Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy.

Globally, hepatocellular carcinoma (HCC) is among the most prevalent and deadly cancers. Hepatitis B virus (HBV) infection is an important etiology and disease progression factor for HCC. Hepatectomy is a widely accepted curative treatment for HCC, but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection. Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy. However, many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently, necessitating the start of remedial antiviral therapy in the perioperative phase. Therefore, it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.

Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids.

Covering: up to June 2024Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from L-tyrosine, exhibiting significant pharmacological properties such as anti-microbial, anti-spasmodic, anti-cancer, cardiovascular protection, and analgesic effects. The industrial production of valuable BIAs relies on extraction from plants; however, challenges concerning their low concentration and efficiency hinder drug development. Hence, alternative approaches, including biosynthesis and chemoenzymatic synthesis, have been explored. Model species like Papaver somniferum and Coptis japonica have played a key role in unraveling the biosynthetic pathways of BIAs; however, many aspects, particularly modified steps like oxidation and methylation, remain unclear. Critical enzymes, e.g., CYP450s and methyltransferases, play a substantial role in BIA backbone formation and modification, which is essential for understanding the origin and adaptive evolution of these plant specialized metabolites. This review comprehensively analyzes the structural diversity of reported BIAs and their distribution in plant lineages. In addition, the progress in understanding biosynthesis, evolution, and catalytic mechanisms underlying BIA biosynthesis is summarized. Finally, we discuss the progress and challenges in metabolic engineering, providing valuable insights into BIA drug development and the sustainable utilization of BIA-producing plants.

Retinal microcirculation changes in prediabetic patients with short-term increased blood glucose using optical coherence tomography angiography.

BACKGROUND: Retinal microcirculation alterations are early indicators of diabetic microvascular complications. Optical coherence tomography angiography (OCTA) is a noninvasive method to assess these changes. This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA. AIM: To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA. METHODS: Fifty volunteers were divided into three groups: Group 1 [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)], Group 2 (both IFG and IGT), and a control group. Retinal microcirculation parameters, including vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics, were measured using OCTA. Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states. RESULTS: One hour after glucose intake, the central VD (P = 0.023), central PD (P = 0.026), and parafoveal PD (P < 0.001) were significantly greater in the control group than in the fasting group. In Group 1, parafoveal PD (P < 0.001) and FAZ circularity (P = 0.023) also increased one hour after glucose intake. However, no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake (P > 0.05). Compared with the control group, Group 1 had a larger FAZ area (P = 0.032) and perimeter (P = 0.018), whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Compared with Group 1, Group 2 had greater central VD (P = 0.013) and PD (P = 0.008) and a smaller FAZ area (P = 0.012) and perimeter (P = 0.010). One hour after glucose intake, Group 1 had a larger FAZ area (P = 0.044) and perimeter (P = 0.038) than did the control group, whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Group 2 had greater central VD (P = 0.042) and PD (P = 0.022) and a smaller FAZ area (P = 0.015) and perimeter (P = 0.016) than Group 1. At fasting, central PD was significantly positively correlated with blood glucose levels (P = 0.044), whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake. CONCLUSION: A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.

Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ring finger domains 1 (UHRF1), exhibits altered expression and aberrant cytosolic localization in cancerous tissues, where it promotes MHC-I ubiquitination and degradation. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the tumor microenvironment (TME), such as TGF-ß, enabling UHRF1 to bind MHC-I. Downregulation of MHC-I results in suppression of the antigen presentation pathway to establish an immune hostile TME. UHRF1 inactivation by genetic deletion synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumour memory response by evoking low-affinity T cells. Our study adds to the understanding of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.

A rare case of bilateral malignant glaucoma after cataract surgery with capsular tension ring implantation: a case report.

BACKGROUND: Bilateral malignant glaucoma induced by a capsular tension ring associated with ring-shaped cysts of the ciliary body post-cataract surgery is rare. Herein, we present a case to highlight the possibility of capsular tension ring-induced malignant glaucoma. CASE PRESENTATION: A 59-year-old woman underwent phacoemulsification combined with capsular tension ring implantation for cataracts and zonular fibre laxity in both eyes. Upon admission, annular ciliary masses were detected in both eyes using ultrasound biomicroscopy. Two months post-surgery, the patient experienced vision deterioration, high intraocular pressure, and an axial shallowing anterior chamber in the right eye, and responded poorly to traditional anti-glaucoma medication. Ten days later, similar symptoms appeared in the left eye. Ultrasound biomicroscopy detected contact between the ciliary body and the capsular tension ring. Subsequently, malignant glaucoma was diagnosed. Anterior and posterior capsulotomies performed peripheral to intraocular lens optics using neodymium: YAG laser restored communication and alleviated the symptoms. A one-year follow-up revealed stable intraocular pressure and anterior chamber in both eyes. CONCLUSIONS: This is the first case report of bilateral malignant glaucoma after cataract surgery induced by capsular tension ring, which is associated with bilateral ring-shaped cysts of the ciliary body. Blockage between the ciliary body and capsular tension ring was confirmed using ultrasound biomicroscopy.

Screening a neurotransmitter-receptor-related inhibitor library identifies clomipramine HCl as a potential antiviral compound against Japanese encephalitis virus.

Background: Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide. JEV exhibits significant neuroinvasiveness and neurotoxicity, resulting in considerable damage to the nervous system. Japanese encephalitis is associated with high morbidity and mortality rate, seriously harming both human health and livestock production. The current lack of specific antiviral drugs means that the development of new therapeutic agents for JEV has become urgent. Methods: Anti-JEV drugs were screened from 111 inhibitors of neurotransmitter receptor-related molecules by high content technology. The antiviral effects of clomipramine HCl were evaluated through plaque assay, real-time quantitative PCR, immunofluorescence assay and western blotting assay. Bioinformatic tools were utilized to cluster the altered signaling pathway members after clomipramine HCl treatment. Finally, the anti-JEV mechanism was deeply resolved in vivo via such molecular biology and virological detection techniques. Results: In this study, we screened nine compounds with significant anti-JEV activity, of which clomipramine HCl demonstrated the most potent antiviral effect and exhibited dose-dependent activity. Mechanistically, clomipramine HCl may activate endoplasmic reticulum stress and modulate the unfolded protein response, thus inhibiting the assembly stage of JEV infection. Conclusion: This study highlights the importance of clomipramine HCl as a promising approach for JEV infection protection, which may lead to new host-directed antiviral approaches to such mosquito-borne viruses.

Solid-Liquid-Gas Three-Phase Indirect Electrolysis Enabled by Affinity Auxiliary Imparted Covalent Organic Frameworks.

The design of efficient heterogenous redox mediators with favorable affinity to substrate and electrolyte are much desired yet still challenging for the development of indirect electrolysis system. Herein, for the first time, we have developed a solid-liquid-gas three-phase indirect electrolysis system based on a covalent organic framework (Dha-COF-Cu) as heterogenous redox mediator for S-S coupling reaction. Dha-COF-Cu with the integration of high porosity, nanorod morphology, abundant hydroxyl groups and active Cu sites is much beneficial for the adsorption/activation of thiols, uniform dispersion and high wettability in electrolyte, and efficient interfacial electron transfer. Notably, Dha-COF-Cu as solid-phase redox mediator exhibits excellent electrocatalytic efficiency for the formation of value-added liquid-phase S-S bond product (yields up to 99%) coupling with the generation of gas-phase product of H2 (~1.40 mmol g-1 h-1), resulting in a powerful three-phase indirect electrolysis system. This is the first work about COFs that can be applied in three-phase indirect electrolysis system, which might promote the development of porous crystalline materials in this field.

Dynamic Reconstruction of Yttrium Oxide-Stabilized Cobalt-Loaded Carbon-Based Catalysts During Thermal Ammonia Decomposition.

Hydrogen production from the decomposition of ammonia is considered an effective approach for addressing challenges associated with hydrogen storage and transportation. However, their relatively high energy consumption and low efficiency hinder practical multi-scenario applications. In this study, Y2O3-stabilized catalysts with Co-loaded onto porous nitrogen-doped carbon (Y2O3-Co/NC) are synthesized by pyrolysis of Y(NO3)3-modified ZIF-67 under an inert atmosphere, followed by annealing in a reducing environment. The introduction of Y2O3 enhanced the recombination and desorption of N atoms and facilitated the gradual dehydrogenation of NHx on the catalyst surface, resulting in improved catalytic activity for the thermal decomposition of ammonia. Benefitting from the electron-donating properties of Y2O3 and N-doped carbon, the optimized catalyst achieved a remarkable NH3 conversion efficiency of 92.3% at a high gas hourly space velocity of 20 000 cm3· g cat - 1 ${\mathrm{g}}_{{\mathrm{cat}}}^{ - {\mathrm{1}}}$ ·h-1 with an encouraging H2 production rate of 20.6 mmol· g cat - 1 ${\mathrm{g}}_{{\mathrm{cat}}}^{ - {\mathrm{1}}}$ ·min-1 at 550 °C. Moreover, the synthesized catalyst undergoes a fast-dynamic reconstruction process, resulting in exceptionally stable catalytic activity during the thermal decomposition of ammonia, rendering it a promising candidate for carbon-free energy thermocatalytic conversion technology.

Electrochemical lithium storage of a biactive organic molecule containing cyano and imine groups.

With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.

Impact of Intolerance of Uncertainty on Depression in College Students During the COVID-19 Pandemic: Coping Strategies as Mediators.

The coronavirus disease (COVID-19) pandemic and associated infection control measures have introduced significant uncertainty, and the unbearable nature of this uncertainty has heightened the risk of mental health issues among college students. This study aimed to assess the impact of unbearable uncertainty during the COVID-19 pandemic on college students' depression and investigate the mediating role of coping strategies between unbearable uncertainty and depression. A cross-sectional survey was conducted with 714 Chinese university students using the Intolerance of Uncertainty Scale (IUS-12), Brief Coping Style Questionnaire, and Beck Depression Inventory (BDI-II). SPSS PROCESS was used for the partial correlation analyses and structural equation modeling. (1) Negative coping strategies were significantly positively correlated with intolerable uncertainty and depressive symptoms, while positive coping strategies were negatively correlated with both intolerable uncertainty and depressive symptoms. Intolerable uncertainty was significantly and positively correlated with depressive symptoms. (2) Intolerance to uncertainty significantly predicted depressive symptoms. Both negative and positive coping strategies played parallel mediating roles in the relationship between unbearable uncertainty and depressive symptoms among college students. This study found that coping strategies played a mediating role in the relationship between unbearable uncertainty and depression during the pandemic in 2019. Future research and interventions should focus on enhancing tolerance of uncertainty and promoting positive coping strategies.