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Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis. CUL2ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase, is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity, leading to degradation of IFT46, a protein component of the intraflagellar transport (IFT) complex B. This results in dysfunctional cilia, which explains certain symptoms that are specific to COVID-19. However, the precise molecular mechanism of how ORF10 recognizes CUL2ZYG11B remains unknown. Here, we determined the crystal structure of CUL2ZYG11B complexed with the N-terminal extension (NTE) of SARS-CoV-2 ORF10 (2.9 Å). The structure reveals that the ORF10 N-terminal heptapeptide (NTH) mimics the Gly/N-degron to bind CUL2ZYG11B. Mutagenesis studies identified key residues within ORF10 that are key players in its interaction with CUL2ZYG11B both in ITC assay and in vivo cells. In addition, we prove that enhancement of CUL2ZYG11B activity for IFT46 degradation by which ORF10-mediated correlates with the binding affinity between ORF10 and CUL2ZYG11B. Finally, we used a Global Protein Stability system to show that the NTH of ORF10 mimics the Gly/N-degron motif, thereby binding competitively to CUL2ZYG11B and inhibiting the degradation of target substrates bearing the Gly/N-degron motif. Overall, this study sheds light on how SARS-CoV-2 ORF10 exploits the ubiquitination machinery for proteasomal degradation, and offers valuable insights for optimizing PROTAC-based drug design based on NTH CUL2ZYG11B interaction, while pinpointing a promising target for the development of treatments for COVID-19.

Gaining insight into the underlying mechanisms driving nanoindentation-induced behavior in tungsten is essential for comprehending its mechanical properties. Although the plasticity of conventional pure tungsten under nanocontact conditions is well understood, these theoretical constructs may become inadequate when applied to irradiated tungsten due to the interplay between helium bubbles and dislocations. Here, we employed an integrated approach, combining crystal defect theories, molecular dynamics simulations, and machine learning, to explore the initiation and progression of dislocations in tungsten containing helium bubbles during nanoindentation, focusing on elucidating the impact of helium bubbles. In contrast to the typical dislocation nucleation in pure tungsten, the presence of helium bubbles mitigates local shear strain, thereby hindering dislocation nucleation and propagation, leading to a reduction of indentation force. Additionally, we conducted a comparative analysis between samples with and without helium bubbles, examining factors such as atomic displacement, strain localization parameters, dislocation line length, and stress component distribution. More importantly, a significant outcome of our study is the establishment of a relationship between the consistent alteration in the shape of helium bubbles and their size during micro-scale nanoindentation, achieved through machine learning techniques. Our findings reveal that the area occupied by helium bubbles post-nanoindentation is inversely correlated with indentation depth and directly linked to helium bubble size. These discoveries represent a notable advancement in understanding the effects of irradiation to a certain degree.

The interaction between irradiation defects and dislocations could lead to macroscopic hardening and embrittlement. In this study, molecular dynamics (MD) and machine learning were conducted to study three-dimensional void- and Cu-cluster-induced kinetics models under interaction with dislocations in body-centered cubic Fe-based alloys. MD Results show that dislocation climb and shear are two types of interaction mechanism based on the defect size. Combined MD results and machine learning, it was found that the dislocation length increased linearly with an increase in the size of the defects after the interaction. In addition, the number of atoms in the Cu-rich cluster and the reduced number of vacancies in the voids had a square relationship with the defect size where 0.85D2 is for Cu-rich cluster and 0.50D2 is for void. Furthermore, atomic-scale three-dimensional irradiation-induced defect kinetics models were developed and incorporated into the crystal plasticity finite element model (CPFEM). We also analyzed the contributions of various defects to the increase in the yield stress during CPFEM simulation. Compared with DBH model, the prediction of MD data-driven CPFEM matches better with the experimental data. Cluster contributed the most to hardening with low obstacle strength due to the higher number density compared with dislocation loops and voids. The loops also contributed to hardening; however, their contribution was smaller than that of the clusters. Although the number density and size of voids were minimized, they may have contributed because of the high obstacle strengths. This work can indeed deepen the understanding of irradiation effect in Fe-based alloys.

Despite the existence of many interventions to mitigate or adapt to the health effects of climate change, their effectiveness remains unclear. Here, we introduce the Comprehensive Evaluation Framework for Intervention on Health Effects of Ambient Temperature to evaluate study designs and effects of intervention studies. The framework comprises three types of interventions: proactive, indirect, and direct, and four categories of indicators: classification, methods, scope, and effects. We trialed the framework by an evaluation of existing intervention studies. The evaluation revealed that each intervention has its own applicable characteristics in terms of effectiveness, feasibility, and generalizability scores. We expanded the framework's potential by offering a list of intervention recommendations in different scenarios. Future applications are then explored to establish models of the relationship between study designs and intervention effects, facilitating effective interventions to address the health effects of ambient temperature under climate change.

In this work we study the effects of different factors of dislocation loop on its obstacle strength when interacting with an edge dislocation. At first, the interaction model for dislocation and dislocation loop is established and the full and partial absorption mechanism is obtained. Then, the effect of temperature, size and burgers vector of dislocation loop are investigated. The relation between the obstacle strength and irradiation dose has been established, which bridges the irradiation source and microscale properties. Except that, the obstacle strength of C, Cr, Ni, Mn, Mo and P decorated dislocation loop is studied. Results show that the obstacle strength for dislocation loop decorated by alloy element decreases in the sequence of Cr, Ni, Mn, C, P and Mo, which could be used to help parameterize and validate crystal plasticity finite element model and therein integrated constitutive laws to enable accounting for irradiation-induced chemical segregation effects.

