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Abstract Ribosomal proteins (RPs) are essential components of ribosomes, playing a role not only in ribosome biosynthesis, but also in various extra-ribosomal functions, some of which are implicated in the development of different types of tumors. As universally acknowledged, hepatocellular carcinoma (HCC) has been garnering global attention due to its complex pathogenesis and challenging treatments. In this review, we analyze the biological characteristics of RPs and emphasize their essential roles in HCC. In addition to regulating related signaling pathways such as the p53 pathway, RPs also act in proliferation and metastasis by influencing cell cycle, apoptosis, angiogenesis, and epithelial-to-mesenchymal transition in HCC. RPs are expected to unfold new possibilities for precise diagnosis and individualized treatment of HCC.

ObjectiveTo establish a predictive model for distinguishing testicular benign or yolk sac tumors in children.MethodsWe retrospectively analyzed data for 119 consecutive patients with unilateral testicular tumors treated at a single institution from June 2014 to July 2020. The patients were divided into the benign (n = 90) and yolk sac (n = 29) tumor groups based on the pathological diagnosis. We recorded patient age, serum markers [serum alpha-fetoprotein (AFP), human chorionic gonadotropin], and tumor ultrasonic findings (maximum diameter, ultrasonic echo, blood flow signal). Predictive factors were identified using descriptive statistical methods. A nomogram was established for preoperative prediction. An additional 46 patients were used as a validation cohort to verify the model.ResultsPatients with testicular yolk sac tumors were younger (median age: 14.0 vs. 34.0 months, P = 0.001) and had a higher incidence of elevated AFP levels (93.1% vs. 2.2%, P

Background Ovarian cancer is an aggressive malignancy with high mortality known for its considerable metastatic potential. This study aimed to explore the expression and functional role of Unc-51 like autophagy activating kinase 2 (ULK2) in the progression of ovarian cancer. Methods ULK2 expression patterns in ovarian cancer tissues as well as benign tumor control samples obtained from our institution were evaluated using immunohistochemistry. Cell counting kit 8 and Transwell assays were applied to assess the effects of ULK2 overexpression on cell proliferation, migration and invasion, respectively. RNA sequencing was performed to explore potential mechanisms of action of ULK2 beyond its classical autophagy modulation. Results Our experiments showed significant downregulation of ULK2 in ovarian cancer tissues. Importantly, low expression of ULK2 was markedly correlated with decreased overall survival. In vitro functional studies further demonstrated that overexpression of ULK2 significantly suppressed tumor cell proliferation, migration, and invasion. RNA sequencing analysis revealed a potential regulatory role of ULK2 in the insulin signaling pathway through upregulation of insulin-like growth factor binding protein-3 (IGFBP3) in ovarian cancer cells. Conclusions In summary, the collective data indicated that ULK2 acted as a tumor suppressor in ovarian cancer by upregulating the expression of IGFBP3. Our study underscores the potential utility of ULK2 as a valuable prognostic marker for ovarian cancer.

Abstract Ample evidence reveals that glycolysis is crucial to tumor progression; however, the underlying mechanism of its drug resistance is still worth being further explored. TRAF6, an E3 ubiquitin ligase, is well recognized to overexpress in various types of cancer, which predicts a poor prognosis. In our study, we discovered that TRAF6 was expressed more significantly in the case of triple‐negative breast cancer (TNBC) than in other of breast cancers, promoting chemoresistance to paclitaxel; that inhibited TRAF6 expression in the chemoresistant TNBC (TNBC‐CR) cells enhanced the sensitivity by decreasing glucose uptake and lactate production; that TRAF6 regulated glycolysis and facilitated chemoresistance via binding directly to PKM2; and that overexpressing PKM2 in the TNBC‐CR cells with TRAF6 knocked down regained significantly TRAF6‐dependent drug resistance and glycolysis. Additionally, we verified that TRAF6 could facilitate PKM2‐mediated glycolysis and chemoresistance in animal models and clinical tumor tissues. Thus, we identified the novel function of TRAF6 to promote glycolysis and drug resistance in TNBC with the regulation of PKM2, which could provide a potential molecular target for TNBC treatment.

