Absorption, transportation, residual distribution of chiral 14C-dufulin in garlics and metabolism of its racemate.

Dufulin is a novel chiral plant antiviral agent. In this study, we investigated the uptake, translocation and accumulation of 14C-dufulin stereoisomers in different tissues of garlic via leaf introduction and root uptake. The behavior of dufulin enantiomers in plants is not stereoselective, and dufulin is more likely to be absorbed by leaves than by roots. The metabolites of 14C-dufulin with high specific activity in garlic were qualitatively and quantitatively analyzed by HPLC-QTOF-MS, and the metabolic pathway involved was elucidated. In the leaf and bulb, dufulin underwent phase I and phase II metabolism and produced four metabolites. The ratios and concentrations of these four metabolites in the bulb, but not in the leaf, met the residue criterion. Overall, our results provide relatively accurate predictions for the risk assessment of dufulin, which will help guide its rational use and ensure its ecological safety and human health.

Different surgical methods for FIGO stage IVB cervical cancer patients receiving chemotherapy: a population-based study.

OBJECTIVE: To assess survival differences between non-extensive surgery (NES) and extensive surgery (ES) in International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer patients receiving chemotherapy from a population-based database, the Surveillance, Epidemiology and End Results. METHODS: Propensity matching was conducted to minimize heterogeneity. Survival analysis was performed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. RESULTS: A total of 154 patients met screening criteria, among whom 84 patients (84/154) underwent NES while 70 patients (70/154) underwent ES. After matching, no survival advantage was observed in ES group compared with NES group (p=0.066; hazard ratio [HR]=1.54; 95% confidence interval [CI]=0.97-2.42). Stratified analyses suggested ES prolonged overall survival in patients with histology other than squamous cell carcinoma and adenocarcinoma (p=0.028; HR=0.36; 95% CI=0.15-0.89) and American Joint Committee on Cancer (AJCC) T stage T1 (p=0.009; HR=0.18; 95% CI=0.05-0.66). Despite no survival benefit after regional lymph node surgery (p=0.629; HR=0.88; 95% CI=0.53-1.47), subgroup analyses demonstrated that patients younger than 50 (p=0.006; HR=0.21; 95% CI=0.07-0.64), with AJCC T stage T1 (p=0.002; HR=0.09; 95% CI=0.02-0.42), T3 (p=0.001; HR=0.02; 95% CI=0.00-0.21), hematogenous metastasis (p=0.036; HR=0.27; 95% CI=0.08-0.92) and without surgery of other sites (p=0.040; HR=0.01; 95% CI=0.00-0.79) might achieve longer survival after regional lymph node surgery. CONCLUSION: In conclusion, ES or regional lymph node surgery may provide survival advantage for certain subgroup of FIGO IVB cervical cancer patients receiving chemotherapy. However, it deserves large scale prospective clinical trials to confirm.

ZBED3 exacerbates hyperglycemia by promoting hepatic gluconeogenesis through CREB signaling.

