Experimental investigation and simulation analysis of cast-steel joints under vertical pressure.

The joint made of cast steel is frequently utilized within a treelike column structure to ensure a smooth transition. It is of great significance in ensuring the overall structural safety, but currently, the mechanical property and bearing capacity of this type of joint cannot be fully understood. This study investigates the load characteristics of three-forked cast steel joints through concrete experiments, finite element analysis, and regression method formula derivation, filling the gap in mechanical properties and calculation formulas of forked cast steel joints. Initially, a comprehensive model of the cast-steel joint, sourced from a practical engineering, underwent vertical load testing. Detailed scrutiny of stress distribution and vertical displacement of the tested joint was conducted based on the experimental outcomes. Subsequently, a finite element model of the tested joint was constructed using SolidWorks and subjected to analysis via ANSYS. The numerical findings were juxtaposed with experimental data and extrapolated to encompass other parametric scenarios. Ultimately, a regression analysis method was employed to derive a calculation formula for the load-carrying capacity of branch-bearing cast-steel joints. The regression analysis method can accurately obtain the load-bearing capacity calculation formula for tree-shaped joint models and can be extended to determine corresponding branch and main pipe dimensions, as well as the deviation angle between branches and the main pipe, under known load conditions. This improves design efficiency and accuracy. Comparative analysis reveals a substantial concurrence among experimental, finite element analysis, and formula-based predictive outcomes. The maximum error between experimental results and those obtained from finite element analysis is 9.02%. The maximum error between the results calculated using the load-bearing capacity formula derived from regression methods and those from finite element analysis is only 1.9%.

Comprehensive analysis of macrophage-related genes in prostate cancer by integrated analysis of single-cell and bulk RNA sequencing.

Macrophages, as essential components of the tumor immune microenvironment (TIME), could promote growth and invasion in many cancers. However, the role of macrophages in tumor microenvironment (TME) and immunotherapy in PCa is largely unexplored at present. Here, we investigated the roles of macrophage-related genes in molecular stratification, prognosis, TME, and immunotherapeutic response in PCa. Public databases provided single-cell RNA sequencing (scRNA-seq) and bulk RNAseq data. Using the Seurat R package, scRNA-seq data was processed and macrophage clusters were identified automatically and manually. Using the CellChat R package, intercellular communication analysis revealed that tumor-associated macrophages (TAMs) interact with other cells in the PCa TME primarily through MIF - (CD74+CXCR4) and MIF - (CD74+CD44) ligand-receptor pairs. We constructed coexpression networks of macrophages using the WGCNA to identify macrophage-related genes. Using the R package ConsensusClusterPlus, unsupervised hierarchical clustering analysis identified two distinct macrophage-associated subtypes, which have significantly different pathway activation status, TIME, and immunotherapeutic efficacy. Next, an 8-gene macrophage-related risk signature (MRS) was established through the LASSO Cox regression analysis with 10-fold cross-validation, and the performance of the MRS was validated in eight external PCa cohorts. The high-risk group had more active immune-related functions, more infiltrating immune cells, higher HLA and immune checkpoint gene expression, higher immune scores, and lower TIDE scores. Finally, the NCF4 gene has been identified as the hub gene in MRS using the "mgeneSim" function.

Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers.

INTRODUCTION: Previous studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers. OBJECTIVES: To assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites. METHODS: A total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975-2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs). RESULTS: In patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]-19·85[95 %CI, 16·69-23·44]; AER 5·77-210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]-19·25[95 %CI, 15·76-23·29]; AER 4·36-159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]-24·71[95 %CI, 16·28-35·96]; AER 1·01-37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group. CONCLUSION: The CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Critical role of zero-valent iron in the efficient activation of H2O2 for 4-CP degradation by bimetallic peroxidase-like.

Peroxidase-like based on double transition metals have higher catalytic activity and are considered to have great potential for application in the field of pollutant degradation. First, in this paper, a novel Fe0-doped three-dimensional porous Fe0@FeMn-NC-like peroxidase was synthesized by a simple one-step thermal reduction method. The doping of manganese was able to reduce part of the iron in Fe-Mn binary oxides to Fe0 at high temperatures. In addition, Fe0@FeMn-NC has excellent peroxidase-like mimetic activity, and thus, it was used for the rapid degradation of p-chlorophenol (4-CP). During the degradation process, Fe0 was able to rapidly replenish the constantly depleted Fe2+ in the reaction system and brought in a large number of additional electrons. The ineffective decomposition of H2O2 due to the use of H2O2 as an electron donor in the reduction reactions from Fe3+ to Fe2+ and from Mn3+ to Mn2+ was avoided. Finally, based on the experimental results of LC-MS and combined with theoretical calculations, the degradation process of 4-CP was rationally analyzed, in which the intermediates were mainly p-chloro-catechol, p-chloro resorcinol, and p-benzoquinone. Fe0@FeMn-NC nano-enzymes have excellent catalytic activity as well as structural stability and perform well in the treatment of simulated wastewater containing a variety of phenolic pollutants as well as real chemical wastewater. It provides some insights and methods for the application of peroxidase-like enzymes in the degradation of organic pollutants.

mResU-Net: multi-scale residual U-Net-based brain tumor segmentation from multimodal MRI.

Brain tumor segmentation is an important direction in medical image processing, and its main goal is to accurately mark the tumor part in brain MRI. This study proposes a brand new end-to-end model for brain tumor segmentation, which is a multi-scale deep residual convolutional neural network called mResU-Net. The semantic gap between the encoder and decoder is bridged by using skip connections in the U-Net structure. The residual structure is used to alleviate the vanishing gradient problem during training and ensure sufficient information in deep networks. On this basis, multi-scale convolution kernels are used to improve the segmentation accuracy of targets of different sizes. At the same time, we also integrate channel attention modules into the network to improve its accuracy. The proposed model has an average dice score of 0.9289, 0.9277, and 0.8965 for tumor core (TC), whole tumor (WT), and enhanced tumor (ET) on the BraTS 2021 dataset, respectively. Comparing the segmentation results of this method with existing techniques shows that mResU-Net can significantly improve the segmentation performance of brain tumor subregions.

Remotely Activated DNA Probe System for the Detection and Imaging of Dual miRNAs.

Cancers remain the leading cause of mortality worldwide. It is crucial to detect cancer at an early stage for improving survival rates. Biomarkers have precise implications for cancer progression. Here, we built a straightforward DNA probe system that could be activated by near-infrared light to detect dual miRNAs with a high specificity. This probe is built on the basis of upconversion nanoparticles, which could emit ultraviolet light and activate DNA probes adsorbed on the outer layer. The DNA probe system is remotely controlled through manipulation of the near-infrared (NIR) light, enabling simultaneous detection of dual miRNAs. The DNA nanosystem could be effectively endocytosed by cancer cells and reflect expression levels of dual miRNAs. Overall, this study demonstrates a promising remote-controlled DNA nanoplatform for the simultaneous detection of dual miRNAs, which has tremendous potential for precise cancer diagnostics and therapies.

Deep learning parametric response mapping from inspiratory chest CT scans: a new approach for small airway disease screening.

OBJECTIVES: Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry. METHODS: We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD. RESULTS: Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p < 0.05). Predicted PRMfSAD showed good SAD stratification performance with ground truth PRMfSAD at thresholds of 15%, 20% and 25% (AUCs were 0.84, 0.78, and 0.84, respectively, p < 0.001). CONCLUSION: Our deep learning method generates high-quality PRM using inspiratory chest CT and effectively stratifies SAD in individuals with normal spirometry.

Unveiling the traits of dry and wet pre-magnetized zero-valent iron-activated peroxymonosulfate: Degradation of oxytetracycline.

It has been previously reported that pre-magnetization could enhance the efficacy of zero-valent iron (ZVI) in removing contaminants. However, little is known about the effects and persistence of different magnetization methods on pre-magnetized ZVI (Pre-ZVI) when used in advanced oxidation processes (AOPs). Gaining a comprehensive understanding of the durability of various pre-magnetization methods in enhancing the removal efficiency of different pollutants will significantly impact the widespread utilization of Pre-ZVI in practical engineering. Herein, we investigated the efficiency of dry and wet Pre-ZVI-activated peroxymonosulfate (PMS) in eliminating oxytetracycline (OTC) and evaluated the durability of Pre-ZVI. Additionally, we examined several factors that influence the degradation process's efficiency. Our results found that the reaction constant k values corresponding to the dry Pre-ZVI/PMS system at the pH values of 3, 7, and 9 varied from approximately 0.0384, 0.0331, and 0.0349 (day 1) to roughly 0.0297, 0.0278, and 0.0314 (day 30), respectively. Meanwhile, the wet Pre-ZVI/PMS system exhibited k values ranging from approximately 0.0392, 0.0349, and 0.0374 (day 1) to roughly 0.0380, 0.0291, and 0.0322 (day 30), respectively. Moreover, we proposed four OTC degradation pathways using LC-MS/MS and density functional theory calculations. The toxicity of the degradation products was assessed using the ecological structure activity relationship and the toxicity estimation software tool. Overall, this study provides insights into the application of Pre-ZVI/PMS that can be selectively used to eliminate tetracycline antibiotics from water.

