Pyramiding of triple Clubroot resistance loci conferred superior resistance without negative effects on agronomic traits in Brassica napus.

Clubroot disease caused by Plasmodiophora brassicae is becoming a serious threat to rapeseed (Brassica napus) production worldwide. Breeding resistant varieties using CR (clubroot resistance) loci is the most promising solution. Using marker-assisted selection and speed-breeding technologies, we generated Brassica napus materials in homozygous or heterozygous states using CRA3.7, CRA08.1, and CRA3.2 loci in the elite parental line of the Zhongshuang11 background. We developed three elite lines with two CR loci in different combinations and one line with three CR loci at the homozygous state. In our study, we used six different clubroot strains (Xinmin, Lincang, Yuxi, Chengdu, Chongqing, and Jixi) which are categorized into three groups based on our screening results. The newly pyramided lines with two or more CR loci displayed better disease resistance than the parental lines carrying single CR loci. There is an obvious gene dosage effect between CR loci and disease resistance levels. For example, pyramided lines with triple CR loci in the homozygous state showed superior resistance for all pathogens tested. Moreover, CR loci in the homozygous state are better on disease resistance than the heterozygous state. More importantly, no negative effect was observed on agronomic traits for the presence of multiple CR loci in the same background. Overall, these data suggest that the pyramiding of triple clubroot resistance loci conferred superior resistance with no negative effects on agronomic traits in Brassica napus.

Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

BACKGROUND AND OBJECTIVES: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. METHODS: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. RESULTS: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). CONCLUSIONS: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02673424.

Progress in the application of ultrasound in glioma surgery.

Brain glioma, which is highly invasive and has a poor prognosis, is the most common primary intracranial tumor. Several studies have verified that the extent of resection is a considerable prognostic factor for achieving the best results in neurosurgical oncology. To obtain gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of existing devices, it is imperative to develop a real-time image-guided resection technique to offer reliable functional and anatomical information during surgery. At present, the application of intraoperative ultrasound (IOUS) has been indicated to enhance resection rates and maximize brain function preservation. IOUS, which is promising due to its lower cost, minimal operational flow interruptions, and lack of radiation exposure, can enable real-time localization and precise tumor size and form descriptions while assisting in discriminating residual tumors and solving brain tissue shifts. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound (CEUS), three-dimensional ultrasound (3DUS), noninvasive ultrasound (NUS), and ultrasound elastography (UE), could assist in achieving GTR in glioma surgery. This article reviews the advantages and disadvantages of IOUS in glioma surgery.

Cost-effectiveness of dostarlimab plus chemotherapy for primary advanced or recurrent endometrial cancer.

Objective: In the double-blind, phase III, placebo-controlled RUBY randomized clinical trial, dostarlimab plus carboplatin-paclitaxel significantly increased survival among patients with primary advanced or recurrent endometrial cancer (EC). We conducted a cost-effectiveness analysis of dostarlimab in combination with chemotherapy in these patients stratified by mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) subgroups from the perspective of a United States payer. Materials and methods: A Markov model with three states was employed to simulate patients who were administered either dostarlimab in combination with chemotherapy or chemotherapy based on the RUBY trial. Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model. Results: In dMMR EC, the combination of dostarlimab and chemotherapy achieved an additional 5.48 QALYs at an incremental cost of $330,747 compared to chemotherapy alone, resulting in an ICER of $60,349.30 per QALY. In pMMR EC, there were 1.51 additional QALYs gained at an extra cost of $265,148, yielding an ICER of $175,788.47 per QALY. With a 15.2% discount on dostarlimab, the ICER decreased to $150,000 per QALY in the pMMR EC. The univariate sensitivity analysis revealed that the cost of dostarlimab, utility of progression-free survival (PFS), and progressive disease (PD) had the most significant impacts on the outcomes. Probabilistic sensitivity analysis revealed that dostarlimab had a 100% likelihood of being considered cost-effective for patients at a WTP threshold of $150,000 per QALY for dMMR EC, whereas this likelihood was only 0.5% for pMMR EC. Conclusion: Dostarlimab in combination with chemotherapy was cost-effective for primary advanced or recurrent dMMR EC from the perspective of a United States payer at a WTP threshold of $150,000 per QALY, but not for pMMR EC. Lowering the prices of dostarlimab could potentially enhance the cost-effectiveness of treatment for pMMR EC.

