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Abstract Background Both initial mechanical stability and subsequent axial interfragmentary micromotion at fracture ends play crucial roles in fracture healing. However, the conversion timing of variable fixation and its effect on and mechanism of fracture healing remain inadequately explored. Methods A magnesium degradation-induced variable fixation plate (MVFP) for femurs was designed, and its conversion timing was investigated both in vitro and in vivo. Then, locking plates and MVFPs with and without a magnesium shim were implanted in rabbit femur fracture models. X-ray photography and micro computed tomography (micro-CT) were performed to observe the healing of the fracture. Toluidine blue and Masson’s trichrome staining were performed to observe new bone formation. The torsion test was used to determine the strength of the bone after healing. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the expression of osteogenesis-related genes in the three groups. Results The MVFP with sample 3 magnesium shim showed greater axial displacement within 15 days in vitro, and its variable capability was likewise confirmed in vivo. X-ray photography and micro-CT indicated increased callus formation in the variable fixation group. Toluidine blue and Masson’s trichrome staining revealed less callus formation on the rigid fixation side of the locking plate, whereas the variable fixation group presented more callus formation, more symmetrical intraosseous calli, and greater maturity. The torsion test indicated greater torsional resistance of the healed bone in the variable fixation group. RT-PCR and western blotting revealed that the expression levels of BMP2 and OPG increased during early fracture stages but decreased in late fracture stages, whereas RANKL expression showed the opposite trend in the variable fixation group. Conclusions MVFP promoted faster and stronger bone healing in rabbits, potentially by accelerating the expression of BMP2 and modulating the OPG/RANKL/RANK signaling axis. This study offers valuable insights for the clinical application of variable fixation technology in bone plates and contributes to the advancement of both internal fixation technology and theory. Level of evidence: level V. Graphical Abstract

Abstract Background Androgens are essential hormones for testicular development and the maintenance of male fertility. Environmental factors, stress, aging, and psychological conditions can disrupt androgen production, impacting the androgen signaling pathway and consequently spermatogenesis. Within the testes, testosterone is produced by Leydig cells and acts on Sertoli cells by activating the androgen receptor (AR), which then translocates to the nucleus to function as a transcription factor. Despite clinical correlations between low testosterone levels and diminished sperm quality, the precise mechanism remains unclear. Methods This study explores the hypothesis that reduced androgen levels impair Sertoli cell function by disrupting AR transcriptional regulation. Using an androgen blockade model with enzalutamide, we investigated the impact of low androgen levels on AR target genes in Sertoli cells through ChIP-seq and RNA-seq assays. Results Our results reveal that androgen blockage increases AR enrichment on the promoter region of Wee1, promoting Wee1 expression, while decreasing binding to the promoter region of Lfng, inhibiting its expression. Increased WEE1 protein inhibits Sertoli cell proliferation, whereas reduced LFNG affects Notch modification, leading to decreased production of glial cell line-derived neurotrophic factor (GDNF), a key growth factor for spermatogonial stem cell self-renewal. Conclusions These findings provide new insights into the molecular mechanisms by which low androgen levels interfere with Sertoli cell functions, offering novel perspectives for the clinical treatment of male reproductive disorders.

Abstract Intertidal algae may adapt to environmental challenges by acquiring genes from other organisms and relying on symbiotic microorganisms. Here, we obtained a symbiont-free and chromosome-level genome of Pyropia haitanensis (47.2 Mb), a type of intertidal algae, by using multiple symbiont screening methods. We identified 286 horizontal gene transfer (HGT) genes, 251 of which harbored transposable elements (TEs), reflecting the importance of TEs for facilitating the transfer of genes into P. haitanensis. Notably, the bulked segregant analysis revealed that two HGT genes, sirohydrochlorin ferrochelatase and peptide-methionine (R)-S-oxide reductase, play a significant role in the adaptation of P. haitanensis to heat stress. Besides, we found Pseudomonas, Actinobacteria, and Bacteroidetes are the major taxa among the symbiotic bacteria of P. haitanensis (nearly 50% of the HGT gene donors). Among of them, a heat-tolerant actinobacterial strain (Saccharothrix sp.) was isolated and revealed to be associated with the heat tolerance of P. haitanensis through its regulatory effects on the genes involved in proline synthesis (proC), redox homeostasis (ggt), and protein folding (HSP20). These findings contribute to our understanding of the adaptive evolution of intertidal algae, expanding our knowledge of the HGT genes and symbiotic microorganisms to enhance their resilience and survival in challenging intertidal environments.

Abstract Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Abstract Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10–30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management. Graphical Abstract

Abstract Background Ubiquitin/ubiquitin-like (Ub/UBL)-related genes have been reported to be associated with the survival of osteosarcoma patients but have not yet been systematically explored. Methods The prognostic value of Ub/UBL-related genes, immune cell infiltration and clinicopathological features of patients were explored by Cox and LASSO regression analyses. A prognostic model was established and then validated in the GSE21257 dataset. The differential expression of hub genes in osteosarcoma was confirmed by qRT-PCR, western blotting and immunohistochemistry. Results Tripartite Motif Containing 8 (TRIM8) and Ubiquitin Like With PHD And Ring Finger Domains 2 (UHRF2) were screened as genes with prognostic value in osteosarcoma. Kaplan–Meier analysis and scatter plots indicated that patients in the high gene significance score group tended to have a worse prognosis. The concordance index, calibration analysis and receiver operating characteristic analysis suggested that the model had good prediction accuracy and high sensitivity and specificity. Decision curve analysis revealed that patients could obtain greater net benefit from this model. Functional analyses of the differentially expressed genes indicated that they were involved in important functions and pathways. TRIM8 and UHRF2 were confirmed to be highly expressed in osteosarcoma cell lines and tissues. Conclusions TRIM8 and UHRF2 are potential prognostic genes in osteosarcoma, and these results provide insights into the roles of these genes and their implications for patient outcomes.

Abstract The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3–4. In addition to stage, intrahepatic metastasis and Child–Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p

The branch impact failure mechanism has gradually received attention from scholars, along with the application of impact cutting methods in plantation forest pruning. In this paper, the impact cutting failure mechanism of Populus tomentosa branches was mainly studied. The impact cutting process of branches was simulated by using Finite Element Method (FEM)-based explicit dynamics. The stress change and deformation characteristics in the branch failure process were studied. A theoretical model of branch impact cutting mechanism with branch diameter, cutting clearance, and branch angle as the main factors was proposed. The model describes the branch cutting damage process and the changing characteristics of cutting force. A branch failure state equation was proposed to describe the branch impact cutting failure patterns. The forest experiment was conducted to validate the branch impact cutting mechanism and the branch failure state equation. This work fills a vacancy of relevant theory and provides a theoretical basis for the future development of forestry and agricultural equipment using impact cutting.

Background: The combination of pyrotinib (Py) with cytotoxic agents proved to be effective in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, the optimal chemotherapy regimen is unknown. This study attempts to explore it from real-world research data. Methods: Information was collected from patients with early-stage HER2-positive BC from 23 centers across the country. They were categorized into the anthracycline group (A group) and non-anthracycline group (non-A group). Patients in the non-A group were further categorized into the platinum group and non-platinum group and the short-cycle (≤4 cycles) taxane group and long-cycle (>4 cycles) taxane group. Total pathological complete response (tpCR, ypT0/is ypN0) and breast pathological complete response (bpCR, ypT0/is) rates were assessed. Results: A total of 107 patients were enrolled. Postoperative pathology indicated a tpCR rate of 36.8 %, a bpCR rate of 42.1 % in the A group, the non-A group had a tpCR rate of 47.8 %, and a bpCR rate of 53.6 %, with P-values of 0.273 and 0.254, respectively. In the long-cycle taxane group, the tpCR and bpCR rates were 60.8 % and 66.7 %, respectively. In the short-cycle taxane group, the tpCR and bpCR rates were 11.1 % and 16.7 %, respectively (both P

transformer is a switch gene for sex determination in many insects, which cooperates with transformer-2 that is expressed in both sexes to regulate female differentiation, particularly in dipterans. Zeugodacus cucurbitae (Coquillett) is a very destructive pest worldwide, however, its sex determination pathway remains largely uncharacterized. Here, we show that the female sex ratio is sharply reduced with knockdown of either transformer or transformer-2 by RNA interference in early embryos of Z. cucurbitae. Most of the males grown from the embryos with transient transformer and transformer-2 suppression mated with wild-type females and produced mixed sex progeny, with one exception that produced only female progeny, and all of the few remaining males failed to mate with wild-type females and produced no progeny. The exceptional male and those males with mating failure were XX pseudomales as determined by the detection of Y chromosome-linked Maleness-on-the-Y, indicating that most XX pseudomales are not viable. The phenotypes of transformer and transformer-2 suggest that they play a key role in regulating sex determination and are required for female sexual development of Z. cucurbitae. Our results will be beneficial to the understanding of sex determination in Z. cucurbitae and can facilitate the development of genetic sexing strains for its biological control.

Abstract Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 μmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 μM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi. Graphical Abstract

Frankliniella intonsa (Trybom) (Thysanoptera: Thripidae) is an important type of thrip and a polyphagous pest, which poses a serious threat to many crops, especially those in tropical regions of China. Its feeding behavior and the damage caused vary among different host plant species and are affected by ambient temperature and plant nutrients as well. The digestion rate is an important index for directly observing the digestion process, but there have been no studies directly measuring the digestion in thrips under the influence of different temperatures and host plants. Here, the digestion rate of F. intonsa was assessed by using a molecular diagnostic tool. We also determined the nutrient content in three host plant (mango, cowpea, and pepper), including soluble proteins, free fatty acids, soluble sugars, and water. The results showed that the high and low temperatures (16 °C and 32 °C) both seemed to accelerate the digestion of F. intonsa compared to the optimal temperature (26 °C) and the protein content of plants played an important role in the digestive response of F. intonsa to temperature changes. The findings can help reveal the feeding damage caused by F. intonsa to different plants and help to better understand its feeding ecology, according to its interaction with the host plant.

Origami robots, inspired by an ancient form of paper folding art, are capable of achieving high displacement in a lightweight and compact design that conventional robots can hardly attain. It, however, remains a challenge to drive origami robots with in situ active materials that imply minimal added mass and complexity and can be easily controlled to achieve multiple actuation modalities. Herein, inspired by the Twisted Tower origami structure, dielectrophoretic liquid zipping actuation concept is employed to develop a modular architecture, capable of achieving complicated motions with multiple degrees of freedom (DoF). The experimental results show a maximum of 3.9 degrees tilting per layer toward any desired direction, a 56.1% contraction of the original length, and 5.4 degrees twisting per layer. Each layer can generate a maximum contractile force of 1.03 N with a maximum 64.7% power efficiency and 2.775 W kg−1 power‐to‐weight ratio. A modified heterochiral arrangement of this modular actuator is proposed to enhance controllability across various movement modes. Its use in robotic‐wrist‐like actuation has been demonstrated, highlighting its significant potential for integration into soft robotic multi‐DoF structures, such as continuum arms.

A fundamental vision technique for industrial robots involves the six degrees of freedom pose estimation of target objects from a single image. However, the direct estimation of the six degrees of freedom object pose solely from a single image is subject to limited accuracy. Various refinement approaches have been proposed to improve the accuracy by utilizing rendered images from a 3D model. Nevertheless, balancing speed and accuracy in an industrial setting remains a challenge for these methods. In this study, we propose a novel six degrees of freedom pose refinement approach centered around matching real image patches. Unlike previous approaches, our method does not rely on a 3D model, resulting in increased speed and accuracy. In the offline phase, we construct an offline database using image patches obtained from real images. During the inference phase, our method initially identifies the image patch within the offline database that is closest to the initial pose. Subsequently, we refine the six degrees of freedom pose by matching the corresponding image patches from the offline database. Experimental results indicate that our six degrees of freedom pose refinement method achieves real-time capability with a frame rate of 71 Frames Per Second (FPS), along with high precision. When the threshold is set to 0.5% of the object diameter, the average distance of dots score on the test data surpasses 70%. Moreover, experiments involving gripping and assembling tasks on an industrial robot demonstrate the ability of our method to autonomously select appropriate grasping angles and positions in real time. It further generates suitable motion paths, ultimately ensuring production efficiency.

Abstract Background The scarcity of pluripotent stem cells poses a major challenge to the clinical application, given ethical and biosafety considerations. While germline stem cells commit to gamete differentiation throughout life, studies demonstrated the spontaneous acquisition of pluripotency by spermatogonial stem cells (SSCs) from neonatal testes at a low frequency (1 in 1.5 × 107). Notably, this process occurs without exogenous oncogenes or chemical supplementation. However, while knockout of the p53 gene accelerates the transformation of SSCs, it also increases risk and hampers their clinical use. Results We report a transformation system that efficiently and stably convert SSCs into pluripotent stem cells around 10 passages with the morphology similar to that of epiblast stem cells, which convert to embryonic stem (ES) cell-like colonies after change with ES medium. Epidermal growth factor (EGF), leukemia inhibitory factor (LIF) and fresh mouse embryonic fibroblast feeder (MEF) are essential for transformation, and addition of 2i (CHIR99021 and PD0325901) further enhanced the pluripotency. Transcriptome analysis revealed that EGF activated the RAS signaling pathway and inhibited p38 to initiate transformation, and synergically cooperated with LIF to promote the transformation. Conclusion This system established an efficient and safe resource of pluripotent cells from autologous germline, and provide new avenues for regenerative medicine and animal cloning.

