Search

Abstract Folk contract documents (FCD) are valuable materials for studying social history, and the paper they use reflects the social realities of different eras and social classes. Research and scientific analysis of numerous FCD samples after the fourteenth century are rare. We conducted a study on 96 Tianshui folk contract documents (TFCD, 107 paper samples) from the Tianshui area of Gansu Province, Northwest China, taking into account both the textual content and the materiality of paper carriers, and interpreted the results from multiple lines of evidence and discussion. Physical performance analysis revealed that the paper used by the northern folk exhibits a lower apparent density, which is not conducive to the long-term preservation of paper. The preservation status investigation, curtain pattern analysis, and fiber analysis show that the paper used in the TFCD differs from traditional cultural paper regarding disease types, production precision, and fiber materials, providing a basis for its protection and restoration. The analysis of chemical components indicated that the aging and yellowing of paper can be correlated with the content of sulfur and carbonyl groups. The feasibility of using pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) analysis to quickly identify papermaking fibers in a large number of paper samples was proposed. By utilizing various techniques to inspect the paper of documents, this study helps to enhance the academic understanding of FCD materials. In addition, it expands the knowledge base of Northwest handmade paper.

Abstract Computer-aided implant surgery has undergone continuous development in recent years. In this study, active and passive systems of dynamic navigation were divided into active dynamic navigation system group and passive dynamic navigation system group (ADG and PDG), respectively. Active, passive and semi-active implant robots were divided into active robot group, passive robot group and semi-active robot group (ARG, PRG and SRG), respectively. Each group placed two implants (FDI tooth positions 31 and 36) in a model 12 times. The accuracy of 216 implants in 108 models were analysed. The coronal deviations of ADG, PDG, ARG, PRG and SRG were 0.85 ± 0.17 mm, 1.05 ± 0.42 mm, 0.29 ± 0.15 mm, 0.40 ± 0.16 mm and 0.33 ± 0.14 mm, respectively. The apical deviations of the five groups were 1.11 ± 0.23 mm, 1.07 ± 0.38 mm, 0.29 ± 0.15 mm, 0.50 ± 0.19 mm and 0.36 ± 0.16 mm, respectively. The axial deviations of the five groups were 1.78 ± 0.73°, 1.99 ± 1.20°, 0.61 ± 0.25°, 1.04 ± 0.37° and 0.42 ± 0.18°, respectively. The coronal, apical and axial deviations of ADG were higher than those of ARG, PRG and SRG (all P

A comparative study of high chromium (Super304H) and high manganese low chromium heat-resistant steel (HT630) was carried out at 650 °C in steam. Results indicate that the high manganese content in HT630 significantly improved its oxidation resistance. It is ascribed to the formation of a dense protective MnCr2O4 oxide layer during oxidation. MnCr2O4 layer effectively inhibits the diffusion of iron, suppresses the growth of iron-rich oxides, promotes the formation of an iron-rich protective interface with the matrix, and improves the overall oxidation resistance.

Abstract Tropilaelaps mercedesae, an ectoparasitic mite of honeybees, is currently a severe health risk to Apis mellifera colonies in Asia and a potential threat to the global apiculture industry. However, our understanding of the physiological and developmental regulation of this pest remains significantly insufficient. Using ultra-high resolution mass spectrometry, we provide the first comprehensive proteomic profile of T. mercedesae spanning its entire post-embryonic ontogeny, including protonymphs, deutonymphs, mature adults, and reproductive mites. Consequently, a total of 4,422 T. mercedesae proteins were identified, of which 2,189 proteins were significantly differentially expressed (FDR

Abstract The genome’s dynamic nature, exemplified by elements like extrachromosomal circular DNA (eccDNA), is crucial for biodiversity and adaptation. Yet, the role of eccDNA in plants, particularly rice, remains underexplored. Here, we identify 25,598 eccDNAs, unveiling the widespread presence of eccDNA across six rice tissues and revealing its formation as a universal and random process. Interestingly, we discover that direct repeats play a pivotal role in eccDNA formation, pointing to a unique origin mechanism. Despite eccDNA’s prevalence in coding sequences, its impact on gene expression is minimal, implying its roles beyond gene regulation. We also observe the association between eccDNA’s formation and minor chromosomal deletions, providing insights of its possible function in regulating genome stability. Further, we discover eccDNA specifically accumulated in rice leaves, which may be associated with DNA damage caused by environmental stressors like intense light. In summary, our research advances understanding of eccDNA’s role in the genomic architecture and offers valuable insights for rice cultivation and breeding.

Abstract Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.

As the fifth generation (5G) mobile communication systems are commercially deployed, they bring new services, enhance user experiences, and offer various opportunities to different industries. Despite its advancements, 5G encounters several challenges. To tackle these issues, global industrial, academic, and standards organizations are actively researching on sixth generation (6G) wireless communication systems. 6G networks are envisioned as a transformative shift in the interactions between the physical, digital, and human realms, paving the way for a pervasive human-centered cyber-physical world. 6G is positioned to be a platform that offers communication and beyond communication services considering both performance and value centric technological development approaches. In this paper, we present the way forward towards the design of 6G endto-end (E2E) system as a consolidated view of leading industry stakeholders and academia in the European level 6G flagship project Hexa-X-II. We discuss the key challenges with 5G and how 6G is expected to tackle those by introducing new technological innovations and supporting novel use case requirements. We provide a comprehensive methodology for the design of a 6G E2E system including ten principles, a blueprint, and a structured design process. The architecture design principles prioritize environmental sustainability, digital inclusiveness, and trustworthiness, considering their impact on the 6G E2E system. The blueprint is described corresponding to the infrastructure, network centric application, and application layers, as well as the pervasive functionalities and the relevant technological innovations. Following the design principles and the system blueprint, the design process is demonstrated as two-way approaches (i.e., 1) key performance and value indicators based design process. 2) top-down versus bottom-up alignment process) through the lens of a collaborative robot use case. Through this use case, a special attention is given to the technological enablers that cover management and orchestration functionalities and their 6G enhancement to go beyond the limitations characterizing the previous network generation. In addition, virtual modelling aspects related to digital twining and simulations for 6G E2E system design are also discussed.

