IDEAL-IQ measurement can distinguish dysplastic nodule from early hepatocellular carcinoma: a case-control study.

Background: Previous studies have confirmed that malignant transformation of dysplastic nodule (DN) into hepatocellular carcinoma (HCC) is accompanied by reduction of iron content in nodules. This pathological abnormality can serve as the basis for magnetic resonance imaging (MRI). This study was designed to identify the feasibility of iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantitative (IDEAL-IQ) measurement to distinguish early hepatocellular carcinoma (eHCC) from DN. Methods: We reviewed MRI studies of 35 eHCC and 23 DN lesions (46 participants with 58 lesions total, 37 males, 9 females, 31-80 years old). The exams include IDEAL-IQ sequence and 3.0T MR conventional scan [including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and Gadopentic acid (Gd-GDPA)-enhanced]. Then, 3 readers independently diagnosed eHCC, DN, or were unable to distinguish eHCC from DN using conventional MRI (CMRI), and then assessed R2* value of nodules [R2* value represents the nodule iron content (NIC)] and R2* value of liver background [R2* value represents the liver background iron content (LBIC)] with IDEAL-IQ. Statistical analysis was conducted using the t-test for comparison of means, the Mann-Whitney test for comparison of medians, the chi-square test for comparison of frequencies, and diagnostic efficacy was evaluated by using receiver operating characteristic (ROC) curve. Results: This study evaluated 35 eHCC participants (17 males, 6 females, 34-81 years old, nodule size: 10.5-27.6 mm, median 18.0 mm) and 23 DN participants (20 males, 3 females, 31-76 years old, nodule size: 16.30±4.095 mm). The NIC and ratio of NIC to LIBC (NIC/LBIC) of the eHCC group (35.926±12.806 sec-1, 0.327±0.107) was lower than that of the DN group (176.635±87.686 sec-1, 1.799±0.629) (P<0.001). Using NIC and NIC/LBIC to distinguish eHCC from DN, the true positive/false positive rates were 91.3%/94.3% and 87.0%/97.1%, respectively. The rates of CMRI, NIC and NIC/LBIC in diagnosis of eHCC were 77.1%, and 94.3%, 97.1%, respectively, and those of DN were 65.2%, 91.3%, and 87.0%, respectively. The diagnosis rate of eHCC and DN by CMRI was lower than that of NIC and NIC/LBIC (eHCC: P=0.03, 0.04, DN: P=0.02, 0.04). Conclusions: Using IDEAL-IQ measurement can distinguish DN from eHCC.

Plant regeneration in the new era: from molecular mechanisms to biotechnology applications.

Plants or tissues can be regenerated through various pathways. Like animal regeneration, cell totipotency and pluripotency are the molecular basis of plant regeneration. Detailed systematic studies on Arabidopsis thaliana gradually unravel the fundamental mechanisms and principles underlying plant regeneration. Specifically, plant hormones, cell division, epigenetic remodeling, and transcription factors play crucial roles in reprogramming somatic cells and reestablishing meristematic cells. Recent research on basal non-vascular plants and monocot crops has revealed that plant regeneration differs among species, with various plant species using distinct mechanisms and displaying significant differences in regenerative capacity. Conducting multi-omics studies at the single-cell level, tracking plant regeneration processes in real-time, and deciphering the natural variation in regenerative capacity will ultimately help understand the essence of plant regeneration, improve crop regeneration efficiency, and contribute to future crop design.

