Hepatitis B cure: Current situation and prospects.

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Forward-backward wavefront manipulation of orthogonal linearly polarized waves based on a metasurface zone plate.

Metasurface zone plates exhibit stronger optical control capabilities than traditional Fresnel zone plates, especially in polarization transformation and multiplexing. However, there are still few studies on metasurface zone plates that can be used for simultaneous control of forward and backward waves. In this work, we propose what is to our knowledge a new scheme that utilizes metasurface zone plates for orthogonal linear polarization separation and wavefront manipulation at the same time. We demonstrate the separation of linearly polarized components and transmission-reflection focusing by using the destructive and constructive interference between different meta-atoms in the super-cell, as well as the phase difference between the super-cells. The metasurface not only needs a simple binary phase design but also shows a working bandwidth more than 30 nm with a central wavelength of 875 nm. This scheme can be extended to other electromagnetic bands such as visible and terahertz ones, providing an important way for the multi-dimensional light field manipulations.

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

Load forecasting method based on CEEMDAN and TCN-LSTM.

Aiming at the problems of high stochasticity and volatility of power loads as well as the difficulty of accurate load forecasting, this paper proposes a power load forecasting method based on CEEMDAN (Completely Integrated Empirical Modal Decomposition) and TCN-LSTM (Temporal Convolutional Networks and Long-Short-Term Memory Networks). The method combines the decomposition of raw load data by CEEMDAN and the spatio-temporal modeling capability of TCN-LSTM model, aiming to improve the accuracy and stability of forecasting. First, the raw load data are decomposed into multiple linearly stable subsequences by CEEMDAN, and then the sample entropy is introduced to reorganize each subsequence. Then the reorganized sequences are used as inputs to the TCN-LSTM model to extract sequence features and perform training and prediction. The modeling prediction is carried out by selecting the electricity compliance data of New South Wales, Australia, and compared with the traditional prediction methods. The experimental results show that the algorithm proposed in this paper has higher accuracy and better prediction effect on load forecasting, which can provide a partial reference for electricity load forecasting methods.

Effects of Mindfulness and Life-Skills Training on Emotion Regulation and Anxiety Symptoms in Chinese Migrant Children: A Randomized Controlled Trial.

PURPOSE: China's rapid urbanization has been associated with increased mental health challenges, especially in rural-to-urban migrant children. This study evaluates the effects of mindfulness and life-skills (LS) training on emotional regulation and anxiety symptoms from a randomized controlled trial aimed at improving the mental health of Chinese migrant children. METHODS: Two intervention arms-mindfulness training (MT) and MT plus LS mentorship (MT + LS)-were compared to a waitlist control group of 368 migrant children aged 9-17 years. Volunteers were trained to deliver interventions to 285 migrant children in small groups of 15 for eight weeks weekly. Social integration varied: migrant children mixed with local children at public schools were considered highly integrated, those in migrant-only classrooms at public schools had intermediate levels of integration, and children in private migrant schools had low integration. Emotion regulation and anxiety symptoms were assessed preintervention, postintervention, and three months postintervention. RESULTS: Postintervention and compared to the control group, children with high social integration in the MT arm showed increased cognitive reappraisal ability (p < .05) but higher physical anxiety (p < .01). Children with high social integration in the MT + LS arm had lower anxiety symptoms of harm avoidance (p < .01) and physical anxiety (p < .05). Children with low social integration in the MT + LS arm showed lower cognitive reappraisal (p < .01) and poorer overall emotion regulation abilities (p < .01). Three months later, children with intermediate integration in the MT + LS arm had lower separation anxiety (p < .05) and harm avoidance anxiety (p < .05). No other groups showed significant improvements in emotion regulation or reducing in anxiety symptoms three months postintervention. DISCUSSION: Mindfulness and LS training may benefit Chinese migrant children who have higher levels of social integration but increase anxiety in those with lower social integration. Future research should consider the sociocultural context in which a treatment is implemented.

