Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
37,097
result(s) for
"Zhou, Lin"
Sort by:
USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy
Anti-PD-1/PD-L1 immunotherapy has achieved impressive therapeutic outcomes in patients with multiple cancer types. However, the underlined molecular mechanism(s) for moderate response rate (15–25%) or resistance to PD-1/PD-L1 blockade remains not completely understood. Here, we report that inhibiting the deubiquitinase, USP8, significantly enhances the efficacy of anti-PD-1/PD-L1 immunotherapy through reshaping an inflamed tumor microenvironment (TME). Mechanistically, USP8 inhibition increases PD-L1 protein abundance through elevating the TRAF6-mediated K63-linked ubiquitination of PD-L1 to antagonize K48-linked ubiquitination and degradation of PD-L1. In addition, USP8 inhibition also triggers innate immune response and MHC-I expression largely through activating the NF-κB signaling. Based on these mechanisms, USP8 inhibitor combination with PD-1/PD-L1 blockade significantly activates the infiltrated CD8
+
T cells to suppress tumor growth and improves the survival benefit in several murine tumor models. Thus, our study reveals a potential combined therapeutic strategy to utilize a USP8 inhibitor and PD-1/PD-L1 blockade for enhancing anti-tumor efficacy.
The regulatory mechanisms of PD-L1 posttranslational modifications are not completely understood. Here the authors show that USP8 negatively regulates PD-L1 protein abundance by removing the K63-linked ubiquitination of PD-L1; while USP8 inhibition increases MHC-I expression and triggers anti-tumour immune responses through activating NF-κB signalling.
Journal Article
The boy from Clearwater. Book 2
\"After his imprisonment in Green Island, Kun-lin struggles to pick up where he left off ten years earlier. He reconnects with his childhood crush Kimiko and finds work as an editor, jumping from publisher to publisher until finally settling at an advertising company. But when manhua publishing becomes victim to censorship, and many of his friends lose their jobs, Kun-lin takes matters into his own hands. He starts a children's magazine, Prince, for a group of unemployed artists and his old inmates who cannot find work anywhere else. Kun-lin's life finally seems to be looking up... but how long will this last? Forty years later, Kun-lin serves as a volunteer at the White Terror Memorial Park, promoting human rights education. There, he meets Yu Pei-yun, a young college professor who provides him with an opportunity to reminisce on his past and how he picked himself up after grappling with bankruptcy and depression. With the end of martial law, Kun-lin and other former New-Lifers felt compelled to mobilize to rehabilitate fellow White Terror victims, forcing him to face his past head-on. While navigating his changing homeland, he must conciliate all parts of himself--the victim and the savior, the patriot and the rebel, a father to the future generation and a son to the old Taiwan--before he can bury the ghosts of his past.\"--Amazon.com.
BOOK
Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma
Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a π-π stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones. ZK53 treatment causes a decrease of the electron transport chain in a ClpP-dependent manner, which results in declined oxidative phosphorylation and ATP production in lung tumor cells. Mechanistically, ZK53 inhibits the adenoviral early region 2 binding factor targets and activates the ataxia-telangiectasia mutated-mediated DNA damage response, eventually triggering cell cycle arrest. Lastly, ZK53 exhibits therapeutic effects on lung squamous cell carcinoma cells in xenograft and autochthonous mouse models.
Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. Here, the authors develop a potent activator ZK53 that is highly selective on human ClpP but inactive toward bacterial ClpP proteins, and show that ZK53 causes cell cycle arrest via ClpP on lung squamous cell carcinoma cells and exhibits therapeutic effects in animal models.
Journal Article
De novo transcriptome sequencing of Rhododendron molle and identification of genes involved in the biosynthesis of secondary metabolites
Background
Rhododendron molle
(Ericaceae) is a traditional Chinese medicinal plant, its flower and root have been widely used to treat rheumatism and relieve pain for thousands of years in China. Chemical studies have revealed that
R. molle
contains abundant secondary metabolites such as terpenoinds, flavonoids and lignans, some of which have exhibited various bioactivities including antioxidant, hypotension and analgesic activity. In spite of immense pharmaceutical importance, the mechanism underlying the biosynthesis of secondary metabolites remains unknown and the genomic information is unavailable.
Results
To gain molecular insight into this plant, especially on the information of pharmaceutically important secondary metabolites including grayanane diterpenoids, we conducted deep transcriptome sequencing for
R. molle
flower and root using the Illumina Hiseq platform. In total, 100,603 unigenes were generated through de novo assembly with mean length of 778 bp, 57.1% of these unigenes were annotated in public databases and 17,906 of those unigenes showed significant match in the KEGG database. Unigenes involved in the biosynthesis of secondary metabolites were annotated, including the TPSs and CYPs that were potentially responsible for the biosynthesis of grayanoids. Moreover, 3376 transcription factors and 10,828 simple sequence repeats (SSRs) were also identified. Additionally, we further performed differential gene expression (DEG) analysis of the flower and root transcriptome libraries and identified numerous genes that were specifically expressed or up-regulated in flower.
Conclusions
To the best of our knowledge, this is the first time to generate and thoroughly analyze the transcriptome data of both
R. molle
flower and root. This study provided an important genetic resource which will shed light on elucidating various secondary metabolite biosynthetic pathways in
R. molle
, especially for those with medicinal value and allow for drug development in this plant.
Journal Article
The boy from Clearwater. Book 1
\"An incredible true story in graphic novel form that lays bare the tortured and triumphant history of Taiwan, an island claimed and fought over by many countries, through the life story of a man who lived through its most turbulent times\"-- Provided by publisher.