Abstract Ischemic stroke stands as a prevalent neurological ailment, where a paucity of methodologies exists for the assessment of functional outcomes post-stroke. Our objective was the development of a WeChat applet for the evaluation of muscle strength and the subsequent evaluation of its validity in ischemic stroke patients experiencing motor dysfunction. The assessment encompassed Lovett and NIHSS, followed by muscle strength values (MSV) and muscle strength ratios (MSR). These metrics were then scrutinized in relation to NIHSS and Lovett, followed by examination of their interrelationships. We enrolled a cohort of 157 patients, with an average age of 65 years, consisting of 96 males and 61 females. Lovett scores in the range of 2–4 and NIHSS scores spanning from 0 to 3 were found to correspond to specific values of MSV and MSR, respectively. Upon conducting correlation analysis, we noted that both MSV and MSR exhibited significant positive correlations with Lovett scores and NIHSS. Remarkably, the correlation of MSR with Lovett scores or NIHSS surpassed that of MSV. The WeChat applet offers a means of digitization and visualization of muscle strength. It correlates well with Lovett score and NIHSS, especially MSR. This bears potential significance in guiding the rehabilitation of stroke patients.

Hypocrellins are major bioactive perylenequinones from Shiraia fruiting bodies and have been developed as efficient photosensitizers for photodynamic therapy. Pseudomonas is the second dominant genus inside Shiraia fruiting bodies, but with less known actions on the host fungus. In this work, the effects of bacterial volatiles from the Shiraia-associated Pseudomonas on fungal hypocrellin production were investigated. Pseudomonas putida No.24 was the most active to promote significantly accumulation of Shiraia perylenequinones including hypocrellin A (HA), HC, elsinochrome A (EA) and EC. Headspace analysis of the emitted volatiles revealed dimethyl disulfide as one of active compounds to promote fungal hypocrellin production. The bacterial volatiles induced an apoptosis in Shiraia hyphal cell, which was associated with the generation of reactive oxygen species (ROS). ROS generation was proved to mediate the volatile-induced membrane permeability and up-regulation of gene expressions for hypocrellin biosynthesis. In the submerged volatile co-culture, the bacterial volatiles stimulated not only HA content in mycelia, but also HA secretion into the medium, leading to the enhanced HA production to 249.85 mg/L, about 2.07-fold over the control. This is the first report on the regulation of Pseudomonas volatiles on fungal perylenequinone production. These findings could be helpful to understand the roles of bacterial volatiles in fruiting bodies and also provide new elicitation method using bacterial volatiles to stimulate fungal secondary metabolite production.

Ewing's sarcoma (ES) is the second most common bone and soft tissue malignancy in children and adolescents with a poor prognosis. The identification of genes with prognostic value may contribute to the prediction and treatment of this disease. The GSE17679, GSE68776, GSE63155, and GSE63156 datasets were downloaded from the Gene Expression Omnibus database and qualified. Prognostic value of differentially expressed genes (DEGs) between the normal and tumor groups and immune cell infiltration were explored by several algorithms. A prognostic model was established and validated. Finally, functional analyses of the DEGs were performed. Proline rich 11 (PRR11) and mast cell infiltration were noted as the key indicators for the prognosis of ES. Kaplan-Meier and scatter plots for the training and two validation sets showed that patients in the low-PRR11 expression group were associated with better outcomes than those in the high-PRR11 expression group. The concordance indices and calibration analyses of the prognostic model indicated good predictive accuracy in the training and validation sets. The area under the curve values obtained through the receiver operating characteristic analysis for 1-, 3-, 5-year prediction were ≥ 0.75 in the three cohorts, suggesting satisfactory sensitivity and specificity of the model. Decision curve analyses suggested that patients could benefit more from the model than the other strategies. Functional analyses suggested that DEGs were mainly clustered in the cell cycle pathway. PRR11 and mast cell infiltration are potential prognostic indicators in ES. PRR11 possibly affects the prognosis of patients with ES through the cell cycle pathway.

A transient ischemic attack (TIA) affects millions of people worldwide. Although TIA risk factors have been identified individually, a systemic quantitative analysis of all health factors relevant to TIA using electronic medical records (EMR) remains lacking. This study employed a data-driven approach, leveraging hospital EMR data to create a TIA patient health factor graph. This graph consisted of 737 TIA and 737 control patient nodes, 740 health factor nodes, and over 33,000 relations between patients and factors. For all health factors in the graph, the connection delta ratios (CDRs) were determined and ranked, generating a quantitative distribution of TIA health factors. A literature review confirmed 56 risk factors in the distribution and unveiled a potential new risk factor “rhinosinusitis” for future validation. Moreover, the patient graph was visualized together with the TIA knowledge graph in the Unified Medical Language System. This integration enables clinicians to access and visualize patient data and international standard knowledge within a unified graph. In conclusion, graph CDR analysis can effectively quantify the distribution of TIA risk factors. The resulting TIA risk factor distribution might be instrumental in developing new risk prediction machine learning models for screening and early detection of TIA.

Abstract Purpose Hepatocellular carcinoma (HCC) is a kind of primary liver cancer. It is a common malignant tumor of digestive system that is difficult to predict the prognosis of patients. As an important epigenetic modification, N7 methyl guanosine (m7G) is indispensable in gene regulation. This regulation may affect the development and occurrence of cancer. However, the prognosis of long non coding RNAs (lncRNAs) in HCC is limited, especially how m7G-related lncRNAs regulate the development of HCC has not been reported. Methods The Cancer Genome Atlas (TCGA) provides us with the expression data and corresponding clinical information of HCC patients we need. We used a series of statistical methods to screen four kinds of m7G-related lncRNAs related to HCC prognosis and through a series of verifications, the results were in line with our expectations. Finally, we also explored the IC50 difference and correlation analysis of various common chemotherapy drugs. Result Our study identified four differentially expressed m7g-related lncRNAs associated with HCC prognosis. Survival curve analysis showed that high risk lncRNAs would lead to poor prognosis of HCC patients. M7G signature's AUC was 0.789, which shows that the prognosis model we studied has certain significance in predicting the prognosis of HCC patients. Moreover, our study found that different risk groups have different immune and tumor related pathways through gene set enrichment analysis. In addition, many immune cell functions are significantly different among different risk groups, such as T cell functions, including coordination of type I INF response and coordination of type II INF response. The expression of PDCD1, HHLA2, CTLA-4 and many other immune checkpoints in different risk groups is also different. Additionally, we analyzed the differences of IC50 and risk correlation of 15 chemotherapeutic drugs among different risk groups. Conclusion A novel lncRNAs associated with m7G predicts the prognosis of HCC.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, which brings the risk of predation to prey. The predation risk is divided into consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories in prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a major invasive threat to global horticulture. While earlier research was primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated a reduced developmental time in the presence of a caged predator (H. patellifera) or predator odors, but showed significantly increased fecundity. Conversely, males displayed no significant change in developmental time. Additionally, neither the female nor male body weight at death was significantly influenced by the predation risk from the caged predator or predator odors. This study investigated the effects of predation risk on the development and reproduction of B. dorsalis, emphasizing the potential importance of odor risk in biological and pest control.

Outbreaks of the oriental fruit fly, Bactrocera dorsalis (Hendel), present significant challenges to global fruit production, necessitating effective control measures that minimize environmental risks and pesticide resistance. This study aimed to develop and evaluate the effectiveness of four distinct push–pull control strategies for managing B. dorsalis outbreaks in a Nephelium lappaceum orchard. These strategies involved the inclusion of low-concentration abamectin, spraying repellent with a drone or manually, using methyl eugenol (ME) or food bait and employing either two types of attractants and repellents or a single type. The findings indicated that incorporating the low-concentration abamectin into the push–pull system, utilizing ME as an attractant instead of food lures and manually applying abamectin and attractants were all effective in reducing the B. dorsalis population size and minimizing fruit damage. While increasing the diversity of repellents and attractants enhanced the long-term effectiveness of the system, it did not result in a significant decrease in B. dorsalis population size or fruit damage rate compared to using a single repellent or attractant. In conclusion, the push–pull strategy emerged as a viable method for managing B. dorsalis outbreaks, offering potential benefits in reducing environmental risks and pesticide resistance. However, the study underscored the importance of the context-specific construction of push–pull strategies to optimize their effectiveness in orchard settings.

Background Treatment of large segmental bone defects is still a major clinical challenge, and bone grafting is the main method. The development of novel bone graft substitutes will help solve this problem. Methods Porous bioceramics hydroxyapatite (HA) scaffolds coated with different ratios of HA/β-tricalcium phosphate (β-TCP) were prepared by 3D printing. The scaffolds were sampled and tested in large segmental bone defect rabbit models. X-ray, micro-computed tomography (CT), hematoxylin and eosin (HE) staining, Van-Gieson staining, and type I collagen staining were performed to find the best scaffolds for large segmental bone defect treatment. Results The average length, diameter, compressive strength, and porosity of the bioceramics scaffolds were 15.05 ± 0.10 mm, 4.98 ± 0.06 mm, 11.11 ± 0.77 MPa, and 54.26 ± 5.38%, respectively. Postoperative lateral radiographs suggested the scaffold group got better bone healing and stability than the blank group. Micro-CT showed new bones grew into the scaffold from the two ends of the fracture along the scaffold and finally achieved bony union. The new bone volume around the scaffolds suggested the 3:7 HA/β-TCP-coated bioceramic scaffolds were more favorable for the healing of large segmental bone defects. The results of HE, Van-Gieson, and type I collagen staining also suggested more new bone formation in 3:7 HA/β-TCP-coated bioceramic scaffolds. Conclusion 3:7 HA/β-TCP-coated porous bioceramics scaffolds are more conducive to the repair of large bone defects in rabbits. The results of this study can provide some reference and theoretical support in this area.

Hydrofluoroolefins are the latest (4th) generation of working fluids (refrigerants) due to zero ozone depletion and very low global warming potential. The R514A is a mixture of R1336mzz(Z) (74.7 %) and R1130(E) (25.3 %) and is considered a class of Hydrofluoroolefins. In this paper, the art of molecular dynamics simulation has been executed to evaluate the dynamical and thermophysical properties of R514A during the condensation process. The effects of temperatures and pressures on dynamical, thermophysical properties and condensation time are computed, analyzed and discussed. Further, the effects of the simulation time step on the properties mentioned above are computed. The simulation outcomes explained that the condensation time significantly depends on condensation temperatures and pressure values. For example, little time is required to complete the condensation cycle of R514A at lower temperatures and higher pressure, and vice versa. The changes in the structure during the condensation process also examine the in-term bonding and nonbinding interaction of R514A in vapor and liquid phases. The mean squared displacement and velocity autocorrelation function explained the average diffusion for the molecules of R1336mzz(Z) and R1130(E), and increased with respect to simulation time with increasing temperature and pressure. The obtained simulation outcomes are reliable, accurate, and in excellent agreement with previously available simulation data. Current investigations indicated that the refrigerant R514A considering sustainable and eco-friendly in numerous applications in the replacement of R123.

ObjectiveEmerging evidence highlighted that perirenal adipose tissue might regulate the cardiovascular and metabolism system through several pathways. This study aimed to assess the association between perirenal fat thickness (PrFT) and subclinical carotid atherosclerosis (SCCA) in type 2 diabetes mellitus (T2DM).MethodA total of 670 participants with complete data were included in this study. The trained reviewer collected demographic and anthropometric information. Laboratory assessments were determined by standard methods. PrFT and SCCA were evaluated by computed tomography and ultrasound. Binomial logistic regression analysis was conducted to assess the association between PrFT and SCCA. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the identifying value of PrFT for SCCA.ResultsOverall, the prevalence of SCCA was 61.8% in T2DM. PrFT was significantly increased in the SCCA group. Growing trends were observed in the prevalence of hypertension, carotid intima-media thickness (cIMT) > 1, plaque, and SCCA across the PrFT quartiles. Spearman correlation analysis revealed that PrFT was positively associated with cIMT (r = 0.401, p < 0.001). This correlation remained significant after adjustment for visceral fat area (VFA), subcutaneous fat area (SFA), and traditional metabolic risk factors (β = 0.184, p < 0.001). Meanwhile, PrFT was independently correlated with plaque, cIMT > 1 mm, and SCCA. The ORs (95% CI) were 1.072 (1.014–1.135), 1.319 (1.195–1.455), and 1.216 (1.119–1.322). Furthermore, PrFT remained correlated considerably with SCCA in subgroup analysis after stratification for age, sex, smoking, hypertension, and body mass index. From the ROC curve analysis, the AUCs (95% CI) of PrFT, VFA, and SFA identifying SCCA were 0.794 (0.760–0.828), 0.760 (0.724–0.796), and 0.697 (0.656–0.737), respectively. The AUC of PrFT was significantly higher than VFA (p = 0.028) and SFA (p < 0.001). The optimal cutoff values of PrFT were 14.0 mm, with a sensitivity of 66.7% and a specificity of 76.2%.ConclusionPrFT was independently associated with cIMT, plaque, cIMT > 1 mm, and SCCA as a superior obesity-related marker of SCCA in T2DM.Clinical trial registrationClinical Trials.Gov, identifier ChiCTR2100052032.

Abstract Background Perylenequinones from Shiraia fruiting bodies are excellent photosensitizers and widely used for anti-cancer photodynamic therapy (PDT). The lower yield of Shiraia perylenequinones becomes a significant bottleneck for their medical application. Branched-chain amino acids (BCAAs) not only serve as important precursors for protein synthesis, but also are involved in signaling pathway in cell growth and development. However, there are few reports concerning their regulation of fungal secondary metabolism. In present study, the eliciting effects of BCAAs including l-isoleucine (l-Ile), l-leucine (l-Leu) and l-valine (l-Val) on Shiraia perylenequinone production were investigated. Results Based on the analysis of the transcriptome and amino acid contents of Shiraia in the production medium, we revealed the involvement of BCAAs in perylenequinone biosynthesis. The fungal conidiation was promoted by l-Val treatment at 1.5 g/L, but inhibited by l-Leu. The spore germination was promoted by both. The production of fungal perylenequinones including hypocrellins A (HA), HC and elsinochromes A-C (EA–EC) was stimulated significantly by l-Val at 1.5 g/L, but sharply suppressed by l-Leu. After l-Val treatment (1.5 g/L) in Shiraia mycelium cultures, HA, one of the main bioactive perylenequinones reached highest production 237.92 mg/L, about 2.12-fold than that of the control. Simultaneously, we found that the expression levels of key genes involved in the central carbon metabolism and in the late steps for perylenequinone biosynthesis were up-regulated significantly by l-Val, but most of them were down-regulated by l-Leu. Conclusions Our transcriptome analysis demonstrated that BCAA metabolism was involved in Shiraia perylenequinone biosynthesis. Exogenous BCAAs exhibit contrasting effects on Shiraia growth and perylenequinones production. l-Val could promote perylenequinone biosynthesis via not only enhancing the central carbon metabolism for more precursors, but also eliciting perylenequinone biosynthetic gene expressions. This is the first report on the regulation of BCAAs on fungal perylenequinone production. These findings provided a basis for understanding physiological roles of BCAAs and a new avenue for increasing perylenequinone production in Shiraia mycelium cultures. Graphical Abstract

Improving the detection accuracy of hyperbola in B-scan images has been a considerable challenge for ground penetrating radar (GPR) to detect tree roots. In this paper, a method for data enhancement and target detection, both based on deep learning was proposed to identify hyperbolas in GPR B-scan images. First, the authors used a cyclic consistent adversarial network (CycleGAN) to augment the original data. In this procedure, the hyperbolic features of the images were preserved and created a wider variety of training samples. Then, the authors could apply the enhanced dataset to the YOLOv5 detection model to evaluate the effectiveness of their method. Meanwhile, the detection effects of Yolov3, Yolov5, Faster R-CNN, and CenterNet detection models on the enhanced dataset were compared. The results showed that applying the enhanced dataset to the Yolov5 detection model exhibited better detection accuracy compared to other combinations of datasets and detection models. The authors demonstrate that the proposed method increases data diversity and the number of samples, improving the precision and recall of hyperbolic curves. These results provide a new method for tree root localization with important effects.

Background: The prognostic value of D-glucuronyl C5-epimerase (GLCE) and mast cell infiltration in Ewing sarcoma (ES) has not been well specified and highlighted, which may facilitate survival prediction and treatment. Methods: Several qualified datasets were downloaded from the GEO website. Common differentially expressed genes between normal subjects and ES patients in GSE17679, GSE45544, and GSE68776 were identified and screened by multiple algorithms to find hub genes with prognostic value. The prognostic value of 64 infiltrating cells was also explored. A prognostic model was established and then validated with GSE63155 and GSE63156. Finally, functional analysis was performed. Results: GLCE and mast cell infiltration were screened as two indicators for a prognostic model. The Kaplan‒Meier analysis showed that patients in the low GLCE expression, mast cell infiltration and risk score groups had poorer outcomes than patients in the high GLCE expression, mast cell infiltration and risk score groups, both in the training and validation sets. Scatter plots and heatmaps also indicated the same results. The concordance indices and calibration analyses indicated a high prediction accuracy of the model in the training and validation sets. The time-dependent receiver operating characteristic analyses suggested high sensitivity and specificity of the model, with area under the curve values between 0.76 and 0.98. The decision curve analyses suggested a significantly higher net benefit by the model than the treat-all and treat-none strategies. Functional analyses suggested that glycosaminoglycan biosynthesis-heparan sulfate/heparin, the cell cycle and microRNAs in cancer were upregulated in ES patients. Conclusions: GLCE and mast cell infiltration are potential prognostic indicators in ES. GLCE may affect the proliferation, angiogenesis and metastasis of ES by affecting the biosynthesis of heparan sulfate and heparin.

Based on the field of the coal chemical industry, exploring the applicability of high-performance heat exchangers for coal water slurry and their flow and heat transfer mechanism is of great significance for promoting the development of clean coal technology. In this paper, the flow pattern and forced convection heat transfer of a pair of tandem heated cylinders with different distances were discussed using the bi-viscous Bingham model by numerical simulation. And a novel spiral wound heat exchanger with variable diameter tubes was proposed. The results illustrate that the heat transfer coefficient under unit pressure drop h/△P of the heat exchanger decreases with the increase of the diameter of the variable tubes. When the diameter of variable tubes is 12 mm, h/△P is 19.83% larger than that of the original structure with uniform tube diameter. The empirical correlation between operating and structural parameters and heat exchanger performance is obtained. The research results provide guidance for the design of coal water slurry preheaters and the structural optimization of spiral wound tube heat exchangers.

Bactrocera dorsalis (Hendel) (B. dorsalis) is an important agricultural invasive pest that causes significant economic losses in tropical and subtropical fruit and vegetable crops. In this study, the proteins related to the sense of smell and taste of B. dorsalis, such as OBP, PBP, OR, IR, SNMP and CSP, were screened based on B. dorsalis transcriptome data. By integrating the compounds that were reported to be attractive to B. dorsalis, similar compounds of hydrocarbon compounds were obtained. Molecular docking was used to predict the binding between the similar compounds and the OBP, PBP, OR, IR, SNMP and CSP proteins. Network pharmacology was used to screen the potentially attractive compounds, and ecological experiments with B. dorsalis were finally conducted to verify the effect of these potentially attractive compounds on B. dorsalis. The results showed that the G protein-coupled receptor [BR: KO04030] and ion channel [BR: KO04040] pathways were closely related to the odor tropism of B. dorsalis. A total of 84 compounds, such as mitemcinal, exemestane and midecamycin, have potential binding effects on the B. dorsalis odor receptor proteins. The results of the ecological experiments showed that 1 mg/mL and 0.1 mg/mL 19-norandrostenedione, 1 mg/mL progesterone compounds was significantly attractive to B. dorsalis males, while 0.1 mg/mL exemestane was significantly attractive to B. dorsalis females. In this study, network pharmacology technology was used to discover the potential attractive compounds for B. dorsalis, which is important for the development and subsequent prevention and control of B. dorsalis. It can provide a reference in improving the success rates of clinical trials of new pest control products and in reducing the time and cost of drug development.

Abstract Background Fungal perylenequinones (PQs) are a class of photoactivated polyketide mycotoxins produced by plant-associated fungi. Hypocrellins, the effective anticancer photodynamic therapy (PDT) agents are main bioactive PQs isolated from a bambusicolous Shiraia fruiting bodies. We found previously that bacterial communities inhabiting fungal fruiting bodies are diverse, but with unknown functions. Bacillus is the most dominant genus inside Shiraia fruiting body. To understand the regulation role of the dominant Bacillus isolates on host fungus, we continued our work on co-culture of the dominant bacterium B. cereus No.1 with host fungus Shiraia sp. S9 to elucidate bacterial regulation on fungal hypocrellin production. Results Results from "donut" plate tests indicated that the bacterial culture could promote significantly fungal PQ production including hypocrellin A (HA), HC and elsinochrome A-C through bacterial volatiles. After analysis by gas chromatograph/mass spectrometer and confirmation with commercial pure compounds, the volatiles produced by the bacterium were characterized. The eliciting roles of bacterial volatile organic compounds (VOCs) on HA production via transcriptional regulation of host Shiraia fungus were confirmed. In the established submerged bacterial volatile co-culture, bacterial volatiles could not only promote HA production in the mycelium culture, but also facilitate the release of HA into the medium. The total production of HA was reached to 225.9 mg/L, about 1.87 times that of the fungal mono-culture. In contrast, the live bacterium suppressed markedly fungal PQ production in both confrontation plates and mycelium cultures by direct contact. The live bacterium not only down-regulated the transcript levels of HA biosynthetic genes, but also degraded extracellular HA quickly to its reductive product. Conclusion Our results indicated that bacterial volatile release could be a long-distance signal to elicit fungal PQ production. Biodegradation and inhibition by direct contact on fungal PQs were induced by the dominate Bacillus to protect themselves in the fruiting bodies. This is the first report on the regulation of Bacillus volatiles on fungal PQ production. These findings could be helpful for both understanding the intimate fungal–bacterial interactions in a fruiting body and establishing novel cultures for the enhanced production of bioactive PQs. Graphical Abstract

Abstract Background Ewing sarcoma (ES) is the second most common primary malignant bone tumor mainly occurring in children, adolescents and young adults with high metastasis and mortality. Autophagy has been reported to be involved in the survival of ES, but the role remains unclear. Therefore, it’s necessary to investigate the prognostic value of autophagy related genes using bioinformatics methods. Results ATG2B, ATG10 and DAPK1 were final screened genes for a prognostic model. KM and risk score plots showed patients in high score group had better prognoses both in training and validation sets. C-indexes of the model for training and validation sets were 0.68 and 0.71, respectively. Calibration analyses indicated the model had high prediction accuracy in training and validation sets. The AUC values of ROC for 1-, 3-, 5-year prediction were 0.65, 0.73 and 0.84 in training set, 0.88, 0.73 and 0.79 in validation set, which suggested high prediction accuracy of the model. Decision curve analyses showed that patients could benefit much from the model. Differential and functional analyses suggested that autophagy and apoptosis were upregulated in high risk score group. Conclusions ATG2B, ATG10 and DAPK1 were autophagy related genes with potential protective function in ES. The prognostic model established by them exhibited excellent prediction accuracy and discriminatory capacities. They might be used as potential prognostic biomarkers and therapeutic targets in ES.

Glioma is one of the most serious central nervous system diseases, with high mortality and poor prognosis. Despite the continuous development of existing treatment methods, the median survival time of glioma patients is still only 15 months. The main treatment difficulties are the invasive growth of glioma and the obstruction of the blood-brain barrier (BBB) to drugs. With rapid advancements in nanotechnology, inorganic nanoparticles (INPs) have shown favourable application prospects in the diagnosis and treatment of glioma. Due to their extraordinary intrinsic features, INPs can be easily fabricated, while doping with other elements and surface modification by biological ligands can be used to enhance BBB penetration, targeted delivery and biocompatibility. Guided glioma theranostics with INPs can improve and enhance the efficacy of traditional methods such as chemotherapy, radiotherapy and gene therapy. New strategies, such as immunotherapy, photothermal and photodynamic therapy, magnetic hyperthermia therapy, and multifunctional inorganic nanoplatforms, have also been facilitated by INPs. This review emphasizes the current state of research and clinical applications of INPs, including glioma targeting and BBB penetration enhancement methods, in vivo and in vitro biocompatibility, and diagnostic and treatment strategies. As such, it provides insights for the development of novel glioma treatment strategies.

Acoustic radiation through a system of double-walled shells, lined with porous foams, and stiffened by annular plates simultaneously is studied. Based on modeling, the porous foams as absorbent fluid property, acoustic characteristics of structure are presented for various sandwich construction by means of vibro-acoustic finite element method with automatic matching layer technology. It is noted that equipping porous foams and annular plates simultaneously enhances the acoustic insulation of structure in the entire frequency domain. The overall sound power level is modified by the density of shell. Moreover, the increase of structural stiffness is shown to effectively reduce the acoustic radiation via rising the thickness of inner shell and the number of annular plates. The foam cores decrease the peak value of structural sound power level through using polyurethane foam cores and increasing filling ratio.

IntroductionThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, the SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Thus, emerging variants have brought new challenges to the prevention of COVID-19 and updated vaccines are urgently needed to provide better protection against the Omicron variant or other highly mutated variants.Materials and methodsHere, we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in the SARSCoV-2 variant challenge.ResultsResults showed that the RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice.ConclusionOur data suggest that RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.

Primula xinningensis Wei Zhang bis & J.W.Shao, a new species from Hunan Province, China, is described. Its leaf morphology is similar to the P. merrilliana complex and flower morphology similar to P. cicutariifolia, but it can be distinguished from the former by the black pollen sac, corolla lobes apex obviously emarginate and can be differed from the latter by cotyledon triangular obovate, plants densely covered with glandular hairs and special habitat (karst caves). The whole plastid genome of this new species is 151, 601–151, 630 bp in length. Based on the whole plastid genome sequences, phylogenetic trees revealed that the new species did not genetically relate to the above two mentioned morphologically similar species, but it was closely related to P. hubeiensis. Currently, only three populations were discovered within a small distribution area, thus, it is preliminarily considered as Vulnerable (VU) according to criteria of the IUCN Red List.

Insects have developed dormancy mechanisms to survive coldness in winters. The specific forms of winter dormancy, however, vary among different geographical and climatic zones and species. While there is extensive research on winter dormancy in insect pests and parasitoids in temperate zones, our understanding of how predatory insects, such as predatory stink bugs in subtropical regions, cope with cold winters and the specific forms of dormancy they undergo remains limited. The effects of winter temperatures on the population dynamics, development, and reproduction of the predatory stink bug Eocanthecona furcellata in the subtropics were investigated through greenhouse and laboratory experiments. E. furcellata exhibits two distinct peaks in population distribution throughout the year: one in April–May and another in October–November. Interestingly, the proportions of adults show an opposite pattern to the population dynamics, with the highest proportions of adults observed during the winter and summer seasons, when temperatures are the lowest and the highest, respectively. Laboratory studies showed that E. furcellata reared at lower temperatures (16 °C, 18 °C, and 20 °C) experienced prolonged development and higher mortality rates for eggs and nymphs compared to higher temperatures (22 °C and 26 °C). Further experiments observed that E. furcellata adults reared at 16 °C, 18 °C, and 20 °C entered into winter dormancy, where ovarian development was either completely halted or slowed down. The observed high proportion of E. furcellata adults and low proportion of nymphs during the cold winter months align well with the dormancy period. This study sheds light on the underlying mechanisms driving the population dynamics of E. furcellata during the subtropical winter. These findings have significant implications in accurately predicting the population dynamics of E. furcellata, implementing effective field release strategies, and optimizing cold storage techniques in the context of biological control programs.

To explore the relationship between PD-L1 expression and gene mutations and survival. PD L1, ALK and MET protein expression were detected by immunohistochemistry, and EGFR gene mutation by RT-PCR in 209 cases of NSCLC. The correlations between PD-L1 expression and gene mutations, clinicopathological features and survival was analyzed. PD-L1 was expressed in 99/209 cases (47.4%) of NSCLC, including score 1 (≥ 1% to < 5%) 23 cases (11%), score 2 (≥ 5% to 50%) 40 cases (19.1%). There were 89 cases (42.6%) of EGFR mutation, 12 (5.7%) of ALK and 90 (43.1%) of MET protein positive. PD-L1 positive expression occurred more frequently in men and non-adenocarcinoma, and was negatively correlated with EGFR mutation and histological differentiation of NSCLC. PD-L1 expression was concordant in primary and metastatic cancers. There was no any effect of PD-L1 expression on overall survival of patients with NSCLC. These results suggested that PD-L1 expression is not an independent risk factor for survival of patients with NSCLC. Because of mutual complementarities of PD-L1 expression and EGFR mutation in NSCLC, both should be simultaneously detected for the patients to achieve eligible treatments.

BackgroundFew studies have compared the prognosis of different reconstruction methods after gastrectomy for gastric cancer (GC) patients with obesity. The aim of the present study was to compare postoperative complications and overall survival (OS) between the following reconstruction methods: Billroth I (B-I), Billroth II (B-II), and Roux-en-Y (R-Y) after gastrectomy for GC patients with visceral obesity (VO).MethodsWe performed a double-institutional dataset study of 578 patients who underwent radical gastrectomy with B-I, B-II, and R-Y reconstructions between 2014 and 2016. VO was defined as a visceral fat area at the level of the umbilicus greater than 100 cm2. Propensity score-matching analysis was performed to balance the significant variables. Postoperative complications and OS were compared between the techniques.ResultsVO was determined in 245 patients, of which 95, 36, and 114 underwent B-I, B-II, and R-Y reconstructions, respectively. B-II and R-Y were fused into the Non-B-I group due to the similar incidence of overall postoperative complications and OS. Therefore, 108 patients were enrolled after matching. The overall postoperative complications incidence and overall operative time in the B-I group were significantly lower than those in the non-B-I group. Further, multivariable analysis showed that B-I reconstruction was an independent protective factor for overall postoperative complications (odds ratio (OR) 0.366, P=0.017). However, no statistical difference in OS was found between the two groups (hazard ratio (HR) 0.644, P=0.216).ConclusionsB-I reconstruction was associated with decreased overall postoperative complications, rather than OS, in GC patients with VO who underwent gastrectomy.

BackgroundMedullary thyroid carcinoma (MTC) is an infrequent form malignant tumor with a poor prognosis. Because of the influence of competitive risk, there may suffer from bias in the analysis of prognostic factors of MTC.MethodsBy extracting the data of patients diagnosed with MTC registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2016, we established the Cox proportional-hazards and competing-risks model to retrospectively analyze the impact of related factors on lymph nodes statistically.ResultsA total of 2,435 patients were included in the analysis, of which 198 died of MTC. The results of the multifactor competing-risk model showed that the number of total lymph nodes (19-89), positive lymph nodes (1-10,11-75) and positive lymph node ratio (25%-53%,>54%), age (46-60,>61), chemotherapy, mode of radiotherapy (others), tumor size(2-4cm,>4cm), number of lesions greater than 1 were poor prognostic factors for MTC. For the number of total lymph nodes, unlike the multivariate Cox proportional-hazards model results, we found that it became an independent risk factor after excluding competitive risk factors. Competitive risk factors have little effect on the number of positive lymph nodes. For the proportion of positive lymph nodes, we found that after excluding competitive risk factors, the Cox proportional-hazards model overestimates its impact on prognosis. The competitive risk model is often more accurate in analyzing the effects of prognostic factors.ConclusionsAfter excluding the competitive risk, the number of lymph nodes, the number of positive and the positive proportion are the poor prognostic factors of medullary thyroid cancer, which can help clinicians more accurately evaluate the prognosis of patients with medullary thyroid cancer and provide a reference for treatment decision-making.

BackgroundElectronic medical records (EMRs) of patients with lung cancer (LC) capture a variety of health factors. Understanding the distribution of these factors will help identify key factors for risk prediction in preventive screening for LC. ObjectiveWe aimed to generate an integrated biomedical graph from EMR data and Unified Medical Language System (UMLS) ontology for LC, and to generate an LC health factor distribution from a hospital EMR of approximately 1 million patients. MethodsThe data were collected from 2 sets of 1397 patients with and those without LC. A patient-centered health factor graph was plotted with 108,000 standardized data, and a graph database was generated to integrate the graphs of patient health factors and the UMLS ontology. With the patient graph, we calculated the connection delta ratio (CDR) for each of the health factors to measure the relative strength of the factor’s relationship to LC. ResultsThe patient graph had 93,000 relations between the 2794 patient nodes and 650 factor nodes. An LC graph with 187 related biomedical concepts and 188 horizontal biomedical relations was plotted and linked to the patient graph. Searching the integrated biomedical graph with any number or category of health factors resulted in graphical representations of relationships between patients and factors, while searches using any patient presented the patient’s health factors from the EMR and the LC knowledge graph (KG) from the UMLS in the same graph. Sorting the health factors by CDR in descending order generated a distribution of health factors for LC. The top 70 CDR-ranked factors of disease, symptom, medical history, observation, and laboratory test categories were verified to be concordant with those found in the literature. ConclusionsBy collecting standardized data of thousands of patients with and those without LC from the EMR, it was possible to generate a hospital-wide patient-centered health factor graph for graph search and presentation. The patient graph could be integrated with the UMLS KG for LC and thus enable hospitals to bring continuously updated international standard biomedical KGs from the UMLS for clinical use in hospitals. CDR analysis of the graph of patients with LC generated a CDR-sorted distribution of health factors, in which the top CDR-ranked health factors were concordant with the literature. The resulting distribution of LC health factors can be used to help personalize risk evaluation and preventive screening recommendations.

In a sono-reactor, complex ultrasound pressure wave signal can be detected, containing multiple information related to acoustic cavitation. In this present study, acoustic cavitation in a cylinder is investigated numerically. Via Fast Fourier Transfer (FFT), the sound pressure signals from sonotrode emitting surface are separated into harmonics, sub/ultra-harmonics and cavitation white noise: (1) the appearance of harmonics proved the non-linear propagation of ultrasound, (2) at the vibratory amplitude from 5∼20μm, only harmonics exists in the frequency spectra, corresponding to expansion and compression of non-condensable gas (NCG), (3) at the vibratory amplitude range of 30∼50μm, the occurrence of sub/ultra-harmonics demonstrated gaseous cavitation occurred, and (4) at the vibratory amplitude higher than 55μm, cavitation white noise arose, pointing out the initiation of vaporous cavitation. Based on the combination of frequency spectra and cavitation zones distribution, the acoustic cavitation state in water liquid is determined.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown etiology that is hard to diagnose early. Therefore, it is imperative to explore novel biomarkers that may contribute to the easy and early diagnosis of AS.Methods: Common differentially expressed genes between normal people and AS patients in GSE73754 and GSE25101 were screened by machine learning algorithms. A diagnostic model was established by the hub genes that were screened. Then, the model was validated in several data sets.Results:IL2RB and ZDHHC18 were screened using machine learning algorithms and established as a diagnostic model. Nomograms suggested that the higher the expression of ZDHHC18, the higher was the risk of AS, while the reverse was true for IL2RB in vivo. C-indexes of the model were no less than 0.84 in the validation sets. Calibration analyses suggested high prediction accuracy of the model in training and validation cohorts. The area under the curve (AUC) values of the model in GSE73754, GSE25101, GSE18781, and GSE11886 were 0.86, 0.84, 0.85, and 0.89, respectively. The decision curve analyses suggested a high net benefit offered by the model. Functional analyses of the differentially expressed genes indicated that they were mainly clustered in immune response–related processes. Immune microenvironment analyses revealed that the neutrophils were expanded and activated in AS while some T cells were decreased.Conclusion:IL2RB and ZDHHC18 are potential blood biomarkers of AS, which might be used for the early diagnosis of AS and serve as a supplement to the existing diagnostic methods. Our study deepens the insight into the pathogenesis of AS.

An efficient method for the synthesis of deuterated homologation of boronate esters was developed. This discovery uses robust deuterated agent 5-(methyl-d3)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethane sulfonate (DMTT) as d2-methylene source. Mechanistically, base promoted deprotonation of DMTT to generate d2-sulfur-methylene ylide intermediate, which attack the boron atom of boronic ester and followed by 1,2-migration to afford the deuterated boronic homologues. The developed protocol provides a unique approach to achieve one-carbon growth under the practical mild conditions.

Abstract Predators can induce phenotypic plasticity in prey through selection driven by predation risk. However, defense plasticity is rarely reported in insects, let alone trans-generational plasticity, meaning the mechanisms underlying plasticity, how it impacts ecosystem evolution and how it might be exploited in pest control are poorly understood. Here we examine the morphological plasticity of small brown planthoppers (SBPHs), Laodelphax striatellus, elicited by caged predators, Paederus fuscipes in the parent or F1 generation and reveal the risk cues mediating these effects. We also uncover the survival outcomes in SBPHs with predator-induced defensive morphological traits by examining their survival probability and behavioral plasticity. Results showed that caged predators or predator odor cue gave rise to a higher proportion of long-winged, female SBPHs in the parent and F1 generations, but the proportion of males and their wing length were unaffected. The visual cue from predators elicited weaker effects. Surprisingly, we discovered these long-winged forms suffered a lower predation rate when attacked by P. fuscipes, owing to an enhanced agility level. Our results suggest the within- and trans-generational plasticity of induced defenses may cause profound effects on SBPH population dynamics and prey-predator interaction. Understanding this interaction and its underlying mechanisms illuminates important aspects of ecosystem evolution and helps predict pest dispersal or migration, which in turn may be exploited for pest control.

Abstract Background Adenosine 5′-triphosphate (ATP) plays both a central role as an intracellular energy source, and a crucial extracellular signaling role in diverse physiological processes of animals and plants. However, there are less reports concerning the signaling role of microbial extracellular ATP (eATP). Hypocrellins are effective anticancer photodynamic therapy (PDT) agents from bambusicolous Shiraia fungi. The co-culture of Shiraia sp. S9 and a bacterium Pseudomonas fulva SB1 isolated from Shiraia fruiting bodies was established for enhanced hypocrellin A (HA) production. The signaling roles of eATP to mediate hypocrellin biosynthesis were investigated in the co-culture. Results The co-culture induced release of eATP at 378 nM to the medium around 4 h. The eATP release was interdependent on cytosolic Ca2+ concentration and reactive oxygen species (ROS) production, respectively. The eATP production could be suppressed by the Ca2+ chelator EGTA or abolished by the channel blocker La3+, ROS scavenger vitamin C and NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). The bacterium-induced H2O2 production was strongly inhibited by reactive blue (RB), a specific inhibitor of membrane purinoceptors, but dependent on the induced Ca2+ influx in the co-culture. On the other hand, the application of exogenous ATP (exATP) at 10–300 µM to Shiraia cultures also promoted fungal conidiation and HA production, both of which were blocked effectively by the purinoceptor inhibitors pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS) and RB, and ATP hydrolase apyrase. Both the induced expression of HA biosynthetic genes and HA accumulation were inhibited significantly under the blocking of the eATP or Ca2+ signaling, and the scavenge of ROS in the co-culture. Conclusions Our results indicate that eATP release is an early event during the intimate bacterial–fungal interaction and eATP plays a signaling role in the bacterial elicitation on fungal metabolites. Ca2+ and ROS are closely linked for activation of the induced ATP release and its signal transduction. This is the first report on eATP production in the fungal–bacterial co-culture and its involvement in the induced biosynthesis of fungal metabolites. Graphic abstract

Abstract The agricultural use of silica (SiO2) nanoparticles (NPs) has the potential to control insect pests while the safety and tritrophic effects on plants and beneficial natural enemies remains unknown. Here, we evaluate the effects of silica NPs on insect pests with different feeding niches, natural enemies, and a plant. Silica NPs were applied at different concentrations (75–425 mg/L) on field-cultivated faba bean and soybean for two growing seasons. The faba bean pests, the cowpea aphid Aphis craccivora and the American serpentine leafminer Liriomyza trifolii, and the soybean pest, the cotton leafworm Spodoptera littoralis, were monitored along with their associated predators. Additional laboratory experiments were performed to test the effects of silica NPs on the growth of faba bean seedlings and to determine whether the rove beetle Paederus fuscipes is attracted to cotton leafworm-infested soybean treated with silica NPs. In the field experiments, silica NPs reduced the populations of all three insect pests and their associated predators, including rove beetles, as the concentration of silica NPs increased. In soybean fields, however, the total number of predators initially increased after applying the lowest concentration. An olfactometer-based choice test found that rove beetles were more likely to move towards an herbivore-infested plant treated with silica NPs than to a water-treated control, suggesting that silica NPs enhance the attraction of natural enemies via herbivore-induced plant volatiles. In the laboratory, while silica NPs inhibited the development of faba bean roots at 400 mg/L, they did not affect germination percentage, germination time, shoot length, or vigor index compared to the control.