Evolutionary Dynamics of Chromatin Structure and Duplicate Gene Expression in Diploid and Allopolyploid Cotton.

Polyploidy is a prominent mechanism of plant speciation and adaptation, yet the mechanistic understandings of duplicated gene regulation remain elusive. Chromatin structure dynamics are suggested to govern gene regulatory control. Here, we characterized genome-wide nucleosome organization and chromatin accessibility in allotetraploid cotton, Gossypium hirsutum (AADD, 2n = 4X = 52), relative to its two diploid parents (AA or DD genome) and their synthetic diploid hybrid (AD), using DNS-seq. The larger A-genome exhibited wider average nucleosome spacing in diploids, and this intergenomic difference diminished in the allopolyploid but not hybrid. Allopolyploidization also exhibited increased accessibility at promoters genome-wide and synchronized cis-regulatory motifs between subgenomes. A prominent cis-acting control was inferred for chromatin dynamics and demonstrated by transposable element removal from promoters. Linking accessibility to gene expression patterns, we found distinct regulatory effects for hybridization and later allopolyploid stages, including nuanced establishment of homoeolog expression bias and expression level dominance. Histone gene expression and nucleosome organization are coordinated through chromatin accessibility. Our study demonstrates the capability to track high-resolution chromatin structure dynamics and reveals their role in the evolution of cis-regulatory landscapes and duplicate gene expression in polyploids, illuminating regulatory ties to subgenomic asymmetry and dominance.

Non-adherent culture method affects the proliferation and apoptosis of mesenchymal stem cells through inhibiting LINC00707 to promote RNF6-mediated QKI ubiquitination.

Exploration of the molecular mechanisms of mesenchymal stem cell (MSC) growth has significant clinical benefits. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in the regulation of the osteogenic differentiation of MSCs. However, the mechanism by which lncRNA affects the proliferation and apoptosis of MSCs is unclear. In this study, sequencing analysis revealed that LINC00707 was significantly decreased in non-adherent human MSCs (non-AC-hMSCs) compared to adherent human MSCs. Moreover, LINC00707 overexpression promoted non-AChMSC proliferation, cell cycle progression from the G0/G1 phase to the S phase and inhibited apoptosis, whereas LINC00707 silencing had the opposite effect. Furthermore, LINC00707 interacted directly with the quaking (QKI) protein and enhanced the E3 ubiquitin-protein ligase ring finger protein 6 (RNF6)-mediated ubiquitination of the QKI protein. Additionally, the overexpression of QKI rescued the promotive effects on proliferation and inhibitory effects on apoptosis in non-AC-hMSCs induced by the ectopic expression of LINC00707. Thus, LINC00707 contributes to the proliferation and apoptosis in non-AChMSCs by regulating the ubiquitination and degradation of the QKI protein.

Diatomic Iron with a Pseudo-Phthalocyanine Coordination Environment for Highly Efficient Oxygen Reduction over 150,000 Cycles.

Atomically dispersed Fe-N-C catalysts emerged as promising alternatives to commercial Pt/C for the oxygen reduction reaction. However, the majority of Fe-N-C catalysts showed unsatisfactory activity and durability due to their inferior O-O bond-breaking capability and rapid Fe demetallization. Herein, we create a pseudo-phthalocyanine environment coordinated diatomic iron (Fe2-pPc) catalyst by grafting the core domain of iron phthalocyanine (Fe-Nα-Cα-Nß) onto defective carbon. In situ characterizations and theoretical calculation confirm that Fe2-pPc follows the fast-kinetic dissociative pathway, whereby Fe2-pPc triggers bridge-mode oxygen adsorption and catalyzes direct O-O radical cleavage. Compared to traditional Fe-N-C and FePc-based catalysts exhibiting superoxo-like oxygen adsorption and an *OOH-involved pathway, Fe2-pPc delivers a superior half-wave potential of 0.92 V. Furthermore, the ultrastrong Nα-Cα bonds in the pPc environment endow the diatomic iron active center with high tolerance for reaction-induced geometric stress, leading to significantly promoted resistance to demetallization. Upon an unprecedented harsh accelerated degradation test of 150,000 cycles, Fe2-pPc experiences negligible Fe loss and an extremely small activity decay of 17 mV, being the most robust candidate among previously reported Fe-N-C catalysts. Zinc-air batteries employing Fe2-pPc exhibit a power density of 255 mW cm-2 and excellent operation stability beyond 440 h. This work brings new insights into the design of atomically precise metallic catalysts.

Luminescent Mechanism and Anti-Counterfeiting Application of Hydrophilic, Undoped Room-Temperature Phosphorescent Silicon Nanocrystals.

Silicon nanocrystals (SiNCs) have attracted extensive attention in many advanced applications due to silicon's high natural abundance, low toxicity, and impressive optical properties. However, these applications are mainly focused on fluorescent SiNCs, little attention is paid to SiNCs with room-temperature phosphorescence (RTP) and their relative applications, especially water-dispersed ones. Herein, this work presents water-dispersible RTP SiNCs (UA-SiNCs) and their optical applications. The UA-SiNCs with a uniform particle size of 2.8 nm are prepared by thermal hydrosilylation between hydrogen-terminated SiNCs (H-SiNCs) and 10-undecenoic acid (UA). Interestingly, the resultant UA-SiNCs can exhibit tunable long-lived RTP with an average lifetime of 0.85 s. The RTP feature of the UA-SiNCs is confirmed to the n-π* transitions of their surface C═O groups. Subsequently, new dual-modal emissive UA-SiNCs-based ink is fabricated by blending with sodium alginate (SA) as the binder. The customized anticounterfeiting labels are also prepared on cellulosic substrates by screen-printing technique. As expected, UA-SiNCs/SA ink exhibits excellent practicability in anticounterfeiting applications. These findings will trigger the rapid development of RTP SiNCs, envisioning enormous potential in future advanced applications such as high-level anti-counterfeiting, information encryption, and so forth.

Ultrahigh Degree of Cationic Disorder, Configurational Entropy in New Type of High-Entropy Pseudobrookite Phase.

High-entropy ceramics exhibit various excellent properties owing to their high configurational entropy, which is caused by multi-principal elements sharing one lattice site. The configurational entropy will further increase significantly if multi-principal elements randomly share two different lattice sites. For this purpose, pseudobrookite phase containing two cationic lattice sites (A and B sites) is selected, and corresponding high-entropy pseudobrookite (M2+ 0.4M3+ 1.2)Ti1.4O5 is synthesized. Herein, the distribution of the 2-valent and 3-valent cations in the A and B sites are analysed in depth. The distance between the A and B sites in the crystal structure models which are constructed by the Rietveld analysis is calculated and defined as distance d. Meanwhile, the atomic column positions in the STEM images are quantified by a model-based mathematical algorithm, and the corresponding distance d are calculated. By comparing the distance d, it is determine that the 2-valent and 3-valent cations are jointly and disorderly distributed in the A and B sites in high-entropy (M2+ 0.4M3+ 1.2)Ti1.4O5. The density functional theory (DFT) simulations also demonstrate that this type of crystal structure is more thermodynamically stable. The higher degree of cationic disorder leads to a higher configurational entropy in high-entropy (M2+ 0.4M3+ 1.2)Ti1.4O5, and endows high-entropy (M2+ 0.4M3+ 1.2)Ti1.4O5 with very low thermal conductivity (1.187-1.249 W m-1 K-1).

Redox Promoted Rapid and Deep Reconstruction of Defect-Rich Nickel Precatalysts for Efficient Water Oxidation.

Understanding the reconstruction mechanism to rationally design cost-effective electrocatalysts for oxygen evolution reaction (OER) is still challenging. Herein, a defect-rich NiMoO4 precatalyst is used to explore its OER activity and reconstruction mechanism. In situ generated oxygen vacancies, distorted lattices, and edge dislocations expedite the deep reconstruction of NiMoO4 to form polycrystalline Ni (oxy)hydroxides for alkaline oxygen evolution. It only needs ≈230 and ≈285 mV to reach 10 and 100 mA cm-2, respectively. The reconstruction boosted by the redox of Ni is confirmed experimentally by sectionalized cyclic voltammetry activations at different specified potential ranges combined with ex situ characterization techniques. Subsequently, the reconstruction route is presented based on the acid-base electronic theory. Accordingly, the dominant contribution of the adsorbate evolution mechanism to reconstruction during oxygen evolution is revealed. This work develops a novel route to synthesize defect-rich materials and provides new tactics to investigate the reconstruction.

Deep learning enables contrast-robust super-resolution reconstruction in structured illumination microscopy.

Structured illumination microscopy (SIM) is a powerful technique for super-resolution (SR) image reconstruction. However, conventional SIM methods require high-contrast illumination patterns, which necessitate precision optics and highly stable light sources. To overcome these challenges, we propose a new method called contrast-robust structured illumination microscopy (CR-SIM). CR-SIM employs a deep residual neural network to enhance the quality of SIM imaging, particularly in scenarios involving low-contrast illumination stripes. The key contribution of this study is the achievement of reliable SR image reconstruction even in suboptimal illumination contrast conditions. The results of our study will benefit various scientific disciplines.

Full field-of-view hexagonal lattice structured illumination microscopy based on the phase shift of electro-optic modulators.

High throughput has become an important research direction in the field of super-resolution (SR) microscopy, especially in improving the capability of dynamic observations. In this study, we present a hexagonal lattice structured illumination microscopy (hexSIM) system characterized by a large field of view (FOV), rapid imaging speed, and high power efficiency. Our approach employs spatial light interference to generate a two-dimensional hexagonal SIM pattern, and utilizes electro-optical modulators for high-speed phase shifting. This design enables the achievement of a 210-µm diameter SIM illumination FOV when using a 100×/1.49 objective lens, capturing 2048 × 2048 pixel images at an impressive 98 frames per second (fps) single frame rate. Notably, this method attains a near 100% full field-of-view and power efficiency, with the speed limited only by the camera's capabilities. Our hexSIM demonstrates a substantial 1.73-fold improvement in spatial resolution and necessitates only seven phase-shift images, thus enhancing the imaging speed compared to conventional 2D-SIM.

CAZ Composite Photocatalysts for H2 Production and Degradation under Visible Light.

g-C3N4/Ag-ZnO (CAZ) composite photocatalysts were synthesized successfully by the hydrothermal method. The photocatalytic performance of photocatalysts was assessed through experiments measuring both hydrogen (H2) production and the degradation of methylene blue (MB). The H2 production rate of 60% CAZ reached 2.450 mmol·g-1·h-1, which was 8.5 times that of g-C3N4. 25% CAZ degraded 99.14% of MB dye within 40 min, and its degradation rate constant was 12.4 times that of g-C3N4. CAZ composite photocatalysts have good synergistic properties in degradation and hydrogen production and exhibit better photocatalytic performance. A Z-scheme photocatalytic system mechanism of CAZ has been proposed for the enhanced H2 production and photocatalytic degradation rate.

Water-Soluble, Self-Healing, and Debonding Primer for the Interface between Silicone Leather and Polydimethylsiloxane Composites.

The exceptional hydrophobicity and antifouling properties of polydimethylsiloxane (PDMS) composites have attracted extensive interest as a result of low surface energy. However, PDMS composites are hardly bound by common primers, greatly limiting their practical applications. To address this issue, an EPMS/VTMS (EV) primer synthesized by hydrolytic polycondensation of 3-[(2,3)-epoxypropoxypropyl]methyldiethoxysilane (EPMS) and vinyltrimethoxysilane (VTMS) in acidic conditions is proposed. Interestingly, the EV primer exhibits exceptional reactivity, self-healing capabilities, and strong adhesion to various substrates, including metals, plastics, and glass. The bonding aluminum plates are easily debonded by immersion in water without any residue left. Subsequently, the EV primer has been applied to the interface between silicone leather and the PDMS composite. Results show that the bonding strength for the silicone leather coated with the EV/PDMS composite is 16 times higher than that of the silicone leather modified with the PDMS composite. Meanwhile, the modified silicone leather exhibits impressive antifouling performance, including aqueous and oily stains, appreciable breathability, and excellent wear resistance, even if suffering from 20 000 cycles of abrasion. These excellent advantages for the modified silicone leather should be attributable to the synergistic effect of the EV primer and the PDMS composite. These findings pave the way to develop an ecofriendly debonding primer for PDMS composites, greatly facilitating applications of silicone leather.

Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance.

The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P  < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P  < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P  < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.

Core-shell engineered g-C3N4@ NaNbO3for enhancing photocatalytic reduction of CO2.

Photocatalytic reduction of carbon dioxide is a technology that effectively utilizes CO2and solar energy. Sodium niobate (NaNbO3) has received much attention in the field of photocatalysis due to its excellent photocatalytic properties. However, the application of NaNbO3in the field of photocatalysis is still limited by poor reaction to visible light and easy recombination of photo-generated carriers. Heterojunction with g-C3N4to construct core-shell structure can effectively improve the above problems. Combining the two can design a core-shell composite material that is beneficial for photocatalytic reduction of CO2. Herein, we prepared a core-shell heterojunction g-C3N4/NaNbO3by uniformly impregnating urea on the surface of NaNbO3chromium nanofibers with NaNbO3nanofibers prepared by electrospinning as a catalyst carrier, and urea as a precursor of g-C3N4. The core-shell structure of g-C3N4/NaNbO3was verified by a series of characterization methods such as XPS, XRD, and TEM. It was found that under the same conditions, the methanol yield of core-shell g-C3N4/NaNbO3was 12.86µmol·g-1·h-1, which is twice that of pure NaNbO3(6.67µmol·g-1·h-1). This article highlights an impregnation method to build core-shell structures for improved photocatalytic reduction of CO2.

Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and dysfunction of RyR2 in the heart of streptozotocin-induced diabetic rats.

BACKGROUND: Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms. METHODS: Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed. RESULTS: There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats. CONCLUSIONS: These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 µl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

The native cistrome and sequence motif families of the maize ear.

Elucidating the transcriptional regulatory networks that underlie growth and development requires robust ways to define the complete set of transcription factor (TF) binding sites. Although TF-binding sites are known to be generally located within accessible chromatin regions (ACRs), pinpointing these DNA regulatory elements globally remains challenging. Current approaches primarily identify binding sites for a single TF (e.g. ChIP-seq), or globally detect ACRs but lack the resolution to consistently define TF-binding sites (e.g. DNAse-seq, ATAC-seq). To address this challenge, we developed MNase-defined cistrome-Occupancy Analysis (MOA-seq), a high-resolution (< 30 bp), high-throughput, and genome-wide strategy to globally identify putative TF-binding sites within ACRs. We used MOA-seq on developing maize ears as a proof of concept, able to define a cistrome of 145,000 MOA footprints (MFs). While a substantial majority (76%) of the known ATAC-seq ACRs intersected with the MFs, only a minority of MFs overlapped with the ATAC peaks, indicating that the majority of MFs were novel and not detected by ATAC-seq. MFs were associated with promoters and significantly enriched for TF-binding and long-range chromatin interaction sites, including for the well-characterized FASCIATED EAR4, KNOTTED1, and TEOSINTE BRANCHED1. Importantly, the MOA-seq strategy improved the spatial resolution of TF-binding prediction and allowed us to identify 215 motif families collectively distributed over more than 100,000 non-overlapping, putatively-occupied binding sites across the genome. Our study presents a simple, efficient, and high-resolution approach to identify putative TF footprints and binding motifs genome-wide, to ultimately define a native cistrome atlas.

Developing a Portable Autofluorescence Detection System and Its Application in Biological Samples.

Advanced glycation end-products (AGEs) are complex compounds closely associated with several chronic diseases, especially diabetes mellitus (DM). Current methods for detecting AGEs are not suitable for screening large populations, or for long-term monitoring. This paper introduces a portable autofluorescence detection system that measures the concentration of AGEs in the skin based on the fluorescence characteristics of AGEs in biological tissues. The system employs a 395 nm laser LED to excite the fluorescence of AGEs, and uses a photodetector to capture the fluorescence intensity. A model correlating fluorescence intensity with AGEs concentration facilitates the detection of AGEs levels. To account for the variation in optical properties of different individuals' skin, the system includes a 520 nm light source for calibration. The system features a compact design, measuring only 60 mm × 50 mm × 20 mm, and is equipped with a miniature STM32 module for control and a battery for extended operation, making it easy for subjects to wear. To validate the system's effectiveness, it was tested on 14 volunteers to examine the correlation between AGEs and glycated hemoglobin, revealing a correlation coefficient of 0.49. Additionally, long-term monitoring of AGEs' fluorescence and blood sugar levels showed a correlation trend exceeding 0.95, indicating that AGEs reflect changes in blood sugar levels to some extent. Further, by constructing a multivariate predictive model, the study also found that AGEs levels are correlated with age, BMI, gender, and a physical activity index, providing new insights for predicting AGEs content and blood sugar levels. This research supports the early diagnosis and treatment of chronic diseases such as diabetes, and offers a potentially useful tool for future clinical applications.

Reconstructed Bismuth Oxide through in situ Carbonation by Carbonate-containing Electrolyte for Highly Active Electrocatalytic CO2 Reduction to Formate.

The catalyst-reconstruction makes it challenging to clarify the practical active sites and unveil the actual reaction mechanism during the CO2 electroreduction reaction (CO2 RR). However, currently the impact of the electrolyte microenvironment in which the electrolyte is in contact with the catalyst is overlooked and might induce a chemical evolution, thus confusing the reconstruction process and mechanism. In this work, the carbonate adsorption properties of metal oxides were investigated, and the mechanism of how the electrolyte carbonate affect the chemical evolution of catalysts were discussed. Notably, Bi2 O3 with weak carbonate adsorption underwent a chemical reconstruction to form the Bi2 O2 CO3 /Bi2 O3 heterostructure. Furthermore, in situ and ex situ characterizations unveiled the formation mechanism of the heterostructure. The in situ formed Bi2 O2 CO3 /Bi2 O3 heterostructure with strong electron interaction served as the highly active structure for CO2 RR, achieving a formate Faradaic efficiency of 98.1 % at -0.8 Vvs RHE . Theoretical calculations demonstrate that the significantly tuned p-orbit electrons of the Bi sites in Bi2 O2 CO3 /Bi2 O3 optimized the adsorption of the intermediate and lowered the energy barrier for the formation of *OCHO. This work elucidates the mechanism of electrolyte microenvironment for affecting catalyst reconstruction, which contributes to the understanding of reconstruction process and clarification of the actual catalytic structure.

