Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 1.416
1.
Water Res ; 257: 121670, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38723347

In this study, the performance of a novel up-flow electrocatalytic hydrolytic acidification reactor (UEHAR) and anoxic/oxic (ANO2/O2) combined system (S2) was compared with that of a traditional anaerobic/anoxic/oxic (ANA/ANO1/O1) system (S1) for treating coking wastewater at different hydraulic retention time (HRT). The effluent non-compliance rates of chemical oxygen demand (COD) of S2 were 45 %, 35 %, 25 % and 55 % lower than S1 with HRT of 94, 76, 65 and 54 h. The removal efficiency of benzene, toluene, ethylbenzene and xylene (BTEX) in S2 was 10.6 ± 2.4 % higher than that in S1. The effluent concentration of volatile phenolic compounds (VPs) in S2 was lower than 0.3 mg/L. The dehydrogenase activity (DHA) and adenosine triphosphate (ATP) of O2 were enhanced by 67.2 ± 26.3 % and 40.6 ± 14.2 % compared with O1, respectively. Moreover, COD was used to reflect the mineralization index of organic matter, and the positive correlation between COD removal rate and microbial activity, VPs, and BTEX was determined. These results indicated that S2 had extraordinary microbial activity, stable pollutant removal ability, and transcendental effluent compliance rate.

2.
Sci Data ; 11(1): 488, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734729

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.


Herbivory , Transcriptome , Animals , Cattle/genetics , Female , Rabbits/genetics , Databases, Genetic , Deer/genetics , Equidae/genetics , Goats/genetics , Horses/genetics , Sheep/genetics
3.
Int J Womens Health ; 16: 831-842, 2024.
Article En | MEDLINE | ID: mdl-38769949

Objective: In this study, we investigated the value of molecular typing combined with integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) semi-quantitative indices in endometrial cancer risk stratification. Methods: A retrospective study was conducted on 86 patients who were pathologically diagnosed with endometrial cancer and underwent surgical treatment after curettage at the Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University between January 2017 and March 2023. Prior to surgery, each patient underwent integrated PET/MRI examination. The postoperative samples were subjected to pathological diagnosis, immunohistochemistry, and POLE gene sequencing. The differences in clinicopathological features between the four molecular subtypes and the differences in integrated PET/MRI semi-quantitative indexes (SUV max, ADC min) between the four molecular subtypes were analyzed. The cutoff value of molecular typing combined with integrated PET/MRI semi-quantitative indices for endometrial cancer risk stratification was determined. Results: There were statistically significant differences in pathological types and tumor grades among the four molecular subtypes of endometrial cancer. The values of the four integrated PET/MRI semi-quantitative indices (SUV max and ADC min) of the molecular subtypes were statistically different. The SUV max was greater in the p53abn mutation group than in the POLE mutation group (P < 0.05). The ADC minimum of the POLE mutation group and the MMR-d group was lower than the NSMP group (P < 0.05). Molecular typing combined with the integrated PET/MRI semi-quantitative SUV max index can predict the low/medium risk group of endometrial cancer and the medium-high/high risk group, and the cut-off value of SUV max for predicting the risk of early endometrial cancer was 14.72 (sensitivity 66.7%, specificity 68.7%). Conclusion: Molecular typing combined with integrated PET/MRI semi-quantitative indicators is useful to achieve risk stratification in patients diagnosed with endometrial cancer and guide individualized treatment.

4.
Article En | MEDLINE | ID: mdl-38771681

Electromyographic (EMG) signals have gained popularity for controlling prostheses and exoskeletons, particularly in the field of upper limbs for stroke patients. However, there is a lack of research in the lower limb area, and standardized open-source datasets of lower limb EMG signals, especially recording data of Asian race features, are scarce. Additionally, deep learning algorithms are rarely used for human motion intention recognition based on EMG, especially in the lower limb area. In response to these gaps, we present an open-source benchmark dataset of lower limb EMG with Asian race characteristics and large data volume, the JJ dataset, which includes approximately 13,350 clean EMG segments of 10 gait phases from 15 people. This is the first dataset of its kind to include the nine main muscles of human gait when walking. We used the processed time-domain signal as input and adjusted ResNet-18 as the classification tool. Our research explores and compares multiple key issues in this area, including the comparison of sliding time window method and other preprocessing methods, comparison of time-domain and frequency-domain signal processing effects, cross-subject motion recognition accuracy, and the possibility of using thigh and calf muscles in amputees. Our experiments demonstrate that the adjusted ResNet can achieve significant classification accuracy, with an average accuracy rate of 95.34% for human gait phases. Our research provides a valuable resource for future studies in this area and demonstrates the potential for ResNet as a robust and effective method for lower limb human motion intention pattern recognition.

5.
J Genet Genomics ; 2024 May 18.
Article En | MEDLINE | ID: mdl-38768655

Stomata play critical roles in gas exchange and immunity to pathogens. While many genes regulating early stomatal development up to the production of young guard cells (GCs) have been identified in Arabidopsis, much less is known about how young GCs develop into mature functional stomata. Here we perform a maturomics study on stomata, with "maturomics" defined as omics analysis of the maturation process of a tissue or organ. We develop an integrative scheme to analyze three public stomata-related single-cell RNA-seq datasets and identify a list of 586 genes that are specifically up-regulated in all three datasets during stomatal maturation and function formation. The list, termed sc_586, is enriched with known regulators of stomatal maturation and functions. To validate the reliability of the dataset, we selected two candidate G2-like transcription factor genes, MYS1 and MYS2, to investigate their roles in stomata. These two genes redundantly regulate the size and hoop rigidity of mature GCs, and the mys1 mys2 double mutatants cause mature GCs with severe defects in regulating their stomatal apertures. Taken together, our results provide a valuable list of genes for studying GC maturation and function formation.

6.
Medicine (Baltimore) ; 103(18): e38058, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701248

To evaluate the right atrial function in patients with 3-branch coronary artery disease (TBCAD) without myocardial infarction by 2D speckle tracking echocardiography (2D-STE) combined with real-time 3-dimensional echocardiography (RT-3DE). Fifty-six patients admitted to our hospital without myocardial infarction with TBCAD were selected. We divided them into 2 groups according to the coronary angiography results: 28 patients in group B (the rate of stenosis is 50% ~< 75%); 28 patients in group C (the rate of stenosis is ≥75%); in addition, 30 healthy volunteers were screened as group A. All subjects underwent RT-3DE to obtain the right atrial volume (RAVmax, RAVmin, and RAVp), and then we calculated the right atrial passive and active ejection fraction (RAPEF, RAAEF), and maximum volume index (RAVImax). In addition, to measure the strain rates (RASRs, RASRe, RASRa) of the right atrium during systole, early diastole, and late diastole, 2D-STE was applied. Correlations between the 2D-STE parameters and the results of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Gensini scores were analyzed by Pearson linear analysis. Compared with group A, RAPEF and RASRe were reduced, while RAAEF and RASRa were elevated in group B (P < .05). RAPEF, RASRs, RASRe, and RASRa were decreased compared with groups A and B, while RAVmax, RAVmin, RAVp, RAVImax, and RAAEF were increased in group C (P < .05). There was a significant correlation between 2D-STE parameters and the results of NT-proBNP and Gensini scores (P < .05). The storage, conduit, and pump functions of the right atrium are reduced in patients with 3-branch coronary artery disease without myocardial infarction; 2D-STE combined with RT-3DE is valuable in the evaluation of the right atrium in patients with coronary artery disease.


Coronary Artery Disease , Echocardiography, Three-Dimensional , Heart Atria , Natriuretic Peptide, Brain , Humans , Male , Echocardiography, Three-Dimensional/methods , Female , Middle Aged , Coronary Artery Disease/physiopathology , Coronary Artery Disease/diagnostic imaging , Natriuretic Peptide, Brain/blood , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Aged , Peptide Fragments/blood , Atrial Function, Right/physiology , Echocardiography/methods , Coronary Angiography/methods
7.
Eur J Epidemiol ; 2024 May 04.
Article En | MEDLINE | ID: mdl-38703249

The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.

8.
Clin Transplant ; 38(5): e15325, 2024 May.
Article En | MEDLINE | ID: mdl-38716770

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.


Graft Rejection , Graft Survival , Hepacivirus , Hepatitis C , Lung Transplantation , Postoperative Complications , Viremia , Humans , Lung Transplantation/adverse effects , Female , Male , Retrospective Studies , Middle Aged , Follow-Up Studies , Prognosis , Hepatitis C/surgery , Hepatitis C/virology , Hepacivirus/isolation & purification , Viremia/virology , Viremia/etiology , Survival Rate , Graft Rejection/etiology , Risk Factors , Tissue Donors/supply & distribution , Adult , Antiviral Agents/therapeutic use , Transplant Recipients
9.
Discov Nano ; 19(1): 88, 2024 May 16.
Article En | MEDLINE | ID: mdl-38753219

With the popularity of smart terminals, wearable electronic devices have shown great market prospects, especially high-sensitivity pressure sensors, which can monitor micro-stimuli and high-precision dynamic external stimuli, and will have an important impact on future functional development. Compressible flexible sensors have attracted wide attention due to their simple sensing mechanism and the advantages of light weight and convenience. Sensors with high sensitivity are very sensitive to pressure and can detect resistance/current changes under pressure, which has been widely studied. On this basis, this review focuses on analyzing the performance impact of device structure design strategies on high sensitivity pressure sensors. The design of structures can be divided into interface microstructures and three-dimensional framework structures. The preparation methods of various structures are introduced in detail, and the current research status and future development challenges are summarized.

10.
Radiol Cardiothorac Imaging ; 6(3): e230196, 2024 Jun.
Article En | MEDLINE | ID: mdl-38752718

Purpose To evaluate the feasibility of leveraging serial low-dose CT (LDCT) scans to develop a radiomics-based reinforcement learning (RRL) model for improving early diagnosis of lung cancer at baseline screening. Materials and Methods In this retrospective study, 1951 participants (female patients, 822; median age, 61 years [range, 55-74 years]) (male patients, 1129; median age, 62 years [range, 55-74 years]) were randomly selected from the National Lung Screening Trial between August 2002 and April 2004. An RRL model using serial LDCT scans (S-RRL) was trained and validated using data from 1404 participants (372 with lung cancer) containing 2525 available serial LDCT scans up to 3 years. A baseline RRL (B-RRL) model was trained with only LDCT scans acquired at baseline screening for comparison. The 547 held-out individuals (150 with lung cancer) were used as an independent test set for performance evaluation. The area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI) were used to assess the performances of the models in the classification of screen-detected nodules. Results Deployment to the held-out baseline scans showed that the S-RRL model achieved a significantly higher test AUC (0.88 [95% CI: 0.85, 0.91]) than both the Brock model (AUC, 0.84 [95% CI: 0.81, 0.88]; P = .02) and the B-RRL model (AUC, 0.86 [95% CI: 0.83, 0.90]; P = .02). Lung cancer risk stratification was significantly improved by the S-RRL model as compared with Lung CT Screening Reporting and Data System (NRI, 0.29; P < .001) and the Brock model (NRI, 0.12; P = .008). Conclusion The S-RRL model demonstrated the potential to improve early diagnosis and risk stratification for lung cancer at baseline screening as compared with the B-RRL model and clinical models. Keywords: Radiomics-based Reinforcement Learning, Lung Cancer Screening, Low-Dose CT, Machine Learning © RSNA, 2024 Supplemental material is available for this article.


Early Detection of Cancer , Lung Neoplasms , Tomography, X-Ray Computed , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/diagnosis , Middle Aged , Male , Female , Early Detection of Cancer/methods , Aged , Tomography, X-Ray Computed/methods , Retrospective Studies , Radiation Dosage , Feasibility Studies , Machine Learning , Mass Screening/methods , Lung/diagnostic imaging , Radiomics
11.
PLoS One ; 19(5): e0303650, 2024.
Article En | MEDLINE | ID: mdl-38753638