The petroleum ether extracts of Chloranthus fortunei(A. Gray) Solms-Laub.with bioactivities: A Rising Source in HCC Drug Treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular Carcinoma (HCC) is an aggressive killer worldwide with high incidence and mortality. The herb Chloranthus fortunei (A. Gray) Solms-Laub is known as "Si Ji Feng" and is classified as a Feng-type medicine in classic Yao medicines. According to Yao's medical beliefs, Chloranthus fortunei has the functions of dispelling Feng, regulating qi, detoxifying, promoting blood circulation, etc. Folk uses its decoctions to treat stagnant liver conditions, such as liver abscesses, cirrhosis, hepatitis, and liver cancer. However, the bioactivity and mechanisms of Chloranthus fortunei extract against HCC have not been reported. AIM OF THE STUDY: To investigate the anti-HCC bioactivity and potential mechanism of the extract of Chloranthus fortunei (CFS). MATERIALS AND METHODS: Using 70% ethanol for reflux extraction of CFS resulted in the CFS ethanol extract, followed by sequential extractions with petroleum ether, chloroform, ethyl acetate, and n-butanol, yielding four fractions. The CCK-8 assay was utilized to examine the cytotoxic effects of 4 fractions on MHCC97-H and HepG2 cells, exploring the most effective component, namely petroleum ether extracts of CFS (PECFS). The major active ingredients of PECFS were identified using LC/MS technology, and the impact on cell proliferation and apoptosis in HCC cells was studied. The key genes and proteins in the pathway were validated using RT-PCR and Western blotting. BALB/c nude mice were chosen for tumor xenotransplantation and PECFS therapy. hinders the proliferation of HCC cells and promotes apoptosis. RESULTS: Among the four fractions, it was found that PECFS have the highest antiproliferative activity against MHCC97-H and HepG2 cells (IC50 = 13.86, 10.55 µg/mL), with sesquiterpene compounds being the primary active constituents. The antiproliferative activity of PECFS on HCC cells was linked to the inhibition of cell cloning, invasion, and metastasis abilities, as well as the arrest of the cell cycle at the G2/M phase. Additionally, exerts pro-apoptotic effects on HCC cells by upregulating the pro-apoptotic protein Bax, downregulating the anti-apoptotic protein Bcl-2, and activating the expression of the Caspase family. Moreover, protein and m-RNA expression data showed that PECFS inhibits HCC cell proliferation and promotes apoptosis by regulating the PI3K/AKT/mTOR pathway. Besides, after PECFS treatment, tumor growth in nude mice was suppressed. CONCLUSION: PECFS can inhibit the viability of HCC cells by acting on the PI3K/AKT/mTOR pathway, demonstrating anti-tumor potential. This study's findings suggest that PECFS may represent a promising source of novel agents for liver cancer treatment, providing scientific evidence for the traditional application of CFS in treating HCC.

Cerium oxide nanoparticles in wound care: a review of mechanisms and therapeutic applications.

Skin wound healing is a complex and tightly regulated process. The frequent occurrence and reoccurrence of acute and chronic wounds cause significant skin damage to patients and impose socioeconomic burdens. Therefore, there is an urgent requirement to promote interdisciplinary development in the fields of material science and medicine to investigate novel mechanisms for wound healing. Cerium oxide nanoparticles (CeO2 NPs) are a type of nanomaterials that possess distinct properties and have broad application prospects. They are recognized for their capabilities in enhancing wound closure, minimizing scarring, mitigating inflammation, and exerting antibacterial effects, which has led to their prominence in wound care research. In this paper, the distinctive physicochemical properties of CeO2 NPs and their most recent synthesis approaches are discussed. It further investigates the therapeutic mechanisms of CeO2 NPs in the process of wound healing. Following that, this review critically examines previous studies focusing on the effects of CeO2 NPs on wound healing. Finally, it suggests the potential application of cerium oxide as an innovative nanomaterial in diverse fields and discusses its prospects for future advancements.

Optofluidic crystallithography for directed growth of single-crystalline halide perovskites.