BACKGROUND: Elevated hepatic glucose production (HGP) is a prominent manifestation of impaired hepatic glucose metabolism in individuals with diabetes. Increased hepatic gluconeogenesis plays a pivotal role in the dysregulation of hepatic glucose metabolism and contributes significantly to fasting hyperglycemia in diabetes. Previous studies have identified zinc-finger BED domain-containing 3 (ZBED3) as a risk gene for type 2 diabetes (T2DM), and its single nucleotide polymorphism (SNPs) is closely associated with the fasting blood glucose level, suggesting a potential correlation between ZBED3 and the onset of diabetes. This study primarily explores the effect of ZBED3 on hepatic gluconeogenesis and analyzes the relevant signaling pathways that regulate hepatic gluconeogenesis. METHODS: The expression level of ZBED3 was assessed in the liver of insulin-resistant (IR)-related disease. RNA-seq and bioinformatics analyses were employed to examine the ZBED3-related pathway that modulated HGP. To investigate the role of ZBED3 in hepatic gluconeogenesis, the expression of ZBED3 was manipulated by upregulation or silencing using adeno-associated virus (AAV) in mouse primary hepatocytes (MPHs) and HHL-5 cells. In vivo, hepatocyte-specific ZBED3 knockout mice were generated. Moreover, AAV8 was employed to achieve hepatocyte-specific overexpression and knockdown of ZBED3 in C57BL/6 and db/db mice. Immunoprecipitation and mass spectrometry (IP-MS) analyses were employed to identify proteins that interacted with ZBED3. Co-immunoprecipitation (co-IP), glutathione S-transferase (GST) - pulldown, and dual-luciferase reporter assays were conducted to further elucidate the underlying mechanism of ZBED3 in regulating hepatic gluconeogenesis. RESULTS: The expression of ZBED3 in the liver of IR-related disease models was found to be increased. Under the stimulation of glucagon, ZBED3 promoted the expression of hepatic gluconeogenesis-related genes PGC1A, PCK1, G6PC, thereby increasing HGP. Consistently, the rate of hepatic gluconeogenesis was found to be elevated in mice with hepatocyte-specific overexpression of ZBED3 and decreased in those with ZBED3 knockout. Additionally, the knockdown of ZBED3 in the liver of db/db mice resulted in a reduction in hepatic gluconeogenesis. Moreover, the study revealed that ZBED3 facilitated the nuclear translocation of protein arginine methyltransferases 5 (PRMT5) to influence the regulation of PRMT5-mediated symmetrical dimethylation of arginine (s-DMA) of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), which in turn affects the phosphorylation of CREB and ultimately promotes HGP. CONCLUSIONS: This study indicates that ZBED3 promotes hepatic gluconeogenesis and serves as a critical regulator of the progression of diabetes.

Long Non-coding RNA FOXD2-AS1 Silencing Inhibits Malignant Behaviors of Ovarian Cancer Cells Via miR-324-3p/SOX4 Signaling Axis.

It is urgent to develop new therapeutic strategies for ovarian cancer (OC). Long-noncoding RNAs (lncRNAs) have participated in multiple biological processes including tumor recurrence and progression. This study aimed to determine the effects and potential regulatory mechanism of lncRNA FOXD2-AS1 in OC progression. Levels of lncRNA FOXD2-AS1 and miR-324-3p in OC tissues and cell lines were analyzed using quantitative real-time PCR (qRT-PCR). The direct target between FOXD2-AS1 or miR-324-3p was determined using bioinformatics tools and further verified by dual-luciferase reporter assay. Cell viability, apoptosis, migration, along invasion were assessed by MTT, flow cytometry, as well as Transwell assays, respectively. In addition, the levels of miR-324-3p, PCNA, MMP9, Bax, Bcl-2, and SOX4 in OC cells were evaluated using qRT-PCR and western blot assays. We observed that lncRNA FOXD2-AS1 was up-regulated while miR-324-3p was down-regulated in OC tissues and cell lines, especially in SKOV3 cells. Moreover, miR-324-3p was a direct target of lncRNA FOXD2-AS1. Meanwhile, SOX4 interacted with miR-324-3p and was negatively regulated by miR-324-3p in SKOV3 cells. Function assays confirmed that lncRNA FOXD2-AS1 silenced depressed cell proliferation, migration, and invasion while accelerating apoptosis. These functions of lncRNA FOXD2-AS1 were attenuated by miR-324-3p inhibition. Our research demonstrated that FOXD2-AS1 silencing restrained cell growth and metastasis of OC via regulating miR-324-3p/SOX4 axis, indicating that lncRNA FOXD2-AS1 could be a novel potential therapeutic target for OC.

Case report: Rapid symptom relief in autoimmune encephalitis with efgartigimod: a three-patient case series.

Introduction: Autoimmune encephalitis (AE) comprises a group of inflammatory brain disorders mediated by autoimmune responses. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and anti-γ-aminobutyric acid-B receptor (GABABR) encephalitis are the most prevalent forms, characterized by the presence of antibodies against neuronal cell-surface antigens. Efgartigimod, an antagonist of the neonatal Fc receptor, has proven efficacy in myasthenia gravis treatment. This clinical case report describes the clinical progression and functional outcomes of AE in three patients who received efgartigimod treatment. Case presentations: Case 1 was a 60-year-old man exhibiting memory impairment and psychiatric disturbances over 11 days. Case 2 was a 38-year-old man with a 1-month history of rapid cognitive decline and seizures. Case 3 was a 68-year-old woman with mental behavioral changes and seizures for 4 months. Anti-GABABR, anti-LGI1, and anti-NMDAR antibodies were confirmed in the respective patients' cerebrospinal fluid or serum. All three patients experienced marked and swift symptomatic relief after four cycles of efgartigimod treatment, with no complication. Conclusion: Current first-line and second-line treatments for AE have limitations, and efgartigimod has demonstrated potential in the rapid and efficacious treatment of AE, emerging as a promising option for the management of this disease.

Genomic Characterization and Establishment of a Genetic Manipulation System for Trichoderma sp. (Harzianum Clade) LZ117.

Trichoderma species have been reported as masters in producing cellulolytic enzymes for the biodegradation of lignocellulolytic biomass and biocontrol agents against plant pathogens and pests. In our previous study, a novel Trichoderma strain LZ117, which shows potent capability in cellulase production, was isolated. Herein, we conducted multilocus phylogenetic analyses based on DNA barcodes and performed time-scaled phylogenomic analyses using the whole genome sequences of the strain, annotated by integrating transcriptome data. Our results suggest that this strain represents a new species closely related to T. atrobrunneum (Harzianum clade). Genes encoding carbohydrate-active enzymes (CAZymes), transporters, and secondary metabolites were annotated and predicted secretome in Trichoderma sp. LZ117 was also presented. Furthermore, genetic manipulation of this strain was successfully achieved using PEG-mediated protoplast transformation. A putative transporter gene encoding maltose permease (Mal1) was overexpressed, which proved that this transporter does not affect cellulase production. Moreover, overexpressing the native Cre1 homolog in LZ117 demonstrated a more pronounced impact of glucose-caused carbon catabolite repression (CCR), suggesting the importance of Cre1-mediated CCR in cellulase production of Trichoderma sp. LZ117. The results of this study will benefit further exploration of the strain LZ117 and related species for their applications in bioproduction.

Multi-resolution visual Mamba with multi-directional selective mechanism for retinal disease detection.

Introduction: Retinal diseases significantly impact patients' quality of life and increase social medical costs. Optical coherence tomography (OCT) offers high-resolution imaging for precise detection and monitoring of these conditions. While deep learning techniques have been employed to extract features from OCT images for classification, convolutional neural networks (CNNs) often fail to capture global context due to their focus on local receptive fields. Transformer-based methods, on the other hand, suffer from quadratic complexity when handling long-range dependencies. Methods: To overcome these limitations, we introduce the Multi-Resolution Visual Mamba (MRVM) model, which addresses long-range dependencies with linear computational complexity for OCT image classification. The MRVM model initially employs convolution to extract local features and subsequently utilizes the retinal Mamba to capture global dependencies. By integrating multi-scale global features, the MRVM enhances classification accuracy and overall performance. Additionally, the multi-directional selection mechanism (MSM) within the retinal Mamba improves feature extraction by concentrating on various directions, thereby better capturing complex, orientation-specific retinal patterns. Results: Experimental results demonstrate that the MRVM model excels in differentiating retinal images with various lesions, achieving superior detection accuracy compared to traditional methods, with overall accuracies of 98.98\% and 96.21\% on two public datasets, respectively. Discussion: This approach offers a novel perspective for accurately identifying retinal diseases and could contribute to the development of more robust artificial intelligence algorithms and recognition systems for medical image-assisted diagnosis.

Changes in food valence of regular diet depending on the experience of high and low preference food.

AIMS: Eating disorders represent an aspect of mental illness involving failure to control eating behaviors. Food valence plays a regulatory role in eating behaviors and changes with eating experiences. Failure to control food valence may be associated with eating disorders. This study presents a newly developed behavior task-food reservation task, which assesses changes in food valence. METHODS: Over three consecutive days, mice were fed a regular diet for 30 min and subsequently were offered either palatable or low-palatable foods for 30 min. RESULTS: Mice decreased regular diet consumption on the days that it was followed by a palatable food-sweet chocolate (SC) or cheese (CH) and increased it when it was followed by a low-palatable food-bitter (dark) chocolate (BC). Our findings indicate that mice can change regular diet consumption by learning whether it will be followed by a palatable or low-palatable food. This suggests that palatable food devaluated the food valence of regular diet, whereas low-palatable food evaluated it. CONCLUSION: We developed a new food reservation task, which allows to assess experience-dependent change in the food valence of a regular diet. This task will contribute to a better understanding of the neural mechanisms underlying those changes.

Single-nucleus transcriptomics reveals subsets of degenerative myonuclei after rotator cuff tear-induced muscle atrophy.

Rotator cuff tear (RCT) is the primary cause of shoulder pain and disability and frequently trigger muscle degeneration characterised by muscle atrophy, fatty infiltration and fibrosis. Single-nucleus RNA sequencing (snRNA-seq) was used to reveal the transcriptional changes in the supraspinatus muscle after RCT. Supraspinatus muscles were obtained from patients with habitual shoulder dislocation (n = 3) and RCT (n = 3). In response to the RCT, trajectory analysis showed progression from normal myonuclei to ANKRD1+ myonuclei, which captured atrophy-and fatty infiltration-related regulons (KLF5, KLF10, FOSL1 and BHLHE40). Transcriptomic alterations in fibro/adipogenic progenitors (FAPs) and muscle satellite cells (MuSCs) have also been studied. By predicting cell-cell interactions, we observed communication alterations between myofibers and muscle-resident cells following RCT. Our findings reveal the plasticity of muscle cells in response to RCT and offer valuable insights into the molecular mechanisms and potential therapeutic targets of RCT.

Morphology Optimization by Non-Halogenated and Twisted Volatile Solid Additive for High-Efficiency Organic Solar Cells.

Recently, volatile solid additives have attracted tremendous interest in the field of organic solar cells (OSCs), which can effectively improve device efficiency without sacrificing the reproducibility and stability of the device. However, the structure of reported solid additives is onefold and its working mechanism needs to be further investigated. Herein, a novel non-halogenated and twisted solid additive 1,4-diphenoxybenzene (DPB) is employed to optimize the morphology of the active layer in OSCs. The properties of additive DPB, morphology of active layer, and carrier dynamics behaviors have been systematically investigated through theoretical calculations, in situ and ex situ spectroscopy, grazing-incidence wide-angle X-ray scattering (GIWAXS), and grazing-incidence small-angle X-ray scattering (GISAXS) measurement, as well as ultrafast spectroscopy technology. The results reveal that the twisted additive DPB selectively interacts with acceptor Y6, and thus forms optimized morphology of active layer with increased molecular crystallinity, tight molecular packing, and favorable phase separation. As a result, the optimized devices deliver a remarkable power conversion efficiency (PCE) of 19.04%, which is the highest value for the D18-Cl:N3 system to date. These results demonstrate that non-halogenated and twisted solid additive DPB has broad prospects in the preparation of highly efficient OSCs, providing theoretical and experimental guidance for the development of high-performance solid additives.

Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3.

Somatostatin receptors (SSTRs) exert critical biological functions such as negatively regulating hormone release and cell proliferation, making them popular targets for developing therapeutics to treat endocrine disorders, especially neuroendocrine tumors. Although several panagonists mimicking the endogenous ligand somatostatin are available, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and regulation of divergent SSTR subtypes. Here, we report four cryoelectron microscopy structures of Gi-coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778. Our structures reveal a conserved recognition pattern of pasireotide in SSTRs attributed to the binding with a conserved extended binding pocket, distinct from SST14, octreotide, and lanreotide. Together with mutagenesis analyses, our structures further reveal the dynamic feature of ligand binding pockets in SSTR1 and SSTR3 to accommodate divergent agonists, the key determinants of ligand selectivity lying across the orthosteric pocket of different SSTR subtypes, as well as the molecular mechanism underlying diversity and conservation of receptor activation. Our work provides a framework for rational design of subtype-selective SSTR ligands and may facilitate drug development efforts targeting SSTRs with improved therapeutic efficacy and reduced side effects.

