCL19. This work provides information for the application potential of a promising vaccination strategy against mucosal infections caused by HSV-2 and other sexually transmitted viruses.IMPORTANCE An effective HSV-2 vaccine should induce antigen (Ag)-specific immune responses against viral mucosal infection. This study reveals that chemokine CCL19 or CCL28 enhanced HSV-2 glycoprotein D ectodomain (gD-306aa)-induced immune responses against vaginal virus challenge. In addition to eliciting robust humoral immune responses, the chemokine-Ag fusion construct also induced Th1- and Th2-like immune responses characterized by the secretion of multiple Ig subclasses and cytokines that were able to be recalled after HSV-2 challenge, while CCL28 appeared to be more effective than CCL19 in promoting gD-elicited immune responses as well as the migration of T cells to secondary lymph tissues. Of importance, both CCL19 and CCL28 significantly facilitated gD to induce protective mucosal immune responses in the genital tract. The above-described findings together highlight the potential of CCL19 or CCL28 in combination with gD as a vaccination strategy to control HSV-2 infection.

Silver sillago (Sillago sihama) is an emerging commercial marine aquaculture species in China. To date, fundamental information on S. sihama, such as genomic information, is lacking, and no data are available on the gonad transcriptome of S. sihama. Here, the first gonadal transcriptomes of S. sihama have been constructed and genes potentially involved in gonadal development and reproduction identified. Illumina sequencing generated 60.18 million clean reads for the testis and 59.10 million for the ovary. All reads were assembled into 74,038 unigenes with a mean length of 1,004 bp and N50 value of 2,190 bp. Among all the predictable unigenes, a total of 34,104 unigenes (46%) were searched against multiple databases, including 33,244 unigenes annotated in the RefSeq Non- Redundant database at NCBI, and 28,924 in Swiss-Prot. By comparing the ovary and testis, 35,367 unigenes were identified as being differentially expressed between males and females, of which 29,127 were upregulated in the testis and 6,240 were upregulated in the ovary. Numerous differentially expressed genes (DEGs) known to be involved in gonadal development and gametogenesis were identified, including amh, dmrt1, gsdf, cyp19a1a, gnrhr, and zps. Using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the top 20 KEGG pathways with highest number of DEGs were found to be involved in regulating gonadal development and gametogenesis in S. sihama. Moreover, 22,666 simple sequence repeats (SSRs) were identified in 14,577 SSR-containing sequences. The findings provide a valuable dataset for future functional analyses of sex-associated genes and molecular marker assisted selection in S. sihama.

Claudin-1 (CLDN1) is overexpressed in gastric cancer and correlated with tumor invasion, metastasis and poor outcome. Here, we both down and up regulated CLDN1 expression in gastric cancer cells to elucidate its role in gastric carcinogenesis and tumor progression. We found that deficiency of CLDN1 inhibited cells migration, invasion, and colony formation in vitro and tumorigenicity, metastasis in vivo. Also, CLDN1 promoted cell aggregation and increased anoikis resistance. Down or up regulation of CLDN1 was accompanied with changes of membrane β-catenin expression as well as Akt and Src activities. When β-catenin was up-regulated in CLDN1-KD cells, cell aggregation and anoikis resistance were restored, and Akt and Src signal pathways were re-activated. Taken together, these findings suggest that CLDN1 is oncogenic in gastric cancer and its malignant potential may be attributed in part to regulation of anoikis, by mediating membrane β-catenin-regulated cell-cell adhesion and cell survival.

The implantation sites, fetus resorption, and abnormal fetuses were studied in pregnant mice treated with different doses of BaP by oral gavage from day 1 to day 10 of gestation. Additionally, apoptosis and related signaling pathway, and the migration and invasion of trophoblasts, were assessed before and after exposure of BPDE in Swan 71 trophoblast cell. Besides, the migration and invasion, and its related signaling pathway, were assessed in villi obtained from women.

Ischemic stroke (IS) is one of the most common cerebrovascular diseases worldwide. The aberrant expression of BCL6 has been previously implicated in the pathogenesis of IS. Meanwhile, miR-31 is known as a target of BCL6, and has also been suggested to diminish cell damage by suppressing the PKD1 expression. Expanding on this relationship, the current study set out to investigate whether BCL6 participates in ischemic stroke by targeting PKD1. Firstly, IS models were established in vitro and in vivo. TUNEL staining and MTT assay were performed to examine the apoptosis and cell survival. In addition, qRT-PCR and Western blot analysis were applied to examine the expression patterns of the BCL6/miR-31/PKD1 axis and its downstream pathway. Bioinformatics analysis was used to predict the target of miR-31. It was found that BCL6 over-expression promoted ODG-induced increase of apoptosis and decreased the cell survival and miR-31 expression levels, whereas the opposite effects were noted in vitro and in vivo models of IS that were treated with shBCL6. Furthermore, miR-31 down-regulation blocked the effect of BCL6 on ODG-induced cell injury. It was also verified that miR-31 directly-targets PKD1. Also, OGD induced the PKD1 expression and activation of the JAK2/STAT3 pathway, while down-regulation of PKD1 inhibited the OGD-induced cell injury and JAK2/STAT3 pathway activation. Lastly, down-regulation of BCL6 in brain brought about a significant reduction in the size of cerebral infarction and oxidative stress levels in IS mice. Collectively, our findings suggest that inhibition of BCL6 may attenuate oxidative stress-induced neuronal damage by targeting the miR-31/PKD1 axis.