Improving the Oxygen Evolution Reaction Kinetics in Zn-Air Battery by Iodide Oxidation Reaction.

Zinc-air batteries (ZABs) have garnered considerable attention as a highly promising contender in the field of energy storage and conversion. Nevertheless, their performance is considerably impeded by the proliferation of dendrites on the Zinc anode and the slow kinetics of the redox reaction on the air cathode. Herein, taking Ag30%@LaCoO3 (Ag30%@LCO) heterojunction catalyst as the cathode, it is demonstrated that adding KI additives to the alkaline electrolyte can not only enhance the oxygen electrocatalytic reaction but also inhibit the formation of zinc anode dendrites, thereby achieving a comprehensive improvement in the performance of ZABs. Under the action of the KI additive, the optimized Ag30%@LCO catalyst shows a decreased overpotential from 460 to 220 mV at j = 10 mA cm-2, while the assembled ZAB shows reduced charging potential (1.8 V), and long cycle stability (180 h). Furthermore, the morphology characterization results indicate a reduction in dendrites on the Zn anode. Both experimental and calculated results indicate that the presence of I- as a reaction modifier alters the trajectory of the conventional oxygen evolution reaction, resulting in a more thermodynamically favorable pathway. The introduction of KI additives as electrolytes provides a straightforward approach to developing comprehensively improved ZABs.

Probing Dual Covalent Irreversible Inhibition of EGFR/FGFR4 by Electrophilic-Based Natural Compounds to Overcome Resistance and Enhance Combination Therapeutic Potentials and Management of Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types in the world and accounts for the majority of cases of primary liver cancer. A crucial part of the carcinogenesis of HCC involves aberrant stimulation of the FGF19-FGFR4 signaling pathway. Therefore, FGFR4 inhibition has become a strategic therapeutic approach for the treatment of HCC. However, the clinical treatment procedure is significantly hampered by the prevalence of kinase inhibitors resistance. It was recently established that the activation of EGFR signaling was found to be one of the primary mechanisms mediating the acquired resistance to FGFR4 inhibitors, moreover, sensitivity to FGFR4 inhibitors was effectively restored by inhibiting EGFR. These results provide compelling evidence that dual inhibition of EGFR and FGFR4 could represent a viable therapeutic approach to overcome resistance, hence enhanced management of HCC. To this end, we proposed a dual irreversible inhibition strategy through covalent binding by naturally occurring electrophilic warhead-bearing compounds (curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A and andrographolide) to covalently target both EGFR and FGFR4 through cysteine residues, Cys797 and Cys552, respectively. Covalent docking and covalent molecular dynamics (MM/MDcov) simulations combined with thermodynamic binding free energy calculations were performed, and the results were compared against known potent and selective covalent EGFR and FGFR4 inhibitors with available X-ray crystal structures, Afatinib and BLU9931, respectively. Curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A, and andrographolide showed relative binding free energies of -22.85, -17.14, -12.98, -21.81, and - 19.00 kcal/mol against EGFR and - 41.06, -29.45, -24.76, -40.11, and - 37.55 kcal/mol against FGFR4, respectively. The mechanisms of binding were emphasized by hydrogen bonding and binding forces analysis as well as active site physicochemical profiling. The findings of this study identified that curcumin, syringolin A and andrographolide-but not eupalmerin acetate or deoxyelephantopin -could be viable dual EGFR and FGFR4 covalent irreversible inhibitors and could be implemented in HCC combination therapy protocols alone or in conjunction with other chemotherapeutic agents. Investigations of this study conclusively indicate dual blockade of EGFR and FGFR4 may be a promising future therapeutic strategy for enhanced management of HCC.

Bioinformatics and functional analysis of EDS1 genes in Brassica napus in response to Plasmodiophora brassicae infection.

Enhanced Disease Susceptibility 1 (EDS1) is a key regulator of plant-pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) responses. In the Brassica napus genome, we identified six novel EDS1 genes, among which four were responsive to clubroot infection, a major rapeseed disease resistant to chemical control. Developing resistant cultivars is a potent and economically viable strategy to control clubroot infection. Bioinformatics analysis revealed conserved domains and structural uniformity in Bna-EDS1 homologs. Bna-EDS1 promoters harbored elements associated with diverse phytohormones and stress responses, highlighting their crucial roles in plant defense. A functional analysis was performed with Bna-EDS1 overexpression and RNAi transgenic lines. Bna-EDS1 overexpression boosted resistance to clubroot and upregulated defense-associated genes (PR1, PR2, ICS1, and CBP60), while Bna-EDS1 RNAi increased plant susceptibility, indicating suppression of the defense signaling pathway downstream of NBS-LRRs. RNA-Seq analysis identified key transcripts associated with clubroot resistance, including phenylpropanoid biosynthesis. Activation of SA regulator NPR1, defense signaling markers PR1 and PR2, and upregulation of MYC-TFs suggested that EDS1-mediated clubroot resistance potentially involves the SA pathway. Our findings underscore the pivotal role of Bna-EDS1-dependent mechanisms in resistance of B. napus to clubroot disease, and provide valuable insights for fortifying resistance against Plasmodiophora brassicae infection in rapeseed.

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status.

Actn2 defects accelerates H9c2 hypertrophy via ERK phosphorylation under chronic stress.

BACKGROUND: In humans, ACTN2 mutations are identified as highly relevant to a range of cardiomyopathies such as DCM and HCM, while their association with sudden cardiac death has been observed in forensic cases. Although ACTN2 has been shown to regulate sarcomere Z-disc organization, a causal relationship between ACTN2 dysregulation and cardiomyopathies under chronic stress has not yet been investigated. OBJECTIVE: In this work, we explored the relationship between Actn2 dysregulation and cardiomyopathies under dexamethasone treatment. METHODS: Previous cases of ACTN2 mutations were collected and the conservative analysis was carried out by MEGA 11, the possible impact on the stability and function of ACTN2 affected by these mutations was predicted by Polyphen-2. ACTN2 was suppressed by siRNA in H9c2 cells under dexamethasone treatment to mimic the chronic stress in vitro. Then the cardiac hypertrophic molecular biomarkers were elevated, and the potential pathways were explored by transcriptome analysis. RESULTS: Actn2 suppression impaired calcium uptake and increased hypertrophy in H9c2 cells under dexamethasone treatment. Concomitantly, hypertrophic molecular biomarkers were also elevated in Actn2-suppressed cells. Further transcriptome analysis and Western blotting data suggested that Actn2 suppression led to the excessive activation of the MAPK pathway and ERK cascade. In vitro pharmaceutical intervention with ERK inhibitors could partially reverse the morphological changes and inhibit the excessive cardiac hypertrophic molecular biomarkers in H9c2 cells. CONCLUSION: Our study revealed a functional role of ACTN2 under chronic stress, loss of ACTN2 function accelerated H9c2 hypertrophy through ERK signaling. A commercial drug, Ibudilast, was identified to reverse cell hypertrophy in vitro.

Palladium-catalyzed amidation of carbazole derivatives via hydroamination of isocyanates.

The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole-N-carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.

Diagnostic performance of Node-RADS score for mesorectal lymph node metastasis in rectal cancer.

PURPOSE: To explore the diagnostic performance of the Node-RADS scoring system on preoperative assessment of mesorectal lymph node metastasis (LNM) status in rectal cancer, in comparison with the ESGAR category and size of lymph node (LN). METHODS: Preoperative clinical and MRI data of 154 rectal adenocarcinoma patients treated with radical resection surgery were retrospectively analyzed. The differences in the clinical, pathological and imaging characteristics between the pN- and pN + groups were surveyed. The correlations of Node-RADS score and ESGAR category to pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological LNM were compared among individual approaches. A nomogram combined the imaging and clinical features was also established and evaluated. RESULTS: Significant differences in CEA, tumor maximum diameter, tumor location, LN short-axis diameter, Node-RADS score and ESGAR category were found between the pN- and pN + groups. Node-RADS correlated significantly with pN stage, LNM number, and LNR (r = 0.665, 0.685, and 0.675, p < 0.001). Node-RADS had the highest AUC (0.862) for predicting pN + status, surpassing ESGAR (AUC = 0.797, p = 0.040) and LN size (AUC = 0.762, p = 0.015). The nomogram had the best diagnostic performance (AUC = 0.901), significantly outperforming Node-RADS alone (p = 0.037). CONCLUSIONS: The Node-RADS scoring system is comparable to the ESGAR category and surpasses short-axis diameter in preoperatively predicting LNM in rectal cancer. Integrating imaging and clinical features will lead to an enhancement in diagnostic performance. Moreover, a clear relationship was demonstrated between the Node-RADS score and the quantity-dependent pathological characteristics of LNM.

