Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.

Hepatic progenitor cells (HPCs) have a bidirectional potential to differentiate into hepatocytes and bile duct epithelial cells and constitute a second barrier to liver regeneration in the adult liver. They are usually located in the Hering duct in the portal vein region where various cells, extracellular matrix, cytokines, and communication signals together constitute the niche of HPCs in homeostasis to maintain cellular plasticity. In various types of liver injury, different cellular signaling streams crosstalk with each other and point to the inducible transcription factor set, including FoxA1/2/3, YB-1, Foxl1, Sox9, HNF4α, HNF1α, and HNF1ß. These transcription factors exert different functions by binding to specific target genes, and their products often interact with each other, with diverse cascades of regulation in different molecular events that are essential for homeostatic regulation, self-renewal, proliferation, and selective differentiation of HPCs. Furthermore, the tumor predisposition of adult HPCs is found to be significantly increased under transcriptional factor dysregulation in transcriptional analysis, and the altered initial commitment of the differentiation pathway of HPCs may be one of the sources of intrahepatic tumors. Related transcription factors such as HNF4α and HNF1 are expected to be future targets for tumor treatment.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Human umbilical cord mesenchymal stem cells alleviate fatty liver ischemia-reperfusion injury by activating autophagy through upregulation of IFNγ.

Liver ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation, and extended criteria donors (e.g., steatosis donor livers) are considered to be more sensitive to ischemia-reperfusion injury in liver transplantation. Currently, the application of human umbilical cord mesenchymal stem cells (hMSCs) has great promise in the treatment of various injuries in the liver. This study aimed to investigate the therapeutic role and mechanism of hMSCs in fatty liver IRI. After more than 8 weeks of high-fat chow feeding, we constructed a fatty liver mouse model and established ischemic injury of about 70% of the liver. Six hours after IRI, liver injury was significantly alleviated in hMSCs-treated mice, and the expression levels of liver enzyme, inflammatory factor TNF-α, and apoptotic proteins were significantly lower than those of the control group, which were also significant in pathological sections. Transcriptomics analysis showed that IFNγ was significantly upregulated in the hMSCs group. Mechanistically, IFNγ, which activates the MAPK pathway, is a potent agonist that promotes the occurrence of autophagy in hepatocytes to exert a protective function, which was confirmed by in vitro experiments. In summary, hMSCs treatment could slow down IRI in fatty liver by activating autophagy through upregulation of IFNγ, and this effect was partly direct.

Resection of unresectable hepatocellular carcinoma after conversion therapy with apatinib and camrelizumab: a case report and literature review.

Hepatocellular carcinoma is a rather common malignant tumor. Most patients with hepatocellular carcinoma receive their diagnosis at an advanced stage, at which surgical resection is no longer appropriate. A growing body of research has demonstrated the value of convention therapy for patients with intermediate-stage hepatocellular carcinoma, while specific application protocols and treatment guidelines are not well developed. Emerging clinical researches suggest that a tyrosine kinase inhibitor in combination with an immune checkpoint inhibitor is a reasonable strategy for unresectable hepatocellular carcinoma. However, there are relatively few reports on the efficacy of apatinib and camrelizumab in the treatment of hepatocellular carcinoma. We were able to successfully remove one patient's hepatocellular carcinoma after 8 cycles of conversion therapy with apatinib (250 mg orally every day) and camrelizumab (200 mg intravenously every 2 weeks). The patient continued to receive the same dose of 16 cycles of apatinib and camrelizumab after hepatectomy. By the time of this study, the patient has completed 18 months of follow-up, and no tumor recurrence or metastasis was found in tumor markers and imaging examinations. Apatinib in combination with camrelizumab is an effective therapy for the treatment of advanced hepatocellular carcinoma, and surgical resection after this conversion therapy may provide patients with long-term oncological benefits. However, this requires more samples to validate the conclusion.

Current Understanding of Marginal Grafts in Liver Transplantation.

