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Abstract Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Abstract Background The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. Methods A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. Results Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. Conclusions We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand. Graphical Abstract

Abstract Marine oil exploration is important yet greatly increases the risk of oil leakage, which will result in severe environment pollution and economic losses. It is an urgent need to develop effective underoil adhesives. However, realizing underoil adhesion is even harder than those underwater, due to the stubborn attachment of a highly viscous oil layer on target surface. Here, inspired by endocytosis, a tough gel tape composed of zwitterionic polymer network and zwitterionic surfactants is developed. The amphiphilic surfactants can form micelle to capture the oil droplets and transport them from the interface to gel via electrostatic attraction of polymer backbone, mimicking the endocytosis and achieving robust underoil adhesion. Benefiting from the oil‐resistance of polymer backbone, the gel further realizes a combination of i) long‐term adhesion with high durability, ii) repeated adhesion in oil, and iii) renewable adhesion efficiency after exhausted use. The tape exhibits an ultra‐high adhesive toughness of 2446.86 J m−2 to stainless steel in silicone oil after 30 days' oil‐exposure; such value of adhesive toughness surpasses many of those achieved in underwater adhesion and is greater than underoil adhesion performance of commercial tape. The strategy illustrated here will motivate the design of sustainable and efficient adhesives for wet environments.

Objectives: Neuregulin 1 (NRG1) is a risk gene for schizophrenia and involved in neurodevelopment and synaptic plasticity. Polymorphisms in NRG1 may affect psychotic symptoms in schizophrenia. This study investigated the effects of the single nucleotide polymorphism (SNP) rs6982890 on peripheral plasma NRG1 immunoreactivity, clinical symptoms and cognitive functions in schizophrenia patients. Material and methods: We recruited subjects from the Han population of northern China from 2010 to 2022. We first genotyped and analyzed 6 NRG1 SNPS in 1304 patients with schizophrenia and 871 healthy controls. Then, 91 patients with schizophrenia and 40 healthy controls were selected to detect the peripheral plasma NRG1 immunoreactivity by ELISA. Among them, 84 patients were divided into rs6982890 genotypes to analyze the correlation between NRG1 immunoreactivity and clinical symptoms. Results: Rs6982890 allelic frequencies were statistically significant between patients and controls. Baseline peripheral plasma NRG1 immunoreactivity in patients were significantly lower than controls. NRG1 immunoreactivity in patients were significantly increased after 8 weeks of antipsychotic treatment and significantly correlated with clinical symptoms and cognitive function. Genotyping of patients with SNP rs6982890 indicated NRG1 immunoreactivity in CC genotype increased significantly after treatment, while CT genotype had no significant change. Baseline NRG1 immunoreactivity with the CT genotype were significantly higher than CC genotype. Conclusions: NRG1 SNP rs6982890 is significantly associated with schizophrenia in the Han population of northern China, and it may affect the effect of antipsychotic drug treatment by regulating the peripheral plasma NRG1 immunoreactivity.

Abstract Background Urban ecological health is crucial for the long-term sustainable development of watershed. Accurately evaluating the health level of the ecological environment helps to develop reasonable strategies for ecological environment restoration and resource management. This paper constructed a comprehensive evaluation index system based on the Pressure-State-Response (PSR) framework and evaluated the ecological health of eleven administrative regions in the Wei River Basin (WRB), northwest China in 1980, 2000, and 2020 using an evaluation model established by fuzzy mathematics. Further, obstacle degrees were used to quantify the contribution of pressure, state, and response modules, as well as individual indicators to ecological health. Results The comprehensive evaluation system constructed based on the PSR framework could effectively reflect the ecological health conditions of different regions in the WRB. During the study period, the ecological health went through a process of first deterioration and then improvement. By 2020, the ecological health of seven administrative regions reached healthy levels. The state module was the main obstacle module of the PSR framework to the ecological health of the most regions. The population density (P1), patch density of construction land (S5), comprehensive elasticity index (S8), soil erosion index (R1), and per capital GDP (R3) were the most crucial individual indicators affecting the ecological health. For different cities, the main obstacle factors varied. In economically developed cities, the limiting effect of P1 was more significant, while in economically underdeveloped cities, the limiting effect of R3 was stronger. Conclusions In response to the special natural environment and socio-economic conditions of arid and semi-arid areas in the WRB, an ecological health evaluation index system suitable for the characteristics of the basin was constructed. The results indicated that, to improve the levels of urban ecological health, it is necessary to restore the natural ecological environment and control population size while accelerating economic construction. Our results can provide scientific support for the ecological health evaluation and protection of the WRB and even the arid and semi-arid areas in northwest China.

RationaleRelapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence.MethodsThis study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use. The test was administered to sixteen naive monkeys and five METH exposed monkeys that had been abstinent for at least 3 months.ResultsMETH exposed monkeys showed a lower sucrose preference score in both the iSPT (z = -2.10, p = 0.036) and the sucrose preference test (z = -2.61, p = 0.009). The sucrose preference score was significantly correlated with the latency of the establishment of stable sucrose-preference (r = -0.76, df = 46, p < 0.001) but not with the other variables. Furthermore, water-sucrose switch latency and switch times were significantly negatively correlated (r = -0.50, df = 20, p = 0.02).ConclusionThese results show reductions in natural reward consumption during long-term methamphetamine abstinence.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

Abstract Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products.

Host remodeling of decellularized extracellular matrix (dECM) material through the appropriate involvement of immune cells is essential for achieving functional organ/tissue regeneration. As many studies have focused on the role of macrophages, only few have evaluated the role of regulatory T cells (Tregs) in dECM remodeling. In this study, we used a mouse model of traumatic muscle injury to determine the role of Tregs in the constructive remodeling of vascular-derived dECM. According to the results, a certain number of Tregs could be recruited after dECM implantation. Notably, using anti-CD25 to reduce the number of Tregs recruited by the dECM was significantly detrimental to material remodeling based on a significant reduction in the number of M2 macrophages. In addition, collagen and elastic fibers, which maintain the integrity and mechanical properties of the material, rapidly degraded during the early stages of implantation. In contrast, the use of CD28-SA antibodies to increase the number of Tregs recruited by dECM promoted constructive remodeling, resulting in a decreased inflammatory response at the material edge, thinning of the surrounding fibrous connective tissue, uniform infiltration of host cells, and significantly improved tissue remodeling scores. The number of M2 macrophages increased whereas that of M1 macrophages decreased. Moreover, Treg-conditioned medium further enhanced material-induced M2 macrophage polarization in vitro. Overall, Treg is an important cell type that influences constructive remodeling of the dECM. Such findings contribute to the design of next-generation biomaterials to optimize the remodeling and regeneration of dECM materials.

Abstract The interrelated side reactions and dendrites growth severely destabilize the electrode/electrolyte interfaces, resulting in the difficult application of aqueous Zn ion batteries (AZIBs). Hydrophobic protective layer possesses natural inhibition ability for side reactions. However, the conventional protective layer with plane structure is difficult to attain joint regulation of side reaction and Zn nucleation. Herein, a novel three‐dimensional (3D) electrically conductive and hydrophobic (3DECH) interface is elaborated to enable stable Zn anode. The as‐prepared 3DECH interface presents a uniform 3D morphology with hydrophobic property, large specific surface area, abundant zincophilic sites, and excellent electroconductivity. Therefore, the 3DECH interface achieves uniform nucleation and dendrite‐free deposition from synergetic benefits: (1) increased nucleation sites and reduced local current density through the special 3D structure and (2) uniform electric potential distribution and rapid Zn2+ transport due to the electroconductive alloy chemistry, thus coupling the hydrophobic property to obtain a highly reversible Zn anode. Consequently, the modified anode achieves a superior coulombic efficiency of 99.88% over 3500 cycles, and the pouch cells using modified anode and LiMn2O4 (LMO) cathode retain a capacity of 84 mAh g−1 after 700 cycles at a reasonable depth discharge of 36%, without dendrite piercing and “dead Zn.”

Superhydrophobic surfaces have been extensively utilized due to their high hydrophobicity and anti-icing properties. Inspired by the shape of a cross flower, research has utilized circular arc curves and Bessel curves to design a cross flower structure model. Using 3D modeling software for modeling and 3D printing technology to prepare biomimetic microstructures in structural design. The structural shape of the microstructure before and after spray coating was detected using ultra depth of field and laser confocal microscopy. Using Ultra-Ever Dry as a low surface energy substance to alter the wettability of microstructure surfaces. Through surface wettability tests, droplet freezing, and droplet impact tests, the cross shaped biomimetic structure designed by the Bessel curve has a maximum droplet freezing time of 4193 s and a minimum droplet impact time of 9.81 ms. The experimental results indicate that the cross shaped biomimetic structure has good hydrophobicity and broad application prospects.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), stands out as one of the most devastating epidemics impacting wheat production worldwide. Resistant wheat varieties had swiftly been overcome due to the emergence of new virulent Pst strains. Effectors secreted by Pst interfere with plant immunity, and verification of their biological function is extremely important for controlling wheat stripe rust. In this study, we identified an effector, Pst-18220, from Puccinia striiformis f. sp. tritici (Pst), which was induced during the early infection stage of Pst. Silencing the expression of Pst-18220 through virus-mediated host-induced gene silencing (HIGS) resulted in a decreased number of rust pustules. In Nicotiana benthamiana, it significantly suppressed cell death induced by Pseudomonas syringae pv. tomato (Pto) DC3000. In Arabidopsis, plants with stable overexpression of Pst-18220 showed increased susceptibility to Pto DC3000, accompanied by a decrease in the expression level of pattern-triggered immunity (PTI)/effector-triggered immunity (ETI)-related genes, namely, AtPCRK1, AtPCRK2, and AtBIK1. These results emphasize the significant role of the Pst candidate effector, Pst-18220, in rust pathogenicity and the suppression of plant defense mechanisms. This broadens our understanding of effectors without any known motif.

Abstract In clinics, hepcidin levels are elevated in various anemia‐related conditions, particularly in iron‐refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron‐refractory anemia, the potential effect of hypoxia and pharmacologically‐mimetic drug FG‐4592 (Roxadustat) are evaluated, a hypoxia‐inducible factor (HIF)‐prolyl hydroxylase (PHD) inhibitor, on mouse models of iron‐refractory iron‐deficiency anemia (IRIDA), anemia of inflammation and 5‐fluorouracil‐induced chemotherapy‐related anemia. The potent protective effects of both hypoxia and FG‐4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG‐4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin‐activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5‐fluorouracil‐induced anemia, which can not be rescued by FG‐4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia‐related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.

Zirconia (ZrO2) is a ceramic material with high-temperature resistance and good insulating properties. Herein, for the first time, the surface of ZrO2 was modified with docosanoic acid (DCA) to improve its self-cleaning and hydrophobic properties. This surface modification transformed the surface of ZrO2 from hydrophilic to superhydrophobic. A two-step spraying method was used to prepare the superhydrophobic surface of ZrO2 by sequentially applying a primer and a topcoat. The primer was a solution configured using an epoxy resin as the adhesive and polyamide as the curing agent, while the topcoat was a modified ZrO2 solution. The superhydrophobic surface of ZrO2 exhibited a contact angle of 154° and a sliding angle of 4°. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and other analytical techniques were used to characterize the prepared zirconia particles and their surfaces. Moreover, results from surface self-cleaning and droplet freezing tests showed that DCA-modified ZrO2 can be well combined, and its coatings show good self-cleaning and anti-icing properties on TA2 bases.

With the advancement of sensor technology, distributed processing technology, and wireless communication, Visual Sensor Networks (VSNs) are widely used. However, VSNs also have flaws such as poor data synchronization, limited node resources, and complicated node management. Thus, this paper proposes a sensor placement optimization method to save network resources and facilitate management. First, some necessary models are established, including the sensor model, the space model, the coverage model, and the reconstruction error model, and a dimensionality reduction search method is proposed. Next, following the creation of a multi-objective optimization function to balance reconstruction error and coverage, a clever optimization algorithm that combines the benefits of Genetic Algorithms (GA) and Particle Swarm Optimization (PSO) is applied. Finally, comparison studies validate the methodology presented in this paper, and the combined algorithm can enhance optimization effect while relatively reducing running time. In addition, a sensor coverage method for large-range target space with obstacles is discussed.