Recombinase polymerase amplification combined with lateral flow dipstick assay for rapid visual detection of A.simplex (s. s.) and A.pegreffii in sea foods.

Anisakiasis is a food-borne parasitic disease mainly caused by the third stage of Anisakis simplex (s. s.) and Anisakis pegreffii. Traditional methods for detecting of Anisakis involve morphology identification such as visual inspection, enzyme digestion, and molecular methods based on PCR, but they have certain limitations. In this study, the internal transcribed spacer 1 (ITS 1) regions of Anisakis were targeted to develop a visual screening method for detecting A. simplex (s. s.) and A. pegreffii in fish meat based on recombinase polymerase amplification (RPA) combined with lateral flow dipstick (LFD). Specific primers and probes were designed and optimized for temperature, reaction time, and detection threshold. LFD produced clear visual results that were easily identifiable after a consistent incubation of 10-20 min at 37 °C. The whole process of DNA amplification by RPA and readout by LFD did not exceed 30 min. In addition, the detection limit is up to 9.5 × 10-4 ng/µL, and the detection of the artificially contaminated samples showed that the developed assay can effectively and specifically detect A. simplex (s. s.) and A. pegreffii, which fully meet the market's requirements for fish food safety supervision.

Triglycerides: A Sensitizer but Not a Trigger for Hypertriglyceridemic Acute Pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing. Although the guideline defines the diagnostic criteria as triglyceride (TG) greater than 11.3 mmol/L, there is actually no specific threshold. Many people with hypertriglyceridemia (HTG) or obvious chyloid blood do not develop acute pancreatitis (AP). AIMS: To explore the role of HTG in the pathogenesis of AP. METHODS: Thirty-six male SD rats were randomly assigned into normal control, AP, HTG, HTG-AP, low-dose fenofibrate and high-dose fenofibrate groups. Serum indices and cytokine levels in serum, and pathological changes in pancreatic tissues were observed. The expression levels of TLR4 and NF-κBp65 in pancreatic tissues were detected by immunohistochemistry and Western blot. RESULTS: In normal rats, HTG alone did not induce AP. However, after establishing the HTG-AP model with Poloxam 407 and L-arginine, serum-free fatty acid and TG levels were positively correlated with the levels of lipase, amylase, IL-1ß, IL-6, pancreatic inflammation scores, and the expressions of TLR4 and NF-κBp65 (all P < 0.001). Expressions of TLR4 and NF-κBp65 were significantly increased in the pancreatic tissues of HTG-AP rats. Fenofibrate effectively decreased TG levels in HTG-AP rats and reduced the expression of TLR4 and NF-κBp65 (all P < 0.001). CONCLUSIONS: HTG does not directly cause AP, but rather increases the susceptibility to AP or aggravates the inflammatory response. It is more like a sensitizer of inflammation rather than an activator.

Light intensity differentially mediates the life cycle of lepidopteran leaf feeders and stem borers.

BACKGROUND: Leaf feeders, such as Spodoptera frugiperda and S. litura, and stem borers Ostrinia furnacalis and Chilo suppressalis, occupy two different niches and are well adapted to their particular environments. Borer larvae burrow and inhabit interior of stems, which are relatively dark. By contrast, the larvae of leaf feeders are exposed to sunlight during feeding. We therefore designed series of experiments to evaluate the effect of light intensity (0, 2000, and 10 000 lx) on these pests with different feeding modes. RESULTS: The development of all four pests was significantly delayed at 0 lx. Importantly, light intensity affected the development of both male and female larvae of borers but only significantly affected male larvae of leaf feeders. Furthermore, the proportion of female offspring of leaf feeders increased with increasing light intensity (S. frugiperda: 33.89%, 42.26%, 57.41%; S. litura: 38.90%, 51.75%, 65.08%), but no significant differences were found in stem borers. This research also revealed that the survival rate of female leaf feeders did not vary across light intensities, but that of males decreased with increasing light intensity (S. frugiperda: 97.78%, 85.86%, 61.21%; S. litura: 95.83%, 73.54%, 58.99%). CONCLUSION: These results improve understanding of how light intensity affects sex differences of important lepidopteran pests occupying different feeding niches and their ecological interactions with abiotic factors in agroecosystems. This article is protected by copyright. All rights reserved.

Activation of the Photosensitive Potential of 2D GaSe by Interfacial Engineering.

Two-dimensional (2D) gallium selenide (GaSe) holds great promise for pioneering advancements in photodetection due to its exceptional electronic and optoelectronic properties. However, in conventional photodetectors, 2D GaSe only functions as a photosensitive layer, failing to fully exploit its inherent photosensitive potential. Herein, we propose an ultrasensitive photodetector based on out-of-plane 2D GaSe/MoSe2 heterostructure. Through interfacial engineering, 2D GaSe serves not only as the photosensitive layer but also as the photoconductive gain and passivation layer, introducing a photogating effect and extending the lifetime of photocarriers. Capitalizing on these features, the device exhibits exceptional photodetection performance, including a responsivity of 28 800 A/W, specific detectivity of 7.1 × 1014 Jones, light on/off ratio of 1.2 × 106, and rise/fall time of 112.4/426.8 µs. Moreover, high-resolution imaging under various wavelengths is successfully demonstrated using this device. Additionally, we showcase the generality of this device design by activating the photosensitive potential of 2D GaSe with other transition metal dichalcogenides (TMDCs) such as WSe2, WS2, and MoS2. This work provides inspiration for future development in high-performance photodetectors, shining a spotlight on the potential of 2D GaSe and its heterostructure.

Seeding Atomic Silver into Internal Lattice Sites of Transition Metal Oxide for Advanced Electrocatalysis.

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO2, we demonstrate how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO2 reduction reaction (eCO2RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol/g/h) and durability (∼ 48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO2RR for Ag nanoparticles and lattice-confined eCO2RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration. This article is protected by copyright. All rights reserved.

Physiology education in China: the current situation and changes over the past 3 decades.

OBJECTIVE: As an experimental biological science, physiology has been taught as an integral component of medical curricula for a long time in China. The teaching effectiveness of physiology courses will directly affect students' learning of other medical disciplines. The purpose of this study is to investigate the current situation and changes in physiology teaching over 30 years in Chinese medical schools. METHODS: National survey was conducted online on the platform SoJump via WeChat and the web. The head of the physiology department in medical school was asked to indicate the information of physiology education from three periods: 1991-2000, 2001-2010, and 2011-2020. The responses of 80 leaders of the Department of Physiology from mainland Chinese medical schools were included in the study for analysis. RESULTS: The survey showed that the class hours, both of theory and practice, had been decreased. During the past 20 years, the total number of physiology teachers, the number of physiology teachers who had been educated in medical schools, and the number of technicians had been reduced, whereas teachers with doctor's degrees had been increased. In addition to traditional didactic teaching, new teaching approaches, including problem-based learning/case-based learning/team-based learning, integrated curriculum and formative evaluation systems, had been employed, mostly for more than 5 years, in some medical schools. CONCLUSION: The present study has provided historical data regarding the current status of physiology education in China and that in the past thirty years by showing that physiology education in China has developed quickly,even it faces many challenges.

Transcranial direct current stimulation combined with swimming exercise improves the learning and memory abilities of vascular dementia rats by regulating microglia through miR-223-3p/PRMT8.

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia worldwide. Previous studies have proven that transcranial direct current stimulation (tDCS) has potential applications in relieving cognitive impairment in VD animal models. The purpose of this study was to probe the mechanism by which tDCS combined with swimming exercise improves the learning and memory abilities of VD model rats. METHOD: The VD rat model was induced using the permanent bilateral common carotid artery occlusion (2-VO) method; tDCS was applied to the rats and then they took part in swimming exercises. Rat memory, platform crossing time, and platform crossing frequency were analyzed via a water maze experiment. Nerve damage in the cortex and hippocampal CA1 area of the rats was observed using Nissl staining. Western blotting, immunohistochemistry, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction (RT - qPCR) were used to determine the expression of related proteins and genes. The levels of oxidative stress were detected by kits. RESULTS: We demonstrated that VD model rats treated with tDCS combined with swimming exercise exhibited significant improvement in memory, and VD model rats exhibited significantly reduced neuronal loss in the hippocampus, and reduced microglial activation and M1 polarization. tDCS combined with swimming exercise protects VD model rats from oxidative stress through the miR-223-3p/protein arginine methyltransferase 8 (PRMT8) axis and inhibits the activation of the TLR4/NF-κB signaling pathway. CONCLUSION: Our results suggest that tDCS combined with swimming exercise improved the learning and memory ability of VD model rats by regulating the expression of PRMT8 through miR-223-3p to affect microglial activation and M1 polarization.

Learning long- and short-term dependencies for improving drug-target binding affinity prediction using transformer and edge contraction pooling.

The accurate identification of drug-target affinity (DTA) is crucial for advancements in drug discovery and development. Many deep learning-based approaches have been devised to predict drug-target binding affinity accurately, exhibiting notable improvements in performance. However, the existing prediction methods often fall short of capturing the global features of proteins. In this study, we proposed a novel model called ETransDTA, specifically designed for predicting drug-target binding affinity. ETransDTA combines convolutional layers and transformer, allowing for the simultaneous extraction of both global and local features of target proteins. Additionally, we have integrated a new graph pooling mechanism into the topology adaptive graph convolutional network (TAGCN) to enhance its capacity for learning feature representations of chemical compounds. The proposed ETransDTA model has been evaluated using the Davis and Kinase Inhibitor BioActivity (KIBA) datasets, consistently outperforming other baseline methods. The evaluation results on the KIBA dataset reveal that our model achieves the lowest mean square error (MSE) of 0.125, representing a 0.6% reduction compared to the lowest-performing baseline method. Furthermore, the incorporation of queries, keys and values produced by the stacked convolutional neural network (CNN) enables our model to better integrate the local and global context of protein representation, leading to further improvements in the accuracy of DTA prediction.

Observation of spatiotemporal optical vortices enabled by symmetry-breaking slanted nanograting.

Providing additional degrees of freedom to manipulate light, spatiotemporal optical vortex (STOV) beams carrying transverse orbital angular momentum are of fundamental importance for spatiotemporal control of light-matter interactions. Unfortunately, existing methods to generate STOV are plagued by various limitations such as inefficiency, bulkiness, and complexity. Here, we theoretically propose and experimentally demonstrate a microscale singlet platform composed of a slanted nanograting to generate STOV. Leveraging the intrinsic topological singularity induced by C2 symmetry and z-mirror symmetry breaking of the slanted nanograting, STOV is generated through the Fourier transform of the spiral phase in the momentum-frequency space to the spatiotemporal domain. In experiments, we observe the space-time evolution of STOV carried by femtosecond pulses using a time-resolved interferometry technique and achieve a generation efficiency exceeding 40%. Our work sheds light on a compact and versatile platform for light pulse shaping, and paves the way towards a fully integrated system for spatiotemporal light manipulation.

Ultra-Stable High-Capacity Polythiophene Derivative for Wide-Potential-Window Supercapacitors.

Conducting polymer (CP)-based supercapacitors show great promise for applications in the field of wearable and portable electronics. However, these supercapacitors face persistent challenges, notably low energy density and inadequate stability. In this study, we introduce a polythiophene derivative, designated as poly(EPE), synthesized via the electrochemical polymerization of 8-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-3,3-dimethyl-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine (EPE). The resulting poly(EPE) polymer exhibits an exemplary 3D porous network-like structure, significantly enhancing its capacitance performance. When employed as the electrode material, the symmetric supercapacitor demonstrates an exceptionally high specific capacitance of 1342 F g-1 at a current density of 4.0 A g-1, along with impressive energy and power densities of 119.3 W h kg-1 and 38.83 kW kg-1, respectively. These capacitance values surpass those of previously reported pristine CP-based supercapacitors. Notably, the supercapacitor showcases outstanding stability, maintaining a retention rate of 92.5% even after 50,000 charge-discharge cycles. These findings underscore the substantial potential of poly(EPE) as an electrode material for the advancement of the supercapacitor technology.

A neurofunctional signature of subjective disgust generalizes to oral distaste and socio-moral contexts.

While disgust originates in the hard-wired mammalian distaste response, the conscious experience of disgust in humans strongly depends on subjective appraisal and may even extend to socio-moral contexts. Here, in a series of studies, we combined functional magnetic resonance imaging with machine-learning-based predictive modelling to establish a comprehensive neurobiological model of subjective disgust. The developed neurofunctional signature accurately predicted momentary self-reported subjective disgust across discovery (n = 78) and pre-registered validation (n = 30) cohorts and generalized across core disgust (n = 34 and n = 26), gustatory distaste (n = 30) and socio-moral (unfair offers; n = 43) contexts. Disgust experience was encoded in distributed cortical and subcortical systems, and exhibited distinct and shared neural representations with subjective fear or negative affect in interoceptive-emotional awareness and conscious appraisal systems, while the signatures most accurately predicted the respective target experience. We provide an accurate functional magnetic resonance imaging signature for disgust with a high potential to resolve ongoing evolutionary debates.

Exposure to Per- and Polyfluoroalkyl Substances in Lung Cancer Patients and Their Associations with Clinical Health Indicators.

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n=282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80% of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95%CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95%CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

Water-Stable High-Entropy Metal-Organic Framework Nanosheets for Photocatalytic Hydrogen Production.

Metal-organic frameworks (MOFs) have emerged as promising platforms for photocatalytic hydrogen evolution reaction (HER) due to their fascinating physiochemical properties. Rationally engineering the compositions and structures of MOFs can provide abundant opportunities for their optimization. In recent years, high-entropy materials (HEMs) have demonstrated great potential in the energy and environment fields. However, there is still no report on the development of high-entropy MOFs (HE-MOFs) for photocatalytic HER in aqueous solution. Herein, the authors report the synthesis of a novel p-type HE-MOFs single crystal (HE-MOF-SC) and the corresponding HE-MOFs nanosheets (HE-MOF-NS) capable of realizing visible-light-driven photocatalytic HER. Both HE-MOF-SC and HE-MOF-NS exhibit higher photocatalytic HER activity than all the single-metal MOFs, which are supposed to be ascribed to the interplay between the different metal nodes in the HE-MOFs that enables more efficient charge transfer. Moreover, impressively, the HE-MOF-NS demonstrates much higher photocatalytic activity than the HE-MOF-SC due to its thin thickness and enhanced surface area. At optimum conditions, the rate of H2 evolution on the HE-MOF-NS is ≈13.24 mmol h-1 g-1, which is among the highest values reported for water-stable MOF photocatalysts. This work highlights the importance of developing advanced high-entropy materials toward enhanced photocatalysis.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

ABSTRACTPreviously, we have reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016 to 2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Development of Membrane-Targeting Fluorescent 2-Phenyl-1H-phenanthro[9,10-d]imidazole-Antimicrobial Peptide Mimic Conjugates against Methicillin-Resistant Staphylococcus aureus.

The escalation of multidrug-resistant bacterial infections, especially infections caused by methicillin-resistant Staphylococcus aureus (MRSA), underscores the urgent need for novel antimicrobial drugs. Here, we synthesized a series of amphiphilic 2-phenyl-1H-phenanthro[9,10-d]imidazole-antimicrobial peptide (AMP) mimic conjugates (III1-30). Among them, compound III13 exhibited excellent antibacterial activity against G+ bacteria and clinical MRSA isolates (MIC = 0.5-2 µg/mL), high membrane selectivity, and low toxicity. Additionally, compared with traditional clinical antibiotics, III13 demonstrated rapid bactericidal efficacy and was less susceptible to causing bacterial resistance. Mechanistic studies revealed that III13 targets phosphatidylglycerol (PG) on bacterial membranes to disrupt membrane integrity, leading to an increase in intracellular ROS and leakage of proteins and DNA, ultimately causing bacterial cell death. Furthermore, III13 possessed good fluorescence properties with potential for further dynamic monitoring of the antimicrobial process. Notably, III13 showed better in vivo efficacy against MRSA compared to vancomycin, suggesting its potential as a promising candidate for anti-MRSA medication.

Effects of temperature anomaly on sperm quality: A multi-center study of 33,234 men.

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values<0.05). After adjusting the relative humidity, the cold-related TA in cold season was negatively associated with the sperm total motility (P-values<0.05). Conclusions: Our results suggest both heat-related and cold-related TAs are associated with decreased sperm quality. The findings highlight the importance of reducing exposure to anomalous temperatures to protect male fertility.

KN046, a bispecific antibody against PD-L1 and CTLA-4, plus chemotherapy as first-line treatment for metastatic NSCLC: A multicenter phase 2 trial.

KN046, a bispecific antibody targeting PD-L1 and CTLA-4, presents a promising therapeutic option for metastatic non-small cell lung cancer (NSCLC). In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. Following four cycles, maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC. The objective response rate is 46.0%, and the median duration of response is 8.1 months. The median progression-free and overall survival are 5.8 and 26.6 months, respectively. The common adverse events include anemia (87.4%), loss of appetite (72.4%), and neutropenia (70.1%). The most prevalent immune-related adverse event is pruritus (28.7%). These findings indicate that first-line treatment with KN046 and chemotherapy is effective and tolerable in metastatic NSCLC patients, warranting further investigation in a larger phase 3 trial. The trial is registered at ClinicalTrials.gov (NCT04054531).

Resolving neuroinflammatory and social deficits in ASD model mice: Dexmedetomidine downregulates NF-κB/IL-6 pathway via α2AR.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals' daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.

Phosphate additives promote humic acid carbon and nitrogen skeleton formation by regulating precursors and composting bacterial communities.

This study aimed to compare the effect of different phosphate additives including superphosphate (CP) and MP [Mg(OH)2 + H3PO4] on nitrogen conversion, humus fractions formation and bacterial community in food waste compost. The results showed the ratio of humic acid nitrogen in total nitrogen (HA-N/TN) in CP increased by 49 %. Ammonium nitrogen accumulation was increased by 75 % (CP) and 44 % (MP). Spectroscopic techniques proved that phosphate addition facilitated the formation of complex structures in HA. CP enhanced the dominance of Saccharomonospora, while Thermobifida and Bacillus were improved in MP. Structural equation modeling and network analysis demonstrated that ammonium nitrogen can be converted to HA-N and has positive effects on bacterial composition, reducing sugars and amino acids, especially in CP with more clustered network and synergic bacterial interactions. Therefore, the addition of phosphate provides a new idea to regulate the retained nitrogen toward humification in composting.

Proton Sponge Nanocomposites for Synergistic Tumor Elimination via Autophagy Inhibition-Promoted Cell Apoptosis and Macrophage Repolarization-Enhanced Immune Response.

Cytoprotective autophagy and an immunosuppressive tumor microenvironment (TME) are two positive promoters for tumor proliferation and metastasis that severely hinder therapeutic efficacy. Inhibiting autophagy and reconstructing TME toward macrophage activation simultaneously are of great promise for effective tumor elimination, yet are still a huge challenge. Herein, a kind of dendrimer-based proton sponge nanocomposites was designed and constructed for tumor chemo/chemodynamic/immunotherapy through autophagy inhibition-promoted cell apoptosis and macrophage repolarization-enhanced immune response. These obtained nanocomposites contain a proton sponge G5AcP dendrimer, a Fenton-like agent Cu(II), and chemical drug doxorubicin (DOX). When accumulated in tumor regions, G5AcP can act as an immunomodulator to realize deacidification-promoted macrophage repolarization toward antitumoral type, which then secretes inflammatory cytokines to activate T cells. They also regulate intracellular lysosomal pH to inhibit cytoprotective autophagy. The released Cu(II) and DOX can induce aggravated damage through a Fenton-like reaction and chemotherapeutic effect in this autophagy-inhibition condition. Tumor-associated antigens are released from these dying tumor cells to promote the maturity of dendritic cells, further activating T cells. Effective tumor elimination can be achieved by this dendrimer-based therapeutic strategy, providing significant guidance for the design of a promising antitumor nanomedicine.