Crystalline Olefin-Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis.

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99% enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Factors Influencing Breast Cancer Awareness in Rural Southwest China: A Cross-Sectional Study.

Background: This study aimed to explore the current knowledge level of breast cancer among rural women in Southwest China and analyze the influencing factors of breast cancer cognition. Methods: From May to November 2022, 1468 rural women were invited to participate in this study. Demographic information and the Chinese version of the Breast Cancer Awareness Measure (C-BCAM) were collected through one-on-one investigations. The data were analyzed using descriptive statistics, chi-square tests, and multiple regression analysis in SPSS 26.0. Results: The study included a total of 1468 rural women with a median age of 54.0 (IQR, 47.0, 60.0).The average score of breast cancer in the study population was 73.0 (IQR, 66.0, 82.0). Among women in Southwest China, the awareness rates of knowledge on breast cancer symptoms, barriers to seeking medical help, and risk factors were 68.8%, 98.4%, and 62.1%, respectively. The awareness rate was found to increase with higher education levels (P<0.001) and decrease with increasing age (P<0.001). Multivariate logistic regression analysis identified three variables that might influence breast cancer awareness: education level, contraceptive measures, and history of breast disease (all P<0.05). Specifically, history of breast disease (Odds ratio (OR) = 1.907, 95% CI = 1.128 ~ 3.223), middle school education (OR = 2.155, 95% CI = 1.585 ~ 2.928), and junior college education and above (OR = 5.536, 95% CI = 1.898 ~ 16.148) were positive factors for women's breast cancer awareness. Conversely, the use of intrauterine devices (OR = 0.523, 95% CI = 0.384 ~ 0.712) was found to be a negative factor for women's breast cancer awareness. Conclusion: This study highlights the insufficient awareness of breast cancer among women in rural area of Southwest China. It emphasizes the necessity of health education to improve female breast cancer awareness.

Utilization of 3D printing technology in hepatopancreatobiliary surgery. / 3D打印技术在肝胆胰外科中的应用进展.

The technology of three-dimensional (3D) printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering, industrial design, and biomedicine. In biomedical science, several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery. For example, 3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies, surgical simulation, intraoperative navigation, medical training, and patient education. Moreover, cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs. With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery, we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Establishment and Characterization of a TP53-Mutated Eyelid Sebaceous Carcinoma Cell Line.

Purpose: Eyelid sebaceous carcinoma (SeC) is the third most frequent eyelid malignancy worldwide and is relatively prevalent in Asian patients. An eyelid SeC cell line model is necessary for experimental research to explore the etiology and pathogenesis of eyelid SeC. This study established and characterized an eyelid SeC cell line with a TP53 mutation that might be useful for analyzing potential treatment options for eyelid SeC. Methods: The eyelid SeC cell line SHNPH-SeC was obtained from a patient with eyelid SeC at Shanghai Ninth People's Hospital (SHNPH), Shanghai JiaoTong University School of Medicine. Immunofluorescence staining was employed to detect the origination and proliferation activity. Short tandem repeat (STR) profiling was performed for verification. Chromosome analysis was implemented to investigate chromosome aberrations. Whole exome sequencing (WES) was used to discover genomic mutations. Cell proliferation assays were performed to identify sensitivity to mitomycin-C (MMC) and 5-fluorouracil (5-FU). Results: SHNPH-SeC cells were successively subcultured for more than 100 passages and demonstrated rapid proliferation and migration. Karyotype analysis revealed abundant chromosome aberrations, and WES revealed SeC-related mutations in TP53, KMT2C, and ERBB2. An in vivo tumor model was successfully established in NOD/SCID mice. Biomarkers of eyelid SeC, including cytokeratin 5 (CK5), epithelial membrane antigen (EMA), adipophilin, p53, and Ki-67, were detected in SHNPH-SeC cells, original tumors, and xenografts. MMC and 5-FU inhibited the proliferation and migration of SHNPH-SeC cells, and SHNPH-SeC cells presented a greater drug response than non-TP53-mutated SeC cells. Conclusions: The newly established eyelid SeC cell line SHNPH-SeC demonstrates mutation in TP53, the most commonly mutated gene in SeC. It presents SeC properties and malignant characteristics that may facilitate the investigation of cellular behaviors and molecular mechanisms of SeC to explore promising therapeutic strategies.