Adenosine A2A Receptor (A2AAR) Ligand Screening Using the 19F-NMR Probe FPPA.

The binding affinity of G protein-coupled receptor (GPCR) ligands is customarily measured by radio-ligand competition experiments. As an alternative approach, 19F nuclear magnetic resonance spectroscopy (19F-NMR) is used for the screening of small-molecule lead compounds in drug discovery; the two methods are complementary in that the measurements are performed with widely different experimental conditions. Here, we used the structure of the A2A adenosine receptor (A2AAR) complex with V-2006 (3-(4-amino-3-methylbenzyl)-7-(furan-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine) as the basis for the design of a fluorine-containing probe molecule, FPPA (4-(furan-2-yl)-7-(4-(trifluoromethyl)benzyl)-7H-pyrrolo[2,3-d]pyramidin-2-amine), for binding studies with A2AAR. A protocol of experimental conditions for drug screening and measurements of drug binding affinities using 1D 19F-NMR observation of FPPA is validated with studies of known A2AAR ligands. 19F-NMR with FPPA is thus found to be a robust approach for the discovery of ligands with new core structures, which will expand the libraries of A2AAR-targeting drug candidates.

Structural Framework-Guided Universal Design of High-Entropy Compounds for Efficient Energy Catalysis.

High-entropy compounds with extraordinary properties due to the synergistic effect of multiple components have exhibited great potential and attracted extensive attention in various fields, including physics, mechanical property analysis, and energy storage. Achieving universal stability and synthesis of high-entropy compounds with a wide range of components and structures continues to be difficult due to the high complexity of multicomponent mixing. Here, we propose a design strategy with high generality for realizing the stability and synthesis of high-entropy compounds that one metal site like the framework in the compound structures with bimetallic sites stabilizes another site to accommodate different elements. Several typical metal compounds with bimetallic sites, including perovskite hydroxides, layered double hydroxide, spinel sulfide, perovskite fluoride, and spinel oxides, have been synthesized into high-entropy compounds. High-entropy perovskite hydroxides (HEPHs) as representative compounds have been synthesized with a highly wide range of components even a septenary component and exhibit great oxygen evolution activity. Our work provides a design platform to develop more high-entropy compound systems with promising development potential for electrocatalysts.

Response to neoadjuvant immune checkpoint inhibitors and chemotherapy in Chinese patients with esophageal squamous cell carcinoma: the role of tumor immune microenvironment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) through programmed cell death 1 blockade improve the survival outcomes of patients with advanced esophageal squamous cell carcinoma (ESCC). Recently, the use of neoadjuvant immunotherapy for the treatment of ESCC has been gradually increasing. We aimed to evaluate the efficacy of neoadjuvant treatment of ICIs with chemotherapy and explore tumor microenvironment (TME) immune profiles of ESCC samples during neoadjuvant therapy. METHODS: Patients with previously untreated, resectable, locally advanced ESCC (stage II or III) in Harbin Medical University Cancer Hospital were enrolled. Each patient received two to four cycles of neoadjuvant ICIs combined with chemotherapy before surgical resection. The TME immune profiles of formalin-fixed paraffin-embedded tumor samples at baseline and after surgery were evaluated by multiplex staining and multispectral imaging. RESULTS: In all, 18 patients were enrolled, and all patients received surgery with R0 resection. The postoperative pathological evaluation indicated that 7 (38.9%) patients had a pathological complete response (pCR) and 11 (61.1%) patients had a partial response. The neoadjuvant therapeutic regimens had acceptable side effect profiles. The TME immune profiles at baseline observed higher densities of stroma CD3 + , PD-1 + , and PD-1 + CD3 + cells in pCR patients than in non-pCR patients. Comparing TME immune profiles before and after neoadjuvant treatment, an increase in CD8 + T cells and a decrease in CD163 + CD68 + M2-like macrophage cells were observed after neoadjuvant treatment. CONCLUSIONS: Neoadjuvant ICIs combined with chemotherapy produced a satisfactory treatment response, demonstrating its anti-tumor efficacy in locally advanced ESCC. Further large-scale studies are required to understand the role of tumor immunities and ICIs underlying ESCC.