BOOK
Prevalence of depression among university students in China: a systematic review and meta-analysis
Background
Depression among university students in China represents a critical public health challenge, with emerging evidence suggesting exacerbated risks during the COVID-19 pandemic. Despite prior regional studies, a comprehensive national analysis comparing pre-pandemic and pandemic-era prevalence, while accounting for profession-specific stressors, remains lacking. This study aims to quantify depression prevalence across Chinese universities, identify high-risk subgroups, and assess the pandemic’s impact.
Methods
A systematic search was conducted on PubMed, CNKI, Wang-fang Database, and Web of Science. The articles were cross-sectional studies focusing on the prevalence of depression among university students in China, with clearly defined criteria for diagnosing depression included. MetaXL 5.3 was used to pool the outcomes and perform a meta-analysis, assessing the prevalence of depression among university students and influential factors such as the impact of COVID-19.
Results
Data from 32 cross-sectional studies (
n
= 93,679) on depression prevalence among students were analyzed. The prevalence estimates ranged from 12.1% to 77.1%, with a summary prevalence of 34.70% after meta-analytic pooling. Subgroup investigations based on major, sample size, geographical region, gender, and the influence of COVID-19 were conducted. Prior to the pandemic, student depression prevalence was 35.0% (95%CI, 26.9%-43.4%), which increased to 38.7% (95%CI, 33.6%-44.0%) during and after the pandemic.
Discussion
This study underscores a substantial mental health burden among Chinese university students, intensified by pandemic-related disruptions. Medical students and those in high-stress regions warrant prioritized interventions. Systemic reforms in healthcare education and regionally tailored mental health policies are urgently needed. Longitudinal studies are critical to track post-pandemic recovery trajectories.
Systematic review registration
CRD42024502949.
Journal Article
Exosomal LncRNA LINC00659 transferred from cancer-associated fibroblasts promotes colorectal cancer cell progression via miR-342-3p/ANXA2 axis
Background
Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumor progression by transferring exosomes to adjacent cells. Our aim was to clarify the role of LINC00659 encapsulated in CAFs-derived exosomes (CAFs-exo) in colorectal cancer (CRC).
Methods
CAFs and normal fibroblasts (NFs) were isolated and cultured. CAFs-exo and NFs-derived exosomes (NFs-exo) were characterized by transmission electron microscope and Western blot. The mRNA level of LINC00659 in CAFs-exo and NFs-exo were measured. Then we analyzed cell proliferation by CCK-8 and clone formation assay, cell migration by cell scratch, and cell invasion by Transwell. Epithelial mesenchymal transformation (EMT) related markers E-cadherin, N-cadherin, Vimentin and Snail-1 expressions were assessed by Western blot. The binding of LINC00659 and miR-342-3p, miR-342-3p and ANXA2 were analyzed by dual-luciferase reporter gene assay.
Results
CAFs and NFs showed a spindle-like morphology. CAFs-exo promoted CRC cell proliferation, migration, invasion and EMT progression. The expression of LINC00659 in CAF-derived exosomes was significantly increased, and fibroblasts could transfer exosomal LINC00659 to CRC cells. We further revealed that transfection of miR-342-3p mimic or sh-ANXA2 could obviously reverse the promotion effect of exosomal LINC00659 on CRC progression. Functional studies reveal that LINC00659 is transferred from CAFs to the cancer cells via exosomes, where it promotes CRC cell proliferation, invasion, migration and EMT progression in vitro. Mechanistically, LINC00659 interacts directly with miR-342-3p to increase ANXA2 expression in CRC cells.
Conclusion
Collected evidence supported that CAFs-derived exosomal LINC00659 promotes CRC cell proliferation, invasion and migration via miR-342-3p/ANXA2axis.
Journal Article
Clinical significance of PCT, CRP, IL-6, NLR, and TyG Index in early diagnosis and severity assessment of acute pancreatitis: A retrospective analysis
To evaluate the clinical utility of PCT, CRP, IL-6, NLR, and TyG index in improving the early diagnosis and severity assessment of acute pancreatitis (AP). This retrospective study included 137 AP patients and 30 healthy controls from Hunan Provincial People’s Hospital (January 2021–September 2023). Univariate and multivariate logistic regression analyses assessed the associations between biomarkers and severe acute pancreatitis (SAP). Receiver operating characteristic (ROC) curves, DeLong test, and Bonferroni correction were used to evaluate predictive performance. Model robustness was validated via 5-fold cross-validation. PCT, CRP, IL-6, NLR, and TyG index levels were significantly elevated in AP patients compared to controls (
P
< 0.001) and correlated with disease severity (
P
< 0.05). CRP and NLR levels differed significantly among mild, moderate, and severe AP (
P
< 0.01). Alcohol consumption and hyperlipidemia were significantly linked to AP severity (P for trend < 0.0001). Multivariate analysis identified hyperlipidemia (OR = 3.030,
P
= 0.040), CRP (OR = 1.011,
P
< 0.001), and NLR (OR = 1.078,
P
= 0.020) as independent SAP predictors. The combined model of CRP + NLR + TyG achieved the highest AUC (0.882, sensitivity = 77.2%, specificity = 88.5%), though it was not significantly better than CRP + NLR or CRP + TyG models (
P
> 0.05). 5-fold cross-validation confirmed consistent performance (mean AUC = 0.817 ± 0.118). PCT, CRP, IL-6, NLR, and TyG index are valuable in diagnosing and assessing AP prognosis. Hyperlipidemia, CRP, and NLR are reliable independent predictors of SAP. Combining multiple biomarkers enhances diagnostic precision and provides guidance for personalized treatment strategies in AP.
Journal Article