Gesture recognition has emerged as a significant research domain in computer vision and human-computer interaction. One of the key challenges in gesture recognition is how to select the most useful channels that can effectively represent gesture movements. In this study, we have developed a channel selection algorithm that determines the number and placement of sensors that are critical to gesture classification. To validate this algorithm, we constructed a Force Myography (FMG)-based signal acquisition system. The algorithm considers each sensor as a distinct channel, with the most effective channel combinations and recognition accuracy determined through assessing the correlation between each channel and the target gesture, as well as the redundant correlation between different channels. The database was created by collecting experimental data from 10 healthy individuals who wore 16 sensors to perform 13 unique hand gestures. The results indicate that the average number of channels across the 10 participants was 3, corresponding to an 75% decrease in the initial channel count, with an average recognition accuracy of 94.46%. This outperforms four widely adopted feature selection algorithms, including Relief-F, mRMR, CFS, and ILFS. Moreover, we have established a universal model for the position of gesture measurement points and verified it with an additional five participants, resulting in an average recognition accuracy of 96.3%. This study provides a sound basis for identifying the optimal and minimum number and location of channels on the forearm and designing specialized arm rings with unique shapes.

The modular multilevel matrix converter (M3C) is a potential frequency converter for low-frequency AC transmission. However, capacitor voltage control of high-voltage and large-capacity M3C is more difficult, especially for voltage balancing between branches. To solve this problem, this paper defines sequence circulating components and theoretically analyzes the influence mechanism of different sequence circulating components on branch capacitor voltage. A fully decoupled branch energy balancing control method based on four groups of sequence circulating components is proposed. This method can control capacitor voltages of nine branches in horizontal, vertical and diagonal directions. Considering influences of both circulating current and voltage, a cross decoupled control is designed to improve control precision. Simulation results are taken from a low-frequency transmission system based on PSCAD/EMTDC, and effectiveness and precision of the proposed branch energy balancing control method are verified in the case of nonuniform parameters and an unbalanced power system.

Abstract Ectoparasitic mites of the genera Varroa and Tropilaelaps have evolved to exclusively exploit honey bees as food sources during alternating dispersal and reproductive life history stages. Here we show that the primary food source utilized by Varroa destructor depends on the host life history stage. While feeding on adult bees, dispersing V. destructor feed on the abdominal membranes to access to the fat body as reported previously. However, when V. destructor feed on honey bee pupae during their reproductive stage, they primarily consume hemolymph, indicated by wound analysis, preferential transfer of biostains, and a proteomic comparison between parasite and host tissues. Biostaining and proteomic results were paralleled by corresponding findings in Tropilaelaps mercedesae, a mite that only feeds on brood and has a strongly reduced dispersal stage. Metabolomic profiling of V. destructor corroborates differences between the diet of the dispersing adults and reproductive foundresses. The proteome and metabolome differences between reproductive and dispersing V. destructor suggest that the hemolymph diet coincides with amino acid metabolism and protein synthesis in the foundresses while the metabolism of non-reproductive adults is tuned to lipid metabolism. Thus, we demonstrate within-host dietary specialization of ectoparasitic mites that coincides with life history of hosts and parasites.

Solid waste filling is an important development direction for filling mining. This research proposes the preparation of solid waste-based cemented paste backfill (SWCPB) to fill the underground mined area by using waste rock and copper slag as the mixed aggregate and granulated blast furnace slag, steel slag, and desulfurization gypsum as raw materials of solid waste binder to reduce the environmental hazards caused by the industrial solid wastes. Based on the response surface method, experiments are designed to analyze the effect patterns of different factors on the mechanical properties of SWCPB. The formation mechanism of SWCPB mechanical properties is explored based on various microscopic analysis techniques. The mix proportions of SWCPB are designed based on machine learning. The results show that the strength of SWCPB increases and then decreases with the increase of the proportion of copper slag, and gradually increases with the increase of the steel slag dosage and binder-aggregate ratio. The alkaline environment provided by the steel slag causes the glass body in granulated blast furnace slag to depolymerize and react with desulfurization gypsum to produce hydration products, which are the main source of mechanical properties formation in SWCPB. The machine learning model constructed in this research paper has high prediction accuracy for the strength of backfill, which can achieve high-precision optimization of backfill mix proportion. The research results could guide the recycling of solid waste and the efficient use of filling mining technology.

Vascular cognitive impairment (VCI) has become a common disease-causing cognitive deficit in humans, second only to Alzheimer's Disease (AD). Chuanzhitongluo capsule (CZTL) is a Traditional Chinese Medicine (TCM) preparation known for its effective protection against cerebral ischemia. However, its potential to ameliorate VCI remains unclear. This study aimed to investigate the cognitive improvement effects of CZTL in a mouse model of VCI. Chronic cerebral hypoperfusion (CCH) was induced in mice by bilateral common carotid artery stenosis (BCAS) to simulate the pathological changes associated with VCI. Spatial learning and memory abilities were assessed using the Morris Water Maze (MWM). RNA sequencing (RNA-Seq) was employed to identify differentially expressed genes (DEGs) in the hippocampus. Levels of inflammatory factors were measured through enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) determined the expression intensity of target proteins. Western Blot (WB) confirmed the final action pathway. Results indicated that CZTL significantly improved the spatial learning and memory abilities of CCH mice, along with alterations in gene expression profiles in the hippocampus. It also reduced neuroinflammation in the hippocampus and upregulated the choline acetyltransferase (ChAT) and α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR), which are in synaptic plasticity and neuronal development. Moreover, CZTL inhibited the NF-κB signaling pathway. In conclusion, CZTL may alleviate neuroinflammation induced by CCH and improve cognitive impairment in CCH mice by regulating the cholinergic anti-inflammatory pathway (CAIP) involving ChAT/α7nAChR/NF-κB.

This research introduces an innovative construction method based on magnesia expansive agent concrete for the seamless construction of hundred-meter scale super-length raft structures, corroborated by the on-site test. The basic principle of this construction method is to use the pre compression stress generated by magnesia expansive agent to offset temperature and shrinkage stress. A temperature-strain monitoring system was employed to gather data, affirming the technique’s applicability and safety. Through the examination of temperature and strain dispersion trends in super-length raft structure, recommendations for the configuration of temperature-strain sensors have been put forth. Through the scrutiny of the temporal evolution pattern of temperature, the specific temporal and spatial coordinates that warrant particular vigilance during the surveillance of the raft’s inner-surface temperature difference were identified. Upon evaluating the correlation between strain dispersion and strain-temperature differential in the raft’s thickness dimension, a novel temperature control index (the bottom-surface temperature difference) was introduced. The threshold for this metric was established at 30°C, derived from empirical test outcomes conducted on-site. Furthermore, the critical regions for monitoring the bottom-surface temperature difference were specified.