Synthesis and Biological Activity of 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] Quinoline for the Treatment of Colorectal Cancer by Modulating PI3K/AKT/mTOR Pathways.

Developing novel drugs from natural products has proven to be a very effective strategy. Neocryptolepine was isolated from Cryptolepis sanguinolenta, a traditional endemic African herb, which exerts a wide range of biological activities such as antimalaria, antibacterial, and antitumor. 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] quinoline (compound 49) was synthesized, and its cytotoxicity was assessed on pancreatic cancer PANC-1 cells, colorectal cancer HCT116 cells, liver cancer SMMC-7721 cells, and gastric cancer AGS cells in vitro. The results of the in vitro assay showed that compound 49 exerted remarkable cytotoxicity on colorectal cancer HCT116 and Caco-2 cells. The cytotoxicity of compound 49 to colorectal cancer HCT116 cells was 17 times higher than that of neocryptolepine and to human normal intestinal epithelial HIEC cells was significantly reduced. Compound 49 exhibited significant cytotoxicity against the colorectal cancer HCT116 and Caco-2 cells, with IC50 of 0.35 and 0.54 µM, respectively. The mechanism of cytotoxicity of compound 49 to colorectal cancer HCT116 and Caco-2 cells was further investigated. The results showed that compound 49 could inhibit colony formation and cell migration. Moreover, compound 49 could arrest the cell cycle at the G2/M phase, promote the production of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The results of Western blot indicated that compound 49 showed cytotoxicity on HCT116 and Caco-2 cells by modulating the PI3K/AKT/mTOR signaling pathway. In conclusion, these results suggested that compound 49 may be a potentially promising lead compound for the treatment of colorectal cancer.

Reticulated Retinoic Acid Synthesis is Implicated in the Pathogenesis of Dry Eye in Aqp5 Deficiency Mice.

Purpose: Abnormalities in aquaporins are implicated in the pathological progression of dry eye syndrome. Retinoic acid (RA) regulates cellular proliferation, differentiation, and apoptosis in the cornea, thereby being associated with dry eye disease (DED). The objective of this study is to explore the underlying mechanisms responsible for RA metabolic abnormalities in corneas lacking aquaporin 5 (AQP5). Methods: Dry eye (DE) models were induced via subcutaneous scopolamine hydrobromide. Aqp5 knockout (Aqp5-/-) mice and DE mice were utilized to assess corneal epithelial alterations. Tear secretion, goblet cell counts, and corneal punctate defects were evaluated. The impact of Aqp5 on RA-related enzymes and receptors was investigated using pharmacological RA or SR (A JunB inhibitor), a transcription factor JunB inhibitor, treatment in mouse corneal epithelial cells (CECs), or human corneal epithelial cells (HCECs). The HCECs and NaCl-treated HCECs underwent quantitative real-time PCR (qRT-PCR), immunofluorescent, Western blot, and TUNEL assays. The regulation of transcription factor JunB on Aldh1a1 was explored via ChIP-PCR. Results: Aqp5 and Aldh1a1 were reduced in both CECs of DE mice and NaCl-induced HCECs. Aqp5-/- mice exhibited DE phenotype and reduced Aldh1a1. RA treatment reduced apoptosis, promoted proliferation, and improved the DE phenotype in Aqp5-/- mice. JunB enrichment in the Aldh1a1 promoter was identified by ChIP-PCR. SR significantly increased Aldh1a1 expression, Ki67, and ΔNp63-positive cells, and decreased TUNEL-positive cells in CECs and HCECs. Conclusions: Our findings demonstrated the downregulation of Aqp5 expression and aberrant RA metabolism in DE conditions. Knockout of Aqp5 resulted in reduced production of RA through activation of JunB, subsequently leading to the manifestation of DE symptoms.

Myeloid-derived growth factor in diseases: structure, function and mechanisms.

Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).

Nitrous oxide (N2O) emission characteristics of farmland (rice, wheat, and maize) based on different fertilization strategies.

