Tumour vasculature at single-cell resolution.

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.

Dissolution-Induced Surface Reconstruction of Ni0.95 Pt0.05 Si/p-Si Photocathode for Efficient Photoelectrochemical H2 Production.

Metal silicide/Si photoelectrodes have demonstrated significant potential for application in photoelectrochemical (PEC) water splitting to produce H2 . To achieve an efficient and economical hydrogen evolution reaction (HER), a paramount consideration lies in attaining exceptional catalytic activity on the metal silicide surface with minimal use of noble metals. Here, this study presents the design and construction of a novel Ni0.95 Pt0.05 Si/p-Si photocathode. Dopant segregation is used to achieve a Schottky barrier height as high as 1.0 eV and a high photovoltage of 420 mV. To achieve superior electrocatalytic activity for HER, a dissolution-induced surface reconstruction (SR) strategy is proposed to in situ convert surface Ni0.95 Pt0.05 Si to highly active Pt2 Si. The resulting SR Ni0.95 Pt0.05 Si/p-Si photocathode exhibits excellent HER performance with an onset potential of 0.45 V (vs RHE) and a high maximum photocurrent density of 40.5 mA cm-2 and a remarkable applied bias photon-to-current efficiency (ABPE) of 5.3% under simulated AM 1.5 (100 mW cm-2 ) illumination. The anti-corrosion silicide layer effectively protects Si, ensuring excellent stability of the SR Ni0.95 Pt0.05 Si/p-Si photoelectrode. This study highlights the potential for achieving efficient PEC HER using bimetallic silicide/Si photocathodes with reduced Pt consumption, offering an auspicious perspective for the cost-effective conversion of solar energy to chemical energy.

Photoelectrocatalytic Utilization of CO2 : A Big Show of Si-based Photoelectrodes.

CO2 is a greenhouse gas that contributes to environmental deterioration; however, it can also be utilized as an abundant C1 resource for the production of valuable chemicals. Solar-driven photoelectrocatalytic (PEC) CO2 utilization represents an advanced technology for the resourcing of CO2 . The key to achieving PEC CO2 utilization lies in high-performance semiconductor photoelectrodes. Si-based photoelectrodes have attracted increasing attention in the field of PEC CO2 utilization due to their suitable band gap (1.1 eV), high carrier mobility, low cost, and abundance on Earth. There are two pathways to PEC CO2 utilization using Si-based photoelectrodes: direct reduction of CO2 into small molecule fuels and chemicals, and fixation of CO2 with organic substrates to generate high-value chemicals. The efficiency and product selectivity of PEC CO2 utilization depends on the structures of the photoelectrodes as well as the composition, morphology, and size of the catalysts. In recent years, significant and influential progress has been made in utilizing Si-based photoelectrodes for PEC CO2 utilization. This review summarizes the latest research achievements in Si-based PEC CO2 utilization, with a particular emphasis on the mechanistic understanding of CO2 reduction and fixation, which will inspire future developments in this field.

Fluorescence Enhancement Method for Aptamer-Templated Silver Nanoclusters and Its Application in the Construction of a ß-Amyloid Oligomer Sensor.

DNA-templated silver nanoclusters (DNA-AgNCs) have attracted significant attention due to their unique fluorescence properties. However, so far, the relatively low quantum yields of the DNA-AgNCs and the complex design of DNA-AgNC-based sensors have limited their application in biosensing or bioimaging. Herein, we report a novel fluorescence enhancement method. The ß-Amyloid Oligomer (AßO) aptamer (AptAßO) with A10/T10 at its 3' end can be directly used as the template to fabricate the AgNCs. When the AgNCs were hybridized with the complementary strand that has 12 bases suspended at its 3' terminal, being the same or complementary to the A/T at the 3' end of the AptAßO, and two-base mismatches in the complementary region of the aptamer excluded A10/T10, a dramatic fluorescence enhancement (maximum: ∼500-fold; maximum quantum yield: 31.5%) can be realized. The fluorescence enhancement should result from the aggregation-induced emission of the AgNCs, which can be attributed to forming the reticular structure of the hybridized product. To some extent, the method developed in this work is extendable. The fluorescence enhancement was also realized from the thrombin aptamer-templated AgNCs through designing the aptamer and the corresponding complementary strand according to the method. Based on the fluorescence enhancement of the AptAßO-templated AgNCs, an "on-off" fluorescence sensor was constructed for the sensitive and selective detection of AßO. This work provides a rational strategy to realize fluorescence enhancement for the aptamer-templated AgNCs and design an aptamer-based fluorescence sensor.

