The emerging roles of liquid-liquid phase separation in tumor immunity.

Recent advancements in tumor immunotherapy, particularly PD-1 targeted therapy, have shown significant promise, marking major progress in tumor treatment approaches. Despite this, the development of resistance to therapy and mechanisms of immune evasion by tumors pose considerable obstacles to the broad application of immunotherapy. This necessitates a deeper exploration of complex immune signaling pathways integral to tumor immunity. This review aims to critically analyze the role of liquid-liquid phase separation (LLPS) within tumor immunity, specifically its impact on immune signaling pathways and its potential to foster the development of novel cancer therapies. LLPS, a biophysical process newly recognized for its ability to spontaneously segregate and organize biomacromolecules into liquid-like condensates through weak multivalent interactions, offers a novel perspective on the formation of signaling clusters and the functionality of immune molecules. The review delves into the micromolecular mechanisms behind the creation of signaling condensates via LLPS and reviews recent progress in adjusting signaling pathways pertinent to tumor immunity, including the T cell receptor (TCR), B cell receptor (BCR), immune checkpoints, and innate immune pathways such as the cGAS-STING pathway, stress granules, and the ADP-heptose-ALPK1 signaling axis. Furthermore, it considers the prospects of utilizing LLPS to generate groundbreaking cancer therapies capable of navigating past current treatment barriers. Through an extensive examination of LLPS's impact on tumor immunity, the review seeks to highlight novel therapeutic strategies and address the challenges and future directions in this rapidly evolving field.

The relationships between perceived parental rearing, social support, PTSD, and depression in people living with HIV in China: a cross-sectional study.

Post-traumatic stress disorder (PTSD) and depression are two major psychological disorders that affect the mental health of people living with HIV (PLWH). The occurrence of PTSD and depression may be linked to perceptions of parental rearing styles in childhood. However, little is known about the relationship between perceived parental rearing styles, and PTSD and depression in the PLWH population. This study investigated 300 PLWH and explored the relationship between perceived parental rearing style, social support, PTSD, and depression. The results indicated that perceived paternal and maternal warmth were negatively associated with PTSD. Perceived maternal warmth and overprotection were negatively associated with depression. Social support acted as a mediator between perceived parental warmth, PTSD, and depression. Therefore, it is necessary to focus on patients who feel they experienced a lack of parental warmth during childhood and provide psychological care and support, which may help reduce the risk of developing PTSD and depression.

Impact of delayed seed drop on rodent-mediated seed dispersal and predation of pine.

Many plants exhibit a canopy seed bank, where seeds persist within the canopy for prolonged periods, gradually descending over time and potentially influencing seed predation and animal-mediated dispersal. However, the impact of delayed seed drop on animal predation and seed dispersal remains unclear. We used Chinese Armand pine seeds to simulate delayed seed drop of the canopy seed bank by releasing 7800 pine seeds in both winter and the following summer over 2 years, tracking their fates to investigate its effect on seed predation and dispersal by rodents in a pine plantation in southwest China. Results showed significant seasonal differences in seed fate. In summer, seeds experienced higher predation rates (62.08% vs 3.80% in winter) and lower scatter-hoarding rates (4.18% vs 15.40% in winter). Additionally, seeds in summer were dispersed farther (4.20 m vs. 3.56 m in winter) and primarily formed single-seed caches, as opposed to multi-seed caches in winter. Although delayed seed drop increased immediate predation risks, favorable summer conditions allowed for rapid germination, reducing long-term exposure to predation. In conclusion, while delayed seed drop increases immediate predation risks and reduces caching, it concurrently enhances dispersal distances and reduces cache size.

Multimodal and multiscale feature fusion for weakly supervised video anomaly detection.

Weakly supervised video anomaly detection aims to detect anomalous events with only video-level labels. In the absence of boundary information for anomaly segments, most existing methods rely on multiple instance learning. In these approaches, the predictions for unlabeled video snippets are guided by the classification of labeled untrimmed videos. However, these methods do not account for issues such as video blur and visual occlusion, which can hinder accurate anomaly detection. To address these issues, we propose a novel weakly supervised video anomaly detection method that fuses multimodal and multiscale features. Firstly, RGB and optical flow snippets are input into pre-trained I3D to extract appearance and motion features. Then, we introduce an Attention De-redundancy (AD) module, which employs an attention mechanism to filter out task-irrelevant redundancy in these appearance and motion features. Next, to mitigate the effects of video blurring and visual occlusion, we propose a Multi-scale Feature Learning module. This module captures long-term and short-term temporal dependencies among video snippets to provide global and local guidance for blurred or occluded video snippets. Finally, to effectively utilize the discriminative features of different modalities, we propose an Adaptive Feature Fusion module. This module adaptively fuses appearance and motion features based on their respective feature weights. Extensive experimental results demonstrate that our proposed method outperforms mainstream unsupervised and weakly supervised methods in terms of AUC. Specifically, our proposed method achieves 97.00% AUC and 85.31% AUC on two benchmark datasets, i.e., ShanghaiTech and UCF-Crime, respectively.

NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways.

Neural cell adhesion molecule (NCAM), a common mammalian cell surface glycoprotein, is the major substrate of polysialic acid (polySia). Polysialylated NCAM occurs in many types of cancer, but rarely in normal adult tissues. The functional role of NCAM hypersialylation in the epithelial-mesenchymal transition (EMT) process remains unclear. The present study indicates that NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways. NCAM and polysialylated NCAM are aberrantly regulated in breast cancer cells. They are both upregulated in normal breast epithelial cells undergoing EMT. Western blot analysis demonstrates that NCAM-140 overexpression induces EMT in breast epithelial cells and promotes cell proliferation and migration through activation of the ß-catenin/slug signaling pathway. Modification of polySia attached to NCAM modulates cell adhesion and promotes cell motility through activation of the EGFR/STAT3 pathway. These observations contribute to clarifying the molecular mechanisms by which polysialic acid and its major substrate, NCAM, modulate cell behaviors, and highlight the significance of increased polysialylated expression on NCAM during EMT and tumor development.

Bisecting GlcNAc modification reverses the chemoresistance via attenuating the function of P-gp.

Rationale: Chemoresistance is a key factor contributing to the failure of anti-breast cancer chemotherapy. Although abnormal glycosylation is closely correlated with breast cancer progression, the function of glycoconjugates in chemoresistance remains poorly understood. Methods: Levels and regulatory roles of bisecting N-acetylglucosamine (GlcNAc) in chemoresistant breast cancer cells were determined in vitro and in vivo. Glycoproteomics guided identification of site-specific bisecting GlcNAc on P-glycoprotein (P-gp). Co-immunoprecipitation coupled mass spectrometry (Co-IP-MS) and proximity labelling MS identified the interactome of P-gp, and the biological function of site-specific bisecting GlcNAc was investigated by site/truncation mutation and structural simulations. Results: Bisecting GlcNAc levels were reduced in chemoresistant breast cancer cells, accompanied by an enhanced expression of P-gp. Enhanced bisecting GlcNAc effectively reversed chemoresistance. Mechanical study revealed that bisecting GlcNAc impaired the association between Ezrin and P-gp, leading to a decreased expression of membrane P-gp. Bisecting GlcNAc suppressed VPS4A-mediated P-gp recruitment into microvesicles, and chemoresistance transmission. Structural dynamics analysis suggested that bisecting GlcNAc at Asn494 introduced structural constraints that rigidified the conformation and suppressed the activity of P-gp. Conclusion: Our findings highlight the crucial role of bisecting GlcNAc in chemoresistance and suggest the possibility of reversing chemoresistance by modulating the specific glycosylation in breast cancer therapy.

Inherent symmetry and flexibility in hepatitis B virus subviral particles.

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo-electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D2- and D4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions.

ATM phosphorylation of CD98HC increases antiporter membrane localization and prevents chronic toxic glutamate accumulation in Ataxia telangiectasia.

Ataxia telangiectasia (A-T) is a rare genetic disorder characterized by neurological defects, immunodeficiency, cancer predisposition, radiosensitivity, decreased blood vessel integrity, and diabetes. ATM, the protein mutated in A-T, responds to DNA damage and oxidative stress, but its functional relationship to the progressive clinical manifestation of A-T is not understood. CD98HC chaperones cystine/glutamate (xc -) and cationic/neutral amino acid (y+L) antiporters to the cell membrane, and CD98HC phosphorylation by ATM accelerates membrane localization to acutely increase amino acid transport. Loss of ATM impacts tissues reliant on SLC family antiporters relevant to A-T phenotypes, such as endothelial cells (telangiectasia) and pancreatic α-cells (fatty liver and diabetes) with toxic glutamate accumulation. Bypassing the antiporters restores intracellular metabolic balance both in ATM-deficient cells and mouse models. These findings provide new insight into the long-known benefits of N-acetyl cysteine to A-T cells beyond oxidative stress through removing excess glutamate by production of glutathione.

