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Abstract Selective defluorinative functionalization of trifluoromethyl group (–CF3) is an attractive synthetic route to the pharmaceutically privileged fluorine-containing moiety. Herein, we report a strategy based on photoexcited copper catalysis to activate the C–F bond of di- or trifluoromethylated arenes for divergent radical C–N coupling with carbazoles and aromatic amines. The use of different ligands can tune the reaction products diversity. A range of substituted, structurally diverse α,α-difluoromethylamines can be obtained from trifluoromethylated arenes via defluorinative C-N coupling with carbazoles, while an interesting double defluorinative C-N coupling is ready for difluoromethylated arenes. Based on this success, a carbazole-centered PNP ligand is designed to be an optimal ligand, enabling a copper-catalyzed C–N coupling for the construction of imidoyl fluorides from aromatic amines through double C-F bond functionalization. Interestingly, a 1,2-difluoroalkylamination strategy of styrenes is also developed, delivering γ,γ-difluoroalkylamines, a bioisostere to β-aminoketones, in synthetically useful yields. The DFT studies reveal an inner-sphere electron transfer mechanism for Cu-catalyzed selective activation of C(sp3)–F bonds.

AbstractRock mass strength parameters are critical when applying the permanent-displacement analysis to landslide susceptibility assessment. Previous studies use limited measured data to assign a constant value for each lithology. Since the rock mass strength is spatially heterogeneous, assigning a constant value to each lithology cannot effectively reflect the spatial heterogeneity of rock mass strength, reducing the reliability of seismic landslide susceptibility assessment. Here we present an analysis of a well-documented seismic landslide inventory and the lithological environment, and develop an empirical model to quantify the rock mass strength heterogeneity. The rock mass strength heterogeneity was subsequently taken as an input of the permanent-displacement analysis to assessing regional seismic landslide susceptibility. Results on two case studies show that considering the rock mass strength heterogeneity would significantly improve seismic landslide susceptibility assessment. The findings of this study are valuable for earthquake emergency rescue and post-earthquake land plans.

This paper develops a wave-to-wire model of a vibro-impact wave energy converter array for stand-alone offshore applications. Nonlinear model predictive control is proposed for maximising the wave power capture of the array, and implemented by AC/DC converters and the space vector pulse width modulation technique. A hybrid energy storage system, consisting of batteries and supercapacitors, is placed parallel to the DC bus via buck-boost DC/DC converters to smooth the array power output, and a Lyapunov-based power management strategy is utilised to control the DC/DC converters for stabilising the DC bus voltage. Intensive numerical simulations are conducted; the results show that the proposed wave-to-wire model is capable to evaluate the performance of the vibro-impact wave energy converter array in various scenarios, and the proposed energy maximisation control and power management strategy can enhance wave power capture and stabilise the power output simultaneously.

As the most abundant class of transcription factors in eukaryotes, C2H2-type zinc finger proteins (C2H2-ZFPs) play critical roles in various biological processes. Despite being extensively studied in mammals, C2H2-ZFPs remain poorly characterized in birds. Recent accumulation of multi-omics data for chicken enables the genome-wide investigation of C2H2-ZFPs in birds. The purpose of this study is to reveal the genomic occurrence and evolutionary signature of chicken C2H2-ZFPs, and further depict their expression profiles across diverse chicken tissues. Here, we annotated 301 C2H2-ZFPs in chicken genome, which are associated with different effector domains, including KRAB, BTB, HOMEO, PHD, SCAN, and SET. Among them, most KRAB-ZFPs lack orthologues in mammals and tend to form clusters by duplication, supporting their fast evolution in chicken. We also annotated a unique and previously unidentified SCAN-ZFP, which is lineage-specific and highly expressed in ovary and testis. By integrating 101 RNA-seq datasets for 32 tissues, we found that most C2H2-ZFPs have tissue-specific expression. Particularly, 74 C2H2-ZFPs—including 27 KRAB-ZFPs—show blastoderm-enriched expression, indicating their association with early embryo development. Overall, this study performs comprehensive annotation and expression profiling of C2H2 ZFPs in diverse chicken tissues, which gives new insights into the evolution and potential function of C2H2-ZFPs in avian species.

In order to improve the wear resistance of copper and enhance the surface properties of copper parts, this article uses BN nanoparticles as a reinforcing phase and the laser remelting method to prepare a Cu/BN remelted layer on the copper surface. The surface morphology, crystal structure, microhardness, and wear resistance of the samples were tested and characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), a microhardness tester, and a friction and wear tester. The effects of laser frequency, pulse width, and energy density on the surface morphology and wear resistance of the samples were analyzed and studied, and the effects of the laser parameters on the properties of the Cu/BN remelted layer were discussed. The research results indicate that laser frequency, pulse width, and energy density have a direct impact on the surface morphology and properties of the Cu/BN remelted layer, but the impact mechanism by the above parameters on the remelted layer is different. The effects of laser frequency on the remelted layer are caused by changes in the overlap mode of the remelting points, while laser pulse width and energy density are achieved through changes in remelting intensity. When the laser frequency is 10 Hz, the pulse width is 10 ms, and the energy density is 165.8 J/mm2, the Cu/BN remelted layer has better surface properties.

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus ♀ × E. tukula ♂), abbreviated as EFT, exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in EFT compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance-regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Multi-omics results highlighted the role of lipid metabolism, particularly “Fatty acid synthesis”, “EPA biosynthesis”, and “Signaling lipids”, in EFT heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of EFT was greater than that of maternal E. fuscoguttatus (8.46% vs. 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in EFT. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4 were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in EFT, taking a significant step towards the molecular basis of heterosis.

BackgroundIn recent years, with the continuous expansion of the application scope of Tranexamic acid (TXA), its usage has surged. Despite numerous studies demonstrating its powerful efficacy, concerns regarding its adverse reactions persist, necessitating comprehensive safety assessment. This study analyzed real-world data from the U.S. Food and Drug Administration to investigate TXA-related adverse events, aiming to elucidate its safety and optimize patient treatment.MethodsThe adverse drug event data concerning TXA from 2004 Q1 to 2023 Q3 were collected. Following data standardization, a variety of signal quantification techniques, including the reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and empirical Bayes geometric mean were used for analysis.ResultsAfter analyzing 16,692,026 adverse event reports, a total of 1,574 cases of adverse events related to TXA were identified, spanning 23 system organ classes and 307 preferred terms. In addition to the common thrombosis-related Vascular disorders (n = 386) and Cardiac disorders (n = 377), adverse reactions in the Nervous system disorders category were also observed (n = 785), including Myoclonus (n = 70), Status epilepticus (n = 43), and Myoclonic epilepsy (n = 17). Furthermore, this study uncovered adverse effects such as Renal cortical necrosis, Hepatic cyst rupture, and Vascular stent stenosis, which were not previously mentioned in the instructions. Although these occurred infrequently, they exhibited high signal strength. Both Retinal artery occlusion and Vascular stent thrombosis disorder were frequent and exhibited high signal strength as well. It is worth noting that 78 cases of adverse reactions were caused by confusion between incorrect product administration.ConclusionOur research suggests that TXA has some adverse reactions that are being overlooked. As a cornerstone medication in hemorrhage treatment, it’s crucial to monitor, identify, and address these adverse reactions effectively.

Background Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date.Methods We evaluated the CMV infection status of patients with GBM’s tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro.Results We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model.Conclusions These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.

Abstract Acetaminophen overdose is a leading cause of acute liver failure (ALF). Despite the pivotal role of the inflammatory microenvironment in the progression of advanced acetaminophen‐induced liver injury (AILI), a comprehensive understanding of the underlying cellular interactions and molecular mechanisms remains elusive. Mas is a G protein‐coupled receptor highly expressed by myeloid cells; however, its role in the AILI microenvironment remains to be elucidated. A multidimensional approach, including single‐cell RNA sequencing, spatial transcriptomics, and hour‐long intravital imaging, is employed to characterize the microenvironment in Mas1 deficient mice at the systemic and cell‐specific levels. The characteristic landscape of mouse AILI models involves reciprocal cellular communication among MYC+CD63+ endothelial cells, MMP12+ macrophages, and monocytes, which is maintained by enhanced glycolysis and the NF‐κB/TNF‐α signaling pathway due to myeloid‐Mas deficiency. Importantly, the pathogenic microenvironment is delineated in samples obtained from patients with ALF, demonstrating its clinical relevance. In summary, these findings greatly enhance the understanding of the microenvironment in advanced AILI and offer potential avenues for patient stratification and identification of novel therapeutic targets.

Mining-induced far-field mine tremors, which often cause strong ground tremors, are receiving more attention due to their increasing occurrence. Investigating the rock burst risk of roadway caused by those tremors is crucial to ensure production safety. In this study, Variational Mode Decomposition was used to investigate the wave characteristics of strong mine tremors. The propagation and attenuation of these tremors were explored using the dynamic analysis of Flac3d. The amplification factor was introduced to assess the impact of these tremors on roadways. Plastic zone volume increment and Brittle Shear Ratio (BSR) are used to assess the roadway failure and the rock burst potential caused by these tremors, respectively. The main findings are as follows: 1) Compared with the main frequency of near-field mine tremor waveform, the far-field mine tremors waveform are mainly low frequency below 5 Hz; 2) In the simulation, peak vibration velocities of P-wave and S-wave follow a power-law decay as the propagation distance increases, with P-wave attenuating faster than S-wave; 3) Under similar conditions, P-wave induce higher vibration velocities than S-wave, but S-wave generally exhibit a greater amplification factor than P-wave; 4) When the direction of dynamic load is consistent with the direction of maximum principal stress, the rock burst potential of roadway is higher, which explains the phenomenon that the rock burst potential of roadway under S-wave loading is higher than that under P-wave.

BackgroundPrevious investigations have demonstrated a correlation between the composition of gut microbiota and the development of thyroid cancer (TC). Nonetheless, there was no consensus on the causal effect of gut microbiota composition on TC risk. Therefore, the present study aimed to perform a bidirectional two-sample Mendelian randomization (MR) analysis to explore potential causal associations between gut microbiota and TC risk.MethodsUtilizing data from the MiBioGen consortium’s genome-wide association studies (GWAS) meta-analysis involving a sample size of 18,340, we identified instrumental variables for 211 gut microbiota taxa. The summary statistics for TC was from relevant large-scale GWAS conducted by the FinnGen consortium. In the first stage, the Inverse-variance weighted (IVW) method was used as the primary estimate method, and the stability of estimations was tested by a battery of sensitivity analyses. In the second stage, a reverse MR analysis was applied to determine whether reverse causality existed.ResultsAccording to the IVW method, we identified 9 genetically predicted gut microbiota that were causally correlated with TC risk. Among them, we observed a positive causal effect of Family Christensenellaceae (OR = 1.664, 95% CI: 1.103–2.511, P = 0.015), Family Victivallaceae (OR = 1.268, 95% CI: 1.009–1.594, P = 0.042), Genus Methanobrevibacter (OR = 1.505, 95% CI: 1.049–2.159, P = 0.027), Genus Ruminococcus2 (OR = 1.846, 95% CI: 1.261–2.704, P = 0.002), Genus Subdoligranulum (OR = 1.907, 95% CI: 1.165–3.121, P = 0.010), Phylum Verrucomicrobia (OR = 1.309, 95% CI: 1.027–1.668, P = 0.029) on TC risk, while Class Betaproteobacteria (OR = 0.522, 95% CI: 0.310–0.879, P = 0.015), Family Family XI (OR = 0.753, 95% CI: 0.577–0.983, P = 0.037), Genus Sutterella (OR = 0.596, 95% CI: 0.381–0.933, P = 0.024) might be correlated with a decreased risk of TC. Subsequently, various sensitivity analyses indicated no heterogeneity, directional pleiotropy or outliers. In addition, reverse analysis demonstrated a negative causal effect of TC risk on the abundance of the gut microbiota (Genus Ruminococcus2, OR = 0.947, 95% CI: 0.907–0.989, P = 0.014).ConclusionGenetic evidence suggested that bidirectional causal associations of specific bacteria taxa and the risk of TC, highlighting the association of the “gut-thyroid” axis. Further exploration of the potential microbiota-related mechanisms might have profound implications for public health in terms of the early prevention and treatment of TC.

Sub-group 4 R2R3-type MYB transcription factors (TFs) are involved in repression of the phenylpropanoid pathway. In this study, we identified and characterized three MYB transcriptional repressors in common tobacco, named NtMYB1, NtMYB2, and NtMYB4, which belong to sub-group 4 members. Tissue expression properties and specificity of stress-induced expression indicated that the NtMYB1, NtMYB2, and NtMYB4 may perform different functions in tobacco. Overexpression of NtMYB1, NtMYB2, and NtMYB4 reduced phenylpropanoids and flaonoid compounds, such as caffeic acid, chlorogenic acid, neochlorogenic acid, and rutin, respectively. Meanwhile, the expression of the most structural genes involved in phenylpropanoids and flavonoids were reduced in the overexpression transgenic lines. In addition, results based on co-expression and expression analyses revealed possible interactions between NtMYB1, NtMYB2, and NtMYB4 and multiple bHLH TFs. Our results showed that the three sub-group 4 R2R3 members exhibited different expression pattern in various tissues and under abiotic stress conditions. Meanwhile, we hypothesized that the three of them involved in the inhibition of phenylpropanoid and flavonoid biosynthesis might be interaction with bHLH TFs.

This study identified literatures from the Web of Science Core Collection on the application of artificial intelligence in wastewater treatment from 2011 to 2022, through bibliometrics, to summarize achievements and capture the scientific and technological progress. The number of papers published is on the rise, and especially, the number of papers issued after 2018 has increased sharply, with China contributing the most in this regard, followed by the US, Iran and India. The University of Tehran has the largest number of papers, WATER is the most published journal, and Nasr M has the largest number of articles. Collaborative network has been developed mainly through cooperation between European countries, China and the US. Remote sensing in developing countries needs to be further integrated with water quality monitoring programs. It is worth noting that artificial neural network is a research hotspot in recent years. Through keyword clustering analysis, 'machine learning' and 'deep learning' are hot keywords that have emerged since 2019. The use of neural networks for predicting the effectiveness of treatment of difficult to degrade wastewater is a future research trend. The rapid advancement of deep learning provides the opportunity to build automated pipeline defect detection systems through image recognition. HIGHLIGHTS Using bibliometrics to explore the application of artificial intelligence in wastewater treatment.; The combination of deep learning has been developed.; Remote sensing technology has become a research hotspot.; Machine learning or deep learning modeling is widely used to build data-driven predictive models.;

Abstract Background Colorectal cancer (CRC) can develop through various pathogenetic pathways, and one of the primary pathways is high microsatellite instability (MSI-H)/deficient mismatch repair (dMMR). This study investigated the correlation between preoperative contrast-enhanced CT (CECT) and clinicopathologic characteristics of colorectal cancer (CRC) according to different mismatch repair (MMR) statuses. Methods From April 2021 to July 2022, a total of 281 CRC patients with preoperative CECT and available MMR status were enrolled from a single centre for this retrospective study. Preoperative CECT features and clinicopathologic characteristics were analysed. Univariate and multivariate logistic regression analyses were used for statistical analysis. A nomogram was established based on the multivariate logistic regression results. Preoperative and postoperative dynamic nomogram prediction models were established. The C-index, a calibration plot, and clinical applicability of the two models were evaluated, and internal validation was performed using three methods. Results In total, 249 patients were enrolled in the proficient mismatch repair (pMMR) group and 32 patients in the deficient mismatch repair (dMMR) group. In multivariate analysis, tumour location (right-hemi colon vs. left-hemi colon, odds ratio (OR) = 2.90, p = .036), the hypoattenuation-within-tumour ratio (HR) (HR > 2/3 vs. HR

Abstract Background Growing evidence supports an association between physical activity (PA) and the risk of osteoarthritis (OA), but this may be influenced by confounding and reverse causality. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to reveal the causal relationship between PA and OA. Methods MR was performed to explore the causation of PA and OA with genetic variants as instrumental variables. The genetic variants were derived from the summary statistics of a large genome-wide association study meta-analysis based on the European population (n = 661,399), including self-reported leisure screen time (LST) and moderate-to-vigorous physical activity (MVPA), and Arthritis Research UK Osteoarthritis Genetics Consortium cohorts (417,596, 393,873 and 403,124 for overall, hip and knee OA, respectively). The major MR analysis used in this work was the inverse variance weighted (IVW) approach, and sensitivity, pleiotropy, and heterogeneity studies were performed to evaluate the validity of the findings. Results IVW estimates indicated that LST had a risk effect on overall OA (odds ratio (OR) = 1.309, 95% confidence interval (CI): 1.198–1.430, P = 2.330 × 10-9), hip OA (OR = 1.132, 95% CI: 1.009–1.269, P = 0.034) and knee OA (OR = 1.435. 95% CI: 1.286–1.602, P = 1.225 × 10-10). In contrast, no causal relationship was found between MVPA and OA (overall OA: OR = 0.895, 95% CI: 0.664–1.205, P = 0.465; hip OA: OR = 1.189, 95% CI: 0.792–1.786, P = 0.404; knee OA: OR = 0.707, 95% CI: 0.490 -1.021, P = 0.064). In addition, we observed significant heterogeneity in instrumental variables, but no horizontal pleiotropy was detected. Conclusions Recent findings demonstrated a protective impact of reducing LST on OA, independent of MVPA. This provides valuable insights into the role of physical activity in OA and offers lifestyle recommendations, such as reducing recreational sedentary behaviors and promoting appropriate exercise, for individuals at risk of OA.

Abstract The demand for energy plants is foreseen to grow as worldwide energy and climate policies promote the use of bioenergy for climate change mitigation. To avoid competing with food production, it’s critical to assess future changes in marginal land availability for energy plant development. Using a machine learning method, boosted regression tree, this study modeled potential marginal land resources suitable for cassava under current and different climate change scenarios, based on cassava occurrence records and environmental covariates. The findings revealed that, currently, over 80% of the 1357.24 Mha of available marginal land for cassava cultivation is distributed in Africa and South America. Under three climate change scenarios, by 2030, worldwide suitable marginal land resources were predicted to grow by 39.71Mha, 66.21 Mha, and 39.31Mha for the RCP4.5, RCP6.0, and RCP8.5 scenarios, respectively; by 2050, the potential marginal land suitable for cassava will increase by 38.98Mha, 83.02 Mha, and 55.43Mha, respectively; by 2080, the global marginal land resources were estimated to rise by 40.82 Mha, 99.74 Mha, and 21.87 Mha from now, respectively. Our results highlight the impacts of climate change on potential marginal land resources of cassava across worldwide, which provide the basis for assessing bioenergy potential in the future.

Abstract Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes. We initiated a multi-institutional single-arm phase I study (NCT02599454) enrolling twenty patients with the primary endpoint of maximum tolerated dose (MTD); secondary endpoints of safety and efficacy; and exploratory mechanistic correlatives. Treatment is well tolerated and full dose atezolizumab (1200 mg) is the MTD. Efficacy signals include early responses (after 2 cycles of ICI, before initiation of SABR) in 17% of patients. Biomarkers of functional adaptive immunity, including T cell activation in the tumor and response to ex-vivo stimulation by circulating T cells, are highly predictive of benefit. These results require validation and are being tested in a phase III randomized trial.