Background: We compared heart rate variability (HRV) indices between people living with HIV (PLWH) and HIV-negative individuals to ascertain the independent association between HIV infection and reduced HRV, and further investigated whether distinct clinical laboratory profiles exist between PLWH with and without reduced HRV. Methods: This cross-sectional analysis included 304 PLWH and 147 HIV-negative individuals with comparable age and sex. Thirty-two routine clinical laboratory indices (including hematology and biochemistry) closest to the survey were extracted from the Electronic Medical Record System. HRV indices were divided into two categories: low (lowest quartile, Q1) and moderate-to-high (combined, Q2‒Q4). Results: The time domain indices, ln(SDNN), ln(RMSSD), and ln(PNN50), as well as the frequency domain indices, ln(HF), ln(LF), and ln(VLF), were all significantly reduced in PLWH versus HIV-negative individuals (all p

In recent years, there has been significant interest in photocatalytic technologies utilizing semiconductors and photosensitizers responsive to solar light, owing to their potential for energy and environmental applications. Current efforts are focused on enhancing existing photocatalysts and developing new ones tailored for environmental uses. Anthraquinones (AQs) serve as redox-active electron transfer mediators and photochemically active organic photosensitizers, effectively addressing common issues such as low light utilization and carrier separation efficiency found in conventional semiconductors. AQs offer advantages such as abundant raw materials, controlled preparation, excellent electron transfer capabilities, and photosensitivity, with applications spanning the energy, medical, and environmental sectors. Despite their utility, comprehensive reviews on AQs-based photocatalytic systems in environmental contexts are lacking. In this review, we thoroughly describe the photochemical properties of AQs and their potential applications in photocatalysis, particularly in addressing key environmental challenges like clean energy production, antibacterial action, and pollutant degradation. However, AQs face limitations in practical photocatalytic applications due to their low electrical conductivity and solubility-related secondary contamination. To mitigate these issues, the design and synthesis of graphene-immobilized AQs are highlighted as a solution to enhance practical photocatalytic applications. Additionally, future research directions are proposed to deepen the understanding of AQs' theoretical mechanisms and to provide practical applications for wastewater treatment. This review aims to facilitate mechanistic studies and practical applications of AQs-based photocatalytic technologies and to improve understanding of these technologies.

This research aimed to determine the effect of dietary guar gum inclusion in high-lipid diets on the liver health of common carp (Cyprinus carpio). Four high-fat diets (10 % crude lipid) containing 0 % (HF), 0.3 % (HFG0.3), 1 % (HFG1), and 3 % (HFG3) of guar gum and a normal-lipid diet (5 % crude lipid; Control) were formulated. The tested diets were evenly and randomly distributed to fifteen tanks, with each tank containing thirty fish (4.53 ± 0.05 g). Fish were fed until apparent satiation for eight weeks. Compared to HF, diets HFG0.3, HFG1, and HFG3 significantly improved feed efficiency, with the HFG0.3 diet enhancing weight gain rate and specific growth rate. The results indicated that HF induced gut dysbiosis, hepatic lipid accumulation, oxidative stress, inflammation, and disturbance in hepatic lipid and cholesterol metabolism. Compared to the HF diet, diets HFG0.3, HFG1, and HFG3 substantially decreased hepatic lipid accumulation and malonaldehyde content, increased catalase activity and the expression of AMP-activated protein kinase (AMPKα2), peroxisomal proliferator-activated receptor alpha (PPARα), cholesterol 7alpha-hydroxylase, and decreased the expression of interleukin-1β (IL-1β). Moreover, the HFG0.3 and HFG1 diets dramatically increased nuclear factor erythroid 2-related factor 2 and liver X receptor expression and decreased protein carbonyl contents and expression of IL-8, nuclear factor kappa B (NF-κB p65), and tumor necrosis factor α. Furthermore, the HFG1 diet significantly increased carnitine palmitoyltransferase 1 and peroxisomal proliferator-activated receptor gamma coactivator 1 expression and reduced expression levels of fibroblast growth factor 19, farnesoid X receptor, and sterol regulatory element-binding protein type 1. The linear discriminant analysis effect size (LEfSe) analysis showed that HFG 0.3 and HFG1 substantially increased the enrichment of beneficial microbiota (e.g., lactic acid bacteria, Cetobacterium, and Fusobacterial) and decreased the enrichment of harmful microbiota (e.g., Proteobacteria, Acinetobacter, and Pseudomonas) compared to HF. These results suggested that guar gum can mitigate high-fat diet-induced liver damage in fish.

ABSTRACT: Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (Ca) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) influence the gene expression of intestinal P and Ca transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)2D3 administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and Ca transporters. The findings demonstrated that broilers (1–21 days old) fed a 1,25(OH)2D3-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and Ca levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), Ca transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)2D3 was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)2D3, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9–14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9–17 days old) treated with the ERK inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9–17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)2D3 (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and Ca absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)2D3 on the absorption of P and Ca in broilers.

Background: Because adverse reactions or drug resistance are often found after current chemotherapies for metastatic colorectal cancer (mCRC), new treatments are still in demand. Shenqi Sanjie Granules (SSG), an antitumor compound preparation of traditional Chinese medicine, has been recognized for its ability in clinical practice of oncotherapy. Nevertheless, the precise effects of SSG in colorectal cancer (CRC) and underlying mechanisms through which SSG inhibits CRC remain uncertain. The current study aimed to evaluate the anti-CRC activity of the Chinese herbal compound preparation SSG and investigate the underlying mechanisms of action. Materials and methods: Initially, nine distinct cancer cell lines, including five CRC cell lines, one breast cancer cell line, two lung adenocarcinoma cell lines and one cervical cancer cell line, were used to evaluate the antitumor activity of SSG, and the mouse CRC cell line CT26 were used for further research. In vitro experiments utilizing diverse assays were conducted to assess the inhibitory effects of the SSG on CT26. Furthermore, subcutaneous syngeneic mouse model and AOM (azoxymethane)/DSS (dextran sodium sulfate) induced in-situ colitis-related mouse CRC model were used to evaluate the antitumor potential and biotoxicity of SSG in vivo. To elucidate the underlying molecular mechanisms, transcriptome sequencing and network pharmacology analysis were performed. Meanwhile, verification is carried out with quantitative real-time PCR (qRT-PCR) and flow cytometry (FCM) analysis. Results: Our in vitro inhibition study showed that SSG could effectively inhibit CRC cell line CT26 growth and metastasis, and induce cell death. Neither of apoptosis inhibitor, necroptosis inhibitor, ferroptosis inhibitor, but the combination of the three diminished SSG-induced cell death, suggesting that multiple cell death pathways were involved. Both the syngeneic CRC model and the in-situ CRC model indicated SSG inhibited CRC in vivo with few toxic side effects. Further mechanistic study suggested SSG treatment activated the ferroptosis pathway, particularly mediated by Hmox1, which was upregulated scores of times. Network pharmacology analysis indicated that the active ingredients of SSG, including Quercetin, Luteolin and Kaempferol were potential components directly upregulated Hmox1 expression. Conclusions: Collectively, our findings indicate that the administration of SSG has the potential to inhibit CRC both in vitro and in vivo. The mechanism by which this compound preparation exerts its action is, at least partly, the induction of ferroptosis through upregulating Hmox-1 by its three active ingredients Quercetin, Luteolin and Kaempferol.

Environmental DNA (eDNA) technology, as an alternative to traditional gillnet surveys, has attracted widespread attention. However, comparisons between eDNA and traditional methods regarding biodiversity and community structure have not yet been fully elucidated. This study compared the ability of eDNA and gillnets for fish monitoring in a large deep reservoir (Qiandao Lake) in East China. The results showed that eDNA exhibited higher taxonomic resolution and detection rates, and significantly larger species diversity and richness indices compared with traditional gillnetting methods. Using abundance and biomass datasets from gillnets revealed significant differences in fish community composition between gillnetting and eDNA survey methods. Gillnet abundance was dominated by small-sized fish species, while gillnet biomass was dominated by larger-sized ones, and the prevailing species detected in eDNA reads included the dominant species from gillnet abundance and biomass, as well as a medium-sized invasive alien fish (Lepomis macrochirus). Non-metric multidimensional scaling (NMDS) showed that the spatial distribution in abundance of fish species sampled by gillnetting was more dispersed than that using eDNA. The explanatory power with the gillnet abundance and biomass together as predictor variables of the eDNA reads increased moderately compared with taking them separately, and the fitting degree of quadratic functions was also improved somewhat compared to linear equations when using biomass to predict eDNA reads. Furthermore, the key environmental factors affecting fish communities differed between the two methods. Current research indicates that eDNA has advantages over gillnets in detecting fish species diversity, and it is recommended to combine it with traditional sampling methods. Under natural aquatic ecosystem conditions, the eDNA reads may comprehensively reflect the biomass and abundance information obtained through gillnetting, but their relationship is complex and requires further research. This study will provide guidance for biodiversity monitoring.

Rationale and objectives: This study aims to evaluate the effectiveness of integrating clinical data and quantitative CT parameters with machine learning techniques in forecasting the short-term outcomes of severe COVID-19 in elderly patients. Materials and methods: In this retrospective study, we analyzed the clinical profiles and chest quantitative CT parameters of 239 elderly patients with severe COVID-19 admitted for treatment. The cohort included 61 deceased patients (death group) and 178 who recovered and were discharged (survival group). The participants were randomly assigned into a training group (n = 167) and a validation group (n = 72). Quantitative CT parameters were measured using the 3D-Slicer software. Univariate and multivariate logistic regression analyses identified independent risk factors for mortality. Predictive models were developed employing four machine learning algorithms: Logistic Regression (LR), Random Forest (RF), Decision Tree (DT), and Support Vector Machine (SVM). Results: Both univariate and multivariate logistic regression analyses revealed age, hypersensitive C-reactive protein (hs-CRP), and solid organ volume percentage (SOV%) as independent predictors of mortality. The Area Under the Curve (AUC) values for the LR, RF, DT, and SVM models in the training group were 0.795, 0.726, 0.854, and 0.589, respectively; for the validation group, they were 0.817, 0.634, 0.869, and 0.754, respectively. The DT algorithm outperformed other models in both the training and validation groups, emerging as the most effective predictive model in this study. Conclusion: The combination of clinical data and quantitative CT parameters with machine learning approaches is highly valuable in predicting the short-term prognosis of severe COVID-19 in the elderly. Among the various models tested, the Decision Tree algorithm-based model proved to be the most accurate and reliable in this context.

The Above-Ground Carbon (AGC) is an important indicator reflecting the carbon sink function of forest ecosystems. The area of coniferous forests in China accounts for about 50 % of the national forest area. Accurately estimating the AGC of coniferous forests plays an important role in evaluating forest carbon sink function. This study takes coniferous forests in Chun’an, Zhejiang Province as an example, using Landsat 8 OLI as the remote sensing data source, and innovatively proposes a multi-scale Geographically Weighted Regression model (MGWR) combined with Co-Kriging (COK), namely MGWR-COK and Ordinary Kriging (OK), namely MGWR-OK, for AGC estimation. This method first processes Landsat8 OLI remote sensing data, extracts and screens variables, and then constructs an MGWR model with AGC survey samples to estimate AGC and calculate residuals; Afterwards, two models, COK and OK, were used to spatially estimate the residuals; Finally, the AGC estimation results are overlaid with the residual estimation results to obtain the spatial distribution of AGC in coniferous forests. The study indicates that: (1) The selected remote sensing feature variables such as Optimized Soil-Adjusted Vegetation Index (OSAVI), Normalized Difference Vegetation Index (NDVI), Entropy (B3_ent_1 and B2_ent_2), Correlation (B4_corr and B5_corr_2) of texture information, B754 with band combination and elevation have a significant impact on AGC estimation. (2) The AGC accuracy R2 estimated by MGWR-OK and MGWR-COK are 0.837 and 0.857, respectively, which are 6 % and 8 % higher than the MGWR model, and the root mean square error is also reduced by 10 % and 12 %, respectively. This indicates that the combination of MGWR and Kriging interpolation can effectively reduce its spatial estimation error. (3) The range of AGC values estimated by the MGWR-COK model is 0.189–62.591 Mg ∙ hm−2, with a mean of 28.795 Mg ∙ hm−2. The spatial distribution shows a characteristic of high in the southeast and low in the northwest, which is consistent with the actual situation in the study area.

Background: Korean red ginseng extract (KRGE) (Family: Araliaceae) is one of the most widely used traditional herbs in Asia. Multiple studies have shown that KRGE has anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. Methods: Sprague-Dawley rats were divided into five groups for PTU-induced hypothyroidism and six groups for LT4-induced hyperthyroidism. At the experiment's conclusion, rats were sacrificed, and blood, thyroid gland, and liver samples were collected. Body weight was recorded weekly, and serum hormone levels were assessed using enzyme-linked immunoassay. Thyroid gland and liver tissues were stained with hematoxylin and eosin. KRGE was prepared in 0.5% CMC and stored at 4 °C before administration. Results: In the LT4-induced hyperthyroidism model, KRGE prevented decreases in body weight, thyroid gland weight, liver weight, serum glucose, and thyroid hormone levels compared to the PTU group. It also reduced increases in T3, T4, and serum aspartate aminotransferase levels after LT4 treatment. Additionally, KRGE improved thyroid gland and liver histopathology, effects not observed in the PTU-induced hypothyroidism model. Conclusion: All things considered, our research points to KRGE's potential protective role in rat hyperthyroidism caused by LT4 by lowering thyroid hormone production.

Microorganisms are closely related to human health, and changes in the microbiome can lead to the occurrence of diseases. With advances in sequencing technology and research, it has been discovered that intratumoral microbiota exists in various cancer tissues and differs in various cancers. Microorganism can colonize tumor tissues through intestine of damaged mucosal barrier, proximity to normal tissues and bloodstream circulation. Increasing evidence suggests that intratumoral microbiota promotes tumor progression by increasing genomic instability, affecting host immune systems, promoting tumor migration, and regulating tumor signaling pathways. This review article summarizes the latest progress in intratumoral microbiome research, including the development history of intratumoral microbiota, their composition and sources within tumors, their distribution in various cancer tissues, as well as their role in cancer development. Furthermore, the application of intratumoral microbiota in clinical settings is emphasized and we innovatively summarize the clinical trials involving microbial applications for cancer diagnosis and treatment across different countries.

Benzene is a common environmental pollutant and significant health hazard. Low-dose benzene exposure is common in most industrial settings, and some workers exhibit hematotoxicity characterized by impaired hematopoietic function. Consequently, understanding the early hematopoietic damage and biomarkers associated with low-dose benzene exposure is of critical importance for health risk assessment. Using data from a 5-year prospective cohort study on benzene exposure and the National Center for Biotechnology Information's Gene Expression Omnibus database, we detected significant downregulation of the ubiquitin-conjugating enzyme UBE2L3 (E2) in benzene-exposed subjects compared to control subjects. Liquid chromatography tandem mass spectrometry and co-immunoprecipitation experiments illustrated the binding interaction between UBE2L3 and the ubiquitin-protein ligase ZNF598 (E3). We applied deep learning algorithms to predict candidate interacting proteins and then conducted validation via co-immunoprecipitation experiments, which showed that ZNF598 engages in binding with the autophagy protein LAMP-2. Subsequent overexpression and knockdown of UBE2L3 coupled with immunofluorescence experiments and transmission electron microscopy revealed that UBE2L3 disrupts the ubiquitination-degradation of LAMP-2 by ZNF598, reduces GPX4 expression levels, and activates an autophagy-dependent ferroptosis pathway. It also leads to increased lipid peroxidation, thereby promoting ferroptosis and contributing to the hematotoxicity induced by benzene. In summary, our results suggest that UBE2L3 may be involved in early hematopoietic damage by modulating the autophagy-dependent ferroptosis signaling pathway in benzene-induced hematotoxicity.

Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder that typically presents in infancy as hypoplastic anemia and developmental abnormalities in approximately 50% of cases. DBAS is caused by haploinsufficiency in one of 24 ribosomal protein genes, with RPS19 mutations accounting for 25% of cases. We generated iPSC lines from two patients with different heterozygous RPS19 mutations (c.191T > C and c.184C > T) and isogenic lines in which the mutations were corrected by Cas9-mediated homology directed repair.

Wastewater treatment plants (WWTPs) are important and energy-intensive municipal infrastructures. High energy consumption and relatively low operating performance are major challenges from the perspective of carbon neutrality. However, water–energy nexus analysis and models for WWTPs have rarely been reported to date. In this study, a cloud-model-based energy consumption analysis (CMECA) of a WWTP was conducted to explore the relationship between influent and energy consumption by clustering its influent’s parameters. The principal component analysis (PCA) and K-means clustering were applied to classify the influent condition using water quality and volume data. The energy consumption of the WWTP is divided into five standard evaluation levels, and its cloud digital characteristics (CDCs) were extracted according to bilateral constraints and golden ratio methods. Our results showed that the energy consumption distribution gradually dispersed and deviated from the Gaussian distribution with decreased water concentration and quantity. The days with high energy efficiency were extracted via the clustering method from the influent category of excessive energy consumption, represented by a compact-type energy consumption distribution curve to identify the influent conditions that affect the steady distribution of energy consumption. The local WWTP has high energy consumption with 0.3613 kW·h·m−3 despite low influent concentration and volumes, across four consumption levels from low (I) to relatively high (IV), showing an unsatisfactory operation and management level. The average oxygenation capacity, internal reflux ratio, and external reflux ratio during high energy efficiency days recognized by further clustering were obtained (0.2924–0.3703 kg O2·m−3, 1.9576–2.4787, and 0.6603–0.8361, respectively), which could be used as a guide for the days with low energy efficiency. Consequently, this study offers a water–energy nexus analysis method to identify influent conditions with operational management anomalies and can be used as an empirical reference for the optimized operation of WWTPs.

