Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma.

BACKGROUND & AIMS: Crotonylation, a crotonyl-CoA-based non-enzymatic protein translational modification, affects diverse biological processes, such as spermatogenesis, tissue injury, inflammation, and neuropsychiatric diseases. Crotonylation shows decreased in hepatocellular carcinomas (HCCs), but the mechanism remains unknown. In this study, we aim to describe the role of glutaryl-CoA dehydrogenase (GCDH) in tumor suppression. METHODS: Three cohorts containing 40, 248 and 17 pairs of samples were used to evaluate the link between GCDH expression levels and the HCC clinical characteristics as well as anti-PD-1 response. Subcutaneous xenograft, orthotopic xenograft, Trp53Δhep/Δhep; MYC- as well as Ctnnboe; METoe- driven mouse models were adopted to validate GCDH effects on HCC suppression. RESULTS: GCDH depletion promoted HCC growth and metastasis, whereas its overexpression reversed these processes. As GCDH converts glutaryl-CoA to crotonyl-CoA to increase crotonylation levels, we performed lysine crotonylome analysis and identified the pentose phosphate pathway (PPP) and glycolysis-related proteins PGD, TKT, and ALDOC as GCDH-induced crotonylation targets. Crotonyl-bound targets showed allosteric effects that controlled their enzymatic activities, leading to decreases in ribose 5-phosphate and lactate production, further limiting the Warburg effect. PPP blockade also stimulated peroxidation, synergizing with senescent modulators to induce senescence in GCDHhigh cells. These cells induced the infiltration of immune cells by the senescence-associated secretory cell phenotype (SASP) to shape an anti-tumor immune microenvironment. Meanwhile, the GCDHlow population was sensitized to anti-programmed cell death protein 1 (PD-1) therapy. CONCLUSION: GCDH inhibits HCC progression via crotonylation-induced suppression of the PPP and glycolysis, resulting in HCC cell senescence. The senescent cell further shapes an anti-tumor microenvironment by SASP. The GCDHlow population is vulnerable to anti-PD-1 therapy because more PD-1+CD8+ T cells are exhibited in GCDHlow population. IMPACT AND IMPLICATIONS: GCDH is a favorable prognostic indicator in liver, lung, and renal cancers. In addition, most of GCDH depletion-induced toxic metabolites originate from the liver, accumulate locally, and cannot cross the blood-brain barrier. Therefore, studies on the correlation between GCDH and liver cancer would contribute to discovering the initiation and progression of hepatocellular carcinoma, of which over 70% of patients occupied >2-fold GCDH downregulation. Given that the GCDHlow and GCDHhigh HCC population can be distinguished based on serum glucose and ammonia levels, it will be worthwhile to evaluate the curative effects of pro-senescent and immune-therapeutic strategies based on the expression levels of GCDH.

Electrohydrodynamic Inkjet Printing of Three-Dimensional Perovskite Nanocrystal Arrays for Full-Color Micro-LED Displays.

Perovskite nanocrystal (PeNC) arrays are showing a promising future in the next generation of micro-light-emitting-diode (micro-LED) displays due to the narrow emission linewidth and adjustable peak wavelength. Electrohydrodynamic (EHD) inkjet printing, with merits of high resolution, uniformity, versatility, and cost-effectiveness, is among the competent candidates for constructing PeNC arrays. However, the fabrication of red light-emitting CsPbBrxI(3-x) nanocrystal arrays for micro-LED displays still faces challenges, such as low brightness and poor stability. This work proposes a design for a red PeNC colloidal ink that is specialized for the EHD inkjet printing of three-dimensional PeNC arrays with enhanced luminescence and stability as well as being adaptable to both rigid and flexible substrates. Made of a mixture of PeNCs, polymer polystyrene (PS), and a nonpolar xylene solvent, the PeNC colloidal ink enables precise control of array sizes and shapes, which facilitates on-demand micropillar construction. Additionally, the inclusion of PS significantly increases the brightness and environmental stability. By adopting this ink, the EHD printer successfully fabricated full-color 3D PeNC arrays with a spatial resolution over 2500 ppi. It shows the potential of the EHD inkjet printing strategy for high-resolution and robust PeNC color conversion layers for micro-LED displays.

LED Junction Temperature Measurement: From Steady State to Transient State.

In this review, we meticulously analyze and consolidate various techniques used for measuring the junction temperature of light-emitting diodes (LEDs) by examining recent advancements in the field as reported in the literature. We initiate our exploration by delineating the evolution of LED technology and underscore the criticality of junction temperature detection. Subsequently, we delve into two key facets of LED junction temperature assessment: steady-state and transient measurements. Beginning with an examination of innovations in steady-state junction temperature detection, we cover a spectrum of approaches ranging from traditional one-dimensional methods to more advanced three-dimensional techniques. These include micro-thermocouple, liquid crystal thermography (LCT), temperature sensitive optical parameters (TSOPs), and infrared (IR) thermography methods. We provide a comprehensive summary of the contributions made by researchers in this domain, while also elucidating the merits and demerits of each method. Transitioning to transient detection, we offer a detailed overview of various techniques such as the improved T3ster method, an enhanced one-dimensional continuous rectangular wave method (CRWM), and thermal reflection imaging. Additionally, we introduce novel methods leveraging high-speed camera technology and reflected light intensity (h-SCRLI), as well as micro high-speed transient imaging based on reflected light (µ_HSTI). Finally, we provide a critical appraisal of the advantages and limitations inherent in several transient detection methods and offer prognostications on future developments in this burgeoning field.

Spatially resolved current density distribution in GaN-based flip-chip green mini-LEDs by microscopic hyperspectral imaging and modified two-level modeling.

A modified two-level model is proposed to study the spatially resolved current density distribution of GaN-based green miniaturized light-emitting diodes (mini-LEDs), combining with microscopic hyperspectral imaging. We found that the spatially resolved current density distribution reveals both the radiative and non-radiative recombination mappings, which can also be provided separately by this model. In addition, higher current density is not necessarily correlated with higher photon emission, especially for the regions around the electrode edges, where the high current density suggests current crowding and defect-related non-radiative recombination. The current density distribution of mini-LEDs is further verified by the laser-beam-induced current (LBIC) and the spatially resolved mappings of peak wavelength and FWHM. The modified two-level model also offers radiative/non-radiative mappings and is proved to be beneficial to determine the micro-zone current density distribution and to reveal the intrinsic radiative/non-radiative recombination mechanism of mini-LEDs.

Tumor-associated macrophages promoting PD-L1 expression in infiltrating B cells through the CXCL12/CXCR4 axis in human hepatocellular carcinoma.

The inflammation-related tumor microenvironment (TME) is one of the major driving forces of hepatocarcinogenesis. We aimed to investigate cell-to-cell communication among Hepatocellular Carcinoma (HCC) through re-analyzing HCC single-cell RNA-seq data, and to confirm such cellular interaction through in vitro and in vivo study. We found a subset of Regulatory B cells with PD-L1 expression (PD-L1+ Bregs), mainly located in adjacent HCC tissues. In co-localization with PD-L1+ Bregs, a subset of Tumor Associated Macrophages with high expression of CXCL12 (CXCL12+ TAMs) was also mainly located in adjacent HCC tissues. Moreover, CXCL12+ TAMs can be stimulated in vitro using an HCC conditional medium. Using CellChat analysis and Multiplex Immunohistochemistry staining (mIHC), CXCL12+ TAMs were found to be first recruited by Cancer-Associated Fibroblasts (CAFs) through a CD74/macrophage migration inhibitory factor (MIF) pattern, and further differentiated into TGF-ß-enriched tissues. Furthermore, CXCL12+ TAMs recruited PD-L1+ Bregs via the CXCL12/CXCR4 axis, and CXCR4 expression was significantly positively correlated to PD-L1 expression in PD-L1+ Bregs. At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC.

Underground Mine Safety and Health: A Hybrid MEREC-CoCoSo System for the Selection of Best Sensor.

This research addresses the paramount issue of enhancing safety and health conditions in underground mines through the selection of optimal sensor technologies. A novel hybrid MEREC-CoCoSo system is proposed, integrating the strengths of the MEREC (Method for Eliciting Relative Weights) and Combined Compromise Solution (CoCoSo) methods. The study involves a three-stage framework: criteria and sensor discernment, criteria weight determination using MEREC, and sensor prioritization through the MEREC-CoCoSo framework. Fifteen criteria and ten sensors were identified, and a comprehensive analysis, including MEREC-based weight determination, led to the prioritization of "Ease of Installation" as the most critical criterion. Proximity sensors were identified as the optimal choice, followed by biometric sensors, gas sensors, and temperature and humidity sensors. To validate the effectiveness of the proposed MEREC-CoCoSo model, a rigorous comparison was conducted with established methods, including VIKOR, TOPSIS, TODIM, ELECTRE, COPRAS, EDAS, and TRUST. The comparison encompassed relevant metrics such as accuracy, sensitivity, and specificity, providing a comprehensive understanding of the proposed model's performance in relation to other established methodologies. The outcomes of this comparative analysis consistently demonstrated the superiority of the MEREC-CoCoSo model in accurately selecting the best sensor for ensuring safety and health in underground mining. Notably, the proposed model exhibited higher accuracy rates, increased sensitivity, and improved specificity compared to alternative methods. These results affirm the robustness and reliability of the MEREC-CoCoSo model, establishing it as a state-of-the-art decision-making framework for sensor selection in underground mine safety. The inclusion of these actual results enhances the clarity and credibility of our research, providing valuable insights into the superior performance of the proposed model compared to existing methodologies. The main objective of this research is to develop a robust decision-making framework for optimal sensor selection in underground mines, with a focus on enhancing safety and health conditions. The study seeks to identify and prioritize critical criteria for sensor selection in the context of underground mine safety. The research strives to contribute to the mining industry by offering a structured and effective approach to sensor selection, prioritizing safety and health in underground mining operations.

Mechanical Framework for Geopolymer Gels Construction: An Optimized LSTM Technique to Predict Compressive Strength of Fly Ash-Based Geopolymer Gels Concrete.

