Single-cell transcriptomics reveals peripheral immune responses in non-segmental vitiligo.

Background: Vitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, but few studies have investigated the cell types and function of circulating immune cells in peripheral blood. Here, single cell RNA-sequencing (scRNA-seq) was used to investigate the mechanisms of peripheral immune responses in vitiligo patients. Methods: Peripheral blood was collected from five patients with progressive non-segmental vitiligo and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Paque density gradient centrifugation, and scRNA-seq was performed on isolated cell populations to obtain single cell transcriptomes and characterize important genes and intracellular signaling pathways. The key findings were validated with qPCR and flow cytometry assays. Results: We identified 10 major cell types by scRNA-seq. Among these cell types, neutrophils were specifically observed in our scRNA-seq data from PBMCs. Peripheral blood effector CD8+ T cells from vitiligo patients did not show significant differences at the transcriptome level compared with healthy controls, whereas regulatory T cells showed pro-inflammatory TH1-like properties. Innate immune cells, including natural killer cells and dendritic cells, showed increased antigen processing and presentation as well as upregulated interferon responses. B cells, monocytes, and neutrophils all showed activation. B cells, especially memory B cells, had upregulated expression of genes related to humoral immunity. Monocytes showed production of proinflammatory cytokines and chemokines. Neutrophils showed strong chemokine ligand-receptor (L-R) pair (CXCR8-CXCR2) autocrine signaling pathway. Conclusion: This study revealed the genetic profile and signaling pathway characteristics of peripheral blood immune cells in vitiligo patients, providing new insights into its pathogenesis, which may facilitate identification of potential therapeutic targets.

Metagenomic sequencing reveals altered gut microbial compositions and gene functions in patients with non-segmental vitiligo.

BACKGROUND: Vitiligo has been correlated with an abnormal gut microbiota. We aimed to systematically identify characteristics of the gut microbial compositions, genetic functions, and potential metabolic features in patients with non-segmental vitiligo. METHODS: Twenty-five patients with non-segmental vitiligo and 25 matched healthy controls (HCs) were enrolled. Metagenomic sequencing and bioinformatic analysis were performed to determine the gut microbiota profiles. Differences in gut microbiota diversity and composition between patients with vitiligo and HCs were analyzed. Gene functions and gut metabolic modules were predicted with the Kyoto Encyclopedia of Gene and Genomes (KEGG) and MetaCyc databases. RESULTS: Compared with HCs, alpha diversity of intestinal microbiome in vitiligo patients was significantly reduced. At the species level, the relative abundance of Staphylococcus thermophiles was decreased, and that of Bacteroides fragilis was increased in patients with vitiligo compared with those of the HCs. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed representative microbial markers of Lachnospiraceae_bacterium_BX3, Massilioclostridium_coli, TM7_phylum_sp_oral_taxon_348 and Bacteroides_fragilis for patients with vitiligo. KEGG gene function analysis showed that the NOD-like receptor signaling pathway was significantly enriched in patients with vitiligo. Gut metabolic modules (GMMs) analysis showed that cysteine degradation was significantly down-regulated, and galactose degradation was up-regulated in patients with vitiligo. A panel of 28 microbial features was constructed to distinguish patients with vitiligo from HCs. CONCLUSIONS: The gut microbial profiles and genetic functions of patients with vitiligo were distinct from those of the HCs. The identified gut microbial markers may potentially be used for earlier diagnosis and treatment targets.

High-Valence Mo Doping and Oxygen Vacancy Engineering to Promote Morphological Evolution and Oxygen Evolution Reaction Activity.

The rational design of high-efficiency, low-cost electrocatalysts for electrochemical water oxidation in alkaline media remains a huge challenge. Herein, combined strategies of metal doping and vacancy engineering are employed to develop unique Mo-doped cobalt oxide nanosheet arrays. The Mo dopants exist in the form of high-valence Mo6+, and the doping amount has a significant effect on the structure morphology, which transforms from 1D nanowires/nanobelts to 2D nanosheets and finally 3D nanoflowers. In addition, the introduction of vast oxygen vacancies helps to modulate the electronic states and increase the electronic conductivity. The optimal catalyst MoCoO-3 exhibits greatly increased active sites and enhanced reaction kinetics. It gives a dramatically lower overpotential at 50 mA cm-2 (288 mV), much smaller than that of the undoped counterpart (418 mV) and comparable to those of the recently reported electrocatalysts. Density functional theory results further verify that the increased electronic conductivity and optimized adsorption energy toward oxygen evolution reaction intermediates are mainly responsible for the enhanced catalytic activity. Moreover, the assembled two-electrode electrolyzer (MoCoO-3||Pt/C) exhibits superior performance with the cell potential decreased by 233 mV to reach a current density of 50 mA cm-2 with respect to the benchmark counterpart catalysts (RuO2||Pt/C). This work might contribute to the rational design of effective, low-cost electrocatalyst materials by combining multiple strategies.

Aggregation-Induced Structural Symmetry Breaking Promotes Charge Separation for Efficient Photocatalytic Hydrogen Production.

Recently, organic semiconductors have received much attention in the field of photocatalysis due to their tunable physicochemical properties. However, organic semiconductor photocatalysts typically suffer from severe charge recombination due to high exciton binding energy. Herein, we found that aggregation of pyrene results in a red-shift of the light absorption from UV to visible light region. Importantly, the aggregation can induce dipole polarization by spontaneous structural symmetry breaking, thus significantly accelerating the separation and transfer of charge carriers. As a result, the pyrene aggregates display enhanced hydrogen photosynthesis activity. Furthermore, the noncovalent interactions allow rational design of physicochemical and electronic properties of pyrene aggregates, further strengthening the charge separation and photocatalytic activity of aggregates. The quantum yield of pyrene aggregates for hydrogen production highly reaches 20.77 % at 400 nm. Moreover, we have also observed pyrene analogues (1-hydroxypyrene, 1-nitropyrene and perylene) after aggregation all display large dipole moments induced by structural symmetry breaking and therefore accelerate the separation of charge carriers, confirming its general principle. This work highlights the achievement of using aggregation-induced structural symmetry breaking to enable the separation and transfer of charge carriers.

Proline-rich 11 (PRR11) promotes the progression of cutaneous squamous cell carcinoma by activating the EGFR signaling pathway.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignancies, and its incidence rate is increasing worldwide. Proline-rich 11 (PRR11) has been reported to be involved in the occurrence and development of various tumors. However, the role of PRR11 in cSCC remains unknown. In the present study, we observed upregulated expression of PRR11 in cSCC tissues and cell lines. Knockdown of PRR11 in the cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing cell cycle arrest during the G1/S phase transition, promoted cell apoptosis, and reduced cell migration and invasion in vitro. Conversely, overexpression of PRR11 promoted cell proliferation, decreased cell apoptosis, and enhanced cell migration and invasion. PRR11 knockdown also inhibited cSCC tumor growth in a mouse xenograft model. Mechanistic investigations by RNA sequencing revealed that 891 genes were differentially expressed genes between cells with PRR11 knockdown and control cells. Enrichment analysis of different genes showed that the epidermal growth factor receptor (EGFR) signaling pathway was the top enriched pathway. We further validated that PRR11 induced EGFR pathway activity, which contributed to cSCC progression. These data suggest that PRR11 may serve as a novel therapeutic target in cSCC.

Extracellular CIRP Upregulates Proinflammatory Cytokine Expression via the NF-kappaB and ERK1/2 Signaling Pathways in Psoriatic Keratinocytes.

Psoriasis is a chronic inflammatory skin disease, and elevation of proinflammatory cytokine levels is a critical driver of the pathogenesis of psoriasis. Extracellular cold-inducible RNA-binding protein (eCIRP) has been shown to play a role in various acute and chronic inflammatory diseases. C23, a short peptide derived from CIRP, competitively binds CIRP receptors and reduces damage in inflammatory diseases. However, the effect of eCIRP in psoriasis has not been studied. In the present study, we investigated the role of eCIRP in the expression of proinflammatory cytokines in keratinocytes. Our data show that eCIRP expression was increased in the sera of psoriasis patients and imiquimod- (IMQ-) induced psoriatic mice and cells stimulated with proinflammatory cytokines (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α; mix M5). Recombinant human CIRP (rhCIRP) promoted the expression of the proinflammatory cytokines TNF-α, IL-6, and IL-8 and the activation of NF-kappaB (NF-κB) and ERK1/2 in cultured keratinocytes. We then found that the above effects of eCIRP could be blocked by C23 in both normal keratinocytes and M5-stimulated psoriatic keratinocytes. In addition, in vivo experiments revealed that C23 could effectively ameliorate IMQ-induced psoriatic dermatitis. TNF-α and IL-6 mRNA expressions were reduced in the skin lesions of mice with C23-treated IMQ-induced psoriasis, and this effect was accompanied by inhibition of the NF-κB and ERK1/2 signaling pathways. In summary, eCIRP plays an important role in the pathogenesis of psoriasis and may become a new target for psoriasis treatment.

Light-Induced Synthesis of Oxygen-Vacancy-Functionalized Ni(OH)2 Nanosheets for Highly Selective CO2 Reduction.

Solar-driven CO2 reduction into fuels and chemicals has gained increasing attention in recent years. In this study, oxygen-vacancies-functionalized Ni(OH)2 (OVs-Ni(OH)2 ) nanosheets are synthesized by a photochemical method to serve as a catalyst for CO2 reduction. Characterization reveals that COOH* is the key intermediate for CO2 -to-CO photoreduction. Experimental results and theoretical calculations confirm that OVs modification can greatly modulate the interaction strength between the OVs-Ni(OH)2 and CO2 , while lowering the energy barrier for COOH* formation, thereby preferentially facilitating CO2 reduction. As a result, the OVs-Ni(OH)2 catalyst exhibits outstanding activity and selectivity for CO2 -to-CO photoreduction with visible light. A CO evolution rate of 31.58 µmol h-1 (0.35 mg catalyst, 90228 µmol h-1 g-1 ) with a selectivity of 98 % over OVs-Ni(OH)2 was achieved, outperforming most analogous reported catalysts. Moreover, even under a low CO2 concentration of 0.04 % (representative of the CO2 concentration in air) and low reaction temperature (273 K, 0 °C), this catalyst can still trigger CO2 reduction. This work provides a new method to synthesize OVs-Ni(OH)2 catalysts for efficient CO2 reduction and establishes a relationship between the OVs and the catalytic activity, which may guide the design of highly selective CO2 reduction catalysts.

A comparative analysis on characteristics and mortalities of four key transmission populations on antiretroviral therapy: a retrospective cohort study in Northwest China.

BACKGROUND: This study explored disparities in characteristics and mortalities among four major transmission groups on antiretroviral therapy in northwest China as well as the survival impact of each transmission route. METHODS: We first examined disparities in demographics and clinical characteristics of the four transmission populations. Kaplan Meier analysis was subsequently conducted to compare survival rates among all groups. At last, Cox proportional hazards regression model was employed to analyze the survival impact of a transmission route among seven main categories of survival factors associated with all-cause mortalities. RESULTS: Survival analysis showed significant differences in all-cause, AIDS- and non-AIDS-related deaths among four HIV populations (all P < 0.05). Using homosexuals as the reference, Cox proportional hazards model further revealed that the risk of all-cause death for blood and plasma donors was significantly higher than that of the reference (aHR: 5.21, 95%CI: 1.54-17.67); the risk of non-AIDS-related death for heterosexuals (aHR: 2.07, 95%CI: 1.01-4.20) and that for blood and plasma donors (aHR: 19.81, 95%CI: 5.62-69.89) were both significantly higher than that of the reference. CONCLUSIONS: Significant disparities were found in characteristics and mortalities among the four transmission groups where mortality disparities were mainly due to non-AIDS-related death. Suggestions are provided for each group to improve their survivorship.

Cooperative effect of bimetallic MOF-derived CoNi(OH)2@NiCo2S4nanocomposite electrocatalysts with boosted oxygen evolution activity.

Highly efficient and inexpensive electrocatalysts for oxygen evolution reaction (OER) are extensively studied for water splitting. Herein, a unique bimetallic nanocomposite CoNi(OH)2@NiCo2S4nanosheet arrays derived from metal-organic-frameworks (MOFs, CoNi-ZIF) is simply fabricated on Ni foam, endowing large specific surface area and outstanding electrical conductivity. Compared with their single-metallic counterparts, the bimetallic composite displays dramatically low overpotential and small Tafel slope as well as outstanding catalytic stability. The overpoptential at 20 mA cm-2for CoNi(OH)2@NiCo2S4is only 230 mV in comparison with Ni(OH)2@Ni3S2(266 mV), Co(OH)2@Co3S4(294 mV) and RuO2(η = 302 mV). First-principle calculations based on density functional theory (DFT) are carried out and reveal that the introduction of Ni in Co(OH)2helps lowered the energy difference of ΔGOOH*-ΔGO*, and thereby boosting the OER reactivity. This study provides an effective approach for the rational construction of low-cost metal hybrids.

Novel polynitro azoxypyrazole-based energetic materials with high performance.

Novel polynitro azoxypyrazole-based energetic compounds 1,2-bis (4-nitro-1H-pyrazol-5-yl) diazene 1-oxide (3) and 1,2-bis (1,4-dinitro-1H-pyrazol-3-yl) diazene 1-oxide (4) were synthesized from 5-amino-pyrazole-4-carbonitrile by optimized reactions. Their structures were characterized by elemental analysis and single-crystal X-ray diffraction techniques. Compound 3 exhibits high thermal stability (239 °C), low mechanical sensitivity (IS = 22 J, FS = 240 N) and moderate detonation performance (Dv = 8272 m s-1, P = 28.1 GPa). Compound 4 shows moderate thermal stability (161 °C), decent mechanical sensitivity and higher detonation performance (Dv = 9228 m s-1, P = 38.7 GPa) compared to that of RDX. These newly developed strategies for constructing novel energetic compounds enrich the content of the ever-expanding energetic materials.

A semi-crystalline carbonaceous structure as a wide-spectrum-responsive photocatalyst for efficient redox catalysis.

Herein, we synthesized an oxygen- and nitrogen-containing carbonaceous structure (ONCS). This ONCS possessed exceptional light-harvesting ranging from the visible to NIR light region. Characterization results confirmed that the ONCS was an n-type semiconductor. The ONCS can efficiently catalyze hydrogen photosynthesis and benzyl alcohol oxidation under visible light, even under NIR light irradiation.

Polymeric Donor-Acceptor Heterostructures for Enhanced Photocatalytic H2 Evolution without Using Pt Cocatalysts.

Polymeric carbon nitride (CN) is a promising material for photocatalytic water splitting. However, CN in its pristine form tends to show moderate activity due to fast recombination of the charge carriers. The design of efficient photocatalytic system is therefore highly desired, but it still remains a great challenge in chemistry. In this work, a pyrene-based polymer able to serve as an electron donor to accelerate the interface charge carrier transfer of CN is presented. The construction of donor-acceptor (D-A) heterojunction was confirmed to significantly restrain the charge recombination and, thus, improve the proton reduction process. This study provides a promising strategy to achieve solar H2 production in an efficient and low-cost manner.

Carbon Vacancies in a Melon Polymeric Matrix Promote Photocatalytic Carbon Dioxide Conversion.

Photosynthetic conversion of CO2 into fuel and chemicals is a promising but challenging technology. The bottleneck of this reaction lies in the activation of CO2 , owing to the chemical inertness of linear CO2 . Herein, we present a defect-engineering methodology to construct CO2 activation sites by implanting carbon vacancies (CVs) in the melon polymer (MP) matrix. Positron annihilation spectroscopy confirmed the location and density of the CVs in the MP skeleton. In situ diffuse reflectance infrared Fourier transform spectroscopy and a DFT study revealed that the CVs can function as active sites for CO2 activation while stabilizing COOH* intermediates, thereby boosting the reaction kinetics. As a result, the modified MP-TAP-CVs displayed a 45-fold improvement in CO2 -to-CO activity over the pristine MP. The apparent quantum efficiency of the MP-TAP-CVs was 4.8 % at 420 nm. This study sheds new light on the design of high-efficiency polymer semiconductors for CO2 conversion.

Structure-Mediated Charge Separation in Boron Carbon Nitride for Enhanced Photocatalytic Oxidation of Alcohol.

Boron carbon nitride (BCN) is a promising earth-abundant photocatalyst for solar energy conversion. However, the photocatalytic activities of BCN materials remain moderate because of the fast electron-hole recombination. Herein, an ordered BCN structure is fabricated by a facile one-step thermal treatment strategy. The ordered structure of BCN is directly evident from powder X-ray diffraction and high-resolution transmission electron microscopy. Importantly, it is found that the long-period ordered structure can intrinsically accelerate the separation and transfer kinetics of photogenerated charge carriers. Benefiting from these advantages, the ordered BCN structure exhibits remarkable performance for photoinduced selective oxidation of benzyl alcohol compared with the pristine BCN counterpart. This work highlights the important role of the crystal structure of light-harvesting materials in affecting electron-hole separation and at the same time points to the ample potential for improving the photocatalytic performance.

Layered Heterostructures of Ultrathin Polymeric Carbon Nitride and ZnIn2 S4 Nanosheets for Photocatalytic CO2 Reduction.

The rational construction of heterostructures by using layered semiconductors with two-dimensional (2D) nanosheet configurations is promising to improve the efficiency of CO2 photoreduction. Herein, the fabrication of layered heterojunction photocatalysts (PCN/ZnIn2 S4 ) by in situ growth of 2D ZnIn2 S4 nanosheets on the surfaces of ultrathin polymeric carbon nitride (PCN) layers is presented for greatly enhanced CO2 conversion with visible light. The solution-processed self-assembly strategy renders the building of uniform and intimate junctions between PCN layers and ZnIn2 S4 subunits, which remarkably accelerates the separation and transfer of photogenerated charge carriers. In addition, the layered composites can also promote CO2 adsorption and strengthen the visible-light absorption. Consequently, the optimized PCN/ZnIn2 S4 sheet-shaped composite shows reinforced photoactivity for deoxygenative CO2 conversion, affording a high CO-production rate of 44.6 µmol h-1 , which is 223 times higher than that of the pristine PCN nanosheets. Moreover, the heterojunction photocatalyst also exhibits high stability during repeated runs for five cycles.

Photochemical Construction of Carbonitride Structures for Red-Light Redox Catalysis.

Metal-free carbonitride(CN) semiconductors are appealing light-transducers for photocatalytic redox reactions owing to the unique band gap and stability. To harness solar energy efficiently, CN catalysts that are active over a wider range of the visible spectrum are desired. Now a photochemical approach has been used to prepare a new-type triazine-based CN structure. The obtained CN shows extraordinary light-harvesting characteristics, with suitable semiconductor-redox potentials. The light absorption edge of the CN reaches up to 735 nm, which is significantly longer than that of the conventional CN semiconductor at about 460 nm. As expected, the CN can efficiently catalyze oxidation of alcohols and reduction of CO2 with visible light, even under red-light irradiation. The results represent an important step toward the development of red-light-responsive triazine-based structures for solar applications.

Modulating Crystallinity of Graphitic Carbon Nitride for Photocatalytic Oxidation of Alcohols.

Exploiting efficient photocatalysts with strengthened structure for solar-driven alcohol oxidation is of great significance. The photocatalytic performance of graphitic carbon nitrides can be considerably promoted by modulating its crystallinity. Results confirmed that a high crystallinity accelerates the separation and transfer of photogenerated charge carriers, thus providing more free charges for photoredox reactions. More importantly, the high crystallinity facilitated the adsorption of benzyl alcohol and desorption of benzaldehyde and simultaneously lowered the energy barrier for O2 activation. As a result, the crystalline carbon nitride exhibited a roughly twelvefold promotion with respect to the normal carbon nitride. The remarkable enhancement of activity can be attributed to the synergistic effects of increased electron-hole separation and increased surface reaction kinetics. These findings will open up new opportunities to modulate the structure of polymers for a wide variety of organic reactions.

Carbon Nitride Aerogels for the Photoredox Conversion of Water.

Aerogel structures have attracted increasing research interest in energy storage and conversion owing to their unique structural features, and a variety of materials have been engineered into aerogels, including carbon-based materials, metal oxides, linear polymers and even metal chalcogenides. However, manufacture of aerogels from nitride-based materials, particularly the emerging light-weight carbon nitride (CN) semiconductors is rarely reported. Here, we develop a facile method based on self-assembly to produce self-supported CN aerogels, without using any cross-linking agents. The combination of large surface area, incorporated functional groups and three-dimensional (3D) network structure, endows the resulting freestanding aerogels with high photocatalytic activity for hydrogen evolution and H2 O2 production under visible light irradiation. This work presents a simple colloid chemistry strategy to construct 3D CN aerogel networks that shows great potential for solar-to-chemical energy conversion by artificial photosynthesis.

Carbon-Doped BN Nanosheets for the Oxidative Dehydrogenation of Ethylbenzene.

Carbon-based catalysts have demonstrated great potential for the aerobic oxidative dehydrogenation reaction (ODH). However, its widespread application is retarded by the unavoidable deactivation owing to the appearance of coking or combustion under ODH conditions. The synthesis and characterization of porous structure of BCN nanosheets as well as their application as a novel catalyst for ODH is reported. Such BCN nanosheets consist of hybridized, randomly distributed domains of h-BN and C phases, where C, B, and N were confirmed to covalent bond in the graphene-like layers. Our studies reveal that BCN exhibits both high activity and selectivity in oxidative dehydrogenation of ethylbenzene to styrene, as well as excellent oxidation resistance. The discovery of such a simple chemical process to synthesize highly active BCN allows the possibility of carbocatalysis to be explored.

Tri-s-triazine-Based Crystalline Carbon Nitride Nanosheets for an Improved Hydrogen Evolution.

Tri-s-triazine-based crystalline carbon nitride nanosheets (CCNNSs) have been successfully extracted via a conventional and cost-effective sonication-centrifugation process. These CCNNSs possess a highly defined and unambiguous structure with minimal thickness, large aspect ratios, homogeneous tri-s-triazine-based units, and high crystallinity. These tri-s-triazine-based CCNNSs show significantly enhanced photocatalytic hydrogen generation activity under visible light than g-C3 N4 , poly (triazine imide)/Li+ Cl- , and bulk tri-s-triazine-based crystalline carbon nitrides. A highly apparent quantum efficiency of 8.57% at 420 nm for hydrogen production from aqueous methanol feedstock can be achieved from tri-s-triazine-based CCNNSs, exceeding most of the reported carbon nitride nanosheets. Benefiting from the inherent structure of 2D crystals, the ultrathin tri-s-triazine-based CCNNSs provide a broad range of application prospects in the fields of bioimaging, and energy storage and conversion.