Irradiation defects are known to impede the dislocation motion in irradiated reactor pressure vessel (RPV) steels. However, consistent experimental studies of the respective irradiation defects and relevant theoretical studies of the interaction mechanism and hardening model are still lacking. In this study, the microstructure and irradiation-induced hardening of RPV steels are investigated using transmission electron microscopy (TEM)/energy-dispersive X-ray spectrometry (EDS) and molecular dynamics (MD) simulations. In A508-Ⅲ steel, 9R, twinned fcc, and other typical Cu-rich cluster structures are observed using TEM after the irradiation experiment. Based on the experimental results, MD simulations are performed to study the interactions between the dislocations and Cu clusters or voids. A mechanism diagram of the interaction mechanism coupling the effects of temperature and defect size is shown for both the Cu clusters and voids. A relevant hardening model is proposed based on the MD data, which is further discussed in relation to the macroscopic mechanical properties. Furthermore, the irradiation-induced hardening of the RPV steel is successfully predicted, which further demonstrates the reliability of the proposed unified hardening model.

Background: Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs). Methods: Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting. Results: The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate. Conclusion: The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes. The translational potential of this article: Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.

Induced pluripotent stem cells (iPSCs) harboring patient derived SAMD9 mutation offer a unique platform to study the multi-organ involvement observed in this rare disease, referred to as myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome. The pluripotent nature of iPSCs allows in vitro differentiation into various somatic cell types representing multiple organ systems affected in SAMD9-mutated patients. Hence, in this paper, we present a CRISPR/Cas9-engineered iPSC model carrying SAMD9 c.2948T>G, p.I983S mutation previously reported in two patients with severe MIRAGE syndrome.

This paper is concerned with a three-component quasilinear chemotaxis system with nonlinear diffusion and singular sensitivity for alopecia areata ut=∇D1(u)∇u−χ1∇uw∇w+w−μ1uγ1,(x,t)∈Ω×(0,∞),vt=∇D2(v)∇v−χ2∇vw∇w+w+ruv−μ2vγ2,(x,t)∈Ω×(0,∞),wt=Δw+u+v−w,(x,t)∈Ω×(0,∞),∂u∂ν=∂v∂ν=∂w∂ν=0,(x,t)∈∂Ω×(0,∞),u(x,0)=u0(x),v(x,0)=v0(x),w(x,0)=w0(x),x∈Ω,associated with homogeneous Neumann boundary conditions in a convex smooth bounded domain Ω⊂R2. For i=1,2, the parameters χi,μi,r are positive and γi≥2. The nonlinear diffusion functions Di(s)∈C2 satisfy Di(s)⩾(s+1)αi for all s≥0. We delve into analyzing the global existence and boundedness of classical solutions for the aforementioned system under specific conditions. Additionally, in the scenario where γi=2, we develop a Lyapunov functional and scrutinize its temporal evolution to ascertain the asymptotic stability of the coexistence state.

X-linked adrenoleukodystrophy (X-ALD) caused by ATP-binding cassette subfamily D member 1 (ABCD1) gene defects is the most common inherited peroxisomal disorder.The female cerebello-brainstem dominant type in which cerebellum and brainstem are mainly involved is very rare. We report a 40-year-old female who was diagnosed as the rare disorder with magnetic resonance imaging (MRI) and genetic analysis mainly. Her initial symptoms were progressive slurred speech and writing disturbance. Her brain MRI showed obvious atrophy of brainstem and cerebellum. She did not have adrenal insufficiency. Genetic analysis showed a heterozygous missense mutation in exon 4 of the coding region of ABCD1 (c.1252C > T, p.Arg418Trp).This is the first report of this particular mutation being associated with the cerebello-brainstem dominant phenotype of X-ALD, as well as the first description of this X-ALD variant in a (heterozygous) female patient.X-ALD should be considered in young and middle-aged patients with slow-progressing ataxia and dysarthria.

Background: Previous studies showed that MSCs could mitigate damage in the pancreas during acute pancreatitis (AP). However, acute mortality associated with AP was more often a result of persistent failure of remote organs, rather than local damage, especially in severe acute pancreatitis (SAP), and the effect of MSCs may vary depending on their origin. Methods: An SAP model was induced in 8-week C57BL/6 J male mice by retrograde injection of 5 % sodium taurocholate solution through the bile duct. SAP mice were divided into the SAP group, UC-MSCs group, and BMSCs group, which were treated with saline, 1 × 106 UC-MSCs, and 1 × 106 BMSCs respectively, through the tail vein. After treatment, serum markers, inflammation, and morphology were assessed in the pancreas, kidneys, lungs, and hearts. Results: MSCs infusion ameliorated the systemic inflammatory response in SAP mice. In the MSCs-treated SAP mice, local tissue injury and inflammation response in the pancreas were alleviated. But more importantly, the renal and lung injury were all significantly and drastically mitigated, and the levels of pro-inflammatory factors such as IL-6, MCP-1, IL-1β, and TNF-α in the kidney, lung and heart were sharply decreased. In terms of origin, UC-MSCs exhibited superior efficacy compared with BMSCs. Furthermore, compared to the normal control mice, UC-MSCs showed an earlier appearance, higher distribution densities, and longer duration of presence in the injured tissue. Conclusions: This study provides compelling evidence supporting the therapeutic potential of MSCs in SAP treatment and particularly their ability to mitigate multi-organ failure. Our results also suggested that UC-MSCs may offer greater advantages over BMSCs in SAP therapy.

Sustainable development of oases enhances the capability of ecosystems to reverse land degradation in arid regions. However, it is unclear to what extent oasisation leads to ecological quality (EQ) degradation in the peripheral environment. To comprehensively evaluate the ecological effects of oasisation, this study developed a remote sensing ecological quality index to characterise spatiotemporal patterns and driving mechanisms of EQ in different oasis-type areas. Results show that the oasis area has increased by 37.4 % in the past 22 years. The EQ of the core area was stable, but EQ declined in newly developed urban areas. The effect range of the oasis on the peripheral regions EQ is 12 km, and the expansion of the oasis is improving the EQ of peripheral regions. The driving factors of EQ varied widely among different oasis areas. The vegetation index showed significant explanatory power (q-mean is 0.45) in each oasis area. Human activities and soil moisture showed the most significant explanatory power (0.76) in the core area, but weak power is observed in the changed and peripheral areas. Climate factors have the strongest influence on the changed and peripheral areas. The findings provide an in-depth understanding of the spatial heterogeneity of EQ and could be implemented in Oasis urban planning and sand prevention belt construction.

