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Non-contact remote sensing techniques, such as terrestrial laser scanning (TLS) and unmanned aerial vehicle (UAV) photogrammetry, have been globally applied for landslide monitoring in high and steep mountainous areas. These techniques acquire terrain data and enable ground deformation monitoring. However, practical application of these technologies still faces many difficulties due to complex terrain, limited access and dense vegetation. For instance, monitoring high and steep slopes can obstruct the TLS sightline, and the accuracy of the UAV model may be compromised by absence of ground control points (GCPs). This paper proposes a TLS- and UAV-based method for monitoring landslide deformation in high mountain valleys using traditional real-time kinematics (RTK)-based control points (RCPs), low-precision TLS-based control points (TCPs) and assumed control points (ACPs) to achieve high-precision surface deformation analysis under obstructed vision and impassable conditions. The effects of GCP accuracy, GCP quantity and automatic tie point (ATP) quantity on the accuracy of UAV modeling and surface deformation analysis were comprehensively analyzed. The results show that, the proposed method allows for the monitoring accuracy of landslides to exceed the accuracy of the GCPs themselves by adding additional low-accuracy GCPs. The proposed method was implemented for monitoring the Xinhua landslide in Baoxing County, China, and was validated against data from multiple sources.

In the context of the San Gavain hydroelectric power station diversion tunnel project in Peru, this paper studies the surrounding rock instability mechanism using a combination of numerical simulation methods and model test and presents the enclosing rock instability criterion based on the catastrophe model. The study demonstrates that the distribution of stress and displacement during tunnel excavation is more affected by the presence of laminated joints; the thinner the layer thickness, the more prominent the influence of laminations, and the higher the deformation of the surrounding rock. With the increase in layer thickness, the resultant displacement shows the law of gradual decrease; when the layer thickness is greater than 16 cm, the rate of decrease gradually slows down, and the maximum displacement is 0.201 mm. The failure mode of the layered perimeter rock tunnel with a 45° inclination angle primarily shows up as tensile deformation at the left arch shoulder and shear slip deformation at the right arch foot under the combined action of blasting disturbance load and excavation. Based on the instability analysis of the fold catastrophe model and cups catastrophe model, the influence of bending deformation between layers of surrounding rock is generally greater than shear slip deformation. The instability criterion Δ＜0 exists in all working conditions, bending instability damage may occur in all cases. When the layer thickness is greater than 24 cm, the shear slip instability criterion is greater than zero for 0–2 ms, and the system is always in a stable state, and when the layer thickness is less than 24 cm, the system may be destabilized at 1.5 ms.

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer. Herein, a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell. The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation, self-renewal, migration, and invasion of lung cancer cell lines at low micromolar concentrations. The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays. In the H460R231Q OE cell-derived xenograft (CDX) model, 37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks (TGI = 54.38%), without obvious toxicities. A pharmacokinetic study revealed that 37 possessed tolerable properties (t1/2 = 1.93 ± 0.91 h, F = 97.2%) after intraperitoneal administration in rats. Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway. Moreover, analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the “Induced-fit” allosteric model in favor to the discovery of potent DOT1L candidates.

Objective: Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss. Methods: To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro. Results: CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68+ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163. Conclusion: Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.

The micromechanical response of a Zr-based bulk metallic glass (BMG) annealed in air below and above its glass transition temperature was studied. Nano-sized particles in different states at different annealing temperatures were found on the surface of the samples, which were identified by energy-dispersive spectroscopy (EDS) as being CuNi elemental composition. The surface microhardness and nanoindentation creep behavior of the BMGs after annealed exhibited interesting results, at low annealing temperatures, the microhardness of the samples showed softening accompanied by poor creep resistance, while at high annealing temperatures, the hardness of the samples shows hardening and creep resistance was enhanced. The consequences of such a temperature-dependent dichotomy were intricately linked to element segregation, which led to microstructural fluctuations. A competing mechanism between the hardening effect of zirconia at the surface and the softening effect of elemental segregation in the formation of microporous structures inside the samples is proposed to account for the divergent mechanical properties due to the annealing temperature. This work presents helpful insights into microstructural changes and micromechanical properties of BMGs during annealing, as well as an experimental support for structural and property modulation of BMGs.

In July 2021, a heavy rainstorm was sweeping across Henan Province, causing geological disasters such as floods, mudslides, and landslides, which seriously threatened the safety of human life and property. Precipitable water vapor (PWV) is related to the occurrence and scale of rainfall. Here, based on Global Navigation Satellite System (GNSS) observations, in-situ meteorological files (GMET), ephemeris products, ERA5 data, and weather station data, the relationship between PWV and rainstorm from July 1st to 30th was studied. The results show that GMET and ERA5 in July 2021 have high consistency in some stations, with a root mean square error (RMSE) for temperature below 1.6 °C, for pressure below 0.5 hPa, and for relative humidity below 9 %. During the week before the heavy rainstorm, the temperature dropped remarkably and the temperature difference decreased, while the relative humidity increased and the relative humidity difference decreased. Compared with ERA5 PWV, the RMSE of GNSS PWV retrieved using real-time ephemeris is 3.238 mm. Different from the normal rainfall, we found that the PWV variation during the Henan rainstorm experienced a unique “accumulation” period. We also observed a clear correlation between PWV and the rainstorm, both temporally and spatially. In addition, the PWV in the severely damaged area was 20 mm higher than the average value of the past decade. Ten days after the rainstorm, the surface of this area had subsided by 1.5–3 mm. Finally, we found that the topography of Henan, the low vortex, the north-biased subtropical high, and the double typhoons all played a role in the successful transport and deposition of water vapor.

Objective: To evaluate the diagnostic utility of fat (hydroxyapatite) density [DFat (HAP)] on dual-energy computed tomography (DECT) for identifying clinical diagnosed multiple myeloma without bone disease (MNBD) that is not visible on conventional CT scans. Material and Methods: In this age-gender-examination sites matched case control prospective study, Chest and/or abdominal images on Revolution CT of MNBDs and control subjects were consecutive enrolled in a 1:2 ratio from October 2022 to November 2023. Multiple myeloma was clinical diagnosed according to criteria of the International Myeloma Working Group. Regions of interest (ROIs) were drawn separately for all thoracolumbar vertebrae in the scanning range by two radiologists. Additionally, a radiologist specializing in musculoskeletal imaging supervised the process. DFat (HAP) was extracted from each ROI. The spine was divided into upper thoracic (UPT), middle and lower thoracic (MLT), thoracolumbar (TL), and middle and lower lumbar (MLL) vertebrae. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic performance of DFat (HAP) in diagnosing multiple myeloma, and the sensitivity, specificity, and accuracy under the optimal cut-off were determined by Youden index (sensitivity + specificity −1). Results: A total of 32 and MNBD patients and 64 control patients were included. The total number of ROIs outlined included MNBD group (n = 493) and control group (n = 986). For all vertebrae, DFat(HAP) got average performance in the diagnosis of MNBD (AUC = 0.733, p

After ischemic stroke (IS), secondary injury is intimately linked to endoplasmic reticulum (ER) stress and body-brain crosstalk. Nonetheless, the underlying mechanism systemic immune disorder mediated ER stress in human IS remains unknown. In this study, 32 candidate ER stress-related genes (ERSRGs) were identified by overlapping MSigDB ER stress pathway genes and DEGs. Three Key ERSRGs (ATF6, DDIT3 and ERP29) were identified using LASSO, random forest, and SVM-RFE. IS patients with different ERSRGs profile were clustered into two groups using consensus clustering and the difference between 2 group was further explored by GSVA. Through immune cell infiltration deconvolution analysis, and middle cerebral artery occlusion (MCAO) mouse scRNA analysis, we found that the expression of 3 key ERSRGs were closely related with peripheral macrophage cell ER stress in IS and this was further confirmed by RT-qPCR experiment. These ERS genes might be helpful to further accurately regulate the central nervous system and systemic immune response through ER stress and have potential application value in clinical practice in IS.