As an environmentally responsible alternative to conventional concrete, geopolymer concrete recycles previously used resources to prepare the cementitious component of the product. The challenging issue with employing geopolymer concrete in the building business is the absence of a standard mix design. According to the chemical composition of its components, this work proposes a thorough system or framework for estimating the compressive strength of fly ash-based geopolymer concrete (FAGC). It could be possible to construct a system for predicting the compressive strength of FAGC using soft computing methods, thereby avoiding the requirement for time-consuming and expensive experimental tests. A complete database of 162 compressive strength datasets was gathered from the research papers that were published between the years 2000 and 2020 and prepared to develop proposed models. To address the relationships between inputs and output variables, long short-term memory networks were deployed. Notably, the proposed model was examined using several soft computing methods. The modeling process incorporated 17 variables that affect the CSFAG, such as percentage of SiO2 (SiO2), percentage of Na2O (Na2O), percentage of CaO (CaO), percentage of Al2O3 (Al2O3), percentage of Fe2O3 (Fe2O3), fly ash (FA), coarse aggregate (CAgg), fine aggregate (FAgg), Sodium Hydroxide solution (SH), Sodium Silicate solution (SS), extra water (EW), superplasticizer (SP), SH concentration, percentage of SiO2 in SS, percentage of Na2O in SS, curing time, curing temperature that the proposed model was examined to several soft computing methods such as multi-layer perception neural network (MLPNN), Bayesian regularized neural network (BRNN), generalized feed-forward neural networks (GFNN), support vector regression (SVR), decision tree (DT), random forest (RF), and LSTM. Three main innovations of this study are using the LSTM model for predicting FAGC, optimizing the LSTM model by a new evolutionary algorithm called the marine predators algorithm (MPA), and considering the six new inputs in the modeling process, such as aggregate to total mass ratio, fine aggregate to total aggregate mass ratio, FASiO2:Al2O3 molar ratio, FA SiO2:Fe2O3 molar ratio, AA Na2O:SiO2 molar ratio, and the sum of SiO2, Al2O3, and Fe2O3 percent in FA. The performance capacity of LSTM-MPA was evaluated with other artificial intelligence models. The results indicate that the R2 and RMSE values for the proposed LSTM-MPA model were as follows: MLPNN (R2 = 0.896, RMSE = 3.745), BRNN (R2 = 0.931, RMSE = 2.785), GFFNN (R2 = 0.926, RMSE = 2.926), SVR-L (R2 = 0.921, RMSE = 3.017), SVR-P (R2 = 0.920, RMSE = 3.291), SVR-S (R2 = 0.934, RMSE = 2.823), SVR-RBF (R2 = 0.916, RMSE = 3.114), DT (R2 = 0.934, RMSE = 2.711), RF (R2 = 0.938, RMSE = 2.892), LSTM (R2 = 0.9725, RMSE = 1.7816), LSTM-MPA (R2 = 0.9940, RMSE = 0.8332), and LSTM-PSO (R2 = 0.9804, RMSE = 1.5221). Therefore, the proposed LSTM-MPA model can be employed as a reliable and accurate model for predicting CSFAG. Noteworthy, the results demonstrated the significance and influence of fly ash and sodium silicate solution chemical compositions on the compressive strength of FAGC. These variables could adequately present variations in the best mix designs discovered in earlier investigations. The suggested approach may also save time and money by accurately estimating the compressive strength of FAGC with low calcium content.

Dual-Ligand Red Perovskite Ink for Electrohydrodynamic Printing Color Conversion Arrays over 2540 dpi in Near-Eye Micro-LED Display.

The lack of stability of red perovskite nanocrystals (PeNCs) remains the main problem that restricts their patterning application. In this work, the dual-ligand passivation strategy was introduced to stabilize PeNCs and inhibit their halogen ion migration during high-voltage electrohydrodynamic (EHD) inkjet printing. The as-printed red arrays exhibit the highest emisson intensity and least blue shift compared with samples with other passivation strategies under a high electric field during EHD inkjet printing. Combining with blue and green PeNC inks, single-color and tricolor color conversion layer arrays were successfully printed, with minimum pixel size of 5 µm and the highest spatial resolution of 2540 dpi. The color coordinate of CsPbBrI2 NCs arrays are located close to the red point, with a color gumat of 97.28% of Rec. 2020 standard. All of these show great potential in the application of color conversion layers in a near-eye micro-LED display.

Decision tree models for the estimation of geo-polymer concrete compressive strength.

The green concretes industry benefits from utilizing gel to replace parts of the cement in concretes. However, measuring the compressive strength of geo-polymer concretes (CSGPoC) needs a significant amount of work and expenditure. Therefore, the best idea is predicting CSGPoC with a high level of accuracy. To do this, the base learner and super learner machine learning models were proposed in this study to anticipate CSGPoC. The decision tree (DT) is applied as base learner, and the random forest and extreme gradient boosting (XGBoost) techniques are used as super learner system. In this regard, a database was provided involving 259 CSGPoC data samples, of which four-fifths of is considered for the training model and one-fifth is selected for the testing models. The values of fly ash, ground-granulated blast-furnace slag (GGBS), Na2SiO3, NaOH, fine aggregate, gravel 4/10 mm, gravel 10/20 mm, water/solids ratio, and NaOH molarity were considered as input of the models to estimate CSGPoC. To evaluate the reliability and performance of the decision tree (DT), XGBoost, and random forest (RF) models, 12 performance evaluation metrics were determined. Based on the obtained results, the highest degree of accuracy is achieved by the XGBoost model with mean absolute error (MAE) of 2.073, mean absolute percentage error (MAPE) of 5.547, Nash-Sutcliffe (NS) of 0.981, correlation coefficient (R) of 0.991, R2 of 0.982, root mean square error (RMSE) of 2.458, Willmott's index (WI) of 0.795, weighted mean absolute percentage error (WMAPE) of 0.046, Bias of 2.073, square index (SI) of 0.054, p of 0.027, mean relative error (MRE) of -0.014, and a20 of 0.983 for the training model and MAE of 2.06, MAPE of 6.553, NS of 0.985, R of 0.993, R2 of 0.986, RMSE of 2.307, WI of 0.818, WMAPE of 0.05, Bias of 2.06, SI of 0.056, p of 0.028, MRE of -0.015, and a20 of 0.949 for the testing model. By importing the testing set into trained models, values of 0.8969, 0.9857, and 0.9424 for R2 were obtained for DT, XGBoost, and RF, respectively, which show the superiority of the XGBoost model in CSGPoC estimation. In conclusion, the XGBoost model is capable of more accurately predicting CSGPoC than DT and RF models.

Ileitis promotes MASLD progression via bile acid modulation and enhanced TGR5 signaling in ileal CD8+ T cells.

BACKGROUND & AIMS: Clinical evidence substantiates a link between inflammatory bowel disease, particularly Crohn's disease (CD), and metabolic dysfunction-associated steatotic liver disease (MASLD). This study aims to explore the underlying molecular mechanisms responsible for this association. METHODS: MASLD was induced by administering high-fat and western diets, while inflammatory bowel disease was induced using DSS (dextran sulfate sodium) and the Il10 knockout (KO) mouse model. The investigation into the role of secondary bile acids (SBAs) in ileitis involved employing metagenomic sequencing, conducting metabolomics detection, performing fecal microbiota transplantation, and constructing CD8+ T cell-specific gene knockout mice. RESULTS: In MASLD+DSS and Il10 KO MASLD mice, we observed ileitis characterized by T-cell infiltration and activation in the terminal ileum. This condition resulted in decreased bile acid levels in the portal vein and liver, inhibited hepatic farnesoid X receptor (FXR) activation, and exacerbated MASLD. Metagenomic and metabolomic analysis of ileal contents revealed increased Clostridium proliferation and elevated SBA levels in MASLD-associated ileitis. Experiments using germ-free mice and fecal microbiota transplantation suggested an association between SBA and MASLD-related ileitis. In vitro, SBAs promoted CD8+ T-cell activation via the TGR5, mTOR, and oxidative phosphorylation pathways. In vivo, TGR5 KO in CD8+ T cells effectively alleviated ileitis and reversed the MASLD phenotype. Clinical data further supported these findings, demonstrating a positive correlation between ileitis and MASLD. CONCLUSION: MASLD-induced changes in intestinal flora result in elevated levels of SBAs in the ileum. In the presence of a compromised intestinal barrier, this leads to severe CD8+ T cell-mediated ileitis through the TGR5/mTOR/oxidative phosphorylation signaling pathway. Ileitis-induced tissue damage impairs enterohepatic circulation, inhibits hepatic FXR activation, and exacerbates the MASLD phenotype. IMPACT AND IMPLICATIONS: Our study provides a comprehensive investigation of the interplay and underlying mechanisms connecting ileitis and metabolic dysfunction-associated steatotic liver disease (MASLD). Secondary bile acids produced by intestinal bacteria act as the critical link between MASLD and ileitis. Secondary bile acids exert their influence by disrupting liver lipid metabolism through the promotion of CD8+ T cell-mediated ileitis. In future endeavors to prevent and treat MASLD, it is essential to thoroughly account for the impact of the intestinal tract, especially the ileum, on liver function via the enterohepatic circulation.

Recent Advance in Electrochromic Materials and Devices for Display Applications.

