The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer.

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.

Discovery of the covalent SARS-CoV-2 Mpro inhibitors from antiviral herbs via integrating target-based high-throughput screening and chemoproteomic approaches.

The main proteases (Mpro ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of Mpro from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-Mpro effect (IC50 = 37.82 µg/mL). Mass spectrometry (MS)-based chemical analysis and chemoproteomic profiling revealed that LJF extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify Mpro . We subsequently verified the anti-Mpro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit severe acute respiratory syndrome coronavirus 2 Mpro in dose- and time- dependent manners, with the IC50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of Mpro from herbal medicines by integrating target-based high-throughput screening and MS-based assays, which would greatly facilitate the discovery of key antiviral constituents from medicinal plants.

Caregiving burden and psychological distress in Chinese spousal caregivers: gender difference in the moderating role of positive aspects of caregiving.

Objectives: This study endeavors to advance the current literature by examining the gender differences in the caregiving experiences and the stress-buffering role of positive aspects of caregiving (PAC) among Chinese spousal caregivers of frail elders in Hong Kong. Method: Forty-nine husband caregivers and 121 wife caregivers of frail elders in Hong Kong (N = 170) responded to the Positive Aspects of Caregiving (PAC) scale, the Zarit Burden Interview (ZBI), the 21-item Depression, Anxiety, and Stress Scales (DASS-21), and demographic questions. These spousal caregivers were diverse in age, and their care receivers were diverse in terms of age and health condition. Results: As predicted, there were significant gender differences in the moderating effects of PAC on the relationships of caregiving burden to depression, anxiety, and overall psychological distress. While PAC significantly buffered the effects of caregiving burden on depression, anxiety, and overall psychological distress for wife caregivers, the moderating effects of PAC were not significant for husband caregivers. Unexpectedly, wife caregivers reported lower PAC, higher caregiving burden, and higher psychological distress. Conclusion: As these findings suggest that PAC is lower but more beneficial for Chinese wife caregivers than Chinese husband caregivers, helping professionals are recommended to use strengths-based interventions that target PAC when working with Chinese wife caregivers.

Negative Mood States or Dysfunctional Cognitions: Their Independent and Interactional Effects in Influencing Severity of Gambling Among Chinese Problem Gamblers in Hong Kong.

Gambling-related cognitions and negative psychological states have been proposed as major factors in the initiation and maintenance of problem gambling (PG). While there are a substantial number of studies supporting the role of cognitive dysfunctions in the initiation and maintenance of PG, very few empirical studies have explored the specific role of negative psychological states in influencing PG behaviours. In addition, very few studies have examined the interaction effects of cognitive dysfunctions and negative psychological states in exerting influence on PG behaviours. Therefore, the present study aims to examine the main and interaction effects of gambling-related cognitions and psychological states on the gambling severity among a group of problem gamblers in Hong Kong. A cross-sectional research design was adopted. A purposive sample of 177 problem gamblers who sought treatment from a social service organization in Hong Kong completed a battery of standardised questionnaires. While gambling-related cognitions were found to exert significant effects on gambling severity, negative psychological states (i.e. stress) significantly moderated the relationship between gambling cognitions and gambling severity. In essence, those participants who reported a higher level of stress had more stable and serious gambling problems than those who reported a lower level of stress irrespective of the level of gambling-related cognitions. The findings of the moderating role of negative emotions in the relationship between cognitive distortions and severity of gambling provide insight towards developing an integrated intervention model which includes both cognitive-behavioural and emotion regulation strategies in helping people with PG.

Evaluating the Effectiveness of an Integrated Cognitive-Behavioural Intervention (CBI) Model for Male Problem Gamblers in Hong Kong: A Matched-Pair Comparison Design.

Very few clinical cognitive-behavioural intervention (CBI) studies were conducted with the Chinese gamblers. There is a lack of attention paid to intervening in negative emotions that may also adversely affect PGs in current CBI treatment modality. This study is the first attempt to systematically and rigorously evaluate both the short-term and longer-term effects of a culturally-attuned CBI group treatment with an emotion regulation component for a group of Chinese PGs in Hong Kong. A quasi-experimental matched-pairs design was adopted and 84 participants were allocated to the CBI (N = 42) and social activity groups (N = 42). There are 3 assessment points in the study: baseline at recruitment, post-intervention at the end of CBI and social activity groups, and at 6-month follow-up. When compared to the social activity group and after controlling for general group effects, there were significantly greater decreases in the severity of gambling, gambling-related cognitions (i.e. interpretive bias), negative psychological states (i.e. stress) and money spent on gambling in the past month in the CBI group between pre- and post-intervention and between pre-intervention and 6-month follow-up. Results also indicated that both reduction in gambling-related cognitions and negative psychological states could mediate the treatment effect of the CBI on the reduction of problematic gambling behaviours. The culturally attuned integrated CBI group treatment with an emotional regulation component appeared to be effective in treating Chinese problem gamblers in Hong Kong and the effects could be sustained at 6-month follow-up.

Advances in molecular basis of response to immunotherapy for penile cancer: better screening of responders.

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future.

Comprehensive analysis of pain genes in prognosis of kidney renal clear cell carcinoma and tumor immunotherapy: A comprehensive bioinformatic study.

Background: The effect of pain genes (NAV1, EHMT2, SP1, SLC6A4, COMT, OPRM1, OPRD1, CYP2D6, and CYP3A4) have not been reported previously in kidney renal clear cell carcinoma (KIRC) patients and thus we made a comprehensive analysis of pain genes in the prognosis of KIRC and tumor immunotherapy. Methods: In this study, TCGA, Kaplan-Meier plotter, Metascape, STRING, Human Protein Atlas, Single Cell Expression Atlas database, LinkedOmics, cBioPortal, MethSurv, CancerSEA, COSMIC database and R package (ggplot2, version 3.3.3) were used for comprehensive analysis of pain genes in KIRC. Pearson and Spearman correlation coefficients were for co-expression analysis. Immunotherapy and TISIDB database were used for tumor Immunotherapy. Results: Representative pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4) were statistically significant (p < 0.0001) in the prognosis of KIRC. Immunotherapy (anti-PD-1 therapy, anti-PD-L1 therapy, and anti-CTLA4 therapy) and immunomodulator (immunoinhibitor, immunostimulator, and MHC molecule) in KIRC were significant associated with pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4), which were the important addition to clinical decision making for patients. Conclusions: Our study uncovered a mechanism for the effect of pain genes on KIRC outcome via the modulation of associated co-expression gene networks, gene variation, and tumor Immunotherapy.

Altered tumor microenvironment heterogeneity of penile cancer during progression from non-lymphatic to lymphatic metastasis.

BACKGROUND: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. METHODS: In this study, using single-cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. RESULTS: The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial-mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. CONCLUSIONS: This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non-lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Discovery and characterization of the covalent SARS-CoV-2 3CLpro inhibitors from Ginkgo biloba extract via integrating chemoproteomic and biochemical approaches.

BACKGROUND: The 3C-like proteases (3CLpros) are cysteine-rich homodimeric proteins and can be covalently modified by numerous natural and synthetic compounds, which in turn, block the proteolytic activity or the formation of enzymatically active dimeric forms. Although herbal medicines have been widely used to treat COVID-19, identification of the key herbal constituents that can covalently modify the 3CLpros in ß-coronaviruses (CoVs) remains a big challenge. AIMS: To construct a comprehensive approach for efficient discovering the covalent SARS-CoV-2 3CLpro inhibitors from herbal medicines. To decipher the key anti-SARS-CoV-2 3CLpro constituents in Ginkgo biloba extract 50 (GBE50) and to study their anti-SARS-CoV-2 3CLpro mechanisms. METHODS: SARS-CoV-2 3CLpro inhibition assay including time-dependent inhibition assays and inactivation kinetic analyses were conducted using a fluorescence-based biochemical assay. The constituents in GBE50 were analyzed by UHPLC-Q-Exactive Orbitrap HRMS. The peptides modified by herbal constituents were characterized by using nanoLC-MS/MS. RESULTS: Following testing the anti-SARS-CoV-2 3CLpro effects of 104 herbal medicines, it was found that Ginkgo biloba extract 50 (GBE50) potently inhibited SARS-CoV-2 3CLpro in dose- and time-dependent manners. A total of 38 constituents were identified from GBE50 by UHPLC-Q-Exactive Orbitrap HRMS, while 26 peptides modified by 18 constituents were identified by chemoproteomic profiling. The anti-SARS-CoV-2 3CLpro effects of 18 identified covalent inhibitors were then validated by performing time-dependent inhibition assays. The results clearly demonstrated that most tested constituents showed time-dependent inhibition on SARS-CoV-2 3CLpro, while gallocatechin and sciadopitysin displayed the most potent anti-SARS-CoV-2 3CLpro effects. CONCLUSION: Collectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CLpro in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CLpro inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.

Cognitive-behavior therapy with and without parental involvement for anxious Chinese adolescents: A randomized controlled trial.

This study evaluated the effectiveness of a culturally attuned group cognitive-behavior therapy (CBT) intervention for Chinese adolescents at risk for anxiety disorders in Hong Kong and the additive effects of parental involvement. A randomized controlled design was adopted. Assessments were gathered at pre- and posttreatment, and 6-month follow-up. Participants (N = 136) were randomly assigned to (a) CBT plus parental involvement (CBT-PI) (n = 46), (b) CBT (n = 45), and (c) social activity (n = 45) conditions. Data were analyzed according to the intention-to-treat principle using multilevel modeling. The CBT-PI condition showed a greater reduction in physical injury fears compared with the CBT condition. The current findings suggest that involving parents in CBT for Chinese adolescents with anxiety problems may provide a small improvement in treatment efficacy. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Differential impacts of social support on mental health: A comparison study of Chinese rural-to-urban migrant adolescents and their urban counterparts in Beijing, China.

BACKGROUND: The number of internal migrant children in China has reached 35.8 million by the end of 2010. Previous studies revealed inconsistent findings regarding the mental health status of rural-to-urban migrant adolescents, as well as the impact of peer, teacher and parental support on the mental health of Chinese adolescent migrants. AIMS: Using a comparative approach, this study attempted to compare the mental health status between migrant and urban-born adolescents and to clarify the specific roles of different sources of social support in the mental health of migrant and urban adolescents. METHOD: A cross-sectional survey using a cluster convenience sampling strategy was performed in Beijing, China. A structured questionnaire was filled out by 368 rural-to-urban migrant adolescents and 325 urban-born adolescents. RESULTS: A significant difference was found only for positive affect (PA) but not for negative affect (NA) between the two groups, favouring the urban-born adolescents. Social support from all the three sources were all predictive of PA among rural-to-urban migrant adolescents, while only peer support contributed to PA among urban-born adolescents. Unexpectedly, teachers' support contributed to an increase in NA among urban-born adolescents. CONCLUSION: The findings contribute to understanding of the mental health status of migrant adolescents in China and the differential impact of the various sources of social support on migrant and urban-born adolescents. Also the findings may inform the development of mental health services and programmes that can potentially benefit a large number of internal migrant adolescents in China.

Mental health literacy, stigma and perception of causation of mental illness among Chinese people in Taiwan.

BACKGROUND: Few studies have been performed to explore mental health literacy and stigmatising attitudes towards mental illness and their relationships with causal beliefs about mental illness among Chinese people in Taiwan. AIMS: Using a comparative approach, this study attempted to compare the mental health literacy and stigmatising attitudes of Taiwanese Chinese with those found among Australian and Japanese participants in other studies and to explore how mental health literacy and stigmatising attitudes relate to different perceptions of causes of mental illness. METHODS: A convenience sample of 287 participants completed a battery of standardised questionnaires. RESULTS: A much lower percentage of Taiwanese people than Australians could correctly identify depression and schizophrenia. The Taiwanese respondents rated psychiatrists and clinical psychologists as more helpful than social workers and general practitioners (GPs) and expressed more uncertainty about the usefulness of certain medications when compared to the Australian and Japanese samples. Interestingly, Taiwanese Chinese hold similarly high levels of stigma towards schizophrenia, but lower levels of stigma towards depression when compared to the Japanese respondents. Taiwanese respondents who have higher levels of mental health literacy about schizophrenia were less willing to interact with people with schizophrenia than those with lower levels of mental health literacy. CONCLUSION: This study underlines the need for public education programmes to improve knowledge of various mental illnesses and to reduce stigmatising attitudes among Taiwanese Chinese. The aforementioned socially and culturally driven beliefs must be taken into consideration so that culturally relevant education programmes can be developed.

Comparing the mental health literacy of Chinese people in Australia, China, Hong Kong and Taiwan: Implications for mental health promotion.

Using data of 200, 522, 572, and 287 Chinese from Australia, China, Hong Kong and Taiwan respectively, this study aimed at comparing the mental health literacy of Chinese people from different communities, and between Chinese communities and the Australian general public. The participants were asked questions that assessed their recognition of depression and schizophrenia. Compared with the Australians, much lower percentages of Chinese in the four Chinese communities could correctly identify depression and early schizophrenia. Commonalities in the preference for 'psychiatrist', 'psychologist', 'Chinese medical doctor', and 'Chinese traditional healer', a lack of knowledge of medications, and a higher likelihood of endorsement of traditional Chinese medicines were found among the four Chinese communities. Differences in the preference for 'general practitioner' and 'social worker', and a higher percentage of endorsement of herbal medicines were observed among the different Chinese communities. Cultural factors such as Chinese perceptions of mental illness, and socio-contextual factors such as differences in mental health care system in the four communities were offered to explain these commonalities and differences. Mental health promotion programmes for Chinese people may need to consider the above-mentioned cultural and socio-contextual factors so that specific promotion programmes can be developed.