Summary: In this study, we obtained the whole genome sequence of GCRV-DY197 and investigated the localization, post-translational modifications, and host interactions of the 11 viral proteins encoded by GCRV-DY197 in grass carp ovary (GCO) cells. The whole genome sequence is 24,704 kb and contains 11 segments (S1–S11). Subcellular localization showed that the VP1, VP2, VP3, VP5, VP56, and VP35 proteins were localized in both cytoplasm and nucleus, whereas the NS79, VP4, VP41, VP6, and NS38 proteins were localized in the cytoplasm. The NS79 and NS38 proteins were phosphorylated, and the ubiquitination modification sites were identified in VP41 and NS38. An interaction network containing 9 viral proteins and 140 host proteins was also constructed. These results offer a theoretical basis for an in-depth understanding of the biochemical characteristics and pathogenic mechanism of GCRV-II.

The investigation of the blasting effects of the borehole considering decoupled eccentric charge is scarce and lacks thorough exploration. The coupled Smoothed Particle Hydrodynamics and Finite Element Method (SPH-FEM) is adopted to study the decoupled eccentric charge blasting effects. The effective stress distribution of rock around the borehole is analyzed and the damage evolution is studied quantitatively with introducing image recognition algorithm. Further, the effect of the decoupling coefficient on blasting effects is investigated. Results show that effective stress distribution presents obvious eccentric characteristics. At the bottom coupling point, the maximum effective stress is observed, and gradually reduces towards the top uncoupling point. The lower part of rock surrounding the borehole exhibits a higher damaged area ratio compared to the upper part for decoupled eccentric charge blasting. With the decoupling coefficient increases from 1.14 to 2.00, the effective stresses at monitoring points are all decreasing and the effective stress ratio first increases and then keeps relatively stable, with the decoupling coefficient of 1.6 as inflection point. As the decoupling coefficient increases to 1.6, the damage extent ratio reaches the peak. The greatest disparity in explosion energy between the coupled and uncoupled sides occurs at a decoupling coefficient of approximately 1.6.

Background: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. Methods: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. Results: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. Conclusion: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

Quantitative Real-time PCR (qRT-PCR) is one of the most widely used methods for gene quantification because it is extremely sensitive, can be highly sequence specific, and has high precision while being easily reproducible in samples. The stability of the reference genes used for data normalization is crucial for exact experimental results and conclusions. In this study, qRT-PCR was used to analyze the expression of eight candidate reference genes including β-actin (ACTB), α-tubulin (TUBA), Elongation factor-1-α (EF1A), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH1, GAPDH2), Hypoxanthine guanine phosphoribosyl transferase1 (HPRT), Ribosomal protein L7 (RPL7), and RNA polymerase II (RNA PoL Ⅱ) in largemouth bass. The expression and stability of above genes were evaluated among eight tissues with or without largemouth bass virus (LMBRaV) infection and assessed using BestKeeper, GeNorm, NormFinder statistical softwares and comparative Ct method, and then analyzed the comprehensive ranking by ReFinder. Our results showed that ACTB was identified as the most suitable genes of different tissues, while TUBA was ranked as the best reference gene in tissues infection with LMBRaV. To verify the screened reference genes, the expression pattern of IFN in spleen during LMBRaV infection was examined. This study provides useful information for gene expression characterization using qRT-PCR, which will benefit for future studies of gene regulation in largemouth bass.

Colon cancer is a common gastrointestinal malignancy that ranks third in incidence among gastrointestinal cancers. Therefore, screening bioactive compounds for treatment of colon cancer is urgently needed. Sanguisorba officinalis L. (SO) has been demonstrated that the extractions or monomers possess potential anti-tumor effect. In this study, we firstly used cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled with (quadrupole) time-of-flight mass spectrometry (UHPLC-(Q) TOF-MS/MS) to identify a novel active ingredient, octyl gallate (OG), from SO methanol extract (SO-MtOH). HCT116 and SW620 cells lines were used for in vitro research, which showed OG presents great anti-colon cancer effect by inhibiting proliferation, inducing apoptosis, and repressing the migration and invasion. Furthermore, SW620 bearing athymic nude mice was used to investigate the potential antitumor activity in vivo, which exhibited OG treatment remarkably lessened the tumor volume. Mechanism studies showed that OG downregulated the PI3K/AKT/mTOR signaling axis and induced apoptosis by upregulating the Bax/Bcl-2 protein and the cleaved caspase-3, caspase-9. In conclusion, our research innovatively applied the method of CMC to intriguingly unearth the potential anti-colon cancer ingredient OG and demonstrated its the great antineoplastic activity, which provide a new insight for researchers efficiently developing the novel apoptosis-inducing compound for colon cancer therapy.

How to quantitatively account for the effect of SC-CO2 (Supercritical Carbon) rock-breaking in different rock sites is the key concern in the engineering application of non-explosive rock-breaking technology and economic comparison and there is a lack of experimental basis for relevant studies. Through the equivalent calculation of industrial emulsion explosives, a typical representative granite and mudstone site was selected, and a field experimental program was designed to compare the equivalence of the rock-breaking effects of SC-CO2 and industrial explosives. Based on the rock-breaking equivalent field experiment, we compared and analyzed the rock-breaking area characteristics and parameter changes, such as rock-breaking volume, the morphology of the rock-breaking area, bulk rate, and unit consumption, between SC-CO2 and industrial explosives. A correction of the equivalent conversion formula based on the volume of broken rock was realized. The study shows that SC-CO2 breaks the rock in an elliptical volume shape, the explosives are round, the range of SC-CO2 fracturing breaks the rock is smaller than the range of explosives breaks the rock, and the unit consumption of CO2 is 6–10 times of the unit consumption of explosives. The rock bulk rate is higher after SC-CO2 breaking, while the explosive blast stress wave distribution is uniform, and the bulk rate is low. SC-CO2 rock-breaking produced by the surface vibration velocity is much smaller than the industrial explosives rock-breaking, industrial explosives blasting point of the combined vibration velocity value of the SC-CO2 rock-breaking point of the combined vibration velocity value of 9–11 times, SC-CO2 rock-breaking vibration impact on the surrounding environment is relatively small. The peak combined stress at the measurement point generated by SC-CO2 rock breaking is higher than that of industrial explosives rock breaking, which is 1.2–1.6 times the corresponding measurement point value in the explosives rock breaking test. The study provides an experimental basis for research on the equivalence of SC-CO2 rock-breaking and industrial explosives rock-breaking.

Organizational resilience is a key concept in the study of sustainable corporate growth and indicates an organization's capacity to recover from adversity. It plays a crucial role in responding to uncertain crises. In recent years, academic interest in organizational resilience has increasingly gained prominence. This research uses CiteSpace and VOSviewer to provide a thorough visual analysis of pertinent international literature based on 342 pieces of closely linked literature about organizational resilience. The findings suggest that organizational resilience research is currently experiencing a development phase. Within this field, there is a substantial number of scholars involved, with the most prolific among them including Aleksic Aleksandar, Prayag Girish, and Griffiths Andrew. The networks of collaboration among these authors, nevertheless, are very scattered. Co-citation network research reveals the academics with the biggest sway in the field. Organizational resilience, conservation of resources theory, crisis management, corporate social responsibility, and emergency management are identified as research hotspots within the keyword co-citation network. Furthermore, to determine which countries and regions are the most influential, this study has created a cooperative network among them. China, the United States, and England are the top three nations with articles published. Not only are the highly cited journals respected in the management sector, but they also showcase noteworthy research accomplishments within the field. The purpose of this study is to investigate potential avenues for future research and offer helpful sources for choosing research subjects and developing theoretical frameworks in this area. The analysis is highly valuable as a reference for research on organizational resilience in different settings in the future.

Parkinson's disease (PD) is a neurodegenerative disorder commonly accompanied by gut dysfunction. EA has shown anti-inflammatory and neuroprotective effects. Here, we aim to explore whether EA can treat Parkinson's disease by restoring the intestinal barrier and modulating NLRP3 inflammasome. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model and EA at the GV16, LR3, and ST36 for 12 consecutive days. The open-field test results indicated that EA alleviated depression and behavioral defects, upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Moreover, EA blocked the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, this study suggested that EA exhibited a protective effect against MPTP-induced PD by alleviating behavioral defects, reversing the block of motor dysfunction, and improving the gut barrier by modulating intestinal NLRP3 inflammasome. Above all, this study could provide novel insights into the pathogenesis and therapy of PD.

Recent advancements in machine learning have spurred an increased integration of AI in critical sectors such as healthcare and criminal justice. The ethical and legal concerns surrounding fully autonomous AI highlight the importance of combining human oversight with AI to elevate decision-making quality. However, trust calibration errors in human-AI collaboration, encompassing instances of over-trust or under-trust in AI recommendations, pose challenges to overall performance. Addressing trust calibration in the design process is essential, and eXplainable AI (XAI) emerges as a valuable tool by providing transparent AI explanations. This paper introduces Calibrated-XAI (C-XAI), a participatory design framework specifically crafted to tackle both technical and human factors in the creation of XAI interfaces geared towards trust calibration in Human-AI collaboration. The primary objective of the C-XAI framework is to assist designers of XAI interfaces in minimising trust calibration errors at the design level. This is achieved through the adoption of a participatory design approach, which includes providing templates, guidance, and involving diverse stakeholders in the design process. The efficacy of C-XAI is evaluated through a two-stage evaluation study, demonstrating its potential to aid designers in constructing user interfaces with trust calibration in mind. Through this work, we aspire to offer systematic guidance to practitioners, fostering a responsible approach to eXplainable AI at the user interface level.

Summary: Composite structures integrated with metasurfaces and nonlinear films have emerged as alternative candidates to enhance nonlinear response. The cooperative interaction between the two components is complicated. Herein, a split-ring resonator (SRR)-type metasurface was fabricated on a free-standing nanocrystal diamond (NCD) film utilizing electron beam lithography, electron beam evaporation, and a lift-off process. The terahertz (THz) radiation from the SRR-NCD under normal incidence originates from the high-order magnetic resonance of SRR because the NCD film cannot produce detectable THz radiation at this incident angle. As increasing the incident angle, the contribution of the THz radiation from the NCD film gradually increases until reaching 40° incident angle limitation. The results indicate that this angular-dependent THz radiation is induced by the interplay between the NCD film and SRR. This study offers a new approach to investigate nonlinear processes in composite structures.

Background: Greenspace is known to have a positive impact on human health and well-being, but its potential effects on visual acuity have not been extensively studied. Objectives: Our aim was to examine the relationship between long-term greenspace exposure and visual acuity in children, while also exploring the potential mechanisms in this association. Methods: We conducted this prospective cohort study based on the Children’s growth environment, lifestyle, physical, and mental health development project (COHERENCE), which screened 286,801 schoolchildren in Guangzhou, China, starting in the 2016/17 academic year and followed them up for three academic years (2017/18-2019/20). Visual acuity was measured using a standardized logarithmic chart, and visual impairment was defined as visual acuity worse than 0.0 logarithm of the minimum angle of resolution (LogMAR) units in the better eye. We used the Normalized Difference Vegetation Index (NDVI), the Soil-Adjusted Vegetation Index (SAVI), and the Enhanced Vegetation Index (EVI) to assess the greenspace surrounding child's geocoded home and school at each visit. Results: Our analysis indicated that higher greenspace exposure was associated with greater visual acuity z-score at baseline and with slower decline in visual acuity z-score during the 3-year follow-up. An interquartile range increase in home-school-based NDVI 300m was associated with a 7% decrease [hazard ratios (HRs): 0.93, 95% confidence interval (CI): 0.92, 0.94] in the risk of visual impairment. We also found that air pollution, physical activity, outdoor time, and recreational screen time partially mediated the greenspace-visual acuity association. Conclusion: Our findings suggest that increasing greenspace exposure could benefit children’s visual acuity development and reduce the risk of visual impairment by reducing air pollution and recreational screen time while increasing physical activity and outdoor time. All results could have potential policy implications, given the individual and societal burdens associated with visual impairment.

Largemouth bass ranavirus (LMBRaV), a double-stranded DNA (dsDNA) virus, leads to considerable mortality and significant economic impacts in the largemouth bass (Micropterus salmoides) aquaculture sector. This study evaluated and screened compounds from Chinese herbs for their activity against LMBRaV. Esculin exhibited the highest rate (73 %) of inhibition on LMBRaV major capsid protein (MCP) gene expression at a concentration of 60 mg/L in a cellular environment. It also significantly reduced the cytopathic effect (CPE), protecting infected cells from LMBRaV-induced nuclear damage and hindering LMBRaV infection by modulating viral entry mechanisms. For in vivo study, esculin increased the survival rate of LMBRaV-infected largemouth bass by 60.0 % and 53.3 %, in prevention experiment and treatment experiment, respectively. Concurrently, esculin significantly reduced viral loads and induced the upregulation of antiviral-associated genes, indicating its potential for immunoregulation. In summary, esculin holds potential for both preventing and treating LMBRaV infections in the aquaculture context.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6–72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Local geometric information and discontinuity features are key aspects of the analysis of the evolution and failure mechanisms of unstable rock blocks in rock tunnels. This study demonstrates the integration of terrestrial laser scanning (TLS) with distinct element method for rock mass characterization and stability analysis in tunnels. TLS records detailed geometric information of the surrounding rock mass by scanning and collecting the positions of millions of rock surface points without contact. By conducting a fuzzy K-means method, a discontinuity automatic identification algorithm was developed, and a method for obtaining the geometric parameters of discontinuities was proposed. This method permits the user to visually identify each discontinuity and acquire its spatial distribution features (e.g. occurrences, spacings, trace lengths) in great detail. Compared with hand mapping in conventional geotechnical surveys, the geometric information of discontinuities obtained by this approach is more accurate and the identification is more efficient. Then, a discrete fracture network with the same statistical characteristics as the actual discontinuities was generated with the distinct element method, and a representative numerical model of the jointed surrounding rock mass was established. By means of numerical simulation, potential unstable rock blocks were assessed, and failure mechanisms were analyzed. This method was applied to detection and assessment of unstable rock blocks in the spillway and sand flushing tunnel of the Hongshiyan hydropower project after a collapse. The results show that the noncontact detection of blocks was more labor-saving with lower safety risks compared with manual surveys, and the stability assessment was more reliable since the numerical model built by this method was more consistent with the distribution characteristics of actual joints. This study can provide a reference for geological survey and unstable rock block hazard mitigation in tunnels subjected to complex geology and active rockfalls.

Herein, prepared Ti40–Ni40–Nb20 (at. %) alloy was utilized as a filler metal to join Al2O3 ceramic. The effect of brazing temperature and holding time on the interfacial microstructure evolution and shear strength of joints were analyzed systematically. The results demonstrated that AlNi2Ti, Ni6Nb7 and layered Ni2Ti4O formed adjacent to Al2O3 ceramic. The microstructure of Al2O3 joint brazed at 1200 °C for 10 min was Al2O3/AlNi2Ti + Ni6Nb7 + Ni2Ti4O/Ti2Ni/TiNi + Nb solid solution (Nbss) eutectic + (Ti,Nb)2Ni/Ti2Ni/Ni2Ti4O + Ni6Nb7 + AlNi2Ti/Al2O3. As brazing temperature or holding time raised, the Ni2Ti4O layer nearby Al2O3 ceramic, AlNi2Ti and Ni6Nb7 developed tremendously whereas TiNi + Nbss eutectic structure gradually increased and tended to coarsen. Eventually, the TiNi + Nbss eutectic structure and (Ti,Nb)2Ni in brazing seam were replaced gradually by bulk Ni6Nb7 because of the depleted Ti element. The shear strength of joints was first increased and then decreased with the increasing of the temperature/holding time. The Al2O3/Al2O3 joints brazed at 1200 °C for 10 min received the maximum shear strength of 93.2 MPa, and the joints fractured primarily at the brazing seam/Al2O3 interface.

Aims: Previous studies have related heat waves to morbidity and mortality of cardiovascular diseases; however, potential mechanisms remained limited. Our aims were to investigate the short-term effects of heat waves on a series of clinical/subclinical indicators associated with cardiovascular health. Methods: Our study used 80,574 health examination records from the Health Management Center of Nanjing Zhongda Hospital during the warm seasons of 2019–2021, including 62,128 participants. A total of 11 recognized indicators of cardiovascular risk or injury were assessed. Air pollution and meteorological data were obtained from the Nanjing Ecological Environment Bureau and the China Meteorological Data Network, respectively. Heat waves were defined as a daily average temperature over the 95th percentile for three or more consecutive days from May to September. We used a combination of linear mixed effects models and distributed lag nonlinear models to assess the lagged effects of heat waves on clinical and subclinical cardiovascular indicators. Stratified analyses based on individuals' characteristics, including gender, age, body mass index (BMI), diabetes, and hypertension, were also performed. Results: Heat waves were related to significant changes in most indicators, with the magnitude of effects generally peaking at a lag of 0 to 3 days. Moreover, the cumulative percentage changes over lag 0–7 days were –0.82 % to –2.55 % in blood pressure, 1.32 % in heart rate, 0.20 % to 2.66 % in systemic inflammation markers, 0.36 % in a blood viscosity parameter, 9.36 % in homocysteine, and 1.35 % to 3.25 % in injuring myocardial enzymes. Interestingly, females and males showed distinct susceptibilities in different indicators. Stronger effects were also found in participants aged 50 years or over, individuals with abnormal BMI status, and patients with diabetes. Conclusion: Short-term exposure to heat waves could significantly alter clinical/subclinical cardiovascular indicator profiles, including blood pressure changes, increased heart rate, acute systemic inflammation, elevated blood viscosity, and myocardial injury.

Global warming is exacerbating water security risks in watershed ecosystems. Hence, it is especially crucial to examine how blue and green water respond to drought in watershed ecosystems. This study utilized the Soil and Water Assessment Tool (SWAT) to investigate temporal and spatial variations in blue and green water resources within the Wujiang River Basin (WRB) across three distinct ecosystems: agriculture, forest, and grassland. Concurrently, the Standardized Precipitation Evapotranspiration Index (SPEI) was employed to assess drought risk in the basin, and the relationship between typical ecosystem blue and green water resources and drought response was further explored. The study's results revealed the following key findings: (1) From 1985 to 2014, the basin recorded an average total of 54129.8 × 106 m3 and 46227.7 × 106 m3 of blue and green water, respectively. Notably, forest ecosystems contributed 50 % and 62 % to the blue and green water resources, respectively. (2) In typical ecosystems, temporal changes in both blue and green water exhibited a pattern of initial increase followed by a decrease. Furthermore, spatial changes along the upstream-to-downstream gradient showed an initial decrease, followed by an increase, and ultimately another decrease. (3) In typical ecosystems, blue water is more affected by dry and wet conditions, while green water is influenced by a combination of dry and wet conditions and land use changes. (4) As drought intensity rises, both blue and green water resources in typical ecosystems decrease. Notably, green water in forest ecosystems is less affected by drought intensity, which contributes to maintaining water resource security in watershed ecosystems. These study findings provide a robust scientific foundation for water resource management and drought mitigation strategies in the basin.

Summary: The role of BACH1 in the process of vascular smooth muscle cell (VSMC) differentiation from human embryonic stem cells (hESCs) remains unknown. Here, we find that the loss of BACH1 in hESCs attenuates the expression of VSMC marker genes, whereas overexpression of BACH1 after mesoderm induction increases the expression of VSMC markers during in vitro hESC-VSMC differentiation. Mechanistically, BACH1 binds directly to coactivator-associated arginine methyltransferase 1 (CARM1) during in vitro hESC-VSMC differentiation, and this interaction is mediated by the BACH1 bZIP domain. BACH1 recruits CARM1 to VSMC marker gene promoters and promotes VSMC marker expression by increasing H3R17me2 modification, thus facilitating in vitro VSMC differentiation from hESCs after the mesoderm induction. The increased expression of VSMC marker genes by BACH1 overexpression is partially abolished by inhibition of CARM1 or the H3R17me2 inhibitor TBBD in hESC-derived cells. These findings highlight the critical role of BACH1 in hESC differentiation into VSMCs by CARM1-mediated methylation of H3R17.