MOF-Derived In2O3 Microrod-Decorated MgIn2S4 Nanosheets: Z-Scheme Heterojunction for Efficient Photocatalytic Degradation of Tetracycline.

The construction of Z-scheme heterostructures using matching band semiconductors is an effective strategy for producing highly efficient photocatalysts. In this study, MgIn2S4(MIS) was grown in situ on In2O3 microrods created with an In-based MOF material (In-MIL-68) as a template to successfully establish a unique MIS-In2O3 heterojunction with a well-matched Z-scheme interface charge transfer channel. Tetracycline (TC) as a typical antibiotic was chosen as the target pollutant to evaluate the photocatalytic activity. After 120 min of visible light irradiation, the MIS-In2O3-(10:1) material had the greatest photocatalytic degradation activity of tetracycline with 96.55%, which was 2.39 and 4.26 times that of MIS and In2O3, respectively. The improved photocatalytic activity is attributed to the in situ growth of MIS on In2O3, forming a Z-scheme heterojunction at the interface, which not only increases the specific surface area, exposes the abundant active site, and improves light utilization but also facilitates the migration and separation of photogenic carriers. The photocatalytic degradation products of TC were detected by liquid chromatography-mass spectrometry (LC-MS), and a preliminary degradation pathway was proposed. Radical capture experiments and ESR analysis confirmed that the main active species were holes (h+), superoxide radicals (•O2-), and superoxide and hydroxyl radicals (•OH). Finally, combined with band position analysis, this study proposes a direct Z-scheme heterojunction mechanism to improve the photocatalytic degradation of tetracycline in MIS under visible light.

Current status and influencing factors of policy identification in health impact assessment: a case study of Zhejiang Province.

BACKGROUND: Health impact assessment (HIA) is a procedure, method and tool for evaluating the potential health impacts of policies, plans and construction projects, as well as the distribution of these impacts on population. Majority of international studies on health impact assessment have focussed on conceptual papers or case evaluations, neglecting participants' views on policies. METHODS: A semi-structured interview with 30 health impact assessment experts was employed in this study, and the Nvivo software was utilized to analyse factors that influence policy identification. Subsequently, a multi-stage stratified random sampling method was adopted to survey 655 pilot staff members involved in health impact assessment in Zhejiang Province. Descriptive statistics were used to describe the current status and identify the factors influencing policy identification. In addition, hierarchical linear regression analysis and structural equation modelling were employed to determine the relationship between policy identification and influencing factors. RESULTS: Statistically significant differences were found among participants in the level of identification of policies across three dimensions. The policy sentiment dimension had the highest score (4.137 ± 0.664), followed by policy cognition (4.075 ± 0.632) and policy evaluation (3.631 ± 0.797) dimensions. Subject trust had a positive impact on policy cognition (ß = 0.503, P < 0.001), policy sentiment (ß = 0.504, P < 0.001) and policy evaluation (ß = 0.465, P < 0.001). Procedural justice had a positive impact on policy sentiment (ß = 0.085, P < 0.01) and policy evaluation (ß = 0.084, P < 0.05), but not policy cognition (ß = 0.056, P > 0.05). Policy identification is influenced by age and average monthly salary among other factors. CONCLUSION: These results highlight the importance of subjective trust and procedural justice in policy identification of health impact assessment. They provide valuable insights to developing interventions to overcome barriers to the implementation and enhancement of global identification of policies. Going forward, cross-sectoral synergies, enhanced international communication and training to increase participants' trust in the policy should be optimized to improve health impact assessment. Additional measures should be taken, such as ensuring seamless communication channels, embedding health impact assessment in administrative mechanisms, and establishing strong oversight and grievance mechanisms to improve fairness and transparency in the implementation and results of health impact assessment.

Non-Coding RNA in Cholangiocarcinoma: An Update.

Cholangiocarcinoma (CCA) is one of the most common tumors with high malignancy. Its incidence is increasing year by year, and it is insidious and easily metastasized, and most patients are already in advanced stages when they are diagnosed. Surgery is an essential treatment for CCA, but the 5-year survival rate is still unsatisfactory due to the low early diagnosis rate and high malignancy of CCA. Therefore, exploring the molecular mechanisms of CCA to find reliable biomarkers and effective therapeutic targets is essential to improve the early diagnosis and survival rate of CCA. Non-coding RNA (ncRNA) is a class of RNA without protein-coding ability, mainly including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). In recent years, numerous pieces of evidence have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA through various mechanisms such as mediating epigenetic, sponge miRNAs regulating the expression of target genes and participating in regulating cancer-related signaling pathways, which provides new approaches and ideas for early diagnosis, prognosis assessment and therapeutic targeting of CCA. In this paper, we review the molecular mechanisms of lncRNAs and circRNAs regulating the progression of CCA in recent years and discuss their potential clinical value in CCA.

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review.

Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

Research progress of circulating non-coding RNA in diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor that carries a significant risk of morbidity and mortality. This type of cancer is prevalent in Asia due to the widespread presence of risk factors. Unfortunately, HCC often goes undetected until it has reached an advanced stage, making early detection and treatment critical for better outcomes. Alpha-fetoprotein (AFP) is commonly used in clinical practice for diagnosing HCC, but its sensitivity and specificity are limited. While surgery and liver transplantation are the main radical treatments, drug therapy and local interventions are better options for patients with advanced HCC. Accurately assessing treatment efficacy and adjusting plans in a timely manner can significantly improve the prognosis of HCC. Non-coding RNA gene transcription products cannot participate in protein production, but they can regulate gene expression and protein function through the regulation of transcription and translation processes. These non-coding RNAs have been found to be associated with tumor development in various types of tumors. Noncoding RNA released by tumor or blood cells can circulate in the blood and serve as a biomarker for diagnosis, prognosis, and efficacy assessment. This article explores the unique role of circulating noncoding RNA in HCC from various perspectives.

Little things with significant impact: miRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has developed into one of the most lethal, aggressive, and malignant cancers worldwide. Although HCC treatment has improved in recent years, the incidence and lethality of HCC continue to increase yearly. Therefore, an in-depth study of the pathogenesis of HCC and the search for more reliable therapeutic targets are crucial to improving the survival quality of HCC patients. Currently, miRNAs have become one of the hotspots in life science research, which are widely present in living organisms and are non-coding RNAs involved in regulating gene expression. MiRNAs exert their biological roles by suppressing the expression of downstream genes and are engaged in various HCC-related processes, including proliferation, apoptosis, invasion, and metastasis. In addition, the expression status of miRNAs is related to the drug resistance mechanism of HCC, which has important implications for the systemic treatment of HCC. This paper reviews the regulatory role of miRNAs in the pathogenesis of HCC and the clinical applications of miRNAs in HCC in recent years.

A DNA framework-based dual signal amplification biosensor for portable detection of SARS-CoV-2 and its mutations.

We developed a rapid and accurate biosensor to detect SARS-CoV-2 and distinguish its mutations. Benefitting from a DNA framework-modified ordered interface and a dual signal amplification strategy, our biosensor could detect SARS-CoV-2 with a detection limit down to 10 fM. It performed well on pseudo virus and SARS-CoV-2 RNA standard materials, revealing the potential application in disease diagnosis and spread, in combination with a home-made smartphone.

Exosomal miRNAs in the microenvironment of pancreatic cancer.

Pancreatic cancer (PC) is highly aggressive having an extremely poor prognosis. The tumor microenvironment (TME) of PC is complex and heterogeneous. Various cellular components in the microenvironment are capable of secreting different active substances that are involved in promoting tumor development. Their release may occur via exosomes, the most abundant extracellular vesicles (EVs), that can carry numerous factors as well as act as a mean of intercellular communication. Emerging evidence suggests that miRNAs are involved in the regulation and control of many pathological and physiological processes. They can also be transported by exosomes from donor cells to recipient cells, thereby regulating the TME. Exosomal miRNAs show promise for use as future targets for PC diagnosis and prognosis, which may reveal new treatment strategies for PC. In this paper, we review the important role of exosomal miRNAs in mediating cellular communication in the TME of PC as well as their potential use in clinical applications.

Long noncoding RNA HAND2-AS1: A crucial regulator of malignancy.

Long non-coding RNAs (LncRNAs) are single-stranded RNAs over 200 nucleotides in length that have no protein-coding function and have long been considered non-functional by-products of transcription. Recent studies have shown that dysregulation of lncRNAs may be involved in the malignant biological behavior of tumors. Targeted regulation of lncRNAs has become a research focus of anti-tumor treatment. LncRNAs heart and neural crest derivatives expressed 2 antisense RNA 1 (HAND2-AS1) was down-regulated in various tumors and can be used as a critical tumor regulator to modulate tumor cells proliferation, apoptosis, metastasis, invasion, metabolism and drug resistance. Additionally, aberrantly expressed HAND2-AS1 was closely related to the clinical pathological characteristics of cancer patients and serve as a promising tumor diagnostic and prognostic biomarker. This article aims to review the roles of HAND2-AS1 in tumorigenesis and development, as well as the underlying molecular mechanisms and clinical significance.

Ferroptosis: From Basic Research to Clinical Therapeutics in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and highly heterogeneous malignancies worldwide. Despite the rapid development of multidisciplinary treatment and personalized precision medicine strategies, the overall survival of HCC patients remains poor. The limited survival benefit may be attributed to difficulty in early diagnosis, the high recurrence rate and high tumor heterogeneity. Ferroptosis, a novel mode of cell death driven by iron-dependent lipid peroxidation, has been implicated in the development and therapeutic response of various tumors, including HCC. In this review, we discuss the regulatory network of ferroptosis, describe the crosstalk between ferroptosis and HCC-related signaling pathways, and elucidate the potential role of ferroptosis in various treatment modalities for HCC, such as systemic therapy, radiotherapy, immunotherapy, interventional therapy and nanotherapy, and applications in the diagnosis and prognosis of HCC, to provide a theoretical basis for the diagnosis and treatment of HCC to effectively improve the survival of HCC patients.

Higher-Quality Pumpkin Cultivars Need to Recruit More Abundant Soil Microbes in Rhizospheres.

Two different qualities of pumpkin, cultivars G1519 and G1511, were grown in the same environment under identical management. However, their qualities, such as the contents of total soluble solids, starch, protein, and vitamin C, were significantly different. Do rhizospheric microbes contribute to pumpkin quality? To answer this question, this study investigated the soil microbial compositions in the rhizospheres of different quality pumpkin cultivars to determine the differences in these soil microbial compositions and thus determine how soil microbes may affect pumpkin quality. Firstly, a randomized complete block design with two pumpkin cultivars and three replications was performed in this study. The soil microbial compositions and structures in the rhizospheres of the two pumpkin cultivars were analyzed using a high-throughput sequencing technique. In comparison with the low-quality pumpkin cultivar (G1519), higher microbial diversity and richness could be found in the rhizospheres of the high-quality pumpkin cultivar (G1511). The results showed that there were significant differences in the soil bacterial and fungal community compositions in the rhizospheres of the high- and low-quality pumpkin cultivars. Although the compositions and proportions of microorganisms were similar in the rhizospheres of the two pumpkin cultivars, the proportions of Basidiomycota and Micropsalliota in the G1519 rhizosphere were much higher than those in the G1511 rhizosphere. Furthermore, the fungal phylum and genus Rozellomycota and Unclassified_p__Rozellomycota were unique in the rhizosphere of the high-quality pumpkin cultivar (G1511). All the above results indicate that soil microbes were enriched differentially in the rhizospheres of the low- and high-quality pumpkin cultivars. In other words, more abundant soil microbes were recruited in the rhizosphere of the high-quality pumpkin cultivar as compared to that of the low-quality cultivar. Rozellomycota and Unclassified_p__Rozellomycota may be functional microorganisms relating to pumpkin quality.

Reprogramming of central carbon metabolism in hepatocellular carcinoma.

In multicellular organisms, nutrient uptake and its metabolism are subject to stringent regulation to maintain cellular integrity and prevent aberrant cell proliferation. However, the altered signaling pathways and gene expression disorders in hepatocellular carcinoma (HCC) induce the transformation of metabolic patterns. The reprogrammed metabolic pattern not only conferred HCC cells viability in nutrient-deficient environments, but also contributed to the formation of a unique immune surveillance barrier. Furthermore, in this metabolic pattern, the accumulation of a large number of oxidation products in cells also activates tumor-related signaling pathways. Therefore, the exploration of underlying molecular mechanisms of the metabolic switch will help to improve therapeutic strategies for HCC. We systematically reviewed the landmark events and current research breakthroughs in the study of glucometabolic reprogramming in HCC. Focusing on the central carbon metabolism, the internal energy conversion in HCC and its cancerous mechanisms were fully explained. Furthermore, we also discussed the HCC-specific acellular regulation, metabolic switch of cancer stem cells, oxidative stress adaptation and the formation of immunosuppressive microenvironment, hoping to provide insights for future basic and clinical research.

RPNs Levels Are Prognostic and Diagnostic Markers for Hepatocellular Carcinoma.

The ribophorin family (RPN) is an essential regulatory subunit of the proteasome. By influencing the ubiquitin-proteasome system activity, ribophorins (RPNs) are responsible for almost all physiology and pathology processes of mammalian cells. Nevertheless, little is known about the role of RPNs in HCC. In this work, we first evaluated the transcriptional levels and the prognostic and diagnostic value of RPNs based on the public database. Firstly, we found all RPNs were surprisingly consistently upregulated in HCC tissues. Moreover, the RPNs' expression pattern is correlated with HCC tumor grade. The TCGA HCC platforms' data indicated that RPN2, RPN3, RPN6, RPN9, RPN10, RPN11, and RPN12 have robust diagnosis values. Then, survival analysis revealed that the high expression of RPN1, RPN2, RPN4, RPN5, RPN6, RPN9, and RPN11 was correlated with unfavourable HCC overall survival. Then, genetic alteration, immune infiltration feature, gene-genes network, and functional enrichment for RPNs indicated that RPNs have many potential biosynthesis activities expert for UPS functions. Moreover, western blot and qRT-PCR results confirmed these results. The silencing of RPN6 and RPN9 significantly reduced HCC cells' proliferation, migration, and invasion ability in vitro. An in vivo tumor model further validated the oncogene effect of RPN6 on HCC cell growth. Moreover, RPN6 and RPN9 could promote cell migratory and invasive potential by affecting the epithelial-mesenchymal transition (EMT) process. In summary, this study suggests that the RPN family has the potential to be potential biomarkers and targets for HCC.

Glucometabolic reprogramming: From trigger to therapeutic target in hepatocellular carcinoma.

Glucose, the central macronutrient, releases energy as ATP through carbon bond oxidation and supports various physiological functions of living organisms. Hepatocarcinogenesis relies on the bioenergetic advantage conferred by glucometabolic reprogramming. The exploitation of reformed metabolism induces a uniquely inert environment conducive to survival and renders the hepatocellular carcinoma (HCC) cells the extraordinary ability to thrive even in the nutrient-poor tumor microenvironment. The rewired metabolism also confers a defensive barrier which protects the HCC cells from environmental stress and immune surveillance. Additionally, targeted interventions against key players of HCC metabolic and signaling pathways provide promising prospects for tumor therapy. The active search for novel drugs based on innovative mutation targets is warranted in the future for effectively treating advanced HCC and the preoperative downstage. This article aims to review the regulatory mechanisms and therapeutic value of glucometabolic reprogramming on the disease progression of HCC, to gain insights into basic and clinical research.

Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer.

Inositol 1,4,5-Triphosphate Receptor Family (ITPRs) are necessary intracellular Ca2+-release channel encoders and participate in mammalian cell physiological and pathological processes. Previous studies have suggested that ITPRs participate in tumorigenesis of multiple cancers. Nevertheless, the diverse expression profiles and prognostic significance of three ITPRs in pancreatic cancer have yet to be uncovered. In this work, we examined the expression levels and survival dates of ITPRs in patients with pancreatic cancer. As a result, we identified that ITPR1 and ITPR3 expression levels are significantly elevated in cancerous specimens. Survival data revealed that over-expression of ITPR2 and ITPR3 resulted in unfavourable overall survival and pathological stage. The multivariate Cox logistic regression analysis showed that ITPR3 could be an independent risk factor for PAAD patient survival. Moreover, to investigate how ITPRs work, co-expressed genes, alterations, protein-protein interaction, immune infiltration, methylation, and functional enrichment of ITPRs were also analyzed. Then, we evaluated these findings in clinical samples. Moreover, the gain and loss of function of ITPR3 were also conducted. The electron microscope assay was employed to explore the role of ITPR3 in pancreatic cancer cell lines' endoplasmic reticulum stress. In summary, our findings demonstrated that ITPR3 has the potential to be drug targets and biomarkers for human pancreatic cancer.