HuaChanSu (HCS) or Cinobufacini injection is an aqueous extract of the dried skin of Bufo bufo gargarigans, and has anti-tumor effects. The aim of this study was to evaluate the possible therapeutic effect of HCS against breast cancer (BRCA) using cytology, network pharmacology, and molecular biology approaches. The half-inhibitory concentration (IC50) of HCS in the BRCA cells was determined by cytotoxicity assay, and were accordingly treated with high and low doses HCS in the TUNEL and scratch assays. The potential targets of HCS in the BRCA cells were identified through functional enrichment analysis and protein-protein interaction (PPI) networks, and verified by molecular docking. The expression levels of key signaling pathways-related proteins in HCS-treated BRCA cells by western blotting. HCS inhibited the proliferation and migration of MCF-7 and MDA-MB-231 cells, and induced apoptosis in a dose-dependent manner. Furthermore, we screened 289 core HCS targets against BRCA, which were primarily enriched in the PI3K-AKT, MAPK chemokines, and other. signaling pathways. In addition, PIK3CA, PIK3CD, and MTOR were confirmed as HCS targets by molecular docking. Consistent with this, we observed a reduction in the expression levels of phosphorylated PI3K, AKT, and MTOR in the HCS-treated BRCA cells. Taken together, our findings suggest that HCS inhibits the growth of BRCA cells by targeting the PI3K-AKT pathway, and warrants further investigation as a therapeutic agent for treating patients with BRCA.


Apoptosis , Breast Neoplasms , Cell Proliferation , Network Pharmacology , Signal Transduction , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Cell Proliferation/drug effects , Apoptosis/drug effects , Signal Transduction/drug effects , Cell Line, Tumor , Molecular Docking Simulation , Cell Movement/drug effects , Animals , Antineoplastic Agents/pharmacology , MCF-7 Cells , Proto-Oncogene Proteins c-akt/metabolism , Protein Interaction Maps/drug effects
12.
Adv Mater ; : e2401640, 2024 May 06.
Article En | MEDLINE | ID: mdl-38710154

Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.

13.
World J Hepatol ; 16(3): 379-392, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38577538

BACKGROUND: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

14.
Mol Cancer ; 23(1): 67, 2024 04 01.
Article En | MEDLINE | ID: mdl-38561768

Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor and has a significant impact on mortality rates. Nevertheless, the swift advancement of contemporary technology has not seamlessly aligned with the evolution of detection methodologies, resulting in a deficit of innovative and efficient clinical assays for GIC. Given that exosomes are preferentially released by a myriad of cellular entities, predominantly originating from neoplastic cells, this confers exosomes with a composition enriched in cancer-specific constituents. Furthermore, exosomes exhibit ubiquitous presence across diverse biological fluids, endowing them with the inherent advantages of non-invasiveness, real-time monitoring, and tumor specificity. The unparalleled advantages inherent in exosomes render them as an ideal liquid biopsy biomarker for early diagnosis, prognosticating the potential development of GIC metastasis.In this review, we summarized the latest research progress and possible potential targets on cancer-derived exosomes (CDEs) in GIC with an emphasis on the mechanisms of exosome promoting cancer metastasis, highlighting the potential roles of CDEs as the biomarker and treatment in metastatic GIC.


Exosomes , Gastrointestinal Neoplasms , Humans , Exosomes/pathology , Biomarkers, Tumor , Biomarkers , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Liquid Biopsy/methods
15.
Front Plant Sci ; 15: 1257882, 2024.
Article En | MEDLINE | ID: mdl-38567136

Introduction: An appropriate supply of ammonium (NH4+) in addition to nitrate (NO3-) can greatly improve plant growth and promote maize productivity. However, knowledge gaps exist regarding the mechanisms by which different nitrogen (N) fertilizer sources affect the enzymatic activity of nitrogen metabolism and non-structural carbohydrates during the post-anthesis period. Methods: A field experiment across 3-year was carried out to explore the effects of four nitrateammonium ratio (NO3-/NH4+ = 1:0 (N1), 1:1 (N2), 1:3 (N3), and 3:1 (N4)) on postanthesis dry matter (DM) and N accumulation, partitioning, transportation, and grain yield in maize. Results: NO3-/NH4+ ratio with 3:1 improved the enzymatic activity of N metabolism and non-structural carbohydrate accumulation, which strongly promoted the transfer of DM and N in vegetative organs to reproductive organs and improved the pre-anthesis DM and nitrogen translocation efficiency. The enzymatic activities of nitrate reductase, nitrite reductase, glutamine synthetase, glutamine oxoglutarate aminotransferase, and non-structural carbohydrate accumulation under N4 treatment were increased by 9.30%-32.82%, 13.19%-37.94%, 4.11%-16.00%, 11.19%-30.82%, and 14.89%-31.71% compared with the other treatments. Mixed NO3--N and NH4+-N increased the total DM accumulation at the anthesis and maturity stages, simultaneously decreasing the DM partitioning of stem, increasing total DM, DM translocation efficiency (DMtE), and contribution of pre-anthesis assimilates to the grain (CAPG) in 2015 and 2017, promoting the transfer of DM from stem to grain. Furthermore, the grain yield increased by 3.31%-9.94% (2015), 68.6%-26.30% (2016), and 8.292%-36.08% (2017) under the N4 treatment compared to the N1, N2, and N3 treatments. Conclusion: The study showed that a NO3-/NH4+ ratio of 3:1 is recommended for high-yield and sustainable maize management strategies in Northwestern China.

16.
Nat Commun ; 15(1): 2984, 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38582903

Metamaterials composed of different geometrical primitives have different properties. Corresponding to the fundamental geometrical forms of line, plane, and surface, beam-, plate-, and shell-based lattice metamaterials enjoy many advantages in many aspects, respectively. To fully exploit the advantages of each structural archetype, we propose a multilayer strategy and topology optimization technique to design lattice metamaterial in this study. Under the frame of the multilayer strategy, the design space is enlarged and diversified, and the design freedom is increased. Topology optimization is applied to explore better designs in the larger and diverse design space. Beam-plate-shell-combined metamaterials automatically emerge from the optimization to achieve ultrahigh stiffness. Benefiting from high stiffness, energy absorption performances of optimized results also demonstrate substantial improvements under large geometrical deformation. The multilayer strategy and topology optimization can also bring a series of tunable dimensions for lattice design, which helps achieve desired mechanical properties, such as isotropic elasticity and functionally grading material property, and superior performances in acoustic tuning, electrostatic shielding, and fluid field tuning. We envision that a broad array of synthetic and composite metamaterials with unprecedented performance can be designed with the multilayer strategy and topology optimization.

17.
Nat Commun ; 15(1): 2862, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38580648

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in the open configuration. Remarkably, Polθi binding to the Polθ-pol:DNA/DNA closed complex traps the polymerase on DNA for more than forty minutes which elucidates the inhibitory mechanism of action. These data reveal a unique small-molecule DNA polymerase:DNA trapping mechanism that induces synthetic lethality in HR-deficient cells and potentiates the activity of PARPi.


BRCA1 Protein , Poly(ADP-ribose) Polymerase Inhibitors , BRCA1 Protein/genetics , BRCA2 Protein/genetics , DNA/metabolism , DNA Repair , DNA-Directed DNA Polymerase/metabolism , Homologous Recombination , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Humans
18.
Sci Rep ; 14(1): 8778, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627433

With the continuous improvement of various armor protection technologies, the armor protection performance has increased significantly, and then the damage performance requirements of armor-piercing ammunition have also increased. In order to improve the penetration ability of the liner, a new three-layer liner structure is designed in this paper. The jet forming process was simulated by AUTODYN software. The mechanism of shaped jet forming of three-layer liner was studied. The reason why the penetration depth of three-layer liner was higher than that of ordinary liner was explained. The influence of three-layer liner on the propagation of detonation wave and the change of pressure when detonation wave acted on liner were found, which provided a new idea for improving the penetration depth of jet. The influence of liner material, cone angle and stand-off on jet forming and penetration was also studied by orthogonal optimization experiment, and the structural parameters with the best penetration performance were obtained. The results show that the pressure at the convergence point increases first and then decreases during the formation of the jet of the three-layer liner. The pressure at the convergence point when the three-layer liner material is from low impedance to high impedance from the outside to the inside is much larger than the pressure at the convergence point from high impedance to low impedance. When the three-layer liner material is Al 2024-Copper-Tantalum from the outside to the inside, the pressure at the convergence point of the three-layer liner at different times is higher than that of the double-layer liner and the single-layer liner. Reasonable matching of different impact impedance materials in the three-layer liner can greatly improve the pressure value of the detonation wave acting on the cone liner. The maximum pressure at the convergence point on the axis is 39.10 GPa, which is 22.00% higher than that of the double-layer liner at the convergence point, and 53.03% higher than that of the single-layer liner at the convergence point. The orthogonal design test scheme is simulated and analyzed. The penetration depth is taken as the observation index, and the range analysis is adopted. The results show that the material matching of the three-layer liner has the greatest influence on the depth of the jet penetrating the target plate, followed by the cone angle of the three-layer liner. Relatively speaking, the stand-off has the least influence on the result. Reasonable matching of materials with different impact impedances in the three-layer liner can maximize the penetration depth of the jet into the target plate.

19.
Environ Int ; 186: 108633, 2024 Apr.
Article En | MEDLINE | ID: mdl-38603814

In the severe pollution area of nanoplastics (NPs) and cadmium ions (Cd2+), the joint effects of their high environmental concentrations on primary producers may differ from those of low environmental doses. Thus, we investigated the physiological changes, cell morphology, molecular dynamic simulation, phenotypic interactions, and metabolomics responses of C. pyrenoidosa to high environmental concentrations of NPs and Cd2+ after 12-d acclimation. After 12-d cultivation, mono-NPs and mono-Cd2+ reduced cell density and triggered antioxidant enzymes, extracellular polymeric substances (EPS) production, and cell aggregation to defend their unfavorable effects. Based on the molecular dynamic simulation, the chlorine atoms of the NPs and Cd2+ had charge attraction with the nitrogen and phosphorus atoms in the choline and phosphate groups in the cell membrane, thereby NPs and Cd2+ could adsorb on the cells to destroy them. In the joint exposure, NPs dominated the variations of ultrastructure and metabolomics and alleviated the toxicity of NPs and Cd2+. Due to its high environmental concentration, more NPs could compete with the microalgae for Cd2+ and thicken cell walls, diminishing the Cd2+ content and antioxidant enzymes of microalgae. NPs addition also decreased the EPS content, while the bound EPS with -CN bond was kept to detoxicate Cd2+. Metabolomics results showed that the NPs downregulated nucleotide, arachidonic acid, and tryptophan metabolisms, while the Cd2+ showed an opposite trend. Compared with their respective exposures, metabolomics results found the changes in metabolic molecules, suggesting the NPs_Cd2+ toxicity was mitigated by balancing nucleotide, arachidonic acid, tryptophan, and arginine and proline metabolisms. Consequently, this study provided new insights that simultaneous exposure to high environmental concentrations of NPs and Cd2+ mitigated microalgae cellular toxicity, which may change their fates and biogeochemical cycles in aquatic systems.


Cadmium , Metabolomics , Microalgae , Cadmium/toxicity , Microalgae/drug effects , Microalgae/metabolism , Molecular Dynamics Simulation , Water Pollutants, Chemical/toxicity , Microplastics/toxicity
20.
Foods ; 13(7)2024 Apr 04.
Article En | MEDLINE | ID: mdl-38611413

Finding stable and bioavailable calcium supplements is crucial for addressing calcium deficiency. In this study, glycated peptide-calcium chelates (WMPHs-COS-Ca) were prepared from walnut meal protein hydrolysates (WMPHs) and chitosan oligosaccharides (COSs) through the Maillard reaction, and the structural properties and stability of the WMPHs-COS-Ca were characterized. The results showed that WMPHs and COSs exhibited high binding affinities, with a glycation degree of 64.82%. After glycation, Asp, Lys, and Arg decreased by 2.07%, 0.46%, and 1.06%, respectively, which indicated that these three amino acids are involved in the Maillard reaction. In addition, compared with the WMPHs, the emulsifying ability and emulsion stability of the WMPHs-COS increased by 10.16 mg2/g and 52.73 min, respectively, suggesting that WMPHs-COS have better processing characteristics. After chelation with calcium ions, the calcium chelation rate of peptides with molecular weights less than 1 kDa was the highest (64.88%), and the optimized preparation conditions were 5:1 w/w for WMPH-COS/CaCl2s, with a temperature of 50 °C, a chelation time of 50 min, and a pH of 7.0. Scanning electron microscopy showed that the "bridging role" of WMPHs-COS changed to a loose structure. UV-vis spectroscopy and Fourier transform infrared spectrometry results indicated that the amino nitrogen atoms, carboxyl oxygen atoms, and carbon oxygen atoms in WMPHs-COS chelated with calcium ions, forming WMPHs-COS-Ca. Moreover, WMPHs-COS-Ca was relatively stable at high temperatures and under acidic and alkaline environmental and digestion conditions in the gastrointestinal tract, indicating that WMPHs-COS-Ca have a greater degree of bioavailability.

...