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well as astrocyte–microglia interaction, which both contribute to evolution of NMOSD lesions. Main body Through transcriptomic and flow cytometry analyses, we found that Bruton’s tyrosine kinase (BTK), a crucial protein of B-cell receptor was upregulated both in the blood and cerebrospinal fluid of NMOSD patients. Blockade of BTK with zanubrutinib, a highly specific BTK inhibitor, mitigated the activation and maturation of B cells and reduced production of causal aquaporin-4 (AQP4) autoantibodies. In a mouse model of NMO, we found that both BTK and pBTK expression were significantly increased in microglia. Transmission electron microscope scan demonstrated that BTK inhibitor ameliorated demyelination, edema, and axonal injury in NMO mice. In the same mice colocalization of GFAP and Iba-1 immunofluorescence indicated a noticeable increase of astrocytes–microglia interaction, which was alleviated by zanubrutinib. The smart-seq analysis demonstrated that treatment with BTK inhibitor instigated microglial transcriptome changes including downregulation of chemokine-related genes and genes involved in the top 5 biological processes related to cell adhesion and migration, which are likely responsible for the reduced crosstalk of microglia and astrocytes. Conclusions Our results show that BTK activity is enhanced both in B cells and microglia and BTK inhibition contributes to the amelioration of NMOSD pathology. These data collectively reveal the mechanism of action of BTK inhibition and corroborate BTK as a viable therapeutic target.

Abstract Background It is unclear whether Saccharomyces boulardii (S. boulardii) supplementation in standard triple therapy (STT) is effective in eradicating Helicobacter pylori (H. pylori) infection in children. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effect of S. boulardii supplementation on H. pylori eradication in children. Methods We conducted electronic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure and Wanfang database from the beginning up to September 2023. A random-effects model was employed to calculate the pooled relative risk (RR) with 95% confidence intervals (CI) through a meta-analysis. Results Fifteen RCTs (involving 2156 patients) were included in our meta-analysis. Results of the meta-analysis indicated that S. boulardii in combination with STT was more effective than STT alone (intention-to-treat analysis : 87.7% vs. 75.9%, RR = 1.14, 95% CI: 1.10–1.19, P < 0.00001; per-protocol analysis : 88.5% vs. 76.3%, RR = 1.15, 95% CI: 1.10–1.19, P < 0.00001). The S. boulardii supplementation group had a significantly lower incidence of total adverse events (n = 6 RCTs, 9.2% vs. 29.2%, RR = 0.32, 95% CI: 0.21–0.48, P < 0.00001), diarrhea (n = 13 RCTs, 14.7% vs. 32.4%, RR = 0.46, 95% CI: 0.37–0.56, P < 0.00001), and nausea (n = 11 RCTs, 12.7% vs. 21.3%, RR = 0.53, 95% CI: 0.40–0.72, P < 0.0001) than STT group alone. Similar results were also observed in the incidence of vomiting, constipation, abdominal pain, abdominal distention, epigastric discomfort, poor appetite and stomatitis. Conclusions Current evidence indicated that S. boulardii supplementing with STT could improve the eradication rate of H. pylori, and concurrently decrease the incidence of total adverse events and gastrointestinal adverse events in children.

Post-heat treatment and in-situ rolling, both can be used to improve the coarse grains and anisotropy that are prevalent in metallic materials, fabricated by wire and arc additive manufacturing (WAAM). In this study, the effect of in-situ rolling and heat treatment on the microstructure, mechanical and corrosion behaviors of WAAM 316L was investigated. The results showed that the microstructure of WAAM 316L changed considerably due to the introduction of rolling deformation, as it was observed that the ferrite was distributed in a reticulated or equiaxed morphology instead of dendritic distribution, columnar grains were found to be engulfed, while a large number of low angle grain boundaries (LAGBs) with high dislocation density were introduced. After heat treatment at 650 °C, there was no significant change in grain morphology, ferrite gradually transformed into σ phase, the tensile strength increased, yield strength and elongation decreased. After heat treatment above 1000 °C, the strength and ductility of the rolled WAAM 316L were higher than those of the unrolled WAAM 316L. As the heat treatment temperature increased, the corrosion resistance first decreased and then increased. In-situ rolling resulted in a decrease in the corrosion current density of the steel and also reduced the stability of the passive film.

Abstract Background Few studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods. Methods Leveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016–2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children’s sex-specific associations were explored. Results After controlling for covariates, one standard deviation (SD) (11.5 μg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 – 26%) and 14% (95% CI: 1 – 29%) increase in SGA, respectively; and one SD (9.6 μg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 – 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22–32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found. Conclusion Consistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

Multimodal knowledge graph completion necessitates the integration of information from multiple modalities (such as images and text) into the structural representation of entities to improve link prediction. However, most existing studies have overlooked the interaction between different modalities and the symmetry in the modal fusion process. To address this issue, this paper proposed a Transformer-based knowledge graph link prediction model (MM-Transformer) that fuses multimodal features. Different modal encoders are employed to extract structural, visual, and textual features, and symmetrical hybrid key-value calculations are performed on features from different modalities based on the Transformer architecture. The similarities of textual tags to structural tags and visual tags are calculated and aggregated, respectively, and multimodal entity representations are modeled and optimized to reduce the heterogeneity of the representations. The experimental results show that compared with the current multimodal SOTA method, MKGformer, MM-Transformer improves the Hits@1 and Hits@10 evaluation indicators by 1.17% and 1.39%, respectively, proving that the proposed method can effectively solve the problem of multimodal feature fusion in the knowledge graph link prediction task.

In this paper, we focus on the well-posedness problem of the three-dimensional incompressible viscous and resistive Hall-magnetohydrodynamics system (Hall-MHD) with variable density. We mainly prove the existence and uniqueness issues of the density-dependent incompressible Hall-magnetohydrodynamic system in critical spaces on .