Crystallization is a fundamental phenomenon which describes how the atomic building blocks such as atoms and molecules are arranged into ordered or quasi-ordered structure and form solid-state materials. While numerous studies have focused on the nucleation behavior, the precise and spatiotemporal control of growth kinetics, which dictates the defect density, the micromorphology, as well as the properties of the grown materials, remains elusive so far. Herein, we propose an optical strategy, termed optofluidic crystallithography (OCL), to solve this fundamental problem. Taking halide perovskites as an example, we use a laser beam to manipulate the molecular motion in the native precursor environment and create inhomogeneous spatial distribution of the molecular species. Harnessing the coordinated effect of laser-controlled local supersaturation and interfacial energy, we precisely steer the ionic reaction at the growth interface and directly print arbitrary single crystals of halide perovskites of high surface quality, crystallinity, and uniformity at a high printing speed of 102 µm s-1. The OCL technique can be potentially extended to the fabrication of single-crystal structures beyond halide perovskites, once crystallization can be triggered under the laser-directed local supersaturation.

Clinical Implementation of Total-Body PET in China.

Total-body (TB) PET/CT is a groundbreaking tool that has brought about a revolution in both clinical application and scientific research. The transformative impact of TB PET/CT in the realms of clinical practice and scientific exploration has been steadily unfolding since its introduction in 2018, with implications for its implementation within the health care landscape of China. TB PET/CT's exceptional sensitivity enables the acquisition of high-quality images in significantly reduced time frames. Clinical applications have underscored its effectiveness across various scenarios, emphasizing the capacity to personalize dosage, scan duration, and image quality to optimize patient outcomes. TB PET/CT's ability to perform dynamic scans with high temporal and spatial resolution and to perform parametric imaging facilitates the exploration of radiotracer biodistribution and kinetic parameters throughout the body. The comprehensive TB coverage offers opportunities to study interconnections among organs, enhancing our understanding of human physiology and pathology. These insights have the potential to benefit applications requiring holistic TB assessments. The standard topics outlined in The Journal of Nuclear Medicine were used to categorized the reviewed articles into 3 sections: current clinical applications, scan protocol design, and advanced topics. This article delves into the bottleneck that impedes the full use of TB PET in China, accompanied by suggested solutions.

Optimized submerged batch fermentation for metabolic switching in Streptomyces yanglinensis 3-10 providing platform for reveromycin A and B biosynthesis, engineering, and production.

The cultivation system requires that the approach providing biomass for all types of metabolic analysis is of excellent quality and reliability. This study was conducted to enhance the efficiency and yield of antifungal substance (AFS) production in Streptomyces yanglinensis 3-10 by optimizing operation conditions of aeration, agitation, carbon source, and incubation time in a fermenter. Dissolved oxygen (DO) and pH were found to play significant roles in AFS production. The optimum pH for the production of AFS in S. yanglinensis 3-10 was found to be 6.5. As the AFS synthesis is generally thought to be an aerobic process, DO plays a significant role. The synthesis of bioactive compounds can vary depending on how DO affects growth rate. This study validates that the high growth rate and antifungal activity required a minimum DO concentration of approximately 20% saturation. The DO supply in a fermenter can be raised once agitation and aeration have been adjusted. Consequently, DO can stimulate the development of bacteria and enzyme production. A large shearing effect could result from the extreme agitation, harming the cell and deactivating its products. The highest inhibition zone diameter (IZD) was obtained with 3% starch, making starch a more efficient carbon source than glucose. Temperature is another important factor affecting AFS production. The needed fermentation time would increase and AFS production would be reduced by the too-low operating temperature. Furthermore, large-scale fermenters are challenging to manage at temperatures that are far below from room temperature. According to this research, 28°C is the ideal temperature for the fermentation of S. yanglinensis 3-10. The current study deals with the optimization of submerged batch fermentation involving the modification of operation conditions to effectively enhance the efficiency and yield of AFS production in S. yanglinensis 3-10.

UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer.

BACKGROUND: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. METHODS: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. RESULTS: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). CONCLUSIONS: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.

Asymmetric Synthesis of Three Alkenyl Epoxides: Crafting the Sex Pheromones of the Elm Spanworm and the Painted Apple Moth.

A concise synthesis of the sex pheromones of elm spanworm as well as painted apple moth has been achieved. The key steps were the alkylation of acetylide ion, Sharpless asymmetric epoxidation and Brown's P2-Ni reduction. This approach provided the sex pheromone of the elm spanworm (1) in 31% total yield and those of the painted apple moth (2, 3) in 26% and 32% total yields. The ee values of three final products were up to 99%. The synthesized pheromones hold promising potential for use in the management and control of these pests.

Cold Air Plasma Inhibiting Tumor-Like Biological Behavior of Rheumatoid Arthritis Fibroblast-Like Synovial Cells via G2/M Cell Cycle Arrest.

Background: Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) have become the core effector cells for the progression of rheumatoid arthritis due to their "tumor-like cell" characteristics, such as being able to break free from growth restrictions caused by contact inhibition, promoting angiogenesis, invading surrounding tissues, and leading to uncontrolled synovial growth. In recent years, cold air plasma (CAP) has been widely recognized for its clear anticancer effect. Inspired by this, this study investigated the inhibitory effect of CAP on the tumor-like biological behavior of RA-FLS through in vitro experiments. Methods: Treatment of RA-FLS with CAP at different time doses (0s, 30s, 60s, 120s). 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay was used to determine the cell viability. Analysis of cell migration and invasion was performed by wound-healing assay, transwell assay and immunofluorescent staining for f-actin, respectively. Flow cytometry technique was used for analysis of cell cycle and determination of reactive oxygen species (ROS). Hoechst staining was used for analysis of cell apoptosis. Protein expression was analyzed by Western blot analysis. Results: Molecular and cellular level mechanisms have revealed that CAP blocks RA-FLS in the G2/M phase by increasing intracellular reactive oxygen species (ROS), leading to increased apoptosis and significantly reduced migration and invasion ability of RA-FLS. Conclusion: Overall, CAP has significant anti proliferative, migratory, and invasive effects on RA-FLS. This study reveals a new targeted treatment strategy for RA.

DNA Extraction and Comparison between Old and Fresh Necrophilic Fly Samples.

A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.

Role of hypoxia-mediated pyroptosis in the development of extending knee joint contracture in rats.

Joint contracture is one of the common diseases clinically, and joint capsule fibrosis is considered to be one of the most important pathological changes of joint contracture. However, the underlying mechanism of joint capsule fibrosis is still controversial. The present study aims to establish an animal model of knee extending joint contracture in rats, and to investigate the role of hypoxia-mediated pyroptosis in the progression of joint contracture using this animal model. 36 male SD rats were selected, 6 of which were not immobilized and were used as control group, while 30 rats were divided into I-1 group (immobilized for 1 week following 7 weeks of free movement), I-2 group (immobilized for 2 weeks following 6 weeks of free movement), I-4 group (immobilized for 4 weeks following 4 weeks of free movement), I-6 group (immobilized for 6 weeks following 2 weeks of free movement) and I-8 group (immobilized for 8 weeks) according to different immobilizing time. The progression of joint contracture was assessed by the measurement of knee joint range of motion, collagen deposition in joint capsule was examined with Masson staining, protein expression levels of HIF-1α, NLRP3, Caspase-1, GSDMD-N, TGF-ß1, α-SMA and p-Smad3 in joint capsule were assessed using western blotting, and the morphological changes of fibroblasts were observed by transmission electron microscopy. The degree of total and arthrogenic contracture progressed from the first week and lasted until the first eight weeks after immobilization. The degree of total and arthrogenic contracture progressed rapidly in the first four weeks after immobilization and then progressed slowly. Masson staining indicated that collagen deposition in joint capsule gradually increased in the first 8 weeks following immobilization. Western blotting analysis showed that the protein levels of HIF-1α continued to increase during the first 8 weeks of immobilization, and the protein levels of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD-N continued to increase in the first 4 weeks after immobilization and then decreased. The protein levels of fibrosis-related proteins TGF-ß1, p-Smad3 and α-SMA continued to increase in the first 8 weeks after immobilization. Transmission electron microscopy showed that 4 weeks of immobilization induced cell membrane rupture and cell contents overflow, which further indicated the activation of pyroptosis. Knee extending joint contracture animal model can be established by external immobilization orthosis in rats, and the activation of hypoxia-mediated pyroptosis may play a stimulating role in the process of joint capsule fibrosis and joint contracture.

