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1.
Pest Manag Sci ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030887

ABSTRACT

BACKGROUND: Crop diseases can lead to significant yield losses and food shortages if not promptly identified and managed by farmers. With the advancements in convolutional neural networks (CNN) and the widespread availability of smartphones, automated and accurate identification of crop diseases has become feasible. However, although previous studies have achieved high accuracy (>95%) under laboratory conditions (Lab) using mixed data sets of multiple crops, these models often falter when deployed under field conditions (Field). In this study, we aimed to evaluate disease identification accuracy under Lab, Field, and Mixed (Lab and Field) conditions using an assembled data set encompassing 14 diseases of apple (Malus × domestica Borkh.), potato (Solanum tuberosum L.), and tomato (Solanum lycopersicum L.). In addition, we investigated the impact of model architectures, parameter sizes, and crop-specific models (CSMs) on accuracy, using DenseNets, ResNets, MobileNetV3, EfficientNet, and VGG Nets. RESULTS: Our results revealed a decrease in accuracy across all models from Lab (98.22%) to Mixed (91.76%) to Field (71.55%) conditions. Interestingly, disease classification accuracy showed minimal variation across model architectures and parameter sizes: Lab (97.61-98.76%), Mixed (90.76-92.31%), and Field (68.56-73.81%). Although CSMs were found to reduce inter-crop disease misclassifications, they also led to a slight increase in intra-crop misclassifications. CONCLUSION: Our findings underscore the importance of enriching data representation and volumes over employing new model architectures. Furthermore, the need for more field-specific images was highlighted. Ultimately, these insights contribute to the advancement of crop disease identification applications, facilitating their practical implementation in farmer's fields. © 2024 Society of Chemical Industry.

2.
Kaohsiung J Med Sci ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023189

ABSTRACT

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

3.
Sci Total Environ ; 948: 174700, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39002575

ABSTRACT

Global warming has led to severe land desertification on the Mongolian plateau. It puts great environmental pressure on vegetation communities. This pressure leads to fragmentation of land use and landscape patterns, thus triggering changes in the spatial distribution patterns of vegetation. The spatial distribution pattern of vegetation is crucial for the performance of its ecosystem services. However, there is not enough research on the relationship between large-scale spatial distribution patterns of vegetation and ecosystem services. Therefore, this study is to construct an ecological spatial network on the Mongolian Plateau based on landscape ecology and complex network theory. Combining pattern analysis methods to analyze the network, we obtained the spatial and temporal trends of forest and grass spatial distribution patterns from 2000 to 2100, and explored the relationship between the topological properties of source patches and ecosystem services in different patterns. It was found that there are four basic patterns of spatial distribution of forest and grass in the Mongolian Plateau. The Core-Linked Ring pattern accounts for 40.74 % and exhibits the highest stability. Under the SSP5-RCP8.5 scenario, source patches are reduced by 22.76 % in 2100. Topological indicators of source patches showed significant correlations with ecosystem services. For example, the CUE of grassland patches in the Centralized Star pattern was positively correlated with betweeness centrality. The most significant improvement in WUE after optimization is 19.90 % compared to pre-optimization. The conclusion of the study shows that the spatial distribution pattern of vegetation can be used to enhance the stability of ecological spatial network and improve ecosystem services at a larger scale. It can provide a certain reference for the study of spatial patterns of vegetation distribution in arid and semi-arid areas.

4.
Mar Drugs ; 22(7)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39057414

ABSTRACT

Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g-1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC50 values of 1.50 mg mL-1 and 1.66 mg mL-1, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC50 value of 0.71 mg mL-1. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Antioxidants , Arachis , Bacillus subtilis , Metalloproteases , Peptides , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Metalloproteases/chemistry , Metalloproteases/pharmacology , Arachis/chemistry , Bacillus subtilis/drug effects , Bacillus subtilis/enzymology , Peptides/pharmacology , Peptides/chemistry , Hydrolysis , Peptidyl-Dipeptidase A/metabolism , Peptidyl-Dipeptidase A/chemistry
5.
Oncoimmunology ; 13(1): 2376264, 2024.
Article in English | MEDLINE | ID: mdl-38988824

ABSTRACT

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.


Subject(s)
Apoptosis , B7-H1 Antigen , CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Animals , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , B7-H1 Antigen/immunology , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Mice , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Tumor Escape/genetics , Cell Line, Tumor , Cell Proliferation , Male , Female , Membrane Proteins/genetics , Membrane Proteins/metabolism , Immune Evasion , Immunoglobulins
6.
Nat Food ; 5(7): 550-556, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39009735

ABSTRACT

Both climate and impact models are essential for understanding and quantifying the impact of climate change on agricultural productivity. Multi-model ensembles have highlighted considerable uncertainties in these assessments, yet a systematic approach to quantify these uncertainties is lacking. We propose a standardized approach to attribute uncertainties in multi-model ensemble studies, based on insights from the Agricultural Model Intercomparison and Improvement Project. We find that crop model processes are the primary source of uncertainty in agricultural projections (over 50%), excluding unquantified hidden uncertainty that is not explicitly measured within the analyses. We propose multidimensional pathways to reduce uncertainty in climate change impact assessments.


Subject(s)
Agriculture , Climate Change , Uncertainty , Crops, Agricultural/growth & development , Models, Theoretical , Humans
7.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3320-3329, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041095

ABSTRACT

This study investigates the specific mechanisms of Huaier-induced mitochondrial apoptosis in colorectal cancer. HCT116 and SW480 cells were subjected to Huaier treatment. Cell proliferation and migration capabilities were examined through CCK-8 and scratch experiments, respectively. Apoptotic cells were clarified with Annexin-PE staining. DCFH-DA staining, malondialdehyde(MDA), and glutathione(GSH) were used to evaluate the oxidative stress damage level of cells. MitoSOX and JC-1 probes were used to selectively target mitochondria reactive oxygen species(mtROS) and mitochondria membrane potential(MMP) for the evaluation of mitochondria damage. Western blot(WB) experiment was performed to determine apoptosis proteins and PINK1/Parkin pathway. Experiments reveal that in different concentrations of Huaier treatment, the proliferation and migration capabilities of HCT116 and SW480 cells were both restrained. Additionally, mitochondrial apoptosis was activated. Compared with the control group, excessive ROS in colorectal cancer cells was generated in the Huaier group, while MDA increased, and GSH decreased, indicating oxidative stress damage. mtROS increased, and MMP decreased in colorectal cancer cells treated with Huaier, indicating mitochondrial damage. WB result revealed that Huaier suppressed the PINK1/Parkin pathway, hindered the clearance of impaired mitochondria, and subsequently facilitated apoptosis. In conclusion, Huaier impairs colorectal cancer cells through oxidative stress and mitochondria damage. Furthermore, it suppressed the PINK1/Parkin pathway, promoting mitochondria apoptosis in colorectal cancer cells.


Subject(s)
Apoptosis , Cell Proliferation , Colorectal Neoplasms , Mitochondria , Oxidative Stress , Reactive Oxygen Species , Humans , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/physiopathology , Apoptosis/drug effects , Oxidative Stress/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Cell Proliferation/drug effects , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Drugs, Chinese Herbal/pharmacology , Membrane Potential, Mitochondrial/drug effects , Cell Movement/drug effects
8.
Clin Nephrol ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037085

ABSTRACT

OBJECTIVE: To investigate the efficacy of sacubitril/valsartan in the treatment of peritoneal dialysis (PD) in patients with diabetes and heart failure with preserved ejection fraction (HFpEF). MATERIALS AND METHODS: Patients with diabetes who underwent PD and had HFpEF (n = 64) were divided into two groups: the experimental group (n = 31), which was administered sacubitril/valsartan, and the control group (n = 33), administered valsartan alone. Data were collected before and after treatment to compare the inter-group changes in cardiac function indexes, residual renal function (RRF), and PD adequacy indexes. RESULTS: Compared with the control group, the N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were lower in the experimental group after treatment (Wilcoxon test, p < 0.05). The descent ranges of NT-proBNP, left ventricular end-systolic dimension, and left ventricular fraction shortening, as well as increases in the amplitude of left ventricular ejection fraction after treatment were better in the experimental group than in the control group (t-test, p < 0.05). The descent ranges of residual renal glomerular filtration rate, residual renal Kt/Vurea, and residual renal creatinine clearance, as well as increases in the amplitude of ß2-microglobulin, were lower in the experimental group than in the control group (Wilcoxon test, p < 0.05). However, there were no significant differences between the two groups in the descent ranges of the PD adequacy indexes (Wilcoxon test, p > 0.05). Hyperkalemia occurred in 8 cases (25.81%) in the experimental group and 13 cases (39.39%) in the control group, while hypotension occurred in 2 cases (6.45%) and 1 case (3.03%), respectively. No other adverse effects were observed in either group. CONCLUSION: The findings suggest that sacubitril/valsartan can safely and effectively improve RRF and cardiac function in patients with diabetes combined with HFpEF receiving PD, but it has little effect on PD adequacy.

9.
J Food Sci ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042473

ABSTRACT

Our previous studies have shown that sulfated Cyclocarya paliurus polysaccharides (SCP3) can alleviate intestinal oxidative stress (OS) damage by improving the antioxidant capacity of the intestine, but its mechanism still needs further exploration. This study aimed to reveal the possible underlying protective mechanism of SCP3 against OS damage of intestinal epithelial cells (IEC-6) based on transcriptome profiling. The results showed that SCP3 could increase the activity of superoxide dismutase and reduce the production of malondialdehyde and reactive oxygen species. In addition, the SCP3 could also alleviate the H2O2-induced high apoptosis rate and mitochondrial membrane potential decrease in IEC-6 cells. RNA-sequencing results showed that there were 2152 differentially expressed genes between the control group and the SCP3 group, and the mitogen-activated protein kinases (MAPK) and PI3K-Akt signaling pathways are the main signaling pathways that contributed to SCP3 protecting IEC-6 cells from OS damage. In summary, the SCP3 plays a role in improving intestinal cell damage by inhibiting OS, which may be closely related to the PI3K/Akt and MAPK signaling pathways. PRACTICAL APPLICATION: This study provides a theoretical basis for the practical application of Cyclocarya paliurus polysaccharides as an antioxidant ingredient in auxiliary medicines and functional foods.

10.
Exp Ther Med ; 28(3): 344, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39006457

ABSTRACT

Cyst excision and Roux-en-Y hepaticojejunostomy (RYHJ) is the standard treatment for choledochal cysts (CCs). In the present study, the results of totally laparoscopic surgery for CCs (TLCCs) in a pediatric population were evaluated. The clinical data of 28 children with CCs between June 2020 and June 2023 were retrospectively reviewed. All patients underwent TLCCs involving cyst excision and RYHJ. The jejunojejunal anastomosis was completed laparoscopically using manual sutures. Age at operation, operative time, postoperative recovery and complications were evaluated. The 28 patients comprised 8 boys and 20 girls who underwent TLCCs at a mean age of 4.2 years (range, 1 month-12.3 years) with a mean weight of 15.9 kg (range, 4.6-43 kg). All patients received ultrasound and magnetic resonance cholangiopancreatography examinations, which revealed a mean cyst diameter and length of 1.74±0.76 cm and 3.85±1.25 cm, respectively. The mean operative time was 214±43.8 min. The mean time until starting an oral diet after surgery was 2.89±1.23 days. Apart from bile leakage and wound infection, no other complications occurred during a median follow-up period of 18 months (range, 4-42 months). TLCCs can be performed safely by skilled surgeons in pediatric patients. TLCCs may be more physiologically compatible and accelerate recovery of intestinal function with reduced trauma and better esthetic outcomes than conventional laparoscopic surgery for CCs. Therefore, TLCCs with manual sutures may be considered as an option for minimally invasive surgery in pediatric patients with CCs.

11.
Food Chem ; 459: 140345, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38986204

ABSTRACT

Considering the high abundance of bound polyphenols (BP) in whole grain dietary fiber (DF), this study utilized multi-omics approach to evaluate the impact of BP of defatted rice bran insoluble DF (RIDF) in modulating obesity. Mice on high-fat diet were gavage-administered RIDF, BP-removed or formulated RIDF. The results indicated that DF significantly reduced serum total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol levels. Moreover, hepatic lipid accumulation and damage induced by high-fat diet were significantly ameliorated with DF intervention. The presence of BP increased the abundance of beneficial bacteria g_Akkermansia and g_Butyricicocus, as well as the expression of butyric acid/propionic acid. Furthermore, the expression of hepatic lipids and lipid-like molecules was significantly decreased under the combined intervention of BP and DF, and this was accompanied by alterations in genes related to lipid, sterol, and cholesterol metabolic biological processes. These findings suggest that BP contribute to the anti-obesity effects of DF.

12.
Shanghai Kou Qiang Yi Xue ; 33(2): 219-224, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-39005103

ABSTRACT

PURPOSE: To summarize the ultrasound, CT and MRI manifestations of Warthin-like mucoepidermoid carcinoma (WT-MEC), and to explore its imaging characteristics, so as to provide reference for clinical and preoperative diagnosis. METHODS: The clinical information and imaging data of ultrasound, CT and MRI of 12 patients with WT-MEC diagnosed by pathology in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were collected, and their specific characteristics were retrospectively summarized. RESULTS: Among the 12 WT-MEC patients, there were 7 males and 5 females, with an average age of (42.7±16) years. Seven cases underwent ultrasound examination, 6 cases underwent CT examination, and 2 cases underwent MRI examination. Radiologically, all the lesions presented as a solitary mass. 11/12 lesions(91.7%) were identified as well-defined margins, and 10/12(83.3%) as solid-cystic masses. All solid-cystic lesions contained multiple cystic areas with variable sizes. On US images, most lesions showed mixed-echoic echogenicity(5/7, 71.4%), poor vascularization (6/7, 85.7%) and acoustic enhancement (6/7, 85.7%). CT revealed all the lesions (6/6, 100%) as a soft-tissue mass with heterogeneous enhancement (5/6, 83.3%). MRI imaging demonstrated the neoplasm with low or iso-signal intensity on plain T1WI and hyperintensity on T2WI. The heterogeneous enhancement was shown on contrast-enhanced T1WI. CONCLUSIONS: Most WT-MECs represent as a solitary, well-defined, solid-cystic mass in the parotid gland. The neoplasm may be characterized by the multiple and variable-sized cystic components within the tumor.


Subject(s)
Carcinoma, Mucoepidermoid , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Ultrasonography , Humans , Carcinoma, Mucoepidermoid/diagnostic imaging , Male , Female , Adult , Ultrasonography/methods , Retrospective Studies , Adenolymphoma/diagnostic imaging , Parotid Neoplasms/diagnostic imaging , Middle Aged
13.
Sci Total Environ ; 948: 174723, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39002603

ABSTRACT

The deep marine sediments represent a major repository of organic matter whilst hosting a great number of uncultivated microbes. Microbial metabolism plays a key role in the recycling of organic matter in the deep marine sediments. D-amino acids (DAAs) and DAA-containing muropeptides, an important group of organic matter in the deep marine sediments, are primarily derived from bacterial peptidoglycan decomposition. Archaea are abundant in the deep ocean microbiome, yet their role in DAA metabolism remains poorly studied. Here, we report bioinformatic investigation and enzymatic characterization of deep marine sedimentary archaea involved in DAA metabolism. Our analyses suggest that a variety of archaea, particularly the Candidatus Bathyarchaeota and the Candidatus Lokiarchaeaota, can metabolize DAAs. DAAs are converted into L-amino acids via amino acid racemases (Ala racemase, Asp racemase and broad substrate specificity amino acid racemase), and converted into α-keto acid via d-serine ammonia-lyase, whereas DAA-containing di-/tri-muropeptides can be hydrolyzed by peptidases (dipeptidase and D-aminopeptidase). Overall, this study reveals the identity and activity of deep marine sedimentary archaea involved in DAA metabolism, shedding light on the mineralization and biogeochemical cycling of DAAs in the deep marine sediments.

14.
Bioorg Chem ; 150: 107593, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38971093

ABSTRACT

Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn2+ can make H2O2 to produce .OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO-, which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer.


Subject(s)
Iodine Radioisotopes , Manganese Compounds , Nitric Oxide , Oxides , Reactive Oxygen Species , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism , Humans , Animals , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxides/chemistry , Oxides/pharmacology , Iodine Radioisotopes/chemistry , Apoptosis/drug effects , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Mice , Drug Screening Assays, Antitumor , Cell Proliferation/drug effects , Molecular Structure , Mice, Inbred BALB C , Ultrasonic Therapy , Cell Survival/drug effects , Dose-Response Relationship, Drug , Ultrasonic Waves , Cell Line, Tumor
15.
Langmuir ; 40(29): 15205-15213, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38990344

ABSTRACT

The size or the curvature of nanoparticles (NPs) plays an important role in regulating the composition of the protein corona. However, the molecular mechanisms of how curvature affects the interaction of NPs with serum proteins still remain elusive. In this study, we employ all-atom molecular dynamics simulations to investigate the interactions between two typical serum proteins and PEGylated Au NPs with three different surface curvatures (0, 0.1, and 0.5 nm-1, respectively). The results show that for proteins with a regular shape, the binding strength between the serum protein and Au NPs decreases with increasing curvature. For irregularly shaped proteins with noticeable grooves, the binding strength between the protein and Au NPs does not change obviously with increasing curvature in the cases of smaller curvature. However, as the curvature continues to increase, Au NPs may act as ligands firmly adsorbed in the protein grooves, significantly enhancing the binding strength. Overall, our findings suggest that the impact of NP curvature on protein adsorption may be nonmonotonic, which may provide useful guidelines for better design of functionalized NPs in biomedical applications.


Subject(s)
Gold , Metal Nanoparticles , Molecular Dynamics Simulation , Gold/chemistry , Metal Nanoparticles/chemistry , Blood Proteins/chemistry , Surface Properties , Protein Binding , Polyethylene Glycols/chemistry , Adsorption , Humans
16.
Nat Commun ; 15(1): 6259, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048559

ABSTRACT

Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10-6) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP.


Subject(s)
Homeostasis , Keratinocytes , Loss of Function Mutation , Mice, Knockout , NF-kappa B , Pityriasis Rubra Pilaris , Skin , Humans , Pityriasis Rubra Pilaris/genetics , Pityriasis Rubra Pilaris/immunology , Pityriasis Rubra Pilaris/pathology , Pityriasis Rubra Pilaris/metabolism , Animals , Keratinocytes/immunology , Keratinocytes/metabolism , Skin/pathology , Skin/immunology , Skin/metabolism , NF-kappa B/metabolism , Female , Case-Control Studies , Mice , Male , Adult , I-kappa B Kinase/genetics , I-kappa B Kinase/metabolism , Middle Aged , Ubiquitination , Signal Transduction , Keratins/metabolism , Keratins/genetics , Young Adult
17.
Article in English | MEDLINE | ID: mdl-38981855

ABSTRACT

BACKGROUND AND AIM: Insomnia has been implicated in gastrointestinal diseases (GIs), but the causal effect between insomnia and GIs and underlying mechanisms remain unknown. METHODS: By using the released summary-level data, we conducted a two-step Mendelian randomization (MR) analysis to examine the relationship between insomnia and four GIs and estimate the mediating role of candidate mediators. The first step was to investigate the causal association between insomnia and GIs using univariable MR analysis. The second step was to estimate the mediation proportion of selected mediators in these associations using multivariable MR analysis. Subsequently, results from different datasets were combined using the fixed-effect meta-analysis. RESULTS: Univariable MR analysis provided strong evidence for the causal effects of insomnia on four GIs after Bonferroni correction for multiple comparisons, including peptic ulcer disease (PUD) (odds ratio [OR] = 1.15, 95% interval confidence [CI] = 1.10-1.20, P = 1.83 × 10-9), gastroesophageal reflux (GORD) (OR = 1.19, 95% CI = 1.16-1.22, P = 5.95 × 10-42), irritable bowel syndrome (IBS) (OR = 1.18, 95% CI = 1.15-1.22, P = 8.69 × 10-25), and inflammatory bowel disease (IBD) (OR = 1.09, 95% CI = 1.03-1.05, P = 3.46 × 10-3). In the mediation analysis, body mass index (BMI) and waist-to-hip ratio (WHR) were selected as mediators in the association between insomnia and PUD (BMI: mediation proportion [95% CI]: 13.61% [7.64%-20.70%]; WHR: 8.74% [5.50%-12.44%]) and GORD (BMI: 11.82% [5.94%-18.74%]; WHR: 7.68% [4.73%-11.12%]). CONCLUSIONS: Our findings suggest that genetically instrumented insomnia has causal effects on PUD, GORD, IBS, and IBD, respectively. Adiposity traits partially mediated the associations between insomnia and GIs. Further clinical studies are warranted to evaluate the protective effect of insomnia treatment on GIs.

18.
Opt Lett ; 49(13): 3564-3567, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950210

ABSTRACT

Vectorial optical fields (VOFs) with extra degrees of freedom hold promise for many photonic applications. However, current methods to generate VOFs are either bulky in size or exhibit limited functionalities. Here, we demonstrate a tunable VOF generator by exciting plasmonic surface lattice resonances (SLRs) with axial symmetry. By meticulously arranging bilayer circular arrays with opposite handedness, we achieve a high Q-factor of 103 via just a few particles despite the general belief that too small array size suppresses the SLRs. This work presents tunable complex VOFs with distinct inhomogeneous spatial polarization distributions, which may enable various applications in integrated and polarization optics.

19.
BMC Gastroenterol ; 24(1): 197, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877387

ABSTRACT

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.


Subject(s)
Adaptive Immunity , DNA Methylation , Gastrointestinal Neoplasms , Genome-Wide Association Study , Immunity, Innate , Mendelian Randomization Analysis , Quantitative Trait Loci , Humans , Immunity, Innate/genetics , Adaptive Immunity/genetics , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , HLA-DR alpha-Chains/genetics , CpG Islands/genetics , Multiomics
20.
Sci Total Environ ; 946: 174227, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38936710

ABSTRACT

The use of observation-dependent methods for crop productivity and food security assessment is challenging in data-sparse regions. This study presents a transferable framework and applies it to North Korea (NK) to assess rice productivity based on climate similarity, transferable machine-learning techniques, and extendable multi-source data. We initially divided the primary phenological stages of rice in the study region and extracted dynamic rice distributions based on Moderate Resolution Imaging Spectroradiometer products and phenological observations. We compared the performances of four representative environmentally driven models (Linear Regression, back-propagation Neural Network, Support Vector Machine, and Random Forest) in simulating rice productivity using an extensive dataset that included multi-angle vegetation monitoring, climate variables, and planting distribution information. The framework integrated an optimal environmentally driven model with agricultural management practices for transferability to predict rice productivity in NK over multiple years. Additionally, two crop growth scenarios (whole growth period (WGP) and seeding-heading period (SHP)) were compared to assess pre-harvest forecasting capabilities and identify dominant factors. Finally, independent datasets from the Food and Agriculture Organization, World Food Program, and Global Gridded Crop Models were used to validate the magnitude and spatial distribution of the predicted results. The results showed that phenological identification based on remote sensing can accurately capture rice growth characteristics and map rice distribution. Random Forest outperformed other models in simulating rice productivity variation, with r-squares of 0.87 and 0.83 in the WGP and SHP, respectively. The solar-induced chlorophyll fluorescence, maximum temperature, and evapotranspiration collectively determined approximately 40 % of the variation in yield simulated using Random Forest. Conversely, planting areas contributed over 42 % of the variation in rice production. Compared to Food and Agriculture Organization statistics, the environmentally driven framework explained 78.72 % and 76.89 % of the production variation and 69.42 % and 71.15 % of the yield variation in NK under the WGP and SHP, respectively. Moreover, the environmental management-driven framework captured over 90 % of the yield variation. The predicted spatial pattern of rice productivity exhibited significant concordance with the World Food Program and Global Gridded Crop Model reports. In summary, the proposed transferable framework for crop productivity assessment contributes to early warnings of production reduction and has the potential for scalability across various crops and data-sparse regions.


Subject(s)
Agriculture , Oryza , Oryza/growth & development , Agriculture/methods , Democratic People's Republic of Korea , Crops, Agricultural/growth & development , Environmental Monitoring/methods , Climate
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