Effects of γ-Aminobutyric Acid on Growth Performance, Immunity, Antioxidant Capacity, and Intestinal Microbiota of Growing Minks.

The present experiment was conducted to investigate the effects of γ-aminobutyric acid (GABA) on the growth performance, immunity, antioxidant capacity, and intestinal microbiota of growing minks. One hundred minks were evenly allocated across five groups, with each group consisting of 10 males and 10 females. The minks in these groups were fed a basal diet supplemented with γ-aminobutyric acid (GABA) at 0 (control), 10, 20, 30, and 40 mg/kg of diet, respectively. The experiment lasted for eight weeks. The results showed that GABA significantly affected immunity, antioxidant capacity, and intestinal microbiota (p < 0.05). Compared to the control minks, minks in 20, 30, and 40 mg/kg GABA group had greater total protein quantitative (TP), immunoglobulin A (IgA), immunoglobulin M (IgM) content, total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) activities in serum as well as interleukin-4 (IL-4) level in jejunal mucosa (p < 0.05), and had less serum blood urea nitrogen (BUN) content (p < 0.05). Furthermore, compared with the control, the supplementation of GABA at 30 mg/kg of diet improved average daily feed intake (ADFI) (p < 0.05), increased immunoglobulin G (IgG) content in serum, interleukin-10 (IL-10) and secreted immunoglobulin A (SIgA) levels in jejunal mucosa, and decreased jejunal mucosal interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-γ (IFN-γ) levels (p < 0.05). The weight and feed intake of males were higher than females, and the feed/gain ratio (F/G) was lower than females (p < 0.05). Males also had greater serum superoxide dismutase (SOD) and GSH-Px activities, and jejunal mucosa IL-2, IL-4, IL-12, SIgA, and IFN-γ levels (p < 0.05), and males had less serum IgA, IgM, and T-AOC contents, and jejunal mucosal tumor necrosis factor-α (TNF-α) level (p < 0.05). The results suggest that the supplementation of GABA at 30 mg/kg of diet can improve immune status and antioxidant capacity, and modulate the intestinal microbiota abundance of growing minks.

Organic-Inorganic Hybrid Halide X-ray Scintillator with High Antiwater Stability.

In recent years, low-dimensional organic-inorganic hybrid metal halides have garnered significant attention for optoelectronic applications due to their exceptional photophysical properties, despite their persistent challenge of low stability. Addressing this challenge, our study introduces 1-[5-(trifluoromethyl)pyridin-2-yl]piperazinium (TFPP) as a cation, harvesting a novel one-dimensional hybrid cadmium-based halide semiconductor (TFPP)CdCl4, which exhibits intense blue-light emission upon UV excitation. Additionally, (TFPP)CdCl4 demonstrates a high scintillation performance under X-ray excitation, producing 16600 ± 500 photons MeV-1 and achieving a low detection limit of 0.891 µGyair s-1. Notably, (TFPP)CdCl4 showcases remarkable stability against water, intense light sources, heating, and corrosive environments, positioning it as a promising candidate for optoelectronic applications. Through a blend of experimental techniques and theoretical analyses, including density functional theory calculations, we elucidate the unique photophysical properties and structural stability of (TFPP)CdCl4. These findings significantly contribute to the understanding of low-dimensional hybrid halide semiconductors, offering valuable insights into their potential application in advanced optoelectronic devices and paving the way for further research in this field.

The trajectory of vesicular proteomic signatures from HBV-HCC by chitosan-magnetic bead-based separation and DIA-proteomic analysis.

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC.

Naturally Occurring Dehydrocostus Lactone Covalently Binds to KARRIKIN INSENSITIVE 2 by Dual Serine Modifications in Orobanche cumana and Arabidopsis.

Parasitic weeds, such as Orobanche and Striga, threaten crops globally. Contiguous efforts on the discovery and development of structurally novel seed germination stimulants targeting HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE 2 (HTL/KAI2) have been made with the goal of weed control. Here, we demonstrate that a natural compound dehydrocostus lactone (DCL) exhibits effective "suicide germination" activity against Orobanche cumana and covalently binds to OcKAI2d2 on two catalytic serine sites with the second modification dependent on the first one. The same interactions and covalent modifications of DCL are also confirmed in AtKAI2. Further in-depth evolution analysis indicates that the proposed two catalytic sites are present throughout the streptophyte algae, hornworts, lycophytes, and seed plants. This discovery is particularly noteworthy as it signifies the first confirmation of a plant endogenous molecule directly binding to KAI2, which is valuable for unraveling the elusive identity of the KAI2 ligand and for targeting KAI2 paralogues for the development of novel germination stimulants.

Characterization of a triple-type chimeric vaccine against human papillomavirus types 18, 45, and 59.

Persistent infection with high-risk human papillomavirus (HPV) types can lead to the development of cancer in HPV-infected tissues, including the cervix, oropharynx, anus, penis, vagina, and vulva. While current HPV vaccines cover approximately 90 % of cervical cancers, nearly 10 % of cases associated with HPV types not included in the vaccines remain unaddressed, notably HPV59. This study describes the development of a chimeric virus-like particle (VLP) targeting HPV18/45/59, proposed as a vaccine candidate for high-risk HPV type (HPV59) currently lacking commercial vaccines. Given that the majority of neutralizing antibody epitopes are located on the surface loops, we engineered a strategic swap of these loops between the closely related HPV18 and HPV45. This methodology was then extended to incorporate surface loops of HPV59, resulting in the lead candidate construct of the H18-45BCEF-59HI chimeric VLP with two surface loops swapping from HPV45 to HPV18. Characterization confirmed that H18-45BCEF-59HI closely resembled the wild-type (WT) backbone types in particle size and morphology, as verified by Transmission Electron Microscopy (TEM), High-Performance Size-Exclusion Chromatography (HPSEC), and Analytical Ultracentrifugation (AUC), and demonstrated similar thermal stability as evidenced by Differential Scanning Calorimetry (DSC). Immunization studies in mice with the chimeric VLPs assessed their immunogenicity, revealing that the H18-45EF-59HI chimeric VLP exhibited optimal cross-neutralization. Additionally, when produced in a Good Manufacturing Practice (GMP)-like facility, the H18-45BCEF-59HI VLP was selected as a promising vaccine candidate for the prevention of HPV18/45/59 infection. This study not only offers a potential solution to the current vaccination gap but also provides a foundational approach for the design of vaccines targeting viruses with multiple subtypes or variants.

An advanced three-dimensional phenotypic measurement approach for extracting Ginkgo root structural parameters based on terrestrial laser scanning.

The phenotyping of plant roots is essential for improving plant productivity and adaptation. However, traditional techniques for assembling root phenotyping information are limited and often labor-intensive, especially for woody plants. In this study, an advanced approach called accurate and detailed quantitative structure model-based (AdQSM-based) root phenotypic measurement (ARPM) was developed to automatically extract phenotypes from Ginkgo tree root systems. The approach involves three-dimensional (3D) reconstruction of the point cloud obtained from terrestrial laser scanning (TLS) to extract key phenotypic parameters, including root diameter (RD), length, surface area, and volume. To evaluate the proposed method, two approaches [minimum spanning tree (MST)-based and triangulated irregular network (TIN)-based] were used to reconstruct the Ginkgo root systems from point clouds, and the number of lateral roots along with RD were extracted and compared with traditional methods. The results indicated that the RD extracted directly from point clouds [coefficient of determination (R 2) = 0.99, root-mean-square error (RMSE) = 0.41 cm] outperformed the results of 3D models (MST-based: R 2 = 0.71, RMSE = 2.20 cm; TIN-based: R 2 = 0.54, RMSE = 2.80 cm). Additionally, the MST-based model (F1 = 0.81) outperformed the TIN-based model (F1 = 0.80) in detecting the number of first-order and second-order lateral roots. Each phenotyping trait fluctuated with a different cloud parameter (CP), and the CP value of 0.002 (r = 0.94, p < 0.01) was found to be advantageous for better extraction of structural phenotypes. This study has helped with the extraction and quantitative analysis of root phenotypes and enhanced our understanding of the relationship between architectural parameters and corresponding physiological functions of tree roots.

Food-based biomaterials: pH-responsive alginate/gellan gum/carboxymethyl cellulose hydrogel beads for lactoferrin delivery.

The present study utilizes a combination of sodium alginate (Alg), gellan gum (GG), and sodium carboxymethyl cellulose (CMC) to fabricate a ternary composite hydrogel system to encapsulate and release lactoferrin (LF). Rheological properties as well as extensive microscopy and spectroscopy characterization are performed on these materials demonstrating that the physical properties of the resultant hydrogels, such as particle size, water content, gray value, and shrinkage rate were related to the concentration of Alg. In addition, most of these hydrogels were found to have reticulated shells and inner laminar structures assembled based on hydrogen bonding and electrostatic forces. Furthermore, the encapsulation efficiency of LF in hydrogels ranged from 78.3 ± 0.3 to 83.5 ± 0.2 %. Notably, a small amount of encapsulated LF was released from the hydrogel beads in an acid environment (up to 2.2 ± 0.3 % in 2 h), while a controlled release manner was found to take place in an alkaline environment. This phenomenon indicated the potential of these hydrogels as promising matrices for bioactive compound loading and adsorption. The release mechanism varied from Alg concentration suggesting the tunable and versatile properties of this ternary composite hydrogel system. Our findings identify the potential of Alg-GG-CMC hydrogel as a delivery system suitable for various applications in the food industry.

HCGAN: hierarchical contrast generative adversarial network for unpaired sketch face synthesis.

Transforming optical facial images into sketches while preserving realism and facial features poses a significant challenge. The current methods that rely on paired training data are costly and resource-intensive. Furthermore, they often fail to capture the intricate features of faces, resulting in substandard sketch generation. To address these challenges, we propose the novel hierarchical contrast generative adversarial network (HCGAN). Firstly, HCGAN consists of a global sketch synthesis module that generates sketches with well-defined global features and a local sketch refinement module that enhances the ability to extract features in critical areas. Secondly, we introduce local refinement loss based on the local sketch refinement module, refining sketches at a granular level. Finally, we propose an association strategy called "warmup-epoch" and local consistency loss between the two modules to ensure HCGAN is effectively optimized. Evaluations of the CUFS and SKSF-A datasets demonstrate that our method produces high-quality sketches and outperforms existing state-of-the-art methods in terms of fidelity and realism. Compared to the current state-of-the-art methods, HCGAN reduces FID by 12.6941, 4.9124, and 9.0316 on three datasets of CUFS, respectively, and by 7.4679 on the SKSF-A dataset. Additionally, it obtained optimal scores for content fidelity (CF), global effects (GE), and local patterns (LP). The proposed HCGAN model provides a promising solution for realistic sketch synthesis under unpaired data training.

Pharmacological targets of SGLT2 inhibition on prostate cancer mediated by circulating metabolites: a drug-target Mendelian randomization study.

Background: The relationship between sodium-glucose cotransporter 2 (SGLT2) inhibitors and prostate cancer is still unknown. Although these inhibitors can influence tumor glycolysis, the underlying mechanism requires further exploration. Methods: A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on prostate cancer; 2) causal effects of 1,400 circulating metabolites or metabolite ratios on prostate cancer; and 3) mediation effects of these circulating metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene and glycated hemoglobin level (HbA1c). Additionally, positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to test the selection of genetic proxies. Phenome Wide Association Study (PheWAS) and MR-PheWAS analysis were used to explore potential treatable diseases and adverse outcomes of SGLT2 inhibitors. Results: Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM [odds ratio (OR) = 0.66 (95% CI 0.53, 0.82), P = 1.57 × 10-4]; prostate cancer [0.34 (0.23, 0.49), P = 2.21 × 10-8] and prostate-specific antigen [0.26 (0.08, 0.81), P = 2.07 × 10-2]. The effect of SGLT2 inhibition on prostate cancer was mediated by uridine level, with a mediated proportion of 9.34% of the total effect. In MR-PheWAS, 65 traits were found to be associated with SLGT2 inhibitors (P < 1.78 × 10-5), and among them, 13 were related to diabetes. Conclusion: Our study suggested that SGLT2 inhibition could lower prostate cancer risk through uridine mediation. More mechanistic and clinical research is necessary to explore how uridine mediates the link between SGLT2 inhibition and prostate cancer.

An advanced TSMK-FVC approach combined with Landsat 5/8 imagery for assessing the long-term effects of terrain and climate on vegetation growth.

Introduction: As an exceptional geographical entity, the vegetation of the Qinghai-Tibetan Plateau (QTP) exhibits high sensitivity to climate change. The Baima Snow Mountain National Nature Reserve (BNNR) is located in the south-eastern sector of the QTP, serving as a transition area from sub-tropical evergreen broadleaf forest to high-mountain vegetation. However, there has been limited exploration into predicting the temporal and spatial variability of vegetation cover using anti-interference methods to address outliers in long-term historical data. Additionally, the correlation between these variables and environmental factors in natural forests with complex terrain has rarely been analyzed. Methods: This study has developed an advanced approach based on TS (Theil-Sen slope estimator) MK (Mann-Kendall test)-FVC (fractional vegetation cover) to accurately evaluate and predict the time and spatial shifts in FVC within the BNNR, utilizing the GEE (Google Earth Engine). The satellite data utilized in this paper consisted of Landsat images spanning from 1986 to2020. By integrating TS and MK methodologies to monitor and assess the FVC trend, the Hurst index was employed to forecast FVC. Furthermore, the association between FVC and topographic factors was evaluated, the partial correlation between FVC and climatic influences was analyzed at the pixel level (30×30m). Results and discussion: Here are the results of this research: (1) Overall, the FVC of the BNNR exhibits a growth trend, with the mean FVC value increasing from 59.40% in 1986 to 68.67% in 2020. (2) The results based on the TS-MK algorithm showed that the percentage of the area of the study area with an increasing and decreasing trend was 59.03% (significant increase of 28.04%) and 22.13% (significant decrease of 6.42%), respectively. The coupling of the Hurst exponent with the Theil-Sen slope estimator suggests that the majority of regions within the BNNR are projected to sustain an upward trend in FVC in the future. (3) Overlaying the outcomes of TS-MK with the terrain factors revealed that the FVC changes were notably influenced by elevation. The partial correlation analysis between climate factors and vegetation changes indicated that temperature exerts a significant influence on vegetation cover, demonstrating a high spatial correlation.

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. CONCLUSION: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Enhanced 3D dose prediction for hypofractionated SRS (gamma knife radiosurgery) in brain tumor using cascaded-deep-supervised convolutional neural network.

Gamma Knife radiosurgery (GKRS) is a well-established technique in radiation therapy (RT) for treating small-size brain tumors. It administers highly concentrated doses during each treatment fraction, with even minor dose errors posing a significant risk of causing severe damage to healthy tissues. It underscores the critical need for precise and meticulous precision in GKRS. However, the planning process for GKRS is complex and time-consuming, heavily reliant on the expertise of medical physicists. Incorporating deep learning approaches for GKRS dose prediction can reduce this dependency, improve planning efficiency and homogeneity, streamline clinical workflows, and reduce patient lagging times. Despite this, precise Gamma Knife plan dose distribution prediction using existing models remains a significant challenge. The complexity stems from the intricate nature of dose distributions, subtle contrasts in CT scans, and the interdependence of dosimetric metrics. To overcome these challenges, we have developed a "Cascaded-Deep-Supervised" Convolutional Neural Network (CDS-CNN) that employs a hybrid-weighted optimization scheme. Our innovative method incorporates multi-level deep supervision and a strategic sequential multi-network training approach. It enables the extraction of intra-slice and inter-slice features, leading to more realistic dose predictions with additional contextual information. CDS-CNN was trained and evaluated using data from 105 brain cancer patients who underwent GKRS treatment, with 85 cases used for training and 20 for testing. Quantitative assessments and statistical analyses demonstrated high consistency between the predicted dose distributions and the reference doses from the treatment planning system (TPS). The 3D overall gamma passing rates (GPRs) reached 97.15% ± 1.36% (3 mm/3%, 10% threshold), surpassing the previous best performance by 2.53% using the 3D Dense U-Net model. When evaluated against more stringent criteria (2 mm/3%, 10% threshold, and 1 mm/3%, 10% threshold), the overall GPRs still achieved 96.53% ± 1.08% and 95.03% ± 1.18%. Furthermore, the average target coverage (TC) was 98.33% ± 1.16%, dose selectivity (DS) was 0.57 ± 0.10, gradient index (GI) was 2.69 ± 0.30, and homogeneity index (HI) was 1.79 ± 0.09. Compared to the 3D Dense U-Net, CDS-CNN predictions demonstrated a 3.5% improvement in TC, and CDS-CNN's dose prediction yielded better outcomes than the 3D Dense U-Net across all evaluation criteria. The experimental results demonstrated that the proposed CDS-CNN model outperformed other models in predicting GKRS dose distributions, with predictions closely matching the TPS doses.