Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. AIM: To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. METHODS: This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. RESULTS: Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. CONCLUSION: Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Protein-coding circular RNA enhances antiviral immunity via JAK/STAT pathway in Drosophila.

RNA interference (RNAi) drives powerful antiviral immunity in plants and animals so that many viruses must express viral suppressor of RNAi (VSR) to establish virulent infection. However, little is known about the immune responses conferring resistance against viruses that have evolved the counter-defensive strategy to suppress antiviral RNAi. In this study, we discover that Drosophila cells infected with Drosophila C virus (DCV), a natural viral pathogen of Drosophila known to harbor a potent VSR, exhibit heightened expression of circular RNA circZfh1. circZfh1 confers virus resistance in the presence of viral suppression of antiviral RNAi. Furthermore, we validate that circZfh1 encodes a 274-amino acid protein, CRAV, essential for its antiviral activity. Notably, CRAV differs from its parental Zfh1 gene in a different reading frame, with the C-terminal 69 amino acids unique to CRAV. Our analysis also reveals the presence of CRAV in species within the melanogaster subgroup, with the C-terminal unique fragment undergoing accelerated evolution. Expression of CRAV upregulates the expression of the cytokine Upd3, which binds to its receptor, stimulating the JAK-STAT pathway and enhancing the immune response to DCV infection. Notably, CRISPR/Cas9 knockout of circZfh1 significantly enhances DCV replication in vitro and in vivo, with circZfh1-knockout adult flies displaying heightened disease susceptibility to DCV. In summary, our findings unveil a Drosophila protein-coding circular RNA that activates an innate immune signaling pathway crucial for virus resistance following the suppression of antiviral RNAi by viruses, thereby elucidating a novel counter-defensive strategy.IMPORTANCEEukaryotic hosts possess a complex, multilayered immune system that guards against pathogen invasion. In fruit flies, RNA interference (RNAi) drives robust antiviral immunity, prompting many viruses to express viral suppressors of RNAi (VSRs) to establish virulent infections. However, little is known about immune responses that confer resistance against viruses with potent VSRs. In this study, we discovered that Drosophila cells infected with Drosophila C virus (DCV), a natural viral pathogen possessing a potent VSR, upregulated the expression of circular RNA circZfh1. circZfh1 exhibits DCV-specific antiviral activity, encoding a 274-amino acid protein, CRAV, crucial for its antiviral effects. As a different reading frame from its parental Zfh1 gene, the C-terminal 69 amino acids are unique to CRAV, undergoing faster evolution. CRAV activates the JAK-STAT pathway, enhancing the immune response to DCV infection. Therefore, our work uncovers a new strategy for suppressing viral counter-defense through protein-coding circular RNA in fruit flies.

Association between Metabolic Syndrome and Outcomes of Large-artery Atherosclerosis Stroke Treated with Reperfusion Therapy.

AIM: We aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy. METHODS: A retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis. RESULTS: A total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p=0.012), disability (p=0.029) and HT (p=0.049) than those without MetS, except for death (p=0.375) and sICH (p=0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95%CI 1.372-6.604]; p=0.006) and disability (adjusted OR, 2.727 [95%CI 1.220-6.098]; p=0.015), but not HT (adjusted OR, 1.872 [95%CI 0.854-4.104]; p=0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95% CI 2.402-39.536]; p=0.001) and disability (adjusted OR, 6.966 [95% CI 1.889-25.692]; p=0.004). CONCLUSION: MetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes.

Integrated multi-omics analysis reveals molecular changes associated with chronic lipid accumulation following contusive spinal cord injury.

Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.

Syntropic spin alignment at the interface between ferromagnetic and superconducting nitrides.

The magnetic correlations at the superconductor/ferromagnet (S/F) interfaces play a crucial role in realizing dissipation-less spin-based logic and memory technologies, such as triplet-supercurrent spin-valves and 'π' Josephson junctions. Here we report the observation of an induced large magnetic moment at high-quality nitride S/F interfaces. Using polarized neutron reflectometry and DC SQUID measurements, we quantitatively determined the magnetization profile of the S/F bilayer and confirmed that the induced magnetic moment in the adjacent superconductor only exists below T C. Interestingly, the direction of the induced moment in the superconductors was unexpectedly parallel to that in the ferromagnet, which contrasts with earlier findings in S/F heterostructures based on metals or oxides. First-principles calculations verified that the unusual interfacial spin texture observed in our study was caused by the Heisenberg direct exchange coupling with constant J∼4.28 meV through d-orbital overlapping and severe charge transfer across the interfaces. Our work establishes an incisive experimental probe for understanding the magnetic proximity behavior at S/F interfaces and provides a prototype epitaxial 'building block' for superconducting spintronics.

Co-expression analyses reveal key Cd stress response-related metabolites and transcriptional regulators in Kentucky bluegrass.

Kentucky bluegrass (Poa pratensis) is known for its high cadmium (Cd) tolerance and accumulation, and it is therefore considered to have the potential for phytoremediation of Cd-contaminated soil. However, the mechanisms underlying the accumulation and tolerance of Cd in Kentucky bluegrass are largely unknown. In this study, we examined variances in the transcriptome and metabolome of a Cd-tolerant variety (Midnight, M) and a Cd-sensitive variety (Rugby II, R) to pinpoint crucial regulatory genes and metabolites associated with Cd response. We also validated the role of the key metabolite, l-phenylalanine, in Cd transport and alleviation of Cd stress by applying it to the Cd-tolerant variety M. Metabolites of the M and R varieties under Cd stress were subjected to co-expression analysis. The results showed that shikimate-phenylpropanoid pathway metabolites (phenolic acids, phenylpropanoids, and polyketides) were highly induced by Cd treatment and were more abundant in the Cd-tolerant variety. Gene co-expression network analysis was employed to further identify genes closely associated with key metabolites. The calcium regulatory genes, zinc finger proteins (ZAT6 and PMA), MYB transcription factors (MYB78, MYB62, and MYB33), ONAC077, receptor-like protein kinase 4, CBL-interacting protein kinase 1, and protein phosphatase 2A were highly correlated with the metabolism of phenolic acids, phenylpropanoids, and polyketides. Exogenous l-phenylalanine can significantly increase the Cd concentration in the leaves (22.27%-55.00%) and roots (7.69%-35.16%) of Kentucky bluegrass. The use of 1 mg/L of l-phenylalanine has been demonstrated to lower malondialdehyde levels and higher total phenols, flavonoids, and anthocyanins levels, while also significantly enhancing the uptake of Cd and its translocation from roots to shoots. Our results provide insights into the response mechanisms to Cd stress and offer a novel l-phenylalanine-based phytoremediation strategy for Cd-containing soil.

Isoliquiritigenin alleviates experimental autoimmune encephalomyelitis by modulating inflammatory and neuroprotective reactive astrocytes.

Multiple sclerosis (MS) is an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that poses significant treatment challenges. Currently, it is believed that inflammatory and neuroprotective reactive astrocytes, along with other resident CNS cells and immune cells, contribute to the pathophysiology of MS. In our study, we found that isoliquiritigenin (ILG), a bioactive chalcone compound, significantly reduces the clinical scores of experimental autoimmune encephalomyelitis (EAE) by 44 % (P < 0.05). Additionally, ILG significantly decreases the pathological scores of spinal cord inflammation and demyelination by 61 % and 65 %, respectively (both P < 0.0001). Furthermore, ILG affects the populations of CD4, Th1, Th17, and Treg cells in vivo. More importantly, ILG significantly promotes the activation of astrocytes in EAE (P < 0.0001). Additionally, ILG treatment indirectly inhibits inflammatory reactive astrocytes and promotes neuroprotective reactive astrocytes. It reduces spleen levels of TNFα, IL1α, C1qa, IL1ß, and IL17A by 95 % (P < 0.001), 98 % (P < 0.01), 46 % (P < 0.05), 97 % (P < 0.001), and 60 % (P < 0.001), respectively. It also decreases CNS levels of TNFα, IL1α, C1qa, IL1ß, and IL17A by 53 % (P < 0.05), 88 % (P < 0.05), 64 % (P < 0.01), 57 % (P < 0.05), and 60 % (P < 0.001), respectively. These results indicate that ILG exerts an immunoregulatory effect by inhibiting the secretion of pro-inflammatory cytokines. Consequently, ILG inhibits inflammatory reactive astrocytes, promotes neuroprotective reactive astrocytes, alleviates inflammation and improves EAE. These findings provide a theoretical basis and support for the application of ILG in the prevention and treatment of MS.

scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

ARHGAP4 Inhibits Proliferation and Growth of SW620 Colon Cancer Cells by Cell Cycle and Differentiation Pathways.

The aim of this study is to explore the mechanism by which ARHGAP4 regulates the proliferation and growth of colon cancer cells, and it relates to the metastasis of colorectal cancer (CRC). Various techniques including western blot, CCK8, qRT-PCR, RNA seq assay, plate cloning, subcutaneous tumorigenesis assays, and bioinformatics tools were employed to identify genes that were upregulated or downregulated upon ARHGAP4 knockdown and their involvement in tumor cell proliferation and growth. The expression of ARHGAP4 in T and M stages of CRC uses immunohistochemistry. The expression levels of ARHGAP4 were found to be high in SW620, SW480, and HCT116 cell lines, while they were being low in HT29, LoVo, and NCM460 cell lines. Depletion of ARHGAP4 resulted in inhibited proliferation and growth in SW620 cells and inhibited subcutaneous tumorigenesis in nude mice, whereas overexpression of ARHGAP4 promoted proliferation and growth in HT29 cells and promoted subcutaneous tumorigenesis in nude mice. A total of 318 upregulated genes and 637 downregulated genes were identified in SW620 cells upon ARHGAP4 knockdown. The downregulated genes were primarily associated with cell cycle pathways, while the upregulated genes were enriched in differentiation-related pathways. Notable upregulated genes involved in cell differentiation included KRT10, KRT13, KRT16, IVL, and CD24, while significant downregulation was observed in genes related to the cell cycle such as CCNA2, CDKN2C, CDKN3, CENPA, and CENPF. ARHGAP4 expression is markedly elevated in the M1 stage of CRC compared to the M0 stage, suggesting ARHGAP4 linked to the metastatic in CRC. ARHGAP4 regulates the proliferation and growth of colon cancer cells by up- and downregulated cell cycle and differentiation-related molecules, which may be related to the metastasis of CRC.

Enhanced medium-chain fatty acid production from sewage sludge by combined electro-fermentation and anaerobic fermentation.

Electro-fermentation (EF) was combined with anaerobic fermentation (AF) to promote medium-chain fatty acid (MCFA) from sewage sludge. Results showed that EF at acidification process significantly increased short-chain fatty acid (SCFA) production of by 0.5 times (82.4 mmol C/L). AF facilitated the chain elongation (CE) process by enhancing the SCFA conversion. Combined EF at acidification and AF at CE (EF-AF) achieved the highest MCFA production of 27.9 mmol C/L, which was 20 %-866 % higher than the other groups. Electrochemical analyses showed that enhanced SCFA and MCFA production was accompanied with good electrochemical performance at acidification and CE. Microbial analyses showed that EF-AF promoted MCFA production by enriching electrochemically active bacteria (EAB, Bacillus sp.). Enzyme analyses indicated that EF-AF promoted MCFA production by enriching the functional enzymes involved in Acetyl-CoA formation and the fatty acid biosynthesis (FAB) pathway. This study provided new insights into the production of MCFA from enhanced sewage sludge.

Application of capsaicin and calcium phosphate-loaded MOF system for tumor therapy involving calcium overload.

Calcium overload therapy refers to the condition of intracellular Ca2+ overload, which causes mitochondrial damage and leads to the uncontrolled release of apoptotic factors into the cytoplasm through the open mitochondrial permeability pore. Based on this, it is playing an increasingly important role in the field of oncology due to its good efficacy and small side effects. However, the regulation of calcium homeostasis by cancer cells themselves, insufficient calcium ions (Ca2+) in tumor sites and low efficiency of calcium entering tumor have limited its efficacy, resulting in unsatisfactory therapeutic effect. Therefore, a novel CAP/BSA@TCP-ZIF-8 nanoparticle drug carrier system was constructed that can provide Ca2+ from exogenous sources for pH-controlled degradation and drug release at the same time. Both in vivo and in vitro experiments have proved that the nanomaterial can activate TRPV1 channels and provide exogenous Ca2+ to cause Ca2+ overload and apoptosis, thus achieving anti-tumor effects.

Root cell wall polysaccharides and endodermal barriers restrict long-distance Cd translocation in the roots of Kentucky bluegrass.

Soil Cd pollution is a significant environmental issue faced by contemporary society. Kentucky bluegrass is considered a potential phytoremediation species, as some varieties have excellent cadmium (Cd) tolerance. However, the mechanisms of Cd accumulation and transportation in Kentucky bluegrass are still not fully understood. The Cd-tolerant Kentucky bluegrass cultivar 'Midnight' (M) exhibits lower Cd translocation efficiency and a higher leaf Cd concentration compared to the Cd-sensitive cultivar 'Rugby II' (R). We hypothesized that Cd translocation from roots to shoots in cultivar M is hindered by the endodermal barriers and cell wall polysaccharides; hence, we conducted Cd distribution, cytological observation, cell wall component, and transcriptomic analyses under Cd stress conditions using the M and R cultivars. Cd stress resulted in the thickening of the endodermis and increased synthesis of cell wall polysaccharides in both the M and R cultivars. Endodermis development restricted the radical transport of Cd from the root cortex to the stele, while the accumulation of cell wall polysaccharides promoted the binding of Cd to the cell wall. These changes further inhibited the long-distance translocation of Cd from the roots to the aerial parts. Furthermore, the M cultivar exhibited limited long-distance Cd translocation efficiency compared to the R cultivar, which was attributed to the enhanced development of endodermal barriers and increased Cd binding by cell wall polysaccharides. This study provides valuable insights for screening high Cd transport efficiency in Kentucky bluegrass based on anatomical structure and genetic modification.

Integrated proteomics, transcriptomics, and metabolomics offer novel insights into Cd resistance and accumulation in Poa pratensis.

Kentucky bluegrass (Poa pratensis L., KB) demonstrates superior performance in both cadmium (Cd) accumulation and tolerance; however, the regulatory mechanisms and detoxification pathways in this species remain unclear. Therefore, phenotype, root ultrastructure, cell wall components, proteomics, transcriptomics, and metabolomics were analyzed under the hydroponic system to investigate the Cd tolerance and accumulation mechanisms in the Cd-tolerant KB variety 'Midnight (M)' and the Cd-sensitive variety 'Rugby II (R)' under Cd stress. The M variety exhibited higher levels of hydroxyl and carboxyl groups as revealed by Fourier transform infrared spectroscopy spectral analysis. Additionally, a reduced abundance of polysaccharide degradation proteins was observed in the M variety. The higher abundance of glutathione S-transferase and content of L-cysteine-glutathione disulfide and oxidized glutathione in the M variety may contribute to better performance of the M variety under Cd stress. Additionally, the R variety had an enhanced content of carboxylic acids and derivatives, increasing the Cd translocation capacity. Collectively, the down-regulation of cell wall polysaccharide degradation genes coupled with the up-regulation of glutathione metabolism genes enhances the tolerance to Cd stress in KB. Additionally, lignification of the endodermis and the increase in carboxylic acids and derivatives play crucial roles in the redistribution of Cd in KB.

Polydopamine Nanocarriers with Cascade-Activated Nitric Oxide Release Combined Photothermal Activity for the Therapy of Drug-Resistant Bacterial Infections.

Antibiotic abuse leads to increased bacterial resistance, and the surviving planktonic bacteria aggregate and secrete extracellular polymers to form biofilms. Conventional antibacterial agents find it difficult to penetrate the biofilm, remove the bacteria wrapped in it, and produce an excellent therapeutic effect. In this study, a dual pH- and NIR-responsive nanocomposite (A-Ca@PDA) was developed to remove drug-resistant bacteria through a cascade of catalytic nitric oxide (NO) release and photothermal clearance. NO can melt in the outer package of the biofilm, facilitating the nanocomposites to have better permeability. Thermal therapy further inhibits the growth of planktonic bacteria. The locally generated high temperature and the burst release of NO together aggravate the biofilm collapse and bacterial death after NIR irradiation. The nanocomposites achieved a remarkable photothermal conversion efficiency of 47.5%, thereby exhibiting significant advancements in energy conversion. The nanocomposites exhibited remarkable efficacy in inhibiting multidrug-resistant (MDR) Escherichia coli and MDR Staphylococcus aureus, thus achieving an inhibition rate of >90%. Moreover, these nanocomposites significantly improved the wound-healing process in the MDR S. aureus-infected mice. Thus, this novel nanocomposite offers a novel strategy to combat drug-resistant bacterial infections.

Environmentally relevant levels of Cd and Mo coexposure induces ferroptosis and excess ferritinophagy through AMPK/mTOR axis in duck myocardium.

Cadmium (Cd) and excess molybdenum (Mo) are multiorgan toxic, but the detrimental impacts of Cd and/or Mo on poultry have not been fully clarified. Thence, a 16-week sub-chronic toxic experiment was executed with ducks to assess the toxicity of Cd and/or Mo. Our data substantiated that Cd and Mo coexposure evidently reduced GSH-Px, GSH, T-SOD, and CAT activities and elevated H2O2 and MDA concentrations in myocardium. What is more, the study suggested that Cd and Mo united exposure synergistically elevated Fe2+ content in myocardium and activated AMPK/mTOR axis, then induced ferroptosis by obviously upregulating ACSL4, PTGS2, and TFRC expression levels and downregulating SLC7A11, GPX4, FPN1, FTL1, and FTH1 expression levels. Additionally, Cd and Mo coexposure further caused excessive ferritinophagy by observably increasing autophagosomes, the colocalization of endogenous FTH1 and LC3, ATG5, ATG7, LC3II/LC3I, NCOA4, and FTH1 expression levels. In brief, this study for the first time substantiated that Cd and Mo united exposure synergistically induced ferroptosis and excess ferritinophagy by AMPK/mTOR axis, finally augmenting myocardium injure in ducks, which will offer an additional view on united toxicity between two heavy metals on poultry.

The role of EUS-guided iodine-125 seed implantation in patients with unresectable ampullary cancer after relief of obstructive jaundice.

Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 (125I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice. Material and methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study. Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group (p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed. Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125I seeds combined with biliary stent in patients with unresectable ampullary cancer.

Advanced application of carbohydrate-based micro/nanoparticles for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a kind of synovitis and progressive joint destruction disease. Dysregulated immune cell activation, inflammatory cytokine overproduction, and subsequent reactive oxidative species (ROS) production contribute to the RA process. Carbohydrates, including cellulose, chitosan, alginate and dextran, are among the most abundant and important biomolecules in nature and are widely used in biomedicine. Carbohydrate-based micro/nanoparticles(M/NPs) as functional excipients have the ability to improve the bioavailability, solubility and stability of numerous drugs used in RA therapy. For on-demand therapy, smart reactive M/NPs have been developed to respond to a variety of chemical and physical stimuli, including light, temperature, enzymes, pH and ROS, alternating their physical and macroscopic properties, resulting in innovative new drug delivery systems. In particular, advanced products with targeted dextran or hyaluronic acid are exploiting multiple beneficial properties at the same time. In addition to those that respond, there are promising new derivatives in development with microenvironment and chronotherapy effects. In this review, we provide an overview of these recent developments and an outlook on how this class of agents will further shape the landscape of drug delivery for RA treatment.

PBAC: A pathway-based attention convolution neural network for predicting clinical drug treatment responses.

Precise and personalized drug application is crucial in the clinical treatment of complex diseases. Although neural networks offer a new approach to improving drug strategies, their internal structure is difficult to interpret. Here, we propose PBAC (Pathway-Based Attention Convolution neural network), which integrates a deep learning framework and attention mechanism to address the complex biological pathway information, thereby provide a biology function-based robust drug responsiveness prediction model. PBAC has four layers: gene-pathway layer, attention layer, convolution layer and fully connected layer. PBAC improves the performance of predicting drug responsiveness by focusing on important pathways, helping us understand the mechanism of drug action in diseases. We validated the PBAC model using data from four chemotherapy drugs (Bortezomib, Cisplatin, Docetaxel and Paclitaxel) and 11 immunotherapy datasets. In the majority of datasets, PBAC exhibits superior performance compared to traditional machine learning methods and other research approaches (area under curve = 0.81, the area under the precision-recall curve = 0.73). Using PBAC attention layer output, we identified some pathways as potential core cancer regulators, providing good interpretability for drug treatment prediction. In summary, we presented PBAC, a powerful tool to predict drug responsiveness based on the biology pathway information and explore the potential cancer-driving pathways.

Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

Research Progress on Sesquiterpenoids of Curcumae Rhizoma and Their Pharmacological Effects.

Curcumae Rhizoma, a traditional Chinese medicine with a wide range of pharmacological activities, is obtained from the dried rhizomes of Curcuma phaeocaulis VaL., Curcuma kwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling. Sesquiterpenoids and curcuminoids are found to be the main constituents of Curcumae Rhizoma. Sesquiterpenoids are composed of three isoprene units and are susceptible to complex transformations, such as cyclization, rearrangement, and oxidation. They are the most structurally diverse class of plant-based natural products with a wide range of biological activities and are widely found in nature. In recent years, scholars have conducted abundant studies on the structures and pharmacological properties of components of Curcumae Rhizoma. This article elucidates the chemical structures, medicinal properties, and biological properties of the sesquiterpenoids (a total of 274 compounds) isolated from Curcumae Rhizoma. We summarized extraction and isolation methods for sesquiterpenoids, established a chemical component library of sesquiterpenoids in Curcumae Rhizoma, and analyzed structural variances among sesquiterpenoids sourced from Curcumae Rhizoma of diverse botanical origins. Furthermore, our investigation reveals a diverse array of sesquiterpenoid types, encompassing guaiane-type, germacrane-type, eudesmane-type, elemane-type, cadinane-type, carane-type, bisabolane-type, humulane-type, and other types, emphasizing the relationship between structural diversity and activity. We hope to provide a valuable reference for further research and exploitation and pave the way for the development of new drugs derived from medicinal plants.