Phthalates (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are frequently detected in females of reproductive age. Many studies have found that environmental PAE and PAH levels are independent risk factors for gestational hypertension. However, exposure to both components is a more realistic scenario. To better assess the health effects of PAEs and PAHs in pregnant women, we explored the associations of exposure to both individual and combined PAEs and PAHs with gestational hypertension. This nested case–control study was a component of a prospective cohort study conducted in Beijing, China. We included 206 women with gestational hypertension and 214 pregnant controls. We used gas chromatography/tandem mass spectrometry (GC–MS/MS) to detect 8 PAEs and 13 PAHs in > 80 % of all collected hair samples. Multiple linear regression models were employed to test the individual associations between each component and gestational hypertension. A quantile-based g-computation (qgcomp) model and a weighted quantile sum (WQS) regression model were used to estimate whether exposure to both PAEs and PAHs increased the risk of gestational hypertension. The individual exposure analyses revealed that diethyl phthalate (DEP), diisobutyl phthalate (DIBP) (both PAEs), benzo(k)fluoranthene (BKF), anthracene, (ANT), and benzo(a)pyrene (BAP) (all PAHs) were positively associated with increased risk of gestational hypertension. In mixed-effect analyses, the qgcomp model indicated that co-exposure to PAEs and PAHs increased the risk of gestational hypertension (odds ratio = 2.01; 95 % confidence interval: 1.02, 3.94); this finding was verified by the WQS regression model. Our findings support earlier evidence that both PAEs and PAHs increase the risk of gestational hypertension, both individually and in combination. This suggests that reductions in exposure to endocrine system-disrupting chemicals such as PAEs and PAHs might reduce the risk of gestational hypertension.

Increasing evidences have revealed a close relationship between various environmental exposures and reproductive health. The real-world complex exposure scenario along with intricate interactions effects of these exposures has high demands of exposome-wide association studies for human risk assessment. With the development of exposomic studies, applying hair exposome to link environmental factors and reproductive health outcomes has obvious potential advantages. However, the reliability of utilizing hair to characterize exposome is always of high concern for researchers. In this review, we briefly summarized studies about the effects of environmental exposures on several typical reproductive health outcomes, described state-of-the-art situation of applying hair exposome for reproductive health risk assessment, elucidated the advantages (e.g., containing abundant exposure factors, low expenses for sampling, and tracing exposure history), and proposed the unsolved issues in this area. We also conducted a comprehensive discussion about the reliability of various hair biomarkers and primarily established the biomarker databases. Finally, a standardized framework on using hair exposome for reproductive health study was proposed to provide fundamental approach for future studies. We concluded that it is promising to apply hair exposome to evaluate the effects of the environmental factors on human reproductive health.

IntroductionRice (Oryza sativa) serves as a vital staple crop that feeds over half the world's population. Optimizing rice breeding for increasing grain yield is critical for global food security. Heading-date-related or Flowering-time-related traits, is a key factor determining yield potential. However, traditional manual phenotyping methods for these traits are time-consuming and labor-intensive.MethodHere we show that aerial imagery from unmanned aerial vehicles (UAVs), when combined with deep learning-based panicle detection, enables high-throughput phenotyping of heading-date-related traits. We systematically evaluated various state-of-the-art object detectors on rice panicle counting and identified YOLOv8-X as the optimal detector.ResultsApplying YOLOv8-X to UAV time-series images of 294 rice recombinant inbred lines (RILs) allowed accurate quantification of six heading-date-related traits. Utilizing these phenotypes, we identified quantitative trait loci (QTL), including verified loci and novel loci, associated with heading date.DiscussionOur optimized UAV phenotyping and computer vision pipeline may facilitate scalable molecular identification of heading-date-related genes and guide enhancements in rice yield and adaptation.

Introduction: Gastric cancer is one of the common malignancies worldwide, and drug resistance is a major factor contributing to the difficulty of treatment in gastric cancer. Zuojinwan (ZJW) has been found to exhibit a certain inhibitory effect on tumor cells. However, the molecular mechanisms of ZJW reversing drug resistance in gastric cancer are still unclear. Method: Human gastric cancer cisplatin-resistant cells SGC-7901/DDP and BGC-823/DDP were divided into control groups, DDP groups (10 μg/mL), 2-DG (5 mM) groups, and ZJW (50 μg/mL) combined with DDP (10 μg/mL) groups. After 48 h of culture, cell proliferation inhibition rate, glucose uptake rate, ATP, and lactate production were detected. Following lentiviral transfection to overexpress GLUT1 and HDAC1, western blot analysis was employed to examine the expression of HDAC1, P53, Ace-p53, and glucose metabolism-related proteins such as GLUT1, LDHA, HK II in the cells. Results: The combination of ZJW and DDP significantly inhibits the proliferation and glycolysis of cisplatin resistant gastric cancer cells. Compared with the DDP group, the combination of ZJW and DDP exhibited a higher inhibition rate (P

Abstract In a previously published clinical trial, we demonstrated that tirofiban was effective and safe in acute ischemic stroke (AIS) patients who did not undergo early recanalization treatments. We aimed to evaluate neuroimaging characteristics and their clinical significance to guide tirofiban treatment. In this post hoc analysis, location of infarcts (anterior circulation stroke [ACS] vs. posterior circulation stroke [PCS]), degree of cerebral artery stenosis (≤69% vs. ≥70% or occlusion), total infarct volume, and ASPECTS were used to predict the treatment effects of tirofiban, defined as the proportions of excellent and favorable functional outcome (modified Rankin Scale [mRS] score of 0–1, 0–2) at 90 days. ACS patients were more likely to achieve excellent (OR 2.08; 95% CI 1.25–3.45; p = 0.004) and favorable functional outcome (OR 2.28; 95% CI 1.24–4.22; p = 0.008) when treated with tirofiban. However, there was no significant difference in PCS patients between tirofiban and the control group. For patients with severe stenosis (≥70% or occlusion), tirofiban treatment improved the proportion of good outcomes (OR 2.84; 95% CI 1.44–5.60; p = 0.002 for mRS 0–1; OR 2.42; 95% CI 1.22–4.77; p = 0.011 for mRS 0–2). Meanwhile, we found that tirofiban improved outcome in patients with ASPECTS 8–10 and was independent of total infarct volume. These findings support the hypothesis that patients with ACS and severe stenosis may be recommended for tirofiban treatment, which can be predicted independent of total infarct volume.