Ultrahigh Modulation Enhancement in All-Optical Si-Based THz Modulators Integrated with Gold Nanobipyramids.

Optical regulation strategy with the aid of hybrid materials can significantly optimize the performance of terahertz devices. Gold nanobipyramids (AuNBPs) with synthetical tunability to the near-infrared band show strong local field enhancement, which improves optical coupling at the interface and benefits the modulation performance. We design AuNBPs-integrated terahertz modulators with multiple structured surfaces and demonstrate that introducing AuNBPs can effectively enhance their modulation depths. In particular, an ultrahigh modulation enhancement of 1 order of magnitude can be achieved in the AuNBPs hybrid metamaterials accompanied by the multifunctional modulation characteristics. By application of the coupled Lorentz oscillator model, the theoretical calculation suggests that the optical regulation with AuNBPs originates from increased damping rate and higher coupling coefficient under pump excitation. Additionally, a terahertz spatial light modulator is constructed to demonstrate multiple imaging display and consume extremely low power, which is promising for the potential application in spatial and frequency selective imaging.

Simultaneous Monitoring of the Adenosine Triphosphate Levels in the Cytoplasm and Nucleus of a Single Cell with a Single Nanowire-Based Fluorescent Biosensor.

Simultaneous monitoring of the ATP levels at various sites of a single cell is crucial for revealing the ATP-related processes and diseases. In this work, we rationally fabricated single nanowire-based fluorescence biosensors, by which the ATP levels of the cytoplasm and nucleus in a single cell can be simultaneously monitored with a high spatial resolution. Utilizing the as-fabricated single nanowire biosensor, we demonstrated that the ATP levels of the cytoplasm were around 20-30% lower than that of the nucleus in both L929 and HeLa cells. Observing the ATP fluctuation of the cytoplasm and nucleus of the L929 and HeLa cells stimulated by Ca2+, oligomycin, or under cisplatin-induced apoptosis, we found that the ATP levels at two cellular sites exhibited discriminative changes, revealing the different mechanisms of the ATP at these two cellular sites in response to the stimulations.

Sensitive and Stable Thermometer Based on the Long Fluorescence Lifetime of Au Nanoclusters for Mitochondria.

Detecting the temperature of intracellular mitochondria with high sensitivity and stability is crucial to understanding the cellular metabolism and revealing the processes of mitochondria-related physiology. In this paper, employing the long fluorescence lifetime of modified Au nanoclusters (mAuNCs) by 4-(carboxybutyl) triphenylphosphonium bromide, we developed a fluorescence lifetime thermometer with high sensitivity and stability for the temperature of the intracellular mitochondria. A high relative temperature sensitivity of 2.8% and excellent photostability were achieved from the present thermometer. After incubation with L929 cells, the mAuNCs could be endocytosed into the cells and targeted the mitochondria, and the temperature changes at the L929 cells' mitochondria, which were stimulated by carbonyl cyanide 3-chlorophenylhydrazone and Ca2+, were successfully detected via the fluorescence lifetime images of the mAuNCs. Furthermore, utilizing the mAuNCs, we clarified the effect of Mg2+ on the temperature of the intracellular mitochondria. The strategy of employing a material with a long fluorescence lifetime and remarkable stability to fabricate the fluorescence lifetime thermometer for mitochondria can be used to design various thermometers for other organelles.

Robust liquid-core nanocapsules as biocompatible and precise ratiometric fluorescent thermometers for living cells.

Intracellular thermometry with favorable biocompatibility and precision is essential for insight into temperature-related cellular events. Here, liquid-core nanocapsule ratiometric fluorescent thermometers (LCN-RFTs) were prepared by encapsulating thermosensitive organic fluorophores (N,N'-di(2-ethylhexyl)-3,4,9,10-perylene tetracarboxylic diimide, DEH-PDI) with hydrophobic solvent (2,2,4-trimethylpentane, TMP) into polystyrene/silica hybrid nanoshells. As the fluorescent thermosensitive unit of the LCN-RFT, the TMP solution of DEH-PDI was responsible for the fluorescence response to temperature. Benefitting from the hydrophilic nanoshells, the LCN-RFTs exhibited favorable anti-interference and biocompatibility. Furthermore, the LCN-RFTs showed an excellent precision of 0.02 °C-0.10 °C in a simulated physiological environment from 10.00 °C to 90.00 °C, and were employed to realize intracellular thermometry with an outstanding precision of 0.06 °C-0.14 °C. This work provides a feasible method of using hydrophobic organic fluorophores for intracellular thermometry by encapsulating them into nanocapsules.

Comparison of electrolyte and glucose levels measured by a blood gas analyzer and an automated biochemistry analyzer among hospitalized patients.

BACKGROUND: Blood gas analyzers are capable of delivering results on electrolytes and metabolites within a few minutes and facilitate clinical decision-making. However, whether the results can be used interchangeably with values measured by chemistry analyzers remains controversial. Blood gas analyzers are capable of delivering results on electrolytes and metabolites within a few minutes and facilitate clinical decision-making. However, whether the results can be used interchangeably with values measured by chemistry analyzers remains controversial. METHODS: In total, arterial and matched venous blood samples were collected from 200 hospitalized patients. Arterial blood samples were evaluated using a RAPIDPOINT 500 to test electrolyte and glucose levels, then the samples were centrifuged and the same parameters were measured with an AU5800. Venous blood samples were processed and tested in accordance with standard operation procedures. Data were compared by using a paired t test, the agreement between the two analyzers was evaluated by using the Bland-Altman test, and sensitivity and specificity were calculated. RESULTS: Paired t tests showed that all parameters tested were significantly different between the two analyzers except chloride. The biases calculated indicated that blood gas analyzers tend to underestimate the parameters, and the linear regression showed a strong correlation between the two analyzers. The sensitivity, specificity and kappa values demonstrated that the diagnostic performance of blood gas analyzers is not satisfactory. CONCLUSION: The significant reduction in parameter estimation and diagnostic performance we observed suggested that clinicians should interpret results from blood gas analyzers more cautiously. The reference interval of blood gas analyzers should be adjusted accordingly, given that values are underestimated.

Si-H induced synthesis of Si/Cu2O nanowire arrays for photoelectrochemical water splitting.

We report a facile and low-cost method to synthesize Si/Cu2O heterojunction nanowire arrays, without SiOx, at the Si/Cu2O interface. The reductive Si-H bonds on the surface of Si nanowires plays a key role in situ by reducing Cu(II) ions to Cu2O nanocubes and avoiding the SiOx interface layer. Different pH values would vary the electrochemical potential of reactions and as a result, different products would be formed. Utilized as a photoanode for water splitting, Si/Cu2O nanowire arrays exhibit good photoelectrochemical performance.

DNA nanostructure-based fluorescence thermometer with silver nanoclusters.

DNA nanostructure-based fluorescence thermometers were fabricated by linking fluorescent silver nanoclusters (AgNCs) and guanine-rich（G-rich）DNA chains via a thermally sensitive DNA stem-loop at terminals 5' and 3'. Variations of temperature alter the distance between the AgNCs and G-rich DNA chain, affecting the interaction between them. As a result, the intensity of fluorescence emission from the AgNCs at 636 nm can be sensitively modulated. It was found that the intensity of such red emission is more temperature sensitive than the equivalent green emission at 543 nm; sensitivity of -3.6%/°C was achieved. Through variation of the melting temperature of the DNA stem-loop, the response temperature range of the thermometers could be readily adjusted. Novel DNA nanostructure-based fluorescence thermometers as described in this work are anticipated to be able to measure the temperature of biological systems at small scales-even a single cell.

Silicon nanowire-based fluorescent nanosensor for complexed Cu2+ and its bioapplications.

A silicon nanowires (SiNWs)-based fluorescent sensor for complexed Cu(2+) was realized. High sensitivity and selectivity of the present sensor facilitate its bioapplications. The sensor was successfully used to detect the Cu(2+) in liver extract. Meanwhile, real-time and in situ monitoring of Cu(2+) released from apoptotic HeLa cell was performed using the as-prepared SiNW arrays-based sensor. These results indicate that the present SiNWs-based sensor would be of potential applications in revealing the physiological and pathological roles of Cu(2+).

SnO2 nanoparticle-coated ZnO nanotube arrays for high-performance electrochemical sensors.

Novel 1D nanostructures offer new opportunities for improving the performance of electrochemical sensors. In this study, highly ordered 1D nanostructure array electrodes composed of SnO2 nanoparticle-coated ZnO (SnO2 @ZnO) nanotubes are designed and fabricated. The composite nanotube array architecture not only endows the electrochemical electrodes with large surface areas, but also allows electrons to be quickly transferred along the nanotubes. Modifying the SnO2 @ZnO nanotube arrays with negatively charged polymer film and employing them as a working electrode, sensitive and selective electrochemical detection of an important neurotransmitter, i.e., dopamine, is realized via the cycle voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Interference from ascorbic acid can be successfully eliminated. The oxidative peak currents recorded from CV linearly depend on the dopamine concentrations from 0.1 to 100 µM with a sensitivity of 2.16 × 10(-7) A µM(-1) cm(-2) and detection limit of 45.2 nM. Using the DPV technique, an improved sensitivity and detection limit of 1.94 × 10(-6) A µM(-1) cm(-2) and 17.7 nM are respectively achieved. Moreover, the SnO2 @ZnO nanotube array electrodes can be reused through simple ultrasonical cleaning and no obvious deterioration is observed in the performance.

Predicting the Prognosis of Bladder Cancer Patients Through Integrated Multi-omics Exploration of Chemotherapy-Related Hypoxia Genes.

Bladder cancer is a prevalent malignancy with high mortality rates worldwide. Hypoxia is a critical factor in the development and progression of cancers. However, whether and how hypoxia-related genes (HRGs) could affect the development and the chemotherapy response of bladder cancer is still largely unexplored. This study comprehensively explored the complex molecular landscape associated with hypoxia in bladder cancer by analyzing 260 hypoxia genes based on transcriptomic and genomic data in 411 samples. Employing the 109 dysregulated hypoxia genes for consensus clustering, we delineated two distinct bladder cancer clusters characterized by disparate survival outcomes and distinct oncogenic roles. We defined a HPscore that was correlated with a variety of clinical features, including TNM stages and pathologic grades. Tumor immune landscape analysis identified three immune clusters and close interactions between hypoxia genes and the various immune cells. Utilizing a network-based method, we defined 129 HRGs exerting influence on apoptotic processes and critical signaling pathways in cancer. Further analysis of chemotherapy drug sensitivity identified potential drug-target HRGs. We developed a Risk Score model that was related to the overall survival of bladder cancer patients based on doxorubicin-target HRGs: ACTG2, MYC, PDGFRB, DHRS2, and KLRD1. This study not only enhanced our understanding of bladder cancer at the molecular level but also provided promising avenues for the development of targeted therapies, representing a significant step toward the identification of effective treatments and addressing the urgent need for advancements in bladder cancer management.

Tracking mitochondrial Cu(I) fluctuations through a ratiometric fluorescent probe in AD model cells: Towards understanding how AßOs induce mitochondrial Cu(I) dyshomeostasis.

Mitochondrial copper signaling pathway plays a role in Alzheimer's disease (AD), especially in relevant Amyloid-ß oligomers (AßOs) neurotoxicity and mitochondrial dysfunction. Clarifying the relationship between mitochondrial copper homeostasis and both of mitochondrial dysfunction and AßOs neurotoxicity is important for understanding AD pathogenesis. Herein, we designed and synthesized a ratiometric fluorescent probe CHC-NS4 for Cu(I). CHC-NS4 possesses excellent ratiometric response, high selectivity to Cu(I) and specific ability to target mitochondria. Under mitochondrial dysfunction induced by oligomycin, mitochondrial Cu(I) levels gradually increased, which may be related to inhibition of ATP7A-mediated Cu(I) exportation and/or high expression of COX. On this basis, CHC-NS4 was further utilized to visualize the fluctuations of mitochondrial Cu(I) levels during progression of AD model cells induced by AßOs. It was found that mitochondrial Cu(I) levels were gradually elevated during the AD progression, which depended on not only AßOs concentration but also incubation time. Moreover, endocytosis maybe served as a prime pathway mode for mitochondrial Cu(I) dyshomeostasis induced by AßOs during AD progression. These results have provided a novel inspiration into mitochondrial copper biology in AD pathogenesis.

Solution fabrication of large-area Si/TiO2 core/shell nanowire arrays modified by Au nanoparticles with high photoactivity for solar water splitting.

Large-area Si/TiO2 core/shell nanowire arrays were prepared for the first time by solution approach, followed by annealing in Ar (SiNWs/TiO2-Ar) and air (SiNWs/TiO2-air) atmosphere, respectively. Au nanoparticles were decorated onto the SiNWs/TiO2-Ar samples (SiNWs/TiO2@AuNPs-Ar) to further improve the photoactivity. XRD results showed that the TiO2 shells have an anatase crystalline structure. Photocurrent of solar water splitting was measured by a three electrode setup, in which the Si/TiO2 core/shell nanowire array served as the working electrode. It was found for the first time that Ar ambience annealing is more helpful improving the photocurrent density. The SiNWs/TiO2-Ar sample enhanced the photocurrent by 6.3 times compared to the SiNWs/TiO2-air sample. Furthermore, the SiNWs/TiO2@AuNPs-Ar arrays exhibited a photocurrent of 0.9 mA/cm2, 3.6 times as high as that of its counterpart without Au nanoparticles.

Super enhancer-driven core transcriptional regulatory circuitry crosstalk with cancer plasticity and patient mortality in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer. Core transcriptional regulatory circuitry (CRC) consists of autoregulated transcription factors (TFs) and their enhancers, which dominate gene expression programs and control cell fate. However, there is limited knowledge of CRC in TNBC. Herein, we systemically characterized the activated super-enhancers (SEs) and interrogated 14 CRCs in breast cancer. We found that CRCs could be broadly involved in DNA conformation change, metabolism process, and signaling response affecting the gene expression reprogramming. Furthermore, these CRC TFs are capable of coordinating with partner TFs bridging the enhancer-promoter loops. Notably, the CRC TF and partner pairs show remarkable specificity for molecular subtypes of breast cancer, especially in TNBC. USF1, SOX4, and MYBL2 were identified as the TNBC-specific CRC TFs. We further demonstrated that USF1 was a TNBC immunophenotype-related TF. Our findings that the rewiring of enhancer-driven CRCs was related to cancer immune and mortality, will facilitate the development of epigenetic anti-cancer treatment strategies.

Single nanowire-based fluorescence lifetime thermometer for simultaneous measurement of intra- and extra-cellular temperatures.

A silicon nanowire-based fluorescence lifetime thermometer (NWFLT) was fabricated for the simultaneous measurement of intra- and extra-cellular temperatures. Using the NWFLT, an obvious heterogeneity of the temperature was found along the longitude direction of the NWFLT, especially between the inside and outside of the cell.

Amorphous Ni-Mo-B-O Bifunctional Electrocatalyst for Simultaneous Production of Hydrogen and Value-added Chemicals.

Hydrogen evolution reaction (HER) coupled with biomass conversion is a sustainable route to produce clean energy H2 and value-added chemicals simultaneously. Herein, an amorphous Ni-Mo-B-O bifunctional electrocatalyst was synthesized through a facile electrodeposition method and employed as a cathode for HER to produce H2 and as an anode for the conversion of hydroxymethylfurfural (HMF) to furandicarboxylic acid (FDCA). Besides leading to the formation of amorphous structures, the introduction of Mo and B can increase the electron density and optimize the electronic structure of the electrocatalyst, thus substantially increasing the catalytic activity of the catalyst. After continuous reaction at a constant potential of 0.58 V vs. Hg/HgO for 8 hours, the conversion of HMF reached 98.86 %, and the selectivity of the target product FDCA was as high as 92.97 %. Finally, a two-electrolyzer system was constructed using the amorphous Ni-Mo-B-O as both cathode and anode to achieve simultaneous H2 production in the cathode chamber and FDCA production in the anode chamber at a low voltage. This work presents a promising strategy for the design and synthesis of high-performance non-noble metal electrocatalysts for efficient and cost-effective H2 production.

Comprehensive analysis of untargeted metabolomics and lipidomics in girls with central precocious puberty.

Objective: Central precocious puberty (CPP) is a rare condition that causes early sexual development in children. Although the cure is effective, the etiology of central precocious puberty is unclear. Methods: In total, 10 girls with central precocious puberty and same number of age-matched female controls were enrolled. Plasma samples were collected from each participant and subjected to untargeted metabolomics and lipidomics. Student's t-tests were employed to compare the mean of each metabolite and lipid. Furthermore, orthogonal partial least-squares discriminant analysis was conducted and the variable importance in the projection was calculated to identify differentially expressed metabolites or lipids. Subsequent bioinformatics was conducted to investigate the potential function of differentially expressed metabolites and lipids. Results: Fifty-nine differentially expressed metabolites were identified based on the criteria used (variable importance in the projection >1 and a P value < 0.05). Kyoto Encyclopedia Genes and Genome (KEGG) enrichment analysis showed that differentially expressed metabolites were enriched in four pathways: beta-alanine metabolism, histidine metabolism, bile secretion, and steroid hormone biosynthesis. As for the lipidomics, 41 differentially expressed lipids were observed and chain length analysis and lipid saturation analysis yielded similar results. Significant differences between the two groups were only observed in (O-acyl) ω-hydroxy fatty acids (OAHFA). Conclusion: The present study showed that antibiotic overuse, increased meat consumption, and obesity may have potential roles in the development of central precocious puberty in girls. Several metabolites have diagnostic value but further research is required.