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1.
Phys Rev Lett ; 132(22): 223202, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38877960

ABSTRACT

Attoclock provides a powerful tool for probing the ultrafast electron dynamics in strong laser fields. However, this technique has remained restricted to single electron or sequential double ionized electron dynamics. Here, we propose a novel attoclock scheme with a polarization-gated few-cycle laser pulse and demonstrate its application in timing the correlated-electron emission in strong field double ionization of argon. Our experimental measurements reveal that the correlated-electron emission occurs mainly through two channels with time differences of 234±22 as and 1043±73 as, respectively. Classical model calculations well reproduce the experimental results and deepen our understanding of ultrafast electron correlation dynamics.

2.
PLoS One ; 19(6): e0302098, 2024.
Article in English | MEDLINE | ID: mdl-38870135

ABSTRACT

Suitable combinations of observed datasets for estimating crop model parameters can reduce the computational cost while ensuring accuracy. This study aims to explore the quantitative influence of different combinations of the observed phenological stages on estimation of cultivar-specific parameters (CPSs). We used the CROPGRO-Soybean phenological model (CSPM) as a case study in combination with the Generalized Likelihood Uncertainty Estimation (GLUE) method. Different combinations of four observed phenological stages, including initial flowering, initial pod, initial grain, and initial maturity stages for five soybean cultivars from Exp. 1 and Exp. 3 described in Table 2 are respectively used to calibrate the CSPs. The CSPM, driven by the optimized CSPs, is then evaluated against two independent phenological datasets from Exp. 2 and Exp. 4 described in Table 2. Root means square error (RMSE) (mean absolute error (MAE), coefficient of determination (R2), and Nash Sutcliffe model efficiency (NSE)) are 15.50 (14.63, 0.96, 0.42), 4.76 (3.92, 0.97, 0.95), 4.69 (3.72, 0.98, 0.95), 3.91 (3.40, 0.99, 0.96) and 12.54 (11.67, 0.95, 0.60), 5.07 (4.61, 0.98, 0.93), 4.97 (4.28, 0.97, 0.94), 4.58 (4.02, 0.98, 0.95) for using one, two, three, and four observed phenological stages in the CSPs estimation. The evaluation results suggest that RMSE and MAE decrease, and R2 and NSE increase with the increase in the number of observed phenological stages used for parameter calibration. However, there is no significant reduction in the RMSEs (MAEs, NSEs) using two, three, and four observed stages. Relatively reliable optimized CSPs for CSMP are obtained by using at least two observed phenological stages balancing calibration effect and computational cost. These findings provide new insight into parameter estimation of crop models.


Subject(s)
Crops, Agricultural , Glycine max , Glycine max/growth & development , Crops, Agricultural/growth & development , Calibration , Models, Biological , Likelihood Functions , Uncertainty
3.
Neurochem Res ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38862726

ABSTRACT

Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.

4.
Ultrason Imaging ; : 1617346241259049, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38903053

ABSTRACT

Three-dimensional (3D) ultrasound imaging can be accomplished by reconstructing a sequence of two-dimensional (2D) ultrasound images. However, 2D ultrasound images usually suffer from low resolution in the elevation direction, thereby impacting the accuracy of 3D reconstructed results. The lateral resolution of 2D ultrasound is known to significantly exceed the elevation resolution. By combining scanning sequences acquired from orthogonal directions, the effects of poor elevation resolution can be mitigated through a composite reconstructing process. Moreover, capturing ultrasound images from multiple perspectives necessitates a precise probe positioning method with a wide angle of coverage. Optical tracking is popularly used for probe positioning for its high accuracy and environment-robustness. In this paper, a novel large-angle accurate optical positioning method is used for enhancing resolution in 3D ultrasound imaging through orthogonal-view scanning and composite reconstruction. Experiments on two phantoms proved that our method could significantly improve reconstruction accuracy in the elevation direction of the probe compared with single-angle parallel scanning. The results indicate that our method holds the potential to improve current 3D ultrasound imaging techniques.

5.
Talanta ; 278: 126449, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38908140

ABSTRACT

Human papillomavirus (HPV) is a prevalent sexually transmitted pathogen associated with cervical cancer. Detecting high-risk HPV (hr-HPV) infections is crucial for cervical cancer prevention, particularly in resource-limited settings. Here, we present a highly sensitive and specific sensor for HPV-16 detection based on CRISPR/Cas12a coupled with enhanced single nanoparticle dark-field microscopy (DFM) imaging techniques. Ag-Au satellites were assembled through the hybridization of AgNPs-based spherical nucleic acid (Ag-SNA) and AuNPs-based spherical nucleic acid (Au-SNA), and their disassembly upon target-mediated cleavage by the Cas12a protein was monitored using DFM for HPV-16 quantification. To enhance the cleavage efficiency and detection sensitivity, the composition of the ssDNA sequences on Ag-SNA and Au-SNA was optimized. Additionally, we explored using the SynSed technique (synergistic sedimentation of Brownian motion suppression and dehydration transfer) as an alternative particle transfer method in DFM imaging to traditional electrostatic deposition. This addresses the issue of inconsistent deposition efficiency of Ag-Au satellites and their disassembly due to their size and charge differences. The sensor achieved a remarkable limit of detection (LOD) of 10 fM, lowered by 9-fold compared to traditional electrostatic deposition methods. Clinical testing in DNA extractions from 10 human cervical swabs demonstrated significant response differences between the positive and negative samples. Our sensor offers a promising solution for sensitive and specific HPV-16 detection, with implications for cancer screening and management.

6.
Cells ; 13(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891036

ABSTRACT

Small extracellular vesicles were shown to have similar functional roles to their parent cells without the defect of potential tumorigenicity, which made them a great candidate for regenerative medicine. The last twenty years have witnessed the rapid development of research on small extracellular vesicles. In this paper, we employed a scientometric synthesis method to conduct a retrospective analysis of small extracellular vesicles in the field of bone-related diseases. The overall background analysis consisted the visualization of the countries, institutions, journals, and authors involved in research. The current status of the research direction and future trends were presented through the analysis of references and keywords, which showed that engineering strategies, mesenchymal stem cell derived exosomes, and cartilage damage were the most concerning topics, and scaffold, osteoarthritis, platelet-rich plasma, and senescence were the future trends. We also discussed the current problems and challenges in practical applications, including the in-sight mechanisms, the building of relevant animal models, and the problems in clinical trials. By using CiteSpace, VOSviewer, and Bibliometrix, the presented data avoided subjective selectivity and tendency well, which made the conclusion more reliable and comprehensive. We hope that the findings can provide new perspectives for researchers to understand the evolution of this field over time and to search for novel research directions.


Subject(s)
Bone Diseases , Extracellular Vesicles , Extracellular Vesicles/metabolism , Humans , Animals , Bone Diseases/pathology , Mesenchymal Stem Cells/metabolism
7.
J Environ Manage ; 362: 121313, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38824887

ABSTRACT

As global climate change progresses, soil will experience prolonged periods of both drought and heavy rainfall, leading to a more frequent drought-re-wetting process that may impact the ecosystem's carbon (C) cycle. However, understanding the extent to which different water conditions and wet-dry cycles alter the process of soil organic carbon (SOC) mineralization remains limited. Therefore, our study focused on the dammed land unique to the Loess Plateau, silted by check dams constructed for erosion control. We implemented three water gradients-drought (30% WHC), water stress (100% WHC), and wet-dry cycling (30-100%)-indoors to observe the SOC mineralization process five times. We identified a transient excitation effect of the wet-dry cycles on SOC mineralization. Soil mineralization decreased gradually with the alternation of wet-dry cycles. The wet-dry cycles not only significantly impacted the contents of SOC and TN but also stimulated the activities of enzymes related to C and N cycles. As the cycle frequency increased, the utilization of C sources by soil microorganisms gradually decreased, and the dominance of carbohydrates, amines, and acids evolved into a single acid, esters, or alcohols. Phosphatase and Chloroflexi were the main factors influencing SOC mineralization under drought stress, while TN and Ascomycota were the primary factors under water stress. SOC and Gemmatimonadetes were the main limiting factors for SOC mineralization under the wet-dry cycles. Additionally, we quantified the direct and interactive contributions of each factor to SOC mineralization. The direct contributions of drought stress, water stress, and the wet-dry cycles to SOC mineralization were 0.961, 0.736, and 0.942, respectively. This study contributes to a more comprehensive understanding of the mechanisms underlying SOC mineralization in the Loess Plateau under changing conditions.


Subject(s)
Carbon , Soil , Soil/chemistry , Droughts , Ecosystem , Climate Change , Carbon Cycle , Water
8.
Sci Rep ; 14(1): 13432, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862586

ABSTRACT

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.


Subject(s)
Breast Neoplasms , Cyclophosphamide , T-Lymphocytes, Regulatory , Humans , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/drug effects , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Aged , Retrospective Studies , Administration, Oral , Middle Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Metastasis , Treatment Outcome
9.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 21-27, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836686

ABSTRACT

This research aimed to investigate the effect of slow-released angiogenin by silicon micro-needle on angiogenesis in the Choke zone of dorsal multiple-territory perforator flap in rats, as well as its mechanism. Thirty-six adult Sprague-Dawley (SD) rats were randomly divided into control group, model group, and four experimental groups. In model group, slow-release saline through a silicon micro-needle was placed in choke II zone of the flap 7 days before the operation. For rats in four experimental groups, angiogenin was released via micro-needle in the choke I and choke II zones of the cross-zone flap 7 days before and 3 days before flap surgery, respectively. A 12 cm × 3 cm cross-zone perforator flap model was made on the back of all five groups. The flap survival rate in slow-release angiopoietin group was statistically higher than that in model group (P<0.05). Angiogenin in choke zone of the flap was increased in slow-release angiogenin group (P<0.05). In slow-release angiogenin group, the micro-vessel density was increased and the arteriovenous diameter was decreased, while the arteriovenous diameter was increased in model group (P<0.05). The levels of vascular endothelial growth factor A (VEGF-A) and angiotensin 1 (ANG-1) in choke zone were both elevated in slow-release angiogenin group (P<0.05). The expression of CD31 was significantly elevated in flaps of experimental groups (P<0.05). Micro-needle to slow release Angiogenin can increase the drug concentration in the tissues of the choke zone, promote the vascularization of rat dorsal crossover area perforator flap, reduce the possibility of flap ischemic necrosis, and improve the flap survival rate.


Subject(s)
Perforator Flap , Rats, Sprague-Dawley , Ribonuclease, Pancreatic , Animals , Ribonuclease, Pancreatic/metabolism , Perforator Flap/blood supply , Male , Silicon/chemistry , Neovascularization, Physiologic/drug effects , Needles , Rats , Vascular Endothelial Growth Factor A/metabolism , Delayed-Action Preparations
10.
Opt Express ; 32(12): 20682-20694, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859444

ABSTRACT

Fiber-bundle-based endoscopy, with its ultrathin probe and micrometer-level resolution, has become a widely adopted imaging modality for in vivo imaging. However, the fiber bundles introduce a significant honeycomb effect, primarily due to the multi-core structure and crosstalk of adjacent fiber cores, which superposes the honeycomb pattern image on the original image. To tackle this issue, we propose an iterative-free spatial pixel shifting (SPS) algorithm, designed to suppress the honeycomb effect and enhance real-time imaging performance. The process involves the creation of three additional sub-images by shifting the original image by one pixel at 0, 45, and 90 degree angles. These four sub-images are then used to compute differential maps in the x and y directions. By performing spiral integration on these differential maps, we reconstruct a honeycomb-free image with improved details. Our simulations and experimental results, conducted on a self-built fiber bundle-based endoscopy system, demonstrate the effectiveness of the SPS algorithm. SPS significantly improves the image quality of reflective objects and unlabeled transparent scattered objects, laying a solid foundation for biomedical endoscopic applications.

11.
Ann Plast Surg ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38896852

ABSTRACT

BACKGROUND: Reconstruction of head and neck soft tissue defects with bone exposure is both challenging and technically demanding for plastic surgeon. Objectives in head and neck soft tissue defects with bone exposure reconstruction are consistent restoration of functionality while also improving appearance. This study retrospectively analyzed the results of head and neck reconstructions using various types of free flaps over the past 4 years. METHODS: A retrospective analysis was conducted from June 2019 to June 2023 on 12 patients treated at our hospital for head and neck soft tissue defects with bone exposure due to various causes. These included 4 cases of trauma from car accidents, 1 burn case, and 7 postoperative malignant tumor removals. The defect sizes ranged from 4 × 6 to 15 × 45 cm. Different free flaps were used for repair based on the defect, including 6 anterolateral thigh flaps, 3 forearm flaps, 2 latissimus dorsi flaps, and 1 dorsalis pedis flap. Flaps were designed and harvested to match the defect size and transplanted via anastomosed vessels. RESULTS: All 12 flaps survived successfully. One patient required flap thinning surgery postoperatively. All patients were followed up for over 3 months, showing good color and texture of the transplanted flaps, satisfactory healing, and significant aesthetic improvement. Donor sites showed significant scarring without functional impairment. CONCLUSION: Free flap repair for head and neck soft tissue defects with bone exposure is feasible and yields good results.

12.
Anal Methods ; 16(23): 3607-3619, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38805018

ABSTRACT

Realizing sensitive and efficient detection of biomolecules and drug molecules is of great significance. Among the detection methods that have been proposed, electrochemical sensing is favored for its outstanding advantages such as simple operation, low cost, fast response and high sensitivity. The unique structure and properties of surfactants have led to a wide range of applications in the field of electrochemical sensors and biosensors for biomolecules and drug molecules. Through the comparative analysis of reported works, this paper summarizes the application modes of surfactants in electrochemical sensors and biosensors for biomolecules and drug molecules, explores the possible electrocatalytic mechanism of their action, and looks forward to the development trend of their applications. This review is expected to provide some new ideas for subsequent related research work.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Surface-Active Agents , Biosensing Techniques/methods , Surface-Active Agents/chemistry , Electrochemical Techniques/methods , Pharmaceutical Preparations/analysis , Pharmaceutical Preparations/chemistry , Humans
13.
Poult Sci ; 103(7): 103820, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759565

ABSTRACT

The "KNDy neurons" located in the hypothalamic arcuate nucleus (ARC) of mammals are known to co-express kisspeptin, neurokinin B (NKB), and dynorphin (DYN), and have been identified as key mediators of the feedback regulation of steroid hormones on gonadotropin-releasing hormone (GnRH). However, in birds, the genes encoding kisspeptin and its receptor GPR54 are genomic lost, leaving unclear mechanisms for feedback regulation of GnRH by steroid hormones. Here, the genes tachykinin 3 (TAC3) and prodynorphin (PDYN) encoding chicken NKB and DYN neuropeptides were successfully cloned. Temporal expression profiling indicated that TAC3, PDYN and their receptor genes (TACR3, OPRK1) were mainly expressed in the hypothalamus, with significantly higher expression at 30W than at 15W. Furthermore, overexpression or interference of TAC3 and PDYN can regulate the GnRH mRNA expression. In addition, in vivo and in vitro assays showed that estrogen (E2) could promote the mRNA expression of TAC3, PDYN, and GnRH, as well as the secretion of GnRH/LH. Mechanistically, E2 could dimerize the nuclear estrogen receptor 1 (ESR1) to regulate the expression of TAC3 and PDYN, which promoted the mRNA and protein expression of GnRH gene as well as the secretion of GnRH. In conclusion, these results revealed that E2 could regulate the GnRH expression through TAC3 and PDYN systems, providing novel insights for reproductive regulation in chickens.


Subject(s)
Avian Proteins , Chickens , Gonadotropin-Releasing Hormone , Protein Precursors , Tachykinins , Animals , Chickens/genetics , Chickens/metabolism , Gonadotropin-Releasing Hormone/metabolism , Gonadotropin-Releasing Hormone/genetics , Tachykinins/genetics , Tachykinins/metabolism , Protein Precursors/genetics , Protein Precursors/metabolism , Avian Proteins/genetics , Avian Proteins/metabolism , Estrogens/metabolism , Enkephalins/genetics , Enkephalins/metabolism , Gene Expression Regulation/drug effects , Female , Male
15.
BMC Psychiatry ; 24(1): 354, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730372

ABSTRACT

BACKGROUND: Little is known about the state of psychological distress of the elderly in China, and research on specific subgroups such as Hakka older adults is almost lacking. This study investigates psychache and associated factors among Hakka elderly in Fujian, China. METHODS: The data analysed in this study were derived from China's Health-Related Quality of Life Survey for Older Adults 2018. The Chinese version of the Psychache Scale (PAS) was used to assess the frequency and intensity of psychache in Hakka older adults. Generalized linear regression analysis was conducted to identify the main socio-demographic factors associated with psychache overall and its frequency and intensity. RESULTS: A total of 1,262 older adults participated, with mean scores of 18.27 ± 6.88 for total PAS, 12.50 ± 4.79 for PAS-Frequency and 5.77 ± 2.34 for PAS-Intensity. On average, females scored higher than males on PAS-Frequency (ß = 0.84, 95% CI = 0.34, 1.35) and PAS-Intensity (ß = 0.48, 95% CI = 0.22, 0.73). Older adults currently living in towns (ß = -2.18, 95% CI = -2.81, -1.54), with their spouse only (ß = -3.71, 95% CI = -4.77, -2.65), or with children (ß = -3.24, 95% CI = -4.26, -2.22) were more likely to score lower on PAS-Frequency. Conversely, older adults who were regular sleepers (ß = -1.19, 95% CI =-1.49, -0.88) or lived with their spouse only (ß = -1.25, 95% CI = -1.78, -0.72) were more likely to score lower on PAS-Intensity. CONCLUSION: Among Hakka elderly, we found a higher frequency and greater intensity of psychache in females, those with poor health status, irregular sleepers, rural residents, solo dwellers, those with below CNY 10,000 in personal savings, and the medically uninsured. The study's findings indicate that policymakers should give more attention to the susceptible population and implement practical interventions to reduce their psychological burden.


Subject(s)
Quality of Life , Humans , Male , Female , China/epidemiology , Aged , Aged, 80 and over , Quality of Life/psychology , Psychological Distress , Middle Aged , Sex Factors
16.
J Agric Food Chem ; 72(21): 12240-12250, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38764183

ABSTRACT

LIM domain binding 3 (LDB3) serves as a striated muscle-specific Z-band alternatively spliced protein that plays an important role in mammalian skeletal muscle development, but its regulatory role and molecular mechanism in avian muscle development are still unclear. In this study, we reanalyzed RNA sequencing data sets of 1415 samples from 21 chicken tissues published in the NCBI GEO database. First, three variants (LDB3-X, LDB3-XN1, and LDB3-XN2) generated by alternative splicing of the LDB3 gene were identified in chicken skeletal muscle, among which LDB3-XN1 and LDB3-XN2 are novel variants. LDB3-X and LDB3-XN1 are derived from exon skipping in chicken skeletal muscle at the E18-D7 stage and share three LIM domains, but LDB3-XN2 lacks a LIM domain. Our results preliminarily suggest that the formation of three variants of LDB3 is regulated by RBM20. The three splice isomers have divergent functions in skeletal muscle according to in vitro and in vivo assays. Finally, we identified the mechanism by which different variants play different roles through interactions with IGF2BP1 and MYHC, which promote the proliferation and differentiation of chicken myoblasts, in turn regulating chicken myogenesis. In conclusion, this study revealed the divergent roles of three LDB3 variants in chicken myogenesis and muscle remodeling and demonstrated their regulatory mechanism through protein-protein interactions.


Subject(s)
Alternative Splicing , Chickens , LIM Domain Proteins , Muscle Development , Muscle, Skeletal , Animals , Chickens/genetics , Muscle, Skeletal/metabolism , Muscle, Skeletal/chemistry , Muscle, Skeletal/growth & development , Muscle Development/genetics , LIM Domain Proteins/genetics , LIM Domain Proteins/metabolism , Myoblasts/metabolism , Avian Proteins/genetics , Avian Proteins/metabolism , Avian Proteins/chemistry , Cell Differentiation , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/chemistry
17.
Biomacromolecules ; 25(5): 3190-3199, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38693753

ABSTRACT

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.


Subject(s)
Anti-Bacterial Agents , Nanoparticles , Nitric Oxide , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Nitric Oxide/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice , Animals , RAW 264.7 Cells , Nanoparticles/chemistry , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Immunotherapy/methods , Vancomycin/pharmacology , Vancomycin/chemistry , Vancomycin/administration & dosage , Bacterial Infections/drug therapy , Trehalose/chemistry , Trehalose/pharmacology
18.
Light Sci Appl ; 13(1): 108, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38714677

ABSTRACT

Strong-field photoelectron holography is promising for the study of electron dynamics and structure in atoms and molecules, with superior spatiotemporal resolution compared to conventional electron and X-ray diffractometry. However, the application of strong-field photoelectron holography has been hindered by inter-cycle interference from multicycle fields. Here, we address this challenge by employing a near-single-cycle field to suppress the inter-cycle interference. We observed and separated two distinct holographic patterns for the first time. Our measurements allow us not only to identify the Gouy phase effect on electron wavepackets and holographic patterns but also to correctly extract the internuclear separation of the target molecule from the holographic pattern. Our work leads to a leap jump from theory to application in the field of strong-field photoelectron holography-based ultrafast imaging of molecular structures.

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