Vascular Endothelial Growth Factor A VEGFA Inhibition: An Effective Treatment Strategy for Psoriasis.

Psoriasis is an inflammatory skin disease mediated by the immune system and characterized by an inflammatory ring, also known as an epithelial immune microenvironment (EIME). The interaction between the epithelial tissue of the skin and the immune system has a crucial role in the immune cycle of psoriasis. Although the formation of new blood vessels in skin lesions provides energy support for the proliferation of epidermal keratinocytes, the role of angiogenesis in psoriasis has not been extensively studied. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis that has an important role in the development of psoriasis. VEGFA promotes angiogenesis and directly stimulates epidermal keratinocytes and infiltrating immune cells, thus contributing to the progression of psoriasis. Measuring VEGFA levels to identify angiogenic characteristics in psoriasis patients may be a predictive biomarker for disease severity and response to anti-angiogenic therapy. Clinical data have shown that anti-angiogenic therapy can improve skin lesions in psoriasis patients. Therefore, this study aimed to uncover the underestimated role of blood vessels in psoriasis, explore the relationship between VEGFA and keratinocytes in the EIME, and inspire innovative drug therapies for the treatment of psoriasis.

Toxic effects and mechanisms of cationic blue SD-GSL on Chlorella vulgaris before and after the biological decolorization process.

Biodegradation is regarded as an efficient way to decolorize azo dyes. However, the changes in the algal toxicity of azo dyes during biodecolorization are still unclear. In this study, the physiological responses of Chlorella vulgaris to the hydrophobic and hydrophilic components of cationic blue SD-GSL (a typical monoazo dye) and its biodecolorization products were investigated. The toxicity of each component to Chlorella vulgaris and the sources of the toxicity were analyzed. The cationic blue SD-GSL components inhibited the algal cell division and superoxide dismutase (SOD) activity at all concentrations, and inhibited the synthesis of chlorophyll-a (Chl-a) at concentrations >100 mg/L, whereas increased the malondialdehyde (MDA) content. The hydrophobic and hydrophilic components of its biodecolorization products had enhanced inhibition rates on cell density (10.7% and 15.6%, respectively), Chl-a content (31.2% and 8.4%, respectively), and SOD activity (13.5% and 1.9%, respectively) of Chlorella vulgaris, and further stimulated an increase in MDA content (4.4% and 7.0%, respectively), indicating that the biodecolorization products were more toxic than the pristine dye. Moreover, the toxic effect of hydrophobic components on Chlorella vulgaris was stronger than that of hydrophilic components. The sensitivity sequence of Chlorella vulgaris to the toxicity of cationic blue SD-GSL and its biodecolorization product components was: Chl-a synthesis > SOD activity > cell division. SUVA analysis and 3D-EEM analysis revealed that the enhanced algal toxicity of the biodecolorization products of cationic blue SD-GSL was attributed to the aromatic compounds, which were mainly concentrated in the hydrophobic components. UPLC-Q-TOF-MS was used to verify dye biodecolorization byproducts. The information obtained from this study helps to understand the decolorization products toxicities of the biologically treated azo dyes, thereby providing new insights into the environmental safety of textile wastewater after traditional biological treatment.

HeadDiff: Exploring Rotation Uncertainty With Diffusion Models for Head Pose Estimation.

In this paper, we propose a probabilistic regression diffusion model for head pose estimation, dubbed HeadDiff, which typically addresses the rotation uncertainty, especially when faces are captured in wild conditions. Unlike conventional image-to-pose methods which cannot explicitly establish the rotational manifold of head poses, our HeadDiff aims to ensure the pose rotation via the diffusion process and in parallel, refine the mapping process iteratively. Specifically, we initially formulate the head pose estimation problem as a reverse diffusion process, defining a paradigm for progressive denoising on the manifold, which explores the uncertainty by decomposing the large gap into intermediate steps. Moreover, our HeadDiff is equipped with an isotropic Gaussian distribution by encoding the incoherence information in our rotation representation. Finally, we learn the facial relationship of nearest neighbors with a cycle-consistent constraint for robust pose estimation versus diverse shape variations. Experimental results on multiple datasets demonstrate that our proposed method outperforms existing state-of-the-art techniques without auxiliary data.

Cordycepin Ameliorates Psoriasis-Like Skin Lesion by Regulating p53/MDM2 Feedback Loop.

Apoptosis is a natural physiological process of programmed cell death. It is essential for maintaining the homeostasis of the body and the immune system. The dysfunction of apoptosis can lead to the development of autoimmune diseases. In psoriasis, the dysfunction of keratinocyte proliferation manifests as an impairment of apoptosis. Cordycepin is the major active component in cordyceps militaris and has pharmacological effects, including regulation of apoptosis. The pharmacological mechanism of Cordycepin in psoriasis remains unclear. In this study, bioinformatics analysis revealed that the mechanism may be associated with the p53 apoptotic pathway. Further, we confirmed in the experiments that cordycepin inhibited the interleukin (IL)-17A-induced proliferation of HaCaT cells and down-regulated the expression of proliferating cell nuclear antigen (PCNA) and Ki-67. Regulating the expression of apoptotic proteins BAX, Bcl-2, and p53 promote apoptosis. Further investigation of the upstream pathway of apoptosis revealed that cordycepin could normalize the abnormal p53-mouse double minute 2 (MDM2) feedback loop. In vivo results showed that the cordycepin gel could effectively improve imiquimod (IMQ)-induced psoriasis-like skin lesions in mice, and the p53-MDM2 pathway was verified at the protein level. In conclusion, the anti-psoriasis effect of Cordycepin and its potential mechanism have not been discussed in detail. However, our work supports the idea that Cordycepin can be further developed as an Active Pharmaceutical Ingredient (API) for the treatment of psoriasis.

High-Performance Aqueous Zinc-Organic Battery with a Photo-Responsive Covalent Organic Framework Cathode.

Covalent organic framework (COF) materials, known for their robust porous character, sustainability, and abundance, have great potential as cathodes for aqueous Zn-ion batteries (ZIBs). However, their application is hindered by low reversible capacity and discharge voltage. Herein, a donor-acceptor configuration COF (NT-COF) is utilized as the cathode for ZIBs. The cell exhibits a high discharge voltage plateau of ≈1.4 V and a discharge capacity of 214 mAh g-1 at 0.2 A g-1 when utilizing the Mn2+ electrolyte additive in the ZnSO4 electrolyte. A synergistic combination mechanism is proposed, involving the deposition/dissolution reactions of Zn4SO4(OH)6·4H2O and the co-(de)insertion reactions of H+ and SO4 2- in NT-COF. Meanwhile, the NT-COF with a donor-acceptor configuration facilitates efficient generation and separation of electron-hole pairs upon light exposure, thereby enhancing electrochemical reactions within the battery. This leads to a reduction in charging voltage and internal overvoltage, ultimately minimizing electricity consumption. Under ambient weather conditions, the cell exhibits an average discharge capacity of 430 mAh g-1 on sunny days and maintains consistent cycling stability for a duration of 200 cycles (≈19 days) at 0.2 A g-1. This research inspires the advancement of Zn-organic batteries for high-energy-density aqueous electrochemical energy storage systems or photo-electrochemical batteries.

Archaea-Inspired Switchable Nanochannels for On-Demand Lithium Detection by pH Activation.

With the rapid development of the lithium ion battery industry, emerging lithium (Li) enrichment in nature has attracted ever-growing attention due to the biotoxicity of high Li levels. To date, fast lithium ion (Li+) detection remains urgent but is limited by the selectivity, sensitivity, and stability of conventional technologies based on passive response processes. In nature, archaeal plasma membrane ion exchangers (NCLX_Mj) exhibit Li+-gated multi/monovalent ion transport behavior, activated by different stimuli. Inspired by NCLX_Mj, we design a pH-controlled biomimetic Li+-responsive solid-state nanochannel system for on-demand Li+ detection using 2-(2-hydroxyphenyl)benzoxazole (HPBO) units as Li+ recognition groups. Pristine HPBO is not reactive to Li+, whereas negatively charged HPBO enables specific Li+ coordination under alkaline conditions to decrease the ion exchange capacity of nanochannels. On-demand Li+ detection is achieved by monitoring the decline in currents, thereby ensuring precise and stable Li+ recognition (>0.1 mM) in the toxic range of Li+ concentration (>1.5 mM) for human beings. This work provides a new approach to constructing Li+ detection nanodevices and has potential for applications of Li-related industries and medical services.

MitoH3: Mitochondrial Haplogroup and Homoplasmic/Heteroplasmic Variant Calling Pipeline for Alzheimer's Disease Sequencing Project.

Background: Mitochondrial DNA (mtDNA) is a double-stranded circular DNA and has multiple copies in each cell. Excess heteroplasmy, the coexistence of distinct variants in copies of mtDNA within a cell, may lead to mitochondrial impairments. Accurate determination of heteroplasmy in whole-genome sequencing (WGS) data has posed a significant challenge because mitochondria carrying heteroplasmic variants cannot be distinguished during library preparation. Moreover, sequencing errors, contamination, and nuclear mtDNA segments can reduce the accuracy of heteroplasmic variant calling. Objective: To efficiently and accurately call mtDNA homoplasmic and heteroplasmic variants from the large-scale WGS data generated from the Alzheimer's Disease Sequencing Project (ADSP), and test their association with Alzheimer's disease (AD). Methods: In this study, we present MitoH3-a comprehensive computational pipeline for calling mtDNA homoplasmic and heteroplasmic variants and inferring haplogroups in the ADSP WGS data. We first applied MitoH3 to 45 technical replicates from 6 subjects to define a threshold for detecting heteroplasmic variants. Then using the threshold of 5% ≤variant allele fraction≤95%, we further applied MitoH3 to call heteroplasmic variants from a total of 16,113 DNA samples with 6,742 samples from cognitively normal controls and 6,183 from AD cases. Results: This pipeline is available through the Singularity container engine. For 4,311 heteroplasmic variants identified from 16,113 samples, no significant variant count difference was observed between AD cases and controls. Conclusions: Our streamlined pipeline, MitoH3, enables computationally efficient and accurate analysis of a large number of samples.