Overview of aristolochic acid nephropathy: an update

Aristolochic acid nephropathy (AAN) is a rapidly progressive renal interstitial fibrosis caused by medical or environmental exposure to aristolochic acid (AA). Since the outbreak of AAN in Belgium was reported nearly 30 years ago, the safety of herbal remedies has drawn considerable attention, and AAN has become a global public health problem. Breakthroughs have been made to better understand the disease, including the toxicity of AAs, the possible mechanisms of AAN, the disease patterns, and the pathological features; however, some critical problems remain unresolved. Because of the insidious onset of the disease, the incidence of AAN and the prevalence of exposure to AAs are unknown and might be largely underestimated. During the past decades, AA-containing herbs have been strictly administrated in many regions and the occurrence of AAN has declined sharply, yet cases of AAN are still sporadically reported. Despite the progress in the understanding of the disease’s pathogenesis, there is no effective treatment for delaying or reversing the renal deterioration caused by AAN. Therefore, the risk of exposure to AAs should be taken seriously by public health workers and clinicians. In this review, we updated the latest data on AAN, summarized the advances throughout these years, and put forward some challenges for future research

Research progress on alternative kombucha substrate transformation and the resulting active components

Kombucha is a customary tea-based beverage that is produced through the process of fermenting a mixture of tea and sugar water with symbiotic culture of bacteria and yeast (SCOBY). Traditional kombucha has various beneficial effects and can improve immunity. The significant market share of Kombucha can be attributed to the growing consumer inclination towards healthy foods within the functional beverage industry. The research focus has recently expanded from the probiotics of traditional black tea kombucha to encompass other teas, Chinese herbs, plant materials, and alternative substrates. There is a lack of comprehensive literature reviews focusing on substance transformation, functional, active substances, and efficacy mechanisms of alternative kombucha substrates. This article aimed to bridge this gap by providing an in-depth review of the biological transformation pathways of kombucha metabolites and alternative substrates. The review offers valuable insights into kombucha research, including substance metabolism and transformation, efficacy, pharmacological mechanism, and the purification of active components, offering direction and focus for further studies in this field

Simultaneous Ni Doping at Atom Scale in Ceria and Assembling into Well-Defined Lotuslike Structure for Enhanced Catalytic Performance

Oxide materials with redox capability have attracted worldwide attentions in many applications. Introducing defects into crystal lattice is an effective method to modify and optimize redox capability of oxides as well as their catalytic performance. However, the relationship between intrinsic characteristics of defects and properties of oxides has been rarely reported. Herein, we report a facile strategy to introduce defects by doping a small amount of Ni atoms (∼1.8 at. %) into ceria lattice at atomic level through the effect of microstructure of crystal on the redox property of ceria. Amazingly, a small amount of single Ni atom-doped ceria has formed a homogeneous solid solution with uniform lotuslike morphology. It performs an outstanding catalytic performance of a reduced T50 of CO oxidation at 230 °C, which is 135 °C lower than that of pure CeO2 (365 °C). This is largely attributed to defects such as lattice distortion, crystal defects and elastic strain induced by Ni dopants. The DFT calculation has revealed that the electron density distribution of oxygen ions near Ni dopant, the reduced formation energy of oxygen vacancy originated from local chemical effect caused by local distortion after Ni doping. These differences have a great effect on increasing the concentration of oxygen vacancies and enhancing the migration of lattice oxygen from bulk to a surface which is closely related to optimized redox properties. As a result, oxygen storage capacity and the associated catalytic reactivity has been largely increased. We have clearly demonstrated the change of crystal lattice and the charge distribution effectively modify its chemical and physical properties at the atomic scale

Galectin-9 contributes to the pathogenesis of atopic dermatitis via T cell immunoglobulin mucin-3

BackgroundAtopic dermatitis (AD), a common type 2 inflammatory disease, is driven by T helper (TH) 2/TH22polarization and cytokines.Galectin-9 (Gal-9), via its receptor T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3), can promote TH2/TH22 immunity. The relevance of this in AD is largely unclear.ObjectivesTo characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms.MethodsWe assessed the expression of Gal-9 and TIM-3 in 30 AD patients, to compare them with those of 30 healthy controls (HC) and to explore possible links with disease features including AD activity (SCORAD), IgE levels, and circulating eosinophils and B cells. We also determined the effects of Gal-9 on T cells from the AD patients.ResultsOur AD patients had markedly higher levels of serum Gal-9 and circulating TIM-3-expressing TH1 and TH17 cells than HC. Gal-9 and TIM-3 were linked to high disease activity, IgE levels, and circulating eosinophils and/or B cells. The rates of circulating TIM-3-positive CD4+ cells were positively correlated with rates of TH2/TH22 cells and negatively correlated with rates of TH1/TH17 cells. Gal-9 inhibited the proliferation and induced the apoptosis of T cells in patients with AD, especially in those with severe AD.ConclusionOur findings suggest thatGal-9, via TIM-3, contributes to the pathogenesis of AD by augmenting TH2/TH22 polarization through the downregulation of TH1/TH17immunity. This makes Gal-9 and TIM-3 interesting to explore further, as possible drivers of disease and targets of novel AD treatment

Omics-based interpretation of synergism in a soil-derived cellulose-degrading microbial community

Reaching a comprehensive understanding of how nature solves the problem of degrading recalcitrant biomass may eventually allow development of more efficient biorefining processes. Here we interpret genomic and proteomic information generated from a cellulolytic microbial consortium (termed F1RT) enriched from soil. Analyses of reconstructed bacterial draft genomes from all seven uncultured phylotypes in F1RT indicate that its constituent microbes cooperate in both cellulose-degrading and other important metabolic processes. Support for cellulolytic inter-species cooperation came from the discovery of F1RT microbes that encode and express complimentary enzymatic inventories that include both extracellular cellulosomes and secreted free-enzyme systems. Metabolic reconstruction of the seven F1RT phylotypes predicted a wider genomic rationale as to how this particular community functions as well as possible reasons as to why biomass conversion in nature relies on a structured and cooperative microbial community

Designing Artificial Two-Dimensional Landscapes via Room-Temperature Atomic-Layer Substitution

Manipulating materials with atomic-scale precision is essential for the development of next-generation material design toolbox. Tremendous efforts have been made to advance the compositional, structural, and spatial accuracy of material deposition and patterning. The family of 2D materials provides an ideal platform to realize atomic-level material architectures. The wide and rich physics of these materials have led to fabrication of heterostructures, superlattices, and twisted structures with breakthrough discoveries and applications. Here, we report a novel atomic-scale material design tool that selectively breaks and forms chemical bonds of 2D materials at room temperature, called atomic-layer substitution (ALS), through which we can substitute the top layer chalcogen atoms within the 3-atom-thick transition-metal dichalcogenides using arbitrary patterns. Flipping the layer via transfer allows us to perform the same procedure on the other side, yielding programmable in-plane multi-heterostructures with different out-of-plane crystal symmetry and electric polarization. First-principle calculations elucidate how the ALS process is overall exothermic in energy and only has a small reaction barrier, facilitating the reaction to occur at room temperature. Optical characterizations confirm the fidelity of this design approach, while TEM shows the direct evidence of Janus structure and suggests the atomic transition at the interface of designed heterostructure. Finally, transport and Kelvin probe measurements on MoXY (X,Y=S,Se; X and Y corresponding to the bottom and top layers) lateral multi-heterostructures reveal the surface potential and dipole orientation of each region, and the barrier height between them. Our approach for designing artificial 2D landscape down to a single layer of atoms can lead to unique electronic, photonic and mechanical properties previously not found in nature

IKKβ Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

SummaryTNFα has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKβ, a major downstream kinase in the TNFα signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKβ-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKβ is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer