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1.
Phys Chem Chem Phys ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39161289

RESUMO

Cobalt has the highest Curie temperature (Tc) among the elemental ferromagnetic metals and has a hexagonal close-packed (HCP) structure at room temperature. In this study, HCP Co was thinned to the thickness of several (n) unit cells along the c-axis and then passivated by halogen atoms, thus being named Co2nX2 (X = F, Cl, Br and I). For Co2X2 and Co3X2, all of them are not only kinetically but also thermodynamically stable from the viewpoint of the phonon spectra and molecular dynamics. Similar to HCP Co, two-dimensional (2D) Co2F2, Co2Cl2 and Co3X2 (X = Cl, Br and I) are still ferromagnetic metals within the Stoner model but Co2X2 (X = Br and I) is a ferromagnetic half-metal with the coexistence of the metallic behavior for one spin and the insulating behavior for the other spin. Taking into account the spin-orbital coupling (SOC), the easy-magnetization axis is within the plane where the magnetization is isotropic, making it look like a 2D XY magnet. Applying a critical biaxial strain could lead to an easy-magnetization axis changing from the in-plane to the out-of-plane direction. Finally, we use classical Monte Carlo simulations to estimate the Curie temperature (Tc) which is as high as 957 and 510 K for Co2F2 and Co2Cl2, respectively, because of the strong direct exchange interaction. Different from being obtained by mechanical or liquid exfoliation from van der Waals layered structures, our study opens up new possibilities to search for novel 2D ferromagnets from the elemental ferromagnets and provides opportunities for realizing realistic ultra-thin spintronic devices.

2.
Asian J Androl ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162146

RESUMO

A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China). Clinical characteristics, including foreskin length, were collected, and sexual function was assessed by the International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires. Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction. Among the 2721 erectile dysfunction (ED) patients and 1064 premature ejaculation (PE) patients, 301 (11.1%) ED patients and 135 (12.7%) PE patients had redundant foreskin, respectively. Men in the PE group were more likely to have redundant foreskin than men in the non-PE group (P = 0.004). Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED (adjusted odds ratio [aOR] = 1.31, adjusted P = 0.04), moderate PE (aOR = 1.38, adjusted P = 0.02), and probable PE (aOR = 1.37, adjusted P = 0.03) after adjusting for confounding variables. Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction, especially in PE patients. Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.

3.
ACS Nano ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143650

RESUMO

Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.

4.
J Agric Food Chem ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137283

RESUMO

Circular bacteriocins are known for their structural stability and effective antimicrobial properties, positioning them as potential natural food preservatives. However, their widespread application is impeded by restricted availability. This research developed a total biosynthesis platform for circular bacteriocins, with a focus on AS-48 by involving recombinant production of the linear precursor in Escherichia coli, followed by enzymatic cyclization of the precursor into cyclic AS-48 using the ligase butelase-1 in vitro. An important discovery is that, aside from fusion tags, the C-terminal motif LE and LEKKK also could affect the expression yield of the precursor. This biosynthesis platform is both versatile and high-yielding, achieving yields of 10-20 mg/L of AS-48. Importantly, the biosynthetic AS-48 exhibited a secondary structure and antimicrobial activities comparable to those of the native molecules. As such, this work proposes an effective synthetic approach for circular bacteriocins, facilitating their advancement and application in the food industry.

5.
J Gynecol Obstet Hum Reprod ; 53(9): 102829, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39096881

RESUMO

BACKGROUND: Elagolix, an approved non-peptide GnRH antagonist, shows promise in relieving endometriosis-related pain, but its short- and mid-term efficacy and potential side effects are still under investigation. OBJECTIVE: The aim is to provide data for therapeutic applications by methodically evaluating elagolix's safety and effectiveness in treating endometriosis-related pain. METHODS: Databases such as PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and others were thoroughly searched. The search time was from the establishment date to September 2023. The study included randomized controlled trials (RCTs) that compared the efficacy of elagolix versus placebo in treating endometriosis-associated pain. After data extraction and literature scanning, quality assessment was carried out using Quality evaluation was carried out using the bias risk assessment tool suggested by the Cochrane Reviewers' Handbook 5.1.0 after literature screening and data extraction. Stata 15.0 was used to do the meta-analysis. RESULTS: In total, five RCTs involving 2056 patients were included in the analysis. The meta-analysis demonstrated a significant superiority of elagolix over placebo in the management of endometriosis-related pain, specifically in endometriosis pain [WMD=-0.77, 95% CI (-1.00, -0.53), P<0.001], as well as in non-menstrual pelvic pain, daily assessment of dysmenorrhea (DYS), and dyspareunia (DYSP), all of which are associated with endometriosis. Regarding safety, no discernible variation was observed in the incidence of serious adverse responses between the elagolix and placebo groups [RR=0.90, 95% CI (0.58, 1.40), P=0.643]. Conversely, the elagolix group exhibited a significantly higher incidence rate of general adverse responses [RR = 1.34, 95% CI (1.18, 1.52), P<0.001] compared to the control group. CONCLUSIONS: The efficacy of elagolix in reducing pain in premenopausal women with endometriosis has been demonstrated over the short- to mid-term. However, careful monitoring for potential adverse effects is essential throughout the treatment duration.

6.
Histochem Cell Biol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093409

RESUMO

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

7.
Front Nutr ; 11: 1383658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988853

RESUMO

Background: High dietary protein intake exacerbates proteinuria in individuals with diabetic kidney disease (DKD). However, studies on the impacts of low protein diet (LPD) on DKD have yielded conflicting results. Furthermore, patient compliance to continuous protein restriction is challenging. Objective: The current study aims to investigate the effects of intermittent protein restriction (IPR) on disease progression of DKD. Methods: Diabetic KK-Ay mice were used in this study. For the IPR treatment, three consecutive days of LPD were followed by four consecutive days of normal protein diet (NPD) within each week. For early intervention, mice received IPR before DKD onset. For late intervention, mice received IPR after DKD onset. In both experiments, age-matched mice fed continuous NPD served as the control group. Kidney morphology, structure and function of mice in different groups were examined. Results: Intermittent protein restriction before DKD onset ameliorated pathological changes in kidney, including nephromegaly, glomerular hyperfiltration, tubular injuries and proteinuria, without improving glycemic control. Meanwhile, IPR initiated after DKD onset showed no renoprotective effects despite improved glucose homeostasis. Conclusion: Intermittent protein restriction before rather than after DKD onset protects kidneys, and the impacts of IPR on the kidneys are independent of glycemic control. IPR shows promise as an effective strategy for managing DKD and improving patient compliance.

8.
J Med Chem ; 67(14): 12314-12330, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38962837

RESUMO

Targeting c-Met is a clinical trend for the precise treatment of HCC, but the potential issue of acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease treatment and overcoming drug resistance due to its special mechanism of action. In this study, we designed and synthesized two series of novel c-Met degraders and conducted a systematic biological evaluation of the optimal compound H11. H11 exhibited good c-Met degradation activity and anti-HCC activity. Importantly, H11 also demonstrated more potent inhibitory activity against Ba/F3-TPR-MET-D1228N and Ba/F3-TPR-MET-Y1230H cell lines than did tepotinib. In summary, H11 displayed potent anti-HCC activity as a degrader and may overcome resistance to type Ib inhibitors, making it a new therapeutic strategy for HCC with MET alterations.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas c-met , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Animais , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas , Proteólise/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/uso terapêutico , Camundongos
9.
Adv Mater ; 36(33): e2401561, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38949414

RESUMO

Digital light processing (DLP) is a 3D printing technology offering high resolution and speed. Printable materials are commonly based on multifunctional monomers, resulting in the formation of thermosets that usually cannot be reprocessed or recycled. Some efforts are made in DLP 3D printing of thermoplastic materials. However, these materials exhibit limited and poor mechanical properties. Here, a new strategy is presented for DLP 3D printing of thermoplastics based on a sequential construction of two linear polymers with contrasting (stiff and flexible) mechanical properties. The inks consist of two vinyl monomers, which lead to the stiff linear polymer, and α-lipoic acid, which forms the flexible linear polymer via thermal ring-opening polymerization in a second step. By varying the ratio of stiff and flexible linear polymers, the mechanical properties can be tuned with Young's modulus ranging from 1.1 GPa to 0.7 MPa, while the strain at break increased from 4% to 574%. Furthermore, these printed thermoplastics allow for a variety of reprocessability pathways including self-healing, solvent casting, reprinting, and closed-loop recycling of the flexible polymer, contributing to the development of a sustainable materials economy. Last, the potential of the new material in applications ranging from soft robotics to electronics is demonstrated.

10.
Int J Biol Macromol ; 276(Pt 2): 133933, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025194

RESUMO

Butelase-1, the fastest known Asn/Asp-specific peptide ligase capable of catalyzing peptide ligation and cyclization, holds promising application prospects in the fields of food and biology. However, limited research exists on its recombinant expression and potential applications in peptide drugs. In this study, the activity of recombinantly-produced butelase-1 was enhanced by co-expressing it with a molecular chaperone in the SHuffle T7 strain. By introducing single or multiple synonymous rare codons at the beginning of the coding regions of beta-strand or alpha-helix, in combination with ribosomal binding site engineering, the activity of butelase-1 could be further improved. Consequently, the butelase-1 with a specific activity of 386.93 U/mg and a catalytic efficiency of 11,048 M-1 s-1 was successfully prepared in E. coli, resulting in a total activity of 8183.54 U/L and a yield of about 100 mg/L. This optimized butelase-1 was then used to efficiently cyclize the redesigned anti-cancer peptide lunasin, leading to enhanced bioavailability and anti-cancer effects. Overall, this study not only provided valuable biotechnology strategies for improving the recombinant expression of butelase-1 but also demonstrated a successful application for enhancing the biological efficacy of anti-cancer peptides.


Assuntos
Antineoplásicos , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Humanos , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Expressão Gênica , Animais , Camundongos
11.
Genomics ; 116(5): 110901, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39047876

RESUMO

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

12.
J Colloid Interface Sci ; 675: 569-579, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38986330

RESUMO

Affinity and storage capacity for zinc ions of the electrode materials are crucial factors on the properties of zinc ion hybrid capacitors (ZHICs). Wasted pulping liquor with abundant carbohydrates, lignin and inorganic matter served as a unique precursor to produce embedded oxygen-doped hierarchical porous carbon directly through a one-step carbonization process in this investigation. In carbonization process, lignin can serve effectively as the carbon framework, carbohydrates not only act as sacrificial templates but also offer a plentiful oxygen source which can increase the affinity for Zn2+, and sodium-containing inorganic substances plays a role as hard templates to optimize the pore structure. The resulting porous carbon under carbonization temperature of 800 °C shows a high specifical area of 2186 m2g-1 with oxygen content of 4.8 %, which can reduce the adsorption energy of Zn2+ from -0.16 eV to -0.32 eV through electrochemical techniques and density functional theory (DFT) calculations, the incorporation of oxygen was demonstrated to enhance the adsorption and desorption kinetics of Zn2+, suggesting a bright future for application in the domain of energy storage. The resulting ZIHC assembly showcases a notable energy density of 84.6 Wh kg-1 at a power density of 359 W kg-1. Remarkably, even after 10,000 charge and discharge cycles, it exhibits exceptional cycle stability with retaining 86.56 % of its capacity. Consequently, this approach provides fresh insights for exploring the facile and commercial fabrication of biomass-derived cathodes for ZIHCs, thereby propelling the progress of eco-friendly energy storage devices.

13.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38949588

RESUMO

Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.


Assuntos
Cardiolipinas , Corantes Fluorescentes , Lipossomas Unilamelares , Cardiolipinas/química , Corantes Fluorescentes/química , Lipossomas Unilamelares/química , Propriedades de Superfície , Lipossomos/química , Cloreto de Sódio/química , Tensoativos/química , Estrutura Molecular
14.
Sci Adv ; 10(28): eadn0960, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996025

RESUMO

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.


Assuntos
Trifosfato de Adenosina , Triterpenos Pentacíclicos , Pró-Fármacos , Espécies Reativas de Oxigênio , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Trifosfato de Adenosina/metabolismo , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Linhagem Celular Tumoral , Triterpenos/química , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Quelantes/química , Quelantes/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos , Liberação Controlada de Fármacos , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos Férricos/química
15.
Anal Chem ; 96(29): 11742-11750, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-38980807

RESUMO

Stroke is an acute injury of the central nervous system caused by the disorders of cerebral blood circulation, which has become one of the major causes of disability and death. Hemorrhage, particularly subarachnoid hemorrhage (SAH), is one of the poorest prognostic factors in stroke, which is related to the thrombolytic therapy, and has been considered very dangerous. In this context, the MR angiography with high sensitivity and resolution has been developed based on biocompatible paramagnetic ultrasmall NaGdF4 nanoprobes. Owing to the appropriate hydrodynamic diameter, the nanoprobe can be confined inside the blood vessels and it only extravasates at the vascular injury site when the bleeding occurs. Relying on this property, the three-dimensional (3D) anatomic structures of artery occlusion of stroke rat can be precisely visualized; reperfusion-related SAH has been successfully visualized and identified. Benefiting from the long blood half-life of the nanoprobe, the observation window of MR angiography can last for the whole period of reperfusion, thereby monitoring the probable SAH in real time during thrombolytic therapy. More importantly, through reconstruction of multiparametric MRI, the arterial occlusion, cerebral ischemic region, and SAH can be simultaneously visualized in vivo in a 3D manner for the first time. Therefore, the current study provides a novel approach for both noninvasive 3D vascular visualization and hemorrhage alert, which possesses great prospects for clinical translation.


Assuntos
AVC Isquêmico , Angiografia por Ressonância Magnética , Hemorragia Subaracnóidea , Animais , Hemorragia Subaracnóidea/diagnóstico por imagem , Ratos , AVC Isquêmico/diagnóstico por imagem , Ratos Sprague-Dawley , Masculino , Gadolínio/química , Reperfusão
16.
J Chem Theory Comput ; 20(12): 5043-5057, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38836623

RESUMO

We present an open-source MLatom@XACS software ecosystem for on-the-fly surface hopping nonadiabatic dynamics based on the Landau-Zener-Belyaev-Lebedev algorithm. The dynamics can be performed via Python API with a wide range of quantum mechanical (QM) and machine learning (ML) methods, including ab initio QM (CASSCF and ADC(2)), semiempirical QM methods (e.g., AM1, PM3, OMx, and ODMx), and many types of ML potentials (e.g., KREG, ANI, and MACE). Combinations of QM and ML methods can also be used. While the user can build their own combinations, we provide AIQM1, which is based on Δ-learning and can be used out-of-the-box. We showcase how AIQM1 reproduces the isomerization quantum yield of trans-azobenzene at a low cost. We provide example scripts that, in dozens of lines, enable the user to obtain the final population plots by simply providing the initial geometry of a molecule. Thus, those scripts perform geometry optimization, normal mode calculations, initial condition sampling, parallel trajectories propagation, population analysis, and final result plotting. Given the capabilities of MLatom to be used for training different ML models, this ecosystem can be seamlessly integrated into the protocols building ML models for nonadiabatic dynamics. In the future, a deeper and more efficient integration of MLatom with Newton-X will enable a vast range of functionalities for surface hopping dynamics, such as fewest-switches surface hopping, to facilitate similar workflows via the Python API.

17.
Virulence ; 15(1): 2367671, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38910312

RESUMO

Viral diseases are among the main threats to public health. Understanding the factors affecting viral invasion is important for antiviral research. Until now, it was known that most viruses have very low plaque-forming unit (PFU)-to-particle ratios. However, further investigation is required to determine the underlying factors. Here, using quantitative single-particle analysis methods, the invasion of Semliki Forest virus (SFV), Japanese encephalitis virus (JEV), and influenza A virus (IAV) containing attachment to the cell surface, entry into the cell, transport towards the cell interior, and fusion with endosomes to release nucleocapsids were quantitatively analysed in parallel. It was found that for SFV with an PFU-to-particle ratio of approximately 1:2, an entry efficiency of approximately 31% limited infection. For JEV, whose PFU-to-particle ratio was approximately 1:310, an attachment efficiency of approximately 27% and an entry efficiency of 10% were the main factors limiting its infection. Meanwhile, for IAV with PFU-to-particle ratios of 1:8100, 5% attachment efficiency, 9% entry efficiency, and 53% fusion efficiency significantly limited its infection. These results suggest that viruses with different infectivities have different limited steps in the invasion process. Moreover, there are significant differences in attachment efficiencies among viruses, emphasizing the pivotal role of attachment in viral invasion. The influence of the virus purification method on virus invasion was also investigated. This study, for the first time, reports the efficiencies of different stages of virus invasion, leading to a better understanding of virus invasion and providing a protocol to quantitatively analyse the virus invasion efficiency.


Assuntos
Vírus da Influenza A , Vírus da Floresta de Semliki , Internalização do Vírus , Vírus da Influenza A/fisiologia , Animais , Vírus da Floresta de Semliki/fisiologia , Humanos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Linhagem Celular , Ligação Viral , Endossomos/virologia
18.
Int J Surg ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857504

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in cancer tissue. The lack of specific biomarkers makes the diagnosis and prognosis of TNBC challenging. METHOD: A comprehensive literature review and bibliometric analysis was performed using CiteSpace, VOSviewer and Scimago Graphica. RESULTS: TNBC biomarker research has been growing rapidly in recent years, reflecting the enormous academic interest in TNBC biomarker research. A total of 127 journals published relevant studies and 1749 authors were involved in the field, with developed countries such as the United States, France, and the United Kingdom contributing greatly to the field. Collaborative network analysis found that the research in this field has not yet formed good communication and interaction, and the partnership should be strengthened in the future in order to promote the in-depth development of TNBC biomarker research. Comprehensive analysis of keywords and co-cited literature, etc. found that TNBC biomarker research mainly focuses on immune checkpoint markers, microenvironment-related markers, circulating tumour DNA, metabolic markers, genomics markers and so on. These research hotspots will help to better understand the molecular characteristics and biological processes of TNBC, and provide more accurate biomarkers for its diagnosis, treatment and prognosis. CONCLUSIONS: The bibliometric analysis highlighted global trends and key directions in TNBC biomarker research. Future developments in TNBC biomarker research are likely to be in the direction of multi-omics integration, meticulous study of the microenvironment, targeted therapeutic biomarkers, application of liquid biopsy, application of machine learning and artificial intelligence, and individualised therapeutic strategies. Young scholars should learn and collaborate across disciplines, pay attention to new technologies and methods, improve their data analysis skills, and continue to follow up on the latest research trends in order to meet the challenges and opportunities in the field of TNBC biomarkers.

19.
Water Sci Technol ; 89(11): 2907-2920, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38877621

RESUMO

In this study, three sequencing batch biofilter granular reactors (SBBGRs) were employed to treat model lignin wastewater containing different lignin models (2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin). After 40 days of cultivation, uniform-shaped aerobic granular sludge (AGS) was successfully developed through nutrient supplementation with synthetic wastewater. During the acclimation stage, the chemical oxygen demand (COD) reduction efficiencies of the three reactors showed a trend of initial decreasing (5-20%) and then recovering to a high reduction efficiency (exceeding 90%) in a short period of time. During the stable operation stage, all three reactors achieved COD reduction efficiencies exceeding 90%. These findings indicated the cultivated AGS's robust resistance to changes in lignin models in water. UV-Vis spectra analysis confirmed the effective degradation of the three lignin models. Microbiological analysis showed that Proteobacteria and Bacteroidetes were always the dominant phyla. At the genus level, while Acinetobacter (15.46%) dominated in the inoculation sludge, Kapabacteriales (7.93%), SBR1031 (11.77%), and Chlorobium (25.37%) were dominant in the three reactors (for 2,6-dimethoxyphenol, 4-methoxyphenol, and vanillin) after degradation, respectively. These findings demonstrate that AGS cultured with SBBGR effectively degrades lignin models, with different dominant strains observed for various lignin models.


Assuntos
Reatores Biológicos , Lignina , Esgotos , Esgotos/microbiologia , Lignina/metabolismo , Lignina/química , Aerobiose , Filtração/métodos , Eliminação de Resíduos Líquidos/métodos , Bactérias/metabolismo
20.
Materials (Basel) ; 17(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38894015

RESUMO

Steel with a combination of strength and plasticity is prevalently demanded for lightweight design and emission reductions in manufacturing. In this study, a high-strength Cr-Ni-Mo martensitic steel treated by quenching and partitioning (Q&P) and ultrasonic surface rolling (USR) processes was studied for both strength and plasticity enhancement. Specimens were austenitized at 850 °C and then quenched to 240 °C via cooling by water, oil, and normalization in quenching. This was followed by partitioning, in which two groups of specimens were heated to 370 °C and 350 °C for 45 min, respectively. At last, all the specimens were quenched to room temperature with the same methods of quenching. The highest tensile strength increased from 681.73 MPa to 1389.76 MPa when compared to as-received (AR) steel after the Q&P process. The USR process with a static force of 800 N further improved the tensile strength of specimens with high tensile strength after the Q&P process, which improved from 1389.76 MPa to 1586.62 MPa and the product's strength and elongation (PSE) increased from 15.76 GPa% to 15.9 GPa%, while the total elongation showed a mitigatory decrease from 11.34% to 10.02%. Tensile fractures were also studied and verified using a combination of strength and plasticity after a combined process of Q&P and USR.

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