Superior nitrate and chromium reduction synergistically driven by multiple electron donors: performance and the related biochemical mechanism.

Nitrate and Cr(VI) are the typical and prevalent co-contaminants in the groundwater, how to synchronously and effectively diminish them has received growing attention. The most problem that currently limits the nitrate and Cr(VI) reduction technology for groundwater remediation is with emphasis on exploring the optimal electron donors. This study investigated the feasibility of utilizing the synergistical effect of inorganic electron donors (pyrite, sulfur) and inherently limited organics to promote synchronous nitrate and Cr(VI) removal, which meets the requirement of naturally low-carbon and eco-friendly technologies. The NO3--N and Cr(VI) removal efficiencies in the pyrite and sulfur involved mixotrophic biofilter (PS-BF: approximately 90.8±0.6% and 99.1±2.1%) were substantially higher than that in a volcanic rock supported biofilter (V-BF: about 49.6%±2.8% and 50.0%±9.3%), which was consistent with the spatial variations of their concentrations. Abiotic and biotic batch tests directly confirmed the decisive role of pyrite and sulfur for NO3--N and Cr(VI) removal via chemical and microbial pathways. A server decline in sulfate production correlated with decreasing COD consumption revealed that there was sulfur disproportionation induced by limited organics. Metagenomic analysis suggested that chemoautotrophic microbes like Sulfuritalea and Thiobacillus were key players responsible for sulfur oxidation, nitrate and Cr(VI) reduction. The metabolic pathway analysis suggested that genes encoding functional enzymes related to complete denitrification, S oxidation, and dissimilatory sulfate reduction were upregulated, however, genes encoding Cr(VI) reduction enzymes (e.g. chrA, chrR, nemA, and azoR) were downregulated in PS-BF, which further explained the synergistical effect of multiple electron donors. These findings provide insights into their potential cooperative interaction of multiple electron donors on greatly promoting nitrate and Cr(VI) removal and have implications for the remediation technology of nitrate and Cr(VI) co-contaminated groundwater.

Effect of cooking methods on volatile compounds and texture properties in maize porridge.

To investigate the optimal processing of maize porridge, the volatile compounds and texture under different cooking methods and time have been studied. A total of 51 volatile compounds were identified in maize porridge. Notably, the major volatiles, aldehydes and esters exhibited a relatively high content in electric pressure cooker (EPC), and esters tend to significantly increase after cooking. Among aldehydes, nonanal and hexanal played a great role in flavor due to their relatively high content. Volatile compounds of maize porridge in different cooking methods could be clearly distinguished by multiple chemometrics. Furthermore, texture analysis revealed that almost all the indicators in the EPC can reach the lowest value at 60 min. To summarize, different cooking methods had a more significant influence on the volatile compounds and texture compared to time. This study helps to improve the sensory attributes of maize porridge, and thus contributes to healthier and more sustainable production.

Easy-to-Lay Poly-N Heterocyclic Additives Enable Long-Term Stabilization of Zinc-Ion Capacitor Anodes under Deep Plating/Stripping.

Addition of organic compounds containing O/N heteroatoms to aqueous electrolytes such as ZnSO4 (ZS) solutions is one of the effective strategies to inhibit Zn anode dendrites and side reactions. However, addressing the stability of Zn plating/stripping at high current densities and areal capacities by this method is still a challenge, especially in capacitors known for high power and long life. Herein, an organic heterocyclic compound of 1, 4, 7, 10-tetraazacyclododecane (TC) containing four symmetrically distributed N atoms is employed as ZS additive, expanding the life of Zn anodes from ≈ 30 h to 1000 and 240 h at deep plating/stripping conditions of 10 and 20 mA cm-2/mAh cm-2, respectively; the cumulative capacity is as high as 5.0 Ah cm-2 with 99% Coulombic efficiency, far exceeding reported additives. TC with higher binding energies than H2O for Zn species tends to adsorb to Zn (002) in a lying manner and participate in the solvation shell of Zn2+, thus avoiding Zn dendrites and side-reaction damage, especially at high current densities. The TC-endowed Zn anode's stability under such extreme conditions is verified in Zn-ion capacitors (i.e., > 94.6% capacity retention after 28 000 cycles), providing new insights into the development of high-power Zn-based energy storage devices.

A first-principles study on the promising thermoelectric properties of SnX (X = S, Se, Te) compounds.

