Improved physicochemical and functional properties of dietary fiber from matcha fermented by Trichoderma viride.

The low-grade matcha is rich in insoluble dietary fiber. Trichoderma viride was used to increase the soluble dietary fiber to improve its functional properties. The soluble dietary fiber content increased from 6.74% to 15.24%. Pectin, hemicellulose, maltose, d-xylose, and glucose contents increased by 63.35% and 11.54%, 2.18, 0.11, and 7.04 mg/g, respectively. Trichoderma viride fermentation disrupted the dense structure of insoluble dietary fiber, resulting in a honeycomb structure and improving crystallinity by 22.75%. These structural changes led to an improved cation exchange capacity from 1.69 to 4.22 mmol/g, an increase in the inhibitory effect of α-amylase from 47.38% to 72.04%, and a 2.13-fold in the ferrous ion scavenging ability, and the IC50 values of superoxide anion was reduced from 7.00 to 1.54 mg/mL, respectively. Therefore, Trichoderma viride fermentation is an excellent method for improving the quality of dietary fiber in matcha processing by-products.

Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models.

Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P < 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.

Beyond VICs: Shedding light on the overlooked VECs in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is prevalent in developed nations and has emerged as a pressing global public health concern due to population aging. The precise etiology of this disease remains uncertain, and recent research has primarily focused on examining the role of valvular interstitial cells (VICs) in the development of CAVD. The predominant treatment options currently available involve open surgery and minimally invasive interventional surgery, with no efficacious pharmacological treatment. This article seeks to provide a comprehensive understanding of valvular endothelial cells (VECs) from the aspects of valvular endothelium-derived nitric oxide (NO), valvular endothelial mechanotransduction, valvular endothelial injury, valvular endothelial-mesenchymal transition (EndMT), and valvular neovascularization, which have received less attention, and aims to establish their role and interaction with VICs in CAVD. The ultimate goal is to provide new perspectives for the investigation of non-invasive treatment options for this disease.

Correlation analysis of secondary metabolites and disease resistance activity of different varieties of Congou black tea based on LC-MS/MS and TCMSP.

To investigate the correlation between the difference of secondary metabolites and the disease-resistance activity of different varieties of Congou black tea. Among a total of 657 secondary metabolites identified, 183 metabolites had anti-disease activity, 113 were key active ingredients in traditional Chinese medicine (TCM), 73.22% had multiple anti-disease activities, and all were mainly flavonoids and phenolic acids. The main enriched metabolic pathways were phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, flavonoid biosynthesis, and metabolic pathways. Flavonoid and phenolic acid secondary metabolites were more correlated with anti-disease activity and key active TCM ingredients. Conclusion: The types of JGY and Q601 Congou black tea of the relative contents show large differences in secondary metabolites. Flavonoid and phenolic acid secondary metabolites were identified as the primary factors contributing to the variation in secondary metabolites among different varieties of Congou black tea. These compounds also exhibited a stronger correlation with disease resistance activity.

Analysis of molecular epidemiological characteristics and antimicrobial susceptibility of vancomycin-resistant and linezolid-resistant Enterococcus in China.

BACKGROUND: This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. METHODS: A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). RESULTS: Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. CONCLUSION: Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.

Simultaneous Determination of Four Catechins in Black Tea via NIR Spectroscopy and Feature Wavelength Selection: A Novel Approach.

As a non-destructive, fast, and cost-effective technique, near-infrared (NIR) spectroscopy has been widely used to determine the content of bioactive components in tea. However, due to the similar chemical structures of various catechins in black tea, the NIR spectra of black tea severely overlap in certain bands, causing nonlinear relationships and reducing analytical accuracy. In addition, the number of NIR spectral wavelengths is much larger than that of the modeled samples, and the small-sample learning problem is rather typical. These issues make the use of NIRS to simultaneously determine black tea catechins challenging. To address the above problems, this study innovatively proposed a wavelength selection algorithm based on feature interval combination sensitivity segmentation (FIC-SS). This algorithm extracts wavelengths at both coarse-grained and fine-grained levels, achieving higher accuracy and stability in feature wavelength extraction. On this basis, the study built four simultaneous prediction models for catechins based on extreme learning machines (ELMs), utilizing their powerful nonlinear learning ability and simple model structure to achieve simultaneous and accurate prediction of catechins. The experimental results showed that for the full spectrum, the ELM model has better prediction performance than the partial least squares model for epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). For the feature wavelengths, our proposed FIC-SS-ELM model enjoys higher prediction performance than ELM models based on other wavelength selection algorithms; it can simultaneously and accurately predict the content of EC (Rp2 = 0.91, RMSEP = 0.019), ECG (Rp2 = 0.96, RMSEP = 0.11), EGC (Rp2 = 0.97, RMSEP = 0.15), and EGCG (Rp2 = 0.97, RMSEP = 0.35) in black tea. The results of this study provide a new method for the quantitative determination of the bioactive components of black tea.

Aging- and alcohol-associated spatial transcriptomic signature in mouse acute pancreatitis reveals heterogeneity of inflammation and potential pathogenic factors.

The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via Visium spatial transcriptomics, eight distinct tissue clusters were revealed from aggregated transcriptomes of aging and young AAP mice: five acinar, two stromal, and one islet, which were then merged into three clusters: acinar, stromal, and islet for the comparative analysis. Compared to young AAP mice, > 1300 differentially expressed genes (DEGs) and approximately 3000 differentially regulated pathways were identified in aging AAP mice. The top five DEGs upregulated in aging AAP mice include Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp with heterogeneous distributions among the clusters. Taken together, this study demonstrates spatial heterogeneity of inflammatory processes in aging AAP mice, offering novel insights into the mechanisms and potential drivers for AAP development. KEY MESSAGES: Mechanisms regarding high mortality of AAP in aging remain undefined. An aging AAP mouse model was developed recapturing clinical exhibition in humans. Spatial transcriptomics identified contrasted DEGs in aging vs. young AAP mice. Top five DEGs were Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp in aging vs. young AAP mice. Our findings shed insights for identification of molecular drivers in aging AAP.

Docosahexaenoic Acid Coordinating with Sodium Selenite Promotes Paraptosis in Colorectal Cancer Cells by Disrupting the Redox Homeostasis and Activating the MAPK Pathway.

Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment.

Increased Gremlin1 Expression in Pancreatic Ductal Adenocarcinoma Promotes a Fibrogenic Stromal Microenvironment.

OBJECTIVE: The pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts (CAFs) and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not adequately defined. METHODS: We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas (TCGA) RNA-sequencing data and characterized the expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies. RESULTS: Grem1 expression is associated with an activated stroma and increased M1 and M2 macrophages. Only full length Grem1 variant 1 and isoform 1 were detectable in human pancreatic cells, and remarkably high levels of Grem1 were observed in pancreatic fibroblasts (P < 0.05). Immunohistochemistry detected Grem1 protein in PDAC tumor cells and stromal cells, which correlated with infiltrating macrophages in PDAC tumors. Grem1 knockdown in CAFs suppressed transforming growth factor (TGF)-ß-induced extracellular matrix proteins (P < 0.05). Grem1 recombinant protein treatment in vitro increased M1 and M2 macrophages (P < 0.05). CONCLUSIONS: Grem1 acts as a profibrogenic factor in the PDAC microenvironment via modulation of fibroblasts and macrophages. Grem1 may have the potential to be developed as a therapeutic target for PDAC.

Lama1 upregulation prolongs the lifespan of the dyH/dyH mouse model of LAMA2-related congenital muscular dystrophy.

LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier. To evaluate its clinical applicability, we establish a Lama2 exon-3 deletion mouse model (dyH/dyH). The dyH/dyH mice exhibit early lethality and typical LAMA2-CMD phenotypes, allowing the evaluation of various endpoints. In dyH/dyH mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation, a nearly doubled median survival is observed, as well as improvements in weight and grip. Significant therapeutical effects are revealed by MRI, serum biochemical indices, and muscle pathology studies. Treating LAMA2-CMD with LAMA1 upregulation is feasible and that early intervention can alleviate symptoms and extend lifespan. Additionally, we reveal limitations of LAMA1 upregulation, including high-dose mortality and non-sustained expression, which require further optimization in future studies.

Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.

Self-Organizing Type-2 Fuzzy Double Loop Recurrent Neural Network for Uncertain Nonlinear System Control.

Nonlinear systems, such as robotic systems, play an increasingly important role in our modern daily life and have become more dominant in many industries; however, robotic control still faces various challenges due to diverse and unstructured work environments. This article proposes a double-loop recurrent neural network (DLRNN) with the support of a Type-2 fuzzy system and a self-organizing mechanism for improved performance in nonlinear dynamic robot control. The proposed network has a double-loop recurrent structure, which enables better dynamic mapping. In addition, the network combines a Type-2 fuzzy system with a double-loop recurrent structure to improve the ability to deal with uncertain environments. To achieve an efficient system response, a self-organizing mechanism is proposed to adaptively adjust the number of layers in a DLRNN. This work integrates the proposed network into a conventional sliding mode control (SMC) system to theoretically and empirically prove its stability. The proposed system is applied to a three-joint robot manipulator, leading to a comparative study that considers several existing control approaches. The experimental results confirm the superiority of the proposed system and its effectiveness and robustness in response to various external system disturbances.

Toxicology study profile of Nicotinamide mononucleotide after acute and 90-day sub chronic dosing in Wistar rats and mutagenicity tests.

Nicotinamide mononucleotide (NMN) is an intermediate in biosynthesis pathway of Nicotinamide adenine dinucleotide (NAD+), an essential cofactor in all living cells involved in fundamental biological processes. Evidence stemming from recent studies have unveiled numerous roles of NAD+ metabolism on aging, longevity, delaying the progression of age-related diseases. A three-study genetic toxicity (genetox) battery (bacterial mutagenesis, in vitro cytogenetics, and in vivo mammalian test) is usually required to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time. The acute oral LD50 of NMN was greater than 2000 mg/kg body weight with 5000 mg/kg body weight as LD50 cut-off value and was classified under "Category 5 or Unclassified" as per Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Based on 90 days repeated dose toxicity test the NOAEL was considered to be NLT 800 mg NMN/kg body weight in Wistar rats. The bacterial reverse mutation test, the in vitro and in vivo chromosomal aberration test, found NMN to be non-mutagenic. In the mammalian bone marrow chromosomal aberration test, it was concluded that NMN is non clastogenic at and up to 2,000 mg/kg body weight in all the animals tested to confirm safety of a new dietary ingredient and this study showed the data from in vivo mutagenicity test for the first time.

Actor-Critic With Synthesis Loss for Solving Approximation Biases.

Approximation biases of value functions are considered a key problem in reinforcement learning (RL). In particular, existing RL algorithms are hindered by overestimation and underestimation biases, i.e., value mismatching between RL's actual returns and action-value approximations limits the performance of RL algorithms. In this article, we first develop a new synthesis loss function for RL's action-value estimation integrating a regularization term and a modified "clipped double Q -learning" structure for solving overestimation and underestimation biases. To minimize the differences between action-value estimations and actual returns in RL, we develop a new discrepancy function to determine the type and magnitude of approximation biases. Then, two coefficients embedded in the synthesis loss are automatically tuned by minimizing the discrepancy function during training to minimize approximation biases. We further design a new actor-critic (AC) algorithm, named AC with synthesis loss (ACSL), by integrating the synthesis loss function and an error-controlled mechanism. Experimental results on continuous control tasks illustrate that the proposed ACSL algorithm outperforms other cutting-edge RL methods in many tasks and that the proposed synthesis loss function is easily implemented into other algorithms and significantly reduces approximation biases while improving performance. The proposed method can successfully handle many complex continuous control tasks and can greatly outperform other state-of-the-art algorithms on most tasks.

Efficacy of microwave ablation with parallel acupuncture guided by ultrasound in treating single hepatocellular carcinoma in high-risk areas: A retrospective analysis of 155 patients.

OBJECTIVE: To investigate the safety and short- and long-term efficacy of ultrasound-guided microwave ablation (MWA) with parallel acupuncture for treating single hepatocellular carcinoma (HCC) in high-risk areas. METHODS: Retrospective analysis was performed on 155 patients with single hepatocellular carcinoma who underwent microwave ablation in our hospital between December 2015 and September 2016. Patients with a tumor distance of ≤5 mm from the risk area were included in the observation group. Patients with a tumor distance of >5 mm from the risk area were placed in the control group. The patients' preoperative general health status, tumor site, tumor size, follow-up data, disease-free survival rate, overall survival rates, local tumor progression, and intrahepatic distant recurrence rate were collected and analyzed. RESULTS: The 1-, 3-, and 5-year overall survival rates for the observation group were 91.8%, 75.5%, and 59.2%, respectively. The 1-, 3-, and 5-year overall survival rates for the control group were 97.2%, 84.0%, and 66.0%, respectively. There were no significant differences between the two groups (P = 0.522). A tumor size of ≤20 mm (HR = 0.488, 95% CI = 0.254-0.940, P = 0.032) was an independent risk factor affecting the overall survival of patients with solitary HCC treated with MWA. The 1-, 3-, and 5-year recurrence-free survival rates for the observation group were 59.2%, 28.6%, and 18.4%, respectively, and those for the control group were 79.2%, 43.4%, and 31.1%, respectively. There was a statistical difference between the two groups (P = 0.007). Tumor size ≤20 mm (HR = 0.468, 95% CI = 0.303-0.723, P = 0.001), tumor location in a risk area (HR = 1.662, 95% CI = 1.121-2.465, P = 0.011), and an α-fetoprotein (AFP) level of <200 ug/L (HR = 0.612, 95% CI = 0.386-0.970, P = 0.036) are independent factors affecting the recurrence-free survival of MWA treatment for HCC. CONCLUSION: Microwave ablation with parallel acupuncture guided by ultrasound is a safe and effective treatment for single hepatocellular carcinoma in high-risk areas.

Accurate Finite Element Simulations of Dynamic Behaviour: Constitutive Models and Analysis with Deep Learning.

Owing to the challenge of capturing the dynamic behaviour of metal experimentally, high-precision numerical simulations have become essential for analysing dynamic characteristics. In this study, calculation accuracy was improved by analysing the impact of constitutive models using the finite element (FE) model, and the deep learning (DL) model was employed for result analysis. The results showed that FE simulations with these models effectively capture the elastic-plastic response, and the ZA model exhibits the highest accuracy, with a 26.0% accuracy improvement compared with other models at 502 m/s for Hugoniot elastic limit (HEL) stress. The different constitutive models offer diverse descriptions of stress during the elastic-plastic response because of temperature effects. Concurrently, the parameters related to the yield strength at quasi-static influence the propagation speed of elastic waves. Calculation show that the yield strength at quasi-static of 6061 Al adheres to y = ax + b for HEL stress. The R-squared (R2) and mean absolute error (MAE) values of the DL model for HEL stress predictions are 0.998 and 0.0062, respectively. This research provides a reference for selecting constitutive models for simulation under the same conditions.

A new method for accurate inversion of Forel-Ule index using MODIS images - revealing the water color evolution in China's large lakes and reservoirs over the past two decades.

The Forel Ule water color index (FUI) based on satellite inversion can characterize the comprehensive characteristics of water quality on a large spatiotemporal scale. The high-frequency observations and rich historical data of the MODIS surface reflectance product (MODIS-500 m) provide important data support for monitoring the FUI of inland lakes. However, MODIS-500 m has only three bands in the visible light range, resulting in significant uncertainty in FUI inversion. To address this problem, this study developed an improved FUI inversion model using 500 synthetic spectra covering natural waters. The model, with a performance threshold set at 170° (FUI = 8), used a segmented algorithm across the entire color space. