DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a rare liver cancer that disproportionately affects adolescents and young adults. Currently, no standard of care is available and there remains a dire need for new therapeutics. Most patients harbor the fusion oncogene DNAJB1-PRKACA (DP fusion), but clinical inhibitors are not yet developed and it is critical to identify downstream mediators of FLC pathogenesis. Here, we identify long noncoding RNA LINC00473 among the most highly upregulated genes in FLC tumors and determine that it is strongly suppressed by RNAi-mediated inhibition of the DP fusion in FLC tumor epithelial cells. We show by loss- and gain-of-function studies that LINC00473 suppresses apoptosis, increases the expression of FLC marker genes, and promotes FLC growth in cell-based and in vivo disease models. Mechanistically, LINC00473 plays an important role in promoting glycolysis and altering mitochondrial activity. Specifically, LINC00473 knockdown leads to increased spare respiratory capacity, which indicates mitochondrial fitness. Overall, we propose that LINC00473 could be a viable target for this devastating disease.

Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells.

In mammals, gene silencing by the RNA-induced silencing complex (RISC) is a well-understood cytoplasmic posttranscriptional gene regulatory mechanism. Here, we show that embryonic stem cells (ESCs) contain high levels of nuclear AGO proteins and that in ESCs nuclear AGO protein activity allows for the onset of differentiation. In the nucleus, AGO proteins interact with core RISC components, including the TNRC6 proteins and the CCR4-NOT deadenylase complex. In contrast to cytoplasmic miRNA-mediated gene silencing that mainly operates on cis-acting elements in mRNA 3' untranslated (UTR) sequences, in the nucleus AGO binding in the coding sequence and potentially introns also contributed to post-transcriptional gene silencing. Thus, nuclear localization of AGO proteins in specific cell types leads to a previously unappreciated expansion of the miRNA-regulated transcriptome.

PINK1 Phosphorylates MIC60/Mitofilin to Control Structural Plasticity of Mitochondrial Crista Junctions.

Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization. Expression of MIC60 restores crista structure and ATP levels of PINK1-null flies and remarkably rescues their behavioral defects and dopaminergic neurodegeneration. In an extension to human relevance, we discover that the PINK1-MIC60 pathway is conserved in human neurons, and expression of several MIC60 coding variants in the mitochondrial targeting sequence found in PD patients in Drosophila impairs crista junction formation and causes locomotion deficits. These findings highlight the importance of maintenance and plasticity of crista junctions to cellular homeostasis in vivo.

A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription In trans.

The enhancer regions of the myogenic master regulator MyoD give rise to at least two enhancer RNAs. Core enhancer eRNA (CEeRNA) regulates transcription of the adjacent MyoD gene, whereas DRReRNA affects expression of Myogenin in trans. We found that DRReRNA is recruited at the Myogenin locus, where it colocalizes with Myogenin nascent transcripts. DRReRNA associates with the cohesin complex, and this association correlates with its transactivating properties. Despite being expressed in undifferentiated cells, cohesin is not loaded on Myogenin until the cells start expressing DRReRNA, which is then required for cohesin chromatin recruitment and maintenance. Functionally, depletion of either cohesin or DRReRNA reduces chromatin accessibility, prevents Myogenin activation, and hinders muscle cell differentiation. Thus, DRReRNA ensures spatially appropriate cohesin loading in trans to regulate gene expression.

IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.

An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.

The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins.

Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells (ESCs) reduced expression of pluripotency factors, increased expression of cell-lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective downregulation of pluripotency factors upon Spt6 depletion may be mechanistically explained by its enrichment at ESC super-enhancers, where Spt6 controls histone H3K27 acetylation and methylation and super-enhancer RNA transcription. In ESCs, Spt6 interacted with the PRC2 core subunit Suz12 and prevented H3K27me3 accumulation at ESC super-enhancers and associated promoters. Biochemical as well as functional experiments revealed that Spt6 could compete for binding of the PRC2 methyltransferase Ezh2 to Suz12 and reduce PRC2 chromatin engagement. Thus, in addition to serving as a histone chaperone and transcription elongation factor, Spt6 counteracts repression by opposing H3K27me3 deposition at critical genomic regulatory regions.

