Search

Abstract Background Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer. Case presentation AC1 A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported. Discussion For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.

Abstract Background Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. Method Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. Results Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77–2.67). The median follow‐up period was 5.1 95% CI [4.7–5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51–10.59], P

Defects are believed to always scatter carriers. Here, the authors find that the quantum gaps in GeTe-based materials do not scatter carriers, which decouple the carriers and phonons transport leading to high thermoelectric performance.

Engineering metals often suffer from a small elastic deformation with a linear stress-strain relationship obeying Hooke’s law. Here the authors observe a large nonlinear tensile elastic deformation with a strain of >4.3% in a bulk Cu alloy that offers potential for elastic strain engineering.

Background and aim: Moxibustion is widely used in China and other East Asian countries to manage the symptom of ankylosing spondylitis (AS). This study investigated the effects of moxibustion intervention on protein expression through proteomics analysis in AS mice. Experimental procedure: Proteoglycan-induced spondylitis (PGISp) was established in Balb/c mice. PGISp mice were intervened with daily moxibustion at ST36, BL23, and DU4 for four weeks. Various biochemical (including pro-inflammatory cytokines and bone metabolism indexes) and histopathological parameters were determined. The effects of moxibustion on protein changes in AS mice were analyzed using data-independent acquisition-mass spectrometry (DIA-MS). The target proteins were then confirmed by Western blot analysis. Results: Moxibustion significantly decreased pro-inflammatory cytokine expression including IL-1β, TNF-α, IL-17, and IL-6, reduced the mRNA expression of RANKL, RANK, ALP, and OCN, and improved the histopathological examination in AS mice. DIA-MS proteomic technique has identified 25 candidate proteins involved in the mechanisms of moxibustion for AS mice, most of which are mainly associated with the regulation of Wnt/β-catenin. Integrated pathway analysis revealed that glycine, serine and threonine metabolism together with lipid metabolism were the most important canonical pathways involved in the anti-AS effect of moxibustion. In line with the multi-omic data, the levels of BPGM, APOC2, APOE, and GPD1 modified in the AS mice, intervened with moxibustion as confirmed by Western blot. In particular, APOE may play a key role in linking the lipid metabolism and the Wnt/β-catenin pathway of new bone formation. Conclusion: In conclusion, moxibustion may reduce pro-inflammatory cytokines and improve bone erosion for AS mice. The regulation of APOE by moxibustion may have a potential inhibitory effect on the Wnt/β-catenin pathway in AS mice. However, due to the lack of silencing or overexpression of key molecules of the signal pathway, whether the beneficial and positive effect of moxibustion involved in the regulation of Wnt/β-catenin signaling pathway by APOE or other aspects, needed to be explored in further study.

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies; its recurrence is associated with high mortality and poor recurrence‐free survival and is affected by multisystem and multilevel pathological changes. To identify the key proteins associated with tumor recurrence and the underlying mechanisms, proteomic profiling of tumor specimens from early recurrence and nonrecurrence patients was performed in this study. Proteomics was applied to identify differentially expressed proteins during the early recurrence of HCC after surgery. Osteosarcoma amplified‐9 (OS‐9) was discovered, and the correlation between OS‐9 expression and the clinicopathological characteristics of patients was analyzed. Invasion and migration were examined in SMMC‐7721 cells with and without OS‐9 overexpression. Proteomics was performed once again using SMMC‐7721 cells with OS‐9 overexpression to further analyze the proteins with altered expression. OS‐9 was overexpressed in the early recurrence group, and OS‐9 overexpression was associated with high serum alpha‐fetoprotein levels and poor recurrence‐free survival in 196 patients with HCC. The invasion and migration abilities of SMMC‐7721 cells were enhanced in the OS‐9 overexpression group. Bioinformatic functional enrichment methods, including Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis, revealed that the hypoxia‐inducible factor 1 (HIF‐1) and tumor necrosis factor (TNF) signaling pathways were activated in the OS‐9 overexpression group. The migration and invasion capacities of OS‐9 overexpressed HCC cell line were weakened while treated with HIF‐1α or TNF‐α inhibitors. Conclusion: Our results suggest that the overexpression of OS‐9 is related to HCC recurrence, thereby contributing to the migration and invasion capacities of HCC cell line by regulating the HIF‐1 and TNF pathways.

A facile and economical approach was developed for the large-scale production of powdered core-shell structured PTFE/Al (CS-PA) energetic materials through ultrasonic-assisted mixing. The low-cost micrometer-sized PTFE and Al particles were used as starting materials. Under high-power ultrasonic waves, the PTFE powder was dispersed into nano-to sub-micrometer-sized particles and then encapsulated the Al microparticles to form the core-shell structure. The heat of combustion, burning rate, and pressurization rate of the powdered CS-PA were measured. The thermal-initiated reaction behavior was further evaluated using thermogravimetry-differential scanning calorimetry. Subsequently, the bulk CS-PA with a uniform microstructure was obtained via cold isostatic pressing of the powdered CS-PA followed by vacuum sintering. For the bulk CS-PA, the quasi-static compression behavior was characterized, and the impact-initiated reaction processes were conducted using the Split Hopkinson Pressure Bar (SHPB) and evaluated by a high-speed camera. Compared to physically mixed PTFE/Al materials, the powdered and bulk CS-PA demonstrated enhanced thermal- and impact-initiated reaction characteristics respectively, proving the effectiveness of our approach for constructing core-shell structures.

Abstract The liver is unique in its ability to regenerate from a wide range of injuries and diseases. Liver regeneration centers around hepatocyte proliferation and requires the coordinated actions of nonparenchymal cells, including biliary epithelial cells, liver sinusoidal endothelial cells, hepatic stellate cells and kupffer cells. Interactions among various hepatocyte and nonparenchymal cells populations constitute a sophisticated regulatory network that restores liver mass and function. In addition, there are two different ways of liver regeneration, self-replication of liver epithelial cells and transdifferentiation between liver epithelial cells. The interactions among cell populations and regenerative microenvironment in the two modes are distinct. Herein, we first review recent advances in the interactions between hepatocytes and surrounding cells and among nonparenchymal cells in the context of liver epithelial cell self-replication. Next, we discuss the crosstalk of several cell types in the context of liver epithelial transdifferentiation, which is also crucial for liver regeneration. Video abstract

The uncertainties of wind turbine (WT) output have large impacts on the optimal operation of integrated energy systems. This paper investigates the two-stage robust optimization (RO) of hybrid energy integration regarding wind volatility. In RO method, the WT output is modeled with an uncertainty budget, which represents the degree of conservatism. Simulation results validate that when the uncertainty budget rises to a maximal value, ESS degradation cost increases 25.7%, and total cost decreases 2.0%. Additionally, demand response program (DRP) exhibits elastic and voluntary merits. With the implementation of DRP, 6139.9$ total savings are achieved compared with the ordinary RO method. Meanwhile, the merits of stochastic optimization (SO) have also been studied. Despite the ESS degradation cost and total cost in SO being lower than those in RO, SO requires accurate probability distribution of uncertain variables in real situations. RO can shortly provide worst-case schemes which are highly appreciated by power utility companies.