A novel lncRNA associated with the prognosis of patients with colorectal cancer resists apoptosis through the LYN/BCL-2 pathway.

PURPOSE: We found a novel lncRNA named lncAC138150.2 related to the overall survival and staging of patients with colorectal cancer (CRC) by bioinformatic analysis using data from the Cancer Genome Atlas (TCGA), and the study aimed to elucidate the function of lncAC138150.2 and underlying mechanisms. METHODS: Target molecules were knocked down by transfection with antisense oligonucleotides (ASOs), siRNAs, or lentiviruses and overexpressed by transfection with plasmids. The function of lncAC138150.2 was determined using histological, cytological, and molecular biology methods. The underlying mechanism of lncAC138150.2 function was investigated using RNA-seq, bioinformatics analysis, and molecular biology methods. RESULTS: The expression of lncAC138150.2 was increased in colorectal tissues compared with paired normal tissues. The lncAC138150.2 knockdown increased apoptosis but did not change the cell proliferation, cell cycle distribution, or cell migration ability of CRC cells, while lncAC138150.2 overexpression decreased CRC apoptosis. lncAC138150.2 was mainly located in the cell nucleus, and each lncAC138150.2 transcript knockdown increased CRC apoptosis. BCL-2 pathway was significantly altered in apoptosis induced by lncAC138150.2 knockdown, which was alleviated by BAX knockdown. The expression of LYN was significantly decreased with lncAC138150.2 knockdown, LYN knockdown increased CRC apoptosis, and its overexpression completely alleviated CRC apoptosis induced by lncAC138150.2 knockdown. CONCLUSION: lncAC138150.2 significantly inhibited CRC apoptosis and affected the prognosis of patients with CRC, through the LYN/BCL-2 pathway.

Sucrose and Ca2+ synergistically regulate the rheological properties of apple high-methoxyl pectin.

The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically affected by calcium ion (Ca2+) and sucrose was investigated using several technical methods. Rheological measurements, including steady-shear flow, thixotropy and dynamic viscoelasticity tests, texture analysis, water-holding capacity (WHC), thermal analyses (TG), and microstructure observation (TEM), were all systemically conducted. The results showed that the main thickening and gelling mechanism of Ca2+ on different HMPs was complex and the presence of sucrose had a synergistic effect on structure formation in HMP systems. Ca2+ was not always conducive to structure formation, and excessive Ca2+ addition may hinder structure formation. HMP systems with lower DE values had higher gel strengths due to the presence of more binding domains. The results of the texture properties, WHC, and thermal characteristics coincided with those obtained from the rheological measurements, which reflect the variations in HMPs affected by Ca2+ and DE. All of these results showed that Ca2+ addition at an appropriate concentration in the presence of sucrose favors HMP gelation even in the absence of acid. The results obtained here are expected to broaden the application of HMPs in acid-free gel food products.

The role of THBS1 and PDGFD in the immune microenvironment of Helicobacter pylori-associated gastric cancer.

BACKGROUND AND STUDY AIMS: Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS: We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS: We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION: We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.

Deselenylative Acylation and Nitration of Monoselenides.

A deselenylative protocol that enables the construction of the C-C and C-N bonds has been disclosed. By using acyl chloride/AgOTf as an efficient acylation reagent, diarylselenides smoothly undergo deselenylative acylation to produce a series of aroyl compounds. In addition, deselenylative nitration can be enabled by a mild nitration reagent consisting of TsCl and AgNO3, furnishing a diverse array of nitroaromatic compounds.

Potential marker genes for chronic obstructive pulmonary disease revealed based on single-cell sequencing and Mendelian randomization analysis.