Development of biocompatible and biodegradable 3D scaffold for biomedical application has been challenging. Herein, the application of a novel nanocomposite 3D scaffold based on poly vinyl alcohol and sodium alginate embedded with Ca2+ doped titanium dioxide nanoparticle (PVA + SA/Ca@TiO2) as bioactive material was investigated. The 3D scaffold was prepared using a solvent casting method and characterized using FTIR, SEM, XRD and TGA to study their physiochemical properties. The spectroscopy techniques were used to confirm the formation of the required poly vinyl alcohol and sodium alginate with Ca doped TiO2 nanoparticles fillers interaction by the identification of bands. The TiOH bonds and the bonds related to the interconnected network between the inorganic and the organic components from hybrids. The PVA + SA/Ca@TiO2 nanocomposite 3D scaffold was demonstrated good bioactivity to promote nucleation and growth of hydroxyapatite (HAp) in the simulated body fluid. The PVA + SA/Ca@TiO2 nanocomposite 3D scaffold supported the growth and proliferation of 3 T3 mouse fibroblast cells with strong proliferation and cell attachment. The biocompatibility and nontoxic character of the 3D scaffold was probed using fibroblast cell with over 90 % of cell viability. It offers a potential for cell attachment and captured for biomedical application.

Tripterygium hypoglaucum (Levl.) Hutch (THH) has long been used as a remedy for rheumatoid arthritis (RA) in China. However, it is unclear whether the anti-RA mechanism of THH is associated with inflammasome or gut-joint axis. In this study, we aimed to explore the critical role of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and bile acid (BA) in the anti-RA mechanism. Complete Freund’s adjuvant (CFA)-injected mice were treated with THH extract (250 mg/kg/d) for 35 days, and joint swelling and disease scores were measured. After THH treatment, the joint swelling and RA disease score in CFA-treated mice significantly subsided. The increased ratios of lymphocytes, monocytes, and white blood cells were attenuated by THH treatment. Notably, THH treatment blocked the inflammation in both joints and colons by suppressing the NLRP3-mediated inflammasome, as indicated by NLRP3, interleukin 1beta (IL-1β), and Caspase-1. Meanwhile, THH significantly remodeled the bile acid (BA) profiles in RA mice. Spearman’s analysis shed light on the close link between BAs, NLRP3 inflammasome, and RA indicators. However, THH treatment failed to improve inflammasome activation, snoptivis, and joint swelling in RA mice with gut microbiota depletion. In summary, we revealed the pivotal role of BA-mediated gut-joint axis and inflammasome in THH’s RA amelioration. In the future, more work should be done to explain the in-depth mechanism between altered BAs and inflammasome.

Protein acetylation modifications play a central and pivotal role in a myriad of biological processes, spanning cellular metabolism, proliferation, differentiation, apoptosis, and beyond, by effectively reshaping protein structure and function. The metabolic state of cells is intricately connected to epigenetic modifications, which in turn influence chromatin status and gene expression patterns. Notably, pathological alterations in protein acetylation modifications are frequently observed in diseases such as metabolic syndrome, cardiovascular disorders, and cancer. Such abnormalities can result in altered protein properties and loss of function, which are closely associated with developing and progressing related diseases. In recent years, the advancement of precision medicine has highlighted the potential value of protein acetylation in disease diagnosis, treatment, and prevention. This review includes provocative and thought-provoking papers outlining recent breakthroughs in acetylation modifications as they relate to cardiovascular disease, mitochondrial metabolic regulation, liver health, neurological health, obesity, diabetes, and cancer. Additionally, it covers the molecular mechanisms and research challenges in understanding the role of acetylation in disease regulation. By summarizing novel targets and prognostic markers for the treatment of related diseases, we aim to contribute to the field. Furthermore, we discuss current hot topics in acetylation research related to health regulation, including N4-acetylcytidine and liquid-liquid phase separation. The primary objective of this review is to provide insights into the functional diversity and underlying mechanisms by which acetylation regulates proteins in disease contexts.

High density polyethylene(HDPE) material is excellent, often made into bellows, and is an important part of the urban drainage system. The blasting seismic dynamic load is one of the key problems affecting the safety of buried pipeline structures. As a commonly used artificial source excitation method, blasting is often used to study the seismic structural response test. Combined with the characteristics of the buried typical stratum of pipelines in urban areas, full-scale blasting tests of embedded HDPE bellows are conducted. The characteristics of vibration acceleration and strain in the empty pipe under blasting vibration are monitored and analyzed. LS-DYNA is used to establish the model based on the field test conditions and verify the rationality of the model. Then, the models of different water levels are added and the dynamic response characteristics of the pipeline are calculated and analyzed. Finally, according to the max allowable stress criterion, the safety of the pipeline is evaluated.

Summary: Background: Pre-procedural computed tomography (CT) imaging assessment of the aortic valvular complex (AVC) is essential for the success of transcatheter aortic valve replacement (TAVR). However, pre-TAVR assessment is a time-intensive process, and the visual assessment of anatomical structures at the AVC shows interobserver variability. This study aimed to develop and validate a deep learning-based algorithm for pre-TAVR CT assessment and anatomical risk factor detection. Methods: This retrospective, multicentre study used AVC CT scans to develop a deep learning-based, fully automated algorithm, which was then internally and externally validated. After loading CT scans into the algorithm, it automatically assessed the essential anatomical structure data required for TAVR planning. CT scans of 1252 TAVR candidates continuously enrolled from Fuwai Hospital were used to establish training and internal validation datasets, while CT scans of 100 patients with aortic valve disease across 19 Chinese hospitals served as an external validation dataset. The validation focused on segmentation performance, localisation and measurement accuracy of key anatomical structures, detection ability of specific anatomical risk factors, and improvement in assessment efficiency. Findings: Relative to senior observers, our algorithm achieved significant consistent performance with remarkable accuracy, efficiency and ease in segmentation, localisation, and the assessment of the aortic annulus perimeter-derived diameter, and other basic planes, coronary ostia height, calcification volume, and aortic angle. The intraclass correlation coefficient values for the algorithm in the internal and external validation datasets were up to 0.998 (95% confidence interval 0.998–0.998), respectively. Furthermore, the algorithm demonstrated high alignment in detecting specific anatomical risk factors, with accuracy, sensitivity, and specificity up to 0.989 (95% CI 0.973–0.996), 0.979 (95% CI 0.936–0.995), 0.986 (95% CI 0.945–0.998), respectively. Interpretation: Our algorithm efficiently performs pre-TAVR assessments by using AVC CT imaging with accuracy comparable to senior observers, potentially improving TAVR planning in clinical practice. Funding: National Key R&D Program of China (2020YFC2008100), CAMS Innovation Fund for Medical Sciences (2022-I2M-C&T-B-044).