ABSTRACTHypertension, a prevalent chronic disease, has been associated with increased COVID-19 severity. To promote the COVID-19 booster vaccination of hypertensive patients, this study investigated the willingness to receive boosters and the related influencing factors based on the health belief model (HBM model). Between June and October 2022, 453 valid questionnaires were collected across three Chinese cities. The willingness to receive a booster vaccination was 72.2%. The main factors that influenced the willingness of patients with hypertension to receive a booster shot were male (χ2 = 7.008, p = .008), residence in rural (χ2 = 4.778, p = .029), being in employment (χ2 = 7.232, p = .007), taking no or less antihypertensive medication (χ2 = 9.372, p = .025), with less hypertension-related comorbidities (χ2 = 35.888, p

The origin and intrafamilial transmission of Human T-Lymphotropic Virus Type 1 (HTLV-1) in non-endemic populations such as China is still unknown. In this study, donors from blood banks/centers in China (including 28 provinces and Shenzhen city) during 2019 and 2021 were screened for HTLV-1/2 antibody, and all the reactive samples were tested using a line immunoassay (LIA) and quantitative polymerase chain reaction (qPCR). Samples that can be detected using qPCR were amplified and sequenced for the long terminal repeat (LTR) region. The positive donors were contacted to identify their relatives. As a result, 4,451,883 blood donors were totally tested, and 50 of them were confirmed to be HTLV-1/2 positive. Viral LTR sequences genotyped from 26 HTLV-1 carriers demonstrated that all had the HTLV-1a genotype, of which Transcontinental and Japanese subgroups accounted for half each. There were 17 family members of 11 index donors detected, and the HTLV-1 infection rate in the spouses of male index donors (83.3%, 5/6) was significantly higher than that in the husbands of female index donors (0.0%, 0/4). However, 7 children of HTLV-1 positive women were tested and found negative. Therefore, our findings indicated that HTLV-1 is spreading silently from high-endemic to low-endemic areas in China. To prevent further HTLV-1/2 transmission, an efficient HTLV-1/2 screening strategy and counseling of the virus carriers are essential.

Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for high-frequency mutations in transmembrane domain (TMD) of S protein in the OBI population. Plasmids with TMD high-frequency mutations were constructed, in vivo and in vitro functional experiments were performed to investigate possible molecular mechanisms of OBI occurrence. We found 22 high-frequency TMD mutations in genotype B OBI strains. Among them, five mutations can lead to impairment of HBsAg secretion; seven mutations had accumulated intracellular HBsAg while extracellular HBsAg didn’t decrease compared to wildtype. This study chose C85R from TMD2, F220C, and F220Y from TMD4 for further exploration. Protein structure predication showed these three mutant HBsAg displayed changed hydrophilic properties and tended to accumulate in the phospholipid bilayer of cell membrane. Mutant HBsAg’s secretion disorder may induce OBI. On the other hand, V168A + V177A from TMD3 expressed increased HBsAg both in intracellular and extracellular levels. This mutation had most unstable natural conformation and may be inclined to transition into V177A or V168A + S174N + V177A. These three mutations were more prone to mixed infection, presenting a state of coexistence, thus approaching the impaired secretion pattern of OBI. This study demonstrated TMD mutations could contribute to the occurrence of OBI and provided a theoretical basis for OBI study and the functional cure of chronic hepatitis B virus infection.

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease with poor prognosis and high mortality rate. In the process of IPF, inflammatory dysregulation of macrophages and massive fibroblast aggregation and proliferation destroy alveoli, which cause pulmonary dysfunction, and ultimately lead to death due to respiratory failure. In the treatment of IPF, crossing biological barriers and delivering drugs to lung interstitium are the major challenges. In order to avoid the side effect of macrophages proliferation, we proposed, designed, and evaluated the strategy which combined macrophage depletion by intervaginal space injection and intravenous targeted therapy on bleomycin mouse model. We found that it inhibited pulmonary macrophages, reduced macrophage depletion in non-target organs, improved pulmonary drug targeting, impeded the progression of pulmonary fibrosis, and accelerated the recovery of pulmonary function. This combination therapeutic strategy shows good biosafety and efficacy, induces a targeted response, and is promising as a practical new clinical approach towards the treatment of pulmonary fibrosis.

Abstract To investigate the urodynamic study (UDS) result in pediatric patients suffering from spastic cerebral palsy (CP). Medical records of patients diagnosed CP having pre-operative UDS results underwent selective dorsal rhizotomy (SDR) from Jan. 2020 to May. 2021 were retrospectively reviewed. Fifty-seven cases diagnosed spastic CP were included in the study (mean age, 6.73 ± 2.84 years), among which, 46 were ambulatory and 11 non-ambulatory. Average gross motor function measure-66 (GMFM-66) score was 62.16 ± 11.39. Reduced bladder capacity was seen in 49.12% of these cases and cases with lower GMFM-66 score possessed a higher incidence rate of having low bladder capacity (p

Abstract Background Stanniocalcin 1 (STC1) plays an integral role in ovarian cancer (OC). However, the functional role of STC1 in metastasis, lipid metabolism and cisplatin (DDP) chemoresistance in OC is not fully understood. Methods Single-cell sequencing and IHC analysis were performed to reveal STC1 expression profiles in patient tissues. Metastasis, lipid metabolism and DDP chemoresistance were subsequently assessed. Cell-based in vitro and in vivo assays were subsequently conducted to gain insight into the underlying mechanism of STC1 in OC. Results Single-cell sequencing assays and IHC analysis verified that STC1 expression was significantly enhanced in OC tissues compared with para-carcinoma tissues, and it was further up-regulated in peritoneal metastasis tissues compared with OC tissues. In vitro and in vivo experiments demonstrated that STC1 promoted metastasis, lipid metabolism and DDP chemoresistance in OC. Simultaneously, STC1 promoted lipid metabolism by up-regulating lipid-related genes such as UCP1, TOM20 and perilipin1. Mechanistically, STC1 directly bound to integrin β6 (ITGB6) to activate the PI3K signaling pathway. Moreover, STC1 was directly regulated by Forkhead box C2 (FOXC2) in OC. Notably, targeting STC1 and the FOXC2/ITGB6 signaling axis was related to DDP chemoresistance in vitro. Conclusions Overall, these findings revealed that STC1 promoted metastasis, lipid metabolism and DDP chemoresistance via the FOXC2/ITGB6 signaling axis in OC. Thus, STC1 may be used as a prognostic indicator in patients with metastatic OC. Meanwhile, STC1 could be a therapeutic target in OC patients, especially those who have developed chemoresistance to DDP.

Abstract Background Chemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets. Methods RNA sequencing of cisplatin‐resistant and ‐sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin‐1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1‐knockout cisplatin‐resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and Fӧrster resonance energy transfer‐fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish. Results FBN1 expression was significantly enhanced in cisplatin‐resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin‐resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin‐sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2‐mediated angiogenesis and glycolysis. Conclusions The FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1‐targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

Abstract Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

IntroductionOccult hepatitis B virus infection (OBI) is an HBsAg negative state in HBV infection with usually inactive HBV replication. However, there were a minority of individuals with positive HBeAg and anti-HBs among OBI blood donors and few studies have focused on this unusual serological pattern.Methods2022 plasma of blood donors that preliminary screened reactive for HBV DNA and non-reactive for HBsAg were collected from 16 provinces in China from 2015 to 2018. HBV DNA and HBsAg in these samples were retested using the Cobas TaqScreen MPX test and ARCHITECT HBsAg Quantitative II assay. Lumipulse HBsAg-HQ assay and polyethylene glycol (PEG)-double precipitation following HCl and trypsin digestion were performed to detect HBsAg from HBsAg-anti-HBs circulating immune complexes (CICs).Results1487 of 2022 samples were positive for Cobas HBV DNA test and non-reactive for ARCHITECT HBsAg assay, while 404 of them were positive using Lumipulse HBsAg-HQ assay. 10 HBsAg-/anti-HBs+/HBeAg+ OBI blood donor samples were further dissociated and HBsAg-CICs were detected in 7 samples. Sequencing analysis showed that D44N, N98T, G73S, Del 56-116, and I161T occurred in the pre-S region, and immune escape mutations such as P127T, F134L, G145R, V168A, and I126T/S in the S region were found.DiscussionIn conclusion, there were a minority of HBsAg-/anti-HBs+/HBeAg+ individuals in OBI blood donors. The undetectable HBsAg in these individuals was mainly due to HBsAg-CICs. Immune escape-associated mutations also happened under the host’s selective pressure. HBsAg dissociation methods or Lumipulse HBsAg-HQ assay is recommended to distinguish these individuals.

Hepatitis delta virus (HDV) coinfected with HBV causes severe viral hepatitis, however, the number of HDV infection may be underestimated. In the present study, we enrolled 1,141,331 blood donations, routinely tested for HBsAg and/or HBV DNA, from 21 blood establishments in China. 2,690 donors were HBsAg and/or HBV DNA positive after screening tests. After verification of HBsAg and HBV DNA, 1,490 samples were HBsAg confirmed-positive, including 1,459 HBV DNA-positive samples, and 825 samples were seronegative but HBV DNA positive. We first analyzed demographic characteristics of involved 2,690 donors with different HBV infection status and found the proportions of males, the older donors, workers and farmers were higher in HBsAg-/HBV DNA+ group. Then we evaluated specificity of HDV IgG and IgM antibody assays with 375 HBsAg and HBV DNA confirmed-negative samples, and 374 were tested negative using the two assays, respectively, suggesting a specificity of 99.73% for both assays (374/375, 95% Cl: 98.51–99.95%). Subsequently, we tested for HDV IgG and IgM of 2,315 HBsAg and/or HBV DNA confirmed-positive samples, and nine showed reactivity for IgG, while two were reactive for IgM. All these 11 reactive samples were tested again with another HDV pan-Ig and IgM testing assays and HDV RNA, and only one donor was identified as HDV IgG positive and HDV RNA negative, showing an HDV seroprevalence of 0.067% (95%CI: 0.012–0.38%) among HBsAg-positive blood donors in China. The positive donor was followed up for 2 years after the donation date, and decreased antibody titer of HDV IgG and HBsAg conversion were observed, and the infection status of the donor was HDV infection with recovery and occult hepatitis B virus infection with genotype C2. These results indicated a low seroprevalence of HDV infection among blood donors and a low risk of HDV transmission through blood transfusion in China.

Abstract Ovarian cancer (OC) is one of the most common malignant tumors in women. OC is associated with the activation of oncogenes, the inactivation of tumor suppressor genes, and the activation of abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role in OC tumorigenesis. Epigenetic processes do not change DNA sequences but regulate gene expression through DNA methylation, histone modification, and non-coding RNA. This review comprehensively considers the importance of epigenetics in OC, with a focus on microRNA and long non-coding RNA. These types of RNA are promising molecular markers and therapeutic targets that may support precision medicine in OC. DNA methylation inhibitors and histone deacetylase inhibitors may be useful for such targeting, with a possible novel approach combining these two therapies. Currently, the clinical application of such epigenetic approaches is limited by multiple obstacles, including the heterogeneity of OC, insufficient sample sizes in reported studies, and non-optimized methods for detecting potential tumor markers. Nonetheless, the application of epigenetic approaches to OC patient diagnosis, treatment, and prognosis is a promising area for future clinical investigation.