Meta-path-based heterogeneous graph neural networks have received widespread attention for better mining the similarities between heterogeneous nodes and for discovering new recommendation rules. Most existing models depend solely on node IDs for learning node embeddings, failing to leverage attribute information fully and to clarify the reasons behind a user’s interest in specific items. A heterogeneous graph neural network for recommendation named MIMA (multi-feature interaction meta-path aggregation) is proposed to address these issues. Firstly, heterogeneous graphs consisting of user nodes, item nodes, and their feature nodes are constructed, and the meta-path containing users, items, and their attribute information is used to capture the correlations among different types of nodes. Secondly, MIMA integrates attention-based feature interaction and meta-path information aggregation to uncover structural and semantic information. Then, the constructed meta-path information is subjected to neighborhood aggregation through graph convolution to acquire the correlations between different types of nodes and to further facilitate high-order feature fusion. Furthermore, user and item embedding vector representations are obtained through multiple iterations. Finally, the effectiveness and interpretability of the proposed approach are validated on three publicly available datasets in terms of NDCG, precision, and recall and are compared to all baselines.

In order to improve the surface quality of copper after laser remelting, this article took laser frequency, pulse width, and energy density as the research objects and used scanning electron microscopy (SEM), a laser confocal three-dimensional measurement instrument, hardness tester, and friction and wear measurement instrument to study the surface morphology, surface roughness, microhardness, and wear resistance of copper, respectively. The results indicate that the frequency, pulse width, and energy density of laser remelting could directly affect the surface quality of the sample, but the influence of frequency and pulse width was more significant. When the laser remelting frequency was 10 Hz, the pulse width was 10 ms, and the energy density was 132.69 J/mm2, the sample exhibited good surface morphology, roughness, and wear resistance. The relevant research in this article can provide a good reference for the laser surface treatment of copper-based materials.

Stress granules (SGs) are cytoplasmic ribonucleoprotein assemblies formed under stress conditions and are related to various biological processes and human diseases. Previous studies have reported the regulatory role of some proteins and linear RNAs in SG assembly. However, the relationship between circular RNAs (circRNAs) and SGs has not been discovered. Here, we screened both linear RNAs and circRNAs in SGs using improved total RNA sequencing of purified SG cores in mammalian cells and identified circular transcripts specifically localized in SGs. circRNAs with higher SG-related RNA-binding protein (RBP) binding abilities are more likely to be enriched in SGs. Furthermore, some SG-enriched circRNAs are differentially expressed in hepatocellular carcinoma (HCC) and adjacent tissues. These results suggest the regulatory role of circRNAs in SG formation and provide insights into the biological function of circRNAs and SGs in HCC.

Optical logic gates play important roles in all-optical logic circuits, which lie at the heart of the next-generation optical computing technology. However, the intrinsic contradiction between compactness and robustness hinders the development in this field. Here, we propose a simple design principle that can possess multiple-input-output states according to the incident circular polarization and direction based on the metasurface doublet, which enables controlled-NOT logic gates in infrared region. Therefore, the directional asymmetric electromagnetic transmission can be achieved. As a proof of concept, a spin-dependent Janus metasurface is designed and experimentally verified that four distinct images corresponding to four input states can be captured in the far-field. In addition, since the design method is derived from geometric optics, it can be easily applied to other spectra. We believe that the proposed metasurface doublet may empower many potential applications in chiral imaging, chiroptical spectroscopy and optical computing.

The ongoing emergence of COVID-19 and the maturation of cold chain technology, have aided in the rapid development of the fresh produce e-commerce industry. Taking into account the characteristics of consumers' demand for fresh products, this paper constructs a location allocation model of a front warehouse for fresh e-commerce with the objective of minimizing the total cost. An improved immune optimization algorithm is proposed in this paper, and the effectiveness of the proposed algorithm is demonstrated by a real case study. The results show that the improved immune optimization algorithm outperforms the traditional genetic algorithm in terms of solution accuracy; the proposed location model can effectively help fresh produce e-commerce enterprises open new front-end warehouses when demand is increasing, as well as provide optimal economic decision-making for front warehouse layout.

Abstract Background Osteoarthritis (OA) and sarcopenia are common musculoskeletal disorders in the aged population, and a growing body of evidence indicated that they mutually influence one another. Nevertheless, there was still substantial controversy and uncertainty about the causal relationship between sarcopenia and OA. We explored the complex association between sarcopenia-related traits and OA using cross-sectional analysis and Mendelian randomization (MR). Methods The cross-sectional study used the data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Weighted multivariable-adjusted logistic regression and subgroup analyses were used to evaluate the correlation between sarcopenia, grip, appendicular lean mass (ALM) and the risk of OA. Then, we further performed MR analysis to examine the causal effect of sarcopenia-related traits (grip strength, ALM) on OA. Instrumental variables for grip strength and ALM were from the UK Biobank, and the summary-level data for OA was derived from the Genetics of Osteoarthritis (GO) Consortium GWAS (n = 826,690). Results In this cross-sectional analysis, we observed that sarcopenia, grip were significantly linked with the risk of OA (OR 1.607, 95% CI 1.233–2.094, P 0.05). Conclusions Our research provided evidence that sarcopenia is correlated with an increased risk of OA, and there was a protective impact of genetically predicted grip strength on OA. These findings needed to be verified in further prospective cohort studies with a large sample size.

Abstract Head and neck squamous cell carcinoma (HNSC) is the most common malignant tumor of head and neck. Due to the insidious nature of HNSC and the lack of effective early diagnostic indicators, the development of novel biomarkers to improve patient prognosis is particularly urgent. In this study, we explored and validated the correlation between cytochrome P450 family 4 subfamily F member 12 (CYP4F12) expression levels and HNSC progression using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets and collected patient samples. We analyzed the association of CYP4F12 expression with clinicopathological features, immune correlation and prognosis. Finally, we analyzed the correlation between CYP4F12 and pathways, and verified by experiments. The results showed that CYP4F12 was low expressed in tumor tissues, participated in a variety of phenotypic changes of HNSC and affected immune cell infiltration. Pathway analysis indicated that CYP4F12 may play a key role in tumor cell migration and apoptosis. Experimental results showed that over-expression of CYP4F12 inhibited cell migration and enhanced the adhesion between cells and matrix by inhibiting epithelial-mesenchymal transition (EMT) pathway in HNSC cells. In conclusion, our study provided insights into the role of CYP4F12 in HNSC and revealed that CYP4F12 may be a potential therapeutic target for HNSC.

Abstract Background Some bladder-related diseases, such as bladder urinary tract infection (UTI) and bladder cancer (BCa), have significant six differences in incidence and prognosis. However, the molecular mechanisms underlying these sex differences are still not fully understood. Understanding the sex-biased differences in gene expression in normal bladder cells can help resolve these problems. Methods We first collected published single-cell RNA sequencing (scRNA-seq) data of normal human bladders from females and males to map the bladder transcriptomic landscape. Then, Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were used to determine the significant pathways that changed in the specific cell populations. The Monocle2 package was performed to reconstruct the differentiation trajectories of fibroblasts. In addition, the scMetabolism package was used to analyze the metabolic activity at the single-cell level, and the SCENIC package was used to analyze the regulatory network. Results In total, 27,437 cells passed stringent quality control, and eight main cell types in human bladder were identified according to classical markers. Sex-based differential gene expression profiles were mainly observed in human bladder urothelial cells, fibroblasts, B cells, and T cells. We found that urothelial cells in males demonstrated a higher growth rate. Moreover, female fibroblasts produced more extracellular matrix, including seven collagen genes that may mediate BCa progression. Furthermore, the results showed that B cells in female bladders exhibited more B-cell activated signals and a higher expression of immunoglobulin genes. We also found that T cells in female bladders exhibited more T-cell activated signals. These different biological functions and properties of these cell populations may correlate with sex differences in UTI and BCa, and result in different disease processes and outcomes. Conclusions Our study provides reasonable insights for further studies of sex-based physiological and pathological disparities in the human bladder, which will contribute to the understanding of epidemiological differences in UTI and BCa.

Abstract Purpose It is known that muscle strength and muscle mass play a crucial role in maintaining bone mineral density (BMD). Despite this, there are uncertainties about how muscle mass, lower extremity muscular strength, and BMD are related. We examined the impact of lower extremity muscle strength and mass on BMD in the general American population using cross-sectional analysis. Methods In the study, we extracted 2165 individuals from the National Health and Nutrition Examination Survey 1999–2002. Multivariate logistic regression models were used to examine the association between muscle strength, muscle mass, and BMD. Fitted smoothing curves and generalized additive models were also performed. To ensure data stability and avoid confounding factors, subgroup analysis was also conducted on gender and race/ethnicity. Results After full adjustment for potential confounders, significant positive associations were detected between peak force (PF) [0.167 (0.084, 0.249) P

The use of slag-based alkali-activated concrete (AAC) could effectively address the issues of resource extraction and carbon emissions caused by traditional Portland cement. In this study, the effects of the fly ash content, water–binder ratio, and alkali activation modulus on the early mechanical properties of AAC were investigated. A total of 105 cube specimens (35 sets) were designed and subjected to compressive strength tests, scanning electron microscope tests, and x-ray diffraction composition analysis. The results indicated that excellent early strength was observed in AAC, with a compressive strength reaching ∼90% of the 28th day strength before 14 days. An increase in the fly ash content and a decrease in the water–binder ratio significantly improved the compressive strength within the same age period. The impact of a lower alkaline activation modulus on strength was found to be insignificant. Based on the experimental results, a calculation method and a constitutive model for early strength were proposed, and the theoretical values exhibited a high level of agreement with the measured values.

Purpose: Treatment of triple-negative breast cancer (TNBC) remains challenging. Intermittent fasting (IF) has emerged as a promising approach to improve metabolic health of various metabolic disorders. Clinical studies indicate IF is essential for TNBC progression. However, the molecular mechanisms underlying metabolic remodeling in regulating IF and TNBC progression are still unclear. Methods: In this study, we utilized a robust mouse model of TNBC and exposed subjects to a high-fat diet (HFD) with IF to explore its impact on the metabolic reprogramming linked to cancer progression. To identify crucial serum metabolites and signaling events, we utilized targeted metabolomics and RNA sequencing (RNA-seq). Furthermore, we conducted immunoblotting, real-time quantitative polymerase chain reaction (RT-qPCR), cell migration assays, lentivirus-mediated Mmp9 overexpression, and Mmp9 inhibitor experiments to elucidate the role of decanoylcarnitine/Mmp9 in TNBC cell migration. Results: Our observations indicate that IF exerts notable inhibitory effects on both the proliferation and cancer metastasis. Utilizing targeted metabolomics and RNA-seq, we initially identified pivotal serum metabolites and signaling events in the progression of TNBC. Among the 349 serum metabolites identified, decanoylcarnitine was picked out to inhibit TNBC cell proliferation and migration. RNA-seq analysis of TNBC cells treated with decanoylcarnitine revealed its suppressive effects on extracellular matrix-related protein components, with a notable reduction observed in Mmp9. Further investigations confirmed that decanoylcarnitine could inhibit Mmp9 expression in TNBC cells, primary tumors, lung, and liver metastasis tissues. Mmp9 overexpression abolished the inhibitory effect of decanoylcarnitine on cell migration. Conclusion: This study pioneers the exploration of IF intervention and the role of decanoylcarnitine/Mmp9 in the progression of TNBC in obese mice, enhancing our comprehension of the potential roles of various dietary patterns in the process of cancer treatment.

BackgroundVulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease.MethodsTo reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography.ResultsMacrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques.ConclusionElevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Tumor microenvironment (TME) is essential for the development and progression of hepatocellular carcinoma (HCC). Exosomes participate in constructing TME by passing biological information, but the regulatory effect of PDL1 in exosomes on anticancer activity of CD8+ T cells in HCC still needs to be further explored. In this study, high level of PDL1 was found in plasma exosomes of HCC patients, which turned out to be significantly associated with the increased number of tumor nodules, the upregulated level of serum AFP, the raised tendency of TNM stage, and the poor prognosis of HCC. The expression of CD8 may be inhibited in HCC that is characterized with high level of PDL1, and the protein level of exosomal PDL1 was determined by intracellular PDL1 abundance. High level of exosomal PDL1 inhibited the proliferation and activation of CD8+ T cells, but exhibited limited effect on the proliferation of hepatic cancer cells. Moreover, the growth of tumors formed by hepatic cancer cells Hepa1–6 in C57L mice was significantly promoted by the exosomal PDL1, which might be caused by the inhibitory effect of exosomal PDL1 on CD8+ T cells. Thus, exosomal PDL1 promotes the development and progression of HCC through inhibiting the anticancer activity of CD8+ T cells. This study provides sights for understanding the oncogenic role of PDL1 and a reasonable explanation for the low efficacy of anti-PD1/PDL1 immunotherapies in HCC.

BackgroundMetagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) shows promising application for complicated infections that cannot be resolved by conventional microbiological tests (CMTs). The criteria for cfDNA sequencing are currently in need of agreement and standardization.MethodsWe performed a retrospective cohort observation of 653 patients who underwent plasma cfDNA mNGS, including 431 with suspected bloodstream infections (BSI) and 222 with other suspected systemic infections. Plasma mNGS and CMTs were performed simultaneously in clinical practice. The diagnostic efficacy of plasma mNGS and CMTs in the diagnosis of blood-borne and other systemic infections was evaluated using receiver operating characteristic (ROC) curves. The sensitivity and specificity of the two methods were analyzed based on the final clinical outcome as the gold standard.ResultsThe mNGS test showed an overall positive rate of 72.3% (472/653) for detecting microorganisms in plasma cfDNA, with a range of 2 to 6 different microorganisms detected in 171 patient specimens. Patients with positive mNGS results were more immunocompromised and had a higher incidence of severe disease (P

Background: Cancer remains one of the leading causes of mortality worldwide. Diet can impact inflammation and consequently affect cancer outcomes. The Dietary Inflammatory Index (DII) can serve as a tool to assess the inflammatory potential of cancer survivors' diets and further predict their survival. Objectives: To investigate the relationship between the DII and the survival of cancer survivors in National Health and Nutrition Examination Survey (NHANES). Methods: An overall sample of 2359 U.S. cancer survivors from the 2005–2014 cohorts of the NHANES were studied. The DII scores were calculated using 28 dietary components and the mortality status was ascertained until December 31, 2015. Based on the multiple analyses, the relationship between DII and all-cause mortality was examined. Results: The weighted mean age at baseline was 65.17 ± 14.46 years, 53.16 % were female and 71.30 % were non-Hispanic white. The average DII was 1.51 ± 1.97. After accounting for multiple covariates, positive associations were observed (P

The coronavirus disease 2019 (COVID-19) pandemic has affected the mental health of individuals worldwide, and the risk of psychiatric sequelae and consequent mental disorders has increased among the general population, health care workers and patients with COVID-19. Achieving effective and widespread prevention of pandemic-related psychiatric sequelae to protect the mental health of the global population is a serious challenge. Salidroside, as a natural agent, has substantial pharmacological activity and health effects, exerts obvious neuroprotective effects, and may be effective in preventing and treating psychiatric sequelae and mental disorders resulting from stress stemming from the COVID-19 pandemic. Herein, we systematically summarise, analyse and discuss the therapeutic effects of salidroside in the prevention and treatment of psychiatric sequelae as well as its roles in preventing the progression of mental disorders, and fully clarify the potential of salidroside as a widely applicable agent for preventing mental disorders caused by stress; the mechanisms underlying the potential protective effects of salidroside are involved in the regulation of the oxidative stress, neuroinflammation, neural regeneration and cell apoptosis in the brain, the network homeostasis of neurotransmission, HPA axis and cholinergic system, and the improvement of synaptic plasticity. Notably, this review innovatively proposes that salidroside is a potential agent for treating stress-induced health issues during the COVID-19 pandemic and provides scientific evidence and a theoretical basis for the use of natural products to combat the current mental health crisis.

Introduction Exaggerated inflammatory response is one of the main mechanisms underlying heterotopic ossification (HO). It has been suggested that the antifibrinolytic drug tranexamic acid (TXA) can exert a significant anti-inflammatory effect during orthopaedic surgery. However, no prospective studies have yet investigated the effects of TXA on HO recurrence in patients following open elbow arthrolysis (OEA).Methods and analysis Here, we present a protocol for a single-centre, randomised, double-blind, placebo-controlled trial to investigate the effectiveness of TXA on HO recurrence after OEA in a single hospital. A minimum sample size of 138 eligible and consenting participants randomised into treatment and control groups in a 1:1 manner will be included. Patients will receive 2 g of intravenous TXA (experimental group) or placebo (normal saline, control group) administered before skin incision. The primary outcome is HO recurrence rate within 12 months after surgery. The secondary outcomes are the serum immune-inflammatory cytokines including erythrocyte sedimentation rate, C reactive protein, interleukin (IL)-6, IL-1β, IL-13 at the first and third day postoperatively, and elbow range of motion and functional score at 1.5, 6, 9 and 12 months after surgery. After completion of the trial, the results will be reported in accordance with the extensions of the Consolidated Standards of Reporting Trials Statement for trials. The results of this study should determine whether TXA can reduce the rates of HO occurrence after OEA.Ethics and dissemination Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (reference number 2022-123-(1)). The results of this study will be disseminated through presentations at academic conferences and publication in peer-reviewed journals.Trial registration number ChiCTR2300068106.

Summary: An emerging argument is that since humans can readily adapt to changing climatic conditions, there is less need to pursue aggressive emissions mitigation strategies. As temperature adaptation is a function of repeated exposure over time, we need empirical approaches that can depict individuals’ temperature history to rigorously examine this claim. Using a longitudinal dataset representative of China, we construct lifetime temperature exposure unique to each individual based on their birth-dates, birth-locations, and movement history. We show that a 1°C increase in individualized temperature anomalies cause a 2% decrease in 1 standard deviation (S.D.) of well-being, where most of the impacts are driven by “hotter-than-expected” weather. In turn, while the adverse impacts of future temperature changes wane after accommodating for adaptation, acclimatization is unlikely to keep pace with future temperature increases except in the net-zero emissions scenario, indicating that stringent greenhouse gas (GHG) emissions cuts are still needed even in this less-pessimistic scenario.

Summary: Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

AbstractDeep gob-side entry (DGSE) shows rock burst risk under the condition of kilometer depth and hard roof. Based on the established conditions of the Tengdong coal mine, theoretical analysis, microseismic (MS) monitoring, and numerical modeling were used to study the rock burst mechanism of DGSE. Results show that MS events mainly occurred on the solid side of DGSE and the intense dynamic load was mainly caused by the breaking of low hard roof strata, which can release 2.64 × 105 J elastic energy per meter. The surrounding stress of DGSE was asymmetrical due to the coal pillar yielding and hanging roof’s weight, and the load of coal pillar is negatively correlated with that of solid. Simulation shows the vertical stress evolution of coal pillar and solid shows significant diversity. Coal pillar’s vertical stress first drops sharply, and then increases gradually, finally stable at 10.6 MPa with the DGSE’s excavation. Contrarily, solid’s vertical stress gradually rises and was finally stable at 40.9 MPa. Under roof dynamic loading, the vibration velocity of the entry’s top was higher than that of the floor which was caused by the increase of the propagation distance and the reflection and diffraction effect of waves. The vibration velocity of the coal pillar was significantly higher than that of the solid which is because higher stress can lead to faster attenuation of vibration velocity. After dynamic loading, the coal pillar’s principal stress and principal stress difference decreased while that of the solid can be divided into two drop areas and one rising area. Periodic pressure relief that was carried out in the rising area can reduce the rock burst risk on the solid side of DGSE.

Background: Acupuncture is often used as an adjunctive therapy for gastric ulcer (GU). However, there is still a lack of evidence on the appropriate and optimal interventions for acupuncture. This study aimed to optimize the acupuncture treatment of gastric ulcers based on expert consensus for guiding acupuncturists in clinical practice. Methods: To conduct this study, research evidence was gathered from databases in both Chinese and English. After discussion, preliminary clinical questions were developed. Following three rounds of multidisciplinary clinical expert consultation, the initial consensus questionnaire was formed after testing and modification by team members. A Delphi consensus was ultimately reached to answer the questionnaire and develop guidance for acupuncture treatment. A 9-point Likert-type scale was used to measure the agreement of expert consensus, where a score of 80% between 7 and 9 was defined as “agreement.” Results: After two rounds of Delphi voting, a total of 35 items reached an agreement. These items can be roughly divided into 6 domains. According to expert consensus, the application of acupuncture for gastric ulcer should follow a semistandardized approach. Based on the syndrome differentiation, the main acupoints recommended are Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), and Sanyinjiao (SP6), while the adjunct acupoints include Taichong (LR3), Guanyuan (CV4), Xuehai (SP10), and Taixi (KI3). In the experience of experts, adverse events associated with acupuncture are typically mild and often manifest as subcutaneous hematomas. Conclusion: There is a lack of definitive acupuncture guidelines that can effectively determine the optimal therapeutic approach for the treatment of gastric ulcer. This expert consensus provides recommendations for clinical research and practice of acupuncture, with a particular focus on the selection of acupoints. However, further exploration through rigorous studies is necessary due to the limited availability of clinical evidence.

Magnetic anomaly signal detection has broad application prospects in offshore defense, which is an urgent problem for realizing remote and long-term monitoring. In this paper, an underwater magnetic anomaly detection model is proposed, and wavelet domain analysis and orthogonal basis decomposition detection methods are introduced. Through the analysis of magnetic anomaly signal characteristics and wavelet decomposition frequency, adaptive layer determination method is proposed, and independent processing flow of denoising orthogonal basis decomposition energy detection was performed. To address the problem of wavelet domain denoising under different decomposition scales, different shrinkage coefficients are used to independently deal with detail coefficients to improve the effect of high-frequency noise suppression. The results show that compared with the traditional wavelet denoising, the signal-to-noise ratio of this method is improved by approximately 27%, and the false recognition rate is reduced by 39%.

Abstract Background Uridine disphosphate (UDP) glycosyltransferases (UGTs) act upon a huge variety of highly diverse and complex substrates, such as phytohormones and specialized metabolites, to regulate plant growth, development, disease resistance, and environmental interactions. However, a comprehensive investigation of UGT genes in tobacco has not been conducted. Results In this study, we carried out a genome-wide analysis of family-1 UDP glycosyltransferases in Nicotiana tabacum. We predicted 276 NtUGT genes, which were classified into 18 major phylogenetic subgroups. The NtUGT genes were invariably distributed among all the 24 chromosomes with structural diversity in exon/intron structure, conserved motifs, and cis-acting elements of promoters. Three groups of proteins which involved in flavonoid biosynthesis, plant growth and development, transportation and modification were identified that interact with NtUGT proteins using the PPI analysis. Expression analysis of NtUGT genes in cold stress, drought stress and different flower color using both online RNA-Seq data and the realtime PCR analysis, suggested the distinct role of NtUGT genes in resistance of cold, drought and in flavonoid biosynthesis. The enzymatic activities of seven NtUGT proteins that potentially involved in flavonoid glycosylation were analyzed, and found that all seven exhibited activity on myricetin; six (NtUGT108, NtUGT123, NtUGT141, NtUGT155, NtUGT179, and NtUGT195) showed activity on cyanidin; and three (NtUGT108, NtUGT195, and NtUGT217) were active on the flavonol aglycones kaempferol and quercetin, which catalyzing the substrates (myricetin, cyanidin or flavonol) to form new products. We further investigated the enzymatic products and enzymatic properties of NtUGT108, NtUGT195, and NtUGT217, suggested their diverse enzymatic activity toward flavonol, and NtUGT217 showed the highest catalyzed efficient toward quercetin. Overexpression of NtUGT217 significantly increase the content levels of the quercetin-3-O-glucoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside in transgenic tobacco leaves. Conclusion We identified 276 UGT genes in Nicotiana tabacum. Our study uncovered valuable information about the phylogenetic structure, distribution, genomic characters, expression patterns and enzymatic activity of NtUGT genes in tobacco. We further identified three NtUGT genes involved in flavonoid biosynthesis, and overexpressed NtUGT217 to validate its function in catalyze quercetin. The results provide key candidate NtUGT genes for future breeding of cold and drought resistance and for potential metabolic engineering of flavonoid compounds.

Abstract Background Cell-assisted lipotransfer (CAL), a technique of autologous adipose transplantation enriched with adipose-derived stem cells (ADSCs), has the potential to improve cosmetic outcomes at irradiated sites. However, many concerns have been raised about the possibility of ADSCs increasing oncological risk in cancer patients. With the increasing demand for CAL reconstruction, there is an urgent need to determine whether CAL treatment could compromise oncological safety after radiotherapy, as well as to evaluate its efficacy in guiding clinical decisions. Methods A PRISMA-compliant systematic review of the safety and efficacy of CAL in breast cancer patients after radiotherapy was conducted. The PubMed, Ovid, Cochrane Library, and ClinicalTrials.gov databases were comprehensively searched from inception to 31 December 2021. Results The search initially yielded 1185 unique studies. Ultimately, seven studies were eligible. Based on the limited outcome evidence, CAL did not increase recurrence risk in breast cancer patients but presented aesthetic improvement and higher volumetric persistence in a long-term follow-up. Although breast reconstruction with CAL also had oncological safety after radiotherapy, these patients needed more adipose tissue and had relatively lower fat graft retention than the non-irradiated patients (P

Abstract Purpose Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) are acknowledged as novel inflammatory markers. However, studies investigating the correlation between inflammatory markers and osteoporosis (OP) remain scarce. We aimed to investigate the relationship between NLR, MLR, PLR and bone mineral density (BMD). Methods A total of 9054 participants from the National Health and Nutrition Examination Survey were included in the study. MLR, NLR and PLR were calculated for each patient based on routine blood tests. Given the complex study design and sample weights, the relationship between inflammatory markers and BMD was evaluated through weighted multivariable-adjusted logistic regression and smooth curve fittings. In addition, several subgroup analyses were conducted to assess the robustness of the outcomes. Results This study observed no significant relationship between MLR and lumbar spine BMD (P = 0.604). However, NLR was positively correlated with lumbar spine BMD (β = 0.004, 95% CI: 0.001 to 0.006, P = 0.001) and PLR was negatively linked to lumbar spine BMD (β = − 0.001, 95% CI: − 0.001 to − 0.000, P = 0.002) after accounting for covariates. When bone density measurements were changed to the total femur and femoral neck, PLR was still significantly positively correlated with total femur (β = − 0.001, 95% CI: − 0.001, − 0.000, P = 0.001) and femoral neck BMD (β = − 0.001, 95% CI: − 0.002, − 0.001, P

Abstract During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.

Abstract While the high-dimensional biological data have provided unprecedented data resources for the identification of biomarkers, consensus is still lacking on how to best analyze them. The recently developed Gaussian mirror (GM) and Model-X (MX) knockoff-based methods have much related model assumptions, which makes them appealing for the detection of new biomarkers. However, there are no guidelines for their practical use. In this research, we systematically compared the performance of MX-based and GM methods, where the impacts of the distribution of explanatory variables, their relatedness and the signal-to-noise ratio were evaluated. MX with knockoff generated using the second-order approximates (MX-SO) has the best performance as compared to other MX-based methods. MX-SO and GM have similar levels of power and computational speed under most of the simulations, but GM is more robust in the control of false discovery rate (FDR). In particular, MX-SO can only control the FDR well when there are weak correlations among explanatory variables and the sample size is at least moderate. On the contrary, GM can have the desired FDR as long as explanatory variables are not highly correlated. We further used GM and MX-based methods to detect biomarkers that are associated with the Alzheimer’s disease-related PET-imaging trait and the Parkinson’s disease-related T-tau of cerebrospinal fluid. We found that MX-based and GM methods are both powerful for the analysis of big biological data. Although genes selected from MX-based methods are more similar as compared to those from the GM method, both MX-based and GM methods can identify the well-known disease-associated genes for each disease. While MX-based methods can have a slightly higher power than that of the GM method, it is less robust, especially for data with small sample sizes, unknown distributions, and high correlations.

To study the drillability and microscopic damage changes of granite after high temperature exposure and to study the influence of different cooling times on drillability after high temperature exposure, granite for high-temperature heat treatment was cooled by different times (2 h, 4 h, 24 h, and 48 h). Through the drillability experiment and the cast thin identification of the processed rock samples, the influence law and mechanism of high temperature on the drillability of granite were obtained, and the influence of different cooling times on the granite drillability was also investigated. The research results show that granite always maintains a high drillability index under the constraints of heat treatment not exceeding 500℃ and natural cooling for 2 h. After cooling 4 h, 24 h, and 48 h, the impact of high temperature on drillability shows three stages (First degradation stage, strengthening stage, second degradation stage). The location and number of microcracks affect the difficulty of rock resistance to crushing. After 400℃ heat treatment, the internal microcracks of the granite begin to increase significantly. When the microcracks generate a large number of microcracks inside the quartz particles, the drillability of the granite is significantly reduced. After heat treatment at 100℃, cooling for no more than 4 h at the same time will significantly affect the drillability of granite. After heat treatment at 200-400℃, the drillability index of granite will increase significantly as the cooling time (4-48 h) continues to increase. The damage caused by 500℃ to granite is irreversible, and 600℃ has completely degraded the granite. Understanding the influence of high temperature and cooling time on the drillability of granite can provide basic theoretical support for the efficient exploitation of hot dry rock resources.

The rare sugar L-sorbose is shown to decrease cell viability and increase apoptotic cells in culture and to enhance the effect of tumor chemotherapy in combination with sorafenib in mouse xenograft models.

Friction stir welding (FSW) is a new solid-state joining process for joining light metals, such as magnesium (Mg) alloys. However, the texture-induced softening mechanism (in stir zone, SZ) tends to cause the worsening of mechanical properties in FSW Mg alloys. In this work, multi-pass hot-rolling and subsequent annealing is used to ameliorate the FSW AZ31 alloy plate. The results show that multi-pass hot-rolling leads to the c-axes of most grains in the SZ approximately perpendicular to the normal direction (ND) transforming into these almost parallel to the ND, accompanied with multiple twin types. After subsequent annealing, twins, as nucleation sites, promote the formation of new grains with off-basal texture, resulting in the weak basal texture. Compared with the FSW plate and the initial plate, the rolled-annealed FSW plate exhibits a relatively uniform hardness distribution and a “strength-ductility” synergy, which are mainly attributed to an appropriate texture feature and a homogeneous grain structure. This work provides a new idea for the development of new high-performance FSW Mg alloys.

Cable termination serves as a crucial carrier for high-speed train power transmission and a weak part of the cable insulation system. Partial discharge detection plays a significant role in evaluating insulation status. However, field testing signals are often contaminated by external corona interference, which affects detection accuracy. This paper proposes a classification model based on wavelet transform (WT) and deep belief network (DBN) to accurately and rapidly identify corona discharge in the partial discharge signals of vehicle-mounted cable terminals. The method utilizes wavelet transform for noise reduction, employing the sigmoid activation function and analyzing the impact of WT on DBN classification performance. Research indicates that this method can achieve an accuracy of over 89% even with limited training samples. Finally, the reliability of the proposed classification model is verified using measured mixed signals.

White pepper, used both as a seasoning in people’s daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper.