Hepatocytic ballooning is a key histological feature in the diagnosis of non‐alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems ...for diagnosing and staging non‐alcoholic fatty liver disease (NAFLD) namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in ‘real life’ situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter‐observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory‐Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.
Carbonate reservoirs worldwide are complex in structure, diverse in form, and highly heterogeneous. Based on these characteristics, the reservoir stimulation technologies and fluid flow ...characteristics of carbonate reservoirs are briefly described in this study. The development methods and EOR technologies of carbonate reservoirs are systematically summarized, the relevant mechanisms are analyzed, and the application status of oil fields is catalogued. The challenges in the development of carbonate reservoirs are discussed, and future research directions are explored. In the current development processes of carbonate reservoirs, water flooding and gas flooding remain the primary means but are often prone to channeling problems. Chemical flooding is an effective method of tertiary oil recovery, but the harsh formation conditions require high-performance chemical agents. The application of emerging technologies can enhance the oil recovery efficiency and environmental friendliness to a certain extent, which is welcome in hard-to-recover areas such as heavy oil reservoirs, but the economic cost is often high. In future research on EOR technologies, flow field control and flow channel plugging will be the potential directions of traditional development methods, and the application of nanoparticles will revolutionize the chemical EOR methods. On the basis of diversified reservoir stimulation, combined with a variety of modern data processing schemes, multichannel EOR technologies are being developed to realize the systematic, intelligent, and cost-effective development of carbonate reservoirs.
In search of magneto‐optic materials, the mononuclear compounds LnIII(depma)(NO3)3(hmpa)2 (Ln=Dy, Gd) were synthesized. The anthracene moieties undergo 4+4 dimerization when irradiated at 365 nm ...without loss of crystallinity. The Dy compound switches from a single‐ion to a single‐molecule magnet with doubling of the spin reversal barrier energy and from yellow‐green to blue‐white emission. The dimerization is reversed by heating at 100 °C or partially on light irradiating at 254 nm. The results suggest that lanthanide phosphonates with anthracene are promising smart materials displaying synergistic magneto‐optic property.
Pairing up: The mononuclear compound DyIII(depma)(NO3)3(hmpa)2 (depma= 9‐diethylphosphono‐methylanthracene, hmpa=hexamethylphosphoramide) undergoes reversible 4+4 photodimerization in a single‐crystal‐to‐single‐crystal manner. This process is accompanied by a change from a single‐ion to a single‐molecule magnet and from yellow‐green to blue‐white emission.
Diabetic nephropathy (DN) is characterized by sterile inflammation with continuous injury and loss of renal inherent parenchyma cells. Podocyte is an essential early injury target in DN. The injury ...and loss of podocytes are closely associated with proteinuria, the early symptom of renal injury in DN. However, the exact mechanism for podocyte injury and death in DN remains ambiguous. In this study we investigated whether pyroptosis, a newly discovered cell death pathway was involved in DN. Diabetic mice were generated by high-fat diet/STZ injections. We showed that the expression levels of caspase-11 and cleavage of gasdermin D (GSDMD-N) in podocytes were significantly elevated, accompanied by reduced expression of podocyte makers nephrin and podocin, loss and fusion in podocyte foot processes, increased inflammatory cytokines NF-κB, IL-1β, and IL-18, macrophage infiltration, glomerular matrix expansion and increased urinary albumin to creatinine ratio (UACR). All these changes in diabetic mice were blunted by knockout of caspase-11 or GSDMD. Cultured human and mouse podocytes were treated with high glucose (30 mM), which significantly increased the expression levels of caspase-11 or caspase-4 (the homolog of caspase-11 in human), GSDMD-N, NF-κB, IL-1β, and IL-18, and decreased the expression of nephrin and podocin. Either caspase-4 or GSDMD knockdown by siRNA significantly blunted these changes. In summary, our results demonstrate that caspase-11/4 and GSDMD-mediated pyroptosis is activated and involved in podocyte loss under hyperglycemia condition and the development of DN.
Many in vitro studies have shown that tea catechins had vevarious health beneficial effects. However, inconsistent results between in vitro and in vivo studies or between laboratory tests and ...epidemical studies are observed. Low bioavailability of tea catechins was an important factor leading to these inconsistencies. Research advances in bioavailability studies involving absorption and metabolic biotransformation of tea catechins were reviewed in the present paper. Related techniques for improving their bioavailability such as nanostructure-based drug delivery system, molecular modification, and co-administration of catechins with other bioactives were also discussed.
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•Metal organic nanotube.•Synthetic strategies.•Formation mechanism.•Crystal structures.•Properties.
This tutorial review provides basic design principles and the current status of ...metal-organic nanotubes (MONTs). As an attractive family of nanotubular materials, MONTs can show precise structures that can be designed and constructed through judicious choice of metal ions and ligands, and also interesting physical and chemical properties that can be embedded within the structures. This review summarizes the recent progress in this topical field including the synthetic approaches towards the nanotubular structures, the formation mechanism, the crystal structures of MONTs reported thus far with finite and infinite sizes, and also the physical and chemical properties. The review concludes with a discussion of future challenges for development of this promising field.
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•The iridium-lanthanide (Ir-Ln) complexes, with features originating from both the iridium complexes and lanthanide ions, attract continuous research enthusiasm because their ...multifunctions and tunable properties.•The research of Ir-Ln complexes can offer meaningful insights into the fundamental science and promote the applications of lanthanide-based luminescent materials in varied fields.•In the proposed review, we intend to provide a comprehensive review of Ir-Ln complexes, including their structures, properties, and applications.
Iridium-lanthanide (Ir-Ln) complexes possess unique features originating from both the Ir complexes and lanthanide ions. The combination of Ir complexes and lanthanide ions can overcome limitations associated with lanthanide ions and allow the fabrication of new multifunctional complexes, thus enabling new applications. In this review, we provide up-to-date advances of Ir-Ln complexes by beginning with general discussions about the properties of Ir-Ln complexes. Structures of Ir-Ln complexes are then discussed by correlating structures with properties, in which structure related photophysical features and luminescent mechanisms are highlighted. Representative applications of Ir-Ln complexes in bioimaging, sensing, and therapy are also presented, followed by perspectives on the development of Ir-Ln complexes.
Photo‐responsive lanthanide‐based single‐molecule magnets (SMM) hold great promise for future switching and memory devices. Herein, we report a dysprosium phosphonate DyIII(SCN)2(NO3)(depma)2(4‐hpy)2 ...(1Dy), which features a supramolecular framework containing layers of hydrogen‐bonding network and pillars of π–π interacted anthracene units. The photocycloaddition reaction of anthracene pairs led to a rapid and reversible single‐crystal‐to‐single‐crystal (SC–SC) structural transition to form the 1D coordination polymer DyIII(SCN)2(NO3)(depma2)(4‐hpy)2n (2Dy), accompanied by photoswitchable SMM properties with the reduction of effective energy barrier by half and the narrowing of the butterfly‐like hysteresis loop. The diluted sample showed a photo‐induced switch of the blocking temperature (TB) from 3.8 K for 1Dy@Y to 2.6 K for 2Dy@Y. This work may inspire the construction of lanthanide‐based molecular materials with targeted photo‐responsive magnetic properties.
A reversible photo‐induced single‐crystal‐to‐single‐crystal structural transformation was achieved for a mononuclear dysprosium‐anthracene compound to form a 1D coordination polymer. This compound displays photoswitchable SMM properties with reduced effective spin‐reversal energy barrier, narrowed butterfly‐like hysteresis loop, and decreased blocking temperature.
Abstract
Background
The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to ...evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine.
Methods
A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission.
Results
In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months.
Conclusions
The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
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