Phenotypic heterogeneity of mycosis fungoides cells leads to the difficulties in determining tumour origin.

Mycosis fungoides (MF) is a low-grade malignant cutaneous T-cell lymphoma that originates from memory T cells. It typically follows a unique and relatively indolent disease course. MF is used to be characterized by a tissue-resident memory T cell (TRM) phenotype, although recent molecular research has revealed its complexity, casting doubt on the cell of origin and the TRM-MF paradigm. Recent clonal heterogeneity studies suggest that MF may originate from immature early precursor T cells. During development, the tumour microenvironment (TME) influences tumour cell phenotype. The exact origin and development trajectory of MF remains elusive. Clarifying the origin of MF cells is vital for accurate diagnosis and effective treatment.

PreMode predicts mode-of-action of missense variants by deep graph representation learning of protein sequence and structural context.

Accurate prediction of the functional impact of missense variants is important for disease gene discovery, clinical genetic diagnostics, therapeutic strategies, and protein engineering. Previous efforts have focused on predicting a binary pathogenicity classification, but the functional impact of missense variants is multi-dimensional. Pathogenic missense variants in the same gene may act through different modes of action (i.e., gain/loss-of-function) by affecting different aspects of protein function. They may result in distinct clinical conditions that require different treatments. We developed a new method, PreMode, to perform gene-specific mode-of-action predictions. PreMode models effects of coding sequence variants using SE(3)-equivariant graph neural networks on protein sequences and structures. Using the largest-to-date set of missense variants with known modes of action, we showed that PreMode reached state-of-the-art performance in multiple types of mode-of-action predictions by efficient transfer-learning. Additionally, PreMode's prediction of G/LoF variants in a kinase is consistent with inactive-active conformation transition energy changes. Finally, we show that PreMode enables efficient study design of deep mutational scans and optimization in protein engineering.

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

A Retrospective Study: Clinical Characteristics and Lifestyle Analysis of Chinese Senile Gluteal Dermatosis Patients.

Purpose: To summarize the clinical, histopathological and therapeutic features of senile gluteal dermatosis. Patients and Methods: Retrospective analysis of 230 cases who visited the outpatient clinic of Hangzhou No. 3 People's Hospital for skin lesions on the buttocks and hips from 2018.8-2023.8 were included in the study, basic clinical information was collected, and they were subjected to physical examination of the buttocks and hips, and 36 cases were senile gluteal dermatosis, of which 7 underwent histopathological biopsy. Results: A total of 230 patients were included, of which 36 were diagnosed with geriatric buttock dermatosis, with a mean age of (84.2±12.6) years, mean body mass index of (21.7±3.8) kg/m2, and a male to female ratio of 2:1. There was a significant correlation between the occurrence of the disease and age, gender, body mass index, sedentary time, type of chair used, and hypertension (P<0.05). The severity of the lesions may be associated with longer sitting time and prolonged use of bamboo chairs (P<0.05). Histopathologic changes were not specific. The skin lesions could subside after general treatment such as improvement of lifestyle, use of pressure-reducing air mattresses, salicylic acid cream, and moisturizing creams. Conclusion: Senile gluteal dermatosis is a common senile physical dermatosis, mainly manifested as brownish scaly plaques, erythema and crusted ulcers, which can often be cured under reasonable treatment.

A Case Report of Dyschromatosis Symmetrica Hereditaria with Glucose-6-Phosphate Dehydrogenase Deficiency.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmented genetic skin disorder with an incompletely understood pathogenesis characterized by reticular hyper- and hypopigmented skin patches on the dorsal aspect of the extremities, freckle-like patches on the face, and unaffected palms and feet. There is no effective treatment available. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has not been reported in the literature of DSH. We describe for the first time a case of DSH with G6PD deficiency and a family history of psychosis.

A rare case of refractory facial phaeohyphomycosis caused by Cladosporium halotolerans successfully treated with aminolevulinic acid photodynamic therapy.

A 55-year-old female presented with a gradually enlarged red plaque and ulceration on the right side of her nose, face and suborbital region for ten years. The histopathologic features indicated infectious granuloma. The results of the fungal culture of the tissue and DNA sequencing identified as Cladosporium halotolerans infection. The patient was diagnosed with phaeohyphomycosis due to Cladosporium halotolerans. In this case, it was unsuitable for surgical treatment since the lesion was located periorbital. Furthermore, the patient had a poor response to oral itraconazole (400 mg/d) for 9 months. Therefore, ALA-PDT was added to the treatment regimen. The patient received ALA-PDT irradiation 5 times at 2-week intervals and achieved significant clinical remission. We believe that ALA-PDT may be an effective and safe adjuvant therapy.

Revealing the Selective Bifunctional Electrocatalytic Sites via In Situ Irradiated X-Ray Photoelectron Spectroscopy for Lithium-Sulfur Battery.

The electrocatalysts are widely applied in lithium-sulfur (Li-S) batteries to selectively accelerate the redox kinetics behavior of Li2 S, in which bifunctional active sites are established, thereby improving the electrochemical performance of the battery. Considering that the Li-S battery is a complex closed "black box" system, the internal redox reaction routes and active sites cannot be directly observed and monitored especially due to the distribution of potential active-site structures and their dynamic reconstruction. Empirical evidence demonstrates that traditional electrochemical test methods and theoretical calculations only probe the net result of multi-factors on an average and whole scale. Herein, based on the amorphous TiO2- x @Ni selective bifunctional model catalyst, these limitations are overcome by developing a system that couples the light field and in situ irradiated X-ray photoelectron spectroscopy to synergistically convert the "black box" battery into a "see-through" battery for direct observation of the charge transportation, thus revealing that amorphous TiO2- x and Ni nanoparticle as the oxidation and reduction sites selectively promote the decomposition and nucleation of Li2 S, respectively. This work provides a universal method to achieve a deeper mechanistic understanding of bidirectional sulfur electrochemistry.

A probabilistic graphical model for estimating selection coefficient of missense variants from human population sequence data.

Accurately predicting the effect of missense variants is a central problem in interpretation of genomic variation. Commonly used computational methods does not capture the quantitative impact on fitness in populations. We developed MisFit to estimate missense fitness effect using biobank-scale human population genome data. MisFit jointly models the effect at molecular level (d) and population level (selection coefficient, s), assuming that in the same gene, missense variants with similar d have similar s. MisFit is a probabilistic graphical model that integrates deep neural network components and population genetics models efficiently with inductive bias based on biological causality of variant effect. We trained it by maximizing probability of observed allele counts in 236,017 European individuals. We show that s is informative in predicting frequency across ancestries and consistent with the fraction of de novo mutations given s. Finally, MisFit outperforms previous methods in prioritizing missense variants in individuals with neurodevelopmental disorders.

Soil pH Determines the Spatial Distribution, Assembly Processes, and Co-existence Networks of Microeukaryotic Community in Wheat Fields of the North China Plain.

Soil microeukaryotes play a pivotal role in soil nutrient cycling and crop growth in agroecosystems. However, knowledge of microeukaryotic community distribution patterns, assembly processes, and co-existence networks is greatly limited. Here, microbial eukaryotes in bulk and rhizosphere soils of the North China Plain were investigated. The results showed that soil pH was the driving factor for the microeukaryotic community composition in the bulk and rhizosphere soils. The soil microeukaryotic community could significantly differ between alkaline and acidic soils. The results indicated that the soil pH had a stronger effect than niche differences on community composition. Partial Mantel tests showed that soil pH and spatial distance had similar effects on the microeukaryotic community composition in the bulk soil. However, in the rhizosphere soil, spatial distance had a stronger effect than soil pH. Infer Community Assembly Mechanisms by Phylogenetic bin-based null model (iCAMP) analysis revealed that drift was the most important process driving microeukaryotic community assembly, with an average relative importance of 37.4-71.1%. Dispersal limitation displayed slightly greater importance in alkaline rhizosphere than in alkaline bulk soils. Meanwhile, the opposite trend was observed in acidic soils. In addition, the contribution of each assembly process to each iCAMP lineage "bin" varied according to the acidic or alkaline conditions of the soil and the niche environment. High proportions of positive links were found within the four ecological networks. Alkaline soil networks, especially the alkaline bulk soil network, showed greater complexity than the acidic soil networks. Natural connectivity analysis revealed that the rhizosphere community had a greater stability than the bulk soil community in alkaline soil. This study provides a foundation for understanding the potential roles of microbial eukaryotes in agricultural soil ecosystem functioning.

Follicular mucinosis successfully treated by photodynamic therapy: Two case reports.

Follicular mucinosis is an epithelial reaction pattern characterized by follicular mucin accumulation. Follicular mucinosis may occur in a primary form or a secondary form associated with skin lymphoma, especially mycosis fungoides. This report describes two patients with these two forms of follicular mucinosis, who both had an excellent response to photodynamic therapy. The condition changes of the secondary follicular mucinosis patient were followed up by repeated pathological biopsies. The expression of CD103, a specific marker of tissue-resident memory T cells, was found to decline when the lesions improved. These results indicate an association between efficacy and pathological changes during the treatment of secondary follicular mucinosis.