Abstract Background All commercial Hepatitis C virus antibody (anti-HCV) assays use a combination of recombinant antigens to detect antibody response. Antibody responses to individual antigenic regions (core, NS3/4 and NS5) used in assays have not been investigated. Methods In this study, we quantified HCV viral load, tested anti-HCV with four commercial assays (Ortho-ELISA, Murex-ELISA, Architect-CMIA and Elecsys-ECLIA) in 682 plasma specimens. In antigenic region ELISA platform, microwells were coated with three antigens: core (c22-3), NS3/4 (c200) and NS5 individually. The signal-to-cutoff (S/Co) values of different assays, and antibody responses to individual antigens were compared. The specimens were divided into HCV RNA positive group, anti-HCV consistent group, and anti-HCV discrepant group. Results Anti-core and anti-NS3/4 were simultaneously detected in 99.2% of HCV RNA positive specimens and showed great consistency with total anti-HCV signals. Responses to the core region were more robust than those to the NS3/4 region in anti-HCV consistent group (p

Abstract Background Although programmed cell death‐ligand 1 (PD‐L1) plays a well‐known function in immune checkpoint response by interacting with programmed cell death‐1 (PD‐1), the cell‐intrinsic role of PD‐L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD‐L1 in the progression and metastasis of ovarian cancer. Methods Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD‐L1‐knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD‐L1 in ovarian cancer. Results Our results showed that PD‐L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD‐L1 was identified to directly interact with vascular endothelial growth factor receptor‐2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD‐L1 was found to be regulated by the oncogenic transcription factor c‐JUN at the transcriptional level, which enhanced the expression of PD‐L1 in ovarian cancer. Furthermore, we demonstrated that PD‐L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti‐angiogenesis and the inhibition of cell migration and invasion. Conclusion Our results demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, suggesting that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

Abstract Background Ovarian cancer is highly lethal and has a poor prognosis due to metastasis. Long non-coding RNAs (lncRNAs) are key regulators of tumor development, but their role in ovarian cancer metastasis remains unclear. Methods The expression of lnc-CTSLP8 in ovarian cancer was analyzed in public databases (TCGA and GEO) and validated via qRT-PCR. Lnc-CTSLP8 overexpression and knockout cell lines were constructed using a lentiviral vector and the CRISP/Cas9 system. Cell proliferation, colony formation, migration, and invasion were analyzed. An ovarian orthotopic tumor mouse model was used for the in vivo study. Changes in autophagosomes, autolysosomes, and mitochondria in ovarian cancer cells were observed via transmission electron microscopy. EMT markers were detected by immunoblotting and immunofluorescence assays. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assays were performed to confirm the interaction between lnc-CTSLP8 and miR-199a-5p. Results A novel pseudogene, lnc-CTSLP8, was identified in ovarian cancer, with significantly elevated expression in metastatic tumor tissues compared to primary ovarian tumors. When overexpressed, lnc-CTSLP8 promoted ovarian cancer in vitro and in vivo by acting as a sponge for miR-199a-5p. Autophagy and EMT in ovarian cancer were also enhanced by lnc-CTSLP8. Mechanistically, lnc-CTSLP8 upregulated CTSL1 as a competitive endogenous RNA and exhibited oncogenic effects. Moreover, CTSL1 inhibitor treatment and miR-199a-5p overexpression abrogated the effects of lnc-CTSLP8 overexpression. Conclusions lnc-CTSLP8 acts as a ceRNA in ovarian cancer and represents a potential therapeutic target for metastatic ovarian cancer.

Background: Rapid progression and early metastasis remain the main cause of high mortality in epithelial ovarian cancer (EOC) patients. The objective of this study was to explore the mechanisms of EOC progression and detect the function of leucine-rich alpha-2-glycoprotein 1 (LRG1) in modulating the pathologic process. Methods: Ultracentrifugation was initially performed to extract exosomes from the urine samples of EOC patients and healthy female subjects. Mass spectrometry (MS) was employed to analyze differentially expressed proteins. Survival analysis was performed to examine the association between LRG1 levels and the prognosis of EOC patients. LRG1 silencing ovarian cancer cell lines were built and cell migration was further evaluated via wound healing and transwell assays. Immunoblot, immunofluorescence and immunohistochemistry analyses were performed. A subcutaneous tumor model was established to study the function of LRG1 in vivo. Results: Exosomal LRG1 was specifically expressed in urine samples of EOC patients and high LRG1 levels were significantly associated with poor prognosis. Function analyses showed that LRG1 was associated with ovarian cancer migration and progression. Mechanistically, LRG1 was significantly related to the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway. Conclusions: LRG1 participated in progression and metastasis of ovarian cancer via activation of the FAK/AKT pathway probably.