End-stage liver disease (ESLD), stemming from a spectrum of chronic liver pathologies including chronic liver failure, acute cirrhosis decompensation and hepatocellular carcinoma, imposes a significant global healthcare burden. Liver transplantation (LT) remains the only treatment for ESLD. However, the escalating mortality on transplant waitlists has prompted the utilization of marginal liver grafts in LT procedures. These grafts primarily encompass elderly livers, steatotic livers, livers from donation after circulatory death, split livers and those infected with the hepatitis virus. While the expansion of the donor pool offers promise, it also introduces concomitant risks. These encompass graft failure, biliary and cardiovascular complications, the recurrence of liver disease and reduced patient and graft survival. Consequently, various established strategies, ranging from improved donor-recipient matching to surgical interventions, have emerged to mitigate these risks. This article undertakes a comprehensive assessment of the current landscape, evaluating the viability of diverse marginal liver grafts. Additionally, it synthesizes approaches aimed at enhancing the quality of such marginal liver grafts. The overarching objective is to augment the donor pool and ameliorate the risk factors associated with the shortage of liver grafts.

Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

Heisenberg-limited spin squeezing in a hybrid system with silicon-vacancy centers.

In this paper, we investigate the spin squeezing in a hybrid quantum system consisting of a Silicon-Vacancy (SiV) center ensemble coupled to a diamond acoustic waveguide via the strain interaction. Two sets of non-overlapping driving fields, each contains two time-dependent microwave fields, are applied to this hybrid system. By modulating these fields, the one-axis twist (OAT) interaction and two-axis two-spin (TATS) interaction can be independently realized. In the latter case the squeezing parameter scales to spin number as ξ R2∼1.61N -0.64 with the consideration of dissipation, which is very close to the Heisenberg limit. Furthermore, this hybrid system allows for the study of spin squeezing generated by the simultaneous presence of OAT and TATS interactions, which reveals sensitivity to the parity of the number of spins Ntot, whether it is even or odd. Our scheme enriches the approach for generating Heisenberg-limited spin squeezing in spin-phonon hybrid systems and offers the possibility for future applications in quantum information processing.

Quantum Phase Transitions in Optomechanical Systems.

In this Letter, we investigate the ground state properties of an optomechanical system consisting of a coupled cavity and mechanical modes. An exact solution is given when the ratio η between the cavity and mechanical frequencies tends to infinity. This solution reveals a coherent photon occupation in the ground state by breaking continuous or discrete symmetries, exhibiting an equilibrium quantum phase transition (QPT). In the U(1)-broken phase, an unstable Goldstone mode can be excited. In the model featuring Z_{2} symmetry, we discover the mutually (in the finite η) or unidirectionally (in η→∞) dependent relation between the squeezed vacuum of the cavity and mechanical modes. In particular, when the cavity is driven by a squeezed field along the required squeezing parameter, it enables modifying the region of Z_{2}-broken phase and significantly reducing the coupling strength to reach QPTs. Furthermore, by coupling atoms to the cavity mode, the hybrid system can undergo a QPT at a hybrid critical point, which is cooperatively determined by the optomechanical and light-atom systems. These results suggest that this optomechanical system complements other phase transition models for exploring novel critical phenomena.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

BACKGROUND: Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS: From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS: Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05). CONCLUSION: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

Animal models of hepatitis E infection: Advances and challenges.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. Although most of HEV infections are asymptomatic, some patients will develop the symptoms, especially pregnant women, the elderly, and patients with preexisting liver diseases, who often experience anorexia, nausea, vomiting, malaise, abdominal pain, and jaundice. HEV infection may become chronic in immunosuppressed individuals. In addition, HEV infection can also cause several extrahepatic manifestations. HEV exists in a wide range of hosts in nature and can be transmitted across species. Hence, animals susceptible to HEV can be used as models. The establishment of animal models is of great significance for studying HEV transmission, clinical symptoms, extrahepatic manifestations, and therapeutic strategies, which will help us understand the pathogenesis, prevention, and treatment of hepatitis E. This review summarized the animal models of HEV, including pigs, monkeys, rabbits, mice, rats, and other animals. For each animal species, we provided a concise summary of the HEV genotypes that they can be infected with, the cross-species transmission pathways, as well as their role in studying extrahepatic manifestations, prevention, and treatment of HEV infection. The advantages and disadvantages of these animal models were also emphasized. This review offers new perspectives to enhance the current understanding of the research landscape surrounding HEV animal models.

Harvesting Inertial Energy and Powering Wearable Devices: A Review.

Amidst the swift progression of microelectronics and Internet of Things technology, wearable devices are gradually gaining ground in the domains of human health monitoring. Recently, human bioenergy harvesting has emerged as a plausible alternative to batteries. This paper delves into harvesting human inertial energy that stimulates inertial masses through human motion and then transmutes the motion of the inertial masses into electrical energy. The inertial energy harvester is better suited for low-frequency and irregular human motion. This review first identifies the sources of human motion excitation that are compatible with inertial energy harvesters and then provides a summary of the operating principles and the comparisons of the commonly used energy conversion mechanisms, including electromagnetic, piezoelectric, and triboelectric transducers. The review thoroughly summarizes the latest advancements in human inertial energy-harvesting technology that are categorized and grouped based on their excitation sources and mechanical modulation methods. In addition, the review outlines the applications of inertial energy harvesters in powering wearable devices, medical health monitoring, and as mobile power sources. Finally, the challenges faced by inertial energy-harvesting technologies are discussed, and the review provides a perspective on the potential developments in the field.

Exosomes and their derivatives as biomarkers and therapeutic delivery agents for cardiovascular diseases: Situations and challenges.

Microvesicles known as exosomes have a diameter of 40 to 160 nm and are derived from small endosomal membranes. Exosomes have attracted increasing attention over the past ten years in part because they are functional vehicles that can deliver a variety of lipids, proteins, and nucleic acids to the target cells they encounter. Because of this function, exosomes may be used for the diagnosis, prognosis and treatment of many diseases. All throughout the world, cardiovascular diseases (CVDs) continue to be a significant cause of death. Because exosomes are mediators of communication between cells, which contribute to many physiological and pathological aspects, they may aid in improving CVD therapies as biomarkers for diagnosing and predicting CVDs. Many studies demonstrated that exosomes are associated with CVDs, such as coronary artery disease, heart failure, cardiomyopathy and atrial fibrillation. Exosomes participate in the progression or inhibition of these diseases mainly through the contents they deliver. However, the application of exosomes in diferent CVDs is not very mature. So further research is needed in this field.

Design of Recyclable Carboxylic Metal-Organic Framework/Chitosan Aerogels for Oil Bleaching.

Novel hierarchical metal-organic framework/chitosan aerogel composites were developed for oil bleaching. UiO-66-COOH-type metal organic frameworks (Zr-MOFs) were synthesized and integrated onto a chitosan matrix with different contents and named MOF-aerogel-1 and MOF-aerogel-2. Due to the compatibility of chitosan, the carboxylic zirconium MOF-aerogels not only maintained the inherent chemical accessibility of UiO-66-COOH, but the unique crystallization and structural characteristics of these MOF nanoparticles were also preserved. Through 3-dimensional reconstructed images, aggregation of the UiO-66-COOH particles was observed in MOF-aerogel-1, while the MOF was homogeneously distributed on the surface of the chitosan lamellae in MOF-aerogel-2. All aerogels, with or without immobilized MOF nanoparticles, were capable of removing carotenoids during oil bleaching. MOF-aerogel-2 showed the most satisfying removal proportions of 26.6%, 36.5%, and 47.2% at 50 °C, 75 °C, and 100 °C, respectively, and its performance was very similar to that of commercial activated clay. The reuse performance of MOF-aerogel-2 was tested, and the results showed its exceptional sustainability for carotenoid removal. These findings suggested the effectiveness of the MOFaerogel for potential utilization in oil bleaching treatments.

Spatial distribution pattern and correlation of dominant species in the arbor layer at a 25 hm2 forest plot in Lushan Mountain, China.

To explore the spatial pattern of zonal tree species in the subtropical subalpine mountain area on Lushan Mountain, a 25 hm2 forest plot was established in Yangtianping area of Lushan Mountain following the technical specification of CTFS in 2021. We classified these species into evergreen conifer species, deciduous broad-leaved species and evergreen broad-leaved species based on their leaf shape and deciduous or not to analyze the spatial pattern of dominant species of different types by spatial point pattern method. The results showed that Pinus taiwanensis, Cornus kousa subsp. chinensis, Platycarya strobilacea, Castanea henryi, Quercus serrata, Cornus controversa, Eurya muricata, Litsea elongata, and Eurya hebeclados were dominant species. Among these species, P. taiwanensis was the constructive one. The spatial pattern of dominant species was clustered at a certain scale, and gradually became to randomly distribution with the increases of scales. Evergreen conifer species was independent with deci-duous broad-leaved species and evergreen broad-leaved species at small scales, but was negatively correlated with them at large scales. Deciduous broad-leaved species and evergreen broad-leaved species were obviously negatively correlated with each other. Deciduous broad-leaved species were positively correlated or independent with each other at small scales, but were negatively correlated with each other at large scales. Evergreen broad-leaved species were positively correlated at small scales, independent at medium scales, and negatively correlated with each other at large scales.

Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.

Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.