When DNA damage responses meet tumor immunity: From mechanism to therapeutic opportunity.

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.

Crystalline-Dependent Discharge Process of Locally Enhanced Electrooxidation Activity on Ni2P.

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.

Dynamin-related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases.

Mitochondria play a key role in the maintenance of neuronal function by continuously providing energy. Here, we will give a detailed review about the recent developments in regards to dynamin-related protein 1 (Drp1) induced unbalanced mitochondrial dynamics, excessive mitochondrial division, and neuronal injury in neural system dysfunctions and neurodegenerative diseases, including the Drp1 knockout induced mice embryonic death, the dysfunction of the Drp1-dependent mitochondrial division induced neuronal cell apoptosis and impaired neuronal axonal transportation, the abnormal interaction between Drp1 and amyloid ß (Aß) in Alzheimer's disease (AD), the mutant Huntingtin (Htt) in Huntington's disease (HD), and the Drp1-associated pathogenesis of other neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Drp1 is required for mitochondrial division determining the size, shape, distribution, and remodeling as well as maintaining of mitochondrial integrity in mammalian cells. In addition, increasing reports indicate that the Drp1 is involved in some cellular events of neuronal cells causing some neural system dysfunctions and neurodegenerative diseases, including impaired mitochondrial dynamics, apoptosis, and several posttranslational modification induced increased mitochondrial divisions. Recent studies also revealed that the Drp1 can interact with Aß, phosphorylated τ, and mutant Htt affecting the mitochondrial shape, size, distribution, axonal transportation, and energy production in the AD and HD neuronal cells. These changes can affect the health of mitochondria and the function of synapses causing neuronal injury and eventually leading to the dysfunction of memory, cognitive impairment, resting tremor, posture instability, involuntary movements, and progressive muscle atrophy and paralysis in patients.

Endoplasmic Reticulum Stress and Autophagy.

In 1945, K. R. Porter et al. observed mouse embryonic fibroblasts (MEFs) and found that the cytoplasmic part of the cell had an unreported reticular structure, so it was named endoplasmic reticulum (ER). The major functions of the endoplasmic reticulum are: synthesis of intracellular proteins and the modification and processing of proteins. It is an important organelle in eukaryotic cells. It is a three-dimensional network structure in which complex and closed intracellular tubular intimal systems are intertwined. When cells are subjected to various strong stimulating factors such as nutrient deficiencies, Ca2+ metabolic imbalance, toxin stimulation, and sustained oxidative stress stimulation, the cell homeostasis will be broken. In order to survive, a series of cell self-protection event will be initiated including the endoplasmic reticulum stress (ERS). The UPR can further promote the expression of the proteins which can help the misfolded and unfolded proteins restore to its normal structure through the activation of PERK, IRE1, and ATF6. However, the co-working of UPR and the ubiquitin-proteasome system still cannot make the endoplasmic reticulum restoring to its normal state, when the stimuli persist or are too strong. The damaged endoplasmic reticulum can be partially engulfed by the autophagic vesicles for degradation when the ERS persists. The degraded endoplasmic reticulum fragments can be reassembled into a new endoplasmic reticulum to restore the normal state of it. Hence, it seems that the autophagy has become the last mean to restore the homeostasis of endoplasmic reticulum.

New records of Chrysochroinae Laporte de Castelnau, 1835 (Coleoptera, Buprestidae) from China.

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.

Soluble inorganic quantum dots as an electrolyte additive to boost lithium-sulfur battery performance.

Herein, MoS2 quantum dots (QDs) are constructed to serve as electrolyte additives for lithium-sulfur batteries, which can 'solidify' soluble polysulfides by chemisorption and promote sulfur conversion chemistry by electrocatalysis. The Li-S cell with MoS2 QDs shows high retained capacity and high-rate capability, much better than the counterpart without MoS2 QDs.

Revision of the rare Buprestis subgenus Akiyamaia Kurosawa, 1988 (Coleoptera: Buprestidae: Buprestinae), with description of two new species.

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.

Crystalline-dependent surface reconstruction at low applied potential region for enhanced oxygen evolution reaction.

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.

Discovery of Benzo[d]oxazoles as Novel Dual Small-Molecule Inhibitors Targeting PD-1/PD-L1 and VISTA Pathway.

The blockers of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway have achieved great clinical success. However, the limited efficacy and low tumor response rate of anti-PD-1/PD-L1 monotherapy limit the clinical application of PD-1/PD-L1 inhibitors. V-domain immunoglobulin suppressor of T-cell activation (VISTA), a novel checkpoint regulator, exhibits potential synergy with PD-1/PD-L1 in enhancing antitumor immunity. Herein, we report the discovery of benzo[d]oxazole B3 as novel dual small-molecule inhibitors targeting PD-1/PD-L1 and VISTA with high PD-1/PD-L1 inhibitory activity and VISTA binding affinity. B3 rescues the immunosuppression of T-cells mediated by PD-L1 and VISTA and activates antitumor immunity effectively. Moreover, B3 could induce degradation of PD-L1 and VISTA in tumor cell. Furthermore, B3 displays significant in vivo antitumor efficacy in a CT26 mouse model. Our results discover B3 as a promising dual PD-1/PD-L1 and VISTA inhibitor, providing a novel therapeutic strategy to overcome the limitations of current anti-PD-1/PD-L1 therapy.

Cations induced in situ electrochemical amorphization for enhanced oxygen evolution reaction.

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.

Discovery of small molecules for autophagy-lysosome degradation of immune checkpoint proteins.

Targeted protein degradation (TPD) technologies, particularly proteolysis targeting chimeras (PROTACs), have emerged as a promising branch of targeted therapy. Current ubiquitin-proteasome-dependent TPD technologies are limited to targeting intracellular proteins. Although the blockade of immune checkpoints has achieved great clinical success, most immune checkpoints are transmembrane proteins, which are difficult to be ubiquitinated and degraded by PROTACs. Herein, we developed a novel discovery strategy of bifunctional small molecules, which could mediate autophagy-lysosome degradation of immune checkpoints. F-1 was demonstrated to activate the autophagy-lysosome system, and conjugation of F-1 with inhibitors targeting programmed cell death-ligand 1 (PD-L1) or V-domain Ig suppressor of T-cell activation (VISTA) generated a new class of small molecules that effectively induce the degradation of PD-L1 or VISTA in tumor cells. The most promising PD-L1 degrader B3 significantly induced PD-L1 degradation in RKO cells through the autophagy-lysosome system and exhibited good tumor-inhibiting effects in vivo. Our work could expand the development of degraders targeting immune checkpoints and provide a promising discovery strategy for future autophagy-lysosome targeting degradation technology.

Optical coherence tomography angiography for assessment of changes of the retina and choroid in different stages of diabetic retinopathy and their relationship with diabetic nephropathy.

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.

New and poorly known species of the genus Brachyllus Brenske, 1896 (Coleoptera: Scarabaeidae: Melolonthinae) from China.

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.

A study of Anthaxia subgen. Thailandia Bílý, 1990 from China (Coleoptera, Buprestidae, Buprestinae).

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.

Dual Nicotinamide Phosphoribosyltransferase (NAMPT) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors for the Treatment of Drug-Resistant Nonsmall-Cell Lung Cancer.

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.

Development and Therapeutic Implications of Tyrosine Kinase 2 Inhibitors.

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.

Revision of the Lucanus boileaui group and notes on L . takeoi Adachi, 2020 from the L . maculifemoratus group (Coleoptera: Lucanidae: Lucaninae).

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.

Analysis of retinal and choroidal characteristics in patients with early diabetic retinopathy using WSS-OCTA.

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.

Symmetrical-waveform alternating current-promoted NiOxHy electrocatalysis for the oxygen evolution reaction.

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.

Coomaniella sunfengyii sp. nov., a new species from Fujian, China (Coleoptera: Buprestidae: Coomaniellini).

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.