Zika virus (ZIKV) infections can cause microcephaly and neurological disorders. However, the early infection events of ZIKV in neural cells remain to be characterized. Here, by using a combination of pharmacological and molecular approaches and the human glioblastoma cell T98G as a model, we first observed that ZIKV infection was inhibited by chloroquine and NH4Cl, indicating a requirement of low intracellular pH. We further showed that dynamin is required as the ZIKV entry was affected by the specific inhibitor dynasore, small interfering RNA (siRNA) knockdown of dynamin, or by expressing the dominant-negative K44A mutant. Moreover, the ZIKV entry was significantly inhibited by chlorpromazine, pitstop2, or siRNA knockdown of clathrin heavy chain, indicating an involvement of clathrin-mediated endocytosis. In addition, genistein treatment, siRNA knockdown of caveolin-1, or overexpression of a dominant-negative caveolin mutant impacted the ZIKV entry, with ZIKV particles being observed to colocalize with caveolin-1, implying that caveola endocytosis can also be involved. Furthermore, we found that the endocytosis of ZIKV is dependent on membrane cholesterol, microtubules, and actin cytoskeleton. Importantly, ZIKV infection was inhibited by silencing of Rab5 and Rab7, while confocal microscopy showed that ZIKV particles localized in Rab5- and Rab7-postive endosomes. These results indicated that, after internalization, ZIKV likely moves to Rab5-positive early endosome and Rab7-positive late endosomes before delivering its RNA into the cytoplasm. Taken together, our study, for the first time, described the early infection events of ZIKV in human glioblastoma cell T98G.

Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis.

Serine hydroxymethyltransferase 2 (SHMT2) has a critical role in serine-glycine metabolism to drive cancer cell proliferation. Yet, the function of SHMT2 in tumorigenesis, especially in human colorectal cancer (CRC) progression, remains largely unclear.

The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression in vitro could promote the proliferation and migration of NPC cells, while promotion of miR-197-3p expression in vivo could significantly inhibit the growth and enhance the radiosensitivity of NPC cells. From the perspective of mechanism, miR-197-3p could inhibit AKT/mTOR phosphorylation activation, inhibit an activated pathway of AKT/mTOR, target Heat Shock 70-kDa Protein 5(HSPA5) related to endoplasmic reticulum homeostasis, inhibit HSPA5-mediated autophagy, and reverse the radioresistance of NPC. Interestingly, exosomal miR-197-3p (EXO-miR-197-3p) reduced the proliferation and migration potential of NPC cells in vitro, and tumor growth and radioresistance of NPC cells in vivo. EXO-miR-197-3p inhibited NPC progression and radioresistance by regulating AKT/mTOR phosphorylation activation and HSPA5-mediated autophagy. In conclusion, our results highlight the potential of EXO-miR-197-3p as an effective radiosensitizer and therapeutic agent for refractory NPC.

Prostate cancer is one of the most severe male malignant tumors, which ranks second in mortality rate among all tumors. Traditional methods of treatment for prostate cancer produce obvious side effects and a high recurrence rate. Cancer stem cells are considered to be a group of cells that determine the proliferation, metastasis, and drug resistance of tumor. Prostate cancer therapy based on microRNAs and prostate cancer stem cells (PCSCs) has been a research hot spot in this field. Previous studies have reported that miR-197 plays an important role in the occurrence and development of prostate cancer, but the molecular mechanism of miR-197 on the development of prostate cancer has not been reported yet. In this study, we verified that miR-197 is significantly overexpressed in prostate cancer tissues and prostate cancer cells. Then, we verified that miR-197 expression affects the proliferation, invasion, and metastasis of prostate cancer cells by regulating integrin subunit alpha V (ITGAV) expression through STAT5 pathway, and the results indicated that the miR-197 inhibitor can be a prostate cancer suppressor. Then we synthesized the AbCD133@GNR@MSNs@miR-197 inhibitor drug carrier, in which 35.42 μg of the miR-197 inhibitor could be loaded in 1 mg of AbCD133@GNR@MSNs. The AbCD133@GNR@MSNs@miR-197 inhibitor demonstrated good photothermal properties and photothermal controlled-release properties. The modified CD133 antibodies on the surface of the nano drug carrier helped more drug carriers to enter the PCSCs. The pharmacodynamic effects of the AbCD133@GNR@MSNs@miR-197 inhibitor on PCSCs in vivo and in vitro were studied under near-infrared radiation. The results showed that the AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could not only significantly suppress the development of PCSCs through ITGAV/STAT5 pathway but also significantly suppress the growth of PCSC solid tumors. In short, our study verified that miR-197 regulates the development of PCSCs through STAT5 pathway by targeting ITGAV, and the AbCD133@MSNs@GNR@miR-197 inhibitor could be a potential suppressor used in prostate cancer treatment. In short, our study found that miR-197 affected the development of prostate cancer by regulating ITGAV. The AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could suppress the development and growth of PCSCs in vitro and in solid tumors not only by targeting the ITGAV but also through photothermal therapy. Our study not only provides a theoretical basis for the clinical treatment of prostate cancer but also provides a research scheme of drug loading and microRNA-based photothermal controlled therapy for prostate cancer.

Due to the lack of sufficient evidence, it is not clear whether robotic-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) is better for prostate cancer. The authors conducted this study by separately pooling and analysing randomised controlled trials (RCTs) and non-randomised studies to compare the perioperative, functional, and oncologic outcomes between RARP and LRP.

To screen genes associated with poor prognosis of clear cell renal cell carcinoma (CcRCC) from the public databases HPA (Human Protein Atlas), UALCAN, and GEPIA (Gene Expression Profiling Interactive Analysis) and to investigate the expression of FKBP10 in CcRCC and the effect on prognosis of the patients and the biological behavior of CcRCC cells.

Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival in patients with castration-resistant prostate cancer (CRPC), but drug resistance remains a considerable clinical challenge.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.