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Abstract TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.

Abstract Background Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. Case description Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. Conclusions This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

Dual-phase amorphous-nanocrystalline Al-x at.% Mo (x = 20, 26, 30) alloy films prepared in the way of dual-phase co-growth directly through magnetron sputtering were studied in terms of thermally induced microstructural evolution and mechanical properties via annealing at 550 °C. It was observed that, the annealed Al-26 and 30 at.% Mo alloy films maintained stable dual-phase amorphous-nanocrysatlline structure and precipitated Al8Mo3 nano-grains dispersed in amorphous matrix uniformly. After annealing, the surface roughness of Al-26 and 30 at.% Mo alloy films remained unchanged of 7.5 nm and the hardness and elastic modulus of them were as high as 13 and 210 GPa which enhanced about 50 % and 24 % than before, respectively. In contrast, the Al-20 at.% Mo alloy film crystallized completely and mainly contained intermetallic Al12Mo phase along with apparent grain coarsening after annealing, which resulted in significant increase of surface roughness and deterioration of hardness. The excellent thermal stability of dual-phase amorphous-nanocrystalline Al-26 and 30 at.% Mo alloy films stem from the small driving force for precipitated Al8Mo3 nano-grain growth, as well as benefit from effect of diffusion field impingement.

Purpose To analyse retinal and choroidal microvasculature features in healthy pregnant women using optical coherence tomography angiography (OCTA).Methods PubMed, Embase, Ovid, Web of Science and Cochrane Library were searched for published studies that compare retinal and choroidal microvasculature characteristics between pregnant females and non-pregnant females from inception to November 2023. The statistics were continuous variables. They were presented as the mean difference (MD) with a corresponding 95% CI. We used Review Manager software 5.4.1 for statistical analysis.Results A total of 5 eligible studies involving 219 eyes in the pregnancy group and 186 eyes in the control group were included in the meta-analysis. The pooled results showed that the retinal deep capillary plexus vascular density (DCP VD) measured by OCTA was significantly higher in healthy pregnant women than in controls (MD 1.53; 95% CI 0.62 to 2.44; I2=0%; p=0.0009). However, differences between the two groups in the retinal superficial capillary plexus VD (SCP VD) (MD 0.41;95% CI −1.26 to 2.09; I2=85%; p=0.63), the foveal avascular zone (FAZ) (MD 0.01; 95% CI −0.01 to 0.03; I2=14%; p=0.18), the choriocapillaris VD (CC VD) (MD 0.76; 95% CI −1.11 to 2.64; I2=79%; p=0.43) were uncertain.Conclusions Our meta-analysis found that the DCP VD of healthy pregnant women was higher than that of non-pregnant controls. However, differences in SCP VD, FAZ and CC VD between the healthy pregnant women and the non-pregnancy controls were uncertain. Our findings can help to get a deeper understanding of retinal and choroidal microvascular characteristics during pregnancy.

Herbal extraction residues (HERs) cause serious environmental pollution and resource waste. In this study, a novel green route was designed for the comprehensive reutilization of all components in HERs, taking Magnolia officinalis residues (MOR) as an example. The reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients (magnolol and honokiol) originally remaining in MOR and to make MOR more accessible for hydrolysis. A metal–organic frame material MIL-101(Cr) with a maximum absorption capacity of 255.64 mg g−1 was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions, and 40 g L−1 reducing sugars were obtained with 81.8% enzymatic hydrolysis rate at 10% MOR solid loading. Finally, 382 mg L−1 β-amyrin was produced from MOR hydrolysates by an engineered yeast strain. In total, 1 kg honokiol, 8 kg magnolol, and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

The Simultaneous Localization and Mapping (SLAM) environment is evolving from static to dynamic. However, traditional SLAM methods struggle to eliminate the influence of dynamic objects, leading to significant deviations in pose estimation. Addressing these challenges in dynamic environments, this paper introduces a semantic-assisted LIDAR tightly coupled SLAM method. Specifically, to mitigate interference from dynamic objects, a scheme for calculating static semantic probability is proposed. This enables the segmentation of static and dynamic points while eliminating both stationary dynamic objects and moving environmental blocking objects. Additionally, in point cloud feature extraction and matching processes, we incorporate constraint conditions based on semantic information to enhance accuracy and improve pose estimation precision. Furthermore, a semantic similarity constraint is included within the closed-loop factor module to significantly enhance positioning accuracy and facilitate the construction of maps with higher global consistency. Experimental results from KITTI and M2DGR datasets demonstrate that our method exhibits generalization ability towards unknown data while effectively mitigating dynamic interference in real-world environments. Compared with current state-of-the-art methods, our approach achieves notable improvements in both accuracy and robustness.

Abstract Introduction In this single-center retrospective cohort study, we investigated the efficacy of letermovir in preventing Cytomegalovirus (CMV) infection in patients with aplastic anemia (AA) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Based on whether or not letermovir was used for preventing CMV infection, the patients were categorized into two groups: letermovir and control groups. The overall survival (OS) rate and cumulative incidence of CMV infection during the first 100 days after allo-HSCT were evaluated. The study included 21 matched pairs of patients, identified through propensity score matching analysis, to compare CMV infection rates, treatment efficacy, and regression. Results The incidence of CMV infection within 100 days after transplantation was significantly lower in the letermovir group than in the control group (26.5 vs. 77.4%, respectively; P

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Xylanase plays a key role in degrading plant cell wall during pathogenic fungi infection. Here, we identified a xylanase gene, VmXyl2 from the transcriptome of Valsa mali and examined its function. VmXyl2 has highly elevated transcript levels during the infection process of V. mali, with 15.02-fold increase. Deletion mutants of the gene were generated to investigate the necessity of VmXyl2 in the development and pathogenicity of V. mali. The VmXyl2 deletion mutant considerably reduced the virulence of V. mali in apple leaves and in twigs, accompanied by 41.22% decrease in xylanase activity. In addition, we found that VmXyl2 induces plant cell necrosis regardless of its xylanase activity, whereas promoting the infection of V. mali in apple tissues. The cell death-inducing activity of VmXyl2 dependent on BRI1-associated kinase-1 (BAK1) but not Suppressor of BIR1-1 (SOBIR1). Furthermore, VmXyl2 interacts with Mp2 in vivo, a receptor-like kinase with leucine-rich repeat. The results offer valuable insights into the roles of VmXyl2 in the pathogenicity of V. mali during its infection of apple trees.

The development of robust alloys capable of maintaining high strength and ductility at cryogenic temperatures has been a long-sought goal, particularly for load-bearing applications in extremely low-temperature environments. In this study, we reported a newly developed face-centered-cubic (FCC) metastable (Ni0·3Co0·4Cr0.3)94Mo6 medium-entropy alloy (Mo-MEA) with an excellent synergy of strength and ductility at 77 K, surpassing the toughest equiatomic NiCoCr MEA. Compared to the equiatomic NiCoCr MEA, the Mo-MEA exhibited a substantial increase in yield strength by 68 % (from 407 to 685 MPa) and a decent enhancement of the ultimate tensile strength by 10 % (from 1289 to 1415 MPa), along with a marginal increase in elongation from 75 % to 78.45 %. Electron backscatter diffraction and transmission electron microscopy revealed the activation of multimodal deformation mechanisms, including dislocations, stacking faults, twinning, and FCC-to-hexagonal-close-packed phase transformation, during the tensile deformation at 77 K.