Gelation of waxy crude oil is the source of its complex macroscopic rheological properties, while the rheological properties of waxy crude oil are the important basic data for pipeline transportation.Herein, two models of waxy crude oil system were established based on the macroscopic experimental data, and the molecular dynamics simulation was carried out using the Materials Studio software. In this way, the microscopic mechanism for gelation process of waxy crude oil was studied from the prospective of molecular dynamics. According to the results, the simulated condensation point value of crude oil is consistent with the experimental value through the judgment based on the density and diffusion coefficient. The sudden change of diffusion coefficient of wax crystal molecules and the deviation of mean square displacement are significantly reduced due to the formation of spatial network structure during crude oil gelation. By characterizing the change of microstructure of crude oil during gelationwith the radial distribution function, it is found that the peak value of radial distribution function between the same types of molecular increases gradually, and the largest degree of aggregation between wax crystals occurs at the condensation point. So, wax crystal molecule is the main factor that affects the condensation point of waxy crude oil. Generally, the research resultscouldprovide a basic theory for the acquisition of basic data concerning the pipeline transportation technology of waxy crude oil.

Abstract Background Zoysiagrass (Zoysia spp.) is a warm-season turfgrass. It is widely used as turfgrasses throughout the world, offers good turf qualities, including salt tolerance, resistance to drought and heat. However, the underlying genetic mechanism of zoysiagrass responsive to salt stress remains largely unexplored. Results In present study, we performed a whole-genome comparative analysis for ten plant genomes. Evolutionary analysis revealed that Chloridoideae diverged from Panicoideae approximately 33.7 million years ago (Mya), and the phylogenetic relationship among three zoysiagrasses species suggested that Zoysia matrella may represent an interspecific hybrid between Zoysia japonica and Zoysia pacifica. Genomic synteny indicated that Zoysia underwent a genus-specific whole-genome duplication (WGD) event approximately 20.8 Mya. The expression bais of homologous genes between the two subgenomes suggested that the B subgenome of Z. japonica contributes to salt tolerance. In additon, comparative genomic analyses revealed that the salt adaptation of Zoysia is likely attributable to the expanded cytochrome P450 and ABA biosynthetic gene families. Furthermore, we further found that many duplicated genes from the extra WGD event exhibited distinct functional divergence in response to salt stress using transcriptomic analysis, suggesting that this WGD event contributed to strong resistance to salt stress. Conclusions Here, our results revealed that expanded cytochrome P450 and ABA biosynthetic gene families, and many of those duplicated genes from recent zoysia-specific WGD event contributed to salt adaptation of zoysiagrass, which provided insight into the genetic underpinning of salt adaptation and valuable information for further studies on salt stress-related traits in Zoysia.

Cell-cell communication is a vital feature involving numerous biological processes. Here, the authors develop SpaTalk, a cell-cell communication inference method using knowledge graph for spatially resolved transcriptomic data, providing valuable insights into spatial intercellular tissue dynamics.

Abstract Background Protozoan parasite secretions can be triggered by various modified media and diverse physicochemical stressors. Equally, host-parasite interactions are known to co-opt the exchange and secretion of soluble biochemical components. Analysis of Eimeria falciformis sporozoite secretions in response to interaction with mouse intestinal epithelial cells (MIECs) may reveal parasite secretory motifs, protein composition and inflammatory activities of E. falciformis extracellular vesicles (EVs). Methods Eimeria falciformis sporozoites were allowed to interact with inactivated MIECs. Parasite secretions were separated into EV and vesicle-free (VF) fractions by discontinuous centrifugation and ultracentrifugation. Secreted EVs were purified in an iodixanol density gradient medium and the protein composition of both EV and VF fractions were analyzed by liquid chromatoraphy-tandem mass spectroscopy. The inflammatory activities of E. falciformis sporozoite EV on MIECs were then investigated. Results During the interaction of E. falciformis sporozoites with inactivated MIECs, the parasite secreted VF and vesicle-bound molecules. Eimeria falciformis vesicles are typical pathogenic protozoan EVs with a mean diameter of 264 ± 2 nm, and enclosed heat shock protein (Hsp) 70 as classical EV marker. Refractile body-associated aspartyl proteinase (or eimepsin), GAP45 and aminopeptidase were the main components of E. falciformis sporozoite EVs, while VF proteins include Hsp90, actin, Vps54 and kinases, among others. Proteomic data revealed that E. falciformis EV and VF proteins are aggregates of bioactive, antigenic and immunogenic molecules which act in concert for E. falciformis sporozoite motility, pathogenesis and survival. Moreover, in MIECs, E. falciformis EVs induced upregulation of gene expression and secretion of IL-1β, IL-6, IL-17, IL-18, MCP1 as well as pyroptosis-dependent caspase 11 and NLRP6 inflammasomes with the concomitant secretion of lactate dehydrogenase. Conclusions Eimeria falciformis sporozoite interaction with MIECs triggered the secretion of immunogenic and antigenic proteins. In addition, E. falciformis sporozoite EVs constitute parasite-associated molecular pattern that induced inflammatory response and cell death. This study offers additional insight in the secretion and protein composition of E. falciformis secretomes as well as the proinflammatory functions of E. falciformis sporozoite EVs. Graphical Abstract

Abstract Background Ubiquitination is essential for many cellular processes in eukaryotes, including 26S proteasome-dependent protein degradation, cell cycle progression, transcriptional regulation, and signal transduction. Although numerous ubiquitinated proteins have been empirically identified, their cognate ubiquitin E3 ligases remain largely unknown. Results Here, we generate a complete ubiquitin E3 ligase-encoding open reading frames (UbE3-ORFeome) library containing 98.94% of the 1515 E3 ligase genes in the rice (Oryza sativa L.) genome. In the test screens with four known ubiquitinated proteins, we identify both known and new E3s. The interaction and degradation between several E3s and their substrates are confirmed in vitro and in vivo. In addition, we identify the F-box E3 ligase OsFBK16 as a hub-interacting protein of the phenylalanine ammonia lyase family OsPAL1–OsPAL7. We demonstrate that OsFBK16 promotes the degradation of OsPAL1, OsPAL5, and OsPAL6. Remarkably, we find that overexpression of OsPAL1 or OsPAL6 as well as loss-of-function of OsFBK16 in rice displayed enhanced blast resistance, indicating that OsFBK16 degrades OsPALs to negatively regulate rice immunity. Conclusions The rice UbE3-ORFeome is the first complete E3 ligase library in plants and represents a powerful proteomic resource for rapid identification of the cognate E3 ligases of ubiquitinated proteins and establishment of functional E3–substrate interactome in plants.

