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Abstract Limited studies examined the interaction effects between summer heat exposure and economic development on the settlement intention, especially for the floating population. Binary logistic regression model was used to examine the association of summer temperature, per capita GRDP (PGRDP), summer temperature × PGRDP with settlement intention. Additive interaction term for summer temperature and PGRDP level was used to test the interactive effects. This study indicates that summer heat exposure will decrease the settlement intention of migrants (OR:1.386, 95% CI: 1.35–1.423), while PGRDP will increase settlement intention (OR: 0.893, 95% CI: 0.870–0.917). There is a negative interaction between summer temperature and PGRDP in the additive model. To a certain extent, summer heat exposure can weaken the attractiveness of economic development for migrants to settle down, they prefer to settle in cities with favorable temperatures and high levels of economic development. Stratified analyses illustrated that summer heat exposure showed lower settlement intention among female, the elderly, engaged in agriculture and industry and living in central China. The government should take measures about mitigation, adaptation and balancing economic development and climate change to reduce the adverse impacts of summer heat, and pay more attention to vulnerable groups and backward regions.

Abstract Microplastics (MPs) have emerged as a significant food‐related risk factor, posing potential threats to human health through dietary intake and the food chain. This review comprehensively analyses the impact of MPs as a novel food safety risk factor on human health (in particular on the gastrointestinal route). Furthermore, we explore the potential mechanisms by which dietary fibers (DFs) may alleviate the health risks associated with MPs. The impact of DFs on human health is intricately linked to factors such as their size, concentration, and composition. We characterize current knowledge and highlight gaps. Although DFs may be a potential strategy to reduce the impact of MPs on organism health, more in‐depth studies are needed to determine their practical effects and application prospects. In particular, research on MPs that actively reduce intake in vivo remains relatively limited and needs to receive more attention from the scientific community.

Abstract The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.

Abstract Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.

Abstract The microRNAs (miRNAs) of their hosts play an important role in regulating both the innate and adaptive immune responses to Cryptosporidium parvum infection. The mechanisms of autophagy and apoptosis are important components of the defense system against C. parvum infection. In this study, we investigate the role of miRNA-199a-3p in regulating MTOR-mediated autophagy and apoptosis in HCT-8 cells induced by C. parvum. The expression of miR-199a-3p increased at 3, 6 and 12 hours postinfection (hpi) but decreased at 24 and 48 hpi. The upregulation of miR-199a-3p promoted autophagy and apoptosis and limited the parasite burden in HCT-8 cells after C. parvum infection. The downregulation of miR-199a-3p inhibited the autophagy and apoptosis induced by C. parvum and enhanced the parasite burden in HCT-8 cells. A luciferase reporter showed that MTOR was a target gene of miR-199a-3p. Suppressed expression of MTOR by small interfering RNA (siRNA) promoted autophagy and apoptosis and limited C. parvum burden in HCT-8 cells. Co-transfection with miR-199a-3p inhibitor or si-mTOR revealed that miR-199a-3p regulates autophagy and apoptosis in HCT-8 cells through MTOR, to resist C. parvum infection. In conclusion, intestinal epithelial cells defend against C. parvum infection by regulating their autophagy and apoptosis through the miR-199a-3p-MTOR axis.

Abstract Obesity is characterized by dysregulated adipogenesis that leads to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing adipogenesis is therefore key to designing therapeutic interventions against obesity. In our study, we analyzed 3’-end sequencing data that we generated from human preadipocytes and adipocytes, as well as previously published RNA-seq datasets, to elucidate mechanisms of regulation via long non-coding RNA (lncRNA), alternative splicing (AS) and alternative polyadenylation (APA). We discovered lncRNAs that have not been previously characterized but may be key regulators of white adipogenesis. We also detected 100 AS events and, using motif enrichment analysis, identified RNA binding proteins (RBPs) that could mediate exon skipping—the most prevalent AS event. In addition, we show that usage of alternative poly(A) sites in introns or 3’-UTRs of key adipogenesis genes leads to isoform diversity, which can have significant biological consequences on differentiation efficiency. We also identified RBPs that may modulate APA and defined how 3’-UTR APA can regulate gene expression through gain or loss of specific microRNA binding sites. Taken together, our bioinformatics-based analysis reveals potential therapeutic avenues for obesity through manipulation of lncRNA levels and the profile of mRNA isoforms via alternative splicing and polyadenylation.

AbstractOpioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.

Sourdough is often considered a healthy choice and quality improver for use in cereal production due to its unique microbial composition and fermentation properties. During sourdough fermentation of cereals, biotransformation of nutrients occurs, resulting in notable changes to proteins, carbohydrates, fats, vitamins, and minerals. Each nutrient undergoes specific transformations, providing various advantages for human health. Proteins undergo hydrolysis to produce small molecular weight peptides and amino acids that are more easily digested and absorbed by the human body. Carbohydrates break down to improve the digestibility and absorption of cereals and lower the glycemic index. Fatty acids experience oxidation to produce new substances with health benefits. Additionally, the application of sourdough fermentation can enhance the texture, flavor, and nutritional value of cereal foods while also extending their shelf life and improving food safety. In conclusion, sourdough fermentation has a broad range of applications in cereal food processing. Further research is encouraged to investigate the mechanisms and processes of sourdough fermentation to develop even more nutritious, healthy, and flavorful cereal-based foods.

ABSTRACT: High Fischer ratio oligopeptides (HFROs) are a group of oligopeptides containing high levels of branched-chain amino acids (BCAA) and low levels of aromatic amino acids (AAA). HFROs have received a lot of attention as they are believed to have significant physiological activities, including antioxidant, liver damage repair, anti-fatigue, anti-tumor and energy supply to the body. HFROs are available from a wide range of sources and both plant and animal proteins can be used to prepare HFROs but the physiological tolerability and rejection of special populations needs to be considered. Enzymatic hydrolysis is the most common method for the preparation of HFROs, but optimization of the separation and purification process is still needed in the future. Diseases caused by disruptions in the balance of BCAA and AAA in the blood, such as hepatic encephalopathy, can be treated by supplementing HFROs with drugs or food. In addition, HFROs are able to reduce fatigue feedback and assist in the treatment of phenylketonuria at the molecular nutrient level. The aim of this review is to review recent research on HFROs and provide new perspectives on the high value use of crops and the development of novel functional and special medical purpose foods.

IntroductionGold nanoparticles (AuNPs) have been developed as treatment materials for various diseases and shown magnificent potential. By contrast to the broad toxicological studies on the single exposure (AuNPs), how the other health risks modulate the toxicological profile of AuNPs remains to be investigated. Plastics are among the most common health risks in daily life due to the broad utilization of plastic products. Therefore, in this study, we aimed to reveal the toxicological effects induced by co-exposure of gold nanorod (AuR) and polystyrene micro- and nano-plastics (hereinafter, referred to as AuRmPS and AuRnPS, respectively) in mice.MethodsSystematic biochemical characterizations were performed to investigate the hepatotoxicity, nephrotoxicity, neurotoxicity, inflammatory responses, alterations in gut microbiota induced by co-exposure, and to analyze the toxicological phenomena from the roles of reactive oxygen species and gut-organ axis.ResultsIt has been found that hepatotoxicity, nephrotoxicity, neurotoxicity, and inflammation were exacerbated in AuRnPS and AuRmPS, and gut microbiota composition was more severely altered in AuRnPS exposure. These results suggest the necessity of reducing plastics exposure in AuNPs-based therapies. Moreover, protection against the nano-sized plastic particles holds higher priority.ConclusionThese findings will facilitate the explorations of methods to reduce therapeutic toxicity and improve biosafety for specific treatments by referring to the orders of importance in protecting different organs.

Abstract Background Cryptosporidium parvum is an apicomplexan zoonotic parasite causing the diarrheal illness cryptosporidiosis in humans and animals. To invade the host intestinal epithelial cells, parasitic proteins expressed on the surface of sporozoites interact with host cells to facilitate the formation of parasitophorous vacuole for the parasite to reside and develop. The gp40 of C. parvum, named Cpgp40 and located on the surface of sporozoites, was proven to participate in the process of host cell invasion. Methods We utilized the purified Cpgp40 as a bait to obtain host cell proteins interacting with Cpgp40 through the glutathione S-transferase (GST) pull-down method. In vitro analysis, through bimolecular fluorescence complementation assay (BiFC) and coimmunoprecipitation (Co-IP), confirmed the solid interaction between Cpgp40 and ENO1. In addition, by using protein mutation and parasite infection rate analysis, it was demonstrated that ENO1 plays an important role in the C. parvum invasion of HCT-8 cells. Results To illustrate the functional activity of Cpgp40 interacting with host cells, we identified the alpha-enolase protein (ENO1) from HCT-8 cells, which showed direct interaction with Cpgp40. The mRNA level of ENO1 gene was significantly decreased at 3 and 24 h after C. parvum infection. Antibodies and siRNA specific to ENO1 showed the ability to neutralize C. parvum infection in vitro, which indicated the participation of ENO1 during the parasite invasion of HCT-8 cells. In addition, we further demonstrated that ENO1 protein was involved in the regulation of cytoplasmic matrix of HCT-8 cells during C. parvum invasion. Functional study of the protein mutation illustrated that ENO1 was also required for the endogenous development of C. parvum. Conclusions In this study, we utilized the purified Cpgp40 as a bait to obtain host cell proteins ENO1 interacting with Cpgp40. Functional studies illustrated that the host cell protein ENO1 was involved in the regulation of tight junction and adherent junction proteins during C. parvum invasion and was required for endogenous development of C. parvum. Graphical Abstract

Visual Place Recognition (VPR) is a fundamental task in robotics and computer vision, where the ability to recognize locations from visual inputs is crucial for autonomous navigation systems. Traditional methods, which rely on handcrafted features or standard convolutional neural networks (CNNs), struggle with environmental changes that significantly alter a place’s appearance. Recent advancements in deep learning have improved VPR by focusing on deep-learned features, enhancing robustness under varying conditions. However, these methods often overlook saliency cues, leading to inefficiencies in dynamic scenes. To address these limitations, we propose an improved MixVPR model that incorporates both self-attention and cross-attention mechanisms through a spatial-wise hybrid attention mechanism. This enhancement integrates spatial saliency cues into the global image embedding, improving accuracy and reliability. We also utilize the DINOv2 visual transformer for robust feature extraction. Extensive experiments on mainstream VPR benchmarks demonstrate that our method achieves superior performance while maintaining computational efficiency. Ablation studies and visualizations further validate the contributions of our attention mechanisms to the model’s performance improvement.

Detection based on LiDAR and camera fusion is increasingly popular for researchers in the autonomous driving domain. Compared to the camera-only and LiDAR-only methods, the fusion-based methods indeed improve the detection accuracy on public-available datasets. However, due to the complexity of the projection or fusion mechanism, few of these methods can run in real time even on an advanced desktop GPU. Thus, in this paper, we propose a new fusion detection model G-Fusion with a light and fast image view-transform module. According to our receptive field analysis of image feature maps, we directly project image features to only one voxel layer located on the ground, then fuse the LiDAR and image features by concatenation and convolution. With this delicately designed module, G-Fusion greatly boosts the state-of-the-art speed performance on the nuScenes dataset, achieving a good balance with the competitive detection scores. Meanwhile, since the precision of sensor extrinsic parameters is important for most fusion-based methods, we also deeply dig into our model’s calibration error tolerance ability and discover the failure noise condition.

In industrial aluminum sheet surface defect detection, false detection, missed detection, and low efficiency are prevalent challenges. Therefore, this paper introduces an improved YOLOv8 algorithm to address these issues. Specifically, the C2f-DSConv module incorporated enhances the network’s feature extraction capabilities, and a small target detection layer (160 × 160) improves the recognition of small targets. Besides, the DyHead dynamic detection head augments target representation, and MPDIoU replaces the regression loss function to refine detection accuracy. The improved algorithm is named YOLOv8n-DSDM, with experimental evaluations on an industrial aluminum sheet surface defect dataset demonstrating its effectiveness. YOLOv8n-DSDM achieves an average mean average precision (mAP50%) of 94.7%, demonstrating a 3.5% improvement over the original YOLOv8n. With a single-frame detection time of 2.5 ms and a parameter count of 3.77 M, YOLOv8n-DSDM meets the real-time detection requirements for industrial applications.

With the exacerbation of environmental issues and the ongoing energy crisis, the large-scale integration of renewable energy resources has significantly increased the demand for flexibility in distribution systems. Establishing a comprehensive flexibility evaluation index system is crucial for the development, promotion, and optimization of AC/DC distribution systems. This paper focuses on the flexibility evaluation of AC/DC distribution systems, proposing a detailed flexibility evaluation index system and a comprehensive evaluation method based on the ANP-Entropy weighting model. The proposed flexibility evaluation index system comprises 18 key indexes categorized into four essential dimensions: overall flexibility performance, flexible resources participation, operational performance, and economic performance. The ANP-Entropy weighting model is employed to perform a thorough evaluation of the flexibility of AC/DC distribution systems. To validate the effectiveness of the proposed evaluation method, a case study is conducted. Additionally, the study explores the impacts of controllable distributed generator (CDG) capacity, energy storage system (ESS) capacity, and voltage source converter (VSC) capacity on the flexibility of AC/DC distribution systems. The results provide valuable insights into optimizing the flexibility and performance of AC/DC distribution systems.

Abstract Interlayer coupling strength dichotomizes two-dimensional (2D) materials into layered and non-layered types. Traditionally, they can be regarded as atomic layers intrinsically linked via van der Waals (vdW) forces or covalent bonds, oriented orthogonally to their growth plane. In our work, we report a material system that differentiates from layered and non-layered materials, termed quasi-layered domino-structured (QLDS) materials, effectively bridging the gap between these two typical categories. Considering the skewed structure, the force orthogonal to the 2D QLDS-GaTe growth plane constitutes a synergistic blend of vdW forces and covalent bonds, with neither of them being perpendicular to the 2D growth plane. This unique amalgamation results in a force that surpasses that in layered materials, yet is weaker than that in non-layered materials. Therefore, the lattice constant contraction along this unique orientation can be as much as 7.7%, tantalizingly close to the theoretical prediction of 10.8%. Meanwhile, this feature endows remarkable anisotropy, second harmonic generation enhancement with a staggering susceptibility of 394.3 pm V−1. These findings endow further applications arranged in nonlinear optics, sensors, and catalysis.

Abstract Terahertz (THz) technologies have become a focus of research in recent years due to their prominent role in envisioned future communication and sensing systems. One of the key challenges facing the field is the need for tools to enable agile engineering of THz wave fronts. Here, we describe a reconfigurable metasurface based on GaN technology with an array-of-subarrays architecture. This subwavelength-spaced array, under the control of a 1-bit digital coding sequence, can switch between an enormous range of possible configurations, providing facile access to nearly arbitrary wave front control for signals near 0.34 THz. We demonstrate wide-angle beam scanning with 1° of angular precision over 70 GHz of bandwidth, as well as the generation of multi-beam and diffuse wave fronts, with a switching speed up to 100 MHz. This device, offering the ability to rapidly reconfigure a propagating wave front for beam-forming or diffusively scattered wide-angle coverage of a scene, will open new realms of possibilities in sensing, imaging, and networking.

Abstract Cleavage and polyadenylation (CPA) is responsible for 3′ end processing of eukaryotic poly(A)+ RNAs and preludes transcriptional termination. JTE-607, which targets CPSF-73, is the first known CPA inhibitor (CPAi) in mammalian cells. Here we show that JTE-607 perturbs gene expression through both transcriptional readthrough and alternative polyadenylation (APA). Sensitive genes are associated with features similar to those previously identified for PCF11 knockdown, underscoring a unified transcriptomic signature of CPAi. The degree of inhibition of an APA site by JTE-607 correlates with its usage level and, consistently, cells with elevated CPA activities, such as those with induced overexpression of FIP1, display greater transcriptomic disturbances when treated with JTE-607. Moreover, JTE-607 causes S phase crisis and is hence synergistic with inhibitors of DNA damage repair pathways. Together, our data reveal CPA activity and proliferation rate as determinants of CPAi-mediated cell death, raising the possibility of using CPAi as an adjunct therapy to suppress certain cancers.

AbstractBackground Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of postoperative nausea and vomiting. The aim of our study was to compare the effective dose in 50% of subjects (ED50) of intravenous butorphanol infusion with or without a single intravenous bolus of palonosetron for preventing pruritus induced by epidural administration of morphine.Methods A total of 120 parturients were randomly assigned to receive an intravenous bolus injection of palonosetron plus continuous infusion of butorphanol (Group P + B) or an intravenous bolus of saline plus continuous infusion of butorphanol (Group B) after epidural administration of morphine. The antipruritic effect was graded as satisfactory (numerical rating scale (NRS) of pruritus ≤3) or unsatisfactory (NRS >3) within 48 h after morphine treatment. The first patient in each group received butorphanol infusion at a rate of 4 µg/kg/h. The infusion dose for each subsequent patient in the corresponding group was increased by 0.2 µg/kg/h after an unsatisfactory response or decreased by 0.2 µg/kg/h after a satisfactory response. The ED50 was calculated for each group and compared using up-down sequential analysis.Results The ED50 (mean [95% confidence interval (CI)]) of the dose of intravenous butorphanol infusion for preventing moderate to severe pruritus was lower in Group P + B (3.29 µg/kg/min [3.25–3.34 µg/kg/min]) than in Group B (3.57 µg/kg/min [3.47–3.67 µg/kg/min]) (p

Seeds from Cassia obtusifolia L., i.e. Semen cassiae (SC) were evaluated as environmentally friendly filler particles for artificial turf. The goal was to avoid unwanted germination problems of SC under wet conditions. This work evaluated the influence of different pretreatments on the germination rate and performance of SC. After the combination of polishing and dry heat (90 °C, 72 h) treatment, the germination rate of SC decreased to 0% and the activation energy increased to 216 kJ/mol. Compared with the untreated SC, the thermal stability of SC improved, with an initial degradation temperature of 214 °C and a pyrolysis residue of 31.9%. Additionally, the resilience and the water absorption of SC as a filler material increased to 4.13% and 169%, respectively. This study provides an effective pretreatment method for the solution of germination problem and the performance improvement of SC. This makes the pretreated SC a prospective candidate as an environmentally protective granular filling material.

With the development of autonomous driving, consensus is gradually forming around vehicle–infrastructure cooperative (VIC) autonomous driving. The VIC environment-sensing system uses roadside sensors in collaboration with automotive sensors to capture traffic target information symmetrically from both the roadside and the vehicle, thus extending the perception capabilities of autonomous driving vehicles. However, the current target detection accuracy for feature fusion based on roadside LiDAR and automotive LiDAR is relatively low, making it difficult to satisfy the sensing requirements of autonomous vehicles. This paper proposes PAFNet, a VIC pillar attention fusion network for target detection, aimed at improving LiDAR target detection accuracy under feature fusion. The proposed spatial and temporal cooperative fusion preprocessing method ensures the accuracy of the fused features through frame matching and coordinate transformation of the point cloud. In addition, this paper introduces the first anchor-free method for 3D target detection for VIC feature fusion, using a centroid-based approach for target detection. In the feature fusion stage, we propose the grid attention feature fusion method. This method uses the spatial feature attention mechanism to fuse the roadside and vehicle-side features. The experiment on the DAIR-V2X-C dataset shows that PAFNet achieved a 6.92% higher detection accuracy in 3D target detection than FFNet in urban scenes.

In urban settings, roadside infrastructure LiDAR is a ground-based remote sensing system that collects 3D sparse point clouds for the traffic object detection of vehicles, pedestrians, and cyclists. Current anchor-free algorithms for 3D point cloud object detection based on roadside infrastructure face challenges related to inadequate feature extraction, disregard for spatial information in large 3D scenes, and inaccurate object detection. In this study, we propose AFRNet, a two-stage anchor-free detection network, to address the aforementioned challenges. We propose a 3D feature extraction backbone based on the large sparse kernel convolution (LSKC) feature set abstraction module, and incorporate the CBAM attention mechanism to enhance the large scene feature extraction capability and the representation of the point cloud features, enabling the network to prioritize the object of interest. After completing the first stage of center-based prediction, we propose a refinement method based on attentional feature fusion, where fused features incorporating raw point cloud features, voxel features, BEV features, and key point features are used for the second stage of refinement to complete the detection of 3D objects. To evaluate the performance of our detection algorithms, we conducted experiments using roadside LiDAR data from the urban traffic dataset DAIR-V2X, based on the Beijing High-Level Automated Driving Demonstration Area. The experimental results show that AFRNet has an average of 5.27 percent higher detection accuracy than CenterPoint for traffic objects. Comparative tests further confirm that our method achieves high accuracy in roadside LiDAR object detection.

Environmental transformations and intensifying desertification across the Qinghai–Xizang Plateau (QXP) are having a significant influence permafrost degradation, heightening the risks associated with carbon emissions, thermal hazards and infrastructural damage. However, the specific response of permafrost to desertification remains insufficiently understood. Here, we employed numerical modeling to examine the sensitivity of the impact of aeolian sand cover (ASC) on permafrost degradation. Our findings reveal that the thickness and moisture content of ASC profoundly affect permafrost degradation. Moreover, the thermal stability of permafrost and the rate of climatic warming modulate this degradation process. The simulation results identify two critical thickness thresholds for ASC: 20 cm and 80–120 cm. Specifically, dry ASC thinner than 20 cm accelerates permafrost degradation driven by desertification, whereas ASC thicker than 20 cm mitigates this effect. Furthermore, increased moisture in ASC extends the thickness threshold to 80–120 cm. These results suggest that climatic variations in the QXP, particularly transitions towards either warming–drying or warming–wetting, will markedly influence the response of permafrost to desertification. Notably, a warming–drying climate may reduce the potential degradation of permafrost caused by desertification. This study provides a critical reference for understanding the impact of aeolian desertification on permafrost in regions beyond the QXP. It holds significant policy implications for environmental conservation and infrastructure development within the plateau.

Abstract Background Cryptosporidium parvum is a zoonotic parasitic protozoan that can infect a variety of animals and humans and is transmitted between hosts via oocysts. The oocyst wall provides strong protection against hostile environmental factors; however, research is limited concerning the oocyst wall at the proteomic level. Methods A comprehensive analysis of the proteome of oocyst wall of C. parvum was performed using label-free qualitative high-performance liquid chromatography (HPLC) fractionation and mass spectrometry-based qualitative proteomics technologies. Among the identified proteins, a surface protein (CpSP1) encoded by the C. parvum cgd7_5140 (Cpcgd7_5140) gene was predicted to be located on the surface of the oocyst wall. We preliminarily characterized the sequence and subcellular localization of CpSP1. Results A total of 798 proteins were identified, accounting for about 20% of the CryptoDB proteome. By using bioinformatic analysis, functional annotation and subcellular localization of the identified proteins were examined for better understanding of the characteristics of the oocyst wall. To verify the localization of CpSP1, an indirect immunofluorescent antibody assay demonstrated that the protein was localized on the surface of the oocyst wall, illustrating the potential usage as a marker for C. parvum detection in vitro. Conclusion The results provide a global framework about the proteomic composition of the Cryptosporidium oocyst wall, thereby providing a theoretical basis for further study of Cryptosporidium oocyst wall formation as well as the selection of targets for Cryptosporidium detection. Graphical Abstract

Abstract Background CDGSH iron sulfur domain 2 (CISD2) is an iron–sulfur protein with a [2Fe–2S] cluster, which is critical for cell proliferation and iron homeostasis. It has been demonstrated that aberrant expression of CISD2 is associated with the progression of multiple cancers. However, the underlying mechanism of CISD2 in regulating tumorigenesis remains obscure. Methods Bioinformatics strategies were used to investigate the protein interaction network and functional annotation of CISD2. In the functional experiment, cell viability was measured by CCK-8 kit. The levels of cellular reactive oxygen species (ROS), intracellular free iron, lipid peroxides, and lysosomal activity were determined by DCF-DA, RPA, C11-BODIPY, and cathepsin B staining, respectively. The glutathione (GSH) content was determined using a GSH assay kit. Results We showed that knockdown of CISD2 significantly accelerated the Erastin-induced ferroptotic cell death with excess lipid peroxidation, GSH exhaustion, and iron accumulation, while overexpression of CISD2 hindered the sensitivity to Erastin. Further assays via confocal microscopy and western blot exhibited that CISD2 knockdown markedly enhanced the lysosomal activity, and activated ferritinophagy under the exposure of Erastin. Pharmacological inhibition of lysosomal function could inhibit the degradation of ferritin heavy chain (FTH), and attenuate the phenotypes of ferroptosis, such as accelerated iron accumulation and lipid peroxidation. Notably, we found that Erastin-induced compensatory elevation of nuclear factor erythroid 2-related factor 2 (NRF2) could be eliminated in CISD2 depletion cells. Mechanically, CISD2 knockdown promoted the degradation of autophagy adaptor p62 and resulted in an increased binding affinity of Keap1 with NRF2, thus leading to the increased ubiquitination and subsequent degradation of NRF2. Enforced expression of NRF2 reversed the sensitivity of shCISD2 cells to ferroptosis both in vitro and in vivo. Conversely, enforced expression of Keap1 exacerbated the degradation of NRF2, reduced the transcriptional expression of FTH and heme oxygenase 1 (HO-1), increased the oxidative damage, and thus further facilitated ferroptosis. Conclusion Taken together, our current results illustrated two parallel mechanisms involved in the shCISD2-mediated ferroptosis. One was that shCISD2 enhanced the accumulation of free iron via ferritinophagy-dependent ferritin turnover; the other was that CISD2 depletion induced the inhibition of the p62–Keap1–NRF2 pathway, which resulted in oxidative stress and ferroptosis.

Deubiquitinases (DUBs) targeting Met1-linked ubiquitin chains have important functions in mammals but are barely studied in plants. Here, the authors identify rice OTUB1 as a Met1-targeting DUB, characterize the structural determinants of this activity, and show that these features are conserved in green plants.

Continuous generation of reactive oxygen species is desirable in the advanced oxidation process. Here, the authors report a self-cycled photoFenton-like with a scalable artificial leaf for production of H2O2 from water with solar-to-H2O2 efficiency of 1.46%.

Blastocystis is a usual intestinal protist that always found in humans and various animals. Currently, the prevalence of Blastocystis in the migratory whooper swan (Cygnus cygnus) is unknown. In our research, we aimed to determine the occurrence, prevalence, subtype distribution and dynamic transmission mechanisms of Blastocystis in the migratory whooper swan in China. We also assessed the zoonotic potential of Blastocystis isolates, as well as possible routes of transmission and impact of this organism on One Health perspective. Fecal samples (n = 770) were collected from whooper swans inhabiting the Sanmenxia Swan Lake National Urban Wetland Park, China. The overall prevalence of Blastocystis was 11.6% (89/770). We identified 9 subtypes of Blastocystis sp., including 5 zoonotic subtypes [ST1 (Cakir et al., 2019 (8)), ST4 (Selma and Karanis, 2011 (4)), ST5 (Stensvold et al., 2009 (1)), ST6 (Fare et al., 2019 (5)) and ST7(58)] and 3 host-specific subtypes [ST10 (Zhao et al., 2018 (7)), ST14 (Tan et al., 2010 (2)), ST23 (Wang et al., 2018 (3)), and ST25 (Stensvold et al., 2009 (1))]. Subtypes ST4, ST5, ST6, ST10, ST14, ST23, and ST25 were first identified in the whooper swan. Among these subtypes, ST23 and ST25 were identified in birds for the first time, indicating that these subtypes are expanding their host range. So far, this is the first research reporting on the prevalence and subtypes distribution of Blastocystis in the migratory whooper swan in China. The findings obtained in this study will provide new insights into the genetic diversity and transmission routes of Blastocystis, and the possible public health concerns posed by this organism.

Background Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms. Methods and Results PI16 levels after MI were measured by enzyme‐linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts. PI16 gain‐ and loss‐of‐function experiments were used to investigate the potential role of PI16 after MI. In vitro, PI16 overexpression inhibited oxygen–glucose deprivation–induced apoptosis in neonatal rat cardiomyocytes, whereas knockdown of PI16 exacerbated neonatal rat cardiomyocyte apoptosis. In vivo, left anterior descending coronary artery ligation was performed on PI16 transgenic mice, PI16 knockout mice, and their littermates. PI16 transgenic mice showed decreased cardiomyocyte apoptosis at 24 hours after MI and improved left ventricular remodeling at 28 days after MI. Conversely, PI16 knockout mice showed aggravated infract size and remodeling. Mechanistically, PI16 downregulated Wnt3a (wingless‐type MMTV integration site family, member 3a)/β‐catenin pathways, and the antiapoptotic role of PI16 was reversed by recombinant Wnt3a in oxygen–glucose deprivation–induced neonatal rat cardiomyocytes. PI16 also inhibited HDAC1 (class I histone deacetylase) expression, and overexpression HDAC1 abolished the inhibition of apoptosis and Wnt signaling of PI16. Conclusions In summary, PI16 protects against cardiomyocyte apoptosis and left ventricular remodeling after MI through the HDAC1‐Wnt3a‐β‐catenin axis.

Cadmium-based semiconductors have a wide range of applications in light-emitting, energy conversion, photodetection and artificial photosynthesis. With the concern about the potential toxicity of Cd, it is necessary to recycle the element from the Cd based semiconductors. Commonly, the precipitation of Cd cations with S2− is deemed as the end point of recycling. However, actually, CdS is easy to be oxidized and released into the environment and accumulate in the food chain. It still remains challenges on how to refine the Cd element and convert it to the raw material. Herein, we demonstrate a facile room temperature method for recycling Cd from CdS. Cd can be produced from CdS within 3 h with the help of the lithium-ethylenediamine solution. DFT calculations further confirm that the high surface energy of (100) and (101) planes are selectively attacked by the solvated electrons in the solution, which is in good accordance with the XRD, STEM-HAADF and XPS characterizations. With a total recovery efficiency of 88%, Cd is successfully recovered from the CdS powder. This method provides a new perspective on the treatment of Cd-based semiconductor waste, which is of great significance for the recycling of cadmium metal.

Nano-bubble irrigation, as a new irrigation technology, can deliver fertilizer-mixed oxygen-enriched water to the root zone of crops, representing a new means for increasing crop yield and carbon sequestration and emission reduction. To systematically analyze the effects of nano-bubble irrigation on crop yield, soil aeration, and soil greenhouse gas (GHG) emissions, as well as evaluating its contribution to the net greenhouse warming potential (NGWP) in greenhouse agriculture, this study was conducted in greenhouse facilities in Zhengzhou, China and focused on tomato plants. A 2-factor, 2-level, completely randomized trial of nitrogen application (low N1: 120 kg/hm2 and normal N2: 180 kg/hm2), conventional irrigation, and nano-bubble irrigation (C: 5 ppm and A: 15 ppm) was conducted. Compared with conventional irrigation, crop yield increased by 18.94% and 16.36% (p < 0.05), CO2 emission by 10.72% and 5.71% (p < 0.05), N2O emission by 29.76% and 35.74% (p < 0.05), and CH4 uptake by 300.67% and 327.67% (p < 0.05) under nano-bubble irrigation. The nano-bubble irrigation increased the crop yield, thus significantly improving the NGWP sink for greenhouse gases. The low-nitrogen and regular-nitrogen treatments increased NGWP by 22.69% and 14.52%, respectively (p < 0.05). This suggests that nano-bubble irrigation can significantly improve soil aeration, increase tomato yield and biomass, and significantly improve crop carbon sequestration. In the future, nano-bubble irrigation can be used along with soil amendments to achieve a more efficient increase in yield and enhance the ability of farmland to sequester carbon and reduce emissions.

In order to make battery recycling process greener and more cost-effective, an innovative whole process electrolysis (WPE) concept is proposed in this work. Herein, proof-of-concept for the WPE battery recycling approach is carried out. A recycling routine producing PbI2 from spent lead-acid battery is designed based on the WPE concept. Details of the recycling routine is discussed, and zero energy consumption & zero waste generation for the whole process can be proved. The WPE battery recycling concept is expected to be an alternative choice to the traditional metallurgical battery recycling approach, to realize more sustainable battery recycling.

ABSTRACT Cryptosporidium is a leading cause of diarrheal disease and mortality in young children worldwide. Cryptosporidium invades small intestinal epithelial cells and forms a unique intracellular niche, a process that may alter gut microbes and their production metabolites. However, the mechanism of interactions between gut microbes, metabolites, and parasites is poorly understood. Here, we first characterized the impacts of Cryptosporidium infection on gut microbiota using a microbiome-to-metabolome association study. BALB/c mice were gavaged with Cryptosporidium muris, and fecal samples were collected at 0, 7, 14, 21, and 28 days postinfection (dpi) to observe changes in the intestinal microbes of the body during parasite infection. The infected group had a significantly increased relative abundance of bacterial taxa, such as Lachnospiraceae and Prevotella (P < 0.05), associated with the biosynthesis of short-chain fatty acids (SCFAs). Metabolites related to the metabolic pathways, steroid hormone biosynthesis, and biosynthesis of unsaturated fatty acids pathway were upregulated at 7 dpi, indicating that related metabolites in the biosynthesis of unsaturated fatty acids may be essential for C. muris reproduction in vivo. The metabolites involved in metabolic pathways, bile secretion, and primary bile acid biosynthesis were upregulated at 14 dpi, and we speculate that these metabolites may be critical to the growth and development of Cryptosporidium oocysts in the host. Correlation analysis revealed that Firmicutes bacteria are significantly associated with α-linolenic acid metabolism pathways (P< 0.05). The gut microbiota changes dynamically, and the metabolites involved in fatty acid and bile acid biosynthesis may play important roles during cryptosporidiosis. Details of the gut microbiota and the metabolome after infection with Cryptosporidium may aid in the discovery of specific diagnostic markers and help us understand the changes in parasite metabolic pathways. IMPORTANCE Cryptosporidiosis is a gastrointestinal disease in humans and animals caused by the protozoan parasite Cryptosporidium. Control and treatment of the disease is challenging due to the lack of sensitive diagnostic tools and effective chemotherapy. The dynamics of gut microbiota and metabolites during Cryptosporidium infection may be the key to finding drugs and targets for parasite infection control. Our results indicate that C. muris infection can disrupt gut microbiota and metabolites, resulting in decreased bacterial abundance at the parasitic site. Unsaturated fatty acid pathway biosynthesis-related metabolites are significantly elevated at the patent period. Interestingly, the metabolite pathway that significantly elevated during peak parasite growth was bile acid, the metabolites of which may be important for the circulation of infection of Cryptosporidium oocysts in the host. The enhancing effects of short-chain fatty acid and bile acid metabolism on the growth and development of Cryptosporidium proposed in this study may provide a theoretical basis for future research on novel drugs and vaccines against this intestinal parasite.

Abstract Background Ferroptosis is a newly identified type of programmed cell death, which preferentially targets iron-rich cancer cells such as hepatocellular carcinoma (HCC). Ferritin heavy chain (FTH) is a major iron storing nanocage to store redox-inactive iron, and harbors ferroxidase activity to prevent the iron-mediated production of ROS. Our previous studies have demonstrated that FTH acts as a protective role to increase the cellular resistance to ferroptosis. However, the specific role of FTH in the development of HCC and ferroptosis resistance remains unclear. Methods The indicated databases were used for bioinformatics analysis. The abilities of cell proliferation, migration were measured by cell proliferation assay, transwell assay and wound healing assay. The levels of reactive oxygen species (ROS), lipid peroxide, free iron, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were determined by DCF-DA, C11-BODIPY, mitoSOX, mitoTracker, JC-10 and TMRM staining, respectively. The mitochondrial oxygen consumption rate was monitored by the Seahorse XF24 Analyzer. Results The pan-cancer analysis was performed and showed that FTH expression is upregulated in multiple cancers, such as LIHC, CHOL, HNSC, compared to corresponding normal tissues. In addition, the level of serum ferritin is positively associated with the progression of hepatitis, cirrhosis liver and hepatocellular carcinoma. Further investigation shed light on the strong correlation between FTH expression and tumor grades, cancer stages and prognosis of HCC. Importantly, the proteins interaction network elucidated that FTH is involved in iron homeostasis maintenance and lysosomal-dependent degradation. Enforced expression of FTH accelerates proliferation, migration and endows HCC cells specifically resistant to ferroptosis, but does not protect against cell death caused by cytotoxic compounds like oxaliplatin, irinotecan, and adriamycin. Mechanically, FTH reconstituted cells exhibit diminished peroxides accumulation, reduce mitochondrial ROS level, attenuate the impaired mitochondrial respiratory and rescue the mitochondrial homeostasis. Notably, FTH expression boosts tumorigenic potential in vivo with increased PCNA staining and lesser lipid peroxides generation. Conclusion These results provide new insights that FTH acts as an oncogene in the carcinogenesis and progression of HCC, and is hopeful to be a potential target for therapeutic intervention through ferroptosis.

Abstract Artificial neural network (ANN) provides a new way for mine water inflow prediction. However, the effectiveness of prediction using ANN model would not be guaranteed if the influencing factors of water inflow are difficult to quantify or there are only a few observation data. Chaos theory can recover the rich dynamic information hidden in time series. By reconstructing water inflow time series in phase space, the multi-dimensional matrix could be obtained, with each column representing an influencing factor of water inflow and its value representing the change of the influencing factor with time. Therefore, a new prediction model of mine water inflow can be established by combining ANN with chaos theory when lacking data on the influencing factors of water inflow. In the present study, the No. 12 coal mine of Pingdingshan China was selected as the study site. The Chaos-GRNN model and Chaos- BPNN model of mine, water inflow were established by using the water inflow data from February 1976 to December 2013. The model was verified by using the water inflow values in the 24 months from 2014 to 2015. The number embedded dimension (M) of influencing factors of water inflow determined by phase space reconstruction was 7, meaning that there were 7 influencing factors of water inflow and 7 neurons in GRNN input layer, and the time delay was 13 months. The value of GRNN input layer neurons was determined accordingly. The maximum Lyapunov index was 0.0530, and the prediction time of GRNN was 19 months. The two models were evaluated by using four evaluation indices (R, RMSE, MAPE, NSE) and violin plot. It was found that both models can realize the long-term prediction of water inflow, and the prediction effectiveness of Chaos-GRNN model is better than that of Chaos-BPNN model.

Background: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. Methods: Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets. Results: Seven hub genes—namely, Ccl3, Ccl4, Ccl7, Cxcl1, Hspa1a, Cd14, and Socs3—were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences (p < 0.001, fold change vs sham, 5–200). At the translational level, however, only Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 showed significant differences, while Cxcl1 and Cd14 did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes. Conclusions: The expression of Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer with limited treatment options. Cisplatin (DDP) is used as a mainstay of chemotherapeutic agents in combination with other drugs or radiotherapy for PDAC therapy. However, DDP exhibits severe side-effects that can lead to discontinuation of therapy, and the acquired drug resistance of tumor cells presents serious clinical obstacles. Therefore, it is imperative to develop a more effective and less toxic therapeutic strategy. We and others have previously discovered that dihydroartemisinin (DHA) represents a safe and promising therapeutic agent to preferentially induce cancer cell ferroptosis. In the present study, we find that DHA could intensively strengthen the cytotoxicity of DDP and significantly reduce its effective concentrations both in vitro and in vivo. Combination of DHA and DDP synergistically inhibits the proliferation and induces DNA damage of PDAC cells. Mechanically, the combinative treatment impairs mitochondrial homeostasis, characterized by destroyed mitochondrial morphology, decreased respiratory capacity, reduced ATP production, and accumulated mitochondria-derived ROS. Further studies show that ferroptosis contributes to the cytotoxic effects in PDAC cells under the challenge of DHA and DDP, together with catastrophic accumulation of free iron and unrestricted lipid peroxidation. Moreover, pharmacologic depleting of the free iron reservoir or reconstituted expression of FTH contributes to the tolerance of DHA/DDP-induced ferroptosis, while iron addition accelerates the ferroptotic cell death. In summary, these results provide experimental evidence that DHA acts synergistically with DDP and renders PDAC cells vulnerable to ferroptosis, which may act as a promising therapeutic strategy.

Abstract Background Cryptosporidium is an opportunistic pathogen that infects a wide variety of vertebrates. The aim of the present study was to characterize Cryptosporidium spp. isolates from Bactrian camels and to foster further understanding of the biological characteristics of the pathogen. Methods Fecal specimens were collected from two 4-year-old Bactrian camels resident at the Kaifeng City Zoo in China and examined for Cryptosporidium. Fecal specimens were screened using the floatation method, and then genomic DNA was extracted from the oocysts and identified by nested-PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene, the actin gene and the Cryptosporidium oocyst wall-protein (COWP) gene. Subtype analysis was performed based on four minisatellite (MS) loci (MS1, MS2, MS3 and MS16) that were aligned and phylogenetically analyzed to determine the species and subtype of Cryptosporidium. We then established a BALB/c mice infection model and further verified the results through clinical status, pattern of oocyst excretion and histological examination. Results Cryptosporidium oocyst isolates from the two Bactrian camels had an average (± standard deviation) size of 7.49 ± 0.13 × 5.70 ± 0.10 μm (n = 50). The sequencing and phylogenetic analysis confirmed the species as C. muris. Multilocus sequence typing analysis indicated that the subtypes were M13, M4, M1 and M5. Following the inoculation of BALB/c mice, we found that the prepatent period and number of oocysts per gram increased with increasing infective dose. Oocysts were first detected in the feces of BALB/c mice at 7–8 days post-infection (dpi), with levels peaking twice thereafter, at 15–16 dpi and 19–20 dpi. Histology and scanning electron microscopy studies showed that the stomach contained gastric pits filled with Cryptosporidium that adhered to the surface of gastric mucosa gland epithelial cells, causing the latter to deform, swell and become disordered. Conclusions The findings of this study indicated that oocysts isolated from Bactrian camels were from C. muris. This is the first report of C. muris isolated from camels in China. More epidemiological data are needed to understand the prevalence and transmission of C. muris in camels in different geographic areas. Graphical abstract

The navigation of small unmanned aerial vehicles (UAVs) mainly depends on global positioning systems (GPSs). However, GPSs are vulnerable to attack by spoofing, which causes the UAVs to lose their positioning ability. To address this issue, we propose a deep learning method to detect the spoofing of GPS signals received by small UAVs. Firstly, we describe the GPS signal dataset acquisition and preprocessing methods; these include the hardware system of the UAV and the jammer used in the experiment, the time and weather conditions of the data collection, the use of Spearman correlation coefficients for preprocessing, and the use of SVM-SMOTE to solve the spoofing data imbalance. Next, we introduce a PCA-CNN-LSTM model. We used principal component analysis (PCA) of the model to extract feature information related to spoofing from the GPS signal dataset. The convolutional neural network (CNN) in the model was used to extract local features in the GPS signal dataset, and long short-term memory (LSTM) was used as a posterior module of the CNN for further processing and modeling. To minimize randomness and chance in the simulation experiments, we used the 10-fold cross-validation method to train and evaluate the computational performance of our spoofing machine learning model. We conducted a series of experiments in a numerical simulation environment and evaluated the proposed model against the most advanced traditional machine learning and deep learning models. The results and analysis show that the PCA-CNN-LSTM neural network model achieved the highest accuracy (0.9949). This paper provides a theoretical basis and technical support for spoofing detection for small-UAV GPS signals.

Abstract Crowd counting has become a noteworthy vision task due to the needs of numerous practical applications, but it remains challenging. State‐of‐the‐art methods generally estimate the density map of the crowd image with the high‐level semantic features of various deep convolutional networks. However, the absence of low‐level spatial information may result in counting errors in the local details of the density map. To this end, a novel framework named Multi‐level Feature Fusion Network (MFFN) for single image crowd counting is proposed. The proposed MFFN, which is constructed in an encoder–decoder fashion, incorporates semantic and spatial information for generating high‐resolution density maps of input crowd images. Skip connections are developed between the encoder and the decoder so that low‐level spatial information and high‐level semantic features can be combined by element‐wise addition. In addition, a dense dilated convolution block is placed behind the encoder, extracting multi‐scale context features to guide feature fusion by a channel attention mechanism. The model is trained by multi‐task learning; semantic segmentation supervision is introduced to enhance feature representation. Extensive experiments are conducted on three crowd counting datasets (ShanghaiTech, UCF_CC_50, UCF‐QNRF), and the results show that MFFN outperforms state‐of‐the‐art methods. In addition, sufficient ablation studies are performed to verify the effectiveness of each component in our proposed method.

Excessive production of visceral adipose is a major risk factor of many diseases. Inhibiting the adipogenesis of mesenchymal stem cells (MSCs) will be an efficient way to block adipose production. We illuminated POU class 2 homeobox associating factor 1 (POU2AF1) may promote MSCs adipogenesis by histone deacetylases 1 (HDAC1) signalling. Human retroperitoneal adipose-derived mesenchymal stem cells were isolated from overweight and control groups of patients. IncRNA microarray was used to identified gene expression levels. Adenovirus transduction and cellular small-interfering RNA transfection were used to achieve overexpression and interference of POU2AF1 or HDAC1. Adipogenesis was identified by Oil-red O staining, triglycende, cholesterol assay, real-time PCR and Western Blot. POU2AF1 expression was upregulated in retroperitoneal adipose tissue of overweight patients, and increased during adipogenesis. Overexpression of POU2AF1 promoted spontaneous adipogenesis without adipogenic treatment. Silencing of endogenous POU2AF1 in MSCs inhibited adipogenesis. Overexpression of POU2AF1 alleviated the translocation of HDAC1 to the nucleus. The mRNA level of HDAC1 was also reduced. Co-transfection of Ad-POU2AF1 and Ad-HDAC1 partially reversed the promotion effect of POU2AF1 overexpression in MSCs spontaneous adipogenic differentiation. POU2AF1 involves in the natural differentiation of human mesenchymal stem cells. Overexpression or silencing POU2AF1 could effectively induce or inhibit the adipogenesis by HDAC1 signaling.

Breast invasive carcinoma (BRCA) is a carcinoma with a fairly high incidence, and the therapeutic schedules are generally surgery and chemotherapy. However, chemotherapeutic drugs tend to produce serious toxic side effects, which lead to the cessation of treatment. Therefore, it is imperative to develop treatment strategies that are more effective and have fewer side effects at the genetic level. Centromeric protein W (CENPW) is an oncogene that plays an important part in nucleosome assembly. To date, no studies have reported the prognostic significance of CENPW in breast carcinoma. In this study, we verified that CENPW expression is up-regulated in breast carcinoma and positively associated with the level of immune cell infiltration. The clinicopathological characteristics further suggest that CENPW expression is correlated with a worse prognosis of breast carcinoma. Interestingly, the CENPW mutation contributes to the poor prognosis. Next, we discovered that the genes interacting with CENPW are mainly concentrated in the cell cycle pathway, and CENPW is co-expressed with CDCA7, which is also highly expressed in breast carcinoma and leads to a worse prognosis. Our subsequent studies verified that knockdown of CENPW significantly inhibits the proliferation and migration of breast carcinoma cells and promotes their apoptosis rate. Notably, inhibition of CEMPW sensitizes breast cancer cells to chemotherapeutic drugs that have been found to induce cell cycle arrest. In summary, these results provide extensive data and experimental evidence that CENPW can serve as a novel predictor of breast cancer and may act as a prospective therapeutic target.

How electron correlation interplays with topological states remains rarely explored. Here, the authors report flat band arising due to electron correlations in magnetic Weyl semimetal Co3Sn2S2 from a combined optical-spectroscopy and simulation study.

Abstract Background Enterocytozoon bieneusi is a parasite that infects humans and a wide range of other animals. The large migratory waterfowl, the whooper swan (Cygnus cygnus), travels through many cities during its migration and can spread parasites. Despite receiving increasing attention worldwide, there have been no reports of E. bieneusi infection occurring in C. cygnus. Therefore, this study aims to assess the prevalence and genetic characteristics of E. bieneusi in C. cygnus in Sanmenxia, China. Methods Altogether, 467 fresh fecal samples were collected in the Swan Wetland Park in Sanmenxia, China. Genomic DNA was extracted from fresh fecal samples (n = 467) and E. bieneusi was identified by nested PCR amplification of the internal transcribed spacer (ITS) region. ITS-positive sequences were aligned and phylogenetically analyzed to determine the genotypes of E. bieneusi. Results The overall prevalence of E. bieneusi in C. cygnus was 7.49% (35/467). Sequencing of the 35 positive samples revealed eight known genotypes (EbpA, EbpC, Henan-III, Henan-IV, BEB6, CD9, Peru6 and PtEb IX) and three novel genotypes (CSW1, CSW2 and CSW3). The phylogenetic tree constructed from the ITS sequences showed that seven genotypes (Peru6, EbpA, EbpC, Henan-III, CSW3, Henan-IV and CSW1) clustered within the zoonotic Group 1 while the remaining novel genotype CSW2 clustered within Group 5. Conclusions To our knowledge, this is the first report of E. bieneusi in C. cygnus. Of public health significance, our results suggest that migratory C. cygnus might play an important role in the water-borne transmission of E. bieneusi. Effective strategies will be necessary to control E. bieneusi infection in C. cygnus, other animals and humans.

Abstract Estrogen plays substantial roles in pain modulation; however, studies concerning sex hormones and nociception often yield confusing results. The discrepancy could be a result of lack of consensus to regard estrogen as a variable when working with animal models; thus, the influence of hormones’ fluctuations on nociception has continually been neglected. In the present study, we designed a novel hormone substitution model to aid us to evaluate the effects of estrogen’s long-term alterations on ovariectomy (OVX)-induced mechanical hyperalgesia and the expression of estrogen receptors(ERs). OVX rats were implanted with slow-release estrogen pellets at differently arranged time points and doses, such that a gradual elevation or decrease of serum estrogen levels following a relatively stable period of estrogen replacement was achieved in rats. Our results demonstrated that gradual estrogen depletion rather than elevation following the stable period of estrogen substitution in OVX rats alleviated OVX-induced mechanical hyperalgesia in a dose-independent manner, and the opposite estrogen increase or decrease paradigms differently regulate the expression of spinal ERs. Specifically, in rats rendered to continuously increased serum estrogen, the early phase estrogen-induced anti-nociception effect in OVX rats was eliminated, which was accompanied by an over-activation of ERα and a strong depression of ERβ, while in the OVX rats subject to gradual decrease of estrogen replacement, both ERα and ERβ increased modestly compared with the OVX group. Thus, the present study demonstrated that estrogen increase or decrease modulate nociception differently through change of spinal ERs.

A characteristic of frozen ground is a tendency to form banded sequences of particle-free ice lenses separated by layers of ice-infiltrated soil, which produce frost heave. In permafrost, the deformation of the ground surface caused by segregated ice harms engineering facilities and has considerable influences on regional hydrology, ecology, and climate changes. For predicting the impacts of permafrost degradation under global warming and segregated ice transformation on engineering and environmental, establishing appropriate mathematical models to describe water migration and ice behavior in frozen soil is necessary. This requires an essential understanding of water migration and segregated ice formation in frozen ground. This article reviewed mechanisms of water migration and ice formation in frozen soils and their model construction and introduced the effects of segregated ice on the permafrost environment included landforms, regional hydrological patterns, and ecosystems. Currently, the soil water potential has been widely accepted to characterize the energy state of liquid water, to further study the direction and water flux of water moisture migration. Models aimed to describe the dynamics of ice formation have successfully predicted the macroscopic processes of segregated ice, such as the rigid ice model and segregation potential model, which has been widely used and further developed. However, some difficulties to describe their theoretical basis of microscope physics still need further study. Besides, how to describe the ice lens in the landscape models is another interesting challenge that helps to understand the interaction between soil ice segregation and the permafrost environment. In the final of this review, some concerns overlooked by current research have been summarized which should be the central focus in future study.

Hepatocellular carcinoma (HCC) is one of the paramount causes of cancer-related death worldwide. Despite recent advances have been made in clinical treatments of HCC, the general prognosis of patients remains poor. Therefore, it is imperative to develop a less toxic and more effective therapeutic strategy. Currently, series of cellular, molecular, and pharmacological experimental approaches were utilized to address the unrecognized characteristics of disulfiram (DSF), pursuing the goal of repurposing DSF for cancer therapy. We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells. Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death. Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu. Mechanically, we found that DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2. Notably, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis. Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu. Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase. In summary, these results provide experimental evidence that inhibition of the compensatory NRF2 elevation strengthens HCC cells more vulnerable to DSF/Cu induced ferroptosis, which facilitates the synergistic cytotoxicity of DSF/Cu and sorafenib.