Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice.

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

PICH, A protein that maintains genomic stability, can promote tumor growth.

Genomic instability is regardedas a hallmark of cancer cells. It can be presented in many ways, among which chromosome instability has received attention. Ultrafine anaphase bridges are a typeof chromatin bridges, the untimely resolution of which can also lead to chromosome instability. PICH can play a role in maintaining chromosome stability by regulating chromosome morphologyand resolving ultrafine anaphase bridges. Recently, PICH has been found to be overexpressed in various cancers. Overexpression of PICH is related to the proliferation of tumors and poor prognosis. In this article, we consider that PICH can maintain genome stability by regulating appropriate chromosome structure, ensuring proper chromosome segregation, and facilitating replication fork reversal. We summarize how PICH regulates chromosome stability, how PICH resolves Ultrafine anaphase bridges with other proteins, and how PICH promotes tumor progression.

Cryo-EM structure of the human subcortical maternal complex and the associated discovery of infertility-associated variants.

The functionally conserved subcortical maternal complex (SCMC) is essential for early embryonic development in mammals. Reproductive disorders caused by pathogenic variants in NLRP5, TLE6 and OOEP, three core components of the SCMC, have attracted much attention over the past several years. Evaluating the pathogenicity of a missense variant in the SCMC is limited by the lack of information on its structure, although we recently solved the structure of the mouse SCMC and proposed that reproductive disorders caused by pathogenic variants are related to the destabilization of the SCMC core complex. Here we report the cryogenic electron microscopy structure of the human SCMC and uncover that the pyrin domain of NLRP5 is essential for the stability of SCMC. By combining prediction of SCMC stability and in vitro reconstitution, we provide a method for identifying deleterious variants, and we successfully identify a new pathogenic variant of TLE6 (p.A396T). Thus, on the basis of the structure of the human SCMC, we offer a strategy for the diagnosis of reproductive disorders and the discovery of new infertility-associated variants.

Assessment of Fungal and Contamination of Ochratoxin A and Patulin in Foods Susceptible to Contamination in the Yangzhou Market, China.

The conducive conditions of warm and humid climates can facilitate mold proliferation and subsequent mycotoxin production during food processing and distribution, thereby posing a potential risk to consumer health. However, there exists a significant lack of research regarding the diversity of molds and the presence of ochratoxin A (OTA) and patulin (PAT) in food products available in the Yangzhou market. This study was conducted to assess OTA contamination levels and fungal presence in 57 cereal-based food samples, as well as PAT contamination levels and fungal presence in 50 types of foods, including apples, hawthorn berries, pears, and their derivatives. Ochratoxin A (OTA) was detected in 17 out of 57 cereal-based food samples, with concentrations ranging from 0.93 to 32.69 µg/kg. The contamination rate was determined to be 31.48%, and no samples exceeded the established regulatory limits. Furthermore, seven apple products were identified as contaminated with patulin (PAT), exhibiting concentrations between 26.85 and 192.78 µg/kg. Additionally, three food samples derived from hawthorn showed PAT contamination levels ranging from 29.83 to 88.56 µg/kg. Through purification on potato dextrose agar (PDA) medium, observation of colony morphology, and analysis of internal transcribed spacer (ITS) sequences, a total of 35 fungal strains belonging to 13 genera were identified in cereal-based foods. The predominant genera in cereals included Talaromyces, Fusarium, Aspergillus, and Penicillium. Additionally, twelve fungal strains from five genera (Penicillium, Cladosporium, Aureobasidium, Curvularia, and Alternaria) were isolated and identified in fruits and their derivatives. The findings indicate that OTA and PAT toxins are one of the important risk factors that threaten consumer health. Furthermore, the contamination of some other toxigenic strains is also a matter of substantial concern, with potential implications for consumer health.

The subcortical maternal complex modulates the cell cycle during early mammalian embryogenesis via 14-3-3.