B-cell lymphoma-2 (BCL-2) superfamily molecules play crucial roles in mitochondrial apoptosis induced by Chinese giant salamander iridovirus (GSIV). As an anti-apoptotic molecule in the BCL-2 family, the molecular mechanism of Bcl-w during GSIV infection remains unknown. In this study, we characterized for the first time an amphibian Bcl-w from Chinese giant salamander Andrias davidianus (AdBcl-w), and its function and regulatory mechanism during GSIV infection were investigated. AdBcl-w possesses the conserved structural features of Bcl-w and shares 35–54% sequence identities with other Bcl-w. mRNA expression of AdBcl-w was most abundant in liver and muscle. The AdBcl-w mRNA expression was regulated during GSIV infection. Western blotting assays revealed that the level of Bcl-w protein was downregulated markedly as the infection progresses. Confocal microscopy showed that overexpressed AdBcl-w was translocated to the mitochondria after infection with GSIV. Flow cytometry analysis demonstrated that compared with control, the apoptotic progress in cells transfected with AdBcl-w was reduced while that in cells transfected with AdBcl-w siRNA was enhanced. The number of virus major capsid protein gene copies was lower and protein synthesis was reduced in AdBcl-w overexpressing cells. In addition, AdBcl-w could bind directly to the pro-apoptotic molecule AdBak, while this interaction was weakened with GSIV infection. Moreover, p53 level was reduced and the mRNA expression levels of crucial regulatory molecules in the p53 pathway were regulated in AdBcl-w overexpressing cells during GSIV infection. These results suggested that AdBcl-w inhibit GSIV replication by regulating the virus induced mitochondrial apoptosis.

Gut microbiota disturbance, autophagy dysregulation, and accumulation of hepatic bile acids (BAs) are essential features of liver injury. Therefore, regulating autophagy and BA metabolism are potential strategies for treating liver diseases. Vine tea has been seen beyond a pleasant tea in food science. Our previous study found that vine tea extract (VTE) intervention alleviated acute liver injury (ALI) by restoring gut microbiota dysbiosis. In this study, we aim to investigate the effect of VTE on carbon tetrachloride (CCl4)-induced hepatic autophagy and BA metabolism disorder in mice. The results showed that VTE effectively suppressed CCl4-induced liver fibrosis and hepatic autophagy. LC-MS/MS assay suggested that VTE affected fecal BA production by reducing the fecal BA levels and improving cholestasis in ALI mice. Besides, VTE inhibited BA synthesis, promoted BA transport in the liver, and enhanced BA reabsorption in the ileum through the farnesoid X receptor (FXR)-related signaling pathway. The hepatic expressions of Fxr and Abca1 were elevated by VTE. Finally, the depletion of gut microbiota in ALI mice had a negative impact on abnormal autophagy and BA metabolism. It was also noted that the administration of VTE did not provide any additional improvement in this regard. Overall, VTE ameliorated ALI by reversing hepatic autophagy and abnormal BA metabolism, and the beneficial effects of VTE on liver injury depended on the existence of gut microbiota.

Biomaterials with exceptional biocompatibility and bioactivity are now pushing the boundaries of bone tissue engineering. In this study, natural Arabic gum biopolymer incorporating titanium dioxide nanoparticles (NAG + TiO2NP) nanocomposite film was fabricated. The FTIR and XRD analysis show the presence of functional groups assigned to NAG biopolymers and highly crystalline anatase TiO2NP. Well dispersed TiO2NP can be seen from SEM micrograph suggesting good interaction between TiO2NP filler and NAG biopolymer matrix to enhance the mechanical characteristics of nanocomposite film. The NAG + TiO2NP nanocomposite film exhibited strong bioactivity to form bone-like apatite and promoted the proliferation of MG-63 cells attributed to their excellent biocompatibility and non-toxicity. The NAG + TiO2NP nanocomposite film also displays high antibacterial activity with (36.33 ± 1.53) mm and (27.00 ± 2.00) mm inhibition zone were recorded against Staphylococcus aureus and Escherichia coli. The findings indicate that the NAG + TiO2NP nanocomposite film, with its improved mechanical properties, high swelling capacity, biodegradability, and non-toxicity, shows promise as a viable option for bone tissue regeneration materials.

Fusion-associated small transmembrane (FAST) proteins can promote cell fusion, alter membrane permeability and trigger apoptosis to promote virus proliferation in orthoreoviruses. However, it is unknown whether FAST proteins perform these functions in aquareoviruses (AqRVs). Non-structural protein 17 (NS17) carried by grass carp reovirus Honghu strain (GCRV-HH196) belongs to the FAST protein family, and we preliminarily explored its relevance to virus infection. NS17 has similar domains to FAST protein NS16 of GCRV-873, comprising a transmembrane domain, a polybasic cluster, a hydrophobic patch and a polyproline motif. It was observed in the cytoplasm and the cell membrane. Overexpression of NS17 enhanced the efficiency of cell-cell fusion induced by GCRV-HH196 and promoted virus replication. Overexpression of NS17 also led to DNA fragmentation and reactive oxygen species (ROS) accumulation, and it triggered apoptosis. The findings illuminate the functions of NS17 in GCRV infection, and provide a reference for the development of novel antiviral strategies.

Hexavalent chromium [Cr(VI)] is a well-known environmental carcinogen. Recent studies revealed that chronic exposure of human bronchial epithelial cells (BEAS-2B, B2B) to Cr(VI) activated several signaling pathways and induced cell malignant transformation and tumor growth. However, new mechanisms of Cr(VI) in inducing carcinogenesis remains to be elucidated. This study showed that miR-199a expression levels were significantly lower in Cr(VI)-transformed Cr-T cells. By using the mouse model, the expression levels of miR-199a were significantly decreased in blood samples and lung tissues of mice intranasally exposed to Cr(VI) for 12 weeks compared to the solvent exposure control. Overexpression of miR-199a inhibited tube formation and angiogenesis. C-X-C motif chemokine ligand 8 (CXCL8, IL8) levels were significantly higher in blood samples of Cr (VI)-exposed workers compared to normal workers, and forced expression of miR-199a in the cells suppressed IL8 levels. miR-199a suppression induced expression of hypoxia-inducible factor 1α (HIF-1α) and nuclear factor kappa B (NF-κB) p65 to increase IL8 expression. With animal experiment, the results showed that miR-199a overexpression inhibited tumor growth and angiogenesis through inhibiting IL8, HIF-1α and NF-κB p65 expression in vivo. These results show that miR-199a/IL8 pathway is important in Cr(VI)-induced carcinogenesis and angiogenesis.

Honeybees play a crucial role as pollinators for crops and are regarded as sensitive bioindicators of environmental health. The widespread use of pesticides poses a severe threat to honeybee survival. However, there is limited information available on the specific risks associated with fipronil exposure in honeybees, particularly concerning the impact on RNA methylation throughout their lifespan. This study aimed to evaluate the effects of sublethal concentrations of fipronil on RNA m6A and m5C methylations, along with the associated genes in honeybee larvae and newly emerged adults. LC-MS/MS analysis revealed a notable hypomethylation of m5C in larvae, while hypermethylation of m6A was observed in the adult brain. Significant changes in the expression of genes such as AmWTAP, AmYTHDF, AmALKBH4, AmALKBH6, AmALKBH8, AmNSUN5, AmNOP2, AmTET1, and AmYBX1 were observed in the adult brain, whereas alterations in the expression of AmNSUN2, AmMETTL14, AmALKBH1, AmALKBH4, AmALKBH6 AmALYREF, AmTET1, and AmYBX1 were observed in the larvae. Notably, the expression of AmALKBH1 was not detected in any fipronil-treated larvae, suggesting its potential as an early risk indicator for honeybee larvae in future assessments. This pioneering study provides insights into the effects of fipronil on RNA methylations in honeybees and explores the possibility of employing RNA methylation as a tool for assessing pesticide risks in this important pollinator species. These findings offer new perspectives on honeybee protection and the development of toxicity evaluation systems for pesticides.

Background: Deep brain stimulation (DBS) is a well-established treatment for the tremor symptoms of Parkinson’s disease (PD) or essential tremor. Various structures can be considered targets to be stimulated in tremor treatment.Case description: We described a case of a patient with tremor-dominant Parkinson's disease (td-PD) and a family history of essential tremor, who underwent one-trajectory subthalamic nucleus (STN) and ventral intermediate nucleus (Vim) DBS surgery via a parietal approach under general anesthesia. Microelectrode recordings were performed to localize the STN and Vim. Two years postoperatively, there was an improvement of 61.64% in total motor symptoms and of 80.77% in tremor symptoms in the off-medication and on-stimulation states compared with that in the preoperative off-medication state. The levodopa equivalent daily dosage was reduced from 450 mg to 300 mg. Conclusion: For patients with td-PD with refractory tremors, one-trajectory STN and Vim DBS surgery could improve symptoms and might provide a wider programming window for postoperative management.

Study region: Wujiang River Basin, China. Study focus: Blue and green water play key roles in water management and sustainable development in the Wujiang River Basin. It is essential to conduct a comprehensive study on the availability of blue and green water resources due to the uneven distribution of water resources in the basin. In this study, the monthly, seasonal, and interannual variations in blue and green water resources were analyzed during 1985–2014, and the changes in blue and green water resources were predicted for the period 2015–2100 based on the 5 Coupled Model Intercomparison Project Phase 6 (CMIP6). New hydrological insights for the region: From 1985–2014, blue water resources were dominant in the Wujiang River basin, accounting for 53.6% of the total water resources. Blue water resources exhibited an increasing trend, while green water resources exhibited a decreasing trend. Precipitation exhibited a much more significant impact on blue water resources than on green water resources. The spatial distribution of blue and green water resources in the basin is uneven, where the blue water resource with an annual average of 629.5 mm, indicating an increase followed by a decreasing trend from upstream to downstream. The green water resources had an annual average of 544.7 mm, with a decrease followed by an increasing trend from upstream to downstream. Delta and multi-model ensemble (MME) can effectively reduce the uncertainties associated with CMIP6 model output. Annual precipitation and mean annual temperature increase from 2015 to 2100 in SSP1–2.6, SSP2–4.5, SSP3–7.0, and SSP5–8.5. Compared to the baseline period, blue water resources show the highest growth in the recent (2015–2040) and intermediate (2041–2070) periods in SSP1–2.6, i.e., by 4.9% and 13.7%, respectively. In the final period (2071–2100), blue water resources exhibit the highest growth in SSP5–8.5, i.e., by 21.5%. The future projections indicated that the uneven spatial distribution of blue water resources in the basin will persist. This study improves our understanding of the blue and green water resources in the Wujiang River Basin under climate change scenarios and can provide valuable insights for integrated water resources management in the Wujiang River Basin.

Precipitable water vapor (PWV) facilitates the exchange of water and energy between the Earth's surface and the surrounding atmosphere. PWV can be retrieved by employing the water vapor absorption channels in Landsat 8. Unfortunately, the conventional split-window covariance-variance ratio (SWCVR) method is susceptible to various factors, resulting in low retrieval accuracy and availability. Therefore, we improve the traditional SWCVR model and propose a new PWV retrieval method using ensemble machine learning to address these limitations. The new method uses Gradient Boosting Decision Tree (GBDT) to establish the model between brightness temperature, GNSS-derived PWV, and related surface parameters. The results of the test set show that the improved SWCVR model has an RMSE, Bias, and availability of 0.4947 g/cm2, 0.0276 g/cm2, and 29.6%, respectively. By contrast, the GBDT model's corresponding values are 0.2870 g/cm2, −0.0094 g/cm2, and 67.9%, respectively. Compared with SWCVR, the GBDT improves the RMSE and availability by 41.99% and 38.3%, respectively. The GBDT algorithm is significantly better than the SWCVR model in low altitude and complex surface coverage areas. From a temporal perspective, the advantages of the GBDT method are more apparent in the summer. Finally, the SWCVR and GBDT models are externally validated using measured PWV data from the sun photometer and radiosonde, and the RMSE is 0.5148 g/cm2 and 0.3775 g/cm2, respectively. Based on the findings, we know that the accuracy of GBDT has significantly improved against the SWCVR.

The Al–Si coatings are commonly used for hot-press-forming (HPF) steel to prevent oxidation in the automobile industry. However, due to the presence of Al–Si coating, undesirable intermetallic compounds are easily formed in the welds of HPF steel. In this work, an environment-friendly and effective nanosecond pulsed laser cleaning process was used to remove the Al–Si coating, and HPF steel with varying thicknesses of coatings was prepared for laser welding. The microstructure and mechanical properties of laser welded HPF steel with different thicknesses of coatings were further investigated. The results showed that there was a threshold of power to remove the Al–Si coatings in the laser cleaning process. The reduced thickness of coatings not only could improve the stability of the welding process due to the diminishing of metal vapor generated by coating ablation, but also decrease the content of the Fe–Al phase in the welded joint, which is detrimental to weld performance. The tensile strength and cupping test pass rate of weld joints gradually increased with the decreasing thickness of coatings to 5 μm. After that, the Al–Si coating almost had no effect on the mechanical properties of the laser weld joints. The laser weld joint with 5 μm-thick of Al–Si coating showed, a tensile strength of 1435.05 MPa, a microhardness of 488.38 HV and a pass rate of 100% for the cupping test.

Radionuclide identification is an important part of the nuclear material identification system. The development of artificial intelligence and machine learning has made nuclide identification rapid and automatic. However, many methods directly use existing deep learning models to analyze the gamma-ray spectrum, which lacks interpretability for researchers. This study proposes an explainable radionuclide identification algorithm based on the convolutional neural network and class activation mapping. This method shows the area of interest of the neural network on the gamma-ray spectrum by generating a class activation map. We analyzed the class activation map of the gamma-ray spectrum of different types, different gross counts, and different signal-to-noise ratios. The results show that the convolutional neural network attempted to learn the relationship between the input gamma-ray spectrum and the nuclide type, and could identify the nuclide based on the photoelectric peak and Compton edge. Furthermore, the results explain why the neural network could identify gamma-ray spectra with low counts and low signal-to-noise ratios. Thus, the findings improve researchers’ confidence in the ability of neural networks to identify nuclides and promote the application of artificial intelligence methods in the field of nuclide identification.

