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Although epimedium herb (EH) has been widely used in ancient Chinese medicine to enhance sexual activity, its pharmacological mechanism is not clear. Modern studies have shown that epimedium herb is rich in icariin (ICA, a flavonoid compound), and 91.2% of icariin is converted to icariside II (ICA II) by hydrolytic enzymes in intestinal bacteria after oral administration. YS-10 is a synthetic derivative of icariside II. The aim of this review was to summarize the contemporary evidence regarding the pharmacokinetics, therapeutic properties, and molecular biological mechanisms of ICA and some ICA derivatives for erectile dysfunction therapy.A detailed search was conducted in the PubMed database using keywords and phrases, such as "icariin" AND "erectile dysfunction", "icariside II" AND "erectile dysfunction". The publication time is limited to last 20 years. Articles had to be published in peer reviewed journals.ICA and its some derivatives showed the specific inhibition on phosphodiesterase type 5 (PDE5) and the promotion of testosterone synthesis. In addition, by regulating various reliable evidence of signaling pathways such as PI3K/AKT, TGFβ1/Smad2, p38/MAPK, Wnt and secretion of various cytokines, ICA and ICA derivatives can activate endogenous stem cells (ESCs) leading to endothelial cell and smooth muscle cell proliferation, nerve regeneration and fibrosis inhibition, repair pathological changes in penile tissue and improve erectile function.ICA and some of its derivatives could be a potential treatment for restoring spontaneous erections. In addition ICA and his derivatives may also be valuable as a regenerative medicine approach for other diseases, but more clinical and basic researches with high quality and large samples are recommended.

Gastrointestinal (GI) diseases, including pathological dysplasia, inflammation, neoplasia and injury, suffer millions of patients globally per year. Organoids, three-dimensional cell mass structures supported by biomaterials in dishes, are currently used as a research model for diseases of the small intestine. However, the traditional enzymatic-digestion method for establishing small-intestinal organoids (EnzyOs) is time consuming and often loses the bulk of crypts, a more efficient and reliable method needs to be developed. In this study, using mouse GI organoids as a model, we formulated a rapid mechanical isolation method that could efficiently isolate and culture villi-crypts into small intestinal organoids (MechOs). Primary duodenum organoids generated by MechOs displayed three types of morphology: spheroid, semi-budding and budding, while EnzyOs produced much less budding. Moreover, primary duodenum organoids from MechOs could be subcultured and presented similar gene expression profiles of small intestine specific markers as that from EnzyOs. Importantly, the MechOs method could also be used to generate other types of organoids derived from the stomach, jejunum-ileum, sigmoid-rectum and bile cysts. Taken together, the results show that MechOs could efficiently and economically generate digestive system organoids, providing a potential basis of epithelial organoids for the clinical treatment of gastroenterological diseases.

Since the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, global public health and the economy have suffered unprecedented damage. Based on the increasing related literature, the characteristics and pathogenic mechanisms of the virus, and epidemiological and clinical features of the disease are being rapidly discovered. The spike glycoprotein (S protein), as a key antigen of SARS-CoV-2 for developing vaccines, antibodies, and drug targets, has been shown to play an important role in viral entry, tissue tropism, and pathogenesis. In this review, we summarize the molecular mechanisms of interaction between S protein and host factors, especially receptor-mediated viral modulation of host signaling pathways, and highlight the progression of potential therapeutic targets, prophylactic and therapeutic agents for prevention and treatment of SARS-CoV-2 infection.

Golgi membrane protein 1 (GOLM1) is aberrantly expressed in many types of solid tumors and contributes to cancer development; however, its role in hematopoietic and lymphoid neoplasms remains unknown. Here, we report that GOLM1 was significantly upregulated in anaplastic large cell lymphoma (ALCL), particularly in anaplastic lymphoma kinase-positive (ALK+) ALCL. Mechanistically, the expression of GOLM1 was induced by nucleophosmin (NPM)-ALK in both ALK-transformed T cells and ALCL cell lines through AKT/mTOR pathway. Knockdown of GOLM1 expression led to a reduction in the growth and viability of ALCL cells with increased spontaneous apoptosis, while ectopic expression of GOLM1 protected ALCL cells from apoptosis induced by staurosporine treatment. Moreover, GOLM1 directly interacted with B-cell lymphoma-extra-large protein (BCL-XL, a crucial anti-apoptosis regulator) and significantly prolonged its stability. Introduction of GOLM1 promoted ALK+ ALCL cells colony formation in vitro and tumor growth in a murine xenograft model. Taken together, our findings demonstrate for the first time that GOLM1 plays a critical role in suppressing apoptosis and promoting the progression of ALK+ ALCL and provide evidence that GOLM1 is a potential biomarker and therapeutic target in ALK-induced hematological malignancies.

Background: Dysregulation of long non-coding RNAs (lncRNAs) expression plays pivotal roles in the initiation and progression of gastric cancer (GC). However, the regulation of lncRNA SNHG15 in GC has not been well studied. Mechanisms for ferroptosis by SNHG15 have not been revealed. Here, we aimed to explore SNHG15-mediated biological functions and underlying molecular mechanisms in GC progression. Methods: The novel SNHG15 was identified by analyzing RNA-sequencing (RNA-seq)data of GC tissues from our cohort and TCGA dataset, and further validated by qRT-PCR in GC cells and tissues. Gain- and loss-of-function assays were performed to examine the role of SNHG15 on GC both in vitro and in vivo. The regulatory mechanisms of SNHG15 were investigated by bioinformatics, RNA FISH, luciferase reporter assay, chromatin immunoprecipitation (ChIP), RNA pull-down, RIP-qPCR and luciferase assays. Results: SNHG15 was highly expressed in GC. The enhanced SNHG15 was positively correlated with malignant stage and poor prognosis in GC patients. Gain- and loss-of-function studies showed that SNHG15 was required for affecting cell growth, migration and invasion both in vitro and in vivo. Mechanistically, the oncogenic transcription factors E2F1 and MYC could bind to the SNHG15 promoter and enhanced its expression. Meanwhile, SNHG15 increased E2F1 and MYC mRNA expression by sponging miR-24-3p. Notably, SNHG15 could also enhance the stability of SLC7A11 in cytoplasm by competitively binding HNRNPA1. In addition, SNHG15 inhibited ferroptosis through a HNRNPA1-dependent regulation of SLC7A11/GPX4 axis. Conclusions: Our results support a novel model in which E2F1- and MYC-activated SNHG15 regulates ferroptosis via HNRNPA1-dependent modulation of SLC7A11/GPX4 axis serves as the critical effectors in GC progression, providing a new therapeutic direction in the treatment of GC.

Background Tumor microenvironment are involved in the progression of prostate cancer as an "accomplice", and cancer cell–secreted exosomes were identified as crucial messengers can carry lncRNAs to participate in intercellular communication. Herein, we report that an lncRNA HOXA-AS3, was correlated positively with the castration resistance and progression of prostate cancer. Methods Indirect co-culture of PC-3 and LNCaP was performed to explore the androgen resistance of prostate cancer. MTT, colony formation test, exosome isolation, identification and uptake test, and western blot confirmed that exosomes promote androgen resistance in LNCaP cells. Further, the molecular mechanism of HOXA-AS3 was proved by bioinformation analysis, Dual-Luciferase Reporter Gene Assays, gene knockout and overexpression experiment, cell proliferation and apoptosis experiment, qPCR, immunofluorescence experiment and rescue experiment. Finally, rats xenografts and prostate tissue section were used to examine the role of HOXA-AS3 in the transformation of ADPC into CRPC. Results Exosome-derived lncRNA HOXA-AS3 promotes the proliferation, migration, invasion and hormone resistance of prostate cancer cells. HOXA-AS3 functions as a competing endogenous RNAs (ceRNA) for miRNA-29b-3p, thereby elevating Mcl-1 and STAT3 expression, inhibiting the release of cytochrome c and the activation of Caspases-9, resulting in the decrease of hormone sensitivity, and finally leads to androgen resistance and progression of prostate cancer. Conclusions lncRNA HOXA-AS3 participates in the castration resistance and progression of prostate cancer through regulating the miR-29b-3p/Mcl-1/STAT3 pathway. lncRNA HOXA-AS3 might have the potential to serve as a candidate intervention targets for prostate cancer treatment.

Background: The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) plays a dynamic role in transcriptional and translational regulation, and is involved in carcinogenesis. However, the regulatory circuitry between lncRNAs and miRNAs in gastric cancer (GC) remains elusive.Methods: The novel SNHG15 was identifed by analyzing RNA-sequencing (RNA-seq) data of GC tissues from our cohort and TCGA dataset, and further validated by qRT-PCR in GC cells and tissues. Gain- and loss-of-function assays were performed to examine the role of SNHG15 on GC both in vitro and in vivo. The regulatory mechanisms of SNHG15 were investigated by bioinformatics, fuorescence in situ hybridization (FISH), luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay. Meanwhile, the oncogenic activity of SNHG15 was explored in both GC cells and animal xenograft studies.Results: SNHG15 is highly expressed in GC. The enhanced SNHG15 exists in GC and positively correlates with malignant stage and poor prognosis in GC patients. Gain- and loss-of-function studies showed that SNHG15 was required for affecting cell growth, migration and invasion both in vitro and in vivo. Mechanistically, the oncogenic transcription factors E2F1 and MYC could bind to the SNHG15 promoter and enhance its expression. Meanwhile, SNHG15 increased E2F1, MYC and CDC25A mRNA expression by sponging miR-24-3p. In addition, SNHG15 could also inhibit ferroptosis through a miR-24-3p-mediated regulation of MDM2/p53/SLC7A11 signalling axis.Conclusions: Our results support a novel model in which the E2F1, MYC/SNHG15/miR-24-3p crosstalk served as the critical effectors in GC tumorigenesis and progression, providing a new therapeutic direction in the treatment of GC.

With the increasing prevalence of obesity worldwide, obesity-related female stress urinary incontinence (FSUI) has become a key health problem. Recent studies indicated that FSUI is primarily caused by obesity-related pathological changes, such as fat droplet deposition, and results in pelvic floor nerve, vascular, and urethral striated muscle injury. Meanwhile, treatments for obesity-associated FSUI (OA-FSUI) have garnered much attention. Although existing OA-FSUI management strategies, including weight loss, pelvic floor muscle exercise, and urethral sling operation, could play a role in symptomatic relief; they cannot reverse the pathological changes in OA-FSUI. The continued exploration of safe and reliable treatments has led to regenerative therapy becoming a particularly promising area of researches. Specifically, micro-energy, such as low-intensity pulsed ultrasound (LIPUS), low-intensity extracorporeal shock wave therapy (Li-ESWT), and pulsed electromagnetic field (PEMF), have been shown to restore the underlying pathological changes of OA-FSUI, which might be related by regulation endogenous stem cells (ESCs) to restore urine control function ultimately in animal experiments. Therefore, ESCs may be a target for repairing pathological changes of OA-FSUI. The aim of this review was to summarize the OA-FSUI-related pathogenesis, current treatments, and to discuss potential therapeutic options. In particular, this review is focused on the effects and related mechanisms of micro-energy therapy for OA-FSUI to provide a reference for future basically and clinical researches.

High plasma lactate is emerging as a critical regulator in development and progression of many human malignancies. Small RNAs derived from cleavage of mature tRNAs have been implicated in many cellular stresses, but the detailed mechanisms that respond to lactic acid (LA; acidic lactate) are not well defined. Here, using an Epstein-Barr virus (EBV)-immortalized B lymphoblastic cell line (LCL) as a model, we report that LA induces cleavage of mature tRNA at the anticodon loop, particularly production of three 5′-tRNA halves (5′-HisGUG, 5′-ValAAC, and 5′-GlyGCC), along with increased expression of RNA polymerase III and angiogenin (ANG). Of these, only the 5′-HisGUG half binds to the chromatin regulator argonaute-2 (AGO2) instead of the AGO1 protein for stability. Notably, the levels of ANG and 5′-HisGUG half expression in peripheral blood mononuclear cells from B cell lymphoma patients are tightly correlated with lactate dehydrogenase (LDH; a lactate indicator) in plasma. Silencing production of the 5′-HisGUG half by small interfering RNA or inhibition of ANG significantly reduces colony formation and growth of LA-induced tumor cells in vitro and in vivo using a murine xenograft model. Overall, our findings identify a novel molecular therapeutic target for the diagnosis and treatment of B cell lymphoma.

Aggressive B-cell lymphoma is one of the most common types of blood malignancy. Robust delivery of genes of interest into target cells, long-term gene expression, and minimal risk of secondary effects are highly desirable for translational medicine including gene therapy and studies on gene function. However, efficient gene delivery into viral or nonviral B-lymphoma cells remains a challenge. Here, we report a strategy for inducing foreign gene expression in B-lymphoma cells by using a vector based on the novel parainfluenza virus PIV5-L (a strain isolated from B cells) that enabled us to study and control the function of a gene product within B-lymphoma cells. Using enhanced green fluorescent protein (eGFP) as a reporter, we successfully rescued PIV5-L and established a one-step system to generate PIV5-L virus-like particles (L-VLPs) with efficient delivery into a broad spectrum of susceptible B-lymphoma cell lines, including Epstein-Barr virus (EBV)- or Kaposi’s sarcoma-associated herpesvirus (KSHV)-transformed B-lymphoblastoid cells. Similar to lentiviral vector, the L-VLP highly expressed exogenous genes and remained stable for long periods without obvious negative effects on cell viability. Taken together, these data demonstrate that the PIV5-L-based system provides a potential new strategy for the delivery of desirable genes and the treatment of cancer. IMPORTANCE B-cell lymphoma is a common aggressive neoplastic disorder of lymphocytes. Delivery of genes of interest into B cells, particularly virus-mediated B-lymphoma cells, is still a challenge. In this study, we report that a system (L-VLP) based on the parainfluenza virus PIV5-L strain isolated from B cells had highly expressed exogenous genes and remained stable without obvious cell toxicity, which provides a potential new strategy for gene delivery and treatment of B-cell cancer.

The demand for telesurgery is rising rapidly, but robust evidence regarding the feasibility of its application in urology is still rare. From March to October 2021, a surgeon-controlled surgical robot in a tertiary hospital in Qingdao was used to remotely conduct robot-assisted laparoscopic radical nephrectomy (RN) in 29 patients located in eight primary hospitals. The median round-trip delay was 26 ms (interquartile range [IQR] 5) and the median distance between the primary hospital and the surgeon was 187 km (IQR 57). Both the master unit and the slave unit were guaranteed by network and mechanical engineers, and surgical assistants were well prepared on the patient side to prevent complications. The primary evaluation metric was the success rate, defined as the percentage of patients who underwent successful remote RN without conversion to other surgical procedures and no major intraoperative or postoperative complications. The results demonstrate that the combination of 5G technology and surgical robots is a novel potential telemedicine-based therapy choice for renal tumors. PATIENT SUMMARY: Our study shows that telesurgery using 5G technology is a safe and feasible treatment option for patients with kidney tumors. The total delay between the remote location and the operating rooms where surgery was being performed was just 200 ms. This approach could reduce health care costs and improve the quality of medical services accessed by patients.

Background Previous study has reported that loss of epithelial androgen receptor (AR) may promote tumor progression and cause TRAMP mouse model die earlier. The detail mechanisms, however, remain unclear. Methods Immunohistochemistry assay, Western blot and real-time PCR were used to detect the expression of epithelial and mesenchymal markers. RNA extraction, RT-PCR, quantitative RT-PCR, BrdU incorporation assays, flow cytometry and other experimental technics were also used in present work. Results Decreased expression of epithelial markers (Cytokeratin 8, NKX3.1 and E-cadherin) and increased expression of mesenchymal markers (α-SMA, Vimentin, and N-cadherin) in were found in AR knockout TRAMP tumors. Further investigation indicated that AR signal deprivation is associated with cell morphology transition, high cell mobility, high cell invasion rate and resistance to anoikis in TRAMP prostate tumor cells. Together, these findings implied knockout AR in TRAMP prostate tumor may lead to EMT, which may result in earlier metastasis, and then cause TRAMP mice die earlier. TGF-β1 is responsible for EMT in AR knockout TRAMP tumor cells. Conclusions In conclusion, ADT therapy induced hormone refractory prostate cancer may gain the ability of metastasis through cell's EMT which is a phase of poor differentiation. Anti-EMT drugs should be developed to battle the tumor metastasis induced by ADT therapy.

Background This research aims to identify the current and future trends in the incidence and death rate of prostate cancer and to provide the necessary data support for making relevant health decisions. Methods This study used the collected data and methodologies to describe the incidence and mortality trends of prostate cancer from 1990 to 2016. Based on the data, this paper projected the future trends in prostate cancer incidence and death rate. Results In 2016, prostate cancer cases [1,435,742; 95% uncertainty interval (UI), 1,293,395-1,618,655] were nearly 2.5-fold the number in 1990 (579,457; 95% UI, 521,564-616,107). Deaths increased by 2.0-fold from 191,687 (95% UI, 168,885-209,254) in 1990 to 380,916 (95% UI, 320,808-412,868) in 2016. The global age-standardized incidence rate (ASIR) increased from 17.75 (95% UI, 18.91-15.95) in 1990 to 22.12 (95% UI, 19.92-24.91) in 2016, changing 24.62%. The global change of age-standardized death rate (ASDR) has declined slightly, but in some regions it shows a trend of growth. By sociodemographic index (SDI) sub-types, prostate cancer will frequently occur in high SDI countries from 1990 to 2030. Simultaneously, the highest mortality will present in low SDI countries. Conclusions Through projecting and analyzing incidence and mortality rate of prostate cancer, from 1990 to 2030, by different ages, regions and SDI sub-types, this result may reveal the relationship between prostate cancer and financial development. At the same time, the result also showed a sufficiently heavy burden of prostate cancer, but the burden varies greatly in each region. The burden is a challenge and will require attention for all levels of society. The current study is beneficial to formulate more specific and efficient policies.

Hypoxia signaling is a key regulator in the development and progression of many types of human malignancies, including viral cancers. The latency-associated nuclear antigen (LANA), encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) during latency, is a multifunctional protein that plays an essential role in viral episome maintenance and lytic gene silencing for inducing tumorigenesis. Although our previous studies have shown that LANA contains a SUMO-interacting motif (LANASIM), and hypoxia reduces SUMOylated KAP1 association with LANASIM, the physiological proteomic network of LANASIM-associated cellular proteins in response to hypoxia is still unclear. In this study, we individually established cell lines stably expressing wild-type LANA (LANAWT) and its SIM-deleted mutant (LANAdSIM) and treated them with or without hypoxia, followed by coimmunoprecipitation and mass spectrometry analysis to systemically identify the hypoxia-responsive profile of LANASIM-associated cellular proteins. We found that in hypoxia, the number of cellular proteins associated with LANAWT instead of LANAdSIM was dramatically increased. Functional network analysis revealed that two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, were significantly enriched for 28 LANASIM-associated proteins in response to hypoxia. HNRNPU was one of the proteins consistently identified that interacted with LANASIM in different proteomic screening systems and responded to hypoxia. This study provides a proteomic profile of LANASIM-associated proteins in hypoxia and facilitates our understanding of the role of the collaboration between viral infection and the hypoxia response in inducing viral persistence and tumorigenesis. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANASIM) and reduces the association with SUMOylated KAP1 upon hypoxic treatment. However, the physiological systematic network of LANASIM-associated cellular proteins in hypoxia is still unclear. Here, we revealed two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, that were significantly enriched for 28 LANASIM-associated proteins in hypoxia. This discovery not only provides a proteomic profile of LANASIM-associated proteins in hypoxia but also facilitates our understanding of the collaboration between viral infection and hypoxic stress in inducing viral persistence and tumorigenesis.

Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females’ fertility and causes different symptoms among pregnant and non-pregnant females remains unknown. Here, we examined the differences in viral loads, SARS-CoV-2-specific antibody titers, proinflammatory cytokines, and levels of T cell activation after SARS-CoV-2 sub-lethal infection between pregnant and non-pregnant human Angiotensin-Converting Enzyme II (ACE2) transgenic mouse models. Both mice showed elevated levels of viral loads in the lung at 4 days post-infection (dpi). However, viral loads in the pregnant group remained elevated at 7 dpi while decreased in the non-pregnant group. Consistent with viral loads, increased production of proinflammatory cytokines was detected from the pregnant group, and the IgM or SARS-CoV-2-specific IgG antibody in serum of pregnant mice featured delayed elevation compared with non-pregnant mice. Moreover, by accessing kinetics of activation marker expression of peripheral T cells after infection, a lower level of CD8+T cell activation was observed in pregnant mice, further demonstrating the difference of immune-response between pregnant and non-pregnant mice. Although vertical transmission did not occur as SARS-CoV-2 RNA was absent in the uterus and fetus from the infected pregnant mice, a lower pregnancy rate was observed when the mice were infected before embryo implantation after mating, indicating that SARS-CoV-2 infection may interfere with mice’s fertility at a specific time window. In summary, pregnant mice bear a weaker ability to eliminate the SARS-CoV-2 virus than non-pregnant mice, which was correlated with lower levels of antibody production and T cell activation.

Reprogramming of energy metabolism is a key for cancer development. Kaposi’s sarcoma-associated herpesvirus (KSHV), a human oncogenic herpesvirus, is tightly associated with several human malignancies by infecting B-lymphocyte or endothelial cells. Cancer cell energy metabolism is mainly dominated by three pathways of central carbon metabolism, including aerobic glycolysis, glutaminolysis, and fatty acid synthesis. Increasing evidence has shown that KSHV infection can alter central carbon metabolic pathways to produce biomass for viral replication, as well as the survival and proliferation of infected cells. In this review, we summarize recent studies exploring how KSHV manipulates host cell metabolism to promote viral pathogenesis, which provides the potential therapeutic targets and strategies for KSHV-associated cancers.

Here we isolated the Fab clones 1-A11, 6-C6, 10-B2, and 15-H10 and confirmed their recognition of LMP1 expressed on the surface of EBV+ B95.8 cells. Recognition of LMP1 on the cell membrane by clone 15-H10 was verified through immunofluorescent assay, while other clones failed the recognition. One of the possible reasons could be the stringent washing in this assay that ruptured the low affinity Fab-LMP1 binding. EBV infection is related with multiple diseases, and conventional approaches used in laboratory diagnostic tests for EBV infection and pathogenesis have their limitations [(generate false positive results or lack the ability to localize the expression of EBV within target cells) ( Young and Rickinson 2004 )]. The LMP1-specific Fab clones reported here need further evaluation in both affinity and specificity in testing EBV+ patient samples, and hopefully it could have potential applications in EBV diagnostics and directly targeting EBV-related tumors in adoptive T cell therapy.

High plasma lactate is associated with poor prognosis of many malignancies, but its role in virally mediated cancer progression and underlying molecular mechanisms are unclear. Epstein-Barr virus (EBV), the first human oncogenic virus, causes several cancers, including B-cell lymphoma. Here, we report that lactate dehydrogenase A (LDH-A) expression and lactate production are elevated in EBV-immortalized B lymphoblastic cells, and lactic acid (LA; acidic lactate) at low concentration triggers EBV-infected B-cell adhesion, morphological changes, and proliferation in vitro and in vivo. Moreover, LA-induced responses of EBV-infected B cells uniquely occurs in viral latency type III, and it is dramatically associated with the inhibition of global viral microRNAs, particularly the miR-BHRF1 cluster, and the high expression of SMAD3, JUN, and COL1A genes. The introduction of miR-BHRF1-1 blocks the LA-induced effects of EBV-infected B cells. Thus, this may be a novel mechanism to explain EBV-immortalized B lymphoblastic cell malignancy in an LA microenvironment.

Purpose As the mechanism of interaction between circular RNAs (circRNAs) and microRNAs (miRNAs) in regulating the development of prostate cancer (PCa) is not clear, this study focuses on investigating these effects. Materials and Methods Sample tissues were collected from the PCa of patients, and microarray analysis of human circRNAs was conducted. The expression of circ_0001686, hsa_miR-411-5p (miR-411-5p) were also detected by qRT-PCR. Circ_0001686 and miR-411-5p mimics were transfected into the PCa cell lines (CWR22RV1and LNCaP) and MTT, colony formation, Transwell, and scratch wound assays were used to analyze the biological behaviors of PCa cells. Si-circ_0001686 and ASO-miR-411-5p were used as negative controls, and dual-luciferase reporter assays were performed to verify the interactions among circ_0001686, miR-411-5p, and SMAD3/TGFBR2. The levels of SMAD3 and TGFBR2 in different treated PCa cells were measured by western blot, and in vivo experiments in a nude mouse model were carried out to strengthen the in vitro findings of miR-411-5p. Results The expression of circ_0001686 was up-regulated, while the expression of miR-411-5p was down-regulated in PCa cells. Moreover, circ_0001686 promoted cell proliferation, migration, and invasion. Molecular mechanism exploration revealed that circ_0001686 could reduce miR-411-5p, affecting the downstream target genes of SMAD3 and TGFBR2. In vitro and in vivo studies verified that miR-411-5p inhibits PCa progression. Conclusions Circ_0001686 can reduce miR-411-5p to increase the expression of SMAD3/TGFBR2, which consequently promotes the proliferation, invasion, and migration of PCa cells.

Background Although several distribution patterns of periprostatic neurovascular bundles have been proposed, variant dissection technique based on these patterns still confused surgeons. The aim of this study was to describe the periprostatic neurovascular bundles and their relationship with the fascicles around prostate and provide the accurate morphologic knowledge of periprostatic tissue for prostate operation. Methods The pelvic viscera were obtained from 26 adult male cadavers. They were embedded in celloidin and cut into successive slices. The slices were explored with anatomic microscopy. 3-Dimensional reconstruction was achieved with celloidin sections and series software. Results The prostatic capsule which surrounded the dorsal, bilateral aspect of the prostate was attached ventrally to anterior fibrous muscular stroma (AFMS). The lower part of the striated sphincter completely embraced the urethral; the upper part of this muscle covered the lower ventral surface of prostate. The upper ventral surface of prostate is covered by the circular muscle of detrusor. The levator fascia and the capsule adhered on the most convex region of the lateral prostate, but separated on the other region. The pelvic neurovascular bundles (PNVB) divided into the anterior and posterior divisions. The anterior division continued as dorsal vascular complex (DVC). The distal part of DVC entered into penile hilum. The posterior division continued as neurovascular bundles, and then as the cavernous supply (CS). The distal part of CS joined into pudendal neurovascular bundles. Conclusions The capsule and AFMS formed a pocket like complex. There were anterior and posterior neurovascular approaches from PNVB to penile hilum.

BACKGROUND: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice. RESULTS: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P

SUMMARYThe global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission.

BACKGROUND: Bladder cancer is a leading cause of cancer-related deaths all over the world. Epidemiological studies of bladder cancer are therefore crucial for policy making. This study was carried out to describe the characteristics of changes in the incidence and mortality of bladder cancer from 1990 to 2016 by age group, gender, geographical region, and sociodemographic index (SDI) and to simultaneously project future trends up to 2030. METHODS: Incidence and mortality trends in bladder cancer from 1990 to 2016 were described based on data and methodologies from the Global Burden of Disease (GBD) Study. The data also allowed the future trends of bladder cancer incidence and mortality to be predicted by ARIMA model. Trends were analyzed by age group, gender, and SDI. Projections to 2030 were sub-analyzed by SDI countries. R software (x64 version 3.5.1), SAS (version 9.3), and SPSS (version 22.0) were used throughout the process. RESULTS: Globally, in 2016, there were 437,442 [95% uncertainty interval (UI), 426,709–447,912] new bladder cancer cases and 186,199 (95% UI, 180,453–191,686) bladder cancer-associated deaths. Between 1990 and 2016, changes in the age-standardized incidence rate (ASIR) of bladder cancer decreased by 5.91% from 7.11 (95% UI, 6.93–7.27) in 1990 to 6.69 (95% UI, 6.52–6.85) in 2016. The age-standardized death rate (ASDR) decreased from 3.58 (95% UI, 3.49–3.68) to 2.94 (95% UI, 2.85–3.03) over the same period of time. In future, the greatest occurrence of bladder cancer will be in high SDI countries, followed by high-middle SDI countries. Moreover, bladder cancer incidence rates may increase substantially in middle SDI countries, while the incidence rates will remain relatively stable for men and women in other SDI countries. From 2017 to 2030, bladder cancer deaths will continue to increase in low SDI countries, while deaths in other SDI countries will continue to decrease. CONCLUSIONS: There was a regional difference in the incidence and mortality trends of bladder cancer between 1990 and 2016. Overall, the situation is not optimistic. From 2017 to 2030, the incidence of bladder cancer will continue to rise, especially in high and high-middle SDI countries, where decision-makers should propose appropriate policies on the screening and prevention of bladder cancer.