Profiling Humoral Immunity After Mixing and Matching COVID-19 Vaccines Using SARS-CoV-2 Variant Protein Microarrays.

In November 2022, 68% of the population received at least one dose of COVID-19 vaccines. Owing to the ongoing mutations, especially for the variants of concern (VOCs), it is important to monitor the humoral immune responses after different vaccination strategies. In this study, we developed a SARS-CoV-2 variant protein microarray that contained the spike proteins from the VOCs, e.g., alpha, beta, gamma, delta, and omicron, to quantify the binding antibody and surrogate neutralizing antibody. Plasmas were collected after two doses of matching AZD1222 (AZx2), two doses of matching mRNA-1273 (Mx2), or mixing AZD1222 and mRNA-1273 (AZ+M). The results showed a significant decrease of surrogate neutralizing antibodies against the receptor-binding domain in all VOCs in AZx2 and Mx2 but not AZ+M. A similar but minor reduction pattern of surrogate neutralizing antibodies against the extracellular domain was observed. While Mx2 exhibited a higher surrogate neutralizing level against all VOCs compared with AZx2, AZ+M showed an even higher surrogate neutralizing level in gamma and omicron compared with Mx2. It is worth noting that the binding antibody displayed a low correlation to the surrogate neutralizing antibody (R-square 0.130-0.382). This study delivers insights into humoral immunities, SARS-CoV-2 mutations, and mixing and matching vaccine strategies, which may provide a more effective vaccine strategy especially in preventing omicron.

Mitigation of age-dependent accumulation of defective mitochondrial genomes.

Unknown processes promote the accumulation of mitochondrial DNA (mtDNA) mutations during aging. Accumulation of defective mitochondrial genomes is thought to promote the progression of heteroplasmic mitochondrial diseases and degenerative changes with natural aging. We used a heteroplasmic Drosophila model to test 1) whether purifying selection acts to limit the abundance of deleterious mutations during development and aging, 2) whether quality control pathways contribute to purifying selection, 3) whether activation of quality control can mitigate accumulation of deleterious mutations, and 4) whether improved quality control improves health span. We show that purifying selection operates during development and growth but is ineffective during aging. Genetic manipulations suggest that a quality control process known to enforce purifying selection during oogenesis also suppresses accumulation of a deleterious mutation during growth and development. Flies with nuclear genotypes that enhance purifying selection sustained higher genome quality, retained more vigorous climbing activity, and lost fewer dopaminergic neurons. A pharmacological agent thought to enhance quality control produced similar benefits. Importantly, similar pharmacological treatment of aged mice reversed age-associated accumulation of a deleterious mtDNA mutation. Our findings reveal dynamic maintenance of mitochondrial genome fitness and reduction in the effectiveness of purifying selection during life. Importantly, we describe interventions that mitigate and even reverse age-associated genome degeneration in flies and in mice. Furthermore, mitigation of genome degeneration improved well-being in a Drosophila model of heteroplasmic mitochondrial disease.

Compulsive drug-taking is associated with habenula-frontal cortex connectivity.

As a critical node connecting the forebrain with the midbrain, the lateral habenula (LHb) processes negative feedback in response to aversive events and plays an essential role in value-based decision-making. Compulsive drug use, a hallmark of substance use disorder, is attributed to maladaptive decision-making regarding aversive drug-use-related events and has been associated with dysregulation of various frontal-midbrain circuits. To understand the contributions of frontal-habenula-midbrain circuits in the development of drug dependence, we employed a rat model of methamphetamine self-administration (SA) in the presence of concomitant footshock, which has been proposed to model compulsive drug-taking in humans. In this longitudinal study, functional MRI data were collected at pretraining baseline, after 20 d of long-access SA phase, and after 5 d of concomitant footshock coupled with SA (punishment phase). Individual differences in response to punishment were quantified by a "compulsivity index (CI)," defined as drug infusions at the end of punishment phase, normalized by those at the end of SA phase. Functional connectivity of LHb with the frontal cortices and substantia nigra (SN) after the punishment phase was positively correlated with the CI in rats that maintained drug SA despite receiving increasing-intensity footshock. In contrast, functional connectivity of the same circuits was negatively correlated with CI in rats that significantly reduced SA. These findings suggest that individual differences in compulsive drug-taking are reflected by alterations within frontal-LHb-SN circuits after experiencing the negative consequences from SA, suggesting these circuits may serve as unique biomarkers and potential therapeutic targets for individualized treatment of addiction.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Reverse-Phase Protein Microarrays for Overexpressed Escherichia coli Lysates Reveal a Novel Tyrosine Kinase.

Tyrosine phosphorylation is one of the most important posttranslational modifications in bacteria, linked to regulating growth, migration, virulence, secondary metabolites, biofilm formation, and capsule production. Only two tyrosine kinases (yccC (etk) and wzc) have been identified in Escherichia coli. The investigation by similarity has not revealed any novel BY-kinases in silico so far, most probably due to their sequence and structural variability. Here we developed a reverse-phase protein array from 4126 overexpressed E. coli clones, lysed, and printed on coated glass slides. These high-density E. coli lysate arrays (ECLAs) were quality controlled by the reproducibility and immobilization of total lysate proteins and specific overexpressed proteins. ECLAs were used to interrogate the relationship between protein overexpression and tyrosine phosphorylation in the total lysate. We identified 6 protein candidates, including etk and wzc, with elevated phosphotyrosine signals in the total lysates. Among them, we identified a novel kinase nrdD with autophosphorylation and transphosphorylation activities in the lysates. Moreover, the overexpression of nrdD induced biofilm formation. Since nrdD is a novel kinase, we used E. coli proteome microarrays (purified 4,126 E. coli proteins) to perform an in vitro kinase assay and identified 33 potential substrates. Together, this study established a new ECLA platform for interrogating posttranslational modifications and identified a novel kinase that is important in biofilm formation, which will shed some light on bacteria biochemistry and new ways to impede drug resistance.

Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

BACKGROUND AND AIMS: HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. APPROACH AND RESULTS: We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase

Seminal Vesicle-Derived Exosomes for the Regulation of Sperm Activity.

The seminal vesicle contributes to a large extent of the semen volume and composition. Removal of seminal vesicle or lack of seminal vesicle proteins leads to decreased fertility. Seminal plasma proteome revealed that seminal fluid contained a wide diversity of proteins. Many of them are known to modulate sperm capacitation and serve as capacitation inhibitors or decapacitation factors. Despite identifying secretory vesicles from the male reproductive tract, such as epididymosomes or prostasomes, isolation, identification, and characterization of seminal vesicle-derived exosomes are still unknown. This chapter aims to review the current understanding of the function of seminal vesicles on sperm physiology and male reproduction and provide ultracentrifugation-based isolation protocols for the isolation of seminal vesicle exosomes. Moreover, via proteomic analysis and functional categorization, a total of 726 proteins IDs were identified in the purified seminal vesicle exosomes fraction. Preliminary data showed seminal vesicle-derived exosomes inhibited sperm capacitation; however, more studies will be needed to reveal other functional involvements of seminal vesicle-derived exosomes on the sperm physiology and, more importantly, how these exosomes interact with sperm membrane to achieve their biological effects.

Epididymosomes: Composition and Functions for Sperm Maturation.

