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Abstract Over 250 million individuals live with chronic hepatitis B (CHB) infection worldwide. A significant proportion of these people often face discrimination defined as the unjust, unfair, or prejudicial treatment of a person on the grounds of their hepatitis B status. Hepatitis B related discrimination has not been widely documented in the literature. This study aims to describe the lived experience of discrimination, document its impact, and shed light on its consequences. A hepatitis B discrimination registry was launched to record self-reported discrimination associated with hepatitis B. The registry included brief demographic questions (age, gender, country of origin), discrimination-specific questions (where, when, and how discrimination occurred), and open-ended questions to detail specific experiences. The registry was distributed to hepatitis B patient/people-focused listservs, social media networks, and community-based organizations around the globe. Descriptive data were analyzed including comparative analysis by country and type of discrimination occurring along with qualitative data (open-ended responses) which were analyzed using thematic analysis techniques A total of 569 individuals responded to the survey between May 2021 and December 2023. Individuals identified as residing in the Philippines (34%; N = 194), Nigeria (11%; N = 60), Pakistan (8%; N = 45), India (6%, N = 34), Uganda (5%; N = 31), the United States of America (4%, N = 26), Ghana (3%; N = 15), Ethiopia (2%; N = 14), and other countries in smaller number with a total of 65 countries reported discrimination at least by one individual. Of these, 461 individuals shared details about their experiences of discrimination with most relating to restrictions on access to work visas, followed by in-country hepatitis B-related employment restrictions, educational-based discrimination, discrimination within the community and health facilities, and the emotional impact of hepatitis B discrimination. This is the largest primary collection of hepatitis B-associated discrimination events and highlights how hepatitis B discrimination clearly has a significant impact on individuals’ lives and limits economic opportunities regardless of physical symptoms. Such impacts likely act as barriers to diagnosis and engagement in care, so need to be addressed to achieve the global hepatitis B elimination goals. The data highlight a need for global, national responses and more systematic responses to discrimination experienced by people with hepatitis B.

Hepatitis B virus (HBV) infection remains a major public health concern worldwide, with approximately 296 million individuals chronically infected. The HBV-encoded X protein (HBx) is a regulatory protein of 17 kDa, reportedly responsible for a broad range of functions, including viral replication and oncogenic processes. In this review, we summarize the state of knowledge on the mechanisms underlying HBx functions in viral replication, the antiviral effect of therapeutics directed against HBx, and the role of HBx in liver cancer development (including a hypothetical model of hepatocarcinogenesis). We conclude by highlighting major unanswered questions in the field and the implications of their answers.

People living with chronic hepatitis B (PLCHB) are recommended to follow a lifelong monitoring regimen and face increased risk of liver cancer. Additionally, PLCHB frequently encounter stigma and discrimination, and relationship disruptions because of their chronic hepatitis B (CHB). Social support plays a key role in coping with chronic illnesses; however, this is inadequately assessed for PLCHB. This study aims to assess the physical, social, and mental impacts of living with CHB, the strategies PLCHB utilize to cope with their disease, and how social support-or lack of-impacts their journey with hepatitis B. The study was promoted through the Hepatitis B Foundation social media platforms, interested individuals filled-in a form expressing their interest to participate. The researcher conducted 24 telephone interviews in English, with PLCHB ≥18 years of age residing in the United States (U.S.) and Canada. Questions focused on the lived experiences of CHB and explored social support mechanisms that helped PLCHB. PLCHB experience a wide range of impacts (physical, social, and mental) that negatively affect their quality of life. Participants reported that receiving social support from their close network of individuals, hepatitis B community, or healthcare providers positively influenced their perspective on their future health and helped them adhere to treatment. The physical, social, and mental impacts of living with hepatitis B significantly affect the quality of life of PLCHB, calling for more research to document these impacts, and design integrated care models to address them. Social support appears to play an essential role in helping PLCHB cope with their disease and should be further studied.

Abstract Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two‐round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system‐level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.

We are grateful to the authors for providing additional data to demonstrate the presence of domestic cat hepadnavirus in lymphoma tissues [...]