Molecular characterization of oxidized organic nitrogen in the polluted urban atmosphere of Beijing.

Oxidized organic nitrogen (OON) serves as a crucial link between volatile organic compounds (VOCs), nitrogen oxides, ozone, and secondary organic aerosol (SOA). However, the comprehension of the molecular composition, formation mechanism, and implications of OON remains limited, particularly in urban environments influenced heavily by anthropogenic emissions. This study presents the field measurements of OON conducted at an urban site in Beijing using chemical ionization mass spectrometry with nitrate as the reagent ion. The molecular characteristics, dominant species, and oxidation states of OON were investigated. Positive matrix factorization analysis disentangled the diverse OON into factors characterized by unique fingerprint features and formation pathways. A modified workflow was used to classify the majority of OON as terpene (3.0 %), isoprene (15.2 %), aliphatic (38.1 %, containing dinitrate), and aromatic (36.0 %, containing aromatic ring retaining) OON. This highlights the significant impact of anthropogenic sources and underscores the need for stringent controls on anthropogenic VOC emissions to mitigate OON formation. Volatility estimates further indicate that aromatic and aliphatic OON, with relatively low volatility, are expected to be the primary contributors to SOA formation by condensation or gas-particle partitioning in urban Beijing. In addition, hazy weather conditions may facilitate multi-generation reactions, leading to the production of large amounts of semi-volatile dinitrate OON and promoting its conversion to SOA.

Targeting Thyroid-Stimulating Hormone Receptor: A Perspective on Small-Molecule Modulators and Their Therapeutic Potential.

TSHR is a member of the glycoprotein hormone receptors, a subfamily of class A G-protein-coupled receptors and plays pivotal roles in various physiological and pathological processes, particularly in thyroid growth and hormone production. The aberrant TSHR function has been implicated in several human diseases including Graves' disease and orbitopathy, nonautoimmune hyperthyroidism, hypothyroidism, cancer, neurological disorders, and osteoporosis. Consequently, TSHR is recognized as an attractive therapeutic target, and targeting TSHR with small-molecule modulators including agonists, antagonists, and inverse agonists offers great potential for drug discovery. In this perspective, we summarize the structures and biological functions of TSHR as well as the recent advances in the development of small-molecule TSHR modulators, highlighting their chemotypes, mode of actions, structure-activity relationships, characterizations, in vitro/in vivo activities, and therapeutic potential. The challenges, new opportunities, and future directions in this area are also discussed.

CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published. They include the following: new faster simulation engines, accessible user interfaces for convenient workflows, and a vast array of simulation and analysis methods that encompass quantum mechanical, atomistic, and coarse-grained levels, as well as extensive coverage of force fields. In addition to providing the current snapshot of the CHARMM development, this review may serve as a starting point for exploring relevant theories and computational methods for tackling contemporary and emerging problems in biomolecular systems. CHARMM is freely available for academic and nonprofit research at https://academiccharmm.org/program.

Refining CycleGAN with attention mechanisms and age-Aware training for realistic Deepfakes.

In the evolving landscape of deep learning technologies, the emergence of Deepfakes and synthetic media is becoming increasingly prominent within digital media production. This research addresses the limitations inherent in existing face image generation algorithms based on Generative Adversarial Networks (GAN), particularly the challenges of domain irrelevancy and inadequate facial detail representation. The study introduces an enhanced face image generation algorithm, aiming to refine the CycleGAN framework. The enhancement involves a two-fold strategy: firstly, the generator's architecture is refined through the integration of an attention mechanism and adaptive residual blocks, enabling the extraction of more nuanced facial features. Secondly, the discriminator's accuracy in distinguishing real from synthetic images is improved by incorporating a relative loss concept into the loss function. Additionally, this study presents a novel model training approach that incorporates age constraints, thereby mitigating the effects of age variations on the synthesized images. The effectiveness of the proposed algorithm is empirically validated through comparative analysis with existing methodologies, utilizing the CelebA dataset. The results demonstrate that the proposed algorithm significantly enhances the realism of generated face images, outperforming current methods in terms of Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index Measure (SSIM), while also achieving notable improvements in subjective visual quality. The implementation of this advanced method is anticipated to substantially elevate the efficiency and quality of digital media production, contributing positively to the broader field of digital media creation.

Flexible Wearable Tri-notched UWB Antenna Printed with Silver Conductive Materials.

The advancement of Internet of Things and associated technologies has led to the widespread usage of smart wearable devices, greatly boosting the demand for flexible antennas, which are critical electromagnetic components in such devices. Additive manufacturing technologies provide a feasible solution for the creation of wearable and flexible antennas. However, performance reliability under deformation and radiation safety near the human body are two issues that need to be solved for such antennas. Currently, there are few reports on compact, flexible ultrawideband (UWB) antennas with more notch numbers, reliable bendability, and radiation safety. In this paper, a UWB antenna with trinotched characteristics for wearable applications was proposed and developed using printable conductive silver materials consisting of silver microflakes or silver nanoparticles. The antenna has a compact size of 18 × 20 × 0.12 mm3 and adopts a gradient feeder and a radiation patch with three folding slots. It was fabricated on transparent and flexible poly(ethylene terephthalate) film substrates, using screen printing and inkjet printing. The measurement results demonstrated that the fabricated antennas could cover the UWB band (2.35-10.93 GHz) while efficiently filtering out interferences from the C-band downlink satellite system (3.43-4.21 GHz), wireless local area networks (4.66-5.29 GHz), and X-band uplink satellite system (6.73-8.02 GHz), which was consistent with the simulation results. The bendability and radiation safety of the antennas were evaluated, proving their feasibility for usage under bending conditions and near the human body. Additionally, it was found that the screen-printed antenna performed better after bending. The research is expected to provide guidance on designing flexible antennas that are both safe to wear and easily conformable.

IGFBP7 promotes the proliferation and differentiation of primary myoblasts and intramuscular preadipocytes in chicken.

Though it is well known that insulin-like growth factor (IGF) binding protein 7 (IGFBP7) plays an important role in myogenesis and adipogenesis in mammals, its impact on the proliferation, differentiation, and lipid deposition in chicken primary myoblasts (CPM) and intramuscular preadipocytes remains unexplored. In the present study, we firstly examined the correlation between SNPs within the genomic sequence of the IGFBP7 gene and carcass and blood chemical traits in a F2 resource population by genetic association analysis, and found that a significant correlation between the SNP (4_49499525) located in the intron region of IGFBP7 and serum high-density lipoproteins (HDL). We then examined the expression patterns of IGFBP7 across different stages of proliferation and differentiation in CPMs and intramuscular preadipocytes via qPCR, and explored the biological functions of IGFBP7 through gain- and loss-of-function experiments and a range of techniques including qPCR, CCK-8, EdU, flow cytometry, Western blot, immunofluorescence, and Oil Red O staining to detect the proliferation, differentiation, and lipid deposition in CPMs and intramuscular preadipocytes. We ascertained that the expression levels of the IGFBP7 gene increased as cell differentiation progresses in CPMs and intramuscular preadipocytes, and that IGFBP7 promotes the proliferation and differentiation of these cells, as well as facilitates intracellular lipid deposition. Furthermore, we investigated the regulatory mechanism of IGFBP7 expression by using co-transfection strategy and dual-luciferase reporter assay, and discovered that the myogenic transcription factors (MRF), myoblast determination factor (MyoD) and myogenin (MyoG), along with the adipocyte-specific transcription factor (TF) CCAAT/enhancer-binding protein α (C/EBPα), can bind to the core transcription activation region of the IGFBP7 promoter located 500 bp upstream from the transcription start site, thereby promoting IGFBP7 transcription and expression. Taken together, our study underscores the role of IGFBP7 as a positive regulator for myogenesis and adipogenesis, while also elucidating the functional and transcriptional regulatory mechanisms of IGFBP7 in chicken skeletal muscle development and intramuscular adipogenesis.

DNA methylation analysis reveals local changes in resistant and susceptible soybean lines in response to Phytophthora sansomeana.

Phytophthora sansomeana is an emerging oomycete pathogen causing root rot in many agricultural species including soybean. However, as of now, only one potential resistance gene has been identified in soybean, and our understanding of how genetic and epigenetic regulation in soybean contributes to responses against this pathogen remains largely unknown. In this study, we performed whole genome bisulfite sequencing (WGBS) on two soybean lines, Colfax (resistant) and Williams 82 (susceptible), in response to P. sansomeana at two time points: 4 and 16 hours post-inoculation to compare their methylation changes. Our findings revealed that there were no significant changes in genome-wide CG, CHG (H = A, T, or C), and CHH methylation. However, we observed local methylation changes, specially an increase in CHH methylation around genes and transposable elements (TEs) after inoculation, which occurred earlier in the susceptible line and later in the resistant line. After inoculation, we identified differentially methylated regions (DMRs) in both Colfax and Williams 82, with a predominant presence in TEs. Notably, our data also indicated that more TEs exhibited changes in their methylomes in the susceptible line compared to the resistant line. Furthermore, we discovered 837 DMRs within or flanking 772 differentially expressed genes (DEGs) in Colfax and 166 DMRs within or flanking 138 DEGs in Williams 82. These DEGs had diverse functions, with Colfax primarily showing involvement in metabolic process, defense response, plant and pathogen interaction, anion and nucleotide binding, and catalytic activity, while Williams 82 exhibited a significant association with photosynthesis. These findings suggest distinct molecular responses to P. sansomeana infection in the resistant and susceptible soybean lines.

Dandelion inspired microparticles with highly efficient drug delivery to deep lung.

Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of ∼ 68.96 % and extra fine particle fraction of ∼ 36.87 %, equivalently ∼ 4.60 mg and ∼ 2.46 mg could reach the lung and alveoli, respectively, when inhaling 10 mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.

Food insecurity trends and disparities according to immigration status in the US households, 2011-2021.

BACKGROUND: Food insecurity related to immigration status remains largely underexplored. This study examined trends and disparities in household food insecurity by immigration status in the United States (US). METHODS: We analyzed data from 427,942 households from the US Current Population Survey Food Security Supplement from 2011 to 2021. Immigration status categories included recent immigrants (< 5 years), long-term immigrants (≥ 5 years), naturalized citizens, and US-born citizens. Food insecurity was assessed using validated questions on consistent access to enough food for an active and healthy life. RESULTS: From 2011 to 2021, food insecurity prevalence declined from 14.9 % (95 % CI, 14.5 %-15.3 %) to 10.2 % (95 % CI, 9.8 %-10.6 %). Among recent immigrants, prevalence decreased from 25.2 % (95 % CI, 23.1-27.4) in 2011 to 15.0 % (95 % CI, 12.8 %-17.2 %) in 2019, then increased to 17.7 % (95 % CI, 14.7 %-20.2 %) in 2020 and 17.4 % (95 % CI, 14.7 %-20.2 %) in 2021. Long-term immigrants' prevalence dropped from 20.4 % (95 % CI, 16.9 %-24.0 %) in 2011 to 10.2 % (95 % CI, 7.2 %-13.1 %) in 2018, then increased to 17.7 % (95 % CI, 13.7 %-21.7 %) in 2021. Naturalized citizens' prevalence decreased from 14.4 % (95 % CI, 12.9 %-15.9 %) to 9.5 % (95 % CI, 8.2 %-10.9 %). US-born citizens' prevalence decreased from 14.2 % (95 % CI, 13.8 %-14.6 %) to 9.7 % (95 % CI, 9.3 %-10.2 %). Compared to the US-born citizens, the adjusted prevalence ratio was 1.63 (95 % CI,1.57-1.69) for recent immigrants, 1.22 (95 % CI, 1.13-1.31) for long-term immigrants, and 0.94 (95 % CI, 0.90-0.98) for naturalized citizens. Significant disparities exist in subgroups. CONCLUSIONS: The findings provide insights for stakeholders to address food insecurity among vulnerable immigrant groups in the US.