Causality of immune cells on primary sclerosing cholangitis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran's Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy. Results: In forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032-1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086-1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630-0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823-0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28- CD127- CD25++ CD8+ T cell AC, CD28- CD25++ CD8+ T cell AC, CD28- CD8+ T cell/CD8+ T cell, CD28- CD8+ T cell AC, and CD45 RA- CD28- CD8+ T cell AC. Conclusion: Our study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.

Advanced Planar Projection Contour (PPC): A Novel Algorithm for Local Feature Description in Point Clouds.

Local feature description of point clouds is essential in 3D computer vision. However, many local feature descriptors for point clouds struggle with inadequate robustness, excessive dimensionality, and poor computational efficiency. To address these issues, we propose a novel descriptor based on Planar Projection Contours, characterized by convex packet contour information. We construct the Local Reference Frame (LRF) through covariance analysis of the query point and its neighboring points. Neighboring points are projected onto three orthogonal planes defined by the LRF. These projection points on the planes are fitted into convex hull contours and encoded as local features. These planar features are then concatenated to create the Planar Projection Contour (PPC) descriptor. We evaluated the performance of the PPC descriptor against classical descriptors using the B3R, UWAOR, and Kinect datasets. Experimental results demonstrate that the PPC descriptor achieves an accuracy exceeding 80% across all recall levels, even under high-noise and point density variation conditions, underscoring its effectiveness and robustness.

Hierarchical Mg/Al hydrotalcite oxide hollow microspheres with excellent adsorption capability towards Congo red.

A novel citrate anion-intercalated Mg/Al layered double hydroxide (CA-LDH) is synthesized via a one-step hydrothermal process. The synthesized CA-LDH is a hollow flower-like microsphere composed of thin nanoflakes (10 nm in thickness). After calcination, the formed Mg/Al layered double oxide (CA-LDO) hollow microspheres possess a high specific surface area of 247.8 m2 g-1 and a high pore volume of 0.97 cm3 g-1, which endow them with excellent adsorption ability towards Congo red (CR). The maximum adsorption capacity of CR onto CA-LDO can reach up to 1883 mg g-1. The significantly improved adsorption capacity of CA-LDO can be attributed to its unique structures of hierarchical hollow microspheres, in which the hierarchical porous shell layer provides enough adsorption sites to anchor the dye molecules, and the hollow core can preserve the absorbed dye. This study provides a promising novel adsorbent which can be used for efficient water remediation.

A novel model for predicting the prognosis of postoperative intrahepatic cholangiocarcinoma patients.

Intrahepatic cholangiocarcinoma (ICC) accounts for 20% of liver malignancies with a 5-year survival rate of 35% at best with limited prognostic predictors. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers. In this study, we developed a modified prognostic model from LIPI called intrahepatic immune prognostic index (IIPI) for ICC. A retrospectively study was conducted at Liver Transplant Center of West China Hospital between January 2015 and January 2023. Hematological factors and clinical features of ICC patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated. In this study, derived neurtrophil to lymphocyte ratio (dNLR), arbohydrate antigen199 (CA199) and carcinoembryonic antigen (CEA) have higher AUC values. LIPI was composed of dNLR and was further modified by combing CA199 and CEA, forming the IIPI. The IIPI consists of four grades which are None, Light, Moderate and Severe. Compared to other prognostic factors, IIPI exhibited better ability to predict overall survival. The multivariate analysis indicated that cirrhosis, differentiation, hilar invasion and IIPI were independent prognostic factors for ICC patients. An IIPI-based nomogram was also established and could predict the overall survival. In addition, the subgroup analyses based on clinical prognostic factors showed that the IIPI exhibited excellent prognostic influence. IIPI model is suitable for predicting the prognosis of postoperative ICC patients. Further research is needed to explore the relationship between postoperative recurrence and metastasis of ICC patients and IIPI.

Three-dimensional S-scheme heterojunction by integration of purple tungsten oxide nanowires and cadmium sulfide nanospheres for effective photocatalytic hydrogen generation.