A Nomogram of Magnetic Resonance Imaging for Preoperative Assessment of Microvascular Invasion and Prognosis of Hepatocellular Carcinoma.

BACKGROUND: Microvascular invasion (MVI) is a predictor of recurrence and overall survival in hepatocellular carcinoma (HCC), the preoperative diagnosis of MVI through noninvasive methods play an important role in clinical treatment. AIMS: To investigate the effectiveness of radiomics features in evaluating MVI in HCC before surgery. METHODS: We included 190 patients who had undergone contrast-enhanced MRI and curative resection for HCC between September 2015 and November 2021 from two independent institutions. In the training cohort of 117 patients, MVI-related radiomics models based on multiple sequences and multiple regions from MRI were constructed. An independent cohort of 73 patients was used to validate the proposed models. A final Clinical-Imaging-Radiomics nomogram for preoperatively predicting MVI in HCC patients was generated. Recurrence-free survival was analyzed using the log-rank test. RESULTS: For tumor-extracted features, the performance of signatures in fat-suppressed T1-weighted images and hepatobiliary phase was superior to that of other sequences in a single-sequence model. The radiomics signatures demonstrated better discriminatory ability than that of the Clinical-Imaging model for MVI. The nomogram incorporating clinical, imaging and radiomics signature showed excellent predictive ability and achieved well-fitted calibration curves, outperforming both the Radiomics and Clinical-Radiomics models in the training and validation cohorts. CONCLUSIONS: The Clinical-Imaging-Radiomics nomogram model of multiple regions and multiple sequences based on serum alpha-fetoprotein, three MRI characteristics, and 12 radiomics signatures achieved good performance for predicting MVI in HCC patients, which may help clinicians select optimal treatment strategies to improve subsequent clinical outcomes.

An MR-based radiomics nomogram including information from the peritumoral region to predict deep myometrial invasion in stage I endometrioid adenocarcinoma: a preliminary study.

OBJECTIVE: To develop and validate an MR-based radiomics nomogram combining different imaging sequences (ADC mapping and T2 weighted imaging (T2WI)), different tumor regions (combined intra- and peritumoral regions), and different parameters (clinical features, tumor morphological features, and radiomics features) while considering different MR field strengths in predicting deep myometrial invasion (MI) in Stage I endometrioid adenocarcinoma (EEA). METHODS: A total of 202 patients were retrospectively analyzed and divided into two cohorts (training cohort, 1.5 T MR, n = 131; validation cohort, 3.0 T MR, n = 71). Axial ADC mapping and T2WI were conducted. Radiomics features were extracted from intra- and peritumoral regions. Least absolute shrinkage and selection operator regression, univariate analysis, and multivariate logistic regression were used to select radiomics features and tumor morphological and clinical parameters. The area under the receiver operator characteristic curve (AUC) was calculated to evaluate the performance of the prediction model and radiomics nomogram. RESULTS: Ten radiomics features, 4 morphological parameters and 1 clinical characteristic were selected. The radiomics nomogram achieved good discrimination between the superficial and deep MI cohorts. The AUC was 0.927 (95% confidence interval [CI]: 0.865, 0.967) in the training cohort and 0.921 (95% CI: 0.872, 0.948) in the validation cohort. The specificity and sensitivity were 92.0 and 78.9% in the training cohort and 83.0 and 77.8% in the validation cohort, respectively. CONCLUSION: The radiomics nomogram showed good performance in predicting the depth of MI in Stage I EEA before surgery and might be useful for surgical patient management. ADVANCES IN KNOWLEDGE: An MR-based radiomics nomogram was useful for predicting deep MI in Stage I EEA patients (AUCtrain = 0.927, AUCvalidation = 0.921). The intra- and peritumoral radiomics features complemented each other. The nomogram was developed and validated with different MR field strengths, suggesting that the model demonstrates good generalizability.

Eco-friendly approach for enhancing the floatability of non-metallic components in waste printed circuit boards: Adding gutter oil during dry grinding.

Waste printed circuit boards (WPCBs) are an attractive secondary resource that is challenging to dispose of due to its complexity. Reverse flotation is an effective method to remove non-metallic particles (NMPs) to obtain metals from WPCBs. Nevertheless, the removal of NMPs is usually inadequate in the present flotation practice. Thus, to provide a clean approach to improve the removal efficiency of NMPs, the method of adding gutter oil during dry grinding process was adopted to enhance the hydrophobic sites on the surface of NMPs to improve the floatability. The surface morphology of NMPs was analyzed by SEM, the results show that the rough morphology inhibited the adhesion of bubbles, while water occupied the cracks and pores, making it challenging for collector adsorption, which result in unstable particle-bubble adhesion. The results of FTIR indicate that both NMPs and gutter oil have -CH3, -CH2, -C = O, -C-O functional groups, which promotes the adsorption of gutter oil on the surface of NMPs. The contact angle (CA) results show that the adsorption of gutter oil on the particle surface is conducive to the formation of enhanced CA. Furthermore, the flotation enhancement effect was verified by flotation kinetic experiments. The accumulated floats yield of NMPs conditioned by gutter oil during grinding is increased from 67.05% (NMPs without conditioning) to 95.02%, and the resin recovery is increased by 31.10%. It is demonstrated that dry grinding with gutter oil can strengthen the floatability of NMPs, which provides a potential approach to increase the flotation efficiency of WPCBs.

Sex-Specific Associations Between Preoperative Hemoglobin and Outcomes After Major Noncardiac Surgery: A Retrospective Cohort Study.

BACKGROUND: Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies. METHODS: This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test. RESULTS: We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women ( P = .539) or men ( P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87-0.98; P = .013) for women and 0.94 (95% CI, 0.90-0.97; P < .001) for men, with no interaction by sex ( Pinteraction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly. CONCLUSIONS: Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.

Preventive effects of 13 different drugs on colorectal cancer: a network meta-analysis.

Introduction: The aim of the study was to evaluate the preventive effect of 13 drugs on colorectal cancer (CRC) and guide the clinical application of these drugs. Material and methods: PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched for randomized controlled trials (RCTs) and cohort studies. The Cochrane bias risk assessment tool and the Newcastle-Ottawa Scale quality evaluation tool were used to evaluate the quality of the included RCTs and cohort studies. The funnel plot was used to analyze publication bias. A network meta-analysis of the extracted data was conducted using Stata16.0 software. Results: A total of 57 studies (34 RCTs and 23 cohort studies) involving 82719 participants were included. The network meta-analysis revealed that the quality of the included studies was good; the funnel plot showed no obvious publication bias. The network meta-analysis showed that the preventive effect of 13 drugs on CRC was better than that of the placebo. Allopurinol (SUCRA: 97.2%) was found to have the best effect, followed by berberine (SUCRA: 89.9%), non-aspirin NSAIDs (SUCRA: 84.5%), statins (SUCRA: 66.5%), metformin (SUCRA: 66.3%), calcium (SUCRA: 48.9%), mesalazine (SUCRA: 44.5%), ursodeoxycholic acid (SUCRA: 42.6%), vitamin D (SUCRA: 41.4%), mercaptopurine (SUCRA: 39.4%), aspirin (SUCRA: 30.4%), folic acid (SUCRA: 24.9%), and eicosapentaenoic acid (SUCRA: 16.3%). Conclusions: The preventive effect of allopurinol on CRC was better than that of the other 13 drugs. These results can help doctors and patients understand the preventative effects of these drugs more intuitively and provide an evidence-based basis for the clinical application of these drugs.

[Effects of electroacupuncture on the secretion function of ovarian cells and kisspeptin/kiss1r system in rats with polycystic ovarian syndrome].

OBJECTIVE: To observe the effects of electroacupuncture （EA） on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome （PCOS）, so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats. METHODS: Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole （0.1 mg/mL, 10 mL•kg-1•d-1）. In the EA group, EA （2 Hz, 2 mA） was used to stimulate "Guanyuan" （CV4） for 20 min each time. In the flutamide group, flutamide solution （50 mg•kg-1•d-1） was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone （T）, luteinizing hormone （LH） and estradiol （E2） in serum, the contents of E2 and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot. RESULTS: Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was decreased （P<0.01） in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was increased （P<0.05, P<0.01）. CONCLUSION: EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.

Characterization of the transcriptional responses of Armillaria gallica 012m to GA3.

Gastrodia elata needs to establish a symbiotic relationship with Armillaria strains to obtain nutrients and energy. However, the signaling cross talk between G. elata and Armillaria strains is still unclear. During our experiment, we found that the vegetative mycelium of Armillaria gallica 012m grew significantly better in the media containing gibberellic acid (GA3) than the blank control group (BK). To explore the response mechanism, we performed an RNA-sequencing experiment to profile the transcriptome changes of A. gallica 012m cultured in the medium with exogenous GA3. The transcriptome-guided differential expression genes (DEGs) analysis of GA3 and BK showed that a total of 1309 genes were differentially expressed, including 361 upregulated genes and 948 downregulated genes. Some of those DEGs correlated with the biological process, including positive regulation of chromosome segregation, mitotic metaphase/anaphase transition, attachment of mitotic spindle microtubules to kinetochore, mitotic cytokinesis, and nuclear division. These analyses explained that GA3 actively promoted the growth of A. gallica to some extent. Further analysis of protein domain features showed that the deduced polypeptide contained 41 candidate genes of GA receptor, and 27 of them were expressed in our samples. We speculate that GA receptors exist in A. gallica 012m. Comparative studies of proteins showed that the postulated GA receptor domains of A. gallica 012m have a higher homologous correlation with fungi than others based on cluster analysis.

Inhalable pH-responsive DNA tetrahedron nanoplatform for boosting anti-tumor immune responses against metastatic lung cancer.

Despite advancements in the treatment of pulmonary cancer, the existence of mucosal barriers in lung still hampered the penetration and diffusion of therapeutic agents and greatly limited the therapeutic benefits. In this work, we reported a novel inhalable pH-responsive tetrahedral DNA nanomachines with simultaneous delivery of immunomodulatory CpG oligonucleotide and PD-L1-targeting antagonistic DNA aptamer (CP@TDN) for efficient treatment of pulmonary metastatic cancer. By precisely controlling the ratios of CpG and PD-L1 aptamer, the obtained CP@TDN could specifically release PD-L1 aptamer to block PD-1/PD-L1 immune checkpoint axis in acidic tumor microenvironment, followed by endocytosis by antigen-presenting cells to generate anti-tumor immune activation and secretion of anti-tumor cytokines. Moreover, inhalation delivery of CP@TDN showed highly-efficient lung deposition with greatly enhanced intratumoral accumulation, ascribing to the DNA tetrahedron-mediated penetration of pulmonary mucosa. Resultantly, CP@TDN could significantly inhibit the growth of metastatic orthotopic lung tumors via the induction of robust antitumor responses. Therefore, our work presents an attractive approach by virtue of biocompatible DNA tetrahedron as the inhalation delivery system for effective treatment of metastatic lung cancer.

Determination of optimal NH4+/K + concentration and corresponding ratio critical for growth of tobacco seedlings in a hydroponic system.

Inherently, ammonium (NH4 +) is critical for plant growth; however, its toxicity suppresses potassium (K+) uptake and vice-versa. Hence, attaining a nutritional balance between these two ions (NH4 + and K+) becomes imperative for the growth of tobacco seedlings. Therefore, we conducted a 15-day experimental study on tobacco seedlings exposed to different concentrations (47 treatments) of NH4 +/K+ at different corresponding 12 ratios simultaneously in a hydroponic system. Our study aimed at establishing the optimal NH4 +-K+ concentration and the corresponding ratio required for optimal growth of different tobacco plant organs during the seedling stage. The controls were the baseline for comparison in this study. Plants with low or excessive NH4 +-K+ concentration had leaf chlorosis or dark greenish colouration, stunted whole plant part biomass, and thin roots. We found that adequate K+ supply is a pragmatic way to mitigate NH4 +-induced toxicity in tobacco plants. The optimal growth for tobacco leaf and root was attained at NH4 +-K+ concentrations 2-2 mM (ratio 1:1), whereas stem growth was optimal at NH4 +-K+ 1-2 mM (1:2). The study provided an insight into the right combination of NH4 +/K+ that could mitigate or prevent NH4 + or K+ stress in the tobacco seedlings.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.