BackgroundDepression is a widespread mental disorder that affects a significant portion of the population. However, the assessment of depression is often subjective, relying on standard questions or interviews. Acoustic features have been suggested as a reliable and objective alternative for depression assessment. Therefore, in this study, we aim to identify and explore voice acoustic features that can effectively and rapidly predict the severity of depression, as well as investigate the potential correlation between specific treatment options and voice acoustic features.MethodsWe utilized voice acoustic features correlated with depression scores to train a prediction model based on artificial neural network. Leave-one-out cross-validation was performed to evaluate the performance of the model. We also conducted a longitudinal study to analyze the correlation between the improvement of depression and changes in voice acoustic features after an Internet-based cognitive-behavioral therapy (ICBT) program consisting of 12 sessions.ResultsOur study showed that the neural network model trained based on the 30 voice acoustic features significantly correlated with HAMD scores can accurately predict the severity of depression with an absolute mean error of 3.137 and a correlation coefficient of 0.684. Furthermore, four out of the 30 features significantly decreased after ICBT, indicating their potential correlation with specific treatment options and significant improvement in depression (p

BackgroundOvarian cancer (OC) is a highly lethal and aggressive gynecologic cancer, with an overall survival rate that has shown little improvement over the decades. Robust models are urgently needed to distinguish high-risk cases and predict reliable treatment options for OC. Although anoikis-related genes (ARGs) have been reported to contribute to tumor growth and metastasis, their prognostic value in OC remains unknown. The purpose of this study was to construct an ARG pair (ARGP)-based prognostic signature for patients with OC and elucidate the potential mechanism underlying the involvement of ARGs in OC progression.MethodsThe RNA-sequencing and clinical information data of OC patients were obtained from The Center Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A novel algorithm based on pairwise comparison was utilized to select ARGPs, followed by the Least Absolute Shrinkage and Selection Operator Cox analysis to construct a prognostic signature. The predictive ability of the model was validated using an external dataset, a receiver operating characteristic curve, and stratification analysis. The immune microenvironment and the proportion of immune cells were analyzed in high- and low-risk OC cases using seven algorithms. Gene set enrichment analysis and weighted gene co-expression network analysis were performed to investigate the potential mechanisms of ARGs in OC occurrence and prognosis.ResultsThe 19-ARGP signature was identified as an important prognostic predictor for 1-, 2-, and 3-year overall survival of patients with OC. Gene function enrichment analysis showed that the high-risk group was characterized by the infiltration of immunosuppressive cells and the enrichment of adherence-related signaling pathway, suggesting that ARGs were involved in OC progression by mediating immune escape and tumor metastasis.ConclusionWe constructed a reliable ARGP prognostic signature of OC, and our findings suggested that ARGs exerted a vital interplay in OC immune microenvironment and therapeutic response. These insights provided valuable information regarding the molecular mechanisms underlying this disease and potential targeted therapies.

Curcumin is well known as a potent antioxidant and free radical scavenger and has great potential for anti-aging applications. In this study, we investigate the molecular mechanism of curcumin in prolonging the lifespan of C. elegans. Four concentrations of curcumin (10, 25, 50, and 100 µM) were administered, and the optimal treatment concentration was determined by analyzing the nematode lifespan, physiology, and biochemistry. Additionally, RNA-seq and qRT-PCR were performed to explore the antioxidant effect of curcumin and its underlying mechanism. Results revealed that curcumin could significantly improve the survival capacity of C. elegans without influencing its growth. Curcumin was observed to significantly decrease the levels of reactive oxygen species (ROS) under extreme conditions such as heat stress and paraquat stress. In addition, curcumin increased the amount of nematode mitochondrial DNA (mtDNA) replication. RNA-seq results revealed that the underlying mechanism of curcumin in C. elegans is related to the mitogen-activated protein kinase (MAPK) pathway. qRT-PCR results confirmed that the expression of oxidative stress-related genes (sod-1, sod-2, sod-3, gst-4) was increased, and the expression of MAPK signaling pathway-related genes (sek-1, pmk-1, nsy-1) was significantly downregulated. Furthermore, the administration of curcumin extended the lifespan of nematodes, potentially through the enhancement of oxidative stress resistance and the downregulation of the MAPK signaling pathway. These findings improve our understanding of both lifespan extension and the potential mechanism of curcumin in C. elegans.

For higher precision phase shift measurement, based on the characteristics of vortex beam, the manuscript introduces phase shift directly through the polar axis rotation of the vortex beam. Compared to traditional grey-scale modulation, the proposed VPAR-PSI method introduces a phase-shifting directly instead of changing the grey-scale, which not only can largely reduce the deviation caused by traditional PSI phase modulation via grey-scale change, but also can effectively avoid the non-linearity between grey-scale and phase of traditional PSI. For verifying the effectiveness of the method proposed in this manuscript, a simulation experiment, sample experiment, and VPAR-PSI and PSI comparison experiment were conducted. The results show that the proposed VPAR-PSI has a high phase-shifting and demodulation accuracy, and can be well implemented to measurement of optical components. The comparative experimental show that compared to conventional PSI, the measurement results of VPAR-PSI have smaller envelope values (mean envelope reduction of 1.4202λ), smaller RMS and standard deviation (the values decreased by 0.3515, 0.3067, and the percentage decreases were 59.69%, 59.71% respectively), proving that the VPAR-PSI technique are more accurate and stable.© 2020 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Global Science and Technology Forum Pte Ltd.

Growing evidence demonstrated that cuproptosis play critical roles in human cancers. We aimed to identify the roles of cuproptosis related genes (CRGs) in prognosis and immunity of Ewing's sarcoma.The data of GSE17674 and GSE63156 were obtained from GEO. The expression of 17 CRGs and immune cells were explored, then correlation was analyzed. Based on CRGs, two molecular clusters were identified by consensus clustering algorithm. KM survival and IME features including immune cells, immune response, checkpoint genes between clusters were evaluated. NFE2L2, LIAS, and CDKN2A were screened out as prognostic signatures by univariate, LASSO and step regression. A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values. The accuracy of risk model was also well validated in external dataset. A nomogram was constructed and evaluated by calibration curves and DCA. Low level of immune cells, immune response, and enriched checkpoint genes were found in high-risk group. GSEA of signatures and GSVA of ES-related pathways revealed the potential molecular mechanism involved in ES progression. Several drugs showed sensitivity to ES samples. DEGs between risk groups were screened out, and function enrichment was conducted. Finally, scRNA analysis of GSE146221 was done. NFE2L2, and LIAS played crucial role in the evolution of ES by pesudotime and trajectory methods. Our study provided new aspects for further research in ES.

IntroductionSerotonin (5-hydroxytryptamine; 5-HT) and GABA (γ-aminobutyric acid) are involved in the regulation of behaviors in the central nervous system. However, it remains unclear whether they modulate olfaction in the peripheral nervous system, and how they modulate olfaction.Methods and resultsOne 5-HT receptor sequence (Lmig5-HT2) and one GABA receptor sequence (LmigGABAb) were identified in locust antennae by transcriptome analysis and polymerase chain reaction experiments. In situ hybridization localized Lmig5-HT2 to accessory cells, while LmigGABAb was localized to olfactory receptor neurons (ORNs) in locust chemosensilla. Single-unit electrophysiological recordings combined with RNA interference (RNAi) experiments indicated ORNs of locusts with knockdown of Lmig5-HT2 (ds-Lmig5-HT2) and LmigGABAb (ds-LmigGABAb) to some odors had significantly higher responses than wild-type and control locusts in the dose-dependent responses. Moreover, the gaps between the responses of ORNs of RNAi ones and those of wild-type and ds-GFP enlarged with an increase in concentrations of odors.DiscussionTaken together, our findings suggest that 5-HT, GABA, and their receptors exist in the insect peripheral nervous system and that they may function as negative feedback to ORNs and contribute to a fine-tuning mechanism for olfaction in the peripheral nervous system.

Plant terpenoid synthase (TPS) family genes participate in metabolite synthesis, hormones, gossypol, etc. Here, we genome-widely identified TPS family genes in 12 land plant species. Four hundred and thirty TPS-related genes were divided into seven subfamilies. The TPS-c in Bryophytes was suggested to be the earliest subfamily, followed by the TPS-e/f and TPS-h presence in ferns. TPS-a, the largest number of genes, was derived from monocotyledonous and dicotyledonous plants. Collinearity analysis showed that 38 out of the 76 TPS genes in G. hirsutum were collinear within G. arboreum and G. raimondii. Twenty-one GhTPS-a genes belong to the cadinene synthase (GhCDN) subfamily and were divided into five groups, A, B, C, D, and E. The special cis-elements in the promoters of 12 GhCDN-A genes suggested that the JA and ethylene signaling pathways may be involved in their expression regulation. When 12 GhCDN-A genes were simultaneously silenced through virus-induced gene silencing, the glandular color of GhCDN-A-silenced plants was lighter than that of the control, supported by a gossypol content decrease based on HPLC testing, suggesting that GhCDN-A subgroup genes participate in gossypol synthesis. According to RNA-seq analysis, gossypol synthesis-related genes and disease-resistant genes in the glandular variety exhibited upregulated expression compared to the glandless variety, whereas hormone signaling-related genes were downregulated. All in all, these results revealed plant TPS gene evolution rules and dissected the TPS subfamily, GhCDN-A, function in gossypol synthesis in cotton.

IntroductionPotassium and phosphorus are essential macronutrients for plant growth and development. However, most P and K exist in insoluble forms, which are difficult for plants to directly absorb and utilize, thereby resulting in growth retardation of plants under P or K deficiency stress. The Aspergillus aculeatus fungus has growth-promoting characteristics and the ability to dissolve P and K.MethodsHere, to investigate the physiological effects of A. aculeatus on bermudagrass under P or K deficiency, A. aculeatus and bermudagrass were used as experimental materials.Results and discussionThe results showed that A. aculeatus could promote tolerance to P or K deficiency stress in bermudagrass, decrease the rate of leaf death, and increase the contents of crude fat as well as crude protein. In addition, A. aculeatus significantly enhanced the chlorophyll a+b and carotenoid contents. Moreover, under P or K deficiency stress, bermudagrass inoculated with A. aculeatus showed higher N, P, and K contents than non-inoculated plants. Furthermore, exogenous A. aculeatus markedly decreased the H2O2 level and CAT and POD activities. Based on our results, A. aculeatus could effectively improve the forage quality of bermudagrass and alleviate the negative effects of P or K deficiency stress, thereby playing a positive economic role in the forage industry.

Microwave and infrared–thermal radiation-compatible shielding fabrics represent an important direction in the development of wearable protective fabrics. Nevertheless, effectively and conveniently integrating compatible shielding functions into fabrics while maintaining breathability and moisture permeability remains a significant challenge. Here, we take hydrophilic PVA-co-PE nanofibrous film-coated PET fabric (NFs/PET) as a flexible substrate and deposit a dielectric/conductive (SiO2/Al) bilayer film via magnetron sputtering. This strategy endows the fabric surface with high electrical conductivity, nanoscale roughness comparable to visible and infrared waves, and a dielectric–metal contact interface possessing localized plasmon resonance and Mie scattering effects. The results demonstrate that the optimized SiO2/Al/NFs/PET composite conductive fabric (referred to as S4-1) possesses favorable X-band electromagnetic interference (EMI) shielding effectiveness (50 dB) as well as excellent long-wave infrared (LWIR) shielding or IR stealth performance (IR emissivity of 0.60). Notably, the S4-1 fabric has a cooling effect of about 12.4 °C for a heat source (80 °C) and an insulating effect of about 17.2 °C for a cold source (−20 °C), showing excellent shielding capability for heat conduction and heat radiations. Moreover, the moisture permeability of the S4-1 fabric is about 300 g/(m2·h), which is better than the requirement concerning moisture permeability for wearable fabrics (≥2500–5000 g/(m2·24 h)), indicating excellent heat and moisture comfort. In short, our fabrics have lightweight, thin, moisture-permeable and excellent shielding performance, which provides novel ideas for the development of wearable multi-band shielding fabrics applied to complex electromagnetic environments.

We propose an FSK/ASK orthogonal modulation system based on a novel noncoherent detection (NCD) scheme, aimed at expanding the system capacity for short-reach optical communications cost-effectively. In the transmitter, the FSK optical signal is generated by simple frequency modulation through a directly modulated distributed feedback laser. Subsequently, by utilizing a Mach–Zehnder modulator for ASK modulation, the FSK/ASK optical signal is obtained. The novel and low-complexity NCD receiver consists of an intensity detection branch and a frequency detection branch. The frequency detection branch is composed of an optical differentiator, a photodetector, and frequency extraction circuits. Notably, the proposed NCD scheme overcomes the limitation of the traditional FSK/ASK-NCD receiver stemming from the trade-off between the detected signal quality of the amplitude and frequency. Furthermore, electronic dispersion compensation (EDC) is available. Through numerical simulations, our findings demonstrate that the proposed FSK/ASK-NCD system, assisted by EDC, achieves a remarkable 100 km transmission span for both 40 Gbps 2FSK/2ASK and 60 Gbps 2FSK/4ASK modulation formats, which surpasses the 2ASK-DD and the 4ASK-DD systems, where the maximum achievable spans are limited to less than 20 km. These results underscore the potential of the proposed system as a robust candidate for future passive optical access networks.

In recent years, there have been significant advancements in the research of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). However, several limitations and challenges still exist. For instance, researchers face constraints regarding experimental conditions and the feasibility of sample acquisition for studying SFTSV. To enhance the quality and comprehensiveness of SFTSV research, we opted to employ PMA-induced THP-1 cells as a model for SFTSV infection. Multiple time points of SFTSV infection were designed to capture the dynamic nature of the virus–host interaction. Through a comprehensive analysis utilizing various bioinformatics approaches, including diverse clustering methods, MUfzz analysis, and LASSO/Cox machine learning, we performed dynamic analysis and identified key genes associated with SFTSV infection at the host cell transcriptomic level. Notably, successful clustering was achieved for samples infected at different time points, leading to the identification of two important genes, PHGDH and NLRP12. And these findings may provide valuable insights into the pathogenesis of SFTSV and contribute to our understanding of host–virus interactions.

Hand gesture recognition is an essential Human–Computer Interaction (HCI) mechanism for users to control smart devices. While traditional device-based methods support acceptable recognition performance, the recent advance in wireless sensing could enable device-free hand gesture recognition. However, two severe limitations are serious environmental interference and high-cost hardware, which hamper wide deployment. This paper proposes the novel system TaGesture, which employs an inaudible acoustic signal to realize device-free and training-free hand gesture recognition with a commercial speaker and microphone array. We address unique technical challenges, such as proposing a novel acoustic hand-tracking-smoothing algorithm with an Interaction Multiple Model (IMM) Kalman Filter to address the issue of localization angle ambiguity, and designing a classification algorithm to realize acoustic-based hand gesture recognition without training. Comprehensive experiments are conducted to evaluate TaGesture. Results show that it can achieve a total accuracy of 97.5% for acoustic-based hand gesture recognition, and support the furthest sensing range of up to 3 m.

With the large-scale construction and commissioning of transmission lines over the past two decades, the grid is facing a large-scale centralized decommissioning of transmission lines. The transmission line’s economic life is crucial to rationalizing its construction and reducing the grid’s development costs. Based on the minimum economic life calculation principle, the static and dynamic transmission line economic life calculation model is established, considering the whole life cycle for transmission line cost. The improved gray GM (1,1) model is applied to forecast cost data during the economic life assessment of transmission lines with fewer samples. Considering the cost uncertainty in life-cycle costing, the interval cost model based on the coefficient of variation wave amplitude is proposed to determine the economic life intervals under different guarantees by using the normal distribution probability density function, which reduces the influence of cost fluctuations on the economic life calculation error. The economic life analysis of a 500 kV transmission line is used as a case study to verify the model’s accuracy and effectiveness. The method shows the economic life intervals under different guarantee degrees based on the most probable economic life determination, which provides theoretical support for calculating the economic life elasticity of transmission lines.

Change detection (CD), a crucial technique for observing ground-level changes over time, is a challenging research area in the remote sensing field. Deep learning methods for CD have made significant progress in remote sensing intelligent interpretation. However, with very high-resolution (VHR) satellite imagery, technical challenges such as insufficient mining of shallow-level features, complex transmission of deep-level features, and difficulties in identifying change information features have led to severe fragmentation and low completeness issues of CD targets. To reduce costs and enhance efficiency in monitoring tasks such as changes in national resources, it is crucial to promote the practical implementation of automatic change detection technology. Therefore, we propose a deep learning approach utilizing heterogeneity enhancement and homogeneity restraint for CD. In addition to comprehensively extracting multilevel features from multitemporal images, we introduce a cosine similarity-based module and a module for progressive fusion enhancement of multilevel features to enhance deep feature extraction and the change information utilization within feature associations. This ensures that the change target completeness and the independence between change targets can be further improved. Comparative experiments with six CD models on two benchmark datasets demonstrate that the proposed approach outperforms conventional CD models in various metrics, including recall (0.6868, 0.6756), precision (0.7050, 0.7570), F1 score (0.6958, 0.7140), and MIoU (0.7013, 0.7000), on the SECOND and the HRSCD datasets, respectively. According to the core principles of change detection, the proposed deep learning network effectively enhances the completeness of target vectors and the separation of individual targets in change detection with VHR remote sensing images, which has significant research and practical value.

As the demand for power supply increases, the investment in the power transmission system constantly increases. An accurate economic evaluation of the power transmission system is essential for future investment decisions and management. Applying a single method in economic evaluation leads to excessive subjective consciousness and unreasonable weight allocation. The Euclidean distance in the traditional TOPSIS method only partially works on the condition that the criteria are linearly correlated. To solve these problems, an economic evaluation method based on improved TOPSIS and BWM-anti-entropy weight is proposed. For the assignment of weights, the method retains the advantages of subjective and objective weighting methods based on the Nash equilibrium, breaks through the limitation of utilizing a single method, which contributes to one-sided results, and enhances the scientific rigor and rationality of the comprehensive weighting process. Furthermore, based on comprehensive weights, the method improves the TOPSIS by introducing the Mahalanobis distance and Pearson correlation coefficients, which can eliminate the influence of linear correlation. Finally, ten 500 kV transmission and transformation projects are analyzed and ranked to verify the method’s feasibility. Empirical analysis shows that the method can effectively evaluate the economic benefits of the power transmission system.

Background: The association between dietary potassium and clinical prognosis is unclear in patients with chronic kidney disease (CKD). Here, we explored the association between dietary potassium intake and all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. Methods: Here, we present a retrospective analysis of a prospective study. Patients that began incident PD in our center between 1 October 2002 and 31 August 2014 were screened. We recorded all demographic and clinical data at baseline. Repeated measurements were recorded at regular intervals to calculate time-averaged values. Spline regression analysis and Cox proportional regression models were used to evaluate the relationship between dietary potassium and mortality. Results: We followed 881 PD patients for 45.0 (21.5, 80.0) months; 467 patients died, of which 189 (40.5%) died of CV death and 93 were still on PD treatment. Compared with those who had baseline dietary potassium ≥1200 mg/d, the majority of patients with lower dietary potassium were female, older, or poorly educated. They were prone to have poorer nutritional status, CV disease, and diabetes mellitus (p < 0.05). In the unadjusted analysis, both baseline and time-averaged dietary potassium p < 0.001~0.01). After adjusting for demographic and laboratory data, the association between potassium intake and all-cause and CV mortality weakened, which even disappeared after additional adjustment for dietary fiber, protein, and energy intake. Conclusions: Dietary potassium in PD patients was not independently associated with all-cause and CV mortality.

Objective The beneficial effects of glycine were tested in piglets with diquat-induced hepatic injury. Methods Thirty-two piglets were assigned by a 2×2 factorial experimental design including glycine supplementation and diquat challenge. After 3 weeks of feeding with a basic diet or a 1% glycine supplemented diet, piglets were challenged with diquat or saline. After 1 week later, the piglets were slaughtered and samples were collected. Results Our results indicated that glycine alleviated diquat induced morphological hepatic injury, decreased the activities of plasma alanine aminotransferase, aspartate aminotransferase and glutamyl transpeptidase in the piglets under diquat challenge, and increased total antioxidant capacity and antioxidative enzyme activity significantly. Adding glycine enhanced the concentrations of hepatic adenosine triphosphate and adenosine diphosphate. Transmission electron microscope observation showed that diquat induced clear hepatocytes ferroptosis and its effect could be alleviated by glycine to a certain degree. Moreover, glycine significantly affected mRNA and protein expression of ferroptosis-related signals in the liver. Conclusion These results demonstrated that glycine attenuated liver damage via inhibiting ferroptosis.

Abstract Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IMPs) family belongs to a highly conserved family of RNA-binding proteins (RBPs) and is responsible for regulating RNA processing including localization, translation and stability. Mammalian IMPs (IMP1-3) take part in development, metabolism and tumorigenesis, where they are believed to play a major role in cell growth, metabolism, migration and invasion. IMPs have been identified that are expressed in ovary, placenta and embryo. The up-to-date evidence suggest that IMPs are involved in folliculogenesis, oocyte maturation, embryogenesis, implantation, and placentation. The dysregulation of IMPs not only contributes to carcinogenesis but also disturbs the female reproduction, and may participate in the pathogenesis of reproductive diseases and obstetric syndromes, such as polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM) and gynecological tumors. In this review, we summarize the role of IMPs in female reproductive pathophysiology, and hope to provide new insights into the identification of potential therapeutic targets.

Abstract Background Previous studies have described and recorded abnormal root morphology; however, most of these studies were based on two-dimensional periapical or panoramic radiographs, and only a few studies have quantified it. We aimed to combine two-dimensional periapical radiographs and three-dimensional cone-beam computed tomography (CBCT) to conduct qualitative judgments and quantitative analyses of normal and conical roots, and explore the clinical diagnostic method of normal and conical roots based on intraoral radiographs and CBCT. Methods The conical root was identified visually on periapical radiographs as the clinical gold standard. All teeth were divided into the cone-rooted teeth (CRT) or normal-rooted teeth (NRT) groups. Furthermore, differences in root length (RL), root surface area (RSA), and root volume (RV) of conical and normal roots in the maxillary premolars on CBCT were compared. Receiver operator characteristic curves were generated, and the area under the curve (AUC) and cut-off values were calculated to evaluate the diagnostic value of RV, RSA, RV/RL, and RSA/RL. Results The RSAs of NRT and CRT were 236.88 ± 27.93 mm2 and 207.98 ± 27.80 mm2, respectively (P = 0.000). The mean RV in the CRT group was lower than that in the NRT group, and the difference was statistically significant (253.40 ± 41.98 mm3 vs. 316.93 ± 49.89 mm3, P = 0.000). The RSA and RV of conical roots in single root premolars were 12.29% and 19.33% less than those of normal roots, respectively. The AUC values of RSA/RL and RV/RL were 0.87 and 0.89, respectively, and the best cut-off values were 19.61 for RSA/RL (if RSA/RL was

Mechanism driving continental growth on modern Earth has long been debated. By interpreting the long deep seismic reflection data across the ongoing India-Eurasia collision zone, the authors report crustal-scale magma accretion onto the south of central Lhasa terrane produced net continental growth.

Abstract Background Phototherapy-triggered immunogenic cell death (ICD) rarely elicits a robust antitumour immune response, partially due to low antigen exposure and inefficient antigen presentation. To address these issues, we developed novel methylene blue-loaded ovalbumin/polypyrrole nanoparticles (MB@OVA/PPY NPs) via oxidative polymerization and π–π stacking interactions. Results The as-prepared MB@OVA/PPY NPs with outstanding photothermal conversion efficiency (38%) and photodynamic properties were readily internalized into the cytoplasm and accumulated in the lysosomes and mitochondria. Upon 808 nm and 660 nm laser irradiation, the MB@OVA/PPY NPs not only ablated tumour cells by inducing local hyperthermia but also damaged residual tumour cells by generating a large amount of reactive oxygen species (ROS), finally triggering the release of many damage-associated molecular patterns (DAMPs). Moreover, the MB@OVA/PPY NPs synergized with DAMPs to promote the maturation and improve the antigen presentation ability of DCs in vitro and in vivo. Conclusions This work reported a PPY NPs-based nanoplatform to encapsulate the therepeutic proteins and absorb the functional molecules for combination therapy of tumours. The results demonstrated that the prepared MB@OVA/PPY NPs could be used as effective nanotherapeutic agents to eliminate solid tumours and trigger a powerful antitumour immune response.

Abstract Background Patatin-like phospholipase domain containing 3 (PNPLA3) is the main nonalcoholic fatty liver disease (NAFLD) susceptibility. Its expression is regulated tightly by nutritional and energy status, but the mechanism of epigenetic regulation of PNPLA3 gene by nutritional dietary factors has not been reported. Here, we investigated the effect and mechanism of Sirtuin 1 (SIRT1) regulated H3K9 deacetylation on PNPLA3 transcriptional expression in vivo and in vitro. Methods Mouse models of fasting/re-feeding transition and nonalcoholic fatty liver induced by high Sucrose diet were constructed; and HepG2 cells were treated with serum- and glucose-free medium or exposed to high glucose and high insulin, to generate fasting and high-glucose-induced lipid deposition cell states. Enrichment levels of histone H3K9 acetylation and sterol responsive element binding protein-1c (SREBP-1c) at the PNPLA3 promoter were observed by ChIP-qPCR. PNPLA3 gene expression was detected by real-time PCR; SIRT1 protein expression was detected by western blot. And lipid deposition was detected by Oil Red O. Results H3K9ac levels at SRE regions of PNPLA3 promoter were found to be decreased in mice during fasting and increase during refeeding, and increased in mice with NAFLD induced by high-sucrose diet. The change pattern of PNPLA3 promoter H3K9Ac physiologically (fasting/refeeding) and pathologically was consistent with that of PNPLA3 gene expression, but opposite to that of SIRT1 protein expression. In HepG2 cells, overexpression of SIRT1 inhibited high-glucose induced hyper-acetylation of H3K9 at PNPLA3 promoter, and silent expression of SIRT1 suppressed fasting-induced hypo-acetylation of H3K9. Overexpression of SIRT1 prevented basal and SREBP-1c-driven PNPLA3 gene expression and also prevented the endogenous binding of SREBP-1c to PNPLA3. Conclusions We first preliminarily revealed SIRT1 may regulate PNPLA3 gene expression by affecting SREBP-1-driven transcription via acetylation modification of H3K9.

Abstract Background Mental retardation is a complex neurodevelopmental disorder. NPAT, a component of the histone locus body (HLB), has been implicated as a candidate gene for mental retardation, with a mechanism yet to be elucidated. Results We identified that mxc, the Drosophila ortholog of NPAT, is required for the development of nervous system. Knockdown of mxc resulted in a massive loss of neurons and locomotion dysfunction in adult flies. In the mxc mutant or RNAi knockdown larval brains, the neuroblast (NB, also known as neural stem cell) cell fate is prematurely terminated and its proliferation potential is impeded concurrent with the blocking of the differentiation process of ganglion mother cells (GMCs). A reduction of transcription levels of histone genes was shown in mxc knockdown larval brains, accompanied by DNA double-strand breaks (DSBs). The subsidence of histone transcription levels leads to prematurely termination of NB cell fate and blockage of the GMC differentiation process. Our data also show that the increase in autophagy induced by mxc knockdown in NBs could be a defense mechanism in response to abnormal HLB assembly and premature termination of NB cell fate. Conclusions Our study demonstrate that Mxc plays a critical role in maintaining neural stem cell fate and GMC differentiation in the Drosophila larval brain. This discovery may shed light on the understanding of the pathogenesis of NPAT-related mental retardation in humans.

Abstract Background Urinary extracellular vesicles (EVs) are a source of biomarkers with broad potential applications across clinical research, including monitoring radiation exposure. A key limitation to their implementation is minimal standardization in EV isolation and analytical methods. Further, most urinary EV isolation protocols necessitate large volumes of sample. This study aimed to compare and optimize isolation and analytical methods for EVs from small volumes of urine. Methods 3 EV isolation methods were compared: ultracentrifugation, magnetic bead-based, and size-exclusion chromatography from 0.5 mL or 1 mL of rat and human urine. EV yield and mass spectrometry signals (Q-ToF and Triple Quad) were evaluated from each method. Metabolomic profiling was performed on EVs isolated from the urine of rats exposed to ionizing radiation 1-, 14-, 30- or 90-days post-exposure, and human urine from patients receiving thoracic radiotherapy for the treatment of lung cancer pre- and post-treatment. Results Size-exclusion chromatography is the preferred method for EV isolation from 0.5 mL of urine. Mass spectrometry-based metabolomic analyses of EV cargo identified biochemical changes induced by radiation, including altered nucleotide, folate, and lipid metabolism. We have provided standard operating procedures for implementation of these methods in other laboratories. Conclusions We demonstrate that EVs can be isolated from small volumes of urine and analytically investigated for their biochemical contents to detect radiation induced metabolomic changes. These findings lay a groundwork for future development of methods to monitor response to radiotherapy and can be extended to an array of molecular phenotyping studies aimed at characterizing EV cargo.

BackgroundFerroptosis is a type of regulatory cell death (RCD) mode that depends on iron-mediated oxidative damage. It has the potential to improve the efficacy of tumor immunotherapy by modulating the tumor microenvironment (TME). Currently, immunotherapy has significantly improved the overall treatment strategy for advanced hepatocellular carcinoma (HCC), but the distinct immune microenvironment and high tolerance to the immune make massive differences in the immunotherapy effect of HCC patients. As a result, it is imperative to classify HCC patients who may benefit from immune checkpoint therapy. Simultaneously, the predictive value of ferroptosis in HCC and its potential role in TME immune cell infiltration also need to be further clarified.MethodsThree ferroptosis molecular models were built on the basis of mRNA expression profiles of ferroptosis-related genes (FRGs), with notable variations in immunocyte infiltration, biological function, and survival prediction. In order to further investigate the predictive impact of immunotherapy response in HCC patients, the ferroptosis score was constructed using the principal component analysis (PCA) algorithm to quantify the ferroptosis molecular models of individual tumors.ResultsIn HCC, there were three totally different ferroptosis molecular models. The ferroptosis score can be used to assess genetic variation, immunotherapy response, TME characteristics, and prognosis. Notably, tumors with low ferroptosis scores have extensive tumor mutations and immune exhaustion, which are associated with a poor prognosis and enhanced immunotherapy response.ConclusionsOur study indicates that ferroptosis plays an indispensable role in the regulation of the tumor immune microenvironment. For HCC, the ferroptosis score is an independent prognostic indicator. Assessing the molecular model of ferroptosis in individual tumors will assist us in better understanding the characteristics of TME, predicting the effect of immunotherapy in HCC patients, and thus guiding a more reasonable immunotherapy program.

Social–emotional competence (SEC) played an important role in promoting the physical and mental development of children, but there exist huge gaps in SEC development between rural left-behind children. This study used propensity score matching (PSM) to investigate 578 rural children about the effects of being left behind as well as individual characteristics and teacher support on their development of SEC. The results showed that being left behind had significant negative effects on the SEC of rural children. The development of SEC varies among left-behind children of different genders and length of left-behind duration. Teacher support had a significant moderating effect on the influence path of SEC, which could effectively mitigate the negative effects of left-behind children. Therefore, this study played an implicative role in studying the development of left-behind children’s SEC. The government and society should provide adequate cultural capital by completing the support system for compensating the lack of cultural capital. Schools and teachers should pay more attention to the development of left-behind children’s SEC through curriculum development and performance evaluation to create a positive atmosphere. Parents should promote SEC development for left-behind children by improving their communication and family parenting styles.

Biological invasions are considerably altering ecosystem structure and functions, especially in coastal ecosystems that are subject to intensive anthropogenic disturbances. Spartina alterniflora has been recognized as the most serious invasive species in coastal China, which has received considerable attention from the government and the public. There is urgent need to control this invasive species at regional and national scales, but such efforts were impeded by lack of time-series data of Spartina spread. Here, we assessed the pixel- and phenology-based algorithm for mapping Spartina saltmarshes, and applied this algorithm to generate annual Spartina saltmarsh maps (30-m spatial resolution) from 1985 to 2020 by using time series Landsat 5/7/8 images. The resulting maps suggest that Spartina has been expanding since 1990 in coastal China, with three noticeable phases (rapid, moderate, and rapid). Along the latitudinal gradient, Spartina exhibited a longer invasion history and more frequent changes at low latitudes. Although human interventions caused the decline of Spartina in certain areas, rapid natural spread was primarily responsible for its extensive and continual invasion. These results provide insights for efficiently managing this invasive species, enhancing the conservation of coastal wetlands, and promoting the sustainability of coastal wetlands.

BackgroundEarly diagnosis for α-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) remains a critical problem. Metabolomics is prevalently involved in the identification of novel biomarkers. This study aims to identify new and effective markers for AFP negative HCC.MethodsIn total, 147 patients undergoing liver transplantation were enrolled from our hospital, including liver cirrhosis patients (LC, n=25), AFP negative HCC patients (NEG, n=44) and HCC patients with AFP over 20 ng/mL (POS, n=78). 52 Healthy volunteers (HC) were also recruited in this study. Metabolomic profiling was performed on the plasma of those patients and healthy volunteers to select candidate metabolomic biomarkers. A novel diagnostic model for AFP negative HCC was established based on Random forest analysis, and prognostic biomarkers were also identified.Results15 differential metabolites were identified being able to distinguish NEG group from both LC and HC group. Random forest analysis and subsequent Logistic regression analysis showed that PC(16:0/16:0), PC(18:2/18:2) and SM(d18:1/18:1) are independent risk factor for AFP negative HCC. A three-marker model of Metabolites-Score was established for the diagnosis of AFP negative HCC patients with an area under the time-dependent receiver operating characteristic curve (AUROC) of 0.913, and a nomogram was then established as well. When the cut-off value of the score was set at 1.2895, the sensitivity and specificity for the model were 0.727 and 0.92, respectively. This model was also applicable to distinguish HCC from cirrhosis. Notably, the Metabolites-Score was not correlated to tumor or body nutrition parameters, but difference of the score was statistically significant between different neutrophil-lymphocyte ratio (NLR) groups (≤5 vs. >5, P=0.012). Moreover, MG(18:2/0:0/0:0) was the only prognostic biomarker among 15 metabolites, which is significantly associated with tumor-free survival of AFP negative HCC patients (HR=1.160, 95%CI 1.012-1.330, P=0.033).ConclusionThe established three-marker model and nomogram based on metabolomic profiling can be potential non-invasive tool for the diagnosis of AFP negative HCC. The level of MG(18:2/0:0/0:0) exhibits good prognosis prediction performance for AFP negative HCC.

The rock chip information (shape, size, and particle size distribution) could comprehensively reflect the characteristics of rock mass and rock-breaking efficiency of TBM. This study is aimed at defining a novel index (effective rock-breaking ratio, Pr) to identify the rock-breaking efficiency of TBM based on the rock chip information. To evaluate this approach, a series of field sieving and measuring tests of rock chips was conducted at the water conveyance tunnel construction projects of China. The rock-breaking efficiency evaluation and tunneling parameter improvement of TBM were researched based on Pr index. The results showed as follows: (1) from the perspective of energy conversion, the rock chip surface area was calculated through the rock chip cumulative volume distribution model. Pr is used to evaluate the rock-breaking efficiency of TBM based on the proportion of surface area of rock chips with particle size larger than 5 mm; (2) Pr has a good linear correlation with coarseness index (CI) and specific energy (SE), the higher the TBM tunneling efficiency, the larger Pr and CI values, the less SE values; (3) Pr increases at first and then decreases with the rise of thrust force of TBM. The optimal thrust force intervals for grade II and III surrounding rocks can be determined to improve the rock-breaking efficiency of TBM. Findings from this study are insightful in terms of accurately evaluating the excavation efficiency and improving the tunneling parameters of TBM.

This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine (PVRV-WIBP) developed for human use. A cohort of 40 participants in stage 1 and 1956 subjects in stage 2 with an age range of 10–50 years were recruited for the phase III clinical trial. For safety analysis in stage 1, 20 participants received either 4-dose or 5-dose regimen of PVRV-WIBP. In stage 2, 1956 subjects were randomly divided into the 5-dose PVRV-WIBP, 5-dose PVRV-LNCD, and 4-dose PVRV-WIBP groups. The serum neutralizing antibody titer against rabies was determined on day 7 or 14 and day 35 or 42. Adverse reactions were recorded for more than 6 months. Most adverse reactions, which were mild and moderate in severity, occurred and resolved within 1 week after each injection in the PVRV-WIBP (4 and 5 doses) and PVRV-LNCD (5 doses) groups. All three groups achieved complete seroconversion 14 days after the initial dose and 14 days after completing the full vaccination schedule, the susceptible subjects in the PVRV-WIBP group (4-dose or 5-dose regimen) displayed higher neutralizing antibody titers against the rabies virus compared to those in the PVRV-LNCD group (5-dose regimen). PVRV-WIBP induced non-inferior immune responses versus PVRV-LNCD as assessed by seroconversion rate. PVRV-WIBP was well tolerated and non-inferior to PVRV-LNCD in healthy individuals aged 10–50 years. The results indicated that PVRV-WIBP (both 4- and 5-dose schedules) could be an alternative to rabies post-exposure prophylaxis.

BackgroundPostmenopausal bleeding (PMB) is a common gynecologic condition. Although it can be a sign of uterine cancer, most patients have benign etiology. However, research on quality of diagnostic evaluation for PMB has been limited to cancer patients. To extend this research, we examined the timeliness of diagnostic evaluation for PMB among patients with benign conditions.MethodsUsing the 2008-2019 MarketScan Research Databases, we identified 499176 patients (456741 with commercial insurance and 42435 with Medicaid insurance) who presented with PMB but did not have gynecologic cancer. For each patient, we measured the time from their PMB reporting to the date of their first diagnostic procedure. The association between patient characteristics and time to first diagnostic procedure was examined using Cox proportional hazards models (for the overall sample and then stratified by insurance type).ResultsOverall, 54.3% of patients received a diagnostic procedure on the same day when they reported PMB and 86.6% received a diagnostic procedure within 12 months after reporting PMB. These percentages were 39.4% and 77.1%, respectively, for Medicaid patients, compared to 55.7% and 87.4%, respectively, for commercially insured patients (pConclusionA sizable proportion of patients did not receive prompt diagnostic evaluation for PMB. Both clinical and non-clinical factors could affect timeliness of evaluation.