Electrochromic devices (ECDs) possess the performance advantages in terms of color adjustability, low power consumption, and visual friendliness, emerging as one of the ideal candidates for energy-efficient smart windows, next-generation displays, and wearable electronics. The optical and electrical characteristics of ECDs can be adjusted by modifying the materials or structure of devices. This review summarizes the recent developments of innovative technologies and key materials of ECDs for display applications, highlighting the key issues and development trends in this area.

The influence of management practices on plant diversity: a comparative study of three urban wetlands in an expanding city in eastern China.

Rapid urbanization has drawn some aquatic environments into the urban texture from the outskirts of cities, and the composition and distribution of plant species in urban wetlands along the urban gradient have changed. Understanding the drivers of these changes will help in the conservation and utilization of urban wetlands. This study investigated the differences in plant diversity and associated influencing factors in three wetlands, Xixi wetland, Tongjian Lake wetland, and Qingshan Lake wetland, which are located in a core area, fringe area, and suburban area of Hangzhou City, respectively. The results showed that a total of 104 families, 254 genera, and 336 species of plants were recorded in the Xixi wetland; 179 species, 150 genera, and 74 families were found in the Qingshan Lake wetland; and 112 species, 96 genera, and 57 families were collected in the Tongjian Lake wetland. The main plant species and flora distribution of the three urban wetlands showed similarities. Indigenous spontaneous vegetation was highest in the Xixi wetland, while cultivated plant species were most abundant in the Tongjian Lake wetland. The introduction of cultivated plants decreased the distance attenuation effect of plant communities, which led to a certain degree of plant diversity convergence among the three wetlands. Eight endangered plants were preserved in the Xixi wetland by planting them in suitable habitats. Ellenberg's indicator values showed that the proportion of heliophilous plants was higher in the Qingshan Lake wetland, while the proportion of thermophilous plants and nitrogen-loving plants in the Tongjian Lake wetland was higher than in the other two wetlands. The importance of artificial interference factors affecting the differences in plant diversity was significantly higher than that of natural environmental factors in urban wetlands. The preservation of spontaneous plants and the introduction of cultivated plants had an importance of 25.73% and 25.38%, respectively. These were the main factors influencing the plant diversity of urban wetlands. The management mode that did not interfere with spontaneous vegetation and confined maintenance to cultivated plants in the Xixi wetland was beneficial for improving wetland plant diversity. Scientific plant reintroduction can also improve wetland plant diversity.

Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma.

BACKGROUND AND AIMS: Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy. APPROACH AND RESULTS: We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies. CONCLUSIONS: We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making.

Carp scales derived double cross-linking hydrogels achieve collagen peptides sustained-released for bone regeneration.

Collagen peptide exhibits a great activity in osteogenic differentiation and wound healing. However, uncontrolled collagen peptide release in bone defects leads to unsatisfactory bone regeneration. In this work, we prepared collagen peptide loaded calcium alginate hydrogel (SA-CP/Ca) derived from Asia carp scales by mixing sodium alginate solution, collagen peptides, calcium carbonate, covalent cross-linking agents N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), and N-hydroxysuccinimide (NHS) in one pot. Physically and chemically double cross-linking realized higher crosslink density, smaller porosity and pore size, and higher energy storage modulus and loss modulus, achieving sustained release of collagen peptides. The release profile is fitted to Keppas-Sahlin model, to find SA-CP/Ca hydrogels are more inclined to release collagen peptides through expansion and degradation. The compatibility and osteogenic ability of SA-CP/Ca are demonstrated in vitro and in vivo.

Advances in pixel driving technology for micro-LED displays.

Micro-LED displays have been recognized as the next-generation display technology. This review focuses on the pixel-driving technology of micro-LED displays. The performance of pixel driving on micro-LED displays is discussed in terms of brightness uniformity, driving speed, grayscale, and frame rate under various driving architectures. Since the memristors possess characteristics similar to those of biological synaptic neurons due to the ion migration mechanism, the neural network approach which combines the memristor arrays with the pixel driving circuit of micro-LEDs could promote the development of smart and efficient displays.

Mutational burden of XPNPEP3 leads to defects in mitochondrial complex I and cilia in NPHPL1.

Nephronophthisis-like nephropathy-1 (NPHPL1) is a rare ciliopathy, caused by mutations of XPNPEP3. Despite a well-described monogenic etiology, the pathogenesis of XPNPEP3 associated with mitochondrial and ciliary function remains elusive. Here, we identified novel compound heterozygous mutations in NPHPL1 patients with renal lesion only or with extra bone cysts together. Patient-derived lymphoblasts carrying c.634G>A and c.761G>T together exhibit elevated mitochondrial XPNPEP3 levels via the reduction of mRNA degradation, leading to mitochondrial dysfunction in both urine tubular epithelial cells and lymphoblasts from patient. Mitochondrial XPNPEP3 was co-immunoprecipitated with respiratory chain complex I and was required for the stability and activity of complex I. Deletion of Xpnpep3 in mice resulted in lower activity of complex I, elongated primary cilium, and predisposition to tubular dilation and fibrosis under stress. Our findings provide valuable insights into the mitochondrial functions involved in the pathogenesis of NPHP.

Insights into cryptic speciation of quillworts in China.

Cryptic species are commonly misidentified because of high morphological similarities to other species. One group of plants that may harbor large numbers of cryptic species is the quillworts (Isoëtes spp.), an ancient aquatic plant lineage. Although over 350 species of Isoëtes have been reported globally, only ten species have been recorded in China. The aim of this study is to better understand Isoëtes species diversity in China. For this purpose, we systematically explored the phylogeny and evolution of Isoëtes using complete chloroplast genome (plastome) data, spore morphology, chromosome number, genetic structure, and haplotypes of almost all Chinese Isoëtes populations. We identified three ploidy levels of Isoëtes in China-diploid (2n = 22), tetraploid (2n = 44), and hexaploid (2n = 66). We also found four megaspore and microspore ornamentation types in diploids, six in tetraploids, and three in hexaploids. Phylogenetic analyses confirmed that I. hypsophila as the ancestral group of the genus and revealed that Isoëtes diploids, tetraploids, and hexaploids do not form monophyletic clades. Most individual species possess a single genetic structure; however, several samples have conflicting positions on the phylogenetic tree based on SNPs and the tree based on plastome data. All 36 samples shared 22 haplotypes. Divergence time analysis showed that I. hypsophila diverged in the early Eocene (∼48.05 Ma), and most other Isoëtes species diverged 3-20 Ma. Additionally, different species of Isoëtes were found to inhabit different water systems and environments along the Yangtze River. These findings provide new insights into the relationships among Isoëtes species in China, where highly similar morphologic populations may harbor many cryptic species.

The XOR-IDH3α axis controls macrophage polarization in hepatocellular carcinoma.

BACKGROUND & AIMS: Tumor-associated macrophages (TAMs) are indispensable in the hepatocellular carcinoma (HCC) tumor microenvironment. Xanthine oxidoreductase (XOR), also known as xanthine dehydrogenase (XDH), participates in purine metabolism, uric acid production, and macrophage polarization to a pro-inflammatory phenotype. However, the role of XOR in HCC-associated TAMs is unclear. METHODS: We evaluated the XOR level in macrophages isolated from HCC tissues and paired adjacent tissues. We established diethylnitrosamine/carbon tetrachloride (CCl4)-induced and orthotopically implanted HCC mouse models using mice with Xdh-specific depletion in the myeloid cell lineage (Xdhf/fLyz2cre) or Kupffer cells (Xdhf/fClec4fcre). We determined metabolic differences using specific methodologies, including metabolomics and metabolic flux. RESULTS: We found that XOR expression was downregulated in HCC TAMs and positively correlated with patient survival, which was strongly related to the characteristics of the tumor microenvironment, especially hypoxia. Using HCC-inflicted mice (Xdhf/fLyz2cre and Xdhf/fClec4fcre), we revealed that XOR loss in monocyte-derived TAMs rather than Kupffer cells promoted their M2 polarization and CD8+ T-cell exhaustion, which exacerbated HCC progression. In addition, the tricarboxylic acid cycle was disturbed, and the generation of α-ketoglutarate was enhanced within XOR-depleted macrophages. XOR inhibited α-ketoglutarate production by interacting with IDH3α catalytic sites (K142 and Q139). The increased IDH3α activity caused increased adenosine and kynurenic acid production in TAMs, which enhanced the immunosuppressive effects of TAMs and CD8+ T cells. CONCLUSIONS: The XOR-IDH3α axis mediates TAM polarization and HCC progression and may be a small-molecule therapeutic or immunotherapeutic target against suppressive HCC TAMs. IMPACT AND IMPLICATIONS: Immunotherapies have been widely applied to the treatment of hepatocellular carcinoma (HCC), but to date they have been associated with unsatisfactory efficacy. The tumor microenvironment of HCC is full of different infiltrating immune cells. Tumor-associated macrophages (TAMs) are vital components in the tumor microenvironment and are involved in HCC progression. Herein, we confirm the downregulation of XOR expression in TAMs isolated from human HCC. The loss of XOR in monocyte-derived macrophages increases IDH3 activity and results in an increase in α-ketoglutarate production, which can promote M2-like polarization. Additionally, XOR-null TAMs derived from monocytes promote CD8+ T-cell exhaustion via the upregulation of immunosuppressive metabolites, including adenosine and kynurenic acid. Given the prevalence and high rate of incidence of HCC and the need for improved therapeutic options for patients, our findings identify potential therapeutic targets that may be further studied to develop improved therapies.

Optical power degradation mechanisms in 271†nm AlGaN-based deep ultraviolet light-emitting diodes.

The degradation of AlGaN-based UVC LEDs under constant temperature and constant current stress for up to 500 hrs was analyzed in this work. During each degradation stage, the two-dimensional (2D) thermal distributions, I-V curves, optical powers, combining with focused ion beam and scanning electron microscope (FIB/SEM), were thoroughly tested and analyzed the properties and failure mechanisms of UVC LEDs. The results show that: 1) the opto-electrical characteristics measured before/during stress indicate that the increased leakage current and the generation of stress-induced defects increase the non-radiative recombination in the early stress stage, resulting in a decrease in optical power; 2) the increase of temperature caused by the deterioration of the Cr/Al layer of p-metal after 48 hrs of stress aggravates the optical power in UVC LEDs. The 2D thermal distribution in conjunction with FIB/SEM provide a fast and visual way to precisely locate and analyze the failure mechanisms of UVC LEDs.

Screening and anti-glioma activity of Chiloscyllium plagiosum anti-human IL-13Rα2 single-domain antibody.

Glioblastoma is a common and fatal malignant tumour of the central nervous system, with high invasiveness. Conventional treatments for this disease, including comprehensive treatment of surgical resection combined with chemoradiotherapy, are ineffective, with low survival rate and extremely poor prognosis. Targeted therapy is promising in overcoming the difficulties in brain tumour treatment and IL-13Rα2 is a widely watched target. The development of new therapies for glioma, however, is challenged by factors, such as the unique location and immune microenvironment of gliomas. The unique advantages of single-domain antibodies (sdAbs) may provide a novel potential treatment for brain tumours. In this study, Chiloscyllium plagiosum was immunized with recombinant IL-13Rα2 protein to produce sdAb and sdAb sequences were screened by multi-omics. The targeted sdAb genes obtained were efficiently expressed in the Escherichia coli prokaryotic expression system, showing a significant binding capacity to IL-13Rα2 in vitro. The cell proliferation and migration inhibitory effects of recombinant variable domain of the new antigen receptor (VNAR) on glioma cells were detected by CCK-8 and cell scratch assays. The sdAb obtained in this study showed high in vitro activity and favourable cell proliferation inhibitory effect on glioma cells, with potential clinical application value. The present study also provides a new direction and experimental basis for the development of targeted therapies for glioma.