Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact.

The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet. Developmental ablation of Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglion cell layer (GCL), leading to a disorganized 3D vascular lattice. We identified enriched PIEZO2 expression in Fam19a4/Nts-RGCs. Piezo2 loss from all retinal neurons or Fam19a4/Nts-RGCs abolished the direct neurovascular contacts and phenocopied the Fam19a4/Nts-RGC ablation deficits. The defective vascular structure led to reduced capillary perfusion and sensitized the retina to ischemic insults. Furthermore, we uncovered a Piezo2-dependent perivascular granule cell subset for cerebellar vascular patterning, indicating neuronal Piezo2-dependent 3D vascular patterning in the brain.

Longitudinal in vivo Ca2+ imaging reveals dynamic activity changes of diseased retinal ganglion cells at the single-cell level.

Retinal ganglion cells (RGCs) are heterogeneous projection neurons that convey distinct visual features from the retina to brain. Here, we present a high-throughput in vivo RGC activity assay in response to light stimulation using noninvasive Ca2+ imaging of thousands of RGCs simultaneously in living mice. Population and single-cell analyses of longitudinal RGC Ca2+ imaging reveal distinct functional responses of RGCs and unprecedented individual RGC activity conversions during traumatic and glaucomatous degeneration. This study establishes a foundation for future in vivo RGC function classifications and longitudinal activity evaluations using more advanced imaging techniques and visual stimuli under normal, disease, and neural repair conditions. These analyses can be performed at both the population and single-cell levels using temporal and spatial information, which will be invaluable for understanding RGC pathophysiology and identifying functional biomarkers for diverse optic neuropathies.

Rational Design of Amorphous Carbon-Coated Laminar-Structured Wood for Integrating Repeatable Early Fire Detection and High-Temperature Affordable Flexible Pressure Sensing in One System.

High-temperature affordable flexible polymer-based pressure sensors integrated with repeatable early fire warning service are strongly desired for harsh environmental applications, yet their creation remains challenging. This work proposed an approach for preparing such advanced integrated sensors based on silver nanoparticles and an ammonium polyphosphate (APP)-modified laminar-structured bulk wood sponge (APP/Ag@WS). Such integrated sensors demonstrated excellent fire warning performance, including a short response time (minimum of 0.44 s), a long-lasting alarm time (>750 s), and reliable repeatability. Moreover, it achieved high-temperature affordable flexible pressure sensing that exhibited an almost unimpaired working range of 0-7.5 kPa and a higher sensitivity (in the low-pressure range, maximum to 226.03 kPa-1) after fire. The high stability was attributed to reliable structural elasticity, and the wood-derived amorphous carbon is capable of repeatable fire warnings. Finally, a Ag@APP/WS-based wireless fire alarm system that realized reliable house fire accident detection was demonstrated, showing great promise for smart firefighting application.

Development and validation of an inflammatory biomarkers model to predict gastric cancer prognosis: a multi-center cohort study in China.

BACKGROUND: Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. METHODS: Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. RESULTS: A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. CONCLUSION: The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.

Efficient nitrogen removal by multi-stage A/O mud membrane composite process with segmented influent: Performance and microbial community structure.

In this paper, a multi-stage A/O mud membrane composite process with segmented influent was constructed for the first time and compared with the traditional activated sludge process and the multi-stage A/O pure membrane process with segmented influent. The nitrogen removal efficiency of the process under different influencing factors was studied. Under the optimum conditions, the highest removal rate of ammonia nitrogen can reach 99%, and the average removal rate of total nitrogen was 80%. The removal rate of COD in effluent reached 93%. The relative abundance of Proteobacteria was the highest in the multi-stage A/O mud membrane composite reactor with segmented influent. The community diversity and richness of activated sludge and biofilm in aerobic pool were the highest. Dechloromonas, Flavobacterium and Rhodobacter were dominant bacteria, and they were aerobic denitrifying bacteria that significantly contributed to the removal rate of ammonia nitrogen.

Compact polarization transceiver module for fiber optic gyroscopes.

This paper reports a transceiver module with a high polarization extinction ratio (PER) for the polarization-maintaining interferometric fiber optic gyroscope (PM-IFOG). This transceiver utilizes a graded-index lens featuring a slanted face coated with a multilayer film, enabling simultaneous collimation and beam splitting. Configurations of the graded-index splitter lens and the corresponding transceiver module are simulated and designed using the ray matrix method and physical optical propagation. The optical loss of the transceiver module is about 3.77 dB, and the PER exceeds 25 dB. The IFOG prototype is implemented by integrating the transceiver module with a PM sensing coil. The bias instability of the IFOG prototype is evaluated to be 0.51°/h by Allan variance. This research contributes to the reduction in size, weight, power consumption, and cost of PM-IFOG systems.

Assessing the causal association between dietary vitamin intake and lymphoma risk: a Mendelian randomisation study.

Observational studies of diet-related vitamins and lymphoma risk results were inconsistent. Our study aimed to estimate the causality between dietary vitamin intake and lymphoma through a Mendelian randomisation (MR) study. We enrolled dietary-related retinol, vitamin C, vitamin E, vitamin B6 and vitamin B12 as exposures of interest, with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) as the outcome. The causal effects were estimated using inverse variance weighting (IVW), MR-Egger regression analysis and weighted median, supplemented by sensitivity analyses. The results revealed that genetically predicted dietary vitamin B12 intake was associated with a reduced HL risk (OR = 0.22, 95% CI 0.05-0.91, p = 0.036). The Q test did not reveal heterogeneity, the MR-Egger test showed no significant intercepts, and the leave-one-out (LOO) analysis did not discover any SNP that affect the results. No causal relationship about dietary vitamin intake on the NHL risk was observed.

Dynamic assessment of seawater quality based on semi-partial subtraction set pair potential method and game theory.

The assessment of seawater quality is a complex process as it involves the influence of several factors and is characterized by dynamic changes in these factors. Herein, a novel model coupled with the semi-partial subtraction set pair potential method (SSSPP) and game theory was discussed for the dynamic assessment of seawater quality. In the proposed model, the identity-discrepancy-contrary degrees were calculated to construct the evaluation matrix, and then the classification and the dynamic risk trends of the seawater quality were determined. A case study and comparison with the single-factor approach and Nemerow index evaluation method were carried out to confirm the accuracy and dependability of the suggested model. The results indicate that the proposed method can be used to measure trends in seawater quality evolution and also to diagnose key indicators affecting seawater quality. It provides a new and effective way to accurately identify the quality of seawater and its trends.

Mechanical processes underlying precise and robust cell matching.

During the development of complicated multicellular organisms, the robust formation of specific cell-cell connections (cell matching) is required for the generation of precise tissue structures. Mismatches or misconnections can lead to various diseases. Diverse mechanical cues, including differential adhesion and temporally varying cell contractility, are involved in regulating the process of cell-cell recognition and contact formation. Cells often start the process of cell matching through contact via filopodia protrusions, mediated by specific adhesion interactions at the cell surface. These adhesion interactions give rise to differential mechanical signals that can be further perceived by the cells. In conjunction with contractions generated by the actomyosin networks within the cells, this differentially coded adhesion information can be translated to reposition and sort cells. Here, we review the role of these different cell matching components and suggest how these mechanical factors cooperate with each other to facilitate specificity in cell-cell contact formation.

Generation of Atp6v1g3-Cre mice for investigation of intercalated cells and the collecting duct.

Kidney intercalated cells (ICs) maintain acid-base homeostasis and recent studies have demonstrated that they function in the kidney's innate defense. To study kidney innate immune function, ICs have been enriched using vacuolar ATPase (V-ATPase) B1 subunit (Atp6v1b1)-Cre (B1-Cre) mice. Although Atp6v1b1 is considered kidney specific, it is expressed in multiple organ systems, both in mice and humans, raising the possibility of off-target effects when using the Cre-lox system. We have recently shown using single-cell RNA sequencing that the gene that codes for the V-ATPase G3 subunit (mouse gene: Atp6v1g3; human gene: ATP6V1G3; protein abbreviation: G3) mRNA is selectively enriched in human kidney ICs. In this study, we generated Atp6v1g3-Cre (G3-Cre) reporter mice using CRISPR/CAS technology and crossed them with Tdtomatoflox/flox mice. The resultant G3-Cre+Tdt+ progeny was evaluated for kidney specificity in multiple tissues and found to be highly specific to kidney cells with minimal or no expression in other organs evaluated compared with B1-Cre mice. Tdt+ cells were flow sorted and were enriched for IC marker genes on RT-PCR analysis. Next, we crossed these mice to ihCD59 mice to generate an IC depletion mouse model (G3-Cre+ihCD59+/+). ICs were depleted in these mice using intermedilysin, which resulted in lower blood pH, suggestive of a distal renal tubular acidosis phenotype. The G3-Cre mice were healthy, bred normally, and produce regular-sized litter. Thus, this new "IC reporter" mice can be a useful tool to study ICs.NEW & NOTEWORTHY This study details the development, validation, and experimental use of a new mouse model to study the collecting duct and intercalated cells. Kidney intercalated cells are a cell type increasingly recognized to be important in several human diseases including kidney infections, acid-base disorders, and acute kidney injury.

Designed Synthesis of Compartmented Bienzyme Biocatalysts Based on Core-Shell Zeolitic Imidazole Framework Nanostructures.

For complex cascade biocatalysis, multienzyme compartmentalization helps to optimize substrate transport channels and promote the orderly and tunable progress of step reactions. Herein, a simple and general synthesis strategy is proposed for the construction of a multienzyme biocatalyst by compartmentalizing glucose oxidase and horseradish peroxidase (GOx and HRP) within core-shell zeolite imidazole frameworks (ZIF)-8@ZIF-8 nanostructures. Owing to the combined effects of biomimetic mineralization and the fine regulation of the ZIF-8 growth process, the uniform shell encloses the seed (core) surface by epitaxial growth, and the bienzyme system is accurately localized in a controlled manner. The versatility of this strategy is also reflected in ZIF-67. Meanwhile, with the ability to covalently bind divalent metal ions, lithocholic acid (LCA) is used as a competitive ligand to improve the pore structure of the ZIF from a single micropore to a hierarchical micro/mesopore network, which greatly increases mass transfer efficiency. Furthermore, the multienzyme cascade reaction is exemplified by the oxidation of o-phenylenediamine (OPD). The findings show that the bienzyme assembly strategy significantly affects the biocatalytic efficiency mainly by influencing the utilization efficiency of the intermediate (Hydrogen peroxide, H2 O2 ) between the step reactions. This study sheds new light on facile synthetic routes to constructing in vitro multienzyme biocatalysts.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

Hydrophobic Carbon Dots Derived from Organic Pollutants and Applications in NIR Anticounterfeiting and Bioimaging.

In an effort to fulfill the strategy of sustainable development, Rhodamine B, a common and toxic organic pollutant in the textile industry, was reported for the first time as a single precursor to develop a kind of novel hydrophobic nitrogen-doped carbon dot (HNCD) through a green and facile one-pot solvothermal method. The HNCDs with an average size of 3.6 nm possess left and right water contact angles of 109.56° and 110.34°, respectively. The HNCDs manifest excitation wavelength-tunable and upconverted fluorescence from the ultraviolet (UV) to the near-infrared (NIR) range. Furthermore, the PEGylation of HNCDs enables them to be used as an optical marker for cell and in vivo imaging. Notably, the HNCDs with solvent-dependent fluorescence can be used for invisible inks with a wide range of light responses from UV-vis-NIR spectra. This work not only provides an innovative way to recycle chemical waste but also expands the potential application of HNCDs in NIR security printing and bioimaging.

Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow.

Interactions between tumorigenic cells and their surrounding microenvironment are critical for tumor progression yet remain incompletely understood. Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1), a common genetic disorder characterized by complex tumors called neurofibromas. Genetic studies indicate that biallelic loss of Nf1 is required in the tumorigenic cell of origin in the embryonic Schwann cell lineage. However, in the physiologic state, Schwann cell loss of heterozygosity is not sufficient for neurofibroma formation and Nf1 haploinsufficiency in at least one additional nonneoplastic lineage is required for tumor progression. Here, we establish that Nf1 heterozygosity of bone marrow-derived cells in the tumor microenvironment is sufficient to allow neurofibroma progression in the context of Schwann cell Nf1 deficiency. Further, genetic or pharmacologic attenuation of c-kit signaling in Nf1+/- hematopoietic cells diminishes neurofibroma initiation and progression. Finally, these studies implicate mast cells as critical mediators of tumor initiation.

MAFB promotes the malignant phenotypes by IGFBP6 in esophageal squamous cell carcinomas.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant diseases in the world. Although the somatic alterations have been fully identified, there are still no targeted drugs at present. Our previous studies revealed that loss of grand H3K27me3 domains mediated transcriptional activation of a series of genes in ESCC. Among them, we focus on the investigation of MAFB, as its high expression is associated with a poor prognosis in ESCC. Functional assays show that knockdown of MAFB significantly suppresses cell growth, migration and invasion. Mechanistic investigation demonstrates that MAFB exerts its function by upregulating IGFBP6. Our findings suggest that MAFB may play a tumor-promoting role and may act as a potential therapeutic target for ESCC.

Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors.

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.

Copper-based Ruddlesden-Popper perovskite oxides activated hydrogen peroxide for coal pyrolysis wastewater (CPW) degradation: Performance and mechanism.

Coal pyrolysis wastewater (CPW) contained all kinds of toxic and harmful components, which would seriously threaten the natural environment and human health. However, the traditional advanced oxidation processes frequently failed to remove phenolic substances. An A2BO4-type perovskite (La2CuO4) was successfully synthesized through sol-gel process and first applied in the treatment of CPW. More than 90% of 3, 5-dimethylphenol (DMP) was removed within 200 min at neutral conditions. Moreover, La2CuO4 also displayed excellent catalytic activity and stability in the actual CPW treatment process. Results demonstrated that DMP was removed through the attack of ∙OH, ∙O2- and 1O2 in La2CuO4/H2O2 system. The La2CuO4 were more favorable for H2O2 activation and have a lower adsorption energy than LaFeO3. XPS of fresh and spent La2CuO4 illustrated that the decomposition of hydrogen peroxide (H2O2) was mainly due to the redox cycle between surface copper and oxygen species. Moreover, the possible degradation pathway of DMP was deduced by identifying degradation products and analyzing density functional theory (DFT) calculations. This research provided a novel strategy for the development of perovskite-based catalytic materials on the treatment of practical CPW.

Multi-Objective Optimal Trajectory Planning for Robotic Arms Using Deep Reinforcement Learning.

This study investigated the trajectory-planning problem of a six-axis robotic arm based on deep reinforcement learning. Taking into account several characteristics of robot motion, a multi-objective optimization approach is proposed, which was based on the motivations of deep reinforcement learning and optimal planning. The optimal trajectory was considered with respect to multiple objectives, aiming to minimize factors such as accuracy, energy consumption, and smoothness. The multiple objectives were integrated into the reinforcement learning environment to achieve the desired trajectory. Based on forward and inverse kinematics, the joint angles and Cartesian coordinates were used as the input parameters, while the joint angle estimation served as the output. To enable the environment to rapidly find more-efficient solutions, the decaying episode mechanism was employed throughout the training process. The distribution of the trajectory points was improved in terms of uniformity and smoothness, which greatly contributed to the optimization of the robotic arm's trajectory. The proposed method demonstrated its effectiveness in comparison with the RRT algorithm, as evidenced by the simulations and physical experiments.

Taurine alleviates heat stress-induced mammary inflammation and impairment of mammary epithelial integrity via the ERK1/2-MLCK signaling pathway.

Heat stress leads to milk production losses and mammary gland inflammation, which may be associated with mammary epithelium damage. Taurine is one of the most abundant free amino acids in mammals which has anti-inflammatory properties. This study aimed to explore the effect of taurine pretreatment on heat stress-induced mammary epithelial integrity disruption and inflammatory damage. In our first experiment on dairy cows our results showed that compared with animals under autumn thermoneutral condition (THI = 62.99 ± 0.71), summer heat stress (THI = 78.01 ± 0.39) significantly reduced milk yield and disrupted mammary epithelial integrity as revealed by increased concentrations of serotonin and lactose in plasma, and increased levels of SA and Na+/K+ in milk. In our second study, 36 lactating mice were randomly divided into three groups (n = 12) for a 9d experiment using a climate chamber to establish a heat stress model. Our findings suggest taurine pretreatment could attenuate heat stress-induced mammary histopathological impairment, inflammation response, and enhance mammary epithelium integrity, which was mainly achieved by promoting the secretion of ZO-1, Occludin, and Claudin-3 through inhibiting activation of the ERK1/2-MLCK signaling pathway in the mammary gland. Overall, our findings indicated that heat stress induced mammary epithelium dysfunction in dairy cows, and emphasized the protective effect of taurine on mammary health under heat stress conditions using a mouse model, which may be achieved by alleviating the mammary epithelium integrity damage and inflammation response.

A Semi-supervised Sensing Rate Learning based CMAB scheme to combat COVID-19 by trustful data collection in the crowd.

The recruitment of trustworthy and high-quality workers is an important research issue for MCS. Previous studies either assume that the qualities of workers are known in advance, or assume that the platform knows the qualities of workers once it receives their collected data. In reality, to reduce costs and thus maximize revenue, many strategic workers do not perform their sensing tasks honestly and report fake data to the platform, which is called False data attacks. And it is very hard for the platform to evaluate the authenticity of the received data In this paper, an incentive mechanism named Semi-supervision based Combinatorial Multi-Armed Bandit reverse Auction (SCMABA) is proposed to solve the recruitment problem of multiple unknown and strategic workers in MCS. First, we model the worker recruitment as a multi-armed bandit reverse auction problem and design an UCB-based algorithm to separate the exploration and exploitation, regarding the Sensing Rates (SRs) of recruited workers as the gain of the bandit Next, a Semi-supervised Sensing Rate Learning (SSRL) approach is proposed to quickly and accurately obtain the workers' SRs, which consists of two phases, supervision and self-supervision. Last, SCMABA is designed organically combining the SRs acquisition mechanism with multi-armed bandit reverse auction, where supervised SR learning is used in the exploration, and the self-supervised one is used in the exploitation. We theoretically prove that our SCMABA achieves truthfulness and individual rationality and exhibits outstanding performances of the SCMABA mechanism through in-depth simulations of real-world data traces.