The practical photocatalytic application of cadmium sulfide (CdS) has been significantly constrained by fast carrier recombination and significant photocorrosion. Therefore, we developed a three-dimensional (3D) step-by-step (S-scheme) heterojunction using the coupling interface between purple tungsten oxide (W18O49) nanowires and CdS nanospheres. The photocatalytic hydrogen evolution rate of optimized W18O49/CdS 3D S-scheme heterojunction can reach 9.7 mmol·h-1·g-1, 7.5 and 16.2 times greater than pure CdS (1.3 mmol·h-1·g-1) and 10 wt%-W18O49/CdS (mechanical mixing, 0.6 mmol·h-1·g-1), proving that the tight S-scheme heterojunction constructed by the hydrothermal method can efficiently enhance the carrier separation. Notably, the apparent quantum efficiency (AQE) of W18O49/CdS 3D S-scheme heterojunction approaches 7.5% and 3.5% at 370 nm and 456 nm, respectively, which is 7.5 and 8.8 times than pure CdS (1.0% and 0.4%). The produced W18O49/CdS catalyst also has relative stability of structure and hydrogen production. Additionally, the H2 evolution rate of W18O49/CdS 3D S-scheme heterojunction is 1.2 times greater than 1 wt%-platinum (Pt)/CdS (8.2 mmol·h-1·g-1), which indicates that the W18O49 can effectively replace the precious metal for boosting the hydrogen production rate.

FLASH radiotherapy: A promising new method for radiotherapy.

Among the treatments for malignant tumors, radiotherapy is of great significance both as a main treatment and as an adjuvant treatment. Radiation therapy damages cancer cells with ionizing radiation, leading to their death. However, radiation-induced toxicity limits the dose delivered to the tumor, thereby constraining the control effect of radiotherapy on tumor growth. In addition, the delayed toxicity caused by radiotherapy significantly harms the physical and mental health of patients. FLASH-RT, an emerging class of radiotherapy, causes a phenomenon known as the 'FLASH effect', which delivers radiotherapy at an ultra-high dose rate with lower toxicity to normal tissue than conventional radiotherapy to achieve local tumor control. Although its mechanism remains to be fully elucidated, this modality constitutes a potential new approach to treating malignant tumors. In the present review, the current research progress of FLASH-RT and its various particular effects are described, including the status of research on FLASH-RT and its influencing factors. The hypothetic mechanism of action of FLASH-RT is also summarized, providing insight into future tumor treatments.

Noncoding RNAs as sensors of tumor microenvironmental stress.

The tumor microenvironment (TME) has been demonstrated to modulate the biological behavior of tumors intensively. Multiple stress conditions are widely observed in the TME of many cancer types, such as hypoxia, inflammation, and nutrient deprivation. Recently, accumulating evidence demonstrates that the expression levels of noncoding RNAs (ncRNAs) are dramatically altered by TME stress, and the dysregulated ncRNAs can in turn regulate tumor cell proliferation, metastasis, and drug resistance. In this review, we elaborate on the signal transduction pathways or epigenetic pathways by which hypoxia-inducible factors (HIFs), inflammatory factors, and nutrient deprivation in TME regulate ncRNAs, and highlight the pivotal roles of TME stress-related ncRNAs in tumors. This helps to clarify the molecular regulatory networks between TME and ncRNAs, which may provide potential targets for cancer therapy.

PCBP1 regulates the transcription and alternative splicing of metastasis­related genes and pathways in hepatocellular carcinoma.

PCBP1 is a multifunctional RNA-binding protein (RBP) expressed in most human cells and is involved in posttranscriptional gene regulation. PCBP1 regulates the alternative splicing, translation and RNA stability of many cancer-related genes and has been identified as a potential tumour suppressor gene. PCBP1 inhibits the invasion of hepatocellular carcinoma (HCC) cells, but there are few studies on the specific regulatory target and mechanism of RBPs in HCC, and it is unclear whether PCBP1 plays a role in tumour metastasis as a splicing factor. We analysed the regulation of gene expression by PCBP1 at the transcriptional level. We obtained and analysed PCBP1-knockdown RNA-seq data and eCLIP-seq data of PCBP1 in HepG2 cells and found that PCBP1 widely regulates the alternative splicing and expression of genes enriched in cancer-related pathways, including extracellular matrix, cell adhesion, small molecule metabolic process and apoptosis. We validated five regulated alternative splicing events affected by PCBP1 using RT-qPCR and found that there was a significant difference in the expression of APOC1 and SPHK1 between tumour and normal tissues. In this study, we provided convincing evidence that human PCBP1 profoundly regulates the splicing of genes associated with tumour metastasis. These findings provide new insight into potential markers or therapeutic targets for HCC treatment.

Treatment Preferences of Residents Assumed to Have Severe Chronic Diseases in China: A Discrete Choice Experiment.

OBJECTIVES: This study aims to elicit the relative importance of treatment attributes that influence residents' choice, assuming they are suffering severe non-communicable diseases (NCDs), to explore how they make trade-offs between these attributes and to estimate the monetary value placed on different attributes and attribute levels. METHODS: A discrete choice experiment (DCE) was conducted with adults over 18 years old in China. Preferences were evaluated based on four treatment attributes: care provider, mode of service, distance to practice and cost. A mixed logit model was used to analyze the relative importance of the four attributes and to calculate the willingness to pay (WTP) for a changed attribute level. RESULTS: A total of 93.47% (2019 of 2160) respondents completed valid questionnaires. The WTP results suggested that participants would be willing to pay CNY 822.51 (USD 124.86), CNY 470.54 (USD 71.41) and CNY 68.20 (USD 10.35) for services provided by experts, with integrated traditional Chinese medicine (TCM) and Western medicine (WM) and with a service distance <=30 min, respectively. CONCLUSIONS: The results suggested that mode of service, care provider, distance to practice and cost should be considered in priority-setting decisions. The government should strengthen the curative service capability in primary health facilities and give full play to the role of TCM in the prevention and treatment of severe chronic diseases.

Role of noncoding RNAs in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a malignant tumour originating from biliary epithelial cells, and is increasing in incidence. Radical surgery is the main treatment. However, the pathogenesis of CCA is unclear. Noncoding RNAs (ncRNAs) are non­protein­coding RNAs produced by genomic transcription that include microRNAs (miRNAs), circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs). They play important roles in gene expression, epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also serve key roles in cancer development. Numerous studies have been carried out on ncRNAs, and associated publications have shown that ncRNAs are closely associated with the physiological and pathological mechanisms of CCA. The findings of these studies can provide new insights into the diagnosis, treatment and prognosis of CCA. The present review summarizes the pathophysiological mechanisms of different types of ncRNAs, including miRNAs, circRNAs and lncRNAs in CCA, and their applications in the diagnosis and treatment of CCA.

Low density lipoprotein receptor (LDLR)-targeted lipid nanoparticles for the delivery of sorafenib and Dihydroartemisinin in liver cancers.

AIMS: Liver cancer is one of the leading causes of cancer mortality worldwide. Inspired by the biological structure and function of low-density lipoprotein (LDL), in this study, an ApopB-100 based targeted lipid nanoparticles was synthesized to improve the therapeutic efficacy in liver cancer treatment. MAIN METHODS: The biological composition of ApopB is similar to LDL which can effectively increase the targeting efficiency of nanoparticles in LDL receptor (LDLR)-overexpressed liver tumors. KEYFINDINGS: We have demonstrated that the co-administration of sorafenib (SRF) and Dihydroartemisinin (DHA) could exhibit synergistic anticancer effect in HepG2 liver cancer cells. DHA produced excessive cellular reactive oxygen species (ROS) and induced greater apoptosis of cancer cells. LDL-based SRF/DHA-loaded lipid nanoparticles (LD-SDN) showed remarkable decrease in the cell viability compared to that of either of single drug treated cancer cells. Combination of SRF+DHA resulted in predominant SubG1 proportion of cells. LD-SDN exhibited the highest SubG1 (%) of cells compared to that of any of the individual drugs. Most importantly, robust antitumor response and delayed tumor growth was observed for LD-SDN treated xenograft tumor model. Ki67 proliferation index of LD-SDN (22.1 ± 5.6%) is significantly lesser compared to that of either control (86.2 ± 6.9%) or SRF (75.4 ± 4.89%) or DHA (69.4 ± 6.9%). SIGNIFICANCES: These data provide strong evidence that LDL-mimetic lipid nanoformulations could be utilized as a biocompatible and tumor targeted platform for the delivery of multiple anticancer drugs in cancer treatment.

Role of non-coding RNA in pancreatic cancer.

Pancreatic cancer is a malignant disease that develops rapidly and carries a poor prognosis. Currently, surgery is the only radical treatment. Non-coding RNAs (ncRNAs) are protein-free RNAs produced by genome transcription; they play important roles in regulating gene expression, participating in epigenetic modification, cell proliferation, differentiation and reproduction. ncRNAs also play key roles in the development of cancer; microRNA (miRNA) and long non-coding RNA (lncRNA) may lead the way to new treatments for pancreatic cancer. miRNAs are short-chain ncRNAs (19-24 nt) that inhibit the degradation of protein translation or their target gene mRNAs to regulate gene expression. lncRNAs contain >200 nt of ncRNA and play important regulatory roles in a number of malignant tumors, in terms of tumor cell proliferation, apoptosis, invasion and distant metastasis. lncRNAs can be exploited for the diagnosis and treatment of pancreatic cancer and have substantial prospects for clinical application. Nevertheless, the molecular mechanism of their regulation and function, as well as the significance of other ncRNAs, such as piwi-interacting RNA, in the pathogenesis of pancreatic cancer, are largely unknown. In this review, the structures of ncRNAs with various classifications, as well as the functions and important roles of ncRNAs in the diagnosis and treatment of pancreatic cancer are reviewed.