Ultra-high brightness Micro-LEDs with wafer-scale uniform GaN-on-silicon epilayers.

Owing to high pixel density and brightness, gallium nitride (GaN) based micro-light-emitting diodes (Micro-LEDs) are considered revolutionary display technology and have important application prospects in the fields of micro-display and virtual display. However, Micro-LEDs with pixel sizes smaller than 10 µm still encounter technical challenges such as sidewall damage and limited light extraction efficiency, resulting in reduced luminous efficiency and severe brightness non-uniformity. Here, we reported high-brightness green Micro-displays with a 5 µm pixel utilizing high-quality GaN-on-Si epilayers. Four-inch wafer-scale uniform green GaN epilayer is first grown on silicon substrate, which possesses a low dislocation density of 5.25 × 108 cm-2, small wafer bowing of 16.7 µm, and high wavelength uniformity (standard deviation STDEV < 1 nm), scalable to 6-inch sizes. Based on the high-quality GaN epilayers, green Micro-LEDs with 5 µm pixel sizes are designed with vertical non-alignment bonding technology. An atomic sidewall passivation method combined with wet treatment successfully addressed the Micro-LED sidewall damages and steadily produced nano-scale surface textures on the pixel top, which unlocked the internal quantum efficiency of the high-quality green GaN-on-Si epi-wafer. Ultra-high brightness exceeding 107 cd/m2 (nits) is thus achieved in the green Micro-LEDs, marking the highest reported results. Furthermore, integration of Micro-LEDs with Si-based CMOS circuits enables the realization of green Micro-LED displays with resolution up to 1080 × 780, realizing high-definition playback of movies and images. This work lays the foundation for the mass production of high-brightness Micro-LED displays on large-size GaN-on-Si epi-wafers.

Targeted Microglial Membrane-Coated MicroRNA Nanosponge Mediates Inhibition of Glioblastoma.

Glioblastoma (GBM) is the most prevalent primary brain tumor. Recent research emphasizes the crucial role of microRNAs (miRs) in GBM pathogenesis, and targeting miRs offers an effective approach for precise GBM therapy. However, inhibiting a single miR may not be sufficient due to the compensatory mechanisms of GBM. Herein, we developed a miR-nanosponge capable of specifically capturing multiple miRs involved in tumor growth, migration, invasion, angiogenesis, and the creation of an immunosuppressive microenvironment, thereby offering a comprehensive treatment for GBM. Coated with BV2 cell membrane (BM) for enhanced blood-brain barrier (BBB) crossing and GBM targeting, the BM@miR-nanosponge targets miR-9, miR-21, miR-215, and miR-221, significantly inhibiting GBM progression and modulating the immune system for a thorough GBM eradication. The BM@miR-nanosponge notably extended the median survival time of GBM-bearing mice and outperformed the standard treatment drug temozolomide (TMZ). This study introduces a comprehensive miR-based strategy for GBM treatment and highlights the importance of targeting multiple miRs associated with tumor survival for effective therapy.

First reported advanced pancreatic cancer with hyperprogression treated with PD-1 blockade combined with chemotherapy: a case report and literature review.

Pancreatic cancer is among the most immune-resistant tumor types due to its unique tumor microenvironment and low cancer immunogenicity. Single-agent immune modulators have thus far proven clinically ineffective. However, a growing body of evidence suggests that combination of these modulators with other strategies could unlock the potential of immunotherapy in pancreatic cancer. Herein, we describe the case of a 59-year-old male with metastatic pancreatic ductal adenocarcinoma, referred to our center to receive immunotherapy (serplulimab, a novel anti-PD-1 antibody) combined with chemotherapy (gemcitabine/nab-paclitaxel). During the initial three treatment cycles, the patient was assessed as having stable disease (SD) according to RECIST 1.1 criteria. However, following two additional cycles of combination therapy, the primary tumor mass increased from 4.9 cm to 13.2 cm, accompanied by the development of new lung lesions, ascites, and pelvic metastases. He succumbed to respiratory failure one month later. Retrospective analysis revealed that the patient had MDM4 amplification, identified as a high-risk factor for hyperprogressive disease (HPD). To our knowledge, this is the first reported case of HPD in pancreatic cancer with multiple metastases treated using combination therapy. We investigated the potential mechanisms and reviewed the latest literature on predictive factors for HPD. These findings suggest that while chemotherapy combined with immunotherapy may hold promise for treating pancreatic cancer, it is imperative to identify and closely monitor patients with high-risk factors for HPD when using immunotherapy.

Whole-exome sequencing reveals Kawasaki disease susceptibility genes and their association with coronary artery lesion.

Objective: This study aimed to explore Kawasaki disease (KD) susceptibility genes and their complications like coronary artery lesions (CAL) using whole exome sequencing (WES). Methods: Between April 1, 2021, and December 31, 2022, our study included 55 pediatric patients diagnosed KD at our center, alongside a cohort of healthy children who sought medical care at our institution during the same timeframe. We extracted peripheral blood DNA from all participants and employed the advanced high-throughput Illumina Next-Generation Sequencing technology for comprehensive analysis. Through bioinformatics evaluation, we identified potential susceptibility genes. Moreover, from the 55 KD patients, we selected 15 for the CAL group and 40 for the non-CAL group. We aimed to investigate whether there were significant differences in the allele frequencies of the targeted susceptibility genes between these subgroups, to explore the risk alleles associated with the development of CAL in KD. Results: HLA-DRB1 rs17882084 and IL6ST rs781455079 genotypes and alleles differed significantly between KD and non-KD (P < 0.05). No differences existed for IL17RC rs143781415 and VEGFB rs776229557 (P > 0.05). No differences in HLA-DRB1 rs17882084, IL6ST rs781455079, and VEGFB rs776229557 genotypes existed between CAL and non-CAL groups (P > 0.05). However, the IL17RC rs143781415 genotype differed significantly between them (P < 0.05). Conclusions: HLA-DRB1 rs17882084 and IL6ST rs781455079 genotypes may be potential KD susceptibility gene candidates. Specifically, HLA-DRB1 rs17882084 GA genotype and A allele, and IL6ST rs781455079 TC genotype and C allele may increase KD risk. Additionally, the IL17RC rs143781415 genotype may increase CAL risk in KD patients.

Monolithic Integration of Full-Color Microdisplay Screen with Sub-5 µm Quantum-Dot Pixels.

Monolithic integration of color-conversion materials onto blue-backlight micro-light-emitting-diodes (micro-LEDs) has emerged as a promising strategy for achieving full-color microdisplay devices. However, this approach still encounters challenges such as the blue-backlight leakage and the poor fabrication yield rate due to unsatisfied quantum dot (QD) material and fabrication process. Here, the monolithic integration of 0.39-inch micro-display screens displaying colorful pictures and videos are demonstrated, which are enabled by creating interfacial chemical bonds for wafer-scale adhesion of sub-5 µm QD-pixels on blue-backlight micro-LED wafer. The ligand molecule with chlorosulfonyl and silane groups is selected as the synthesis ligand and surface treatment material, facilitating the preparation of high-efficiency QD photoresist and the formation of robust chemical bonds for pixel integration. This is a leading record in micro-display devices achieving the highest brightness larger than 400 thousand nits, the ultrahigh resolution of 3300 PPI, the wide color gamut of 130.4% NTSC, and the ultimate performance of service life exceeding 1000 h. These results extend the mature integrated circuit technique into the manufacture of micro-display device, which also lead the road of industrialization process of full-color micro-LEDs.

Uncovering the protective mechanism of baicalin in treatment of fatty liver based on network pharmacology and cell model of NAFLD.

Excessive nonesterified fatty acids (NEFA) impair cellular metabolism and will induce fatty liver formation in dairy cows during the periparturient. Baicalin, an active flavonoid, has great potential efficacy in alleviating lipid accumulation and ameliorating the development of fatty liver disease. Nevertheless, its mechanism remains unclear. Here, the potential mechanism of baicalin on system levels was explored using network pharmacology and in vitro experiments. Firstly, the target of baicalin and fatty liver disease was predicted, and then the protein-protein interaction (PPI) network was constructed. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) (q-value) pathway enrichment is performed through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. Finally, the results of the network analysis of the in vitro treatment of bovine hepatocytes by NEFA were confirmed. The results showed that 33 relevant targets of baicalin in the treatment of liver fatty were predicted by network pharmacology, and the top 20 relevant pathways were extracted by KEGG database. Baicalin treatment can reduce triglyceride (TAG) content and lipid droplet accumulation in NEFA-treated bovine hepatocytes, and the mechanism is related to inhibiting lipid synthesis and promoting lipid oxidation. The alleviating effect of baicalin on fatty liver may be related to the up-regulation of solute vector family member 4 (SLC2A4), Down-regulated AKT serine/threonine kinase 1 (AKT1), Peroxisome proliferator-activated receptor gamma (PPARG), Epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), Interleukin 6 (IL-6) were associated. These results suggested that baicalin may modulate key inflammatory markers, and lipogenesis processes to prevent fatty liver development in dairy cows.

Effects of environment and human activities on rice planting suitability based on MaxEnt model.

Rice is one of the major food crops, and the study of suitable planting areas for rice plays an important role in improving rice yield and optimizing the production layout. This study used Maximum Entropy (MaxEnt) model to simulate and predict the distribution of suitable rice planting areas in China from 1981 to 2020 by combining the climate, soil, and human activities, analyzed the spatial and temporal changes of suitable rice planting areas in China, and determined the main factors affecting rice planting suitability. The results indicated that the main factors influencing the distribution of suitable planting areas for rice in China were gross domestic product (GDP), population density (Pop), and annual sunshine duration (Sun), with human activities playing a dominant role. The high suitable planting areas of rice were mainly distributed in Hubei, Hunan, Jiangxi, Anhui, Guangdong, southeastern Sichuan and western Guizhou. The total suitable planting areas for rice were 346.00 × 104 km2, 345.66 × 104 km2, 347.01 × 104 km2, and 355.57 × 104 km2 from 1981 to 1990, 1991 to 2000, 2001 to 2010 and 2011 to 2020, respectively. With the passage of time, the area of unsuitable areas for rice gradually decreased, and the area of medium suitable areas increased, with large changes in the area of high- and low-suitable areas. Moreover, due to the transfer of a large number of rural laborers to the cities in recent years, the tension between people and land caused by the population explosion has led to the increasing impact of Pop on rice suitable areas and the relatively weakening of the impact of GDP on rice production interventions. The results can be used to provide scientific evidence for the management of rice cultivation and food production safety, with a view to reducing the impacts of climate change on agricultural production in the context of global climate change.

Impacts of future climate change on rice yield based on crop model simulation-A meta-analysis.

Rice is one of the world's major food crops. Changes in major climatic factors such as temperature, rainfall, solar radiation and carbon dioxide (CO2) concentration have an important impact on rice growth and yield. However, many of the current studies that predict the impact of future climate change on rice yield are affected by uncertainties such as climate models, climate scenarios, model parameters and structure, and showing great differences. This study was based on the assessment results of the impact of climate change on rice in the future of 111 published literature, and comprehensively analyzed the impact and uncertainty of climate change on rice yield. This study utilized local polynomial (Loess) regression analysis to investigate the impact of changes in mean temperature, minimum temperature, maximum temperature, solar radiation, and precipitation on relative rice yield variations within a complete dataset. A linear mixed-effects model was used to quantitatively analyze the relationships between the restricted datasets. The qualitative analysis based on the entire dataset revealed that rice yields decreased with increasing average temperature. The precipitation changed between 0 and 25 %, it was conducive to the stable production of rice, and when the precipitation changed >25 %, it would cause rice yield reduction. The change of solar radiation was less than -1.15 %, the rice yield increases with the increase of solar radiation, and when the change of solar radiation exceeds -1.15 %, the rice yield decreases. Elevated CO2 concentrations and management practices could mitigate the negative effects of climate change. The results of a quantitative analysis utilizing the mixed effects model revealed that average temperature, precipitation, CO2 concentration, and adaptation methods all had a substantial impact on rice production, and elevated CO2 concentrations and management practices could exert positive influences on rice production. For every 1 °C and 1 % increase in average temperature and precipitation, rice yield decreased by 3.85 % and 0.56 %, respectively. For every 100 ppm increase in CO2 concentration, rice yield increased by 7.1 %. The variation of rice yield under different climate models, study sites and climate scenarios had significant variability. Elevated CO2 concentrations and management practices could compensate for the negative effects of climate change, benefiting rice production. This study comprehensively collected and analyzed a wide range of literature and research, which provides an in-depth understanding of the impacts of climate change on rice production and informs future research and policy development.

Microbial etch: A novel construction method of functionalized biochar for enhanced uranium extraction in radioactive wastewater.

Nuclear energy is playing an increasingly important role on the earth, but the nuclear plants leaves a legacy of radioactive waste pollution, especially uranium-containing pollution. Straw biochar with wide sources, large output, low cost, and easy availability, has emerged as a promising material for uranium extraction from radioactive wastewater, but the natural biomass with suboptimal structure and low content of functional groups limits the efficiency. In this work, microbial etch was first came up to regulate the biochar's structure and function. The surface of the biochar becomes rougher and more microporous, and the mineral contents (Ca, P) indirectly increased by microbial etch. The biochar was modified by calcium phosphate and exhibited a remarkable uranium extraction capacity of 590.8 mg g-1 (fitted value). This work provides a cost-effective and sustainable method for preparing functionalized biochar via microbial etch, which has potential for application to uranium extraction from radioactive wastewater.

Hybrid Membrane-Camouflaged Biomimetic Immunomodulatory Nanoturrets with Sequential Multidrug Release for Potentiating T Cell-Mediated Anticancer Immunity.

Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and immunologically "cold" tumors severely compromise its immunotherapeutic outcomes. As such, the reversal of the immunosuppressive tumor microenvironment (TME) has been the premise for improving the effectiveness of AA-based immunotherapy, which hinges upon advanced AA delivery and amplified immune-activating strategies. Herein, a novel Escherichia coli (E. coli) outer membrane vesicle (OMV)-red blood cell (RBC) hybrid membrane (ERm)-camouflaged immunomodulatory nanoturret is meticulously designed based on gating of an AA-immobilized metal-organic framework (MOF) onto bortezomib (BTZ)-loaded magnesium-doped mesoporous silica (MMS) nanovehicles, which can realize immune landscape remodeling by chemotherapy-assisted ascorbate-mediated immunotherapy (CAMIT). Once reaching the acidic TME, the acidity-sensitive MOF gatekeeper and MMS core within the nanoturret undergo stepwise degradation, allowing for tumor-selective sequential release of AA and BTZ. The released BTZ can evoke robust immunogenic cell death (ICD), synergistically promote dendritic cell (DC) maturation in combination with OMV, and ultimately increase T cell tumor infiltration together with Mg2+. The army of T cells is further activated by AA, exhibiting remarkable antitumor and antimetastasis performance. Moreover, the CD8-deficient mice model discloses the T cell-dependent immune mechanism of the AA-based CAMIT strategy. In addition to providing a multifunctional biomimetic hybrid nanovehicle, this study is also anticipated to establish a new immunomodulatory fortification strategy based on the multicomponent-driven nanoturret for highly efficient T cell-activation-enhanced synergistic AA immunotherapy.

Minimization of heavy metal adsorption in struvite through effective separation and manipulation of flow field.

The admixture of heavy metals on struvite during the P recovery process from wastewater will affect its value for safe agricultural application, but it is not clear how to effectively separate heavy metals from struvite. Herein, a two-stage separation reactor (static and dynamic) has been developed to achieve efficient separation of heavy metals and struvite. The generation of struvite from real swine wastewater would naturally precipitate to the lowest layer under static conditions, leading to an enrichment of heavy metals (75 % Cu and 84 % Zn) in suspension. Meanwhile, phosphorus recovery from real swine wastewater results in the generation of a large amount of fines flowing out of the reactor due to the effects of suspended solids (SS), etc., making it necessary to recover phosphorus by static separation. For the dynamic separation step, we also analyzed the characteristics of struvite formation at different rotational speeds in a continuous reaction system. The results demonstrated that the shear rate of the fluid affects the particle size of struvite, which in turn determines the rate and the distribution of struvite in either primary or secondary recovery tanks. The implementation of zonal regulation in the flow field can produce a higher phosphorus efficiency (from 85.8 to 95.5 % at pH=8.1-8.2, from 93.8 to 98.5 % at pH=9.0-9.1) and a lower alkali consumption (55.56 % of alkali cost), which is favorable for the separation of struvite crystals and heavy metals (the amount of Cu and Zn metals separated increased by more than 50 %), and ultimately yield high quality of struvite. The findings in this study will provide insights for the separation and reduction of heavy metals through a combined method with dynamic and static in a continuous system, providing a reference for the safe application of struvite in agriculture.

Heavy metal sorption on struvite recovered from livestock wastewaters and release properties of granular forms.

Phosphorus recovery from wastewater is receiving more attention due to its non-renewable property. As copper (Cu) and zinc (Zn) usually occur in livestock wastewater, this study focused on metal sorption in struvite from swine wastewater and the release properties of granular struvite in solution with varying pH conditions (2, 4, 7). The results demonstrated pH values presented a slightly decreasing trend with increasing Cu/Zn ratio, and Zn exhibited higher sorption performance on struvite crystals than that of Cu. Under the high content of metals in the wastewater, Cu/Zn ratios in the wastewater contributed to varying metal binding forms and mechanisms, resulting in the difference in the leaching properties of nutrients and metal. For the granular struvite manufactured with the adhesion of alginate, the P release percentage achieved 30.3-40.5% after 96 h in the wastewater of pH 2, whereas they were only 5.63-8.92% and 1.05-1.50% in the wastewater of pH 4 and 7, respectively. Acid wastewater contributed to the release of two metals, and the release amount of Zn was higher than that of Cu, which is associated with their sorption capacity in crystals. During the latter soil leaching test of adding granular struvite, the NH4+-N and PO43--P concentration in the effluent ranged from 0.34 to 1.26 and 0.62 to 2.56 mg/L after 96 h, respectively. However, the Cu and Zn could not be measured due to lower than the detection limit under varying treatments. Struvite might be accompanied by quicker metal leaching and slower nutrient leaching when surface sorption dominates in wastewater with lower metal concentrations.

N-Indole-Substituted Imidazolylidene Pd-PEPPSI Precatalysts: Enhanced Performance with a 3,5-Diisopropyl-4-indolyl Moiety.

Pd-PEPPSI complexes of N-(4-indolyl)-N'-phenylimidazol-2-ylidene (IIn) ligands with a 5-isopropyl-4-indolyl moiety are synthesized and evaluated in heteroarene C-H arylation, Suzuki-Miyaura cross-coupling, and Buchwald-Hartwig amination reactions. The IIn-Pd complex bearing a 3,5-diisopropyl-4-indolyl substituent (C5) exhibits the best catalytic activity in this series and substantially outperforms commercial precatalyst PEPPSI-Pd-IPr. The results also suggest that the alkyl group at position 3 of the 4-indolyl moiety shows stronger impacts than that at position 5.

Multi-omics strategy reveals potential role of antimicrobial resistance and virulence factor genes responsible for Simmental diarrheic calves caused by Escherichia coli.

Escherichia coli (E. coli) is reported to be an important pathogen associated with calf diarrhea. Antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) pose a considerable threat to both animal and human health. However, little is known about the characterization of ARGs and VFGs presented in the gut microbiota of diarrheic calves caused by E. coli. In this study, we used multi-omics strategy to analyze the ARG and VFG profiles of Simmental calves with diarrhea caused by E. coli K99. We found that gut bacterial composition and their microbiome metabolic functions varied greatly in diarrheic calves compared to healthy calves. In total, 175 ARGs were identified, and diarrheal calves showed a significantly higher diversity and abundance of ARGs than healthy calves. Simmental calves with diarrhea showed higher association of VFGs with pili function, curli assembly, and ferrienterobactin transport of E. coli. Co-occurrence patterns based on Pearson correlation analysis revealed that E. coli had a highly significant (P < 0.0001) correlation coefficient (>0.8) with 16 ARGs and 7 VFGs. Metabolomics analysis showed that differentially expressed metabolites in Simmental calves with diarrhea displayed a high correlation with the aforementioned ARGs and VFGs. Phylotype analysis of E. coli genomes showed that the predominant phylogroup B1 in diarrheic Simmental calves was associated with 10 ARGs and 3 VFGs. These findings provide an overview of the diversity and abundance of the gut microbiota in diarrheic calves caused by E. coli and pave the way for further studies on the mechanisms of antibiotic resistance and virulence in the calves affected with diarrhea.IMPORTANCESimmental is a well-recognized beef cattle breed worldwide. They also suffer significant economic losses due to diarrhea. In this study, fecal metagenomic analysis was applied to characterize the antibiotic resistance gene (ARG) and virulence factor gene (VFG) profiles of diarrheic Simmental calves. We identified key ARGs and VFGs correlated with Escherichia coli isolated from Simmental calves. Additionally, metabolomics analysis showed that differentially expressed metabolites in Simmental calves with diarrhea displayed a high correlation with the aforementioned ARGs and VFGs. Our findings provide an insight into the diversity and abundance of the gut microbiota in diarrheic calves caused by Escherichia coli and pave the way for further studies on the mechanisms of antibiotic resistance and virulence in the diarrheal calves from cattle hosts.

Multiple Synergistic Effects of the Microglia Membrane-Bionic Nanoplatform on Mediate Tumor Microenvironment Remodeling to Amplify Glioblastoma Immunotherapy.

Glioblastoma (GBM) is a lethal brain tumor with high levels of malignancy. Most chemotherapy agents show serious systemic cytotoxicity and restricted delivery effectiveness due to the impediments of the blood-brain barrier (BBB). Immunotherapy has developed great potential for aggressive tumor treatments. Disappointingly, its efficacy against GBM is hindered by the immunosuppressive tumor microenvironment (TME) and BBB. Herein, a multiple synergistic immunotherapeutic strategy against GBM was developed based on the nanomaterial-biology interaction. We have demonstrated that this BM@MnP-BSA-aPD-1 can transverse the BBB and target the TME, resulting in amplified synergetic effects of metalloimmunotherapy and photothermal immunotherapy (PTT). The journey of this nanoformulation within the TME contributed to the activation of the stimulator of the interferon gene pathway, the initiation of the immunogenic cell death effect, and the inhibition of the programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) signaling axis. This nanomedicine revitalizes the immunosuppressive TME and evokes the cascade effect of antitumor immunity. Therefore, the combination of BM@MnP-BSA-aPD-1 and PTT without chemotherapeutics presents favorable benefits in anti-GBM immunotherapy and exhibits immense potential for clinical translational applications.

Involvement and regulation of the left anterior cingulate cortex in the ultrasonic communication deficits of autistic mice.

Introduction: Autism spectrum disorder (ASD) is a group of diseases often characterized by poor sociability and challenges in social communication. The anterior cingulate cortex (ACC) is a core brain region for social function. Whether it contributes to the defects of social communication in ASD and whether it could be physiologically modulated to improve social communication have been poorly investigated. This study is aimed at addressing these questions. Methods: Fragile X mental retardation 1 (FMR1) mutant and valproic acid (VPA)-induced ASD mice were used. Male-female social interaction was adopted to elicit ultrasonic vocalization (USV). Immunohistochemistry was used to evaluate USV-activated neurons. Optogenetic and precise target transcranial magnetic stimulation (TMS) were utilized to modulate anterior cingulate cortex (ACC) neuronal activity. Results: In wild-type (WT) mice, USV elicited rapid expression of c-Fos in the excitatory neurons of the left but not the right ACC. Optogenetic inhibition of the left ACC neurons in WT mice effectively suppressed social-induced USV. In FMR1-/-- and VPA-induced ASD mice, significantly fewer c-Fos/CaMKII-positive neurons were observed in the left ACC following USV compared to the control. Optogenetic activation of the left ACC neurons in FMR1-/- or VPA-pretreated mice significantly increased social activity elicited by USV. Furthermore, precisely stimulating neuronal activity in the left ACC, but not the right ACC, by repeated TMS effectively rescued the USV emission in these ASD mice. Discussion: The excitatory neurons in the left ACC are responsive to socially elicited USV. Their silence mediates the deficiency of social communication in FMR1-/- and VPA-induced ASD mice. Precisely modulating the left ACC neuronal activity by repeated TMS can promote the social communication in FMR1-/- and VPA-pretreated mice.

Establishment of a two-hit mouse model of environmental factor induced autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of developmental diseases characterized by social dysfunction and repetitive stereotype behaviors. Besides genetic mutations, environmental factors play important roles in the development of ASD. Valproic acid (VPA) is widely used for modeling environmental factor induced ASD in rodents. However, traditional VPA modeling is low-in-efficiency and the phenotypes often vary among different batches of experiments. To optimize this ASD-modeling method, we tested "two-hit" hypothesis by single or double exposure of VPA and poly:IC at the critical time points of embryonic and postnatal stage. The autistic-like behaviors of mice treated with two-hit schemes (embryonic VPA plus postnatal poly:IC, embryonic poly:IC plus postnatal VPA, embryonic VPA plus poly: IC, or postnatal VPA plus poly:IC) were compared with mice treated with traditional VPA protocol. The results showed that all single-hit and two-hit schemes produced core ASD phenotypes as VPA single treatment did. Only one group, namely, mice double-hit by VPA and poly:IC simultaneously at E12.5 showed severe impairment of social preference, social interaction and ultrasonic communication, as well as significant increase of grooming activity and anxiety-like behaviors, in comparation with mice treated with the traditional VPA protocol. These data demonstrated that embryonic two-hit of VPA and poly:IC is more efficient in producing ASD phenotypes in mice than the single-hit of VPA, indicating this two-hit scheme could be utilized for modeling environmental factors induced ASD.

Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia.

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.

N-Type polymeric mixed conductors for all-in-one aqueous electrolyte gated photoelectrochemical transistors.

An organic photoelectrochemical transistor (OPECT) is an organic electrochemical transistor (OECT) that utilizes light to toggle between ON and OFF states. The current response to light and voltage fluxes in aqueous media renders the OPECT ideal for the development of next-generation bioelectronic devices, including light-assisted biosensors, light-controlled logic gates, and artificial photoreceptors. However, existing OPECT architectures are complex, often requiring photoactive nanostructures prepared through labor-intensive synthetic methods, and despite this complexity, their performance remains limited. In this study, we develop aqueous electrolyte-compatible optoelectronic transistors using a single n-type semiconducting polymer. The n-type film performs multiple tasks: (1) gating the channel, (2) generating a photovoltage in response to light, and (3) coupling and transporting cations and electrons in the channel. We systematically investigate the photoelectrochemical properties of a range of n-type polymeric mixed conductors to understand the material requirements for maximizing phototransistor performance. Our findings contribute to the identification of crucial material and device properties necessary for constructing high-performance OPECTs with simplified design features and a direct interface with biological systems.

Quiescent Adult Neural Stem Cells: Developmental Origin and Regulatory Mechanisms.

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small in number and restricted to the sub-ventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, and the olfactory epithelium, is a gift of evolution for the adaptive brain function which requires persistent plastic changes of these regions. It is known that most adult NSCs are latent, showing long cell cycles. In the past decade, the concept of quiescent NSCs (qNSCs) has been widely accepted by researchers in the field, and great progress has been made in the biology of qNSCs. Although the spontaneous neuronal regeneration derived from adult NSCs is not significant, understanding how the behaviors of qNSCs are regulated sheds light on stimulating endogenous NSC-based neuronal regeneration. In this review, we mainly focus on the recent progress of the developmental origin and regulatory mechanisms that maintain qNSCs under normal conditions, and that mobilize qNSCs under pathological conditions, hoping to give some insights for future study.