The drive for continuous innovation in large-scale infrastructure necessitates advancements in techniques, addressing the challenges of constructing super-length concrete structures. This study investigated the emerging shift from traditional united expanding agent (UEA) to magnesia expansive agent (MEA) in conjunction with expansive strengthening bands (ESBs), marking a pivotal transition in ensuring monolithic integrity. Despite a decade of exploration, MEA–ESB implementation in real-world projects remains underdocumented, with scholarly focus primarily confined to material characterization. This research integrated empirical on-site tests of MEA–ESB with high-fidelity numerical simulations in ABAQUS. The finite element model (FEM) validation against actual test data underscored the precision of our modeling, capturing the complex thermomechanical behavior of the system. We introduced a sophisticated parametric analysis framework, elucidating the influence of critical parameters like the ESB-to-raft-width ratio and MEA concrete expansion rates. This granular understanding facilitated the fine-tuning of design parameters, advancing the practical application of MEA methodologies. A groundbreaking contribution entailed the formulation of predictive models for early-stage cracking, anchored in the guidelines of the ACI Committee 207 and refined through extensive parametric exploration. These formulae empower engineers to anticipate and mitigate cracking risks during the design phase, thereby enhancing project safety and efficiency. Notably, this study identified limitations in current prediction models, highlighting the need for future research to incorporate comprehensive lifecycle considerations, including hydration heat effects and time-dependent mechanical property evolution.

Aging is an irreversible process of natural degradation of bodily function. The increase in the aging population, as well as the rise in the incidence of aging-related diseases, poses one of the most pressing global challenges. Hemp seed oil, extracted from the seeds of hemp (Cannabis sativa L.), possesses significant nutritional and biological properties attributed to its unique composition of polyunsaturated fatty acids and various antioxidant compounds. However, there is limited knowledge regarding the anti-aging mechanism of hemp seed oil. This study aimed to evaluate the beneficial effects and potential mechanisms of hemp seed oil in a D-galactose (D-gal)-induced aging rat model through a combined analysis of metabolomics and 16S rRNA gene sequencing. Using nuclear magnetic resonance (NMR)-based metabolomics, significant alterations in serum and urine metabolic phenotypes were observed between the D-gal-induced aging rat model and the healthy control group. Eight and thirteen differentially expressed metabolites related to aging were identified in serum and urine, respectively. Treatment with hemp seed oil significantly restored four and ten potential biomarkers in serum and urine, respectively. The proposed pathways primarily included energy metabolism, amino acid metabolism, one-carbon metabolism, and lipid metabolism. Furthermore, 16S rRNA gene sequencing analysis revealed significant changes in the gut microbiota of aged rats. Compared to the model group, the hemp seed oil group exhibited significant alterations in the abundance of 21 bacterial taxa at the genus level. The results indicated that hemp seed oil suppressed the prevalence of pathogenic bacterial genera such as Streptococcus, Rothia, and Parabacteroides. Additionally, it facilitated the proliferation of the genera Lachnospirace_NK4B4_group and Lachnospirace_UCG_001, while also enhancing the relative abundance of the genus Butyricoccus; a producer of short-chain fatty acids (SCFAs). These findings provided new insights into the pathogenesis of aging and further supported the potential utility of hemp seed oil as an anti-aging therapeutic agent.

Low-coverage line-belt-pattern protective forests offer significant advantages in terms of wind and sand control measures. It is important to study the windbreak effectiveness of sand-fixing forests with different spacing for the construction and optimization of plant shelterbelt configurations. The effect of plant spacing on the flow field around a row of trees was investigated using the k-ε turbulence model coupled with the porous media model. In order to accurately simplify the complex and stochastic plant constitutive features, we simplify the plant canopy to a circular platform geometry, which introduces a porous media model, and the plant trunk is simulated as a solid cylinder. The simulation results show that windbreaks only affect wind profiles up to 1.25-times the height of the tree; on the leeward side of the canopy, large-spaced shelterbelts provide greater protection in the near-wake zone, while small-spaced shelterbelts are more effective at reducing velocity in the re-equilibration zone. The flow field recovery properties of the trunk and canopy indicate that the canopy wake zone is longer. In this study, we also quantitatively analyze the relationship between average wind protection effectiveness as a function of plant spacing and streamwise distance from the leeward side of the canopy, and the given parameterized scheme shows a power exponential relationship between wind protection effectiveness and plant spacing and a logarithmic relationship with streamwise distance. This scheme can provide a predictive assessment of the effects during the implementation of the plant shelterbelt.

Experimental research and numerical simulations of the structural response to shock waves with pulse durations of hundreds of milliseconds, or even seconds, are extremely challenging. This paper takes typical single-layer and sandwich cylindrical shells as the research objects. The response rules of cylindrical shells under long-duration blast loadings were studied. The results show that when the pulse duration is greater than or equal to 4~5 times the first-order period of the structure, the maximum response of the structure tends to be consistent, that is, the maximum response of the cylindrical shells with different vibration shapes shows a saturation effect as the pulse duration increases. This study established the relationship between the saturation loading time and the inherent characteristics of the structure. It was found that the saturation effect was applicable under the following conditions, including different load waveforms, elastic–plastic deformation of the structure, and the loading object being a sandwich shell. This will help transform the long-duration explosion wave problem into a finite pulse-duration shock wave problem that can be realized by both experiments and numerical simulations.

All-silicon terahertz absorbers have attracted considerable interest. We present a design and numerical study of an all-silicon polarization-insensitive terahertz metamaterial absorber. The meta-atoms of the metamaterial absorber are square silicon rings which can be viewed as gratings. By properly optimizing the structure of the meta-atom, we achieve a broadband absorptivity that is above 90% ranging from 0.77 THz to 2.53 THz, with a relative bandwidth of 106.7%. Impedance matching reduces the reflection of the terahertz waves and the (0, ±1)-order diffraction induce the strong absorption. The absorption of this absorber is insensitive to the polarization of the terahertz wave and has a large incident angle tolerance of up to 60 degrees. The all-silicon metamaterial absorber proposed here provides an effective way to obtain broadband absorption in the terahertz regime. Metamaterial absorbers have outstanding applications in terahertz communication and imaging.

A new method based on a digital twin is proposed for fault diagnosis, in order to compensate for the shortcomings of the existing methods for fault diagnosis modeling, including the single fault type, low similarity, and poor visual effect of state monitoring. First, a fault diagnosis test platform is established to analyze faults under constant and variable speed conditions. Then, the obtained data are integrated into the Unity3D platform to realize online diagnosis and updated with real-time working status data. Finally, an industrial test of the digital twin model is conducted, allowing for its comparison with other advanced methods in order to verify its accuracy and application feasibility. It was found that the accuracy of the proposed method for the entire reducer was 99.5%, higher than that of other methods based on individual components (e.g., 93.5% for bearings, 96.3% for gear shafts, and 92.6% for shells).