Abstract Horse chestnut (Aesculus chinensis) is an important medicinal tree that contains various bioactive compounds, such as aescin, barrigenol-type triterpenoid saponins (BAT), and aesculin, a glycosylated coumarin. Herein, we report a 470.02 Mb genome assembly and characterize an Aesculus-specific whole-genome duplication event, which leads to the formation and duplication of two triterpenoid biosynthesis-related gene clusters (BGCs). We also show that AcOCS6, AcCYP716A278, AcCYP716A275, and AcCSL1 genes within these two BGCs along with a seed-specific expressed AcBAHD6 are responsible for the formation of aescin. Furthermore, we identify seven Aesculus-originated coumarin glycoside biosynthetic genes and achieve the de novo synthesis of aesculin in E. coli. Collinearity analysis shows that the collinear BGC segments can be traced back to early-diverging angiosperms, and the essential gene-encoding enzymes necessary for BAT biosynthesis are recruited before the splitting of Aesculus, Acer, and Xanthoceras. These findings provide insight on the evolution of gene clusters associated with medicinal tree metabolites.

The noise reduction effect of noise barriers has been extensively studied, but the effect on pollutant dispersion remains unclear. A computational fluid dynamics (CFD) simulation is conducted to investigate the effects of different heights, lengths, and types of noise barriers and different wind speeds on pollutant dispersion in street canyons with viaducts. The field synergy theory of the convective mass transfer process is used for quantitative analysis of pollutant dispersion in street canyons. The results show that as the height and length of the noise barrier increase, the pollutant dispersion capacity decreases. As the wind speed increases, the rate of decrease in the average CO concentration declines. The effect of the wind speed on the synergistic improvement of the speed and concentration gradient vectors differs for different types of noise barriers. The performance follows the order: fully-closed noise barrier > left noise barrier > right noise barrier > semi-closed noise barrier. The different noise barrier types significantly impact the flow field and pollutant dispersion and reduce the CO concentration to varying degrees, except for the fully-closed type. The average CO concentration in the pedestrian breathing zone is reduced by a maximum of 55.85% on the leeward side and by 53% on the windward side, indicating that an appropriate noise barrier on the viaduct reduces noise pollution and improves the air quality in street canyons, especially in the pedestrian breathing zone.

In this paper, the environmental and economic indicators based on the reactive power pricing are proposed so as to formulate the novel environmental economic power dispatch (NEED) problems for electricity trading. Here, a new way of calculating total cost is proposed based on the reactive power pricing instead of the pure fuel cost, which leads to the NEED problems. In addition, an improved tunicate swarm algorithm (ITSA) is proposed to deal with the NEED problems. Different from the original tunicate swarm algorithm (TSA), adaptive weight parameter and mutation process are used to improve the disadvantages of TSA which converges too fast and easily falls into local optimum. In combination with the Pareto dominance rule, the ITSA can be more effective in dealing with the NEED problems. In order to examine the performance of the ITSA, simulation tests of ITSA, TSA, and particle swarm optimization (PSO) are conducted in IEEE30 node system. During the experimental process, optimized objective functions include total cost considering reactive cost, pollution emission and power loss. The final comparison results show that the ITSA is able to get better distributed Pareto front (PF) and superior best compromise solution (BCS), which proves the high efficiency of the ITSA in dealing with the NEED problems.

Grasp detection serves as the fundamental element for achieving successful grasping in robotic systems. The encoder–decoder structure has become widely adopted as the foundational architecture for grasp detection networks due to its inherent advantages of speed and accuracy. However, traditional network structures fail to effectively extract the essential features required for accurate grasping poses and neglect to eliminate the checkerboard artifacts caused by inversion convolution during decoding. Aiming at overcoming these challenges, we propose a novel generative grasp detection network (LGAR-Net2). A transposed convolution layer is employed to replace the bilinear interpolation layer in the decoder to remove the issue of uneven overlapping and consequently eliminate checkerboard artifacts. In addition, a loss-guided collaborative attention block (LGCA), which combines attention blocks with spatial pyramid blocks to enhance the attention to important regions of the image, is constructed to enhance the accuracy of information extraction. Validated on the Cornell public dataset using RGB images as the input, LGAR-Net2 achieves an accuracy of 97.7%, an improvement of 1.1% over the baseline network, and processes a single RGB image in just 15 ms.

ABSTRACT Fusarium sacchari is one of the primary pathogens causing pokkah boeng disease in sugarcane in China. Common fungal extracellular membrane (CFEM) domain-containing proteins only exist in fungi and play a significant role in the interaction of pathogens and plants. However, the CFEM proteins in F. sacchari were not identified and functionally resolved. Of the 20 FsCFEM proteins identified from the genome of F. sacchari, 16 FsCFEM genes were cloned, while 4 FsCFEM proteins (Fs06761, Fs08184, Fs10706, and Fs13617) were identified as effector proteins that could suppress the programmed cell death triggered by BCL2-associated X protein in Nicotiana benthamiana. Subcellular localization analysis revealed that these four effectors could enter plant cells and are mainly located in the cell membrane and nucleus. By the yeast YTK12 secretion system, the signal peptides of four CFEM proteins were functionally verified. The expression levels of these four effector proteins were significantly increased in the F. sacchari-infected sugarcane plants. Through fungal gene knockout, three genes (Fs06761, Fs08184, and Fs13617) were found to be important pathogenic factors for pathogens. Our results support that the FsCFEM effector proteins were virulence effectors and might be involved in regulating plant immunity. IMPORTANCE Common fungal extracellular membrane (CFEM) domain-containing protein has long been considered an essential effector, playing a crucial role in the interaction of pathogens and plant. Strategies aimed at understanding the pathogenicity mechanism of F. sacchari are eagerly anticipated to ultimately end the spread of pokkah boeng disease. Twenty FsCFEM proteins in the genome of F. sacchari have been identified, and four FsCFEM effector proteins have been found to suppress BCL2-associated X protein-triggered programmed cell death in N. benthamiana. These four effector proteins have the ability to enter plant cells and inhibit plant immunity. Furthermore, the expression of these four FsCFEM effector proteins significantly increases during the infection stage, with the three of them playing an essential role in achieving full virulence. These study findings provide a direction toward further exploration of the immune response in sugarcane. By applying these discoveries, we can potentially control the spread of disease through techniques such as host-induced gene silencing.

BackgroundTo explore the mechanism of OIP5-AS1/CD147/TRPM7 axis to gastric cancer (GC) metastasis.MethodsBioinformatic analysis was performed to pick up the candidate genes associated with regulation GC metastasis. Using GC cell lines, AGS and MKN-45 as research objects, identify the effect of candidate genes on GC metastasis, judge cell proliferation status by MTT assay and cell clone number, and detect cell migration by Transwell and Wound-healing assay. The molecular mechanism of CD147/OIP5/TRPM7 axis regulating GC metastasis was further explored by RNA sequencing. The key signaling pathways were subsequently verified by flow cytometry and WB.ResultsBioinformatic analysis suggested OIP5-AS1/CD147/TRPM7 axis may be involving in GC metastasis. The RNA interference experiment proved that after gene interference, the proliferation ability of GC cells decreased significantly (P

The utilization of herbal extraction residues (HERs) for production of valuable products has gained significant momentum in recent years. In this study, Lianhua Qingwen residue (LQR) was selected as a representative HER for enzymatic saccharification. By subjecting starch-containing raw unpretreated LQR to direct hydrolysis using a combination of cellulolytic and amylolytic enzyme, a glucan conversion of around 60 % was achieved within 48 h. To further enhance the hydrolysis rate and yield, ultrasound treatment of LQR samples was conducted. Investigation into the effect of ultrasound treatment on subsequent enzymatic saccharification revealed a noteworthy acceleration in the saccharification rate of LQR, exceeding 20 % within 10 h of hydrolysis time. Notably, this enhancement was achieved even when the substrate concentration was high at 10 % under optimized conditions of 5 min of sonication at a power intensity of 1.20 kW/cm2 and a temperature of 50 °C. The improvement in efficiency can be attributed to the disruptive effect of ultrasound treatment on the structure of LQR, leading to a reduction in particle size. Consequently, the LQR particles exhibited better contact with the enzyme, promoting a more efficient saccharification process. These findings suggest that ultrasound technology holds considerable potential for enhancing the enzymatic saccharification of HERs.

AbstractBackground High expression of immune checkpoints (ICs) and senescence molecules (SMs) contributes to T cell dysfunction, tumor escape, and progression, but systematic evaluation of them in co-expression patterns and prognosis in acute myeloid leukemia (AML) was lacking.Methods Three publicly available datasets (TCGA, Beat-AML, and GSE71014) were first used to explore the effect of IC and SM combinations on prognosis and the immune microenvironment in AML, and bone marrow samples from 68 AML patients from our clinical center (GZFPH) was further used to validate the findings.Results High expression of CD276, Bcl2-associated athanogene 3 (BAG3), and SRC was associated with poor overall survival (OS) of AML patients. CD276/BAG3/SRC combination, standard European Leukemia Net (ELN) risk stratification, age, and French-American-British (FAB) subtype were used to construct a nomogram model. Interestingly, the new risk stratification derived from the nomogram was better than the standard ELN risk stratification in predicting the prognosis for AML. A weighted combination of CD276 and BAG3/SRC positively corrected with TP53 mutation, p53 pathway, CD8+ T cells, activated memory CD4+ T cells, T-cell senescence score, and Tumor Immune Dysfunction and Exclusion (TIDE) score estimated by T-cell dysfunction.Conclusion High expression of ICs and SMs was associated with poor OS of AML patients. The co-expression patterns of CD276 and BAG3/SRC might be potential biomarkers for risk stratification and designing combinational immuno-targeted therapy in AML.Key MessagesHigh expression of CD276, BAG3, and SRC was associated with poor overall survival of AML patients.The co-expression patterns of CD276 and BAG3/SRC might be potential biomarkers for risk stratification and designing combinational immuno-targeted therapy in AML.

Abstract Background Acute myeloid leukemia (AML) is an aggressive heterogeneous hematological malignancy with remarkably heterogeneous outcomes. This study aimed to identify potential biomarkers for AML risk stratification via analysis of gene expression profiles. Methods RNA sequencing data from 167 adult AML patients in the Cancer Genome Atlas (TCGA) database were obtained for overall survival (OS) analysis, and 52 bone marrow (BM) samples from our clinical center were used for validation. Additionally, siRNA was used to investigate the role of prognostic genes in the apoptosis and proliferation of AML cells. Results Co‐expression of 103 long non‐coding RNAs (lncRNAs) and mRNAs in the red module that were positively correlated with European Leukemia Network (ELN) risk stratification and age was identified by weighted gene co‐expression network analysis (WGCNA). After screening by uni‐ and multivariate Cox regression, Kaplan–Meier survival, and protein–protein interaction analysis, four genes including the lncRNA LOC541471, GDAP1, SOD1, and STK25 were incorporated into calculating a risk score from coefficients of the multivariate Cox regression model. Notably, GDAP1 expression was the greatest contributor to OS among the four genes. Interestingly, the risk score, ELN risk stratification, and age were independent prognostic factors for AML patients, and a nomogram model constructed with these factors could illustrate and personalize the 1‐, 3‐, and 5‐year OS rates of AML patients. The calibration and time‐dependent receiver operating characteristic curves (ROCs) suggested that the nomogram had a good predictive performance. Furthermore, new risk stratification was developed for AML patients based on the nomogram model. Importantly, knockdown of LOC541471, GDPA1, SOD1, or STK25 promoted apoptosis and inhibited the proliferation of THP‐1 cells compared to controls. Conclusions High expression of LOC541471, GDAP1, SOD1, and STK25 may be biomarkers for risk stratification of AML patients, which may provide novel insight into evaluating prognosis, monitoring progression, and designing combinational targeted therapies.

The development of strong and ductile alloys for application in cryogenic temperatures has long been sought after. In this work, we have developed a face-centered cubic Ni10Co56.5V33.5 multi-principal element alloy (MPEA) that exhibits a balanced combination of high strength and good ductility at 77 K, based on the considerations of large local lattice distortion (LLD) and low stacking fault energy. The small-grained Ni10Co56.5V33.5 MPEA exhibits a yield strength of 1400 MPa and an ultimate tensile strength of 1890 MPa, while preserving a good ductility of 23%. Moreover, precession electron diffraction and transmission electron microscopy revealed multiple deformation mechanisms, including wavy dislocations, atypically severely twisted dislocation bands, hierarchical stacking faults, and deformation twins, which are implicated in the alloy’s outstanding mechanical performance. These insights offer a strategic guide for the design of strong and ductile alloys, particularly for utilization in extreme environments.

Population aging is a global problem, and improving the well-being of older adults is an urgent issue. Voice assistants (VAs) offer hands-free voice control and friendly human-computer interaction, making them a significant solution to address the aging problem. Most extant research on VAs is fragmented, and there are relatively few studies conducted from the perspective of emotional needs. This work proposes a comprehensive research model extending the technology acceptance model (TAM) by incorporating the influencing factors subordinate to two research directions: usability and emotional needs. Usability needs include three factors: perceived convenience, security/privacy, and Internet self-efficacy. Emotional needs include humanized interaction, perceived enjoyment, and perceived companionship. A structural equation model (SEM) was used to validate the model empirically with a sample of 425 older users of VAs. The analysis results are quite consistent with the research assumptions, and the findings illustrate that companionship is the most critical factor affecting older adults' intention to adopt VA use, which demonstrates the pivotal role of VAs in meeting the emotional needs of the elderly. The most unexpected observation was seen for the relationship between perceived ease of use and behavioral intention, which was non-significant. This result confirms that when a technology is perceived as very easy to use, perceived ease of use has little to no impact on individuals' intention to use that technology. The novelty of this study lies in the investigation of older adults' behavioral intentions toward using VAs, providing valuable insights for the design and development of VAs tailored for the elderly population. Beyond the academic realm, this research serves as direct inspiration for designers, developers, and policymakers in the fields of assistive technologies and geriatric care. It offers practical insights into creating VAs that effectively address the emotional needs of older adults and enhance their quality of life. Furthermore, elderly individuals are poised to experience significant benefits from the outcomes of this study，the insights garnered from this study empower the elderly to embrace technological advancements that align with their preferences and comfort levels. This study contributes to a more comprehensive understanding of VAs and their potential to enhance the well-being of older adults, while also paving the way for future investigations in this domain. As underscored by this study's emphasis on the significance of emotional needs in technology acceptance, it encourages the adoption of more user-centered design strategies in the development of future VAs.

The skeleton of 2-trifluoromethyl quinoline is the core structure of many natural products and pharmaceutical molecules. The synthesis of this scaffold is limited by metal catalysis, harsh conditions, toxic or hazardous reagents and solvents, and lower atom-economy. Herein, a novel method for the synthesis of 2-trifluoromethyl quinolines via the [4 + 2] cyclization of β-keto esters or 1,3-diketones with various substituted o-aminobenzaldehydes using the metal free catalyst in EtOH is reported. This atom- and step-economical protocol features simple operation, broad substrate scope, and good functional-group compatibility. The synthetic utility of this methodology was highlighted by easy gram-scale synthesis and late-stage functionalization, which would promote the vigorous development of quinoline chemistry. Moreover, the in vitro antifungal activities of the 2-trifluoromethyl quinolines against F. graminearum (from wheat), F. graminearum (from corn), F. moniliforme, F. oxysporum, and R. solani were investigated to further potential utility of these compounds.

ObjectiveAfter the end of COVID-19, medical staff were immediately faced with a high workload, leading to widespread occupational burnout. This study aims to explore the level and influencing factors of burnout among medical staff during this period, as well as its relationship with anxiety and depression.MethodsThe participants’ levels of burnout were assessed using Maslach Burnout Inventory-Human Services Survey (MBI-HSS), and the reliability and validity of the questionnaire were evaluated through Cronbach’s α and Confirmatory Factor Analysis (CFA). Independent sample t-test, chi-square test, and Pearson analysis were employed to determine the correlation between two sets of variables. Univariate and multivariate logistic regression analyses were conducted to identify significant factors influencing burnout. Finally, nomograms were used to predict the probability of burnout occurrence.ResultsThis study collected a total of 1,550 questionnaires, and after excluding 45 questionnaires that were duplicates or incomplete, a sample of 1,505 (97.1%) participants were included in the final statistical analysis. Both Cronbach’s α and the fit indices of CFA demonstrated excellent adaptability of the Chinese version of MBI-HSS in this study. The overall prevalence rates for emotional exhaustion (EE), depersonalization (DP), and diminished personal accomplishment (PA) were 52.4, 55.3, and 30.6%, respectively. Obtaining psychological support, health condition, relationship with family members, and insufficient sleep were identified as common contributing factors to burnout among medical staff. Additionally, age and promotion pressure were also associated with burnout among doctors, and exceeding legal working hours was an important factor for nurse burnout. The C-index for the nomograms predicting burnout among doctors and nurses was 0.832 and 0.843, respectively. Furthermore, burnout exhibited a significant linear correlation with anxiety and depression.ConclusionAfter the end of COVID-19, medical staff in high workload environments were facing severe burnout, which might lead to anxiety and depression. The occupational burnout of medical staff needed to be taken seriously and actively intervened.

Objective Microwave ablation (MWA) is a safe and effective local therapy, however, its efficacy in stage I subpleural nonsmall cell lung cancer (NSCLC) compared to that of sublobar resection (SLR) is unclear. This study aimed to compare the efficacy of the two treatments for stage I NSCLC ≤1 cm from the pleura.Methods After propensity score matching (PSM), 70 patients with stage I subpleural NSCLC who underwent either SLR or MWA (35 patients each) from 2014 to 2018 were included. The margin pathology of SLR was negative. MWA reached a sufficient ablative margin. MWA group were stratified according to the minimal ablative margin, with 10 patients each in the 5–10 mm group and the >10 mm group after PSM. The local recurrence-free survival (LRFS), relapse-free survival (RFS), overall survival (OS), and treatment-related complications were compared.Results For patients with stage I subpleural NSCLC, the LRFS of patients in the SLR group (35.657 ± 0.338 months, 95% CI: 34.995–36.319) was significantly better than that in the MWA group (31.633 ± 1.574 months, 95% CI: 28.548–34.719, p = 0.021). The RFS was also significantly better in the SLR group (35.629 ± 0.338 months, 95% CI: 34.966–36.292) than in the MWA group (29.387 ± 1.866 months, 95% CI: 25.730–33.044, p = 0.007), but there were no significant differences in terms of the 3-year OS (p = 0.079) and incidence of complications (14.3% vs. 11.4%, p = 0.653). The minimal ablative margin of >10 mm was not significantly associated with the LRFS (p = 0.929).Conclusion MWA for stage I subpleural NSCLC showed similar survival outcomes and complication rates to SLR, but poorer local tumor control.

The applicability of first-generation of Chinese land surface reanalysis dataset （CRA40/Land） has been evaluated with the observations from 2231 national meteorological stations and further compared with the ERA5 and CFSR datasets in terms of the spatial and temporal variations of monthly air temperature and precipitation.Triangulation linear interpolation is used to interpolate grid data into stations， and station data into grid.The China mainland is divided into four regions according to the stations distribution and topographic features.The bias， standard deviation ratio， root mean square error （RMSE）， correlation coefficient and model skill of the 3 reanalysis datasets in four regions are computed to compare the accuracy and evaluate the application.The comparative results suggest that the CRA40， ERA5 and CFSR datasets can reproduce similar spatio-temporal distribution patterns of the monthly air temperature and precipitation with the observations in Mainland of China.In particular， they all show much better performance in the eastern China than in western China and in winter than in summer.For the monthly air temperature， the mean errors of the 3 reanalysis datasets are generally within 2 ℃， with slightly better performance for the CRA40 and ERA5 datasets.For the monthly precipitation， the errors of the 3 reanalysis datasets show large differences， the CRA40 performs the best and shows the highest applicability over Mainland of China among the 3 datasets.

Abstract Background Accurate identification of protein complexes in protein-protein interaction (PPI) networks is crucial for understanding the principles of cellular organization. Most computational methods ignore the fact that proteins in a protein complex have a functional similarity and are co-localized and co-expressed at the same place and time, respectively. Meanwhile, the parameters of the current methods are specified by users, so these methods cannot effectively deal with different input PPI networks. Result To address these issues, this study proposes a new method called MP-AHSA to detect protein complexes with Multiple Properties (MP), and an Adaptation Harmony Search Algorithm is developed to optimize the parameters of the MP algorithm. First, a weighted PPI network is constructed using functional annotations, and multiple biological properties and the Markov cluster algorithm (MCL) are used to mine protein complex cores. Then, a fitness function is defined, and a protein complex forming strategy is designed to detect attachment proteins and form protein complexes. Next, a protein complex filtering strategy is formulated to filter out the protein complexes. Finally, an adaptation harmony search algorithm is developed to determine the MP algorithm’s parameters automatically. Conclusions Experimental results show that the proposed MP-AHSA method outperforms 14 state-of-the-art methods for identifying protein complexes. Also, the functional enrichment analyses reveal that the protein complexes identified by the MP-AHSA algorithm have significant biological relevance.

Abstract The green peach aphid, Myzus persicae, is one of the most economically important pests in peach-growing areas around the world. In many countries, the application of insecticides is the main method to control and reduce the population of M. persicae. In this study, we investigated the effects and persistence of thiamethoxam against M. persicae by foliar spraying and root irrigation. The residues of thiamethoxam and clothianidin in peach were determined to assess food safety. The results showed that thiamethoxam treatment significantly reduced the population of M. persicae through foliar spraying and root irrigation. And the persistence of root irrigation on M. persicae was significantly longer than that of spraying. Thiamethoxam and clothianidin were absorbed by the roots, transported to other parts of the plant, and concentrated in the leaves, especially new leaves. The final residues of thiamethoxam and clothianidin in peaches were below the maximum residue limit (MRLs). These results suggested that thiamethoxam is more effective in M. persicae control through root irrigation than foliar spraying. The persistence of root irrigation on M. persicae was significantly longer than that of spraying. These results shed some light upon the control of M. persicae by root irrigation of thiamethoxam.

Abstract Background The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect. Methods Here, PD-L1- and CD44-responsive multifunctional nanoparticles were developed using a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). Results PEI-OA greatly improved the drug loading capacity and encapsulation efficiency of the nanoplatform, while the anti-PD-L1 antibody significantly increased its cellular uptake compared to other treatment formulations. Pharmacodynamic experiments confirmed that the anti-PD-L1 antibody can strongly inhibit primary breast cancer and increase levels of CD4+ and CD8+ T cell at the tumor site. In addition, chloroquine reversed the “immune-cold” environment and improved the anti-tumor effect of both chemotherapeutics and immune checkpoint inhibitors, while it induced strong immune memory and prevented lung metastasis. Conclusions Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment.

Abstract Objective To analyze the genotypes and phenotypes of a child with developmental dysplasia of the hip (DDH), developmental delays, recurrent fever, hypothyroidism and cleft palate. Methods G-banding karyotyping analysis and next-generation sequencing (NGS) were performed for the patient. The genotypes of the parents of the patient were verified by copy number variation analysis and Sanger sequencing to determine the source of variations. Results The karyotype of the patient was 46, XX. A 10.44 Mb deletion (chr18:67562936-78005270del) at 18q22.2q23 was found by NGS. We identified 2 HSPG2 mutations (chr1: 22206699, c.2244C > A, exon 17, p.H748Q; chr1: 22157321–22157321, c.11671 + 154insA, intron). One mutation was inherited from the father, and the other was inherited from the mother. Conclusion This is the first 18q deletion syndrome case accompanied by DDH. Most phenotypes of this patient, such as developmental delays and cleft palate, may be related to the 18q22.2q23 deletion, but no variants in genes related to DDH were found in this deletion region. DDH may be related to mutations of HSPG2.

BackgroundNasopharyngeal cancer (NPC) has a high incidence in Southern China and Asia, and its survival is extremely poor in advanced patients. MiRNAs play critical roles in regulating gene expression and serve as therapeutic targets in cancer. This study sought to disclose key miRNAs and target genes responsible for NPC prognosis and endocrine metabolism.Materials and methodsThree datasets (GSE32960, GSE70970, and GSE102349) of NPC samples came from Gene Expression Omnibus (GEO). Limma and WGCNA were applied to identify key prognostic miRNAs. There were 12 types of miRNA tools implemented to study potential target genes (mRNAs) of miRNAs. Univariate Cox regression and stepAIC were introduced to construct risk models. Pearson analysis was conducted to analyze the correlation between endocrine metabolism and RiskScore. Single-sample gene set enrichment analysis (ssGSEA), MCP-counter, and ESTIMATE were performed for immune analysis. The response to immunotherapy was predicted by TIDE and SubMap analyses.ResultsTwo key miRNAs (miR-142-3p and miR-93) were closely involved in NPC prognosis. The expression of the two miRNAs was dysregulated in NPC cell lines. A total of 125 potential target genes of the key miRNAs were screened, and they were enriched in autophagy and mitophagy pathways. Five target genes (E2F1, KCNJ8, SUCO, HECTD1, and KIF23) were identified to construct a prognostic model, which was used to divide patients into high group and low group. RiskScore was negatively correlated with most endocrine-related genes and pathways. The low-risk group manifested higher immune infiltration, anticancer response, more activated immune-related pathways, and higher response to immunotherapy than the high-risk group.ConclusionsThis study revealed two key miRNAs that were highly contributable to NPC prognosis. We delineated the specific links between key miRNAs and prognostic mRNAs with miRNA–mRNA networks. The effectiveness of the five-gene model in predicting NPC prognosis as well as endocrine metabolism provided a guidance for personalized immunotherapy in NPC patients.

ABSTRACT Protein phosphatase complex Nem1/Spo7 plays crucial roles in the regulation of various biological processes in eukaryotes. However, its biological functions in phytopathogenic fungi are not well understood. In this study, genome-wide transcriptional profiling analysis revealed that Nem1 was significantly upregulated during the infection process of Botryosphaeria dothidea, and we identified and characterized the phosphatase complex Nem1/Spo7 and its substrate Pah1 (a phosphatidic acid phosphatase) in B. dothidea. Nem1/Spo7 physically interacted with and dephosphorylated Pah1 to promote triacylglycerol (TAG) and subsequent lipid droplet (LD) synthesis. Moreover, the Nem1/Spo7-dependently dephosphorylated Pah1 functioned as a transcriptional repressor of the key nuclear membrane biosynthesis genes to regulate nuclear membrane morphology. In addition, phenotypic analyses showed that the phosphatase cascade Nem1/Spo7-Pah1 was involved in regulating mycelial growth, asexual development, stress responses, and virulence of B. dothidea. IMPORTANCE Botryosphaeria canker and fruit rot caused by the fungus Botryosphaeria dothidea is one of the most destructive diseases of apple worldwide. Our data indicated that the phosphatase cascade Nem1/Spo7-Pah1 plays important roles in the regulation of fungal growth, development, lipid homeostasis, environmental stress responses, and virulence in B. dothidea. The findings will contribute to the in-depth and comprehensive understanding of Nem1/Spo7-Pah1 in fungi and the development of target-based fungicides for disease management.

ABSTRACT Fusarium sacchari is one of the primary pathogens causing Pokkah Boeng disease (PBD) in sugarcane in China. Pectate lyases (PL), which play a critical role in pectin degradation and fungal virulence, have been extensively studied in major bacterial and fungal pathogens of a wide range of plant species. However, only a few PLs have been functionally investigated. In this study, we analyzed the function of the pectate lyase gene, FsPL, from F. sacchari. FsPL is a key virulence factor of F. sacchari and can induce plant cell death. FsPL also triggers the pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) response in Nicotiana benthamiana, as reflected by increases in reactive oxygen species (ROS) production, electrolyte leakage, and callose accumulation, as well as the upregulation of defense response genes. In addition, our study also found that the signal peptide of FsPL was necessary for induced cell death and PTI responses. Virus-induced gene silencing showed that FsPL-induced cell death in Nicotiana benthamiana was mediated by leucine-rich repeat (LRR) receptor-like kinases BAK1 and SOBIR1. Thus, FsPL may not only be a critical virulence factor for F. sacchari but may also induce plant defense responses. These findings provide new insights into the functions of pectate lyase in host-pathogen interactions. IMPORTANCE Pokkah Boeng disease (PBD) is one of the main diseases affecting sugarcane in China, seriously damaging sugarcane production and economic development. Therefore, it is important to clarify the pathogenic mechanisms of this disease and to provide a theoretical basis for the breeding of PBD-resistant sugarcane strains. The present study aimed to analyze the function of FsPL, a recently identified pectate lyase gene from F. sacchari. FsPL is a key virulence factor of F. sacchari that induces plant cell death. Our results provide new insights into the function of pectate lyase in host-pathogen interactions.

BackgroundProgrammed cell death (PCD) is an overwhelming factor affecting tumor cell metastasis, but the mechanism of PCD in ovarian cancer (OV) is still uncertain.MethodsTo define the molecular subtypes of OV, we performed unsupervised clustering based on the expression level of prognosis related PCD genes in the Cancer Genome Atlas (TCGA)-OV. COX and least absolute shrinkage and selection operator (LASSO) COX analysis were used to identify the OV prognostic related PCD genes, and the genes identified according to the minimum Akaike information criterion (AIC) were the OV prognostic characteristic genes. According to the regression coefficient in the multivariate COX analysis and gene expression data, the Risk Score of OV prognosis was constructed. Kaplan-Meier analysis was conducted to assess the prognostic status of OV patients, and receiver operating characteristic (ROC) curves were conducted to assess the clinical value of Risk Score. Moreover, RNA-Seq date of OV patient derived from Gene Expression Omnibus (GEO, GSE32062) and the International Cancer Genome Consortium (ICGC) database (ICGC-AU), verifying the robustness of the Risk Score via Kaplan-Meier and ROC analysis.Pathway features were performed by gene set enrichment analysis and single sample gene set enrichment analysis. Finally, Risk Score in terms of chemotherapy drug sensitivity and immunotherapy suitability was also evaluated in different groups.Results9-gene composition Risk Score system was finally determined by COX and LASSO COX analysis. Patients in the low Risk Score group possessed improved prognostic status, immune activity. PI3K pathway activity was increased in the high Risk Score group. In the chemotherapy drug sensitivity analysis, we found that the high Risk Score group might be more suitable for treatment with PI3K inhibitors Taselisib and Pictilisib. In addition, we found that patients in the low-risk group responded better to immunotherapy.ConclusionRisk Score of 9-gene composition of PCD signature possesses promising clinical potential in OV prognosis, immunotherapy, immune microenvironment activity, and chemotherapeutic drug selection, and our study provides the basis for an in-depth investigation of the PCD mechanism in OV.

In this study, colorimetric and antioxidant films were developed by using cassava starch (CS), κ-carrageenan (KC) and black nightshade fruit anthocyanins (BNA), and their physical and functional properties were investigated. We found BNA presented significant color changes in different pH solutions. And incorporation of BNA significantly increased the tensile strength, water vapor permeability, UV–vis light barrier property, pH-sensitivity and antioxidant activity of CS-KC film. Results of structural characterization indicated that H-bonds were formed between CS, KC and BNA in films and the film compactness was significantly improved by BNA incorporation. Results of the rheological property assay showed the films had high apparent viscosity with an obvious shear-thinning behavior. When applied to monitoring the quality change of Cyclina sinensis, CS-KC-BNA films exhibited significant color changes with the degradation process of C. sinensis qualities. Our results suggested CS-KC-BNA films could be utilized in smart packaging in food industry.

The purpose of this study was to explore the therapeutic effect of the oral administration of pseudo-ginsenoside RT4 (RT4) on ulcerative colitis (UC), and to determine the rate of absorption and distribution of RT4 in mice with UC. Balb/c mice were induced using dextran sulfate sodium salts (DSS) to establish the UC model, and 10, 20, or 40 mg/kg of RT4 was subsequently administered via gavage. The clinical symptoms, inflammatory response, intestinal barrier, content of total short-chain fatty acids (SCFAs), and gut microbiota were investigated. Caco-2 cells were induced to establish the epithelial barrier damage model using LPS, and an intervention was performed using 4, 8, and 16 µg/mL of RT4. The inflammatory factors, transient electrical resistance (TEER), and tight-junction protein expression were determined. Finally, pharmacokinetic and tissue distribution studies following the intragastric administration of RT4 in UC mice were performed. According to the results in mice, RT4 decreased the disease activity index (DAI) score, restored the colon length, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and boosted the levels of immunosuppressive cytokine IL-10, increased the content of SCFAs, improved the colonic histopathology, maintained the ultrastructure of colonic mucosal epithelial cells, and corrected disturbances in the intestinal microbiota. Based on the results in caco-2 cells, RT4 reduced the levels of TNF-α, IL-6, and IL-1β; protected integrity of monolayers; and increased tight-junction protein expression. Additionally, the main pharmacokinetic parameters (Cmax, Tmax, t1/2, Vd, CL, AUC) were obtained, the absolute bioavailability was calculated as 18.90% ± 2.70%, and the main distribution tissues were the small intestine and colon. In conclusion, RT4, with the features of slow elimination and directional distribution, could alleviate UC by inhibiting inflammatory factors, repairing the intestinal mucosal barrier, boosting the dominant intestinal microflora, and modulating the expression of SCFAs.

Objective: Body weight change and obesity follow the variance of excess energy input balanced against tightly controlled EE (energy expenditure). Since insulin resistance can reduce energy storage, we investigated whether genetic disruption of hepatic insulin signaling reduced adipose mass with increased EE. Methods: Insulin signaling was disrupted by genetic inactivation of Irs1 (Insulin receptor substrate 1) and Irs2 in hepatocytes of LDKO mice (Irs1L/L·Irs2L/L·CreAlb), creating a state of complete hepatic insulin resistance. We inactivated FoxO1 or the FoxO1-regulated hepatokine Fst (Follistatin) in the liver of LDKO mice by intercrossing LDKO mice with FoxO1L/L or FstL/L mice. We used DEXA (dual-energy X-ray absorptiometry) to assess total lean mass, fat mass and fat percentage, and metabolic cages to measure EE (energy expenditure) and estimate basal metabolic rate (BMR). High-fat diet was used to induce obesity. Results: Hepatic disruption of Irs1 and Irs2 (LDKO mice) attenuated HFD (high-fat diet)-induced obesity and increased whole-body EE in a FoxO1-dependent manner. Hepatic disruption of the FoxO1-regulated hepatokine Fst normalized EE in LDKO mice and restored adipose mass during HFD consumption; moreover, hepatic Fst disruption alone increased fat mass accumulation, whereas hepatic overexpression of Fst reduced HFD-induced obesity. Excess circulating Fst in overexpressing mice neutralized Mstn (Myostatin), activating mTORC1-promoted pathways of nutrient uptake and EE in skeletal muscle. Similar to Fst overexpression, direct activation of muscle mTORC1 also reduced adipose mass. Conclusions: Thus, complete hepatic insulin resistance in LDKO mice fed a HFD revealed Fst-mediated communication between the liver and muscle, which might go unnoticed during ordinary hepatic insulin resistance as a mechanism to increase muscle EE and constrain obesity.

An environmentally benign highly atom-economic protocol for the construction of the CC bond has been developed under catalyst- and solvent-free conditions. This protocol involves the efficient coupling of 2-methyl quinazolinones with 3-(trifluoroacetyl)coumarins for the access of quinazolinone derivatives in excellent yields (up to 90 %). The crystal structure of compound 3di was investigated by X-ray diffraction analysis. The biological activities, such as in vitro antifungal activity of the quinazolinone derivatives against Fusarium graminearum, Fusarium moniliforme, Fusarium oxysporum, Phytophthora parasitica var nicotianae, and Rhizoctonia solani Kuhn, were investigated. The bioassay results indicated that most of the target products exhibited promising fungicidal activities, and compound 3 cl exhibited 95 % fungicidal activity against R. solani, with an EC50 value of 10.6 μg/mL.

Apple ring rot caused by Botryosphaeria dothidea is an important disease that leads to severe quality deterioration and yield loss at pre-harvest and postharvest stages. Therefore, it is urgent to develop safe and efficient measures to control this disease. The objective of the present study was to investigate the biocontrol features of Pseudomonas syringae B-1 against B. dothidea and explore its mechanism of action utilizing in vitro and in vivo assays. The results showed that P. syringae B-1 strongly reduced the incidence of apple ring rot and lesion diameter by 41.2 and 90.2%, respectively, in comparison to the control fruit. In addition, the control efficiency of strain B-1 against B. dothidea infection depended on its concentration and the interval time. P. syringae B-1 cells showed higher inhibitory activities than its culture filtrates on the mycelial growth and spore germination of B. dothidea. Moreover, P. syringae B-1 treatment alleviated electrolyte leakage, lipid peroxidation, and H2O2 accumulation in B. dothidea-infected apple fruit by increasing antioxidant enzyme activities, including peroxidase, catalase, superoxide dismutase, and ascorbate peroxidase. We also found that strain B-1 treatment enhanced four defense-related enzyme activities and stimulated the accumulation of three disease-resistant substances including phenolics, lignin, and salicylic acid (SA) in apple fruit. In addition, strain B-1 triggered the upregulated expression of defense-related genes such as PR genes (PR1, PR5, GLU, and CHI) and two genes involved in the biosynthesis of SA (SID2 and PAD4) to promote the resistance potential in apple fruit. Hence, our results suggest that P. syringae B-1 is a promising strategy against B. dothidea, mainly through reducing oxidative damage, activating defense-related enzymes, accumulating disease-resistant substances, and triggering the expression of resistance-correlated genes in apple fruit.

Many crystals in nature have simple interatomic microstructures, such as simple cubic (SC), body-centered cubic (BCC), and face-centered cubic (FCC) lattice symmetries, making these structures extremely stable. Inspired by these arrangements, a series of architected micro-channel heat exchangers with rationally designed 3D microstructures were established. A multi-physics mathematical model using thermal-fluid-structure interaction (TFSI) was employed to investigate the coupled heat transfer performance and mechanical properties of these architected heat exchangers. When compared with the corrugated straight plate (CSP) microchannel heat exchanger, the thermal-hydraulic performance factors (TPC) of FCC and BCC microchannel heat transfer were 2.20 and 1.70 times that of SC microchannel heat exchanger, respectively. The micro-channel heat exchanger with FCC architectures could enhance the convective heat transfer performance by 201.0%, while the micro-channel heat exchanger with SC architectures reduced the Von-Mises equivalent (VME) stress by 20.0% when compared with the conventional 2D CSP heat exchanger. The proposed architected micro-channel heat exchangers could find a wide range of potential applications ranging from power electronics in electric vehicles to concentrated solar power systems, where both good convective heat transfer performance and high mechanical strength are simultaneously pursued.

Abstract Background Apple Glomerella leaf spot (GLS) and apple bitter rot (ABR) are two devastating foliar and fruit diseases on apples. The different symptoms of GLS and ABR could be related to different transcriptome patterns. Thus, the objectives of this study were to compare the transcriptome profiles of Colletotrichum gloeosporioides species complex isolates GC20190701, FL180903, and FL180906, the pathogen of GLS and ABR, and to evaluate the involvement of the genes on pathogenicity. Results A relatively large difference was discovered between the GLS-isolate GC20190701 and ABR-isolates FL180903, FL180906, and quite many differential expression genes associated with pathogenicity were revealed. The DEGs between the GLS- and ABR-isolate were significantly enriched in GO terms of secondary metabolites, however, the categories of degradation of various cell wall components did not. Many genes associated with secondary metabolism were revealed. A total of 17 Cytochrome P450s (CYP), 11 of which were up-regulated while six were down-regulated, and five up-regulated methyltransferase genes were discovered. The genes associated with the secretion of extracellular enzymes and melanin accumulation were up-regulated. Four genes associated with the degradation of the host cell wall, three genes involved in the degradation of cellulose, and one gene involved in the degradation of xylan were revealed and all up-regulated. In addition, genes involved in melanin syntheses, such as tyrosinase and glucosyltransferase, were highly up-regulated. Conclusions The penetration ability, pathogenicity of GLS-isolate was greater than that of ABR-isolate, which might indicate that GLS-isolate originated from ABR-isolates by mutation. These results contributed to highlighting the importance to investigate such DEGs between GLS- and ABR-isolate in depth.

Populus laurifolia is one of the most valuable tree species in the world and an important silvicultural tree species in the Xinjiang Uygur Autonomous Region, China. In July 2017, an unreported brown leaf spot disease was observed on P. laurifolia in Altay City, Xinjiang. The causal agent of this leaf spot disease was isolated, and Koch’s postulates were performed to confirm its pathogenicity. Based on a morphological characterization and phylogenetic analyses, the causal organism was identified to be a fungal species, Coniolariella gamsii. The optimum mycelial growth conditions for C. gamsii are on PLPDA (Populus leaves potato dextrose agar) medium, at 28 °C, in the dark. The sporulation time when using PLPDA medium (12 days) is much less than that for PDA medium (25 days). Pathogenicity tests revealed that C. gamsii can also infect two other Populus species (P. bolleana and P. tomentosa). This is the first report of C. gamsii causing brown leaf spot disease on P. laurifolia, and the optimum culture and sporulation conditions have also been optimized for the first time. This study provides a theoretical basis for the diagnosis of this disease and the monitoring of the disease’s occurrence and epidemic status.

This study leverages advanced data mining and machine learning techniques to delve deeper into the impact of sports activities on physical health and provide a scientific foundation for informed sports selection and health promotion. Guided by the Elastic Net algorithm, a sports performance assessment model is meticulously constructed. In contrast to the conventional Least Absolute Shrinkage and Selection Operator (Lasso) algorithm, this model seeks to elucidate the factors influencing physical health indicators due to sports activities. Additionally, the incorporation of the Random Forest algorithm facilitates a comprehensive evaluation of sports performance across distinct dimensions: wrestling-type sports, soccer-type sports, skill-based sports, and school physical education. Employing the Top-K criterion for evaluation and juxtaposing it with the high-performance Support Vector Machine (SVM) algorithm, the accuracy is scrutinized under three distinct criteria: Top-3, Top-5, and Top-10. The pivotal innovation of this study resides in the amalgamation of the Elastic Net and Random Forest algorithms, permitting a holistic contemplation of the influencing factors of diverse sports activities on physical health indicators. Through this integrated methodology, the research achieves a more precise assessment of the effects of sports activities, unveiling a range of impacts various sports have on physical health. Consequently, a more refined assessment tool for sports performance detection and health development is established. Capitalizing on the Elastic Net algorithm, this research optimizes model construction during the pivotal feature selection phase, effectively capturing the crucial influencing factors associated with different sports activities. Concurrently, the integration of the Random Forest algorithm augments the predictive prowess of the model, enabling the sports performance assessment model to comprehensively unveil the extent of impact stemming from various sports activities. This study stands as a noteworthy contribution to the arena of sports performance assessment, offering substantial insights and advancements to both sports health and research methodologies.

BackgroundRotator cuff injuries are common, and morbidity increases with age. The asymptomatic full-thickness tear rate is 40% in the over 75-year-old population.PurposeThis study aimed to systematically review the literature on the outcomes of rotator cuff repair among >75 years old patients.Study designSystematic review.MethodsA systematic review of the literature was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed in the electronic databases of PubMed, Medline, Embase, and The Cochrane Library. Studies in English evaluating repair of full-thickness rotator cuff tears in patients aged >75 years were included.ResultsSix studies were reviewed, including 311 patients (313 shoulders) treated with arthroscopic and/or open rotator cuff repair. Sixty-one patients were lost to follow-up, leaving 252 shoulders with outcome data. Patients in this age group demonstrated a significant improvement in the clinical and functional scores after rotator cuff repair, with a high satisfaction rate. The mean American Shoulder and Elbow Surgeons scores improved from 43.8 (range, 42.0–45.5) preoperatively to 85.3 (range, 84.0 to 86.5) postoperatively, and the mean Constant scores improved from 45.4 (range, 34.7–55.5) to 78.6 (range, 67.0–91.6). Pain, evaluated in all studies by the visual analog scale for pain, showed a significant improvement at the last follow-up compared with the mean preoperative score. Furthermore, range of motion and return to daily activities and sports gained marked improvements.ConclusionRotator cuff repair in patients aged >75 years could achieve high clinical success rates with good outcomes and pain relief. Although patients in this age group are at a high risk of retear, rotator cuff repair may offer a good option with significant functional and clinical improvement.

A one-pot two-step reaction of 2-(trifluoromethyl)-2-hydroxy-2H-chromene with aryl ketone afforded α-trifluoromethylated tertiary alcohols bearing coumarins. The atomic economic and simply manipulative reaction involved premier treatment of reaction mixtures with CH3COOH and NH4OAc in one-pot process. The reaction proceeded to give the title compounds in moderate to good yields.

Nasal administration of Traditional Chinese medicine (TCM) has a long history of applications. With the gradual maturing of technology and pharmacological advances, nasal preparations of TCM have undergone significant changes. Nasal TCM formulations are used not only for treatment of pneumonia, asthma, sinusitis and allergic rhinitis but also Alzheimer's disease and Parkinson's disease, as antidepressants and antiepileptics, and in ischemia reperfusion. However, according to the analysis of nasal preparations of TCM currently on the market, most of them were compound preparations, which were used to treat allergic rhinitis (AR), common cold, headache and other local treatments, with a small range of diseases. At the same time, the dosage forms were mainly traditional dosage forms, aerosols and sprays, but there were no new dosage forms, which can not meet the clinical needs in terms of variety number, variety diversity and disease types. In this manuscript, we reviewed the development and applications of different nasal preparations of TCM from the aspects of nasal structure, origin, factors affecting absorption and common dosage forms, pharmacodynamics, targeting of nasal delivery and safety. In the near future, we expect that more nasal preparations of Chinese medicine with independent intellectual property rights will be marketed to meet the needs of clinical disease management.

Abstract We aimed to investigate outcomes of different post-remission treatment (PRT) choices based on dynamic measurable residual disease (MRD) by multiparameter flow cytometry in favorable-risk AML (FR-AML). Four hundred and three younger patients with FR-AML in first complete remission (CR1) were enrolled in this registry-based cohort study, including 173 who received chemotherapy (CMT), 92 autologous stem cell transplantation (auto-SCT), and 138 allogeneic SCT (allo-SCT). The primary endpoint was the 5-year overall survival (OS). Subgroup analyses were performed based on dynamic MRD after the 1st, 2nd, and 3rd courses of chemotherapy. In subgroups of patients with negative MRD after 1 or 2 course of chemotherapy, comparable OS was observed among the CMT, auto-SCT, and allo-SCT groups (p = 0.340; p = 0.627, respectively). But CMT and auto-SCT had better graft-versus-host-disease-free, relapse-free survival (GRFS) than allo-SCT in both subgroups. For patients with negative MRD after three courses of chemotherapy, allo-SCT had better disease-free-survival than CMT (p = 0.009). However, OS was comparable among the three groups (p = 0.656). For patients with persistently positive MRD after 3 courses of chemotherapy or recurrent MRD, allo-SCT had better OS than CMT and auto-SCT (p = 0.011; p = 0.029, respectively). Dynamic MRD might improve therapy stratification and optimize PRT selection for FR-AML in CR1.

BackgroundWith the ongoing development of the information society, the Internet and smartphones have become an essential way of life, but also fostered the problem of mobile phone dependence. Physical activity and subjective well-being have both been shown to correlate with mobile phone dependence, but the impact of subjective well-being on the relationship between physical activity and mobile phone dependence is not fully understood. This study investigates subjective well-being as a potential mediating variable in the relationship. It also investigates whether psychological capital moderates the association between subjective well-being and mobile phone dependence.MethodsA total of 9,569 students from 38 universities in Jiangsu Province were selected. Participants were surveyed via the online questionnaire distribution platform Questionnaire Star. Common method bias test and Pearson correlation tests were used to analyze the study indicators, and the theoretical model for this study was validated using Process plug-in developed by Hayes and set at p