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Alkaline water electrolysis is apreferred technology for large-scale green hydrogen production. For most active transition metal-based catalysts during anodic oxygen evolution reaction (OER), the atomic structure of the anodic catalysts' surface often undergoes reconstruction to optimize the reaction path and enhance their catalytic activity. The design and maintenance of highly active sites during this reconstruction process remain critical and challenging for most OER catalysts. In this study, we explored the effects of crystal structures in pre-catalysts on surface reconstruction at low applied potential. Through experimental observation and theoretical calculation, we found out that catalysts with specific crystal structures exhibit superior surface remodeling ability, which enables them to better adapt to the conditions of the oxygen evolution reaction and achieve efficient catalysis. The discharge process enables the formation of abundant phosphorus vacancies on the surface, which in turn affects the efficiency of the entire oxygen evolution reaction. The optimized crystal structure of the catalyst results in an increase as high as 58.5 mA/cm2 for Ni5P4, which is twice as high as that observed for Ni2P. These results provide essential theoretical foundations and technical guidance for designing more efficient catalysts for oxygen evolution reactions.
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DNA damage is a prevalent phenomenon in the context of cancer progression. Evidence suggests that DNA damage responses (DDR) are pivotal in overcoming tumor immune evasion. Alternatively, traditional radiotherapy and chemotherapy operate by inducing DNA damage, consequently stimulating the immune system to target tumors. The intricate interplay between signaling pathways involved in DDR and immune activation underscores the significance of considering both factors in developing improved immunotherapies. By delving deeper into the mechanisms underlying immune activation brought on by DNA damage, it becomes possible to identify novel treatment approaches that boost the anticancer immune response while minimizing undesirable side effects. This review explores the mechanisms behind DNA damage-induced antitumor immune responses, the importance of DNA damage in antitumor immunity, and potential therapeutic approaches for cancer immunotherapy targeting DDR. Additionally, we discuss the challenges of combination therapy and strategies for integrating DNA damage-targeting therapies with current cancer immunotherapy. In summary, this review highlights the critical role of DNA damage in tumor immunology, underscoring the potential of DDR inhibitors as promising therapeutic modalities for cancer treatment.
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Dano ao DNA , Imunoterapia , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Animais , Transdução de Sinais , Reparo do DNARESUMO
Background: Chrysochroinae Laporte de Castelnau, 1835 is the very colourful subfamily of Buprestidae. There are 127 species and subspecies of the subfamily which have been recorded in China. New information: In this paper, we reported three genera, two subgenera and five species of the subfamily Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) which are all newly recorded from China. These reported taxa belong to two tribes and four genera: Chrysochroa (Chroodema) corbetti (Kerremans, 1893), Chrysochroa (Pyranthe) fulgens ephippigera White, 1843, Demochroa (Demoxantha) gratiosa indica Csiki, 1900, Xanthocatabonvouloirii (Deyrolle, 1861) (all the above four being Chrysochroini) and Cardiaspismouhotii E. Saunders, 1866 (Dicercini). The five newly-recorded species are briefly described, illustrated and supplemented with relevant biological information.
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In this paper, two new species of Buprestis subgenus Akiyamaia Kurosawa, 1988 are described: B. (A.) gengmini Qi & Song, new species from Yunnan Province, China and B. (A.) wenii Qi & Song, new species from Yen Bai Province, Vietnam. The descriptions and illustrations of two new species are provided, and the diagnostic characters are provided to distinguish the two new species from other related species. A key is given for identification of all Akiyamaia species.The holotype of B. (A.) costipennis (Fairmaire, 1891) and pictures of living individuals are illustrated for the first time.
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Besouros , Animais , Distribuição Animal , ChinaRESUMO
Surface reconstruction is widely existed on the surface of transition metal-based catalysts under operando oxygen evolution reaction (OER) condition. The design and optimize the reconstruction process are essential to achieve high electrochemical active surface and thus facilitate the reaction kinetics, whereas still challenge. Herein, we exploit electrolyte engineering to regulate reconstruction on the surface of Fe2O3 catalysts under operando OER conditions. The intentional added cations in electrolyte can participate the reconstruction process and realize a desirable crystalline to amorphous structure conversion, contributing abundant well-defined active sites. Spectroscopic measurements and density functional theory calculation provide insight into the underlying role of amorphous structure for electron transfer, mass transport, and intermediate adsorption. With the assistant of Co2+ cations, the enhanced current density as large as 17.9 % can be achieved at 2.32 V (vs RHE). The present results indicate the potential of electrolyte engineering for regulating the reconstruction process and provide a generalized in-situ strategy for advanced catalysts design.
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Tumor cells can evade immune surveillance through overexpressing programmed cell death-ligand 1 (PD-L1) to interact with programmed cell death-1 (PD-1). Besides, tumor-intrinsic PD-L1 is involved in tumor progression without interaction with PD-1, which provides more challenges for the discovery of PD-L1 inhibitors. Herein, we report the discovery of novel PD-L1 inhibitors using the fragment coupling strategy. Among them, B9 was found to inhibit the PD-1/PD-L1 interaction with the best IC50 value of 1.8 ± 0.7 nM. Beyond the blockade of the PD-1/PD-L1 axis, B9 promotes the dimerization, internalization, and degradation of PD-L1. Furthermore, B9 displayed high in vivo antitumor efficacy in the CT26 mouse model and activated the immune microenvironment and induced PD-L1 degradation of PD-L1 in the tumor. These results show that B9 is a promising lead PD-L1 inhibitor through the blockade of PD-1/PD-L1 interaction and functional inhibition of the PD-L1 signal pathway.
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Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Animais , Camundongos , Dimerização , Receptor de Morte Celular Programada 1/metabolismo , Transdução de SinaisRESUMO
Here we describe a symmetrical waveform alternating current strategy that provides a solution for obtaining gradient oxygen vacancies (VO) in situ. The unique gradient VO provides multiple stairs to reduce the reaction kinetics and thus contributes to a total increase of up to 84.7% in current density.
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A new species Coomaniella sunfengyii Liao, Su, Qi & Song, sp. nov. from Fujian Province, China, is described and placed in the Coomaniella macropus species-group. The description, illustrations, host plant information and diagnostic characters of the new species are provided.
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Besouros , Animais , Distribuição Animal , Estruturas Animais , China , MacropodidaeRESUMO
Introduction: Diabetic retinopathy (DR) is one of the most common and destructive microvascular complications of DM, and has become a major cause of irreversible visual impairment. The purpose of this study was to evaluate the changes in fundus microcirculation in non-diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetic mellitus (T2DM) using widefield swept-source optical coherence tomography angiography (WSSOCTA), and to investigate the correlation with laboratory indices of T2DM. Methods: Eighty nine, 58 and 28 eyes were included in the NDR, NPDR and Control groups, respectively, were enrolled in this study. The 12mm×12mm fundus images obtained by WSS-OCTA were divided into 9 regions (supratemporal, ST; temporal, T; inferotemporal, IT; superior, S; central macular area, C; inferior, I; supranasal, SN; nasal, N; inferonasal, IN) to evaluate changes in vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris, and mid-large choroidal vessel (MLCV), as well as changes in inner retinal thickness (IRT), outer retinal thickness (ORT), and choroidal thickness (CT). Results: Compared with control group, MLCV VD (I, N, IN) was significantly decreased in NDR group, SCP VD (IT, C, I) and DCP VD (T, IT, I) were significantly decreased in NPDR group. In NPDR group, DCP VD (IT) was significantly decreased compared with that in NDR group. Compared with control group, CT (ST, T, IT, S, SN, IN) was significantly declined in NDR group, and IRT (ST, IT) and ORT (ST, N) were significantly increased in NPDR group. In NPDR group, IRT (ST) and ORT (T, S) were significantly increased compared with NDR group. Correlation analysis showed that age, body mass index, fasting blood glucose, fasting insulin, fasting C-peptide, and estimated glomerular filtration rate in T2DM patients were statistically correlated with retinal and choroidal thickness/VD. Discussion: Structural and blood flow changes in the choroid occur before the onset of DR and precede changes in the retinal microcirculation, and MLCV thickness/VD is a more sensitive imaging biomarker for the clinical detection of DR. WSS-OCTA enables large-scale non-invasive visual screening and follow-up of the retinal and choroidal vasculature in DR patients, providing a new strategy for the prevention and monitoring of DR in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Retina/diagnóstico por imagem , Retinopatia Diabética/diagnóstico , Corioide/diagnóstico por imagem , Corioide/irrigação sanguíneaRESUMO
Discovery of small-molecule inhibitors against programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis provides a promising alternative to overcome the inevitable defects of PD-1/PD-L1 monoclonal antibodies (mAbs). Here, we report a series of indanes as novel small-molecule inhibitors of PD-1/PD-L1 interaction. Thirty-one indanes were synthesized and the structure-activity relationships (SARs) demonstrated that conformational restriction with (S)-indane is superior in potency to inhibit the interaction of PD-1 and PD-L1. Compound D3 was found to be the most potent inhibitor with an IC50 value of 2.2 nM against PD-1/PD-L1 interaction. Cell-based assay showed that D3 significantly induced immune activity of peripheral blood mononuclear cells (PBMCs) against MDA-MB-231 cells and could restore the immune function of T cells by promoting secretion of the IFN-γ. The above results indicate that compound D3 is a promising PD-1/PD-L1 inhibitor that deserves further development.
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Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Leucócitos Mononucleares , Relação Estrutura-AtividadeRESUMO
In this paper, the subgenus Thailandia Bílý, 1990 of the genus Anthaxia Eschscholtz, 1829 from China is reported, including two species: A. (T.) svatoplukbilyi Qi & Song, sp. nov. from Guangxi and A. (T.) rondoni Baudon, 1962 from Yunnan. The description and illustrations of the new species are provided, the illustrations and information of A. (T.) rondoni from Yunnan are given for the first time, and the diagnostic characters are provided to distinguish the new species from other related species.
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A new stag beetle is described from Yunnan Province, China: Lucanus jiaozishanus Qi, He, Su & Song, new species. It is the third species of the L. boileaui group which are distributed only in Southwestern China and Northeastern Myanmar. The differences of the new species with the more related taxa (L. boileaui Planet, 1897, L. ludivinae Boucher, 1998 and L. takeoi Adachi, 2020) are discussed. A new synonymy, L. bidentis Schenk, 2013 = L. boileaui, is proposed. Keys to males and females of the L. boileaui group are provided. The variation of males, the female and the host plant of L. takeoi (L. maculifemoratus group) are illustrated for the first time.
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Besouros , Masculino , Feminino , Animais , ChinaRESUMO
Three new species of the genus Brachyllus Brenske, 1896 are described from China including Brachyllus songhaitiani Zhao, Qi, Su & Liao, new species from Fujian and Jiangxi, B. dongzhiweii Zhao, new species from Xizang and B. tangzhaoyangi Zhao, new species from Guangxi. Brachyllus langeri Keith, 2008 is downgraded to a subspecies of B. rougeriei Keith, 2003 and reported from China for the first time. Newly collected material of B. deuveianus Keith, 2003 allows better definition of its variability. A distribution map for this genus is also presented.
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Besouros , Animais , ChinaRESUMO
Given the prevalence of diabetes worldwide, diabetic retinopathy (DR) has become the most prominent cause of blindness. However, DR can be diagnosed only when it is severe enough to be clinically detectable. Several studies have evaluated the correlation between DR and diabetic nephropathy (DN) by utilizing optical coherence tomography angiography (OCTA). Compared with other diagnostic techniques, such as fluorescein angiography and fundus photography, OCTA has the ability to directly reflect the condition of the retinal and choroidal microcirculation at an early stage. This review focuses on the following aspects: the advantages of OCTA, the pathophysiology of DR, changes in OCTA images in patients with DR, and the relationships between OCTA parameters and renal function.
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Diabetes Mellitus , Nefropatias Diabéticas , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Nefropatias Diabéticas/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagem , Angiofluoresceinografia/métodos , Corioide/diagnóstico por imagemRESUMO
Janus kinases (JAKs) are central components in cytokine signaling pathways. A number of small molecule JAK inhibitors have been approved to treat a wide range of inflammatory and autoimmune diseases. Due to safety concerns of pan-JAK inhibition, the thrust of current research is toward the discovery of isoform-selective JAK inhibitors. Selective inhibition of tyrosine kinase 2 (TYK2) has the potential to balance efficacy and safety. Substantial efforts have been made to develop selective TYK2 inhibitors: Deucravacitinib (BMS-986165) is a representative allosteric inhibitor that has been approved by the FDA, and ropsacitinib (PF-06826647) is an active site-directed inhibitor currently being evaluated in clinical trials. Herein, we outline the key roles of TYK2 in diseases, review the advances of selective TYK2 inhibitors, and finally discuss future perspectives and challenges in the development of TYK2 inhibitors.
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Doenças Autoimunes , Inibidores de Janus Quinases , Humanos , TYK2 Quinase , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/metabolismo , Doenças Autoimunes/tratamento farmacológicoRESUMO
Depleting NAD+ by blocking its biosynthesis has emerged as an attractive anticancer strategy. Simultaneous blockade of NAD+ production from the salvage and de novo synthesis pathways by targeting NAMPT and IDO1 could achieve more effective NAD+ reduction and, subsequently, more robust antitumor efficacy. Herein, we report the discovery of the first series of dual NAMPT and IDO1 inhibitors according to multitarget drug rationales. Compound 10e has good and balanced inhibitory potencies against NAMPT and IDO1, and significantly inhibits both proliferation and migration of a NSCLC cell line resistant to taxol and FK866 (A549/R cells). Compound 10e also displays potent antitumor efficacy in A549/R xenograft mouse models with no significant toxicity. Moreover, this compound enhances the susceptibility of A549/R cells to taxol in vitro and in vivo. This work provides an efficient approach to targeting NAD+ metabolism in the area of cancer therapy, especially in the context of drug resistance.
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Neoplasias Pulmonares , Nicotinamida Fosforribosiltransferase , Humanos , Animais , Camundongos , Nicotinamida Fosforribosiltransferase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase , NAD/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
The state-of-the-art transition-based electrocatalysts in alkaline media generally suffer from unavoidable surface reconstruction during oxygen evolution reaction measurements, leading to the collapse and loss of the crystalline matrix. Low potential discharge offers a gentle way for surface reconstruction and thus realizes the manipulation of the real active site. Nevertheless, the absence of a fundamental understanding focus on this discharge region renders the functional phase, either the crystalline or amorphous matrix, for the controllable reconstruction still undecidable. Herein, we report a scenario to employ different crystalline matrices as electrocatalysts for discharge region reconstruction. The representative low crystalline Ni2P (LC-Ni2P) possesses a relatively weak surface structure compared with highly crystalline or amorphous Ni2P (HC-Ni2P or A-Ni2P), which contributes abundant oxygen vacancies after the discharge process. The fast discharge behavior of LC-Ni2P leads to the uniform distribution of these vacancies and thus endows the inner interface with reactant activating functionality. A high increase in current density of 36.7% is achieved at 2.32 V (vs RHE) for the LC-Ni2P electrode. The understanding of the discharge behavior in this study, on different crystalline matrices, presents insights into the establishment of controllable surface reconstruction for an effective oxygen evolution reaction.
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Several antibodies targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) have been approved by the U.S. Food and Drug Administration (FDA) for cancer therapy. Although many small-molecule inhibitors of the PD-1/PD-L1 pathway have been reported, no small-molecule inhibitors have been approved for cancer treatment. In this work, a series of novel benzamide derivatives were designed, synthesized, and evaluated to find effective inhibitors of the PD-1/PD-L1 interaction. The most potent compound D2 exhibited better activity than that of BMS202, with an IC50 of 16.17 nM. D2 could activate the antitumor immunity of T cells efficiently in PBMCs. The proposed binding mode of compound D2 was investigated by docking analysis. These results indicate that compound D2 is a promising lead compound that can be used for further development.
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The genus Chrysodema currently recorded from China contains 6 species/subspecies: C. (Chrysodema) aurostriata Saunders, 1866 from Yunnan, C. (C.) lewisii nakatai Frank Sekerka, 2020, C. (C.) eximia berliozi Descarpentries, 1948, C. (Pseudochrysodema) dalmanni dalmanni (Mannerheim, 1837), C. (P.) dalmanni penghuensis Hattori Ong, 2020 and C. (P.) yasumatsui Kurosawa, 1954 all from Taiwan. In this study, one new species, Chrysodema (Chrysodema) hainanensis sp. nov. from Hainan Island, China is described, illustrated, and the variation is given. The host plant Toona ciliata is new for the genus Chrysodema. The differences of the new species to its related species and subspecies are discussed and keyed. C. (C.) aurostriata from Yunnan probably belonged toC. (C.)vrabeci and still need verification. C. (C.) tonkinea Kerremans, 1909 was recorded from Guangxi (new country record). All Chrysodema species and subspecies recorded from China except C. (P.) dalmanni penghuensis and the unverified C. (C.) aurostriata were examined, and a key is given for identification.
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Besouros , Distribuição Animal , Animais , ChinaRESUMO
A new stag beetle fossil is described from the Yixian Formation in northeastern China. A new genus is established based on this well-preserved specimen. Prolucanus beipiaoensis gen. et sp. nov. is firmly placed in the extant lucanid subfamily Lucaninae based on its broad prosternal process and geniculate antennae. Our discovery represents the first fossil record of Lucaninae from the Late Mesozoic of China and the oldest reliable record belonging to the subfamily. We also summarize the fossil species of stag beetles found in China and the described fossil species of the subfamily Lucaninae found in the world. A key to all fossil genera of Lucanidae from China is provided.