In Situ Monitored (N, O)-Doping of Flexible Vertical Graphene Films with High-Flux Plasma Enhanced Chemical Vapor Deposition for Remarkable Metal-Free Redox Catalysis Essential to Alkaline Zinc-Air Batteries.

Rechargeable zinc-air batteries (ZABs) have attracted great interests for emerging energy applications. Nevertheless, one of the major bottlenecks lies in the fabrication of bifunctional catalysts with high electrochemical activity, high stability, low cost, and free of precious and rare metals. Herein, a high-performance metal-free bifunctional catalyst is synthesized in a single step by regulating radicals within the recently invented high-flux plasma enhanced chemical vapor deposition (HPECVD) system equipped with in situ plasma diagnostics. Thus-derived (N, O)-doped vertical few-layer graphene film (VGNO) is of high areal population with perfect vertical orientation, tunable catalytic states, and configurations, thus enabling significantly enhanced electrochemical kinetic processes of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with reference to milestone achievements to date. Application of such VGNO to aqueous ZABs (A-ZABs) and flexible solid-state ZABs (S-ZABs) exhibited high discharge power density and excellent cycling stability, which remarkably outperformed ZABs using benchmarked precious-metal based catalysts. The current work provides a solid basis toward developing low-cost, resource-sustainable, and eco-friendly ZABs without using any metals for outstanding OER and ORR catalysis.

MVP predicts the pathogenicity of missense variants by deep learning.

Accurate pathogenicity prediction of missense variants is critically important in genetic studies and clinical diagnosis. Previously published prediction methods have facilitated the interpretation of missense variants but have limited performance. Here, we describe MVP (Missense Variant Pathogenicity prediction), a new prediction method that uses deep residual network to leverage large training data sets and many correlated predictors. We train the model separately in genes that are intolerant of loss of function variants and the ones that are tolerant in order to take account of potentially different genetic effect size and mode of action. We compile cancer mutation hotspots and de novo variants from developmental disorders for benchmarking. Overall, MVP achieves better performance in prioritizing pathogenic missense variants than previous methods, especially in genes tolerant of loss of function variants. Finally, using MVP, we estimate that de novo coding variants contribute to 7.8% of isolated congenital heart disease, nearly doubling previous estimates.

Cr(VI) removal by Penicillium oxalicum SL2: Reduction with acidic metabolites and form transformation in the mycelium.

Bioremediation of Cr(VI) contamination using microorganisms is a promising method for reducing its environmental risks. The objective of this study was to clarify Cr(VI) removal by Penicillium oxalicum SL2 in terms of indirect Cr(VI) reduction by metabolites, interaction sites, and form transformation of chromium. Strain SL2 could sequentially remove Cr(VI) in the bioreactor. Oxalic acid produced by the fungus contributed to Cr(VI) reduction. Scanning transmissiony X-ray microscop (STXM) analysis suggested strain SL2 could partly reduce Cr(VI) to Cr(III) in the cell. Amine, carboxyl, and phosphate groups were related to Cr(VI) removal. Chromium K-edge X-ray absorption near edge structure (XANES) analysis implied Cr(III)-Cys potentially acted as an intermediate for the formation of chromium oxalate complexes during the process of treatment. This study would support the application of strain SL2 in Cr(VI) bioremediation and expand knowledge on the interaction of chromium with fungus.

PDA-assisted formation of ordered intermetallic CoPt3 catalysts with enhanced oxygen reduction activity and stability.

Structurally ordered intermetallic alloys with definite composition and distinct structure show great potential as electro-catalysts for the oxygen reduction reaction (ORR). However, their fabrication with small particle size remains a challenge since grain growth caused by high temperature annealing is unavoidable for the formation of the ordered phase. Here we propose an effective space-confined strategy to prepare an intermetallic alloy with small size (CoPt3/C-S) through annealing of the disordered Pt-Co alloy coated with polydopamine (PDA). The CoPt3/C-S intermetallic catalyst exhibits over 7-fold higher ORR activity and comparable stability compared to large intermetallic nanoparticles (CoPt3/C-L) prepared by direct heat-treatment without PDA. The superior ORR performance of the CoPt3/C-S catalyst can be attributed to the abundant active sites and unsaturated coordinated bonds caused by its special electronic structure, as proved by XPS and XAS tests. This work not only proposes a feasible synthesis route for small intermetallic nanoparticles but also provides a valid strategy to improve the ORR performance of ordered intermetallic catalysts.

A surrogate reporter system for multiplexable evaluation of CRISPR/Cas9 in targeted mutagenesis.

Engineered nucleases in genome editing manifest diverse efficiencies at different targeted loci. There is therefore a constant need to evaluate the mutation rates at given loci. T7 endonuclease 1 (T7E1) and Surveyor mismatch cleavage assays are the most widely used methods, but they are labour and time consuming, especially when one must address multiple samples in parallel. Here, we report a surrogate system, called UDAR (Universal Donor As Reporter), to evaluate the efficiency of CRISPR/Cas9 in targeted mutagenesis. Based on the non-homologous end-joining (NHEJ)-mediated knock-in strategy, the UDAR-based assay allows us to rapidly evaluate the targeting efficiencies of sgRNAs. With one-step transfection and fluorescence-activated cell sorting (FACS) analysis, the UDAR assay can be completed on a large scale within three days. For detecting mutations generated by the CRISPR/Cas9 system, a significant positive correlation was observed between the results from the UDAR and T7E1 assays. Consistently, the UDAR assay could quantitatively assess bleomycin- or ICRF193-induced double-strand breaks (DSBs), which suggests that this novel strategy is broadly applicable to assessing the DSB-inducing capability of various agents. With the increasing impact of genome editing in biomedical studies, the UDAR method can significantly benefit the evaluation of targeted mutagenesis, especially for high-throughput purposes.

Dependent Relationship between Quantitative Lattice Contraction and Enhanced Oxygen Reduction Activity over Pt-Cu Alloy Catalysts.

Lattice contraction has been regarded as an important factor influencing oxygen reduction reaction (ORR) activity of Pt-based alloys. However, the relationship between quantitative lattice contraction and ORR activity has rarely been reported. Herein, using Pt-Cu alloy nanoparticles (NPs) with similar particle sizes but different compositions as examples, we investigated the relationship between quantitative lattice contraction and ORR activity by defining the shrinking percentage of Pt-Pt bond distance as lattice contraction percentage. The results show that the ORR activities of Pt-Cu alloy NPs exhibit a well-defined volcano-type dependent relationship toward the lattice contraction percentage. The dependent correlation can be explained by the Sabatier principle. This study not only proposes a valid descriptor to bridge the activity and atomic composition but also provides a reference for understanding the composition-structure-activity relationship of Pt-based alloys.

[Composition, structure and function of anammoxosome--A review].

Anaerobic ammonia oxidation (Anammox) is one of the highlights in the microbiology and environmental research. Anammox is the metabolic function of anaerobic ammonium oxidation bacteria (AnAOB). Different from aerobic ammonia oxidizing bacteria (AAOB), AnAOB has its characteristics in phylogenetics, cytology, physiology, etc. Especially, it has the unique organelle called anammoxosome. Anammoxosome is the place where the metabolism takes place. The research of anammoxosome is the basis to figure out the anammox performance. This article discusses the composition, structure and function of the anammoxosome.

Composition-controlled synthesis of carbon-supported Pt-Co alloy nanoparticles and the origin of their ORR activity enhancement.

The ability to precisely tune the chemical compositions and electronic structures of nanoalloy catalysts is essential to achieve the goals of high activity and selectivity for the oxygen reduction reaction (ORR) on the catalysts by design. In this work, we synthesized carbon-supported Pt-Co alloy nanoparticles with controlled bimetallic compositions (Pt/Co atomic ratio = 81 : 19, 76 : 24, 59 : 41, 48 : 52, 40 : 60 and 26 : 74) by regulating solution pH and the amount of Pt and Co precursor salts to elucidate the effect of catalyst composition on ORR activity. The obtained Pt-Co alloy nanoparticles have face-centred cubic (fcc) structures and are well-dispersed on the surface of the carbon support with a narrow particle size distribution (2-4 nm diameters). The electrocatalysis experiments in alkaline solution reveal a strong correlation between ORR activity and the alloy composition of the catalysts. Interestingly, the mass-specific activities of the catalysts manifest a typical double-volcano plot as a function of alloy composition. In this Pt-Co alloy series, the catalyst with a Pt : Co atomic ratio of 76 : 24 exhibits the best ORR performance, which is remarkably higher than that of the commercial Pt/C (E-TEK). X-ray photoelectron spectroscopy (XPS) measurements demonstrate that the electronic structures of these catalysts can be tuned by controlling their alloy compositions, which are highly correlated with the trends in ORR activity. The origin of the enhancement in ORR activity may be strongly related to the unique chemical surface structures of the catalysts.