Cat ownership is common in Chile, but data on the regional prevalence of infectious agents are limited. A sero-molecular survey of 120 client- or shelter-owned domestic cats in greater Santiago was performed. Whole blood DNA was tested for the novel hepatitis-B-like virus, domestic cat hepadnavirus (DCH) by conventional PCR (cPCR) and quantitative PCR (qPCR), and for feline leukaemia virus (FeLV) by qPCR. Point-of-care serology for FeLV p27 antigen and antibodies recognising feline immunodeficiency virus (FIV) p15 and p24 was performed. DCH DNA was detected in the serum of 2/120 cats (1.67%). Sequencing and phylogenetic analysis showed that the DCH detected in Chile occupies a position outside the main clustering of DCH in the near-complete genome tree. Progressive (antigen-positive, provirus-positive) and regressive (antigen-negative, provirus-positive) FeLV infections were identified in 6/120 (5%) and 9/120 (7.5%) of cats. A total of 2/120 (1.7%) cats had dual FeLV/FIV infection, and another 2 cats had FIV infection alone. This study shows that the global footprint of DCH includes South America with a low molecular frequency in Chile, similar to that reported in the USA. Progressive FeLV infection is relatively common in urban Chile, and male cats are at greater risk than females. Testing and control measures for pathogenic retroviruses are indicated. The potential impact of FeLV, FIV and DCH on Chile’s wildcat species is worthy of further investigation.

Here, Biswas et al. present and characterize a second-generation model of HBV infection in rhesus macaques, showing that extended infection requires suppression of host immunity.

Chronic hepatitis B is a major cause of liver disease worldwide and is currently incurable. Hepatitis B virus (HBV) covalently closed circular (ccc) DNA is a key form of the virus responsible for its persistence and is the transcriptional template for all viral transcripts. The field is focussed on methods to clear HBV cccDNA but this been limited by technical difficulties in its quantification due to: identical sequence to other forms of HBV DNA; low copy number per cell; and high resistance to denaturation by heat, leading to difficulty using polymerase chain reaction or hybridization methods for detection. A number of assays have been developed in order to overcome these hurdles either directly or detecting cccDNA levels indirectly via its transcriptional products. In this review, we summarize the approaches to cccDNA quantification that are currently used, and outline key open questions in the cccDNA biology field which remain to be answered due to the limitations of current methods.

We write to comment on Piewbang C et al [...]

Chronic hepatitis B affects >300 million people worldwide and is a major cause of liver disease, causing ~800,000 deaths each year [...]

Background & Aims: The chronicity of HBV (and resultant liver disease) is determined by intrahepatic persistence of the HBV covalently closed circular DNA (cccDNA), an episomal form that encodes all viral transcripts. Therefore, cccDNA is a key target for new treatments, with the ultimate therapeutic aim being its complete elimination. Although established cccDNA molecules are known to be stable in resting hepatocytes, we aimed to understand their fate in dividing cells using in vitro models. Methods: We infected HepG2-NTCP and HepaRG-NTCP cells with HBV and induced mitosis by passaging cells. We measured cccDNA copy number (by precise PCR assays) and HBV-expressing cells (by immunofluorescence) with wild-type HBV. We used reporter viruses expressing luciferase or RFP to track number of HBV-expressing cells over time after mitosis induction using luciferase assays and live imaging, respectively. Results: In all cases, we observed dramatic reductions in cccDNA levels, HBV-positive cell numbers, and cccDNA-dependent protein expression after each round of cell mitosis. The rates of reduction were highly consistent with mathematical models of a complete cccDNA loss in (as opposed to dilution into) daughter cells. Conclusions: Our results are concordant with previous animal models of HBV infection and show that HBV persistence can be efficiently overcome by inducing cell mitosis. These results support therapeutic approaches that induce liver turnover (e.g. immune modulators) in addition to direct-acting antiviral therapies to achieve hepatitis B cure. Lay summary: Chronic hepatitis B affects 300 million people (killing 884,000 per year) and is incurable. To cure it, we need to clear the HBV genome from the liver. In this study, we looked at how the virus behaves after a cell divides. We found that it completely clears the virus, making 2 new uninfected cells. Our work informs new approaches to develop cures for chronic hepatitis B infections.

Abstract Background Postoperative complications following major abdominal surgery are frequent despite progress in surgical technique and perioperative care. Early and enhanced postoperative mobilisation has been advocated to reduce postoperative complications, but it is still unknown whether it can independently improve outcomes after major surgery. Fitness trackers (FTs) are a promising tool to improve postoperative mobilisation, but their effect on postoperative complications and recovery has not been investigated in clinical trials. Methods This is a multicentre randomised controlled trial with two parallel study groups evaluating the efficacy of an enhanced and early mobilisation protocol in combination with FT-based feedback in patients undergoing elective major abdominal surgery. Participants are randomly assigned (1:1) to either the experimental group, which receives daily step goals and a FT giving feedback about daily steps, or the control group, which is mobilised according to hospital standards. The control group also receives a FT, however with a blackened screen; thus no FT-based feedback is possible. Randomisation will be stratified by type of surgery (laparoscopic vs. open). The primary endpoint of the study is postoperative morbidity within 30 days measured via the Comprehensive Complication Index. Secondary endpoints include number of steps as well as a set of functional, morbidity and safety parameters. A total of 348 patients will be recruited in 15 German centres. The study will be conducted and organised by the student-led German Clinical Trial Network SIGMA. Discussion Our study aims at investigating whether the implementation of a simple mobilisation protocol in combination with FT-based feedback can reduce postoperative morbidity in patients undergoing major abdominal surgery. If so, FTs would offer a cost-effective intervention to enhance postoperative mobilisation and improve patient outcomes. Trial registration Deutsches Register Klinischer Studien (DRKS, German Clinical Trials Register): DRKS00016755 , UTN U1111-1228-3320. Registered on 06.03.2019.

Domestic cat hepadnavirus (DCH) is an emerging virus related to the hepatitis B virus (HBV). The pathogenic potential of DCH in cats remains to be established. The molecular prevalence of DCH varies widely in the regions investigated so far. The aim of this study was to determine the prevalence, load, and risk factors for DCH detection among cats in Hong Kong, and to generate molecular and epidemiological data on the DCH strains circulating in cats in Hong Kong. DCH DNA was detected using DCH-specific qPCR in 57/513 (11.1%) residual diagnostic blood samples from owned cats. The median viral load was 8.85 × 103 copies/mL of whole blood (range for the 5th to the 95th percentile, 3.33 × 103 to 2.2 × 105 copies per mL). Two outliers had higher viral loads of 1.88 × 107 copies/mL and 4.90 × 109 copies/mL. DCH was detected in cats from 3 months to 19 years of age. Sex, age, neuter status, breed, or elevated serum alanine aminotransferase were not statistically associated with DCH DNA detection. On phylogenetic analysis based on 12 complete genome sequences, the Hong Kong DCH viruses clustered in Genotype A with viruses from Australia and Asia (clade A1), distinct from viruses from Europe (clade A2). Sequence analysis found that DCH has similar epsilon and direct repeat regions to human HBV, suggesting a conserved method of replication. Based on our findings, the DCH strains circulating in Hong Kong are a continuum of the Asiatic strains.

Hepadnaviruses are partially double-stranded DNA viruses that infect a variety of species. The prototypical virus in this family is the human hepatitis B virus, which chronically infects approximately 400 million people worldwide and is a risk factor for progressive liver disease and liver cancer. The first hepadnavirus isolated from carnivores was a domestic cat hepadnavirus (DCH), initially identified in Australia and subsequently detected in cats in Europe and Asia. As with all characterized hepadnaviruses so far, DCH infection has been associated with hepatic disease in its host. Prevalence of this infection in the United States has not been explored broadly. Thus, we utilized conventional and quantitative PCR to screen several populations of domestic cats to estimate DCH prevalence in the United States. We detected DCH DNA in 1 out of 496 animals (0.2%) in the U.S. cohort. In contrast, we detected circulating DCH DNA in 7 positive animals from a cohort of 67 domestic cats from Australia (10.4%), consistent with previous studies. The complete consensus genome of the U.S. DCH isolate was sequenced by Sanger sequencing with overlapping PCR products. An in-frame deletion of 157 bp was identified in the N-terminus of the core open reading frame. The deletion begins at the direct repeat 1 sequence (i.e., the 5′ end of the expected double-stranded linear DNA form), consistent with covalently closed circular DNA resultant from illegitimate recombination described in other hepadnaviruses. Comparative genome sequence analysis indicated that the closest described relatives of the U.S. DCH isolate are those previously isolated in Italy. Motif analysis supports DCH using NTCP as an entry receptor, similar to human HBV. Our work indicates that chronic DCH prevalence in the U.S. is likely low compared to other countries.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the fourth leading cause of cancer-related death. The most common risk factor for developing HCC is chronic infection with hepatitis B virus (HBV). Early stages of HBV-related HCC (HBV-HCC) are generally asymptomatic. Moreover, while serum alpha-fetoprotein (AFP) and abdominal ultrasound are widely used to screen for HCC, they have poor sensitivity. Thus, HBV-HCC is frequently diagnosed at an advanced stage, in which there are limited treatment options and high mortality rates. Serum biomarkers with high sensitivity and specificity are crucial for earlier diagnosis of HCC and improving survival rates. As viral–host interactions are key determinants of pathogenesis, viral biomarkers may add greater diagnostic power for HCC than host biomarkers alone. In this review, we summarize recent research on using virus-derived biomarkers for predicting HCC occurrence and recurrence; including circulating viral DNA, RNA transcripts, and viral proteins. Combining these viral biomarkers with AFP and abdominal ultrasound could improve sensitivity and specificity of early diagnosis, increasing the survival of patients with HBV-HCC. In the future, as the mechanisms that drive HBV-HCC to become clearer, new biomarkers may be identified which can further improve early diagnosis of HBV-HCC.

Abstract Human hepatitis delta virus (HDV) causes the most severe form of viral hepatitis. Approximately 15–25 million people are chronically infected with HDV. As a satellite virus of the human hepatitis B virus (HBV), HDV uses the HBV-encoded envelope proteins for egress from and de novo entry into hepatocytes. So far, in vitro production of HDV particles is restricted to co-transfection of cells with HDV/HBV encoding cDNAs. This approach has several limitations. In this study, we established HuH7-END cells, which continuously secrete infectious HDV virions. The cell line was generated through stepwise stable integration of the cDNA of the HDV antigenome, the genes for the HBV envelope proteins and the HBV/HDV receptor NTCP. We found that HuH7-END cells release infectious HDV particles up to 400 million copies/milliliter and support virus spread to co-cultured cells. Due to the expression of NTCP, HuH7-END cells are also susceptible to de novo HDV entry. Virus production is stable for >16 passages and can be scaled up for preparation of large HDV virus stocks. Finally, HuH7-END cells are suitable for screening of antiviral drugs targeting HDV replication. In summary, the HuH7-END cell line provides a novel tool to study HDV replication in vitro.

Hepatitis B virus (HBV) is the major cause of liver diseases and liver cancer worldwide. After infecting hepatocytes, the virus establishes a stable episome (covalently closed circular DNA, or cccDNA) that serves as the template for all viral transcripts. Specific and accurate quantification of cccDNA is difficult because infected cells contain abundant replicative intermediates of HBV DNA that share overlapping sequences but arranged in slightly different forms. HBV cccDNA can be detected by Southern blot or qPCR methods which involve enzymatic digestion. These assays are laborious, have limited sensitivity, or require degradation of cellular DNA (which precludes simple normalization). The method described in this protocol, cccDNA inversion quantitative (cinq)PCR, instead uses a series of restriction enzyme-mediated hydrolysis and ligation reactions that convert cccDNA into an inverted linear amplicon, which is not amplified or detected from other forms of HBV DNA. Importantly, cellular DNA remains quantifiable during sample preparation, allowing normalization and markedly improving precision. Further, a second linear fragment (derived from enzymatic digestion of a separate region of the HBV DNA genome and is present in all forms of HBV DNA) can be used to simultaneously quantify total HBV levels.Graphic abstract:Selective detection of HBV cccDNA and total HBV DNA using cinqPCR (Reproduced from Tu et al., 2020a).

Background & Aims: Chronic HBV infection cannot be cured by current therapeutics owing to their limited ability to reduce covalently closed circular (ccc)DNA levels in the livers of infected individuals. Therefore, greater understanding of the molecular determinants of cccDNA formation and persistence is required. One key issue is the extent to which de novo nucleocapsid-mediated replenishment (reimport) contributes to cccDNA levels in an infected hepatocyte. Methods: We engineered an infectious HBV mutant with a genome encoding a stop codon at position T67 in the HBV core open reading frame (ΔHBc HBV). Importantly, ΔHBc HBV virions cannot initiate nucleocapsid synthesis upon infection. Long-term in vitro HBV infection markers were followed for up for 9 weeks in HepG2-NTCP cells (A3 clone) and HBV DNA was quantified using a newly-developed, highly-precise PCR assay (cccDNA inversion quantitative PCR). Results: ΔHBc and wild-type (WT) HBV resulted in comparable expression of HBV surface antigen (HBsAg), which could be blocked using the entry inhibitor Myrcludex B, confirming bona fide infection via the receptor sodium taurocholate cotransporting polypeptide (NTCP). In primary human hepatocytes, Huh7-NTCP, HepG2-NTCP, and HepaRG-NTCP cells, comparable copy numbers of cccDNA were formed. cccDNA levels, transcription of viral RNA, and HBsAg secretion remained comparably stable in WT and ΔHBc HBV-infected cells for at least 9 weeks. Conclusions: Our results imply that de novo synthesised HBc plays a minor role in transcriptional regulation of cccDNA. Importantly, we show that initially-formed cccDNA is stable in hepatocytes without requiring continuous replenishment in in vitro infection systems and contribution from de novo DNA-containing nucleocapsids is not required. Thus, short-term therapeutic targeting of capsid-reimport is likely an inefficient strategy in eliminating cccDNA in chronically infected hepatocytes. Lay summary: The hepatitis B virus can maintain itself in the liver for a patient's lifetime, causing liver injury and cancer. We have clarified exactly how it maintains itself in an infected cell. This now means we have a better idea at how to target the virus and cure a chronic infection.

Viral hepatitis remains one of the most significant health issues globally, directly responsible for over 1 million deaths each year and affecting almost 300 million people around the world. Scientific research in recent decades has brought about improvements in the lives of people living with chronic viral hepatitis. On the 29 July 2021, the Australian Centre for Hepatitis Virology (ACHV) for the first time held a public educational forum for the general public. The main aim of this event was to inform the affected community about the importance of scientific research and give an overview of upcoming developments in the field. Here, we provide a detailed report of the panel discussion (including its organisation, execution, and lessons learned to incorporate into future events) and provide strategies that can be used by other scientific societies to hold similar events in their own communities.

Hepatitis B virus (HBV) is a globally-distributed pathogen and is a major cause of liver disease. HBV (or closely-related animal hepadnaviruses) can integrate into the host genome, but (unlike retroviruses) this integrated form is replication-defective. The specific role(s) of the integrated HBV DNA has been a long-standing topic of debate. Novel in vitro models of HBV infection combined with sensitive molecular assays now enable researchers to investigate this under-characterised phenomenon with greater ease and precision. This review covers the contributions these systems have made to understanding how HBV DNA integration induces liver cancer and facilitates viral persistence. We summarise the current findings into a working model of chronic HBV infection and discuss the clinical implications of this hypothetical framework on the upcoming therapeutic strategies used to curb HBV-associated pathogenesis.

In this Special Issue, we have brought together a broad range of studies on hepatitis B virus (HBV) covering diagnosis, pathogenesis, monitoring, and treatment [...]

Chronic hepatitis B (CHB) is one of the most widespread liver diseases in the world. It is currently incurable and can lead to liver cirrhosis and cancer. The considerable impacts on society caused by CHB through patient mortality, morbidity, and economic loss are well-recognised in the field. This is, however, a narrow view of the harms, given that people living with CHB can be asymptomatic for the majority of their life-long infection. Of less-appreciated importance are the psychosocial harms, which can continue throughout an affected person’s lifetime. Here we review the broad range of these impacts, which include fear and anxiety; financial loss and instability; stigma and discrimination; and rejection by society. Importantly, these directly affect patient diagnosis, management, and treatment. Further, we highlight the roles that the research community can play in taking these factors into account and mitigating them. In particular, the development of a cure for hepatitis B virus infection would alleviate many of the psychosocial impacts of CHB. We conclude that there should be a greater recognition of the full impacts associated with CHB to bring meaningful, effective, and deliverable results to the global community living with hepatitis B.

In hepatocellular carcinoma (HCC), somatic genome-wide DNA mutations are numerous, universal and heterogeneous. Some of these somatic mutations are drivers of the malignant process but the vast majority are passenger mutations. These passenger mutations can be deleterious to individual protein function but are tolerated by the cell or are offset by a survival advantage conferred by driver mutations. It is unknown if these somatic deleterious passenger mutations (DPMs) develop in the precancerous state of cirrhosis or if it is confined to HCC. Therefore, we studied four whole-exome sequencing datasets, including patients with non-cirrhotic liver (n = 12), cirrhosis without HCC (n = 6) and paired HCC with surrounding non-HCC liver (n = 74 paired samples), to identify DPMs. After filtering out putative germline mutations, we identified 187±22 DPMs per non-diseased tissue. DPMs number was associated with liver disease progressing to HCC, independent of the number of exonic mutations. Tumours contained significantly more DPMs compared to paired non-tumour tissue (258-293 per HCC exome). Cirrhosis- and HCC-associated DPMs do not occur predominantly in specific genes, chromosomes or biological pathways and the effect on tumour biology is presently unknown. Importantly, for the first time we have shown a significant increase in DPMs with HCC.

Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies.

The classical paradigm of liver injury asserts that hepatic stellate cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM) of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC.Non-diseased, fibrotic and cirrhotic livers were examined for MMP activity and markers of fibrosis in humans and mice. CD147 expression and MMP activity were co-localised by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147 in hepatocytes and in-vivo in mice with CCl4 induced liver injury using ãCD147 antibody intervention.In liver fibrosis in both human and mouse tissue MMP expression and activity (MMP-2, -9, -13 and -14) increased with progressive injury and localised to hepatocytes. Additionally, as expected, MMPs were abundantly expressed by activated HSC. Further, with progressive fibrosis there was expression of CD147, which localised to hepatocytes but not to HSC. Functionally significant in-vitro regulation of hepatocyte MMP production by CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and -9 expression/activity. Further, in-vivo α-CD147 antibody intervention decreased liver MMP-2, -9, -13, -14, TGF-β and α-SMA expression in CCl4 treated mice compared to controls.We have shown that hepatocytes produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo. Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be targeted by future anti-fibrogenic agents.

Abstract The disodium salt of 9,10‐anthraquinone‐2,7‐disulphonic acid (2,7‐AQDS) is an interesting platform for developing anthraquinone derivative negolytes for aqueous organic flow batteries. Recently, ammonium sulphate supporting electrolytes have been considered for improved stability and solubility. This work advances the 2,7‐AQDS/ferrocyanide flow battery with an ammonium sulphate supporting electrolyte (pH 5) by studying the suitability of six commercially available cation exchange membranes: E‐620, NR‐212, FS‐930, F‐1075‐PK, F‐1850 and N‐115. Cell cycling under galvanostatic regime plus potential hold was performed to determine coulombic efficiency, energy efficiency and accessible capacity for each membrane as well as capacity fade rate for three selected membranes under extended operation. Cell cycling under galvanostatic control only was carried out to observe transient membrane behavior alongside accessible capacity and apparent capacity fade rate. It was found that the capacity set by the limiting negolyte is consistent with 1.5 electrons per 2,7‐AQDS molecule and that energy efficiency shows a simple direct relationship to membrane thickness, with one exception. Meanwhile, four membranes displayed similar apparent capacity fade rates at this laboratory scale irrespective of their thickness, with capacity loss explained in terms of crossover. The best overall performance was attained by the thinnest membranes, E‐620 and NR‐212.

The glacier ice algae Ancylonema alaskanum and Ancylonema nordenskiöldii grow in harsh dynamic environments on bare ice surfaces. In these environments, they contribute to the continuous darkening of the ice surface, which in turn accelerates the ice melt. However, investigation into their adaptation and resilience in these environments is necessary in order to understand their robustness and potential for increasing the intensity of blooms. In this study, it was examined how variations in environmental parameters such as pH, salinity, light and temperature impacted the photophysiology of the glacier ice algae during a bloom in Greenland. Through in situ incubations and pulse-amplitude-modulation (PAM) fluorometric measurements, the photophysiological responses of algal cells were assessed. Results suggest that light intensity significantly influences glacier ice algae photophysiology, with cells exhibiting better performance (in terms of a higher theoretical maximum light coefficient and maximum quantum efficiency) under lower light intensity. Moreover, while light emerges as the primary driver of photophysiology, glacier ice algae demonstrate tolerance to a broad range of pH and temperatures four times higher than those experienced during Greenland’s summer.

The present study reports new records of the Collembola (Arthropoda: Hexapoda) from the Bula Hyrcanian forest located in Mazandaran province, north of Iran. The results show two genera Spatulosminthurus Betsch & Betsch-Pinot, 1984 (Sminthuridae) and Wankeliella Rusek, 1975 (Tullbergiidae) and five species including Anurophorus alpinus Potapov & Stebaeva, 1990 (Isotomidae), Pseudosinella cf. decipiens Denis, 1924 and P. immaculata (Lie Pettersen, 1896) (Entomobryidae), Superodontella tyverica Kaprus, 2009 (Odontellidae), and Wankeliella bescidica Smolis & Skarżyński, 2004 (Tullbergiidae) are new records for Collembola fauna of Iran.

Sweet potato (Ipomoea batatas L. Lam), the third most significant root and tuber crop globally, is crucial for improving livelihoods, health, and food security, particularly in sub-Saharan Africa. Despite its potential, sweet potato production in Ghana remains dominated by small-scale farmers, with yields often falling below the expected average of 2 tons per hectare. This study investigates the determinants and extent of adoption of Orange Flesh Sweet Potato (OFSP) varieties among smallholder farmers in the northeastern hills of Ghana. Utilizing cross-sectional data from 342 farmers across four districts in the Upper East and Northern regions, the Cragg double-hurdle model was used to analyze the factors influencing OFSP adoption. The results indicate that factors such as gender, family size, membership in Farmer-Based Organizations (FBOs), access to vines, training frequency, off-farm income, and farmers’ perceptions of early maturity and high yield potential significantly influence OFSP adoption. Furthermore, farm size, access to formal credit, market proximity, vine access, duration of OFSP consumption, regional differences, and yield levels were identified as key variables affecting the intensity of adoption. The study recommends that policymakers collaborate with banking and cooperative institutions to enhance access to vines and formal credit, thereby fostering higher adoption rates.

Modelling catalytic fixed bed reactors with a small tube-to-particle diameter ratio requires a detailed description of the interactions between fluid flow, intra-particle transport, and the chemical reaction(s) within the catalyst. Particle-resolved computational fluid dynamics (PRCFD) simulations are the most promising approach to predict the behaviour of these reactors accurately, since they take into account the local packed bed structure explicitly. In this work, a conjugated heat and mass transfer model for use in PRCFD simulations is presented in order to couple the fluid flow through the fixed bed with transport and reaction in the porous catalyst, while guaranteeing the no-slip boundary condition at the fluid–solid interface. For this purpose, the solutions of the solid and fluid domain are computed separately and are coupled by calculation and updating the boundary condition at the particle surface. Owing to the consideration of secondary gradients, the developed transfer model is also valid for unstructured calculation meshes containing non-orthogonal cells at the fluid–solid interface. Such meshes are often used to resolve complex geometries, such as a packed bed, in a computationally efficient manner. The coupling approach is validated using cases for which an analytical solution or literature correlations derived from experimental data are available. The simulation results of a short catalytic packed bed with rings catalysing the partial oxidation of n-butane to maleic anhydride exemplify the potential of PRCFD involving reactions to analyse the catalyst performance in great detail.

Background: Ovarian cancer (OC) patients have an increased risk for a mental health illness (MHI) after their cancer diagnosis, but limited research exists on whether this risk differs by race/ethnicity. Hence, we used SEER-Medicare data to evaluate racial/ethnic differences in MHI incidence among OC patients aged 65+. Methods: Non-Hispanic (NH) Black, NH White, and Hispanic women diagnosed with OC in 2008–2015 without a mental health history 12 months prior to their cancer diagnosis were identified from SEER-Medicare. Cox proportional hazards regression evaluated new MHI incidence in the first five years post diagnosis and the differences by race/ethnicity. Hazard ratios (HR) and 95% confidence intervals (CI) adjusted for demographic/clinical covariates and healthcare access (HCA) dimensions. Results: We identified 5441 OC patients, including 364 NH Black (6.7%), 4982 NH White (91.6%), and 95 Hispanic (1.7%) patients. About 41% of NH White, 33.3% of NH Black, and 37.2% of Hispanic OC patients were diagnosed with MHI during the follow-up period between 2008 and 2016. In the fully adjusted model, NH Black OC patients were less likely to be diagnosed with any MHI (aHR: 0.67, 95% CI: 0.54, 0.82), depression (aHR: 0.66, 95% CI: 0.51, 0.85), and anxiety disorder (aHR: 0.64, 95% CI: 0.49, 0.84), while Hispanic OC patients were less likely to be diagnosed with anxiety disorder (aHR: 0.56, 95% CI: 0.33, 0.95) compared to NH White OC patients. Discussion: NH Black OC patients are less likely to receive a clinical MHI diagnosis compared to NH White OC patients. Further studies on racial differences in MHI incidence after OC diagnosis in primary cohorts are needed to better estimate population-level prevalence less vulnerable to exposure misclassification and to account for patient-level factors impacting MHI.