The subcortical maternal complex (SCMC) is essential for safeguarding female fertility in mammals. Assembled in oocytes, the SCMC maintains the cleavage of early embryos, but the underlying mechanism remains unclear. Here, we report that 14-3-3, a multifunctional protein, is a component of the SCMC. By resolving the structure of the 14-3-3-containing SCMC, we discover that phosphorylation of TLE6 contributes to the recruitment of 14-3-3. Mechanistically, during maternal-to-embryo transition, the SCMC stabilizes 14-3-3 protein and contributes to the proper control of CDC25B, thus ensuring the activation of the maturation-promoting factor and mitotic entry in mouse zygotes. Notably, the SCMC establishes a conserved molecular link with 14-3-3 and CDC25B in human oocytes/embryos. This study discloses the molecular mechanism through which the SCMC regulates the cell cycle in early embryos and elucidates the function of the SCMC in mammalian early embryogenesis.

Amino-Alkyl Group Dual-Functional Modification Synergistically Regulated Lipase-Carrier Interactions and Enhanced Phytosterol Ester Synthesis Efficiency.

Precisely controlling enzyme conformation to enhance catalytic performance is a highly sought-after yet challenging goal in the immobilization of biocatalysts. Excessively strong enzyme-carrier interactions can restrict enzyme dynamics and reduce catalytic efficiency, while excessively weak interactions may lead to enzyme leakage, thereby reducing reusability. In this study, we developed a novel strategy to finely regulate the interaction between the carrier and the enzyme through the adjustment of the ratio of amino and octadecyl functional groups. The expressed activity of the novel immobilized lipase, CRL@AOMR, was 1.32- and 2.34-fold higher than that of the monofunctional macroporous resin. Moreover, the synthesis of various phytosterol esters in solvent-free systems was conducted as a model reaction to investigate the utilization of CRL@AOMR in different reactions. Under optimized conditions, an impressive yield of 96.1% for phytosterol oleate was achieved and a yield of 76.2% was maintained even after six cycles of utilization (288 h). This study demonstrates the potential feasibility of developing immobilization strategies via dual modification of amino and alkyl groups, which is a potential general strategy for other enzymes with surface lysine.

Lipase Substrate Anchoring Dynamics Guided the Rational Design of Novel Deep Eutectic Solvents for Glucose Ester Synthesis.

Glucose esters, heralded for their emulsifying and solubilizing properties, have found increasing application in food, pharmaceutical, and cosmetic sectors. However, the environmental impact of chemical synthesis and the problem of enzyme inactivation in enzymatic synthesis have hindered their application. To this end, deep eutectic solvents (DESs) with stabilized enzyme activity and better solubility properties are considered a promising solution. In the study, 12 kinds of hydrophilic DESs and 22 kinds of hydrophobic DESs were screened, and we examined their efficiency in the synthesis of glucose esters. The results indicated that d,l-menthol-based DESs have excellent performance, with the highest yield of 92.85%. The molecular dynamics simulations suggested that it can be attributed to DESs changing the size of substrate binding pocket, which in turn affects the substrate anchoring ability and the catalytic efficiency of lipase. To further evaluate the effects of the solvent on the substrate anchoring ability of enzymes, a novel strategy, namely, substrate anchoring index, which is based on the stability of the tetrahedral intermediate, was proposed and used for the designing of more efficient DESs. Fortunately, novel DESs based on cyclohexanone (menthol analogues) were successfully developed with a yield of 98.85%.

Citric acid modulated strong magnetic CoFe-LDH/CoFe2O4 coupled dielectric barrier discharge plasma for efficient levofloxacin degradation: Enhanced internal electric field and accelerated electron migration.

A novel citric acid (CA) modulation strategy was developed to prepare strong magnetic CoFe-LDH/CoFe2O4-C composites, which were combined with dielectric barrier discharge (DBD) to effectively degrade levofloxacin (LEV) in wastewater. Kelvin probe force microscopy (KPFM) test showed that CA modulation facilitated a more powerful internal electric field to drive rapid charge migration. The addition of CoFe-LDH/CoFe2O4-C increased LEV degradation from 78.2 % to 98.6 % and reduced energy efficiency from 24.77 to 8.93 kWh m-3. Quenching experiments and electron paramagnetic resonance (EPR) spectra showed the CoFe-LDH/CoFe2O4-C could take full advantage of the active substances originating from DBD plasma and highlighted the role of 1O2 and ·O2-. Density functional theory (DFT) calculation revealed that the heterojunction can not only drive faster electron migration but also reduce the energy barrier of O3 decomposition. Possible degradation pathways for LEV were proposed. This study opened up a new avenue for the synthesis of applicable catalysts for plasma systems in water treatment areas.

Experimental studies on the cooling and heating performance of a highly emissive coating.

In this study, the cooling effect below ambient air temperature, heat dissipation properties and heating energy efficacy of a superomniphobic self-cleaning (SSC) highly emissive (HE) coating were systematically investigated. Except at midday, the SSC-HE coating with an extremely high solar reflectance of 0.985 showed a better cooling effect than a 10-cm-thick polyurethane insulation layer. The coating substantially reduced the interior air temperature of a well-insulated system by as much as 6.9 °C. The SSC-HE coating enabled the roof surface and room temperatures of the brick bungalow to be 3.4 and 10.2 °C below the ambient air temperature, respectively. Compared with the sunshade and spray water, the SSC-HE coating exhibited better cooling effect. The SSC topcoat allowed the battery cabinet of an HE-coated distributed telecommunication base station to remain its original sub-ambient cooling effect for a long time. Regardless of the location of the HE-coated metal facility, the ultrahigh emissivity of the coating enabled it to exhibit excellent heat dissipation performance during both day and night, even under adiabatic conditions. Additionally, under identical room temperature settings, the HE-coated electric oil heater not only showed faster heating but also had heating energy efficiency of 5.9 % and 4.4 % relative to heaters coated with aluminium- and black paints, respectively. Under identical heating power consumption levels, compared to black paint-coated heater, the HE-coated heater endowed the surrounding environment with a higher equilibrium air temperature, improving the thermal comfort of the indoor environment.

A safer cell-based yellow fever live attenuated vaccine protects mice against YFV infection.

The live attenuated yellow fever vaccine (YF17D) has caused controversial safety issues in history with low-yield problems, which has led to a large population being unable to be vaccinated and vaccine shortage in facing recent outbreaks. Here, we report a safer live attenuated vaccine candidate, YF17D-Δ77, which contains 77 nucleotides deletion in the 3' untranslated region (3' UTR) of the YF17D genome. YF17D-Δ77 exhibited no neurotropism and decreased viscerotropism and caused significantly lower lethality in mice compared to YF17D. Mechanistically, the deletion enhanced the sensitivity of the virus to type I and type II interferon responses, which hindered viral replication. Encouragingly, YF17D-Δ77 provided comparable immune protection in mice as did YF17D. Even 10 PFU of YF17D-Δ77 completely protected mice against YFV-Asibi challenge. In addition, the Δ77 mutation showed excellent stability after successive passages in Vero cells. Collectively, the data suggest that further development of YF17D-Δ77 as vaccine candidate is warranted.

Association of glycerolipid metabolism with gut microbiota disturbances in a hamster model of high-fat diet-induced hyperlipidemia.

Background: High-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear. Methods: Hamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids. Results: The gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices. Conclusion: The findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.

Determining the evaporation and evolution of surface water in a large catchment using isotopes and multiple models.

The evolution and formation mechanisms of chemical components in surface water can reflect changes in the geological background of a basin and the extent of human interference. The Yangtze River basin is the largest water source area in China, yet its main ion sources and formation mechanisms are not fully understood. This study uses a combination of hydrochemistry, stable isotopes (δ18O, δD), the Craig-Gordon model, and the APCS-MLR model to quantitatively assess the water source replenishment and evaporation intensity of surface water in the Yangtze River. The study reveals the primary ion sources and controlling factors of surface water in the Yangtze River. The results show that the hydrochemical type in the upstream is mainly HCO3--Ca2+ and Na+-K+, while in the midstream and downstream it is primarily HCO3--Ca2+ and SO42--Ca2+. The evolution of hydrochemical types is mainly controlled by rock weathering and human inputs. The surface water sources in the Yangtze River are directly replenished by precipitation, with the evaporation ratio in the upstream (0.66) being higher than in the midstream (0.63) and downstream (0.47). The lc-excess in the upstream (-0.32 ‰) is lower than in the midstream (1.21 ‰) and downstream (-0.27 ‰), indicating more intense evaporation in the upstream. The hydrochemical composition of the Yangtze River surface water mainly comes from geological factors (80.5 %), industrial factors (11.1 %), agricultural factors (6.4 %), and unknown factors (2.0 %). This study enhances the understanding of the chemical composition, water source replenishment, ion sources, and evolution mechanisms of the Yangtze River surface water, providing a basis for maintaining water quality and sustainable development in the Yangtze River basin.

High-Temperature Superconductivity in Perovskite Hydride Below 10 GPa.

Hydrogen and hydride materials have long been considered promising materials for high-temperature superconductivity. However, the extreme pressures required for the metallization of hydrogen-based superconductors limit their applications. Here, a series of high-temperature perovskite hydrides is designed that can be stable within 10 GPa. The research covered 182 ternary systems and ultimately determined that eight new compounds are stable within 20 GPa, of which five exhibited superconducting transition temperatures exceeding 120 K within 10 GPa, including KGaH3 (146 K at 10 GPa), RbInH3 (130 K at 6 GPa), CsInH3 (153 K at 9 GPa), RbTlH3 (170 K at 4 GPa) and CsTlH3 (163 K at 7 GPa). Excitingly, KGaH3 and RbGaH3 are thermodynamically stable at 50 GPa. Among these perovskite hydrides, alkali metals are responsible for providing a fixed amount of charge and supporting alloy framework composed of hydrogen and IIIA group elements to maintain stable crystal structure, while the cubic hydrogen alloy framework formed by IIIA group elements and hydrogen is crucial for high-temperature superconductivity. This work will inspire further experimental exploration and take an important step in the exploration of low-pressure stable high-temperature superconductors.

Effect of electrical stimulation on the fusion rate after spinal surgery: a systematic review and meta-analysis.

Electrical stimulation is an important adjuvant therapy for spinal surgery, but whether receiving electrical stimulation can improve the fusion rate after spinal surgery is still controversial. The purpose of this study was to analyse and evaluate the effect of electrical stimulation on the fusion rate after spinal surgery. We systematically searched for related articles published in the PubMed, Embase and Cochrane Library databases on or before September 30, 2023. The odds ratio (OR) with 95% confidence interval (CI) and the fusion rates of the experimental group and the control group were calculated by a random-effects meta-analysis model. The analysis showed that receiving electrical stimulation significantly increased the probability of successful spinal fusion (OR 2.66 [95% CI 1.79-3.97]), and the average fusion rate of the electrical stimulation group (86.8%) was significantly greater than that of the control group (73.7%). The fusion rate in the direct current (DC) stimulation group was 2.33 times greater than that in the control group (OR 2.33 [95% CI 1.37-3.96]), and that in the pulsed electromagnetic field (PEMF) group was 2.60 times greater than that in the control group (OR 2.60 [95% CI 1.29-5.27]). Similarly, the fusion rate in the capacitive coupling (CC) electrical stimulation group was 3.44 times greater than that in the control group (OR 3.44 [95% CI 1.75-6.75]), indicating that regardless of the type of electrical stimulation, the fusion rate after spinal surgery improved to a certain extent. Electrical stimulation as an adjuvant therapy seems to improve the fusion rate after spinal surgery to a certain extent, but the specific effectiveness of this therapy needs to be further studied.

Novel therapeutic approach for psoriasis: Upregulating FcRn to inhibit ferroptosis and alleviate lesional skin.

Psoriasis, a chronic inflammatory skin disease, is characterized by complex immune dysregulation and oxidative stress responses. The neonatal Fc receptor (FcRn) plays a crucial role in the development of autoimmune diseases. Analysis of clinical psoriasis samples demonstrated a negative correlation between FcRn expression in skin lesions and disease severity. However, the role of FcRn in this process remains unclear. This study aimed to investigate the involvement of FcRn in the pathogenesis and progression of psoriasis. In an imiquimod (IMQ)-induced psoriasis-like mouse model, FcRn expression was significantly decreased in the lesional skin, and transcriptome sequencing of the skin revealed activation of the ferroptosis pathway in psoriasis. This led to the hypothesis that FcRn could potentially regulate ferroptosis via the signal transducer and activating transcription factor 3 (STAT3)/solute carrier family 7 member 11 (SLC7A11) axis. Further experiments showed exacerbated psoriasis-like lesional skin and ferroptosis in FcRn-knockout mice, whereas intervention with the ferroptosis inhibitor Fer-1 or STAT3 inhibitor Stattic alleviated these symptoms. Critical binding sites for the transcription factor STAT3 were identified in the SLC7A11 promoter region at positions -1185 and -564 using the luciferase reporter assays and chromatin immunoprecipitation. The administration of 1,4-naphthoquinone (NQ), an FcRn agonist, effectively alleviated psoriasis-like skin lesions by inhibiting ferroptosis. This study highlights the molecular mechanisms of action of FcRn in psoriasis and provides an experimental basis for the development of novel therapeutic strategies targeting FcRn.

Characterisation and evolution of the PRC2 complex and its functional analysis under various stress conditions in rice.

The polycomb repressive complex 2 (PRC2) is a chromatin-associated methyltransferase responsible for catalysing the trimethylation of H3K27, an inhibitory chromatin marker associated with gene silencing. This enzymatic activity is crucial for normal organismal development and the maintenance of gene expression patterns that preserve cellular identity, subsequently influencing plant growth and abiotic stress responses. Therefore, in this study, we investigated the evolutionary characteristics and functional roles of PRC2 in plants. We identified 209 PRC2 genes, including E(z), Su(z), Esc, and Nurf55 families, using 18 representative plant species and revealed that recent gene replication events have led to an expansion in the Nurf55 family, resulting in a greater number of members compared to the E(z), Su(z), and Esc families. Furthermore, protein structure and motif composition analyses highlighted the potential functional site regions within PRC2 members. In addition, we selected rice, a representative monocotyledonous plant, as the model species for food crops. Our findings revealed that SDG711, SDG718, and MSI1-5 genes were induced by abscisic acid (ABA) and/or methyl jasmonate (MeJA) hormones, suggesting that these genes play an important role in abiotic stress and disease resistance. Further experiments involving rice blast fungus treatments confirmed that the expression of SDG711 and MSI1-5 was induced by Magnaporthe oryzae strain GUY11. Multiple protein interaction assays revealed that the M. oryzae effector AvrPiz-t interacts with PRC2 core member SDG711 to increase H3K27me3 levels. Notably, inhibition of PRC2 or mutation of SDG711 enhanced rice resistance to M. oryzae. Collectively, these results provide new insights into PRC2 evolution in plants and its significant functions in rice.

Advances in understanding the roles of plant HAT and HDAC in non-histone protein acetylation and deacetylation.

MAIN CONCLUSION: This review focuses on HATs and HDACs that modify non-histone proteins, summarizes functional mechanisms of non-histone acetylation as well as the roles of HATs and HDACs in rice and Arabidopsis. The growth and development of plants, as well as their responses to biotic and abiotic stresses, are governed by intricate gene and protein regulatory networks, in which epigenetic modifying enzymes play a crucial role. Histone lysine acetylation levels, modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), are well-studied in the realm of transcriptional regulation. However, the advent of advanced proteomics has unveiled that non-histone proteins also undergo acetylation, with its underlying mechanisms now being clarified. Indeed, non-histone acetylation influences protein functionality through diverse pathways, such as modulating protein stability, adjusting enzymatic activity, steering subcellular localization, influencing interactions with other post-translational modifications, and managing protein-protein and protein-DNA interactions. This review delves into the recent insights into the functional mechanisms of non-histone acetylation in plants. We also provide a summary of the roles of HATs and HDACs in rice and Arabidopsis, and explore their potential involvement in the regulation of non-histone proteins.

Preparation of High-Performance Transparent Al2O3 Dielectric Films via Self-Exothermic Reaction Based on Solution Method and Applications.

As the competition intensifies in enhancing the integration and performance of integrated circuits, in accordance with the famous Moore's Law, higher performance and smaller size requirements are imposed on the dielectric layers in electronic devices. Compared to vacuum methods, the production cost of preparing dielectric layers via solution methods is lower, and the preparation cycle is shorter. This paper utilizes a low-temperature self-exothermic reaction based on the solution method to prepare high-performance Al2O3 dielectric thin films that are compatible with flexible substrates. In this paper, we first established two non-self-exothermic systems: one with pure aluminum nitrate and one with pure aluminum acetylacetonate. Additionally, we set up one self-exothermic system where aluminum nitrate and aluminum acetylacetonate were mixed in a 1:1 ratio. Tests revealed that the leakage current density and dielectric constant of the self-exothermic system devices were significantly optimized compared to the two non-self-exothermic system devices, indicating that the self-exothermic reaction can effectively improve the quality of the dielectric film. This paper further established two self-exothermic systems with aluminum nitrate and aluminum acetylacetonate mixed in 2:1 and 1:2 ratios, respectively, for comparison. The results indicate that as the proportion of aluminum nitrate increases, the overall dielectric performance of the devices improves. The best overall performance occurs when aluminum nitrate and aluminum acetylacetonate are mixed in a ratio of 2:1: The film surface is smooth without cracks; the surface roughness is 0.747 ± 0.045 nm; the visible light transmittance reaches up to 98%; on the basis of this film, MIM devices were fabricated, with tested leakage current density as low as 1.08 × 10-8 A/cm2 @1 MV and a relative dielectric constant as high as 8.61 ± 0.06, demonstrating excellent electrical performance.

Essential role of postoperative follow-up in the management of clear cell sarcoma.

Clear cell sarcoma (CCS) is a rare melanocytic soft tissue sarcoma known for its propensity to metastasize to the lymph nodes and typically has an unfavorable prognosis. Currently, surgical resection is the primary treatment for localized CCS, while radiotherapy and chemotherapy are preferred for metastatic cases. The roles of adjuvant chemotherapy, radiotherapy, and lymph node dissection are controversial. Although immunotherapy has emerged as a promising avenue in CCS treatment research, there are no established clinical standards for postoperative follow-up. This editorial discusses a recent article by Liu et al, with a focus on current diagnostic modalities, treatment approaches, and the challenging prognosis associated with CCS. Our aim is to underscore the importance of long-term patient follow-up in CCS management.

Androgen receptor-induced molecules and androgen contribute synergistically to male-predominance of hepatocellular carcinoma.

We aimed to clarify the mechanisms of male predominance of hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC). Androgen receptor (AR) facilitates HCC cell growth, which was augmented by androgen (dihydrotestosterone [DHT]) and attenuated by anti-androgen (flutamide). AR upregulated the expressions of BIRC7, IGFBP3, and NTSR1 via increasing their promoter activities, which were enhanced by DHT. Wild-type HBV X (WT-HBx) upregulated AR transcription, which depended on DHT; whereas the effect of C-terminal carboxy-truncated HBx on AR transcription was independent of DHT. BIRC7, IGFBP3, and NTSR1 increased the growth of HCC. High expression of BIRC7 and NTSR1 contributes to poor HCC outcomes in male patients, but not in female patients. Downregulation of NTSR1 inhibits tumor growth in male mice rather than in female mice. Conclusively, AR promotes HCC at least partially via upregulating BIRC7, IGFBP3, and NTSR1, which is enhanced by androgen and HBx. BIRC7 and NTSR1 facilitate HCC progression in a male-predominant manner.