Abstract Background To observe the changes in hemodynamic, stress and inflammatory responses during labor and their labor outcomes after continuous spinal anesthesia labor analgesia for hypertensive pregnant women, and to evaluate whether the continuous spinal anesthesia had any advantages compared to continuous epidural analgesia for hypertensive pregnant women and their newborns. Methods A total of 160 hypertensive pregnant women were selected and randomly divided into continuous spinal anesthesia analgesia group (CSA group) and continuous epidural analgesia group (EA group). Participant age, height, weight and gestational week were recorded; MAP, VAS score, CO and SVR were recorded after the onset of regular uterine contractions (T0), 10 min after analgesia (T1), 30 min (T2), 60 min (T3), when the uterine opening was complete (T4) and when the fetus was delivered (T5); the duration of the first stage of labor and the second stage of labor were recorded; the number of cases of treatment with oxytocin and antihypertensive therapy, mode of delivery, eclampsia and postpartum hemorrhage were counted; pregnant women Bromage scores were recorded at T2. We also recorded neonatal weight, Apgar scores at 1, 5 and 10 min after birth; arterial blood gas analysis of the umbilical cord was performed in newborns; finally, TNF-α, IL-6, and cortisol in pregnant women venous blood were measured at T0, T5, and 24 h after delivery (T7). The number of successful compressions and the total drug dosage administered by the analgesic pump were recorded for both groups. Results The first stage of labor in CSA was longer than EA (P

Abstract Endobronchial stent exacerbates the formation of granulation tissue. Radiotherapy maybe a durable treatment option for granulation hyperplasia. In this study, we explore the results of external beam radiotherapy (EBRT) for granulation hyperplasia after airway stent placement. A total of 30 New Zealand rabbits were assigned in three groups, Control group (n = 12), low dosage (LD, 12 Gy in 4 fractions and twice a week) group (n = 9) and high dosage (HD, 20 Gy in 4 fractions and twice a week) group (n = 9). Post-stenting 1 week, LD and HD group started to receive EBRT. Bronchoscopy, Haematoxylin–eosin (HE), Masson’s trichrome (MTS), Safranin O (SO) and immunohistochemical (IHC) staining protocols were performed to evaluate the histopathological changes of trachea. A total of 30 stents were successfully implanted in 30 rabbits. No procedure-related death and complications happened. Post-stenting 4 w, 8 w and 12 w, the ventilate area ratio (VAR) and qualitative histological scoring (QHS) in the LD group and HD group lower than the Control group. Post-stenting 12w, the immunohistochemical results revealed that the positive percentage of TGF-β and VEGF in the LD group and HD group were lower than the Control group. In conclusion, the present study investigated the efficacy of EBRT in reducing stent related granulation tissue formation in the rabbit trachea. Higher dosage EBRT with a better result in inhibiting granulation hyperplasia.

Abstract The ability of colorectal cancer (CRC) cells to escape from natural killer (NK) cell immune surveillance leads to anti-tumor treatment failure. The long non-coding RNA (lncRNA) ELFN1-AS1 is aberrantly expressed in multiple tumors suggesting a role as an oncogene in cancer development. However, whether ELFN1-AS1 regulates immune surveillance in CRC is unclear. Here, we determined that ELFN1-AS1 enhanced the ability of CRC cells to escape from NK cell surveillance in vitro and in vivo. In addition, we confirmed that ELFN1-AS1 in CRC cells attenuated the activity of NK cell by down-regulating NKG2D and GZMB via the GDF15/JNK pathway. Furthermore, mechanistic investigations demonstrated that ELFN1-AS1 enhanced the interaction between the GCN5 and SND1 protein and this influenced H3k9ac enrichment at the GDF15 promotor to stimulate GDF15 production in CRC cells. Taken together, our findings indicate that ELFN1-AS1 in CRC cells suppresses NK cell cytotoxicity and ELFN1-AS1 is a potential therapeutic target for CRC.

Abstract Environmental exposure to ambient polycyclic aromatic hydrocarbons (PAHs) can disturb the immune response. However, the evidence on adverse health effects caused by exposure to PAHs emitted from specific sources among different vulnerable subpopulations is limited. In this cross‐sectional study, we aimed to evaluate whether exposure to source‐specific PAHs could increase systemic inflammation in older adults. The present study included community‐dwelling older adults and collected filter samples of personal exposure to PM2.5 during the winter of 2011. Blood samples were collected after the PM2.5 sample collection. We analyzed PM2.5 bound PAHs and serum inflammatory cytokines (interleukin (IL)1β, IL6, and tumor necrosis factor alpha levels. The Positive Matrix Factorization model was used to identify PAH sources. We used a linear regression model to assess the relative effects of source‐specific PM2.5 bound PAHs on the levels of measured inflammatory cytokines. After controlling for confounders, exposure to PAHs emitted from biomass burning or diesel vehicle emission was significantly associated with increased serum inflammatory cytokines and systemic inflammation. These findings highlight the importance of considering exposure sources in epidemiological studies and controlling exposures to organic materials from specific sources.

Summary: Environmental variation selects for the adaptive plasticity of maternal provisioning. Even though developing honeybees find themselves in a protected colony environment, their reproductively specialized queens actively adjust their maternal investment, even among worker-destined eggs. However, the potentially adaptive consequences of this flexible provisioning strategy and their mechanistic basis are unknown. Under natural conditions, we find that the body size of larvae hatching from small eggs in large colonies converges with that of initially larger larvae hatching from large eggs typically produced in small colonies. However, large eggs confer a persistent body size advantage when small and large eggs are cross-fostered in small and large colonies, respectively. We substantiate the increased maternal investment by identifying growth-promoting metabolomes and proteomes in large eggs compared to small eggs, which are primarily enriched in amino acid metabolism and cell maturation. Thus, our study provides a comprehensive adaptive explanation for the worker egg size plasticity of honeybees.

Using numerical simulation methods in additive manufacturing (AM) processes can effectively reduce the cost of process exploration. This study presents a multi-scale simulation study based on the powder bed model for grain growth in the laser powder bed fusion (L-PBF) process of the Inconel 718 material. The finite volume method (FVM) and cellular automaton (CA) model were used to reproduce the process. The simulation results were consistent with the experimental results in terms of melt pool morphology, grain structure, and average grain size. The processes of the competitive and epitaxial growth of grains were discussed. The effects of laser power, scanning speed, hatch distance, and scanning strategy on microstructure were further analyzed through pole figure, grain area distribution, CA nucleation and capture event. The results demonstrated the feasibility of this method in predicting the evolution of microstructures in the L-PBF process and provide a reference for future research.

