Personal Competence or Environmental Characteristics? Factors Influencing Happiness among Ageing Adults in Hong Kong Around the Period of COVID-19 Pandemic.

Drawing upon person-environment fit perspective, this study examines the joint and interactive influences of personal competence and environmental characteristics on the happiness of ageing adults around the period of COVID-19 pandemic. Data was collected in two rounds, before and during the pandemic, with 2,028 participants aged 55 years and older in Hong Kong. Personal competence encompassed financial status, physical health, and mental capital, while environmental characteristics included experiences of ageism, perceived social conditions, and age-friendly policies. Ordinary least squares regression was used to examine personal and environmental influences on happiness. Results indicated a significant decline in happiness following the onset of COVID-19 pandemic. Mental capital was found to have the strongest positive influence on happiness, followed by physical health, financial status, and social conditions. Mental capital mitigated the negative relationship between experiences of ageism and happiness. Practical interventions are informed to improve the well-being of ageing adults during pandemic.

Childhood Interpersonal Trauma and Depression of Middle-Aged and Older Adults in China: The Mediation Effect of Social Integration.

Objectives: This study investigates the associations between five types of childhood interpersonal trauma (CIT) and depression in mid-later life, as well as the mediation roles of social integration in the associations. Methods: Two waves of data from a nationally representative survey in China were used, with participants aged 45 years and older (N = 14,180). Measures of CIT included physical abuse, physical neglect, emotional neglect, bullying victimization, and exposure to interparental violence. Binary logistic regression and Karlson-Holm-Breen mediation analysis were used as statistical methods. Results: People who were bullied, physically abused, and witnessed interparental violence during childhood were more likely to develop depression in mid-later years. The associations between CIT and depression were mediated by satisfaction with marriage, satisfaction with children, and perceived social support. Discussion: Although CIT elevates the risk of depression in later life, effective interventions that strengthen integration across family and social domains could benefit mental health.

Experience of Chinese Recent Retirees on the Effects of Retirement on Healthy Ageing in Shenzhen and Hong Kong.

This study examined perspectives of recent retirees in Shenzhen and Hong Kong on how retirement influenced their healthy ageing. It investigated retirees' perceptions of healthy ageing and the ways in which healthy ageing connected with retirees' transition into retirement. A qualitative design with narrative interviews was used to interview twelve recent retirees in Shenzhen and thirteen in Hong Kong. The participants elaborated their perspectives on healthy ageing, which covered physical, mental, social, and financial domains. Retirees in both cities identified healthy ageing as maintaining an independent life and avoiding becoming a burden on family members. This study found that retirement declined physical health (in parallel with raised awareness of health promotion), posed both negative and positive influences on mental health, and shrank peripheral social networks of retirees. In addition, regional social welfare systems have different impacts on retirees' financial security and social participation. Retirees in Hong Kong reported higher stress of financial security and a strong desire for labor participation. Migrant-local welfare gaps were documented by retirees in Shenzhen. This study suggested that retirement planning, establishing a multi-pillar retirement-protection system, and narrowing the welfare gap between migrants and local residents should be implemented to reinforce healthy ageing.

Single-cell transcriptomes and runx2b-/- mutants reveal the genetic signatures of intermuscular bone formation in zebrafish.

Intermuscular bones (IBs) are mineralized spicules, present in the myosepta of many, but not all, teleost species. IBs are often small and sharp, and they consequently limit how the fish can be processed; the IBs may cause injury or trauma if lodged in consumers' throats or mouths, and therefore affect the appeal of the fish to many consumers. The development of IBs in teleosts is still not fully understood and the molecular basis of IB development remains to be established. Here, the characteristics of IB tissue are evaluated based on single-cell transcriptomics in wild-type zebrafish. The analysis defined 18 distinct cell types. Differentiation trajectories showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation. In particular, the functions of 10 candidate genes were evaluated via CRISPR-Cas9 mutants. Among those, runx2b-/- mutants completely lost IBs, while swimming performance, growth and bone mineral density were not significantly different from runx2b+/+ zebrafish. Comparative single-cell RNA sequencing (scRNA-seq) analysis in runx2b-/- and runx2b+/+ zebrafish revealed the role of osteoblasts in IB formation. In addition, differentially expressed genes were enriched in the transforming growth factor ß/bone morphogenetic protein (TGF-ß/BMP) pathway after runx2b deletion. This study provides evidence for the crucial role of runx2b regulation in IB formation. Genetic breeding can target runx2b regulation and generate strains of commercial fish species without IBs, which can improve the safe consumption and economic value of many farmed fish species.

[Metagenomic and Metatranscriptomic Analysis of Nitrogen Removal Functional Microbial Community of Petrochemical Wastewater Biological Treatment Systems].

Petrochemicals are one of the pillar industries of China. Despite this, the treatment of petrochemical wastewater has long been seen as a massive challenge in the field of water pollution control, hindering the high-quality and sustainable development of the petrochemical industry. The majority of petrochemical enterprises and zones are located near rivers or seas, so their wastewater discharges can easily cause watershed or regional water ecological risks. Specifically, nitrogen pollution in petrochemical wastewater poses a significant threat to water ecological safety and human health. Sludge samples were collected from a petrochemical wastewater A/O nitrogen removal process line in a chemical industry zone in Shanghai. Metagenomic and metatranscriptomic methods were used to analyze the community structure of microorganisms, the functional characteristics of nitrogen removal bacteria, and the key nitrogen metabolism pathways in different sludges during the period when effluent water quality was stable and fluctuating. During the study, it was found that the nitrite and nitrate removal was relatively stable in this process, but ammonia oxidation fluctuated easily. In the study of microbial communities, it was found to be a nitrification-denitrification pathway that primarily removed nitrogen from the A/O process, and no genes related to ANAMMOX were detected. Approximately 90% of the functional genes responsible for removing nitrogen were responsible for denitrification, whereas only 0.17% of them were involved in the conversion of ammonia nitrogen in the nitrification process. Moreover, the abundance of ammonia-oxidizing bacteria in the process was extremely low, and the main genus was Nitrosomonas. It is likely that this is the main cause of fluctuations in ammonia nitrogen concentration in effluent due to water quality shocks in the process line.

A Meta-Analysis on the Influence of Age-Friendly Environments on Older Adults' Physical and Mental Well-Being.

The importance of age-friendly environments (AFEs) for older adults has been empirically and theoretically highlighted by the extant literature. However, the strength of the association between environments and older adults' well-being has not been comprehensively quantified. Given the different attributes of the physical and mental dimensions, this meta-analysis aims to synthesise and quantify the association between AFEs and the physical and mental well-being of older adults. Fourteen eligible studies were included in this analysis: among which eight explored the link between AFEs and physical well-being, and eleven investigated AFEs in association with mental well-being. A random-effects model showed a small but significant correlation between AFEs and the mental well-being of older adults (r = 0.160, 95% CI [0.084, 0.224], p < 0.001), and the correlation between AFEs and physical well-being was also significant (r = 0.072, 95% CI [0.026, 0.118], p < 0.01). The number of environmental factors involved in AFEs moderated the association with physical well-being, from which the association was only significant among studies focusing on fewer environmental factors (n < 6). Results of this meta-analysis indicated that AFEs may be more effective in promoting the emotions of older adults, compared to ameliorating their physical functioning. The limitations of current empirical studies and directions for future research in the field of environmental gerontology were also discussed.

Saline short-term shock and rapid recovery on anammox performance.

Anaerobic ammonia oxidation (anammox) is an environmental-friendly biological nitrogen removal process, which has been developed as a promising technology in industrial wastewater treatment. However, anammox nitrogen removal under high saline conditions still faces many challenges. This study investigated the performance of anammox sludge under saline short-term shock and the strategy of rapid recovery. Salinity concentration, saline exposure time, and NaCl/Na2SO4 ratio were selected as three critical factors for short-term shock. The activity inhibition of anammox sludge were tested by using response surface methodology (RSM). Our results showed that, compared with the NaCl/Na2SO4 ratio, the salinity concentration and saline exposure time were the significant factor causing the anammox inhibition. The addition of glycine betaine (GB) in moderate amounts (0.1-5 mM) was found to help anammox to resist in relative low saline shock intensities (e.g., IC25 and IC50), with the activity retention rate of 94.7%. However, glycine betaine was not worked effectively under relatively high saline shock intensities (e.g., complete inhibition condition). Microbial community analysis revealed that Brocadiaceae accounted for only about 7.6%-13.2% at inhibited conditions. Interestingly, 16S rRNA analysis showed that the abundance of activated Brocadiaceae remarkably decreased with time after high-level saline shock. This tendency was consistent with the results of qPCR targeted hzsA gene. Finally, based on quorum sensing, the anammox activity was recovered to 93.5% of original sludge by adding 30% original sludge. The study realized the rapid recovery of anammox activity under complete inhibition, promoting the development and operation of salt-tolerant anammox process.

Influence of intergenerational relationships on depressive symptoms in ageing Chinese adults in Hong Kong: Mediating effects of sense of loneliness.

BACKGROUND: Mental health of older adults could be positively predicted by harmonious parent-adult children relationships, although the mechanism has not been sufficiently demonstrated. This study employed sense of loneliness as mediator to examine the influence of multiple domains of intergenerational relationships on depressive symptoms in ageing Chinese adults. METHODS: Data was extracted from a representative survey in Hong Kong among Chinese adults aged over 50 with at least one adult child (n = 801). Four key domains (structural-associational, consensual-normative, affectual closeness, and intergenerational conflict) were adopted to measure the intergenerational relationship quality. Depressive symptoms were assessed using the five-item Geriatric Depression Scale. The mediating role of sense of loneliness in the association between intergenerational relationships and depressive symptoms were tested by the PROCESS macro in SPSS. RESULTS: The influence of overall intergenerational relationship quality and its four subdomains on depressive symptoms were significantly mediated by sense of loneliness. Among the four domains, affectual closeness presented the strongest association with older people's depressive symptoms. The effect of intergenerational conflict on depressive symptoms was completely mediated by sense of loneliness, and the effects of remaining three domains were partially mediated. The domain of consensual-normative solidarity received the lowest rating by Chinese older adults. CONCLUSION: The psychological pathway that loneliness links intergenerational relationships and depressive symptoms was supported in this study. With respect to improving intergenerational relationships, enhancing affectual connection between older parents and adult children was essential to prevent mental problems. This study calls for more attention to the protective role of diverse social relationships in improving mental health through multiple pathways.

Functional Differentiation of BMP7 Genes in Zebrafish: bmp7a for Dorsal-Ventral Pattern and bmp7b for Melanin Synthesis and Eye Development.

Bone morphogenetic protein 7 (BMP7) belongs to the transforming growth factor ß (TGF-ß) family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes, bmp7a and bmp7b, which have clearly differentiated structures. To fully understand the functional differentiation of bmp7a and bmp7b in fish species, we successfully constructed bmp7a and bmp7b gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that bmp7a mutation caused abnormal development of the embryo's dorsal-ventral pattern that led to death; bmp7b mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in bmp7b mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of wnt7ba and gna14 in bmp7b mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in bmp7b mutants led to defects in phototransduction, and seven DEGs (rgs9a, rgs9b, rcvrn2, guca1d, grk1b, opn1mw4, and gc2) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of bmp7a and bmp7b in teleosts and the first report about the inhibitory effect of bmp7b on melanogenesis may provide useful information for the future research on human melanoma-related diseases.

The anammox coupled partial-denitrification process in an integrated granular sludge and fixed-biofilm reactor developed for mainstream wastewater treatment: Performance and community structure.

This study describes an integrated granular sludge and fixed-biofilm (iGB) reactor innovatively designed to carry out the anammox/partial-denitrification (A/PD) process for nitrogen removal with mainstream municipal wastewater. The iGB-A/PD reactor consists of anammox granules inoculated in the lower region of reactor and an acclimated fixed-biofilm positioned in the upper region. Compared to the other reported A/PD systems for mainstream wastewater treatment, this iGB-A/PD reactor is notable due to its higher quality effluent with a total inorganic nitrogen (TIN) of ∼3 mg•L-1 and operation at a high nitrogen removal rate (NRR) of 0.8 ± 0.1 kg-N•m-3•d-1. Reads-based metatranscriptomic analysis found that the expression values of hzsA and hdh, key genes associated with anammox, were much higher than other functional genes on nitrogen conversion, confirming the major roles of the anammox bacteria in nitrogen bio-removal. In both regions of the reactor, the nitrate reduction genes (napA/narG) had expression values of 56-99 RPM, which were similar to that of the nitrite reduction genes (nirS/nirK). The expression reads from genes for dissimilatory nitrate reduction to ammonium (DNRA), nrfA and nirB, were unexpectedly high, and were over the half of the levels of reads from genes required for nitrate reduction. Kinetic assays confirmed that the granules had an anammox activity of 16.2 g-NH4+-N•kg-1-VSS•d-1 and a nitrate reduction activity of 4.1 g-N•kg-1-VSS•d-1. While these values were changed to be 4.9 g- NH4+-N•kg-1-VSS•d-1and 4.3 g-N•kg-1-VSS•d-1 respectively in the fixed-biofilm. Mass flux determination found that PD and DNRA was responsible for ∼50% and ∼25% of nitrate reduction, respectively, in the whole reactor, consistent with high effluent quality and treatment efficiency via a nitrite loop. Metagenomic binning analysis revealed that new and unidentified anammox species, affiliated with Candidatus Brocadia, were the dominant anammox organisms. Myxococcota and Planctomycetota were the principal organisms associated with the PD and DNRA processes, respectively.

Comparison of Myosepta Development and Transcriptome Profiling between Blunt Snout Bream with and Tilapia without Intermuscular Bones.

Intermuscular bones (IBs) are small spicule-like bones located in the myosepta of basal teleosts, which negatively affect the edibleness and economic value of fish. Blunt snout bream (Megalobrama amblycephala, with epineural and epipleural IBs) and tilapia (Oreochromis niloticus, without epineural and epipleural IBs) are two major aquaculture species and ideal models for studying the formation mechanisms of fish IBs. Here, we compared myosepta development between M. amblycephala and O. niloticus, based on histological analysis, transcriptome profiling, and expression analysis of bone-related genes. The histological results showed that dye condensation began to appear in the myosepta 20 days post hatching (dph) in M. amblycephala, and IBs could be clearly observed 50 dph in the myosepta, based on different staining methods. However, in O. niloticus, dye condensation was not observed in the myosepta from 10 to 60 dph. Differentially expressed genes (DEGs) at different developmental stages were screened by comparing the transcriptomes of M. amblycephala and O. niloticus, and KEGG analysis demonstrated that these DEGs were enriched in many bone-related pathways, such as focal adhesion, calcium, and Wnt signaling pathways. Quantitative PCR was performed to further compare the expression levels of some bone-related genes (scxa, scxb, runx2a, runx2b, bgp, sp7, col1a2, entpd5a, entpd5b, phex, alpl, and fgf23). All the tested genes (except for alpl) exhibited higher expression levels in M. amblycephala than in O. niloticus. A comparison of the dorsal and abdominal muscle tissues between the two species also revealed significant expression differences for most of the tested genes. The results suggest that scxa, scxb, runx2a, runx2b, entpd5a, col1a2, and bgp may play important roles in IB development. Our findings provide some insights into the molecular mechanisms of IB formation, as well as clues for further functional analysis of the identified genes to better understand the development of IBs.

Biodegradable Nanoprodrugs: "Delivering" ROS to Cancer Cells for Molecular Dynamic Therapy.

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next-generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin-modified MgO2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg2+ . This reaction simultaneously produces abundant H2 O2 to induce cell death and damage the structure of transferrin to release Fe3+ , which will react with H2 O2 to produce highly toxic ·OH to kill tumor cells.

Online Learning Algorithm Based on Adaptive Control Theory.

This paper proposes a new online learning algorithm which is based on adaptive control (AC) theory, thus, we call this proposed algorithm as AC algorithm. Comparing to the gradient descent (GD) and exponential gradient (EG) algorithm which have been applied to online prediction problems, we find a new form of AC theory for online prediction problems and investigate two key questions: how to get a new update law which has a tighter upper bound on the error than the square loss? How to compare the upper bound for accumulated losses for the three algorithms? We obtain a new update law which fully utilizes model reference AC theory. Moreover, we present upper bound on the worst-case expected loss for AC algorithm and compare it with previously known bounds for the GD and EG algorithm. The loss bound we get in this paper is a time-varying function, which provides increasingly accurate estimates for upper bound. The AC algorithm has a much smaller loss only if the number of the samples meets certain conditions which can be seen in this paper. We also performed experiments which show that our update law is reasonably feasible and our upper bound is quite tight on both simple artificial and real data sets. The main contributions of this paper are twofold. First of all, we develop a new online algorithm called AC algorithm, and second, we obtain improved bounds, see Theorems 2-4 in this paper.

Knockdown of long non-coding RNA HOTAIR sensitizes hepatocellular carcinoma cell to cisplatin by suppressing the STAT3/ABCB1 signaling pathway.

Long non-coding RNA HOX transcript antisense RNA (HOTAIR) has been demonstrated to exhibit oncogenic activity in several types of cancer, including hepatocellular carcinoma (HCC). However, the association between HOTAIR and HCC multidrug resistance remains uncertain. The present study aimed to investigate the role of HOTAIR in HCC chemoresistance; it was found that knockdown of HOTAIR expression in HCC Huh7 cells resulted in decreased cell proliferation and increased chemosensitivity to cisplatin. Furthermore, expression levels of ATP binding cassette subfamily B member 1 (ABCB1) mRNA and protein were decreased in Huh7 cells upon HOTAIR-knockdown. In addition, HOTAIR-knockdown reduced the levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), and inhibition of STAT3 phosphorylation reduced HOTAIR-mediated ABCB1 expression. Together, these findings indicated that knockdown of HOTAIR in Huh7 cells decreased STAT3 activity and ABCB1 expression, and increased chemosensitivity to cisplatin. Thus HOTAIR could serve as a novel potential therapeutic target to reverse multidrug resistance in HCC.

Asymptomatic syringomyelia accompanied with metastatic cerebellar and spinal intramedullary lymphoma: A case report.

RATIONALE: Asympotamic syringomyelia accompanied with metastatic cerebellar and thoracic spinal intramedullary lymphoma is rare in clinical practice. If the intramedullary lymphoma is large enough, the patient will rapidly develop neurologic signs of spinal injury. The prognosis of this type of complication is always bad. PATIENT CONCERNS: Rapid and correct diagnosis and treatment is important for metastatic extranodal lymphoma with B cell of origin. DIAGNOSES: Syringomyelia accompanied with metastatic cerebellar and thoracic spinal intramedullary lymphoma. INTERVENTIONS: The patient was treated with a combination of systemic chemotherapy and focal radiotherapy and intrathecal therapy. OUTCOMES: Resolution of metastatic lymphoma was not continued after conservative medical management and the patient died finally due to multiple organ failure. LESSONS: Syringomyelia can develop due to the metastatic thoracic intramedullary lymphoma in patients with diffuse malignant large B cell lymphoma. Early and accurate diagnosis, anti-lymphoma treatment, and timely neurosurgical intervention may delay the development of the disease.

Knockdown of Hotair suppresses proliferation and cell cycle progression in hepatocellular carcinoma cell by downregulating CCND1 expression.

The long noncoding RNA, homeobox transcript antisense RNA (Hotair), has been demonstrated to have an important role in regulating various biological processes in various cancers, including hepatocellular carcinoma (HCC). However, the importance of Hotair in HCC proliferation and cell cycle progression remains to be elucidated. In the present study, knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells. In addition, the expression levels of CCND1 mRNA and its cyclin D1 protein product were reduced in Huh7 cells following knockdown of HOTAIR. Knockdown of HOTAIR reduced the expression of phosphorylated signal transducer and activator of transcription 3 (STAT3) and HOTAIR knockdown combined with STAT3 inhibition led to an additional decrease in cyclin D1 expression. The present study suggested that Hotair may have a critical role in the proliferation of HCC by regulating cell cycle, STAT3 activity and cyclin D1 expression. Therefore, Hotair may be a novel potential therapeutic target for HCC treatment.

Correlations between diffusion tensor imaging and levels of consciousness in patients with traumatic brain injury: a systematic review and meta-analysis.

Traumatic brain injury (TBI) often leads to impaired consciousness. Recent diffusion tensor imaging studies associated consciousness with imaging metrics including fractional anisotropy (FA) and apparent diffusion coefficient (ADC). We evaluated their correlations and determined the best index in candidate regions. Six databases were searched, including PubMed and Embase, and 16 studies with 701 participants were included. Data from region-of-interest and whole-brain analysis methods were meta-analysed separately. The FA-consciousness correlation was marginal in the whole-brain white matter (r = 0.63, 95% CI [0.47, 0.79], p = 0.000) and the corpus callosum (CC) (r = 0.60, 95% CI [0.48, 0.71], p = 0.000), and moderate in the internal capsule (r = 0.48, 95% CI [0.24, 0.72], p = 0.000). Correlations with ADC trended negative and lacked significance. Further subgroup analysis revealed that consciousness levels correlated strongly with FA in the CC body (r = 0.66, 95% CI [0.43, 0.89]), moderately in the splenium (r = 0.58, 95% CI [0.38, 0.78]), but insignificantly in the genu. In conclusion, FA correlates better with consciousness levels than ADC in TBI. The degree of correlation varies among brain regions. The CC (especially its splenium and body) is a reliable candidate region to quantitatively reflect consciousness levels.

Hepatitis C virus core protein increases Snail expression and induces epithelial-mesenchymal transition through the signal transducer and activator of transcription 3 pathway in hepatoma cells.

AIM: Aberrant expression of Snail, a mediator of epithelial-mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified. METHODS: HepG2 and Huh7 stable cell lines were established by transfection with pcDNA-HCVc. HepG2-HCVc and Huh7-HCVc cells were co-administered with AG490. Cell migration and invasiveness were tested. STAT3 and Snail expression was analyzed by Real-time PCR and Western blot. RESULTS: We found that HCV core is capable of increasing Snail expression and inducing EMT in hepatoma cells. HCV core-induced Snail expression was accompanied by activation of signal transducer and activator of transcription 3 (STAT3), inhibition of STAT3 abrogated HCV core-induced Snail expression and EMT. Furthermore, chromatin immunoprecipitation showed that phosphorylated STAT3 directly binds to the Snail promoter. CONCLUSION: Collectively, these results suggest that HCV core would play a role in hepatocellular carcinoma invasiveness and metastasis by activating the STAT3 pathway, increasing Snail expression and subsequently triggering EMT. These findings would advance the understanding of HCV-mediated invasiveness and metastasis, and might provide a new potential therapeutic target for HCV-related hepatocellular carcinoma.

Hepatitis C virus core protein regulates OCT4 expression and promotes cell cycle progression in hepatocellular carcinoma.

Hepatitis C virus (HCV) core protein plays an important role in the development of hepatocellular carcinoma. octamer-binding protein 4 (OCT4) is critically essential for the pluripotency and self-renewal of embryonic stem cells. Abnormal expression of OCT4 has been detected in several human solid tumors. However, the relationship between HCV core and OCT4 remains uncertain. In the present study, we found that HCV core is capable of upregulating OCT4 expression. The effect of HCV core-induced OCT4 overexpression was abolished by RNAi-mediated scilencing of HCV core. In addition, HCV core-induced OCT4 overexpression resulted in enhanced cell proliferation and cell cycle progression. Inhibition of OCT4 reduced the CCND1 expression and induced G0/G1 cell cycle arrest. Furthermore, OCT4 protein directly binds to CCND1 promoter and transactivates CCND1. These findings suggest that HCV core protein regulates OCT4 expression and promotes cell cycle progression in hepatocellular carcinoma providing new insight into the mechanism of hepatocarcinogenesis by HCV infection.

pH-responsive iron manganese silicate nanoparticles as T1-T2* dual-modal imaging probes for tumor diagnosis.

Magnetic resonance imaging (MRI) probes can be concentrated in tumors through grafting targeting agents. However, the clinical application of such targeted MRI probes is largely limited because specific agents are only used to target specific characteristics of cancer cells. The development of the MRI probes that can be used regardless of tumor types or their developmental stages is highly appreciated. The acidic tumor microenvironments and acidic organelles (endosomes/lysosomes) in cancer cells are universal phenomena of solid tumors, and nanoparticles can also accumulate in tumor tissues by enhanced permeability and retention (EPR) effect. Here, we reported the synthesis of pH-responsive T1-T2* dual-modal contrast agents based on iron manganese silicate (FeMn(SiO4)) hollow nanospheres, which can release Mn(2+) ions in acidic environments, exhibiting excellent ability as agents for magnetic resonance and red fluorescence imaging. MRI for mouse models revealed that the nanoprobes could accumulate in tumors via EPR effect and then distinguish tumors from normal tissues with the synergistic effect of T1 and T2* signal only 10 min after intravenous injection. Fluorescence imaging demonstrated that the nanoprobes could be endocytosed into cancer cells and located at their lower pH compartments. Moreover, the hollow nanospheres showed no obvious toxicity and inflammation to the major organs of mice, which made them attractive diagnostic agents for different types of cancers.