BACKGROUND: Progress is being made in the prevention and treatment of chronic obstructive pulmonary disease (COPD), but it is still unsatisfactory. With the development of genetic technology, validated genetic information can better explain COPD. OBJECTIVE: The study utilized scRNA-seq and Mendelian randomization analysis of eQTLs to identify crucial genes and potential mechanistic pathways underlying COPD pathogenesis. MEHODS: Single-cell sequencing data were used to identify marker genes for immune cells in the COPD process. Data on eQTLs for immune cell marker genes were obtained from the eQTLGen consortium. To estimate the causal effect of marker genes on COPD, we selected an independent cohort (ukb-b-16751) derived from the UK Biobank database for two-sample Mendelian randomization analysis. Subsequently, we performed immune infiltration analysis, gene set enrichment analysis (GSEA), and co-expression network analysis on the key genes. RESULTS: The 154 immune cell-associated marker genes identified were mainly involved in pathways such as vacuolar cleavage, positive regulation of immune response and regulation of cell activation. Mendelian randomization analysis screened four pairs of marker genes (GZMH, COTL1, CSTA and CD14) were causally associated with COPD. These four key genes were significantly associated with immune cells. In addition, we have identified potential transcription factors associated with these key genes using the Cistrome database, thus contributing to a deeper understanding of the regulatory network of these gene expressions. CONCLUSIONS: This eQTLs Mendelian randomization study identified four key genes (GZMH, COTL1, CSTA, and CD14) causally associated with COPD, providing new insights for prevention and treatment of COPD.

Bile acid-microbiota crosstalk in hepatitis B virus infection.

Hepatitis B virus (HBV) is a hepatotropic non-cytopathic virus characterized by liver-specific gene expression. HBV infection highjacks bile acid metabolism, notably impairing bile acid uptake via sodium taurocholate cotransporting polypeptide (NTCP), which is a functional receptor for HBV entry. Concurrently, HBV infection induces changes in bile acid synthesis and the size of the bile acid pool. Conversely, bile acid facilitates HBV replication and expression through the signaling molecule farnesoid X receptor (FXR), a nuclear receptor activated by bile acid. However, in HepaRG cells and primary hepatocytes, FXR agonists suppress HBV RNA expression and the synthesis and secretion of DNA. In the gut, the size and composition of the bile acid pool significantly influence the gut microbiota. In turn, the gut microbiota impacts bile acid metabolism and innate immunity, potentially promoting HBV clearance. Thus, the bile acid-gut microbiota axis represents a complex and evolving relationship in the context of HBV infection. This review explores the interplay between bile acid and gut microbiota in HBV infection and discusses the development of HBV entry inhibitors targeting NTCP.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Influence of rice husk ash on the mechanical properties of ultra-high strength engineered cementitious composites (UHS-ECC).

Generally, UHS-ECC should consume massive cement, which is negative to its sustainability as cement production leads to 8% of global CO2 emissions. To decrease the cost of production and carbon emissions of UHS-ECC, rice husk ash was employed to replace the cement as a supplementary cementitious material in this study. Experiment results illustrate that blending rice husk ash (RHA) would decrease the fluidity of mortar. Furthermore, the green UHS-ECC shows a maximum compressive strength of 130.3 MPa at 28 days when RHA content was 20% of cement. The ultimate tensile strength of UHS-ECCs first increased and then decreased, while both tensile strain and strain energy presented an opposite tendency. At the micro-scale, if RHA content was lower than 20% of cement, incorporating RHA can significantly decreasing fiber bridging complementary energy of UHS-ECC, thus reducing pseudo strain hardening energy (PSHenergy) index, which finely agrees with the degradation of ductility of UHS-ECCs. To guarantee the features of ultra-high strength, acceptable workability, and high tensile ductility, the RHA dosage should not be in excess 20% of cement. These researched results are prospected to the contribution of pozzolanic RHA on the efficient usage of sustainable UHS-ECC.