Fertilizer application is the basis for ensuring high yield, high quality and high efficiency of farmland. In order to meet the demand for food with the increasing of population, the application of nitrogen fertilizer will be further increased, which will lead to problems such as N2O emission and nitrogen loss from farmland, it will easily deteriorate the soil and water environment of farmland, and will not conducive to the sustainable development of modern agriculture. However, optimizing fertilizer management is an important way to solve this problem. While, due to the differences in the study conditions (geographical location, environmental conditions, experimental design, etc.), leading to the results obtained in the literatures about the N2O emission with different nitrogen fertilizer application strategies have significant differences, which requiring further comprehensive quantitative analysis. Therefore, we analyzed the effects of nitrogen fertilizer application strategies (different fertilizer types and fertilizer application rates) on N2O emissions from the fields (rice, wheat and maize) based on the Meta-analysis using 67 published studies (including 1289 comparisons). For the three crops, inorganic fertilizer application significantly increased on-farm N2O emissions by 19.7-101.05% for all three; and organic fertilizer increased N2O emissions by 28.16% and 69.44% in wheat and maize fields, respectively, but the application of organic fertilizer in rice field significantly reduced N2O emissions by 58.1%. The results showed that overall, the application of inorganic fertilizers resulted in higher N2O emissions from farmland compared to the application of organic fertilizers. In addition, in this study, the average annual temperature, annual precipitation, soil type, pH, soil total nitrogen content, soil organic carbon content, and soil bulk weight were used as the main influencing factors of N2O emission under nitrogen fertilizer strategies, and the results of the study can provide a reference for the development of integrated management measures to control greenhouse gas emissions from agricultural soils.

Multilayer stacked ultra-wideband perfect solar absorber and thermal emitter based on SiO2-InAs-TiN nanofilm structure.

In this paper, a broadband solar absorber is constructed and simulated based on the finite difference time domain method (FDTD). The modeled structure of the absorber consists of cyclic stacking of five absorber cells with different periods on refractory metal W, where a single absorber cell is composed of a three-layer SiO2-InAs-TiN square film. Due to the Fabry-Perot resonance and the surface plasmon resonance (SPR), an absorptivity greater than 90% within a bandwidth of 2599.5 nm was achieved for the absorber. Notably, one of these bands, 2001 nm, is a high-efficiency absorption with an absorption rate greater than 99%. The average absorption efficiency reaches 99.31% at an air mass of 1.5 (AM 1.5), and the thermal radiation efficiencies are 97.35% and 97.83% at 1000 K and 1200 K, respectively. At the same time, the structure of the absorber is also polarization-independent, and when the solar incidence angle is increased to 60°, it still achieves an average absorption of 90.83% over the entire wavelength band (280 nm to 3000 nm). The novelty of our work is to provide a design idea based on a unit structure with multiple cycles, which can effectively expand the absorption bandwidth of the absorber in the visible-near-infrared wavelengths. The excellent performances make the structure widely used in the field of solar energy absorption.

Dihydroartemisinin remodels tumor micro-environment and improves cancer immunotherapy through inhibiting cyclin-dependent kinases.

Cancer immunotherapies are ineffective in nonresponding patients due to absence of immune responses. Here, we identified that dihydroartemisinin (DHA) induced immunogenic cell death (ICD) in hepatocellular carcinoma (HCC), proved by release or surface expose of damage-associated molecular patterns and in vivo protective vaccine activity. Mechanistically, DHA can inhibit cyclin-dependent kinases (CDKs), leading to a buildup of intracellular reactive oxygen species (ROS), which induces immunogenic cell death. In both Hepa1-6 and H22 tumor bearing mice, DHA exerted anti-tumor activity through increasing tumor-infiltrating CD8+ T cells with expression of activation makers (CD25 and CD69), secretion of intracellular cytokines (IFN-γ and TNF-α) and activated dendritic cells expressing MHCⅡ, CD80 and CD86. In hepa1-6 tumor bearing mice, DHA decreased immunosuppressive myeloid-derived suppressor cells. Furthermore, DHA enhanced the anti-PD-1 antibody and chimeric antigen receptor (CAR) T cell-mediated tumor suppression through recruitment and activation of endogenous CD8+ T cells. Overall, we demonstrated that by inhibiting CDKs, DHA can remodel tumor micro-environment to amplify anti-tumor immune responses in HCC. These findings provide a promising therapy option for HCC patients.