Liensinine inhibits IL-1ß-stimulated inflammatory response in chondrocytes and attenuates papain-induced osteoarthritis in rats.

Osteoarthritis (OA) is a joint disease caused by inflammation of cartilage and synovial tissue. Suppressing the process of inflammatory reaction and the generation of oxidative stress is an effective strategy to alleviate the progression of OA. Liensinine is one of the main components of lotus seeds, which has anti-hypertensive and anti-arrhythmia activities. In this study, we aimed to determine the anti-inflammatory effect of liensinine in an OA. Here, we found that liensinine significantly inhibited the inflammatory response of SW1353 cells and primary chondrocytes by inhibiting the release of inflammatory cytokines and oxidative stress. Moreover, we showed that liensinine was able to inhibit the activation of the NF-κB signaling pathway in IL-1ß-induced SW1353 cells. Lastly, we found that liensinine significantly ameliorated cartilage damage and inflammatory response in papain-induced rats. Our study demonstrated a significant protective effect of liensinine against OA, which might be by inhibiting the activation of the NF-κB signaling pathway, and provide a new insight for the treatment of OA using liensinine.

The association between vitamin D and the progression of diabetic nephropathy: insights into potential mechanisms.

Aims: Vitamin D deficiency (VDD) is prevalent in the population, with inadequate intake, impaired absorption and metabolism as the main causative factors. VDD increases the risk of developing chronic diseases such as type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), but the molecular mechanisms underlying this phenomenon are not known. The aim of this study was to investigate the association and potential mechanisms of vitamin D levels with the progression of DN by analyzing general clinical data and using bioinformatics methods. Methods: The study included 567 diabetes mellitus type 2 (T2DM) patients from the Rocket Force Characteristic Medical Center as the case group and 221 healthy examinees as the normal control group. T2DM patients were categorized into T2DM, early diabetic nephropathy (EDN), and advanced diabetic nephropathy (ADN) based on the progression of diabetic nephropathy. The renal RNA-seq and scRNA-seq data of patients with DN were mined from public databases, and the differential expression of vitamin D-related genes in normal-EDN-ADN was analyzed by bioinformatics method, protein interaction network was constructed, immune infiltration was evaluated, single cell map was drawn, and potential mechanisms of VD and DN interaction were explored. Results: Chi-square test showed that vitamin D level was significantly negatively correlated with DN progression (p < 0.001). Bioinformatics showed that the expression of vitamin D-related cytochrome P450 family genes was down-regulated, and TLR4 and other related inflammatory genes were abnormally up-regulated with the progression of DN. Vitamin D metabolism disturbance up-regulate "Nf-Kappa B signaling pathway," B cell receptor signaling pathway and other immune regulation and insulin resistance related pathways, and inhibit a variety of metabolic pathways. In addition, vitamin D metabolism disturbance are strongly associated with the development of diabetic cardiomyopathy and several neurological disease complications. Conclusion: VDD or vitamin D metabolism disturbance is positively associated with the severity of renal injury. The mechanisms may involve abnormal regulation of the immune system by vitamin D metabolism disturbance, metabolic suppression, upregulation of insulin resistance and inflammatory signalling pathways.

Cuproptosis: Mechanism and Application in Lymphoma.

The cell death field has profited from the increasing attention of the scientific community and has been shown to lie at the very basis of cancer initiation and progression. Cuproptosis is a recently proposed method of cell death in 2022, and it is different from any previously reported method. The principle is that copper ions lead to aggregation and instability of intracellular proteins. An increasing number of researchers are dedicated to enriching the mechanism of cuproptosis and exploring its relationship with cancer. Studies have found that intracellular copper levels have an impact on the occurrence and development of lymphoma. The complexity of lymphoma and the limitations of treatment necessitate in-depth studies of the disease. We will review the mechanism of cuproptosis and its potential in lymphoma therapy.

Biodegradable Ruthenium-Rhenium Complexes Containing Nanoamplifiers: Triggering ROS-Induced CO Release for Synergistic Cancer Treatment.

The constrained effectiveness of photodynamic therapy (PDT) has impeded its widespread use in clinical practice. Urgent efforts are needed to address the shortcomings faced in photodynamic therapy, such as photosensitizer toxicity, short half-life, and limited action range of reactive oxygen species (ROS). In this study, a biodegradable copolymer nanoamplifier is reported that contains ruthenium complex (Ru-complex) as photosensitizer (PS) and rhenium complex (Re-complex) as carbon monoxide (CO)-release molecule (CORM). The well-designed nanoamplifier brings PS and CORM into close spatial proximity, significantly promotes the utilization of light-stimulated reactive oxygen species (ROS), and cascaded amplifying CO release, thus enabling an enhanced synergistic effect of PDT and gas therapy for cancer treatment. Moreover, owing to its intrinsic photodegradable nature, the nanoamplifier exhibits good tumor accumulation and penetration ability, and excellent biocompatibility in vivo. These findings suggest that the biodegradable cascaded nanoamplifiers pave the way for a synergistic and clinically viable integration of photodynamic and gas therapy.

Placental Transmogrification of the Lung Presenting as Cystic-Solid Mass: A Case Report.

The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.

Foliar-selenium enhances plant growth and arsenic accumulation in As-hyperaccumulator Pteris vittata: Critical roles of GSH-GSSG cycle and arsenite antiporters PvACR3.

It is known that selenium (Se) enhances plant growth and arsenic (As) accumulation in As-hyperaccumulator Pteris vittata, but the associated mechanisms are unclear. In this study, P. vittata was exposed to 50 µM arsenate (AsV) under hydroponics plus 25 or 50 µM foliar selenate. After 3-weeks of growth, the plant biomass, As and Se contents, As speciation, malondialdehyde (MDA) and glutathione (GSH and GSSG) levels, and important genes related to As-metabolism in P. vittata were determined. Foliar-Se increased plant biomass by 17 - 30 %, possibly due to 9.1 - 19 % reduction in MDA content compared to the As control. Further, foliar-Se enhanced the As contents by 1.9-3.5 folds and increased arsenite (AsIII) contents by 64 - 136 % in the fronds. The increased AsV reduction to AsIII was attributed to 60 - 131 % increase in glutathione peroxidase activity, which mediates GSH oxidation to GSSG (8.8 -29 % increase) in the fronds. Further, foliar-Se increased the expression of AsIII antiporters PvACR3;1-3;3 by 1.6 - 2.1 folds but had no impact on phosphate transporters PvPht1 or arsenate reductases PvHAC1/2. Our results indicate that foliar-Se effectively enhances plant growth and arsenic accumulation by promoting the GSH-GSSG cycle and upregulating gene expression of AsIII antiporters, which are responsible for AsIII translocation from the roots to fronds and AsIII sequestration into the fronds. The data indicate that foliar-Se can effectively improve phytoremediation efficiency of P. vittata in As-contaminated soils.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

Human yolk sac-derived innate lymphoid-biased multipotent progenitors emerge prior to hematopoietic stem cell formation.

Hematopoietic stem cell (HSC)-independent lymphopoiesis has been elucidated in murine embryos. However, our understanding regarding human embryonic counterparts remains limited. Here, we demonstrated the presence of human yolk sac-derived lymphoid-biased progenitors (YSLPs) expressing CD34, IL7R, LTB, and IRF8 at Carnegie stage 10, much earlier than the first HSC emergence. The number and lymphopoietic potential of these progenitors were both significantly higher in the yolk sac than the embryo proper at this early stage. Importantly, single-cell/bulk culture and CITE-seq have elucidated the tendency of YSLP to differentiate into innate lymphoid cells and dendritic cells. Notably, lymphoid progenitors in fetal liver before and after HSC seeding displayed distinct transcriptional features, with the former closely resembling those of YSLPs. Overall, our data identified the origin, potential, and migratory dynamics of innate lymphoid-biased multipotent progenitors in human yolk sac before HSC emergence, providing insights for understanding the stepwise establishment of innate immune system in humans.

Delocalized Orbitals Over Metal Clusters and Organic Linkers Enable Boosted Charge Transfer in Metal-Organic Framework for Overall CO2 Photoreduction.

The conversion of CO2 to C2 through photocatalysis poses significant challenges, and one of the biggest hurdles stems from the sluggishness of the multi-electron transfer process. Herein, taking metal-organic framework (PFC-98) as a model photocatalyst, we report a new strategy to facilitate charge separation. This strategy involves matching the energy levels of the lowest unoccupied node and linker orbitals of the MOF, thereby creating the lowest unoccupied crystal orbital (LUCO) delocalized over both the node and linker. This feature enables the direct excitation of electrons from photosensitive linker to the catalytic centers, achieving a direct charge transfer (DCT) pathway. For comparison, an isoreticular MOF (PFC-6) based on analogue components but with far apart frontier energy level was synthesized. The delocalized LUCO caused the presence of an internal charge-separated state (ICS), prolonging the excited state lifetime and further inhibiting the electron-hole recombination. The presence of an internal charge-separated state (ICS) prolongs the excited state lifetime and further inhibits the electron-hole recombination. Moreover, it also induced abundant electrons accumulating at the catalytic sites, enabling the multi-electron transfer process. As a result, the material featuring delocalized LUCO exhibits superior overall CO2 photocatalytic performance with high C2 production yield and selectivity.

Social anxiety and attentional bias to negative emotional information: the relationship and intervention.

BACKGROUND: According to the cognitive behavioral model of social anxiety, attentional bias to negative emotional information causes and maintains anxiety. The goal of attentional bias modification (ABM) is to reduce anxiety by reducing attention bias to negative emotional information. METHOD: We used questionnaires and experiments to explore the improvement effect of ABM training on social anxiety in college students. In Study 1, we used dot-probe tasks to investigate the attentional bias to negative emotional information and the relationship with social anxiety severity in college students. In Study 2, college students with high social anxiety were divided into two groups: attentional bias modification training task group (ABM) and attention control condition task group (ACC). The ABM group received a continuous intervention for 10 days to observe changes in social anxiety levels and attentional bias scores in the pretest and posttest stages. RESULTS: The results showed that the correlation of attentional bias to negative emotional information and social anxiety severity was significant. Meanwhile, the high social anxiety participants responded more quickly to negative emotional information. After the intervention, social anxiety levels and attentional bias scores of the training group were significantly reduced. CONCLUSIONS: The results showed that attentional bias modification training can reduce attentional bias to negative emotional information in college students with social anxiety and effectively improve their social anxiety.

YAP/TAZ enhances P-body formation to promote tumorigenesis.

The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

Multipocket Cage Enables the Binding of High-Order Bulky and Drug Guests Uncovered by MS Methodology.

Achieving high guest loading and multiguest-binding capacity holds crucial significance for advancement in separation, catalysis, and drug delivery with synthetic receptors; however, it remains a challenging bottleneck in characterization of high-stoichiometry guest-binding events. Herein, we describe a large-sized coordination cage (MOC-70-Zn8Pd6) possessing 12 peripheral pockets capable of accommodating multiple guests and a high-resolution electrospray ionization mass spectrometry (HR-ESI-MS)-based method to understand the solution host-guest chemistry. A diverse range of bulky guests, varying from drug molecules to rigid fullerenes as well as flexible host molecules of crown ethers and calixarenes, could be loaded into open pockets with high capacities. Notably, these hollow cage pockets provide multisites to capture different guests, showing heteroguest coloading behavior to capture binary, ternary, or even quaternary guests. Moreover, a pair of commercially applied drugs for the combination therapy of chronic lymphocytic leukemia (CLL) has been tested, highlighting its potential in multidrug delivery for combined treatment.

Roles of micro-alloyed Y and Gd in improving the corrosion resistance and mechanical properties of pure Mg.

The microstructure, corrosion resistance and mechanical properties of extruded pure Mg, Mg-2Y and Mg-2Gd were studied by means of scanning electron microscope (SEM), X-ray diffraction (XRD), electron backscatter diffraction (EBSD), scanning probe microscope (SPM), immersion test, electrochemical test and tensile test. The results demonstrated that Mg-2Y and Mg-2Gd were composed of Mg, Mg24Y5, and Mg5Gd phases with the addition of Y and Gd. The addition of Y and Gd to pure Mg noticeably reduced the grain size and textural strength of the alloy. Mg-2Gd alloy had the smallest grain size and the lowest textural strength. The corrosion rate of Mg-2Gd was the slowest due to the influence of grain size. Y slowed the corrosion of pure Mg in the early stages due to the grain refinement, but speeded up the corrosion because of the galvanic corrosion produced by the precipitation of the second phase in the latter stages. The elongation of pure Mg, Mg-2Y, and Mg-2Gd were 16.5 %, 38.67 %, and 48.67 %, respectively. The inclusion of Y and Gd refined the grain, softened the texture strength, and activated basal slip, which improved the elasticity of alloys. Gd was more significant than Y in improving the corrosion resistance and mechanical properties of pure Mg.

Multifunctional Lithium Phytate/Carbon Nanotube Double-Layer-Modified Separators for High-Performance Lithium-Sulfur Batteries.

Li dendrite and the shuttle effect are the two primary hindrances to the commercial application of lithium-sulfur batteries (LSBs). Here, a multifunctional separator has been fabricated via successively coating carbon nanotubes (CNTs) and lithium phytate (LP) onto a commercial polypropylene (PP) separator to improve the performance of LSBs. The LP coating layer with abundant electronegative phosphate group as permselective ion sieve not only reduces the polysulfide shuttle but also facilitates uniform Li+ flux through the PP separator. And the highly conductive CNTs on the second layer act as a second collector to accelerate the reversible conversion of sulfide species. The synergistic effect of LP and CNTs further increases the electrolyte wettability and reaction kinetics of cells with a modified separator and suppresses the shuttle effect and growth of Li dendrite. Consequently, the LSBs present much enhanced rate performance and cyclic performance. It is expected that this study may generate an executable tactic for interface engineering of separator to accelerate the industrial application process of LSBs.

Stereochemical Control of Redox CoII/CoIII-Cages with Switchable Cotton Effects Based on Labile-Static States.

The structural dynamics of artificial assemblies, in aspects such as molecular recognition and structural transformation, provide us with a blueprint to achieve bioinspired applications. Here, we describe the assembly of redox-switchable chiral metal-organic cages Λ8/Δ8-[Pd6(CoIIL3)8]28+ and Λ8/Δ8-[Pd6(CoIIIL3)8]36+. These isomeric cages demonstrate an on-off chirality logic gate controlled by their chemical and stereostructural dynamics tunable through redox transitions between the labile CoII-state and static CoIII-state with a distinct Cotton effect. The transition between different states is enabled by a reversible redox process and chiral recognition originating in the tris-chelate Co-centers. All cages in two states are thoroughly characterized by NMR, ESI-MS, CV, CD, and X-ray crystallographic analysis, which clarify their redox-switching behaviors upon chemical reduction/oxidation. The stereochemical lability of the CoII-center endows the Λ8/Δ8-CoII-cages with efficient chiral-induction by enantiomeric guests, leading to enantiomeric isomerization to switch between Λ8/Δ8-CoII-cages, which can be stabilized by oxidation to their chemically inert forms of Λ8/Δ8-CoIII-cages. Kinetic studies reveal that the isomerization rate of the Δ8-CoIII-cage is at least an order of magnitude slower than that of the Δ8-CoII-cage even at an elevated temperature, while its activation energy is 16 kcal mol-1 higher than that of the CoII-cage.