Abstract Background So far, the prevalence of human T-lymphotropic virus (HTLV) type 1 and 2 in some highly populated countries such as China is still unknown. In this study, a multi-center nationwide serological survey was designed and performed, to reveal the seroprevalence of HTLV infection among Chinese blood donors. Results Among 8,411,469 blood donors from 155 blood establishments, 435 were finally confirmed as HTLV carriers. The prevalence of HTLV infection in China varied in different provinces: Fujian had the highest prevalence of 36.240/100,000 (95% CI 31.990–41.050) and eleven provinces did not find HTLV-seropositive donors in the three years. no HTLV-2 infection was found. The overall prevalence of HTLV-1 in China decreased from 2016 to 2018. Female was identified as an independent risk factor of HTLV infection in China. Besides, seroconversion was observed in two of seven seroindeterminate donors 85 and 250 days after their last donation, respectively. Conclusions The seroprevalence of HTLV infection in most areas of China among blood donors is quite low, but it varies significantly in different geographic areas. Screening anti-HTLV-1/2 antibody and follow-up of serointederminate donors are essential to ensure blood safety especially in areas where we have found HTLV infected donors.

Idiopathic pulmonary fibrosis is a fatal interstitial disease characterized by fibroblast proliferation and differentiation and abnormal accumulation of extracellular matrix, with high mortality and an increasing annual incidence. Since few drugs are available for the treatment of pulmonary fibrosis, there is an urgent need for high-efficiency therapeutic drugs and treatment methods to reduce the mortality associated with pulmonary fibrosis. The interstitium, a highly efficient transportation system that pervades the body, plays an important role in the occurrence and development of disease, and can be used as a new route for disease diagnosis and treatment. In this study, we evaluated the administration of hydroxysafflor yellow A phytosomes via intervaginal space injection (ISI) as an anti-pulmonary fibrosis treatment. Our results show that this therapeutic strategy blocked the activation of p38 protein in the MAPK-p38 signaling pathway and inhibited the expression of Smad3 protein in the TGF-β/Smad signaling pathway, thereby reducing secretion of related inflammatory factors, deposition of collagen in the lungs of mice, and destruction of the alveolar structure. Use of ISI in the treatment of pulmonary fibrosis provides a potential novel therapeutic modality for the disease.

Abstract Background Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome caused by partial 4p deletion highly variable in size in individual patients. The core WHS phenotype is defined by the association of growth delay, typical facial characteristics, intellectual disability and seizures. The WHS critical region (WHSCR) has been narrowed down and NSD2 falls within this 200 kb region. Only four patients with NSD2 variants have been documented with phenotypic features in detail. Case presentation Herein, we report the case of a 12-year-old boy with developmental delay. He had dysmorphic facial features including wide-spaced eyes, prominent nasal bridge continuing to forehead, abnormal teething and micrognathia. He also had mild clinodactyly of both hands. Using whole-exome sequencing, we identified a pathogenic mutation in NSD2 [c.4029_4030insAA, p.Glu1344Lysfs*49] isolated from peripheral blood DNA. Sanger confirmation of this variant revealed it as a de novo truncating variant in the family. Conclusion Here, we reported a boy with de novo truncating variant in NSD2 with atypical clinical features comparing with 4p16.3 deletion related WHS. Our finding further supported the pathogenesis of truncating variants in NSD2 and delineated the possible symptom spectrum caused by these variants.

Liver fibrosis is an urgent public health problem which is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed a significant decrease in collagen deposition and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin, and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell–substrate junctions and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism, and related changes in biomechanics.

Serological tests have been widely used for detecting human T-cell lymphotropic virus type 1/2 (HTLV-1/2) antibodies in the endemic areas, but their performance in low-risk populations is rarely reported. The aim of this study was to evaluate the performance of four HTLV-1/2 screening assays and to discuss a strategy for diagnosis of HTLV-1/2 infection in a non-endemic area. At the present study, 1546 specimens repeatedly reactive (RR) by one screening ELISA were collected from blood centers/banks from January 2016 to April 2019. Avioq-ELISA, Murex-ELISA, Roche-ECLIA and Fujirebio-CLIA were independently performed on each plasma sample and compared to WB and LIA confirmatory tests. Positive or indeterminate specimens with blood available were quantified by qPCR. The results showed that 48 samples were finally confirmed as HTLV-1 positive, 13 were HTLV positive, 151 were indeterminate, and 387 were negative. All the WB-positive samples were also LIA-positive. Roche-ECLIA showed the highest sensitivity that was able to detect 91.8% positives and combined with the Murex-ELISA would significantly increase the positive detection rate (98.4%). In addition, LIA yield more indeterminate and HTLV-untyped results than WB (152 vs. 27), but was able to resolve infection status of some individuals with an indeterminate WB. Besides, 3 WB indeterminate and 1 LIA-untyped samples were confirmed as HTLV-1 positive by qPCR. Based on these findings, we put forward a proper test strategy for HTLV-1/2 diagnosis in low-prevalence areas. If possible, the Roche-ECLIA with the highest sensitivity is suggested as a second screening assay in primary labs. If not, all RR specimens are recommended to be firstly retested by Roche-ECLIA and Murex-ELISA in the reference lab. Secondly, samples reactive to any one of the two tests were quantified by qPCR, and then the NAT-negatives were furtherly submitted to LIA for confirmation. Thereby, the cost can be reduced and the diagnostic accuracy would be improved.

Cellulosic pulps were prepared from Stellera chamaejasme roots using soda, soda-anthraquinone (soda-AQ), and kraft pulping processes. S. chamaejasme is composed of 73.5% holocellulose, 39.7% α-cellulose, and 17.6% lignin, similar to wheat straw and other non-wood plant materials. The ethanol–benzene extractives content of 9.2% is higher than other non-woods. The conditions used for all pulping experiments were as follows: a liquid/solid ratio of 5:1; a time-to-maximum temperature of 100 min; a maximum temperature of 160 °C; and a time-at-maximum temperature of 50 min. The results showed that the pulp yield was 31.27 to 36.83%, the kappa number was 16.32 to 19.42, and the pulps’ intrinsic viscosity was 854 to 976 mL/g. Tear index, tensile index, burst index, and brightness of the papers made from the above unbleached pulps were 12.60 to 13.62 mN•m2/g, 20.57 to 22.56 mN/g, 2.16 to 2.38 kPa•m2/g, and 15.3 to 18.3%, respectively.

Small ribosomal protein subunit S7 (RPS7) has been reported to be associated with various malignancies, but the role of RPS7 in ovarian cancer remains unclear. In this study, we found that silencing of RPS7 by a specific shRNA promoted ovarian cancer cell proliferation, accelerated cell cycle progression, and slightly reduced cell apoptosis and response to cisplatin treatment. Knockdown of RPS7 resulted in increased expression of P85α, P110α, and AKT2. Although the basal levels of ERK1/2, MEK1/2, and P38 were inconsistently altered in ovarian cancer cells, the phosphorylated forms of MEK1/2 (Ser217/221), ERK1/2 (Thr202/Tyr204), JNK1/2 (Thr183/Tyr185), and P38 (Thr180/Tyr182) were consistently reduced after RPS7 was silenced. Both the in vitro anchorage-independent colony formation and in vivo animal tumor formation capability of cells were enhanced after RPS7 was depleted. We also showed that silencing of RPS7 enhanced ovarian cancer cell migration and invasion. In sum, our results suggest that RPS7 suppresses ovarian tumorigenesis and metastasis through PI3K/AKT and MAPK signal pathways. Thus, RPS7 may be used as a potential marker for diagnosis and treatment of ovarian cancer.