Breast cancer is one of the most prevalent malignancies affecting women worldwide, underscoring the urgent need for more effective and specific treatments. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy to develop new lead compounds by selectively targeting oncoproteins for degradation. In this study, we designed, synthesized and evaluated a CRBN-based PROTAC, L055, which targets CDK9. Our findings demonstrate that L055 effectively inhibits the proliferation, induces cell cycle arrest, and decreases the survival of ERα-positive breast cancer cells in vitro. L055 specifically binds to CDK9, facilitating its degradation via the CRBN-dependent proteasomal pathway. Additionally, L055 suppressed the growth of organoids and tumors derived from T47D and MCF7 cells in nude mice. Thus, L055 represents a potential novel therapeutic agent for ERα-positive breast cancer and potentially other malignancies.

Background: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. Methods: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE−/− mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE−/− mice. Results: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE−/− mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE−/− mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. Conclusions: Upon HCD feeding in ApoE−/− mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.

Objective and rationale: Hospital-acquired falls are common and serious adverse events in medical institutions, with high incidence and injury rates. Studying the occurrence patterns of hospital-acquired falls is important for preventing falls in hospitalized patients. However, the effect of meteorological factors on hospital-acquired falls has not been elucidated. Therefore, this study explored the impact of meteorological parameters on hospital-acquired falls in Chongqing, China, and provided new ideas for the clinical prevention of falls in patients. Methods: Correlation analysis and distributed lag nonlinear models were employed to analyze the relationship between 3890 cases of hospital-acquired falls and meteorological data in 13 hospitals in 11 districts and counties in Chongqing from January 2013 to April 2023. Results: The number of hospital-acquired falls demonstrated a nonlinear correlation with the daily average relative humidity and negatively correlated with sunshine duration; however, temperature, air pressure, and wind speed were not correlated. Compared to the reference humidity (87 %), the immediate effects of daily average relative humidity (65–68 % and 90–97 %) increased the risk of hospital-acquired falls on the same day (relative risk [RR]:1.027–1.243). When the daily average relative humidity was 95–97 %, lags of 0–1 d and 8–12 d had greater effects on falls (RR:1.073–1.243). The daily average relative humidities of 62–74 % and 91–97 % were statistically significant at cumulative relative risk (CRR)of 4, 7, 10, and 14 d with a cumulative lag (CRR: 1.111–4.277). On sex and age stratification, the lag and cumulative effects of relative humidity more significantly impacted falls in women and patients aged ≥65 years. Conclusion: Daily average relative humidity had a nonlinear correlation and lag effect on hospital-acquired falls; therefore, medical institutions should pay attention to the effect of relative humidity on hospital-acquired falls in patients, especially old and female patients.

Summary: Inhibition of nucleic acid targets is mediated by Argonaute (Ago) proteins guided by RNA or DNA. Although the mechanisms underpinning the functions of eukaryotic and “long” prokaryotic Ago proteins (pAgos) are well understood, those for short pAgos remain enigmatic. Here, we determine two cryoelectron microscopy structures of short pAgos in association with the NADase-domain-containing protein Sir2-APAZ from Geobacter sulfurreducens (GsSir2/Ago): the guide RNA-target DNA-loaded GsSir2/Ago quaternary complex (2.58 Å) and the dimer of the quaternary complex (2.93Å). These structures show that the nucleic acid binding causes profound conformational changes that result in disorder or partial dissociation of the Sir2 domain, suggesting that it adopts a NADase-active conformation. Subsequently, two RNA-/DNA-loaded GsSir2/Ago complexes form a dimer through their MID domains, further enhancing NADase activity through synergistic effects. The findings provide a structural basis for short-pAgo-mediated defense against invading nucleic acids.

Summary: Current studies in early cancer detection based on liquid biopsy data often rely on off-the-shelf models and face challenges with heterogeneous data, as well as manually designed data preprocessing pipelines with different parameter settings. To address those challenges, we present AutoCancer, an automated, multimodal, and interpretable transformer-based framework. This framework integrates feature selection, neural architecture search, and hyperparameter optimization into a unified optimization problem with Bayesian optimization. Comprehensive experiments demonstrate that AutoCancer achieves accurate performance in specific cancer types and pan-cancer analysis, outperforming existing methods across three cohorts. We further demonstrated the interpretability of AutoCancer by identifying key gene mutations associated with non-small cell lung cancer to pinpoint crucial factors at different stages and subtypes. The robustness of AutoCancer, coupled with its strong interpretability, underscores its potential for clinical applications in early cancer detection.

To study the bond performance of ultra-high performance concrete (UHPC) and steel bar after freeze-thaw cycles (FTCs), the eccentric pull-out test of 10 groups of reinforced UHPC bond specimens, the compressive test of 24 cube specimens and the splitting tensile test of 24 cube specimens were carried out. The degradation of UHPC mechanical properties and bond performance of UHPC and steel bar after FTCs were studied. The influence of UHPC strength, cover thickness, and bond length on bond strength after FTCs was analyzed. The relationship between mechanical and bond properties is established by using compressive strength and average bond strength as indexes. A formula for calculating average bond strength of UHPC after FTCs was developed. The results show that the elastic modulus loss, compressive strength loss, and splitting tensile strength loss after FTCs increase slowly at first and then rapidly. With the increase of FTCs, the relationship between dynamic elastic modulus and compressive strength, compressive strength, and splitting tensile strength showed strong linear characteristics. UHPC strength is an important factor affecting the average bond strength after FTCs, followed by the cover thickness. After 600 freeze-thaw cycles, the failure mode of the UHPC bond specimen changed. The compressive strength and the average bond strength show a strong linear relationship in the process of 900 FTCs. The average bond strength between UHPC and steel bar decreased by 13.76 ∼ 17.23 % after 900 freeze-thaw cycles.

Background: Few studies have examined the association between green space and life expectancy, and only one study has looked at that data for small areas in the United States. These studies have found a positive association between green space and life expectancy. This study investigates the association between green space and small-area life expectancy in Chicago, a city in the United States with distinct environmental and socioeconomic characteristics and the largest U.S. life expectancy gap between neighborhoods. Methods: We conducted a spatial analysis using the green space metrics of normalized difference vegetation index (NDVI), park access, and tree canopy. Additionally, we included 18 lifestyle, environmental, and social covariates. Diagnostic analytics included multiple linear regression, Moran I test for spatial dependence, and principal component analysis with CAR Gaussian model. We performed a simulation to predict life expectancy gain if NDVI was brought to median levels. Results: Our study revealed that after adjusting for covariates and spatial dependence (Moran I test p = 0.012) with a CAR Gaussian model, NDVI (credible interval = 0.292-0.894) demonstrated significance at a 5 % level, while tree canopy (credible interval = -0.404-0.109) and park access (credible interval = -0.258-0.161) did not. Excluding non-significant variables (tree canopy and park access) from the CAR Gaussian model, the median effect of NDVI on life expectancy was 0.491 (95 % credible interval: 0.24–0.718). Projecting this effect to tracts below the median NDVI predicted a gain of 476,000 years of life expectancy for Chicago residents. Conclusion: This study provides evidence that green space and LE are positively correlated, suggesting the potential to increase green space to address current LE gaps. Future research should investigate the mechanisms by which green space correlates to lifespan.

For wearable smart textile sensors, stability, accuracy and multi-functionality are key objectives. Achieving the optimal application requires delicately balancing the crucial physical properties of strain sensors, presenting a key technological challenge. This study addresses these challenges by presenting several properties and potential applications of a triple hierarchic polymeric knitted fabric. The fabric incorporates an internal conductive network constructed with silver nanowires (AgNWs) and polydopamine (PDA) coating on its outer surface. This innovative textile successfully strikes a balance between strain sensing and electromagnetic interference shielding while concurrently exhibiting biocompatibility and antimicrobial properties. Significantly, acknowledging the susceptibility of measurements from polymer-based strain sensor materials to time drift, we introduce both a modeling approach and a novel calibration technique. This advancement facilitates the generation of stable cyclic sensing signals, even under substantial deformations of up to 80 % at a high stretching speed. Importantly, it provides a practical solution for addressing signal drift observed in flexible sensors when utilized in environments characterized by long-term and large deformations.

Background: Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure. Methods: Male mice were subjected to TP at doses of 15, 30, and 60 μg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood–testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining. Results: TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells. Conclusion: This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1’s tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

To assess the energy saving and emission reduction effects of recycling technology, the quantitative analysis of energy consumption and carbon emission of recycled asphalt pavement is conducted of asphalt mixture production, transportation, paving and compaction. Firstly, the calculation model for energy consumption and carbon emissions of recycled asphalt pavement is established during the construction stage. In addition, the energy consumption and carbon emission of four recycling technologies, including the HCPR, HIR, CCPR and CIR, were compared. Finally, the FCE method is used to evaluate the actual effect of energy saving and emission reduction from the perspectives of the ecological benefit and the economic benefit. The research results indicate the most serious stage of energy consumption is the new material production stage, and the most serious stage of carbon emission is the asphalt mixture production stage of recycled asphalt pavement. Taking the HCPR technology as an example are calculated in detail. The energy consumption of the HCPR technology in the four stages of the construction stage was 17.59 MJ, 344.45 MJ, 228.51 MJ and 25.85 MJ, respectively, and the emissions in the four stages of the construction stage were 1307.89 g, 5971.28 g, 19,251.24 g and 1949.82 g, respectively. For different recycling technologies in the construction stage, the energy-saving ratios of HCPR, HIR and CCPR are 13.62%, 9.61% and 19.24% respectively when compared with the typical scheme, which have a certain energy-saving effect. However, the energy consumption of CIR reduced by 43.63%, which the energy saving effect is most significant. Moreover, the emission reduction ratios of HCPR, HIR and CCPR are 2.3%, 9.23% and 1.01% respectively when compared with the typical scheme, the emission of CIR reduced by 30.76%, so the emission reduction effect of CIR is most significant. Furthermore, the comprehensive evaluation score of the CIR technology with the most significant energy saving and emission reduction effect is 0.8021 in terms of ' ecological benefits ' and 0.8074 in terms of ' economic benefits '. In summary, it is recommended to adopt CIR technology in the engineering project, which can achieve the most significant energy-saving and emission reduction effects.

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg2+ (from nMgO) and Ca2+ (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN in vitro. Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects in vivo. Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.

Integrating microchannel flow boiling heat transfer with nanofluids is an effective method for cooling electronic devices. However, traditional methods have significant limitations in achieving facile synthesis of nanofluids with desirable properties. In this study, we propose a straightforward synthesis strategy using microfluidic reactors, which enables continuous and high-throughout synthesis of Al2O3 nanofluids with high purity and long-term stability. These nanofluids were found to enhance boiling heat transfer performance by delaying bubbles coalescence, increasing surface nucleation sites, improving the nucleation rate, and enhancing wettability by observation of the bubble behavior. Specifically, the critical heat flux (CHF) and corresponding heat transfer coefficient (HTC) are increased by a maximum of 32 % and 26 %, respectively, with negligible change in pressure drop. Moreover, the heat transfer performance deteriorates with increasing concentration of alumina nanofluids. These findings not only provide guidance of microchannel flow boiling with nanofluids, but also present valuable insights for the application of nanofluids in two-phase cooling systems for electronic devices.

Liposomes have been widely studied as drug carriers for clinical application, and the key issue is how to achieve effective delivery through targeting strategies. Even though certain cell-level targeting or EPR effect designs have been developed, reaching sufficient drug concentration in intracellular regions remains a challenge due to the singularity of functionality. Herein, benefiting from the unique features of tumor from tissue to cell, a dual-thermosensitive and dual-targeting liposome (DTSL) was creatively fabricated through fine microstructure tailoring, which holds intelligent both tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties. At the micro level, DTSL can actively capture tumor cells and accompany the enhanced HF effect stimulated by self-constriction, which achieves a synergistic promotion effect targeting tissues to cells. As a result, this first active-then passive targeting process makes drug delivery more accurate and effective, and after dynamic targeting into cells, the nucleus of DTSL undergoes further thermally responsive contraction, fully releasing internal drugs. In vivo experiments showed that liposomes with dual targeting and dual thermosensitive features almost completely inhibited tumor growth. Summarized, these results provide a reference for a rational design and microstructural tailoring of the liposomal co-delivery system of drugs, suggesting that active-to-passive dual-targeting DTSL can function as a new strategy for cancer treatment.

Direct shear tests were conducted on sandstone specimens under different constant normal stresses to study the coalescence of cracks between non-persistent flaws and the shear sliding characteristics of the shear-formed fault. Digital image correlation and acoustic emission (AE) techniques were used to monitor the evolution of shear bands at the rock bridge area and microcracking behaviors. The experimental results revealed that the shear stresses corresponding to the peak and sub-peak in the stress-displacement curve are significantly affected by the normal stress. Strain localization bands emerged at both the tip of joints and the rock bridge, and their extension and interaction near the peak stress caused a surge in the AE hit rate and a significant decrease in the AE b value. Short and curvilinear strain bands were detected at low normal stress, while high normal stress generally led to more microcracking events and longer coplanar cracks at the rock bridge area. Furthermore, an increase in normal stress resulted in a higher AE count rate and more energetic AE events during friction sliding along the shear-formed fault. It was observed that the elastic energy released during the crack coalescence at the pre-peak stage was much greater than that released during friction sliding at the post-peak stage. More than 75% of AE events were located in the low-frequency band (0–100 kHz), and this proportion continued to rise with increasing normal stress. Moreover, more AE events of low AF value and high RA value were observed in specimens subjected to high normal stress, indicating that greater normal stress led to more microcracks of shear nature.

The effects of ScCO2 on pore structure should be investigated in order to properly apply supercritical carbon dioxide (ScCO2) fracturing on tight sandstone. ScCO2 treatment was applied to three sets of tight sandstone samples. The pore structure was characterized using a combination of high-pressure mercury intrusion porosimetry and nuclear magnetic resonance. Furthermore, the pore size distribution’s multi-fractal dimensions were estimated. After SCCO2 treatment, the number of transitional pores decreased significantly, while the number of mesopores and macropores increased. At all scales, the fractal dimension characteristics indicate that pore structure gets more complicated and heterogeneous. Furthermore, due to their larger contact area, large pores have a higher fractal dimension than small pores. The accumulative pore volume of the calcite-rich group increases and a decreasing trend occurs for the calcite-rare group. The content of calcite sharply decreased while clay, feldspar, and plagioclase content have a slight drop after ScCO2 treatment, which affects the alternation of pore structure. Thus, the accumulative porosity volume and pore connectivity do not always increase after ScCO2 exposure because re-precipitation and fine migration can potentially clog pores and channels.

Background: The immune-inflammatory pathway plays a critical role in myocardial infarction development. However, few studies have systematically explored immune-related genes in relation to myocardial infarction prognosis using bioinformatic analysis. Our study aims to identify differentially expressed immune-related genes(DEIRGs) in ST-segment elevation myocardial infarction (STEMI) patients and investigate their association with clinical outcomes. Materials and methods: We conducted a systematic review of Gene Expression Omnibus datasets, selecting GSE49925, GSE60993, and GSE61144 for analysis. DEIRGs were identified using GEO2R and overlapped across the chosen datasets. Functional enrichment analysis elucidated the DEIRGs' biological functions and pathways. We established an optimal prognostic prediction model using LASSO penalized Cox proportional hazards regression. The signature's clinical utility was evaluated through survival analysis, ROC curve assessment, and decision curve analysis. Additionally, we constructed a prognostic nomogram for survival rate prediction. External validation was performed using our own plasma samples. Results: The resulting prognostic signature integrated two dysregulated DEIRGs (S100A12 and IL2RB) and two clinical variables (serum creatinine level and Gensini score). This signature effectively stratified patients into low- and high-risk groups. Survival analysis, ROC curve analysis, and decision curve analysis demonstrated its robust predictive performance and clinical utility within the first two years post-disease onset. External validation confirmed significant outcome differences between risk groups. Conclusions: Our study establishes a prognostic signature that combines DEIRGs and clinical variables for STEMI patients. The signature exhibits promising predictive capabilities for patient stratification and survival risk assessment.

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P

Synergistic regional emission reduction (SRER) is an important part of the strategy to achieve carbon neutrality. In this paper, a system efficiency value-added model is proposed to measure the strength of SRER network relationships for 40,186 sets of city pairs and the SRER levels of 284 cities in China from 2011 to 2021. Subsequently, the evolution characteristics of the SRER network, the spatial and temporal characteristics of urban SRER levels, and the driving factors of the SRER network evolution are further analyzed. The results are as follows: SRER network is shifting from a fan-shaped network pattern of “three-region clustering and sporadic coverage” to a shuttle-shaped nested network pattern of “east-west linkage and multi-region support”. Time series analysis found that urban SRER level in China showed fluctuating growth characteristics during the study period. Spatial analysis reveals that the spatial autocorrelation of urban SRER level is decreasing, and the spatial distribution range is expanding towards the southwest. Emission reduction comparative advantages (CAER), green innovation division of labor (GIDL) and urban economic linkages (LCEL) are driver factors of SRER network evolution. This study proposes an evaluation method for the urban SRER level from network relationships perspective. Subsequently, network evolution characterization, spatial and temporal characterization, and driving factor analysis were conducted. The results of the study provide important theoretical guidance and inspiration for grasping the current status and enhancement paths of China's urban SRER level.

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.