Using a fractional-order replication dynamic equation to describe the process of learning and modifying strategies, this paper tries to develop a fractional-order game model of green and low-carbon (GLC) innovation evolution in manufacturing enterprises. The uniqueness, local stability, and global stability of the evolutionary dynamics are discussed to determine the evolutionary stable strategy (ESS) of the game. The discretized form of the fractional-order game model, the ESS of the discretized game, and the sensitivity analysis of parameters are studied. Then, the influence of variable parameters on the ESS is analyzed using phase diagrams and bifurcation diagrams. The results show that: manufacturing industry can develop into a stable situation where all enterprises adopt GLC innovative technologies if their incomes exceed their investment; decreasing the fractional order of the model, the convergence rate to ESS will increase, but the stability of the system will decrease.

Refill friction stir spot welding (RFSSW) of high strength aluminum alloy has a wide application prospect. However, there are few studies between the microstructure and macroscopic corrosion behavior, causing a significant impediment in corrosion protection of the joint. Therefore, the microstructure and corrosion behavior of 7050 aluminum alloy RFSSW joint was investigated in this paper. Due to the difference of microstructure, the joint can be divided into five zones, namely stir zone (SZ), thermo-mechanically affected zone (TMAZ), heat affected zone-I (HAZ-I), heat affected zone-II (HAZ-II) and base metal (BM). Therein, the grain size and the micron-sized second phase particles of SZ were fine, while other areas were coarse. And they were mainly Al2CuMg and Al7Cu2Fe. After intergranular corrosion and exfoliation corrosion tests, it was indicated that the grain morphology and second phase particles did not significantly affect the corrosion susceptibility, but the continuous degree of intergranular nano-precipitates was the key factor. A coefficient r was defined to quantitatively characterize the continuous degree of intergranular nano-precipitates. The HAZ-II and TMAZ exhibited high corrosion sensitivity with a high value of r, while HAZ-I and SZ exhibited low corrosion sensitivity with a low r. The corrosion mechanism was also briefly discussed.

Wire-based additive manufacturing (AM) shows a promising prospect in fabricating large-scale titanium aerospace components at a high deposition rate and low cost. The currently used wire-based AM processes commonly utilize a lateral feeding method with an acute angle to form a deposit, which reduces the flexibility and increases the difficulty of control in making complex components. In this work, a novel coaxial laser metal wire deposition (LMWD) process was used to fabricate the most widely used titanium alloy, Ti6Al4V. The coaxial wire feeding was achieved by a coaxial laser head through a vertically fed wire surrounded by an annular shape beam at focal plane. The surface quality, microstructure and mechanical properties of the deposited Ti6Al4V were examined. To show the characteristic of the coaxial LMWD process, conventional lateral LMWD was also conducted for comparison. The deposited Ti6Al4V wall showed a high surface quality and a microstructure with a mix of equiaxed β grains and columnar prior-β grains rather than coarse prior-β grains. The refined microstructure resulted in a low anisotropy in mechanical properties. The mechanism of the equiaxed β grains formation was also discussed. The combined effect of the reduced thermal gradient and the heterogeneous nucleation from the coaxial wire feeding played an important role in determining the refined microstructures in coaxial LMWD.

Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.

After the high-density polyethylene (HDPE) sheath crack, the hanger steel wires of large-span suspension bridge are prone to corrosion under the erosion of the marine rainfall environment. This study investigates the influence of the outer rust layer on the impressed current cathodic protection (ICCP) and the corrosion behavior of hanger steel wires. The corrosion morphology and corrosion products of the wire are analyzed by SEM and XRD. The result shows that in the simulated marine rainfall environment, both ICCP and removal of the outer rust layer can reduce the corrosion rate of hanger steel wires. Especially the removal of the outer rust layer can significantly improve the cathodic protection efficiency. Removing the initial outer rust layer on the surface before applying ICCP is a benefit for forming a complete and dense corrosion product layer. In addition, it contributes to the generation of Zn5(OH)8Cl2H2O and Al2O3 with stable structures in the corrosion products. These corrosion products benefit to forming a passivation film, which helps isolate the iron matrix from harmful substances.

Summary: Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88–0.92 in the internal verification and 0.83–0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

Food-derived carbon quantum dots (CQDs) can relatively easily be synthesized and chemically manipulated for a broad spectrum of biomedical applications. However, their toxicity may hinder their actual use. Here, Spinacia oleracea-derived CQDs i.e., CQD-1 and CQD-2, were synthesized by means of different shredding methods and followed by a microwave-assisted hydrothermal approach. Subsequently, these CQDs were analyzed in vitro and in an in vivo mice model to test their biocompatibility and potential use as bioimaging agents and for activation of osteogenic differentiation.When comparing CQD-1 and CQD-2, it was found that CQD-1 exhibited 7.6 times higher photoluminescent (PL) emission intensity around 411 nm compared to CQD-2. Besides, it was found that the size distribution of CQD-1 was 2.05 ± 0.08 nm, compared with 2.14 ± 0.04 nm for CQD-2. Upon exposure to human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro, CQD-1 was endocytosed into the cytoplasm and significantly increased the differentiation of hBMSCs up to 10 μg mL−1 after 7 and 14 days. Apparently, the presence of relatively low doses of CQD-1 showed virtually no toxic or histological effects in the major organs in vivo. In contrast, high doses of CQD-1 (1 mg mL-1) caused cell death in vitro ranging from 35% on day 1 to 80% on day 3 post-exposure, and activated the apoptotic machinery and increased lymphocyte aggregates in the liver tissue. In conclusion, S. oleracea-derived CQDs have the potential for biomedical applications in bioimaging and activation of stem cells osteogenic differentiation. Therefore, it is postulated that CQD-1 from S. oleracea remains potential prospective material at appropriate doses and specifications.

Tumor DNA vaccine as an effective therapeutic approach can induce systemic immunity against malignant tumors, but its therapeutic effect is still not satisfactory in advanced renal cancer. Herein, a novel DNA vaccine containing dual antigens of fibrinogen-like protein 1 (FGL1) and carbonic anhydrase IX (CAIX) was developed and intramuscularly delivered by PLGA/PEI nanoparticles for renal cancer therapy. Compared with PLGA/PEI-pCAIX immunization, PLGA/PEI-pFGL1/pCAIX co-immunization significantly inhibited the subcutaneous tumor growth and promoted the differentiation and maturation of CD11c+ DCs and CD11c+CD11b+ DCs subset. Likewise, the increased capabilities of CD8 T cell proliferation, CTL responses, and multi-functional CD8+ T cell immune responses were observed in PLGA/PEI-pFGL1/pCAIX vaccine group. Interestingly, depletion of CD8+ T cells by using CD8 mAb resulted in a loss of anti-tumor function of PLGA/PEI-pFGL1/pCAIX vaccine, suggesting that the anti-tumor activity of the vaccine was dependent on CD8+ T cell immune responses. Furthermore, PLGA/PEI-pFGL1/pCAIX co-immunization also suppressed the lung metastasis of tumor mice by enhancing the multi-functional CD8+ T cell responses. Therefore, these results indicate that PLGA/PEI-pFGL1/pCAIX vaccine could provide an effective protective effect for renal cancer by enhanced DC-mediated multi-functional CD8+ T cell immune responses. This vaccine strategy offers a potential approach for solid or metastatic tumor treatment.