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BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Fibroblast growth factor receptor 1 (FGFR1) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l−1, follicle-stimulating hormone (FSH) levels were 1.0 IU l−1, and testosterone levels were 1.3 nmol l−1. In contrast, the de novo group had LH levels of 0.2 IU l−1, FSH levels of 0.5 IU l−1, and testosterone levels of 0.9 nmol l−1, indicating milder hypothalamus–pituitary–gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

This study employed optical microscopy (OM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) to investigate the impact of vanadium (V) on the microstructure and mechanical properties of gray cast iron (GCI) HT250. Additionally, Thermo-Calc software was employed to explore the influence of V on the solidification process. The results indicate that adding trace amounts of V in GCI forms a face-centered cubic VC phase, with the precipitation temperature of the VC phase gradually increasing. When the V content reaches 0.28 wt%, the VC phase begins to precipitate during the eutectic reaction. The incorporation of V consumes carbon, reducing the graphite content and promoting the formation of type D graphite. As the V content increases, there is an enlargement in the pearlite area ratio, a decrease in the pearlite layer spacing, and a reduction in the size of eutectic cells. These microstructural alterations lead to enhanced mechanical properties. The tensile strength peaks at 336 MPa with a V content of 0.77 wt%, representing a 29% increase compared to samples without added V. Similarly, the Vickers hardness increases with increasing V content, reaching a peak of 373 HV at 0.92 wt% V, a 27% increase compared to samples without V addition. However, at this point, the tensile strength decreases to 322 MPa.

AimsTo develop and validate an individualized nomogram for differentiating the histologic subtypes (adenocarcinoma and squamous cell carcinoma) of subpleural non-small cell lung cancer (NSCLC) based on ultrasound parameters and clinical data.MethodsThis study was conducted retrospectively between March 2018 and December 2019. Patients were randomly assigned to a development cohort (DC, n=179) and a validation cohort (VC, n=77). A total of 7 clinical parameters and 16 ultrasound parameters were collected. Least absolute shrinkage and selection operator regression analysis was employed to identify the most significant predictors utilizing a 10-fold cross-validation. The multivariate logistic regression model was applied to investigate the relevant factors. An individualized nomogram was then developed. Receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were applied for model validation in both DC and VC.ResultsFollowing the final regression analysis, gender, serum carcinoembryonic antigen, lesion size and perfusion defect in contrast-enhanced ultrasound were entered into the nomogram. The model showed moderate predictive ability, with an area under the ROC curve of 0.867 for DC and 0.838 for VC. The calibration curves of the model showed good agreement between actual and predicted probabilities. The ROC and DCA curves demonstrated that the nomogram exhibited a good predictive performance.ConclusionWe developed a nomogram that can predict the histologic subtypes of subpleural NSCLC. Both internal and external validation revealed optimal discrimination and calibration, indicating that the nomogram may have clinical utility. This model has the potential to assist clinicians in making treatment recommendations.

ABSTRACT Introduction Staged bilateral surgery is widely used to treat synchronous multiple primary lung cancer (SMPLC); however, the prognostic factors for survival outcomes remain unclear. This study aimed to identify prognostic factors and construct a predictive model for overall survival (OS) and recurrence‐free survival (RFS) in patients with SMPLC who underwent staged bilateral surgery. Methods The study included 256 patients diagnosed with SMPLC and treated with staged bilateral surgery at our hospital between January 2010 and July 2017. Multivariate Cox proportional‐hazard regression was used to identify prognostic factors for OS and RFS. Additionally, a predictive model was constructed using time‐dependent receiver operating characteristic curves. Results Among the 256 patients, 10 (3.95%) succumbed to the disease and 24 (9.41%) experienced recurrence. Smoking (hazard ratio [HR]: 5.128; 95% confidence interval [CI]: 1.442–18.233; p = 0.012) and most advanced pathological TNM (pTNM) stage (II + III) (HR: 12.938; 95% CI: 2.650–63.176; p = 0.002) were identified as significant predictors of poor OS. A prognostic model was developed for predicting OS, with a 5‐year area under the curve (AUC) of 0.854. Furthermore, most advanced pTNM stage (II + III) was associated with poor RFS (HR: 5.964; 95% CI: 2.669–13.327; p

The instability of the inverse problem is caused by its nonlocal and non-causal nature. This study addresses the inverse problem of determining the physical parameters of semiconductor devices. Based on statistical inversion theory, the probability distribution (posterior distribution) of the SBHs has been estimated by convolutional neural networks. Regularization techniques were then applied to such a distribution to accurately determine the SBHs of semiconductor devices. The results reveal that the fluctuations in the predicted SBHs by convolutional neural networks are similar to the amplitude between the upper and lower envelopes of the free decay curve. The method achieves a maximum relative error below 3.4% when using theoretical diode current–voltage data as input and maintains a relative error of less than 7% when compared to traditional methods when using experimental current–voltage data. Furthermore, the proposed method offers a mathematical interpretation of the inverse problem and demonstrates the capability of the proposed method to extract the physical parameters of semiconductor devices with a small amount of data.

Although new-type energetic materials have been investigated extensively, there is a challenge on how to integrate energy density and mechanical properties of energetic materials simultaneously. Herein, a versatile approach was proposed to design energetic materials with high energy density, reactivity, and flexibility based on a bio-inspired strategy. By mimicking the “brick-and-mortar” structure within a natural nacre, the energetic film with alternative layers of polytetrafluoroethylene (PTFE) and boron (B) was successfully fabricated. The nacre-mimetic PTFE/B energetic film exhibited excellent reaction heat (4413.9 J⋅g−1) and bright combustion flame, which may originate from the exothermic reaction mechanism between fluorine (F) and B. Even more remarkably, such PTFE/B energetic film revealed prominent mechanical flexibility reported for the first time. These findings indicate that the nacre-mimetic strategy provides an effective route to engineer energetic materials with high energy density, reactivity, and flexibility.

A new spleenwort species, Asplenium guodanum, was found and described from Danxia landform region in Guangdong, China. The new species has close resemblance to A. subcrenatum Ching ex S.H.Wu in morphology, but can be distinguished by having plants small, stipes and rachises not covered with fibrous scales, relatively fewer pairs of pinnae, pinnae short, pinna margin weakly biserrate, pinna apex acute and lower pinnae obviously reduced. Phylogenetic analyses, based on six plastid markers (atpB, rbcL, rps4 & rps4-trnS and trnL & trnL-F) of the new species and its relatives, support a close relationship between A. guodanum and A. subcrenatum. Only one population with no more than 50 individuals were found and, therefore, it is recommended to be classified as Critically Endangered (CR) following IUCN Red List Criteria.

A transient heat conduction equation has been proposed to describe the cooling process of a hot two-dimensional electron gas layer in a GaN-based transistor. This equation serves as the basis for a physical analytical model that explains the impacts of hot electrons in the hot two-dimensional electron gas layer via quantum coupling on the threshold voltage of GaN-based transistors. The temperature of the two-dimensional electron gas layer decreases to ambient temperature as time increases, and the threshold voltage shifts caused by such a temperature will recover with time. The proposed model accurately reflects the observed recovery of threshold voltage over time in experiments. At the same time, it offers insight into how the gate voltage, the source-drain voltage, and the ambient temperature can shift the threshold voltage in these transistors. The simplicity and analytic nature of this proposed model not only provide a physical origin of the threshold voltage instability in GaN-based devices but also offer the possibility for improving device reliability by selecting appropriate device physical parameters.

BackgroundDuring the disease cycle, plant pathogenic fungi exhibit a morphological transition between hyphal growth (the phase of active infection) and the production of long-term survival structures that remain dormant during "overwintering." Verticillium dahliae is a major plant pathogen that produces heavily melanized microsclerotia (MS) that survive in the soil for 14 or more years. These MS are multicellular structures produced during the necrotrophic phase of the disease cycle. Polyketide synthases (PKSs) are responsible for catalyzing production of many secondary metabolites including melanin. While MS contribute to long-term survival, hyphal growth is key for infection and virulence, but the signaling mechanisms by which the pathogen maintains hyphal growth are unclear.ResultsWe analyzed the VdPKSs that contain at least one conserved domain potentially involved in secondary metabolism (SM), and screened the effect of VdPKS deletions in the virulent strain AT13. Among the five VdPKSs whose deletion affected virulence on cotton, we found that VdPKS9 acted epistatically to the VdPKS1-associated melanin pathway to promote hyphal growth. The decreased hyphal growth in VdPKS9 mutants was accompanied by the up-regulation of melanin biosynthesis and MS formation. Overexpression of VdPKS9 transformed melanized hyphal-type (MH-type) into the albinistic hyaline hyphal-type (AH-type), and VdPKS9 was upregulated in the AH-type population, which also exhibited higher virulence than the MH-type.ConclusionsWe show that VdPKS9 is a powerful negative regulator of both melanin biosynthesis and MS formation in V. dahliae. These findings provide insight into the mechanism of how plant pathogens promote their virulence by the maintenance of vegetative hyphal growth during infection and colonization of plant hosts, and may provide novel targets for the control of melanin-producing filamentous fungi.

Abstract Esophagogastric variceal bleeding (EVB) is one of the common digestive system emergencies with poor prognosis and high rate of rebleeding after treatment. To explore the effects of endoscopic therapy and drug therapy on the prognosis and rebleeding of patients with EVB, and then select better treatment methods to effectively improve the prognosis. From January 2013 to December 2022, 965 patients with EVB who were hospitalized in gastroenterology Department of the 940 Hospital of Joint Logistic Support Forces of PLA were retrospectively analyzed. Patients were divided into endoscopic treatment group (ET, n = 586) and drug treatment group (DT, n = 379). Propensity score matching (PSM) analysis was performed in both groups, and the general information, efficacy and length of hospital stay were recorded. The patients were followed up for 3 months after bleeding control to determine whether rebleeding occurred. There were 286 cases in each group after PSM. Compared with DT group, ET had higher treatment success rate (P 0.05). Compared with drug therapy, endoscopic treatment of EVB has short-term efficacy advantages, and can effectively reduce the incidence of rebleeding and mortality within 3 months.

Abstract Objectives To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs). Materials and methods Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis. Results One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs. Conclusion Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making. Trial registration This trial is registered on www.chictr.org.cn : ChiCTR2000031231. Registered March 25, 2020. Critical relevance statement A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer. Key points • CEUS can help identify and diagnose SLN in early breast cancer preoperatively. • Combining lymphatic and grayscale US findings can predict axillary tumor burden. • The nomogram showed a high diagnostic value in validation cohorts. Graphical Abstract

The genus Rhododendron exhibits an immense diversity of flower colors and represents one of the largest groups of woody plants, which is of great importance for ornamental plant research. This review summarizes recent progress in deciphering the genetic basis for flower coloration in Rhododendron. We describe advances in phylogenetic reconstruction and genome sequencing of Rhododendron species. The metabolic pathways of flower color are outlined, focusing on key structural and regulatory genes involved in pigment synthesis. Gene duplications and losses associated with color diversification are discussed. In addition, the application of multi-omics approaches and analysis of gene co-expression networks to elucidate complex gene regulatory mechanisms is emphasized. This synthesis of current knowledge provides a foundation for future research on the evolution of flower color diversity within the Rhododendron lineage. Ultimately, these discoveries will support breeding endeavors aimed at harnessing the genetics of flower coloration and developing novel cultivars that exhibit desired floral traits.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

The 7A04 Al alloy is a commonly used lightweight metal material; however, its low wear resistance limits its application. In this study, the wear resistance of this alloy was improved by preparing micro-arc oxidation (MAO) coatings, MAO/MoS2 composite coatings, and hard-anodized (HA) coatings on its surface. The friction and wear behaviors of these three coatings with diamond-like coated (DLC) rings under oil lubrication conditions were investigated using a ring–block friction tester. The wear rates of the coatings on the block surfaces were determined using laser confocal microscopy, and the wear trajectories of the coatings were examined using scanning electron microscopy. The results indicated that, among the three coatings, the MAO/MoS2 coating had the lowest coefficient of friction of 0.059, whereas the HA coating had the lowest wear rate of 1.47 × 10−6 mm/Nm. The MAO/MoS2 coatings exhibited excellent antifriction properties compared to the other coatings, whereas the HA coatings exhibited excellent anti-wear properties. The porous structure of the MAO coatings stored lubricant and replenished the lubrication film under oil lubrication. Meanwhile, the introduced MoS2 enhanced the densification of the coating and functioned as a solid lubricant. The HA coating exhibited good wear resistance owing to the dense structure of the amorphous-phase aluminum oxide. The mechanisms of abrasive and adhesive wear of the coatings under oil lubrication conditions and the optimization of the tribological properties by the solid–liquid synergistic lubrication effect were investigated. This study provides an effective method for the surface modification of Al alloys with potential applications in the aerospace and automotive industries.

This paper introduces a multi-objective optimization problem (MPO) for the forming process parameters of disc forgings using grey relational analysis (GRA) and the response surface methodology (RSM). Firstly, an experimental design based on the Box–Behnken design (BBD) principle was established, and simulations were performed in Deform to obtain response data. Secondly, GRA was used to transform the MPO into a grey relational degree (GRD) problem, and the entropic weight method was integrated to ascertain the influence weights of each variable on GRD. Then, a quadratic polynomial prediction model based on the RSM was constructed, and its accuracy was ensured through model validation. Finally, the optimal process parameter combination was determined through the particle swarm optimization algorithm, which included a friction coefficient of 0.3, an initial temperature of 1250 °C, and a downward pressing speed of 7.5 mm/s. The results of the experimental investigation indicate that optimized process parameters significantly reduce the forming load, equivalent stress, and damage value, effectively enhancing the overall quality of forged parts.

Innate immune systems are key defenses of animals and particularly important in species that lack the sophisticated adaptive immune systems as found in vertebrates. Here, we were interested to quantify variation in innate immune responses of insects in hosts that differ in their parasite susceptibility. To do this, we studied immune responses in honey bees, which can host a remarkable number of different parasites, which are major contributors of declining bee health and colony losses. The most significant parasite of honey bees is the mite Varroa destructor, which has infested the majority of global honey bee populations, and its control remains a major challenge for beekeepers. However, a number of nonmanaged honey bees seem able to control Varroa infections, for example, the Eastern honey bee Apis ceranacerana or the African honey bee Apis mellifera scutellata. These bees therefore make interesting study subjects to identify underlaying resistance traits, for example, by comparing them to more susceptible bee genotypes such as Western honey bees (A. melliferaligustica). We conducted a series of interlinked experiments and started with behavioral assays to compare the attractiveness of bee larvae to mites using different honey bee genotypes and castes. We found that 6-day-old larvae are always most attractive to mites, independently of genotype or castes. In a next step, we compared volatile profiles of the most attractive larvae to test whether they could be used by mites for host selection. We found that the abundance of volatile compounds differed between larval ages, but we also found significant differences between genotypes and castes. To further study the expected underlaying physiological differences between potentially resistant and susceptible host larvae, we compared the larval hemolymph proteomes of the three honey bee genotypes and two castes in response to mite exposure. We identified consistent upregulation of immune and stress-related genes in Varroa-exposed larvae, which differed between genotypes and castes. Tolerant honey bee castes and genotypes were characterized by stronger or more distinct immune esponses. In summary, we provide first insights into the complex involvement of the innate immune system of tolerant honey bees against mite infestations, which could be used for future breeding purposes.

BackgroundNeuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion.MethodsWe conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis.ResultsA total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5 cm (36.5%) and >5 cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P

Abstract Background Melanin plays important roles in morphological development, survival, host–pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. Results We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. Conclusions Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Recently, an emerging category green of energetic material ammonium dinitramide (ADN) has exhibited promising application in propellants due to its outstanding merits in energy release and environmental friendliness. It can be considered to substitute traditional oxidizer of ammonium perchlorate (AP) in military systems and aerospace. In this paper, a novel spherical energetic composite ADN/copper alginate (CA) with a microporous structure was designed and prepared by the W/O gel emulsion method, and a desirable porous microsphere structure was obtained. Multiple characterization techniques were used to investigate the structure and properties of ADN/CA composites. The results showed that ADN crystals were homogeneously encapsulated in an alginate-gel matrix. Thermal decomposition temperature was reduced to 151.7 °C compared to ADN, while the activation energy of them was reduced from 129.73 kJ/mol (ADN) to 107.50 kJ/mol (ADN/CA-4). In addition, as-prepared samples had lower impact and frictional sensitivity than ADN. The mechanism of sensitivity reduction and decomposition are also discussed. Constant-volume combustion tests show that peak pressure of the ADN/CA-4 achieves 253.4 kPa and pressurization rate of 2750.4 kPa/s. Hence, this has a promising application in improving the combustion performance and safety performance of solid propellants.

Verticillium dahliae is a destructive soil-borne pathogen of many economically important dicots. The genetics of pathogenesis in V. dahliae has been extensively studied. Spt-Ada-Gcn5 acetyltransferase complex (SAGA) is an ATP-independent multifunctional chromatin remodeling complex that contributes to diverse transcriptional regulatory functions. As members of the core module in the SAGA complex in Saccharomyces cerevisiae, Ada1, together with Spt7 and Spt20, play an important role in maintaining the integrity of the complex. In this study, we identified homologs of the SAGA complex in V. dahliae and found that deletion of the Ada1 subunit (VdAda1) causes severe defects in the formation of conidia and microsclerotia, and in melanin biosynthesis and virulence. The effect of VdAda1 on histone acetylation in V. dahliae was confirmed by western blot analysis. The deletion of VdAda1 resulted in genome-wide alteration of the V. dahliae transcriptome, including genes encoding transcription factors and secreted proteins, suggesting its prominent role in the regulation of transcription and virulence. Overall, we demonstrated that VdAda1, a member of the SAGA complex, modulates multiple physiological processes by regulating global gene expression that impinge on virulence and survival in V. dahliae.

Verticillium dahliae is a soil-borne fungal pathogen that can cause severe vascular wilt in many plant species. Kelch repeat proteins are essential for fungal growth, resistance, and virulence. However, the function of the Kelch repeat protein family in V. dahliae is unclear. In this study, a Kelch repeat domain-containing protein DK185_4252 (VdLs.17 VDAG_08647) included in the conserved VdPKS9 gene cluster was identified and named VdKeR1. Phylogenetic analysis demonstrated a high degree of evolutionary conservation of VdKeR1 and its homologs among fungi. The experimental results showed that the absence of VdKeR1 impaired vegetative growth, microsclerotia development, and pathogenicity of V. dahliae. Osmotic and cell wall stress analyses suggested that VdKeR1-deleted mutants were more tolerant to NaCl, sorbitol, CR, and CFW, while more sensitive to H2O2 and SDS. In addition, analyses of the relative expression level of sqe and the content of squalene and ergosterol showed that VdKeR1 mediates the synthesis of squalene and ergosterol by positively regulating the activity of squalene epoxidase. In conclusion, these results indicated that VdKeR1 was involved in the growth, stress resistance, pathogenicity, and ergosterol metabolism of V. dahliae. Investigating VdKeR1 provided theoretical and experimental foundations for subsequent control of Verticillium wilt.

As a typical energetic composite, polytetrafluoroethylene (PTFE)/aluminum (Al) has been widely applied in explosives, pyrotechnics, and propellants due to its ultra-high energy density and intense exothermic reaction. In this work, the radial gradient (RG) structure of PTFE/Al cylinders with three different PTFE morphologies (200 nm and 5 μm particles and 5 μm fiber) and content changes are prepared by 3D printing technology. The effect of radial gradient structure on the pressure output of PTFE/Al has been studied. Compared with the morphology change of PTFE, the change of component content in the gradient structure has an obvious effect on the pressure output of the PTFE/Al cylinder. Furthermore, the relationships of the morphology, content of PTFE and the combustion reaction of the PTFE/Al cylinder reveal that the cylinder shows a more complex flame propagation process than others. These results could provide a strategy to improve the combustion and pressure output of PTFE/Al.

Abstract. Patients with chronic liver diseases (CLDs) have high hospitalization and mortality rates when combined with severe coronavirus disease 2019 (COVID-19) because of defects in humoral and cellular immunity, known as immune dysfunction. COVID-19 vaccines effectively reduce the risk of severe illness and mortality caused by the virus. Several studies have confirmed the safety and efficacy of the COVID-19 vaccine in patients with CLD, and the existing expert consensus recommends that patients with stable CLD be prioritized for the COVID-19 vaccine. In addition, clinical trials are ongoing to determine the optimal strategy for patients with CLD to receive the COVID-19 vaccine. In this study, we review the progress of research on the safety and efficacy of COVID-19 vaccination in patients with CLD, aiming to provide better recommendations for the vaccination in this population.

Background: Primary hepatic lymphoepithelioma-like carcinoma (LELC) is a malignant tumor with a low incidence, but the number of case reports has increased in recent years. The prognosis of hepatic LELC is better than hepatocellular carcinoma (HCC). The differentiation between hepatic LELC and HCC has clinical value during follow-up treatment. The purpose of our study was to compare contrast-enhanced ultrasound (CEUS) imaging features in patients with hepatic LELC and HCC. Methods: Twelve patients with an average age of 60.1±9.5 years and histopathologically confirmed hepatic LELC were included in the study. Forty-three patients with an average age of 57.4±9.0 years and a histopathological diagnosis of HCC were designated as the control group by means of propensity score matching (1:4). The clinical data, B-mode ultrasound (BMUS), and CEUS features were retrospectively analyzed between patients with hepatic LELC and HCC. Results: The serum a-fetoprotein (58.1% [25/43] vs.16.7% [2/12]; p=0.017) and des-gamma-carboxy prothrombin levels (74.4% [32/43] vs.16.7% [2/12]; p=0.001) were not significantly elevated in patients with hepatic LELCs compared to HCCs. LELCs were mainly hypoechoic based on BMUS, while the echogenicity of HCCs varied (p=0.016). A halo sign was less common in patients with hepatic LELCs than HCCs (16.7% [2/12] vs. 58.1% [25/43]; p=0.011). Of hepatic LELCs, 75% (9/12) had homogeneous hyperenhancement based on CEUS, whereas 58.1% (25/43) of HCCs had heterogeneous hyperenhancement (p=0.004). Early washout was noted in 91.7% (11/12) of hepatic LELCs compared to 46.5% (20/43) of HCCs (p=0.005). Furthermore, hepatic LELCs were more likely to exhibit peripheral rim-like hyperenhancement (83.3% [10/12] vs. 11.6% [5/43]; p < 0.001). Conclusion: BMUS and CEUS are helpful in discriminating between hepatic LELC and HCC. A hypoechoic mass, the rare halo sign, homogeneous hyperenhancement in the arterial phase, higher frequencies of early washout, and peripheral rim-like hyperenhancement are useful ultrasound features that can help differentiate hepatic LELCs from HCCs.

Abstract Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin‐binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self‐renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson’s disease (PD). Although dysfunction of the olfactory system has been recognized as an important predictor of cognitive decline, the exact mechanism by which aberrant olfactory circuits contribute to cognitive dysfunction in PD is unclear. Here, we provide the first evidence for abnormal functional connectivity across olfactory bulb (OB) and piriform cortex (PC) or entorhinal cortex (EC) by clinical fMRI, and dysfunction of neural coherence in the olfactory system in PD mice. Moreover, we discovered that 2 subpopulations of mitral/tufted (M/T) cells in OB projecting to anterior PC (aPC) and EC precisely mediated the process of cognitive memory respectively by neural coherence at specific frequencies in mice. In addition, the transcriptomic profiling analysis and functional genetic regulation analysis further revealed that biorientation defective 1 (Bod1) may play a pivotal role in encoding OBM/T-mediated cognitive function. We also verified that a new deep brain stimulation protocol in OB ameliorated the cognitive function of Bod1-deficient mice and PD mice. Together, aberrant coherent activity in the olfactory system can serve as a biomarker for assessing cognitive function and provide a candidate therapeutic target for the treatment of PD.

Xanthoceras sorbifolium (yellowhorn) is a woody oil plant with super stress resistance and excellent oil characteristics. The yellowhorn oil can be used as biofuel and edible oil with high nutritional and medicinal value. However, genetic studies on yellowhorn are just in the beginning, and fundamental biological questions regarding its very long-chain fatty acid (VLCFA) biosynthesis pathway remain largely unknown. In this study, we reconstructed the VLCFA biosynthesis pathway and annotated 137 genes encoding relevant enzymes. We identified four oleosin genes that package triacylglycerols (TAGs) and are specifically expressed in fruits, likely playing key roles in yellowhorn oil production. Especially, by examining time-ordered gene co-expression network (TO-GCN) constructed from fruit and leaf developments, we identified key enzymatic genes and potential regulatory transcription factors involved in VLCFA synthesis. In fruits, we further inferred a hierarchical regulatory network with MYB-related (XS03G0296800) and B3 (XS02G0057600) transcription factors as top-tier regulators, providing clues into factors controlling carbon flux into fatty acids. Our results offer new insights into key genes and transcriptional regulators governing fatty acid production in yellowhorn, laying the foundation for efforts to optimize oil content and fatty acid composition. Moreover, the gene expression patterns and putative regulatory relationships identified here will inform metabolic engineering and molecular breeding approaches tailored to meet biofuel and bioproduct demands.

Abstract Coriaria nepalensis Wall. (Coriariaceae) is a nitrogen-fixing shrub which forms root nodules with the actinomycete Frankia. Oils and extracts of C. nepalensis have been reported to be bacteriostatic and insecticidal, and C. nepalensis bark provides a valuable tannin resource. Here, by combining PacBio HiFi sequencing and Hi-C scaffolding techniques, we generated a haplotype-resolved chromosome-scale genome assembly for C. nepalensis. This genome assembly is approximately 620 Mb in size with a contig N50 of 11 Mb, with 99.9% of the total assembled sequences anchored to 40 pseudochromosomes. We predicted 60,862 protein-coding genes of which 99.5% were annotated from databases. We further identified 939 tRNAs, 7,297 rRNAs, and 982 ncRNAs. The chromosome-scale genome of C. nepalensis is expected to be a significant resource for understanding the genetic basis of root nodulation with Frankia, toxicity, and tannin biosynthesis.

In this study, scanning electron microscopy (SEM), electron backscatter diffraction analysis (EBSD), and electron probe microanalysis (EPMA) were used to investigate the impact of rare-earth Sc on the interface microstructure and mechanical properties of Al/steel bimetallic composites fabricated by liquid–solid casting. With the addition of 0.3% Sc, the morphology of eutectic Si changed from needle-like to fibrous and granular. The addition of Sc did not change the types of intermetallic compounds in the Al/steel reaction layer, which comprised the Al5Fe2, τ1-Al2Fe3Si3, Al13Fe4, τ5-Al7Fe2Si, and τ6-Al9Fe2Si2 phases. The thickness of the first layer decreased, whereas that of the second layer increased as the Sc content increased to 0.3%. Furthermore, the Al5Fe2 and τ1 phase percentages of the reaction layer decreased, whereas the Al13Fe4, τ5, and τ6 phase percentages increased. Sc was mainly enriched in the front of the ternary compound layer (τ6) near the Al side. The addition of 0.3% Sc reduced the grain size of each phase in the interfacial reaction layer and did not change the preferred orientation of the Al5Fe2, Al13Fe4, τ5, and τ6 phases, but increased the polar density of the Al13Fe4, τ5, and τ6 phases and decreased the polar density of the Al5Fe2 phase. With the addition of 0.3% Sc, the average nanohardness of the reaction layer decreased by 5% and the bonding strength increased by 48%.

Abstract Background Immune checkpoint inhibitors are the most studied forms of immunotherapy for triple-negative breast cancer (TNBC). The Cancer Genome Map (TCGA) and METABRIC project provide large-scale cancer samples that can be used for comprehensive and reliable immunity-related gene research. Methods We analyzed data from TCGA and METABRIC and established an immunity-related gene prognosis model for breast cancer. The SDC1 expression in tumor and cancer associated fibroblasts (CAFs) was then observed in 282 TNBC patients by immunohistochemistry. The effects of SDC1 on MDA-MB-231 proliferation, migration and invasion were evaluated. Qualitative real-time PCR and western blotting were performed to identify mRNA and protein expression, respectively. Results SDC1, as a key immunity-related gene, was significantly correlated with survival in the TCGA and METABRIC databases, while SDC1 was found to be highly expressed in TNBC in the METABRIC database. In the TNBC cohort, patients with high SDC1 expression in tumor cells and low expression in CAFs had significantly lower disease-free survival (DFS) and fewer tumor-infiltrating lymphocytes (TILs). The downregulation of SDC1 decreased the proliferation of MDA-MB-231, while promoting the migration of MDA-MB-231 cells by reducing the gene expression of E-cadherin and TGFb1 and activating p-Smad2 and p-Smad3 expression. Conclusion SDC1 is a key immunity-related gene that is highly expressed TNBC patients. Patients with high SDC1 expression in tumors and low expression in CAFs had poor prognoses and low TILs. Our findings also suggest that SDC1 regulates the migration of MDA-MB-231 breast cancer cells through a TGFb1-Smad and E-cadherin-dependent mechanism.

Terpenes and terpenoids are key natural compounds for plant defense, development, and composition of plant oil. The synthesis and accumulation of a myriad of volatile terpenoid compounds in these plants may dramatically alter the quality and flavor of the oils, which provide great commercial utilization value for oil-producing plants. Terpene synthases (TPSs) are important enzymes responsible for terpenic diversity. Investigating the differentiation of the TPS gene family could provide valuable theoretical support for the genetic improvement of oil-producing plants. While the origin and function of TPS genes have been extensively studied, the exact origin of the initial gene fusion event - it occurred in plants or microbes - remains uncertain. Furthermore, a comprehensive exploration of the TPS gene differentiation is still pending. Here, phylogenetic analysis revealed that the fusion of the TPS gene likely occurred in the ancestor of land plants, following the acquisition of individual C- and N- terminal domains. Potential mutual transfer of TPS genes was observed among microbes and plants. Gene synteny analysis disclosed a differential divergence pattern between TPS-c and TPS-e/f subfamilies involved in primary metabolism and those (TPS-a/b/d/g/h subfamilies) crucial for secondary metabolites. Biosynthetic gene clusters (BGCs) analysis suggested a correlation between lineage divergence and potential natural selection in structuring terpene diversities. This study provides fresh perspectives on the origin and evolution of the TPS gene family.