Deciphering the role of Enterococcus faecium cytidine deaminase in gemcitabine resistance of gallbladder cancer.

Gemcitabine-based chemotherapy is a cornerstone of standard care for gallbladder cancer (GBC) treatment. Still, drug resistance remains a significant challenge, influenced by factors such as tumor-associated microbiota impacting drug concentrations within tumors. Enterococcus faecium, a member of tumor-associated microbiota, was notably enriched in the GBC patient cluster. In this study, we investigated the biochemical characteristics, catalytic activity, and kinetics of the cytidine deaminase of E. faecium (EfCDA). EfCDA showed the ability to convert gemcitabine to its metabolite 2',2'-difluorodeoxyuridine. Both EfCDA and E. faecium can induce gemcitabine resistance in GBC cells. Moreover, we determined the crystal structure of EfCDA, in its apo form and in complex with 2', 2'-difluorodeoxyuridine at high resolution. Mutation of key residues abolished the catalytic activity of EfCDA and reduced the gemcitabine resistance in GBC cells. Our findings provide structural insights into the molecular basis for recognizing gemcitabine metabolite by a bacteria CDA protein and may provide potential strategies to combat cancer drug resistance and improve the efficacy of gemcitabine-based chemotherapy in GBC treatment.

BMSCs promote alveolar epithelial cell autophagy to reduce pulmonary fibrosis by inhibiting core fucosylation modifications.

BACKGROUND: Idiopathic pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease characterized by alveolar epithelial cell (AEC) injury and fibroblast activation. Inadequate autophagy in AECs may result from the activation of several signaling pathways following AEC injury, with glycoproteins serving as key receptor proteins. The core fucosylation (CF) modification in glycoproteins is crucial. Mesenchymal stem cells derived from bone marrow (BMSCs) have the ability to regenerate damaged tissue and treat PF. This study aimed to elucidate the relationship and mechanism of interaction between BMSCs, CF modification, and autophagy in PF. METHODS: C57BL/6 male mice, AEC-specific FUT8 conditional knockout (CKO) mice, and MLE12 cells were administered bleomycin (BLM), FUT8 siRNA, and mouse BMSCs, respectively. Experimental techniques including tissue staining, Western blotting, immunofluorescence, autophagic flux detection, and flow cytometry were used in this study. RESULTS: First, we found that autophagy was inhibited while FUT8 expression was elevated in PF mice and BLM-induced AEC injury models. Subsequently, CKO mice and MLE12 cells transfected with FUT8 siRNA were used to demonstrate that inhibition of CF modification induces autophagy in AECs and mitigates PF. Finally, mouse BMSCs were used to demonstrate that they alleviate the detrimental autophagy of AECs by inhibiting CF modification and decreasing PF. CONCLUSIONS: Suppression of CF modification enhanced the suppression of AEC autophagy and reduced PF in mice. Additionally, through the prevention of CF modification, BMSCs can assist AECs deficient in autophagy and partially alleviate PF.

Presynaptic regulators in memory formation.

The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate the roles of two pivotal presynaptic regulators, the small GTPase Rab3, enriched at synaptic vesicles, and the cell adhesion protein Neurexin-1, in the formation of distinct memory phases within the Drosophila mushroom body Kenyon cells. Our findings suggest that both proteins play crucial roles in memory-supporting processes within the presynaptic terminal, operating within distinct plasticity modules. These modules likely encompass remodeling and maturation of existing active zones (AZs), as well as the formation of new AZs.

Pentagalloylglucose alleviates acetaminophen-induced acute liver injury by modulating inflammation via cGAS-STING pathway.

BACKGROUND: The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear. MATERIALS AND METHODS: A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI. RESULTS: PGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1. CONCLUSIONS: PGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.

Ultrathin and Self-Supporting MOF/COF-Based Composite Membranes for Hydrogen Separation and Purification from Coke Oven Gas.

Coke oven gas (COG) is considered to be one of the most likely raw materials for large-scale H2 production in the near or medium term, with membrane separation technologies standing out from traditional technologies due to their less energy-intensive structures as well as simple operation and occupation. Based on the "MOF-in/on-COF" pore modification strategy, the COF membrane (named the PBD membrane) and ZIF-67 were used as assembly elements to design advanced molecular sieving membranes for hydrogen separation. The composition and microstructure of membranes before and after ZIF-67 loading as well as ZIF-67-in-PBD membranes under different preparation conditions (metal ion concentration, metal-ligand ratio, and reaction time) were investigated by various characterizations to reveal the synthesis regularity and microstructure regulation. Furthermore, H2/CH4 separation performances and separation mechanisms were also analyzed and compared. Finally, a dense, continuous, ultrathin, and self-supporting ZIF-67-in-PBD membrane with a Co2+ concentration of 0.02 mol/L, a metal-ligand ratio of 1:4, and a reaction time of 6 h exhibited the largest specific surface area, micropore proportion, and the best H2/CH4 separation selectivity (α = 33.48), which was significantly higher than the Robeson upper limit and was in a leading position among reported MOF membranes. The separation mechanism was mainly size screening, and adsorption selectivity also contributed a little.

A prediction nomogram for hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: The present study aimed to develop and validate a new nomogram for predicting the incidence of hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients receiving antiviral therapy from real-world data. METHODS: The nomogram was established based on a real-world retrospective study of 764 patients with HBV from October 2008 to July 2020. A predictive model for the incidence of HCC was developed by multivariable Cox regression, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram were assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Risk group stratification was performed to assess the predictive capacity of the nomogram. The nomogram was compared to three current commonly used predictive models. RESULTS: A total of 764 patients with HBV were recruited for this study. Age, family history of HCC, alcohol consumption, and Aspartate aminotransferase-to-Platelet Ratio Index (APRI) were all independent risk predictors of HCC in CHB patients. The constructed nomogram had good discrimination with a C-index of 0.811. The calibration curve and DCA also proved the reliability and accuracy of the nomogram. Three risk groups (low, moderate, and high) with significantly different prognoses were identified (p < 0.001). The model's performance was significantly better than that of other risk models. CONCLUSIONS: The nomogram was superior in predicting HCC risk among CHB patients who received antiviral treatment. The model can be utilized in clinical practice to aid decision-making on the strategy of long-term HCC surveillance, especially for moderate- and high-risk patients.

Recent developments and challenges in resistance-based hydrogen gas sensors based on metal oxide semiconductors.

In recent years, the energy crisis has made the world realize the importance and need for green energy. Hydrogen safety has always been a primary issue that needs to be addressed for the application and large-scale commercialization of hydrogen energy, and precise and rapid hydrogen gas sensing technology and equipment are important prerequisites for ensuring hydrogen safety. Based on metal oxide semiconductors (MOS), resistive hydrogen gas sensors (HGS) offer advantages, such as low cost, low power consumption, and high sensitivity. They are also easy to test, integrate, and suitable for detecting low concentrations of hydrogen gas in ambient air. Therefore, they are considered one of the most promising HGS. This article provides a comprehensive review of the surface reaction mechanisms and recent research progress in optimizing the gas sensing performance of MOS-based resistive hydrogen gas sensors (MOS-R-HGS). Particularly, the advancements in metal-assisted or doped MOS, mixed metal oxide (MO)-MOS composites, MOS-carbon composites, and metal-organic framework-derived (MOF)-MOS composites are extensively summarized. Finally, the future research directions and possibilities in this field are discussed.

Mining of potentially stem cell-related miRNAs in planarians.

Stem cells and regenerative medicine have recently become important research topics. However, the complex stem cell regulatory networks involved in various microRNA (miRNA)-mediated mechanisms have not yet been fully elucidated. Planarians are ideal animal models for studying stem cells owing to their rich stem cell populations (neoblasts) and extremely strong regeneration capacity. The roles of planarian miRNAs in stem cells and regeneration have long attracted attention. However, previous studies have generally provided simple datasets lacking integrative analysis. Here, we have summarized the miRNA family reported in planarians and highlighted conservation in both sequence and function. Furthermore, we summarized miRNA data related to planarian stem cells and regeneration and screened potential involved candidates. Nevertheless, the roles of these miRNAs in planarian regeneration and stem cells remain unclear. The identification of potential stem cell-related miRNAs offers more precise suggestions and references for future investigations of miRNAs in planarians. Furthermore, it provides potential research avenues for understanding the mechanisms of stem cell regulatory networks. Finally, we compiled a summary of the experimental methods employed for studying planarian miRNAs, with the aim of highlighting special considerations in certain procedures and providing more convenient technical support for future research endeavors.

Phantom study of a self-shielded X-ray bone age assessment instrument against scattered radiation in children.

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.

Recent Developments and Challenges in Solid-Contact Ion-Selective Electrodes.

Solid-contact ion-selective electrodes (SC-ISEs) have the advantages of easy miniaturization, even chip integration, easy carrying, strong stability, and more favorable detection in complex environments. They have been widely used in conjunction with portable, wearable, and intelligent detection devices, as well as in on-site analysis and timely monitoring in the fields of environment, industry, and medicine. This article provides a comprehensive review of the composition of sensors based on redox capacitive and double-layer capacitive SC-ISEs, as well as the ion-electron transduction mechanisms in the solid-contact (SC) layer, particularly focusing on strategies proposed in the past three years (since 2021) for optimizing the performance of SC-ISEs. These strategies include the construction of ion-selective membranes, SC layer, and conductive substrates. Finally, the future research direction and possibilities in this field are discussed and prospected.

Renal stiffness measured by shear wave elastography and its relationship with perirenal fat in patients with chronic kidney disease.

PURPOSE: This study aimed to utilize shear wave elastography (SWE) to assess changes in renal stiffness and its influencing factors in patients with chronic kidney disease (CKD) across different estimated glomerular filtration rate (eGFR) categories. It also sought to determine the correlation between perirenal fat (PF) and renal stiffness at various stages of CKD. METHODS: A total of 190 CKD patients and 50 healthy controls were evaluated. Clinical parameters, conventional renal ultrasound measurements, PF, and renal stiffness trends were assessed separately. Factors independently associated with renal stiffness and PF were further analyzed. RESULTS: Renal parenchymal stiffness was significantly higher in the Albumin-CKD G1-2 (ALB-CKD G1-2) and CKD G3 groups than in the control group (p < 0.05). The parenchymal stiffness of the CKD G3 group was higher than that of the ALB-CKD G1-2 group (p < 0.05). The independent factors of renal parenchymal stiffness varied at different stages of disease development, with eGFR and PF being significant factors in the CKD G3 group. PF was elevated in the ALB-CKD G1-2 and CKD G3 groups compared to the control group, and the independent factors of PF varied across different stages, although waist circumference remained a common factor. CONCLUSION: Using SWE to detect renal elastic moduli can effectively assess changes in renal stiffness in patients with CKD with varying eGFRs. PF is an independent factor of renal stiffness in patients with CKD G3, providing a foundation for early diagnosis and clinical treatment.

Extracellular matrix-regulator MMPA is required for the orderly proliferation of neoblasts and differentiation of ectodermal progenitor cells in the planarian Dugesia japonica.

Matrix metalloproteinases (MMPs) are members of a family of zinc-dependent metallopeptidase proteins that are widely found in plants, animals, and microorganisms. As the regulators of the extracellular matrix and basement membrane, MMPs play an important role in embryogenesis, development, innate immunity, and regeneration. However, the function of MMP family in planarian, a model for regeneration research, is still ambiguous. Here, we cloned 5 MMPs genes from Dugesia japonica and found that DjMMPA was associated with the process of regeneration, neoblasts cell maintenance confusion and destruction. Loss of DjMMPA led to homeostasis confusion and eventually death, owing to neoblasts proliferation disorder. Additionally, DjMMPA RNAi-treated animals had impaired regeneration after amputation. Furthermore, knockdown of DjMMPA had noticeable defects in cell differentiation of ectoderm, especially in eyes and neural progenitor cells, possibly by inhibiting Wnt signaling. Our results suggest that extracellular matrix-regulator MMPA is required for the orderly proliferation of neoblasts and differentiation of ectodermal progenitor cells in the planarian, which provide valuable information for further explorations into the molecular mechanism of MMPS, stem cells, and regeneration.

Roles of Cobalt-Coordinated Polymeric Perylene Diimide in Hematite Photoanodes for Improved Water Oxidation.

Interfacial charge recombination is a permanent issue that impedes the photon energy utilization in photoelectrochemical (PEC) water splitting. Herein, a conjugated polymer, urea linked perylene diimide polymer (PDI), is introduced to the designation of hematite-based composite photoanodes. On account of its unique molecule structure with abundant electronegative atoms, the O and N atoms with lone electron pairs can bond with Fe atoms at the surface of Zr4+ doped α-Fe2 O3 (Zr:Fe2 O3 ) and thus establish charge transfer channels for expediting hole separation and migration. Meanwhile, PDI molecules can passivate the surface states in Zr:Fe2 O3 , which is in favor of suppressing carrier recombination. Particularly, Co2+ is used to coordinate with PDI (Co-PDI) to accelerate hole extraction as well as utilization, and the as-obtained Co-PDI form type-II heterojunction with Zr:Fe2 O3 . Such a photoanode configuration takes advantage of the unique molecule structure of PDI, and the target Co-PDI/Zr:Fe2 O3 photoanodes eventually attain a photocurrent density of 2.17 mA cm-2 , which is inspirational for unearthing the potential use of conjugative molecules in PEC fields.

CNTs Bridged Basal-Plane-Active 2H-MoS2 Nanosheets for Efficient Robust Electrocatalysis.

2D 2H-phase MoS2 is promising for electrocatalytic applications because of its stable phase, rich edge sites, and large surface area. However, the pristine low-conductive 2H-MoS2 suffers from limited electron transfer and surface activity, which become worse after their highly likely aggregation/stacking and self-curling during applications. In this work, these issues are overcome by conformally attaching the intercalation-detonation-exfoliated, surface S-vacancy-rich 2H-MoS2 onto robust conductive carbon nanotubes (CNTs), which electrically bridge bulk electrode and local MoS2 catalysts. The optimized MoS2 /CNTs nanojunctions exhibit outstanding stable electroactivity (close to commercial Pt/C): a polarization overpotential of 79 mV at the current density of 10 mA cm-2 and the Tafel slope of 33.5 mV dec-1 . Theoretical calculations unveil the metalized interfacial electronic structure of MoS2 /CNTs nanojunctions, enhancing defective-MoS2 surface activity and local conductivity. This work provides guidance on rational design for advanced multifaceted 2D catalysts combined with robust bridging conductors to accelerate energy technology development.

Exploration of AB3Si3 (A = Na/K/Rb/Cs) compounds under moderate pressure.

We discovered the composition of ternary AB3Si3 (A = Na/K/Rb/Cs) compounds in the moderate pressure range of 0-100 GPa using first-principles structural prediction and systematically analyzed their structures, stability, electronic and optical properties within the framework of density functional theory. The AB3Si3 compounds exhibit a diverse phase diagram, including nine structures that are selected based on formation energies, along with a known clathrate RbB3Si3 structure with Pm3̄n symmetry. All predicted phases are thermodynamically and dynamically stable within the studied pressure range. In particular, the KB3Si3 compound with a direct band gap of 1.0 eV is identified as a promising candidate for photovoltaic materials beyond silicon-based materials, among which boron atoms form a unique regular octahedral structure; in contrast, NaB3Si3 and RbB3Si3 compounds are shown to have metallicity. Our findings enrich crystal structures of alkali-metal borosilicides and provide valuable insights into their potential applications.

Clinical risk factors and outcomes of young patients with acute ST segment elevation myocardial infarction: a retrospective study.

BACKGROUND: This study aimed to analysis the clinical characteristics and prognosis of acute STEMI in patients aged ≤ 45 years. METHODS: Seven hundred and one patients with STEMI from Liaocheng People's Hospital from January 2018 to March 2021 were included in this study. Clinical characteristics, management, and outcomes (average follow-up: 11.5 months) were compared between patients aged ≤ 45 years and those aged > 45 years. RESULTS: Of the patients with STEMI who underwent primary percutaneous coronary intervention, 108 (15.4%) were aged ≤ 45 years. Compared to the older group, the younger patient group included more males, current smokers, and those with alcohol use disorder (AUD) or a family history of ischaemic heart disease (IHD). The culprit vessel in young patients was the left anterior descending (LAD) artery (60% vs. 45.9%, P = 0.031), which may have been due to smoking (odds ratio, 3.5; 95% confidence interval: 1.12-10.98, P = 0.042). Additionally, young patients presented with higher low-density lipoprotein and lower high-density lipoprotein levels than older patients; uric acid levels were also significantly higher in younger patients than that in the older group. Diabetes showed a trend toward major adverse cardiovascular events (MACE) in both groups; age and sex were both independent predictors of MACE in older patients. CONCLUSION: More patients who were smokers, had AUD, or a family history of IHD were present in the young patient group. Hyperuricaemia (but not dyslipidaemia) was a prevalent risk factor in patients aged ≤ 45 years. Diabetes should be controlled to reduce cardiovascular events in young patients.

Degradation of tetracycline by peroxymonosulfate activated with Mn0.85Fe2.15O4-CNTs: Key role of singlet oxygen.

Tetracycline (TC) is a kind of electron-rich organic, and singlet oxygen (1O2) oxidative pathway-based advanced oxidation processes (AOPs) have represented outstanding selective degradation to such pollutants. In this paper, an excellent prepared strategy for 1O2 dominated catalyst was adopted. A catalyst composed of non-stoichiometric doping Mn-Fe bimetallic oxide supported on CNTs (0.3-Mn0.85Fe2.15O4-CNTs) was synthesized and optimized by regulating the non-stoichiometric doping ratio of Mn & Fe and the loading amount of CNTs. Through optimization and control experiments, the optimized catalyst represented 94.9% of TC removal efficiency within 60 min in neutral condition under relatively low concentrations of Mn0.85Fe2.15O4-CNTs (0.4 g/L) and PMS (0.8 mM). Through SEM and XRD characterization, Mn0.85Fe2.15O4-CNTs was a hybrid of cubic Mn0.85Fe2.15O4 uniformly dispersing on CNTs. By the characterization of XPS and FT-IR, more CO bonds and low-valent Mn (II) & Fe (II) appeared in Mn0.85Fe2.15O4-CNTs. Reactive oxygen species (ROS) was determined by radical quenching experiments and electron spin resonance (EPR) spectroscopy, and 1O2 was verified to be the dominated ROS. The mechanism for PMS' activation was speculated, and more low-valent Mn (II) and Fe (II) contributed to the production of free-radical (•OH & SO4•-), while the reaction between PMS and the enhanced CO bond on Mn0.85Fe2.15O4-CNTs played a crucial part in the generation of 1O2. In addition, through the comparative degradation of four different organics with distinct charge densities, the excellent selectivity of 1O2-based oxidative pathway to electron-rich pollutants was found. This paper supplied a good strategy to prepare catalyst for PMS activation to form a 1O2-dominated oxidative pathway.

Analysis of the Volatile Flavor Compounds of Pomegranate Seeds at Different Processing Temperatures by GC-IMS.

This study sought to reveal the mechanism of flavor generation when pomegranate seeds are processed, as well as the contribution of volatile organic components (VOCs) to flavor formation. Gas chromatography-ion mobility spectrometry (GC-IMS), combined with relative odor activity (ROAV) and statistical methods, was used for the analysis. The results showed that 54 compounds were identified from 70 peaks that appeared in the GC-IMS spectrum. Then, the ROAV results showed 17 key volatile components in processing pomegranate seeds, and 7 flavor components with large differential contributions were screened out using statistical methods. These included γ-butyrolactone, (E)-3-penten-2-one (dimer), pentanal, 1-propanethiol, octanal, and ethyl valerate (monomer). It is suggested that lipid oxidation and the Maillard reaction may be the main mechanisms of flavor formation during the processing of pomegranate seeds. Furthermore, this study lays the experimental and theoretical foundations for further research on the development of flavor products from pomegranate seeds.

Methylation of the HCBP6 promoter is associated with primary biliary cholangitis pathogenesis.

Hepatitis C virus core-binding protein 6 (HCBP6), first characterized in our laboratory and also referred to as FUNDC2, is involved in lipid and glucose metabolism, platelet activation, and platelet survival. Here we demonstrate that hypermethylation of mitochondrial HCBP6 is linked Primary Biliary Cholangitis (PBC) pathogenesis. Serum and liver levels of HCBP6 in PBC patients were reduced in comparison with controls. Further research confirmed a correlation between CpG1 hypermethylation and HCBP6 levels. Taken together, our results reveal another new feature of HCBP6.

Filament Engineering of Two-Dimensional h-BN for a Self-Power Mechano-Nociceptor System.

The switching variability caused by intrinsic stochasticity of the ionic/atomic motions during the conductive filaments (CFs) formation process largely limits the applications of diffusive memristors (DMs), including artificial neurons, neuromorphic computing and artificial sensory systems. In this study, a DM device with improved device uniformity based on well-crystallized two-dimensional (2D) h-BN, which can restrict the CFs formation from three to two dimensions due to the high migration barrier of Ag+ between h-BN interlayer, is developed. The BN-DM has potential arrayable feature with high device yield of 88%, which can be applied for building a reservoir computing system for digital pattern recognition with high accuracy rate of 96%, and used as an artificial nociceptor to sense the external noxious stimuli and mimic the important biological nociceptor properties. By connecting the BN-DM to a self-made triboelectric nanogenerator (TENG), a self-power mechano-nociceptor system, which can successfully mimic the important nociceptor features of "threshold", "relaxation" and "allodynia" is designed.