SnSe has emerged as an outstanding thermoelectric material due to its exceptional performance. In this study, first-principles calculations are employed to investigate the thermoelectric properties of materials within the SnX family, where X can be either S, Se, or Te. Initially, we assessed the stability of SnX (X = S, Se, Te). We found that SnS exhibits better mechanical and thermal stability than SnSe and SnTe. We then conduct phonon and electronic transport analysis. Following the general rule that heavier atoms have lower thermal conductivity, SnTe demonstrates lower thermal conductivity due to its low group velocity compared with SnS and SnSe. Regarding electrical transport properties, the band gaps for SnS, SnSe, and SnTe are 0.56, 0.54, and 0.35 eV, respectively. Notably, the small band gap and higher degeneracy in its band valleys for SnTe make it more effective for achieving a high power factor. The maximum ZT values are determined to be 1.41, 1.41, and 1.87 for SnS, SnSe, and SnTe, respectively. Remarkably, ZTmax of SnTe exceeds that of SnSe by 32.6%. Overall, the results clearly demonstrate that SnTe exhibits superior thermoelectric properties compared to SnSe and SnS. This study provides valuable insights into the electronic structure, thermal conductivity, and mechanical and thermal stability of materials within the SnSe family, such as SnS or SnTe, without the need for extensive and costly experimental work.

Elucidation of Spatial Cooperativity in Chemo-Immunotherapy by a Sequential Dual-pH-Responsive Drug Delivery System.

Combining immune checkpoint blockade with chemotherapy through nanotechnology is promising in terms of safety and efficacy. However, the distinct subcellular distribution of each ingredient's action site makes it challenging to acquire an optimal synergism. Herein, a dual-pH responsive hybrid polymeric micelle system, HNP(αPDL16.9, Dox5.3), is constructed as a proof-of-concept for the spatial cooperativity in chemo-immunotherapy. HNP retains the inherent pH-transition of each polymer, with stepwise disassembly under discrete pH thresholds. Within weakly acidic extracellular tumor environment, αPDL1 is first released to block the checkpoint on cell membranes. The remaining intact Doxorubicin-loaded micelle NP(Dox)5.3 displays significant tropism toward tumor cells and releases Dox upon lysosomal pH for efficient tumor immunogenic cell death without immune toxicity. This sequential-released pattern boosts DC activation and primes CD8+ T cells, leading to enhanced therapeutic performance than single agent or an inverse-ordered combination in multiple murine tumor models. Using HNP, the indispensable role of conventional type 1 DC (cDC1) is identified in chemo-immunotherapy. A co-signature of cDC1 and CD8 correlates with cancer patient survival after neoadjuvant Pembrolizumab plus chemotherapy in clinic. This study highlights spatial cooperativity of chemo- and immuno-agents in immunoregulation and provides insights into the rational design of drug combination for future nanotherapeutics development.

Aqueous Cellulose Solution Adhesive.

In the context of sustainable development, research on a biomass-based adhesive without chemical modification as a substitute for petroleum-based adhesive is now crucial. It turns out to be challenging to guarantee a simple and sustainable method to produce high-quality adhesives and subsequently manufacture multifunctional composites. Herein, the inherent properties of cellulose were exploited to generate an adhesive based on a cellulose aqueous solution. The adhesion is simple to prepare structurally and functionally complex materials in a single process. Cellulose-based daily necessities including straws, bags, and cups were prepared by adhering cellulose films, and smart devices like actuators and supercapacitors assembled by adhering hydrogels were also demonstrated. In addition, the composite boards bonded with natural biomass wastes, such as wood chips, displayed significantly stronger mechanical properties than the natural wood or commercial composite boards. Cellulose aqueous adhesives provide a straightforward, feasible, renewable, and inventive bonding technique for material shaping and the creation of multipurpose devices.

Ferroptosis: An important mechanism of disease mediated by the gut-liver-brain axis.

AIMS: As a unique iron-dependent non-apoptotic cell death, Ferroptosis is involved in the pathogenesis and development of many human diseases and has become a research hotspot in recent years. However, the regulatory role of ferroptosis in the gut-liver-brain axis has not been elucidated. This paper summarizes the regulatory role of ferroptosis and provides theoretical basis for related research. MATERIALS AND METHODS: We searched PubMed, CNKI and Wed of Science databases on ferroptosis mediated gut-liver-brain axis diseases, summarized the regulatory role of ferroptosis on organ axis, and explained the adverse effects of related regulatory effects on various diseases. KEY FINDINGS: According to our summary, the main way in which ferroptosis mediates the gut-liver-brain axis is oxidative stress, and the key cross-talk of ferroptosis affecting signaling pathway network is Nrf2/HO-1. However, there were no specific marker between different organ axes mediate by ferroptosis. SIGNIFICANCE: Our study illustrates the main ways and key cross-talk of ferroptosis mediating the gut-liver-brain axis, providing a basis for future research.

Current therapies and progress in the treatment of advanced gastric cancer.

Gastric cancer (GC) remains one of the most life-threatening disease worldwide with poor prognosis because of the absence of effective treatment and the delay in diagnosis. Due to the delay of diagnosis, a large proportion of GC patients are diagnosed as advanced GC, with extreme short lifespan. In the past few years, some pivotal progress and novel therapies was proposed, and conducted into clinical researches and practice. In this study, we summarized the development of several novel immunotherapy or targeted treatment modalities for advanced GC, including immune checkpoint inhibitors, anti-angiogenic therapy and cancer vaccines. Additionally, the advantage and potential weakness in each of these therapeutic methods are also listed. Finally, we discussed the promising research direction of advanced GC treatment, and the limitation in basic and clinical research of advanced GC, including the combination of immunotherapy and targeted therapy.

Comparative evaluation of SPE methods for biotoxicity assessment of water and wastewater: Linkage between chemical extracting efficiency and biotoxicity outcome.

Biotoxicity assessment results of environmental waters largely depend on the sample extraction protocols that enrich pollutants to meet the effect-trigger thresholds of bioassays. However, more chemical mixture does not necessarily translate to higher combined biotoxicity. Thus, there is a need to establish the link between chemical extracting efficiency and biotoxicity outcome to standardize extraction methods for biotoxicity assessment of environmental waters. This study compares the performance of five different extraction phases in solid phase extraction (SPE), namely HLB, HLB+Coconut, C18 cartridge, C18 disk and Strata-X, and evaluated their chemical extracting efficiencies and biotoxicity outcomes. We quantitatively assessed cytotoxicity, acute toxicity, genotoxicity, estrogenic activity, and neurotoxicity of the extracts using in vitro bioassays and characterized the chemical extracting efficiencies of the SPE methods through chemical recoveries of 23 model compounds with different polarities and total organic carbon. Using Pareto ranking, we identified HLB+Coconut as the optimal SPE method, which exhibited the highest level of water sample biotoxicity and recovered the most chemicals in water samples. We found that the biotoxicity outcomes of the extracted water samples significantly and positively correlated with the chemical extracting efficiencies of the SPE methods. Moreover, we observed synchronous changing patterns in biotoxicity outcome and chemical extracting efficiencies in response to increasing sample volumes per cartridge (SVPC) during SPE. Our findings underscore that higher chemical extracting efficiency of SPE corresponds to higher biotoxicity outcome of environmental water samples, providing a scientific basis for standardization of SPE methods for adequate assessment of biotoxicities of environmental waters.

Enhanced Recovery of Oil Mixtures from Calcite Nanopores Facilitated by CO2 Injection.

Slow production, preferential recovery of light hydrocarbons, and low recovery factors are common challenges in oil production from unconventional reservoirs dominated by nanopores. Gas injection-based techniques such as CO2 Huff-n-Puff have shown promise in addressing these challenges. However, a limited understanding of the recovery of oil mixtures on the nanopore scale hinders their effective optimization. Here, we use molecular dynamics simulations to study the recovery of an oil mixture (C10 + C19) from a single 4 nm-wide calcite dead-end pore, both with and without CO2 injection. Without CO2 injection, oil recovery is much faster than expected from oil vaporization and features an undesired selectivity, i.e., the preferential recovery of lighter C10. With CO2 injection, oil recovery is accelerated and its selectivity toward C10 is greatly mitigated. These recovery behaviors are understood by analyzing the spatiotemporal evolution of C10, C19, and CO2 distributions in the calcite pore. In particular, we show that interfacial phenomena (e.g., the strong adsorption of oil and CO2 on pore walls, their competition, and their modulation of transport behavior) and bulk phenomena (e.g., solubilization of oil by CO2 in the middle portion of the pore) play crucial roles in determining the oil recovery rate and selectivity.

Evolution of Grain Boundary Character Distribution in B10 Alloy from Friction Stir Processing to Annealing Treatment.

In this study, the grain boundary character distribution (GBCD) of a B10 alloy was optimized, employing thermomechanical processing consisting of friction stirring processing (FSP) and annealing treatment. Using electron backscatter diffraction, the effects of rotational speed of FSP and annealing time on the evolution of GBCD were systematically investigated. The GBCD evolution was analyzed concerning various parameters, such as the fraction of low-Σ coincidence site lattice (CSL) boundaries, the average number of grains per twin-related domain (TRD), the length of longest chain (LLC), and the triple junction distribution. The experimental results revealed that the processing of a 1400 rpm rotational speed of FSP followed by annealing at 750 °C for 60 min resulted in the optimum grain boundary engineering (GBE) microstructure with the highest fraction of low-Σ CSL boundaries being 82.50% and a significantly fragmented random boundary network, as corroborated by the highest average number of grains per TRD (14.73) with the maximum LLC (2.14) as well as the highest J2/(1 - J3) value (12.76%). As the rotational speed of FSP increased from 600 rpm to 1400 rpm, the fraction of low-Σ CSL boundaries monotonously increased. The fraction of low-Σ CSL boundaries first increased and then decreased with an increase in annealing time. The key to achieving GBE lies in inhibiting the recrystallization phenomenon while stimulating abundant multiple twinning events through strain-induced boundary migration.

A signal "switch-on" photoelectrochemical sensor based on a 3D-FM/BiOI heterostructure for the sensitive detection of l-ascorbic acid.

A highly efficient 3D flower MoS2 (3D-FM)-based heterostructure photocatalyst (3D-FM/BiOI) was successfully obtained via a simple hydrothermal synthesis strategy. 3D-FM/BiOI showed prominent photoelectrochemical performance, distinguished stability and good selectivity. The introduction of 3D-FM, by promoting the photoelectric property attributed to it, facilitated the separation of photogenerated electron-hole pairs. Since the redox process of l-ascorbic acid (l-AA) resulted in an increasing photocurrent of 3D-FM/BiOI, a signal "switch-on" photoelectrochemical sensor (PECS) was designed to sensitively determine l-AA for the first time. Under optimized conditions, the 3D-FM/BiOI PECS worked over a wide range from 1 µM to 0.8 mM with a low detection limit of 0.05 µM (S/N = 3). The PECS was successfully exploited for l-AA sensing in human urine with excellent accuracy and applicability, demonstrating its practical precision and superb serviceability. Furthermore, the 3D-FM/BiOI PECS exhibited satisfactory selectivity and stability, providing a great potential platform for the construction of an l-AA sensor in various practical samples and complicated environments.

Causal Association Between Allergic Diseases and Dementia: Evidence from Multivariate Mendelian Randomization Study.

Background: The link between allergic diseases and dementia remains controversial, and the genetic causality of this link is unclear. Objective: This study investigated the causal relationship between allergic diseases and dementia using univariate and multivariate Mendelian randomization (MR) methods. Methods: We selected genome-wide association studies including 66,645 patients with allergic diseases and 12,281 patients with dementia, with statistical datasets derived from the FinnGen Consortium of European origin. After a rigorous screening process for single nucleotide polymorphisms to eliminate confounding effects, MR estimation was performed mainly using the inverse variance weighting method and the MR-Egger method. Sensitivity analyses were performed using Cochran's Q test, MR-PRESSO test, MR Pleiotropy residuals and leave-one-out analysis. Results: Univariate and multivariate MR together demonstrated a causal relationship between atopic dermatitis and reduced vascular dementia (VaD) risk (OR = 0.89, 95% CI: 0.81-0.99, p = 0.031; OR = 0.85, 95% CI: 0.76-0.95, p = 0.003). MVMR confirmed asthma was associated with a reduction in the risk of Alzheimer's disease (AD) (OR = 0.82, 95% CI: 0.71-0.94, p = 0.005) and may be associated with a reduction in the risk of VaD (OR = 0.80, 95% CI: 0.65-0.99, p = 0.042); allergic rhinitis may be causally associated with an increased risk of AD (OR = 1.16, 95% CI: 1.00-1.35, p = 0.046) and VaD (OR = 1.29, 95% CI: 1.03-1.62, p = 0.027). In sensitivity analyses, these findings were reliable. Conclusions: MR methods have only demonstrated that allergic rhinitis dementia is associated with an increased risk of developing dementia. Previously observed associations between other allergic diseases and dementia may be influenced by comorbidities and confounding factors rather than causality.

High-substituted hydroxypropyl cellulose prepared by homogeneous method and its clouding and self-assembly behaviors.

Hydroxypropyl cellulose (HPC) is a sustainable cellulose derivative valued for its excellent biocompatibility and solubility and is widely used in various fields. Recent scientific research on high-substituted HPC mainly focused on its efficient preparation and phase transition behavior. Herein, a novel strategy of high-substituted HPC synthesis was demonstrated by employing DMSO/TBAF·3H2O as a cellulose solvent, exhibiting more efficiency than traditional approaches. High-substituted HPC prepared has remarkable thermal stability, exceptional hydrophilicity, and satisfactory solubility. Phase transition behavior of HPC with varying molar degrees of substitution (MS) was delved and a notable negative correlation between MS and cloud point temperature (TCP), was revealed, particularly evident at an MS of 12.3, where the TCP drops to 33 °C. Moreover, a unique self-assembly behavior featuring structural color and responsiveness to force in a solvent-free environment emerged when the MS exceeded 10.4. These insights comprehensively strengthen the understanding and knowledge of high-substituted HPC, simultaneously paving the way for further HPC investigation and exploitation.

Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-ß/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.

Polyethylene glycol regulates the pitch and liquid crystal behavior of cellulose nanocrystal-based photonic crystals.

Inspired by iridescent color in natural creations, cellulose nanocrystal (CNC) photonic crystals artificially created by nanotechnology have great application prospects due to their potential to control light propagation in the linear and nonlinear regimes. One of the most important development directions of photonic crystals is the diversification of colors, usually by adjusting the pitch. However, few researchers notice the effect of polymer molecular weight and content on pitch regulation and the interaction between polymer and CNC liquid crystals. Polyethylene glycol (PEG) were used as polymers to regulate the pitch of CNC photonic crystals and investigate the changes in microstructure, crystal structure, thermal properties, and liquid crystal texture of the composites by changing the PEG content and molecular weight. Different photonic crystal construction systems show that when the molecular weight of PEG is 0.4 k, it can be filled between CNCs to regulate the pitch of photonic crystals, while when the molecular weight of PEG is 20 k, it cannot always be filled between CNCs in evaporation-induced self-assembly (EISA) process due to the depletion interaction, which cannot effectively regulate the pitch. This study reveals the relationship between PEG and CNC liquid crystals, which supports the development of photonic crystals and the pitch regulation.

Curcumin-loaded chitosan-based hydrogels accelerating S. aureus-infected wound healing.

The damaged skin for some reasons is vulnerable to invasion by bacteria and other harmful microorganisms, leading to delay of the wound healing. In order to promote the infected wound healing, curcumin was loaded with chitosan-based hydrogel was formed through phenylborate ester bonding and its properties and effects on the S. aureus-infected wound healing was tested. It was found the hydrogel showed good antioxidation on the intracellular reactive oxygen species, inhibition on the growth of S. aureus, and acceleration the infected skin healing. The ablity of hydrogel due to its regulating inflammation, promoting angiogenesis and collagen synthesis in the wound site. This research work suggested that the developed multifunctional hydrogel might be a beneficial treatment for the infected wound healing.

Refining prediction of stroke in sinus node dysfunction patients without atrial fibrillation using a P-combined score: a multi-centre study.

AIMS: Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS. METHODS AND RESULTS: In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell's C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort. CONCLUSION: Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.

By screening the risk factors of ischaemic stroke for isolated sinus node dysfunction (sinus node dysfunction without atrial fibrillation), we developed and validated a new scoring system­P-combined score, which is a combination of an abnormal P-wave terminal force in electrocardiogram-lead V1 (PTFV1) and the CHA2DS2-VASc score. We constructed the P-combined score in the following way: abnormal PTFV1 (2 points), age (1 point for 65­74 years and 2 points for ≥75 years), sex (1 point for female), congestive heart failure (1 point), hypertension (1 point), diabetes mellitus (1 point), vascular disease (1 point), and thrombotic event (2 points). Based on our analysis, we found that the P-combined score showed a strong performance (with a C-statistic of 0.716 for 5 years), which was better than the CHA2DS2-VASc score (C-statistic of 0.678 for 5 years). We also found that the performance of the P-combined score was rigorous in an independent cohort from two external centres (with a C-statistic of 0.808 for 5 years) and outperformed the CHA2DS2-VASc score (C-statistic of 0.747 for 5 years).

Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation.

Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor integrin ß1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule α-catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of integrin ß1 and α-catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation.