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Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Various factors in the tumor environment (TME) can lead to the activation of endoplasmic reticulum stress (ERS), thereby affecting the occurrence and development of tumors. The objective of our study was to develop and validate a radiogenomic signature based on ERS to predict prognosis and systemic combination therapy response. Methods Using data from The Cancer Genome Atlas Program (TCGA) as a training cohort and data from International cancer genome consortium (ICGC) as a testing cohort. Univariate Cox regression and multivariate Cox regression analysis were used to identify prognostic-related genes and construct a model. HCC single-cell data obtained from Gene Expression Omnibus (GEO) were used to map gene signatures and explore inter-cellular signaling communications. Finally, a radiogenomic signature was used to predict the objective response rate (ORR) and overall survival (OS). Results A total of four gene signatures related to ERS, including Stanniocalcin-2 (STC2), Melanoma-Associated Antigen 3 (MAGEA3), BR Serine/Threonine-Protein Kinase 2 (BRSK2), DEAD/H-Box Helicase 11 (DDX11) were identified. Macrophages were significantly different between high-risk and low-risk groups. The high-risk group showed higher targeting programmed cell death-1 (PD-1) and mutated tumor protein p53 (TP53) scores. Drug sensitivity analysis found that most sensitive drugs target the phosphatidylinositol 3-kinase/ mechanistic target of rapamycin (PI3K/mTOR) signaling pathway. Further research revealed the expression of STC2 in the endothelial cells (ECs), particularly plasmalemma vesicle associated protein (PLVAP) + ECs, and may regulate the reprogramming and function of macrophages. Furthermore, we identified nine radiomic features and established a radiogenomic signature based on ERS that can predict prognosis and response to systemic combination therapy. This signature can guide systemic combination therapy for patients with unresectable HCC. Conclusions We established an ERS prognostic model that can predict patient prognosis. We also found that ERS is closely related to the TME and is mainly manifested in the interaction between tumor-associated endothelial cells (TAEs) and tumor-associated macrophages (TAMs). Moreover, we constructed a radiogenomic signature based on the ERS. This signature can guide subsequent combination therapy for patients with unresectable HCC.

Soil C:N:P stoichiometry is a powerful tool for determining soil nutrient cycling and limitations in agroecosystems and provides a basis for optimizing fertilizer strategies in crop production under partial root-zone drying irrigation (PRDI). PRDI is of particular interest in improving soil C:N:P stoichiometry in non-N-fixing crops because it enhances resource-use efficiency, which is critical for water management and soil health in arid agroecosystems. However, its effect on the soil C:N:P stoichiometry in N-fixing crops remains poorly understood. In this study, a three-year field experiment was conducted using alfalfa as a representative N-fixing crop to investigate the effect of PRDI on soil C, N, and P concentrations and their stoichiometry. The field experiment involved two irrigation methods, PRDI and conventional furrow irrigation (CFI), with four irrigation volumes set at 70 %, 85 %, 100 %, and 115 % evapotranspiration (ETc). This study showed that PRDI increased soil porosity, soil organic C and total N concentrations, decreased soil bulk density and did not affect soil total P concentrations. Furthermore, PRDI increased the soil C:N:P ratio and irrigation modes contributed more to the abovementioned variables than irrigation volumes. These findings suggest that PRDI might expose alfalfa to P limitation and present a pattern of how PRDI influences soil C:N:P stoichiometry in N-fixing crops. Therefore, this study provides valuable guidance for policymakers, agricultural practitioners, and researchers, with compelling evidence for developing sustainable water and nutrient management practices in the agroecosystems of arid regions.

Glucose deprivation (GD), a common metabolic stress condition, has been recognized as a potent inducer of necroptotic cell death. Our previous findings suggested that the mitochondrial protein, Noxa, may be involved in mediating the release of mitochondrial DNA during GD-induced ZBP1-dependent necroptotic pathway. However, the functional significance of Noxa in necroptosis under GD treatment remains unclear. Here, we investigated the role of Noxa in GD-induced necroptosis and the underlying molecular mechanisms governing its expression. We revealed that Noxa is required for the induction of necroptosis under GD. We also demonstrated that the upregulation of Noxa induced by GD is mediated by ATF4, a key transcription factor. These results provide insights into the regulatory mechanisms underlying Noxa dynamics during GD treatment and highlights its potential as a therapeutic target in cancer therapy and necroptosis-related diseases.

Ningxia A Heat Supply Company adopted the large temperature difference long-distance heating technology.During two consecutive heating seasons from 2019 to 2021， significant scaling， pitting corrosion of stainless steel and corrosion of carbon steel were observed in the secondary pipeline network， which severely impacted the heating effect for residents during the winter.The heat supply company conducted research and development on scale and corrosion inhibitors，as well as studies on the critical conditions for pitting corrosion，based on the characteristics of its water quality and operating conditions.Ultimately， an anti-corrosion and anti-scaling strategy centered on the addition of TC-type scale and corrosion inhibitors was determined.Through industrial trials， random inspections of the heat exchanger plates revealed no significant pitting or scaling， and the results of carbon steel corrosion coupon tests indicated that the corrosion rate of the inner pipeline walls was effectively controlled.This ensured the safe and economical operation of the heating system.The corrosion and scale prevention strategy has shown great potential for broader application in the same type of heating systems.

Bioturbation caused by herbivorous fossorial mammals creates extensive bare patches through their burrowing activities. Understanding changes in plant-soil carbon (C), nitrogen (N), and phosphorus (P) stoichiometry during the vegetation recovery of these bare patches is crucial for elucidating the restoration mechanisms of disturbed grassland ecosystems. This study considered plateau pika (Ochotona curzoniae) as the focal species and categorized the bare patches into short-term and long-term bare patches using a spatial substitution strategy, with surrounding vegetated surfaces in disturbed alpine meadows as controls. Results showed that P concentration in plant roots was 32.58% higher in long-term bare patches compared to short-term bare patches. However, no significant changes were observed in C and N concentrations in either plant shoots or roots during vegetation recovery process. Soil N concentrations were 38.78% lower in short-term bare patches and 36.65% lower in long-term bare patches compared to vegetated surfaces. The C:N ratio in plant shoots was 18.26% lower in short-term bare patches than in vegetated surfaces, whereas the soil C:N ratio was 39.42% higher in long-term bare patches compared to vegetated surfaces. However, no changes were observed in the C:P and N:P ratio of both plant and soil during vegetation recovery process of bare patches. These findings indicate that P concentration in plant roots can serve as a reliable indicator of the vegetation recovery process of bare patches caused by plateau pikas. Furthermore, plants in short-term bare patches prioritize rapid growth through resource allocation, while in long-term bare patches, they enhance nutrient use efficiency to achieve greater stability and resilience. These insights into plant-soil nutrient dynamics provide a deeper understanding of ecosystem resilience and recovery processes in disturbed alpine meadows, offering a valuable foundation for more targeted grassland management strategies.