This article provides an overview of literature pertaining to epididymosome origin, composition and their functional significance. Broadly, epididymosomes are defined as extracellular vesicles that are secreted by the epididymal epithelium and thereafter facilitate intercellular communication within the male reproductive tract. Epididymosomes fulfil this communication role via their encapsulation and delivery of a diverse macromolecular payload to recipient cells. This complex cargo includes proteins, lipids, and nucleic acids, which are delivered to maturing spermatozoa, thereby influencing their viability and function. Additionally, epididymosomes have been implicated in the post-translational modification of intrinsic sperm proteins, protection of sperm from oxidative stress and immune surveillance, and in the transmission of epigenetic information capable of mediating intergenerational effects. Hence, continued research into the biogenesis, cargo composition, and functional significance of epididymosomes holds promise for advancing male reproductive health and fertility treatments.

Equilibrative nucleoside transporter 3 supports microglial functions and protects against the progression of Huntington's disease in the mouse model.

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3-/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.

The interplay of metabolic dysfunction-associated fatty liver disease and viral hepatitis on liver disease severity: A large community-based study in a viral endemic area.

BACKGROUND AND AIM: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its interplay with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of liver disease severity is elusive. METHODS: A mass surveillance program was conducted in a viral hepatitis endemic area. The objective was to identify MAFLD/non-MAFLD subjects with advanced liver disease. RESULTS: Two thousand two hundred and forty-two (41.7%) of the 5378 subjects were identified as having MAFLD, and 375 (7.0%) had advanced liver disease. The proportions of anti-HCV and HBsAg seropositivity were 19.3% and 9.7%, respectively. The proportions of advanced fibrosis in subjects with non-viral hepatitis (NBNC), HBV and HCV infection were 2.8%, 5.7% and 23.4%, respectively. Subjects with MAFLD had a significantly higher proportion of advanced fibrosis (8.7% vs 5.7%, P < 0.001). Factors associated with advanced fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 4.8/3.7-6.0, P < 0.001), male sex (OR/CI: 1.3/1.0-1.7, P = 0.019), anti-HCV seropositivity (OR/CI: 5.9/4.6-7.5, P = 0.019), MAFLD-lean metabolic dysregulation (MS) (OR/CI: 2.6/1.3-5.2, P = 0.005; compared with the non-MAFLD group) and MAFLD-diabetes (OR/CI: 1.5/1.1-2.1, P = 0.008; compared with the non-MAFLD group). MAFLD did not aggravate liver disease severity in patients with viral hepatitis. However, among NBNC subjects, factors associated with advanced liver disease included MAFLD-lean MS group (OR/CI: 9.1/2.4-34.6, P = 0.001; compared with non-MAFLD group) and MAFLD-DM group (OR/CI: 2.0/1.2-3.2, P = 0.004; compared with non-MAFLD group). CONCLUSIONS: MAFLD patients with diabetes and metabolic dysregulation had a higher risk of advanced liver disease. The effect was more significant in non-viral hepatitis subjects in a community level.

Self-assembled mesoporous silica decorated with biogenic carbon dot nanospheres hybrid nanomaterial for efficient removal of aqueous Methoxy-DDT via a Short-Bed Adsorption column technique.

Methoxy-DDT is an organochlorine pesticide extensively used in agricultural practices as a DDT substitute. Methoxy-DDT has been found and quantified in several investigations in groundwater, drinking water, sediment, and various biota. Therefore, designing efficient and cost-effective adsorbents for removing methoxy-DDT is vital. In this work, we embedded Ficus benghalensis L. derived carbon dots (CDs) in mesoporous silica (MS) to fabricate MS-CDs nanohybrid material. MS-CDs nanohybrid exhibited remarkable selectivity and removal efficiency towards methoxy-DDT, outperforming other endocrine disruptors. Parameters for industrial-scale fixed-bed adsorption columns, such as bed capacity, length, and breakthrough times, were analyzed. The kinetic study revealed that pseudo-second-order (PSO) adsorption and isotherm analysis confirmed the Langmuir model as the best fit. Small bed adsorption (SBA) column analysis was carried out using spiked Yamuna river water, and the breakthrough curves were demonstrated by varying MS-CDs bed height. The maximum adsorption capacity obtained for methoxy-DDT was 17.16 mg/g at breakthrough and 49.98 mg/g at exhaustion. The adsorbent showed 86.53% removal efficiency in the 5th cycle, demonstrating good reusability. These results indicate that the developed material MS-CDs-based organic sphere is an effective adsorbent for aqueous methoxy-DDT adsorption and can be applied to wastewater treatment.

Novel MoS2-In2O3-WS2 (2D/3D/2D) ternary heterostructure nanocomposite material: Efficient photocatalytic degradation of antimicrobial agents under visible-light.

Fabrication of ternary composited photocatalytic nanomaterials with strong interaction is vital to deriving the fast charge separation for efficient photodegradation of organic contaminants in wastewater under visible light. In this work, novel ternary 2D/3D/2D MoS2-In2O3-WS2 multi-nanostructures were synthesized using facile hydrothermal processes. XRD, FTIR, and XPS results confirmed the phase, functional groups, and element composition of pure MoS2, MoS2-In2O3, and MoS2-In2O3-WS2 hybrids. UV-DRS spectra of the MoS2-In2O3-WS2 ternary hybrid indicate maximum absorption in the visible light range with a band-gap energy value of 2.4 eV. The surface of the 2D WS2 nanosheet structure tightly blends and densely disperses 2D MoS2 nanosheets and 3D In2O3 nanocubes. This confirmed the formation of the MoS2-In2O3-WS2 ternary hybrid in the form of 2D/3D/2D multi-nanostructures, which is also indicated from SEM and HR-TEM images. The synthesized MoS2-In2O3-WS2 ternary hybrid showed maximum photocatalytic activity under visible-light for antimicrobial agents such as triclosan (TCS) and trichlorocarban (TCC). The photocatalytic activity of TCS was revealed to be 95% at 90 min, while that of TCC was 93% at 100 min. The reusability and stability tests of the prepared MoS2-In2O3-WS2 ternary hybrid after four consecutive photocatalytic cycles were analyzed by FTIR and SEM, which indicated that the prepared ternary hybrid was very stable. Overall results suggested that the developed MoS2-In2O3-WS2 (2D/3D/2D) multi-nanostructures are environmentally friendly and low-cost nanocomposites as a potential photocatalyst for the removal of antimicrobial agents from wastewater.

Carbon and graphene quantum dots based architectonics for efficient aqueous decontamination by adsorption chromatography technique - Current state and prospects.

Aquatic ecosystems and potable water are being exploited and depleted due to urbanization and the encouragement of extensive industrialization, which induces the scarcity of pure water. However, current decontamination methods are limited and inefficient. Various innovative remediation strategies with novel nanomaterials have recently been demonstrated for wastewater treatment. Carbon dots (C-dots) and graphene quantum dots (GQ-dots) are the most recent frontiers in carbon nanomaterial-based adsorption studies. C-dots are extremely small (1-10 nm) quasi-spherical carbon nanoparticles (mostly sp3 hybridized carbon), whereas GQ-dots are fragments of graphene (1-20 nm) composed of primarily sp2 hybridized carbon. This article highlights the function of C-dots and GQ-dots with their specifications and characteristics for the efficient removal of organic and inorganic contaminants in water via adsorption chromatography. The alteration of adsorption attributes with the hybrid blending of these dots has been critically analyzed. Moreover, various top-down and bottom-up approaches for synthesizing C-dots and GQ-dots, which ultimately affect their morphology and structure, are described in detail. Finally, we review the research deficit in the adsorption of diverse pollutants, fabrication challenges, low molecular weight, self-agglomeration, and the future of the dots by providing research prospects and selectivity and sensitivity perspectives, the importance of post-adsorption optimization strategies and the path toward scalability at the tail of the article.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.