AbstractBackground Diabetic kidney disease (DKD) is a leading cause of kidney failure worldwide. Anxiety has been associated with disease progression in non-diabetes patients. We aimed to examine the prospective association between anxiety and progression of DKD in type 2 diabetes.Methods We conducted a prospective cohort study of 2040 participants with type 2 diabetes at the Diabetes Center of Shanghai General Hospital between May 2017 and June 2020. Anxiety disorders at baseline were diagnosed by a structured clinical interview based on the 10th Revision of International Classification of Disease (ICD). Progression of DKD was identified as the transition from one urinary albumin excretion rate (AER) stage to the next or the development of kidney failure during the follow-up period.Results At baseline, 403 (19.8%) had a diagnosis of anxiety disorders, of whom 107 (26.6%) also received a depression diagnosis. During a median follow-up time of 3.2 years, deterioration of the kidney status occurred in 340 (16.7%) individuals. After adjustment for potential confounders including depression or an anxiety × depression interaction term, anxiety disorders were independently related to an increased risk of progression of DKD (HR 1.539, 95% CI 1.130–2.095, p = 0.006; HR 1.536, 95% CI 1.111–2.122, p = 0.009, respectively).Conclusions Anxiety disorders at baseline, independent of possible confounders, were associated with the progression of DKD in type 2 diabetes. Whether therapeutic interventions for anxiety reduce the risk needs to be investigated.

The development of the eco-economy has become an important way to promote sustainable development and address climate change worldwide. Implementing eco-economic developmental policy globally or locally requires establishing precise indicators. Currently, there are many studies on eco-economy indicators at the academic level, but the eco-economy indicators researched at the academic level are difficult to be implemented and applied by local governments in China, and there is a knowledge gap between the political sector and the academic sector in the process of cooperation. This mainly stems from the lack of whole-process research and analysis that combines government practice and academic research. We attempt to analyze the differences in the understanding of eco-economic indicators between academics and government decision-makers through the study of the establishment process of China's local eco-economic indicator system. We try to find out the reasons for the knowledge gap between academics and government decision-makers, and to build a knowledge bridge between government practice and academic research. At the same time, China, as the largest developing country and an emerging country in the construction of ecological civilization, is worth studying and learning from its experience in the construction of eco-economic indicators. Therefore, we systematically study the connotation of China's eco-economy and the development process of the indicators. And we combine with the practical experience, describe the method and specific process of constructing eco-economy indicators at the provincial scale of the Chinese government. Meanwhile, we put forward the limitations of the construction of the eco-economy indicator system in Liaoning Province. In addition, we analyze in detail the characteristics and attributes of the ecological economy indicators in Liaoning Province, as well as the relationship of these indicators to the implementation of national strategies and to the SDGs. The discipline contributions and scientific and technological concerns of the indicator system's creation are reviewed, and additional improvement ideas are presented. It is expected that the practice of eco-economic indicators in China will further promote eco-economy development and provide methodological reference for countries to measure the level of eco-economic development.

Background & Aims: Bulevirtide (BLV) is a small lipopeptide agent that specifically binds to the sodium taurocholate cotransporting polypeptide (NTCP) bile salt transporter and HBV/HDV receptor on the surface of human hepatocytes and inhibits HDV and HBV entry. As a satellite virus of HBV, HDV virions are formed after assembly of HDV RNA with the HBV envelope proteins (HBsAg). Because both viruses exist as eight different genotypes, this creates a potential for high diversity in the HBV/HDV combinations. To investigate the sensitivity of various combinations of HBV/HDV genotypes to BLV, clinical and laboratory strains were assessed. Methods: For the laboratory strains, the different envelopes from HBV genotypes A through H were combined with HDV genotypes 1–8 in cotransfection assays. Clinical plasma isolates were obtained from clinical studies and academic collaborations to maximise the diversity of HBV/HDV genotypes tested. Results: The mean BLV EC50 against HDV laboratory strains ranged from 0.44 to 0.64 nM. Regardless of HBV and HDV genotypes, the clinical isolates showed similar sensitivities to BLV with mean values that ranged from 0.2 to 0.73 nM. Conclusions: These data support the use of BLV in patients infected with any HBV/HDV genotypes. Impact and implications: This study describes the potent activity of BLV against multiple laboratory strains spanning all HBV/HDV A–H/1–8 genotype combinations and the most diverse collection of HDV clinical samples tested to date, including HBV/HDV genotype combinations less frequently observed in the clinic. Overall, all isolates and laboratory strains displayed similar in vitro nanomolar sensitivity to BLV. This broad-spectrum antiviral activity of BLV has direct implications on potential simplified treatment for any patient infected with HDV, regardless of genotype, and supports the new 2023 EASL Clinical Practice Guidelines on HDV that recommend antiviral treatment for all patients with CHD.

BackgroundThe incidence of acute ischemic stroke caused by large vessel occlusion is relatively infrequent in the young adult population. We sought to evaluate their clinical outcomes after endovascular treatment (EVT) and stroke etiology compared with older patients.MethodsWe examined data from the ANGEL-ACT registry, a nationwide study in China focusing on EVT for acute ischemic stroke. We compared two age groups:

Summary: Cancer is a major health threat and a leading cause of human death worldwide. Surgical resection is the primary treatment for most cancers; however, some patients develop locoregional recurrence. Here, we developed an in situ cancer therapeutic system aimed to locally treat cancer and prevent postoperative recurrence. A functional scaffold, based on alginate/gelatin and crosslinked with copper ions, was fabricated by 3D printing and showed an excellent photothermal effect under near-infrared (NIR) irradiation. The combination of copper ions and NIR effectively killed thyroid cancer cells and patient-derived organoids, indicating a synergetic and broad-spectrum antitumor effect on thyroid cancer through the chemo-photothermal therapy. This implantable stent is designed to provide effective treatment in the vicinity of the tumor site and can be degraded without secondary surgery. The copper-loaded hydrogel scaffold may be a potential candidate for local cancer treatment and pave the way for precise and effective cancer therapy.

Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPARγ) expression. PPARγ inhibition is an efficient therapeutic strategy for aged- and GC-related skeletal disorders. This study aimed to evaluate the effect of PPARγ inhibition on aged GC-treated female rats. It was hypothesised that bisphenol A diglycidyl ether (BADGE) could inhibit marrow adiposity and improve osteogenesis by inhibiting PPARγ, thereby preventing GC-induced osteoporosis (GIO). Female Sprague–Dawley rats (n = 32, age = 18 months) were randomly allocated to one of the following groups: (1) control, (2) BADGE (30 mg/kg/day, intraperitoneal), (3) methylprednisolone (MP; 30 mg/kg/day, subcutaneous), and (4) MP + BADGE. After eight weeks of treatment, bone density (BD) and trabecular bone microarchitectures were quantified by micro-computed tomography (CT), and BM adipocytes were quantified by histopathology. Additionally, mRNA and protein expression of adipogenic and osteogenic markers were quantified by reverse transcription-quantitative polymerase chain reaction. Furthermore, serum bone turnover biomarker levels were quantified by enzyme-linked immunosorbent assay. MP treatment led to marrow adipogenesis and bone deterioration. However, rats treated with MP + BADGE showed lower marrow adipogenesis, as indicated by smaller marrow adipocyte diameter, decreased density and area percentages, reduced expression of marrow adipogenic genes and proteins, improved BD and trabecular microarchitectures, increased expression of osteogenic genes and proteins, and higher levels of serum bone formation markers. These results were consistent with the differences observed between control and BADGE mono-treated rats. In conclusion, BADGE treatment attenuates BM adiposity and improves bone formation in aged GC-treated female rats by inhibiting PPARγ. Therefore, PPARγ might be a potential target for treating GIO in older populations.

Having the Fifth Generation (5G) mobile communication system recently rolled out in many countries, the wireless community is now setting its eyes on the next era of Sixth Generation (6G). Inheriting from 5G its focus on industrial use cases, 6G is envisaged to become the infrastructural backbone of future intelligent industry. Especially, a combination of 6G and the emerging technologies of Digital Twins (DT) will give impetus to the next evolution of Industry 4.0 (I4.0) systems. This article provides a survey in the research area of 6G-empowered industrial DT system. With a novel vision of 6G industrial DT ecosystem, this survey discusses the ambitions and potential applications of industrial DT in the 6G era, identifying the emerging challenges as well as the key enabling technologies. The introduced ecosystem is supposed to bridge the gaps between humans, machines, and the data infrastructure, and therewith enable numerous novel application scenarios.

The definition of the fundamental concepts and the design of the architectural framework for network slicing in fifth-generation communication systems have been successfully concluded; the standardization activities are almost over; and the commercial deployment has already commenced worldwide. To compete for digital supremacy and to be seen as front-runners in the international technological race, researchers from various regions and countries have begun exploring the technical requirements, envisioning potential applications, identifying innovative enablers, developing testbeds for the preliminary validation of several terrestrial and non-terrestrial technologies, and conceptualizing the architectural design for the next generation of mobile communication systems – the sixth-generation (6G) – aiming to connect the human, physical, and digital worlds with a high level of intelligence and openness for the 2030s. In support of such an ambitious vision, this article extends the end-to-end network slicing concepts, methods, solutions, and functioning architectures towards 6G. To this intent, the study first presents several decisive motivating trends behind such an extension of network slicing in order to make forthcoming mobile networks fully slicing-aware. Following that, the paper attempts to highlight the intelligentization of a number of key enabling technologies that will bring a renaissance to network slicing in the next decade. It then proposes a unified architectural framework and its principal building blocks in several layers, paving the way for the implementation of an open and intelligent network and network slicing in 6G. The proposed architectural solution harmonizes the most recent specifications of the relevant de jure and de facto standards development organizations in their applicable layers with the aim of architecting a pre-standard-compliant and preliminary framework for slicing the 6G network. Finally, the article is intended to spur interest and lay the groundwork for further investigations and subsequent research and development by highlighting a number of open research challenges and directions in this flourishing field.

Protected grape cultivation develops rapidly because of huge economic benefits. However, adverse environmental conditions (insufficient sunlight, high temperature, etc.) in protected cultivation led to low-quality berries. This study aimed to evaluate the effects of berry thinning on the quality attributes of two table grape cultivars (Baoguang and Cuiguang) under linkage greenhouse conditions. Three treatments (L, light berry thinning; M, moderate berry thinning; H, heavy berry thinning) were compared with the control (C, no berry thinning). Berry thinning increased berry weight, total soluble solids (TSS), fructose, glucose, the ratio of TSS to titratable acidity (TA), anthocyanin contents, berry firmness, and mineral contents (Ca, Fe, Na, Mg). Conversely, TA and organic acid profiles were decreased by berry thinning. Cultivars showed significant effects on most of the berry quality parameters. The interaction of cultivars by berry-thinning treatments affected sugar and acid components, anthocyanin contents, and mineral elements.

Abstract Backgrounds Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed. Methods Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively. Results We established 9 patient-derived PTC organoid models, 5 of which harbor BRAFV600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAFV600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAFV600E-mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone. Conclusions These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.

Various geostatistical models have been used in epidemiological research to evaluate ambient air pollutant exposures at a fine spatial scale. Few studies have investigated the performance of different exposure models on population-weighted exposure estimates and the resulting potential misclassification across various modeling approaches. This study developed spatial models for NO2 and PM2.5 and conducted exposure assessment in Beijing, China. It explored three spatial modeling approaches: variable dimension reduction, machine learning, and conventional linear regression. It compared their model performance by cross-validation (CV) and population-weighted exposure estimates. Specifically, partial least square (PLS) regression, random forests (RF), and supervised linear regression (SLR) models were developed based on an ordinary kriging (OK) framework for NO2 and PM2.5 in Beijing, China. The mean squared error-based R2 (R2mse) and root mean squared error (RMSE) in leave-one site-out cross-validation (LOOCV) were used to evaluate model performance. These models were used to predict the ambient exposure levels in the urban area and to estimate the misclassification of population-weighted exposure estimates in quartiles between them. The results showed that the PLS-OK models for NO2 and PM2.5, with the LOOCV R2mse of 0.82 and 0.81, respectively, outperformed the other models. The population-weighted exposure to NO2 estimated by the PLS-OK and RF-OK models exhibited the lowest misclassification in quartiles. For PM2.5, the estimates of potential misclassification were comparable across the three models. It indicated that the exposure misclassification made by choosing different modeling approaches should be carefully considered, and the resulting bias needs to be evaluated in epidemiological studies.

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem–loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding.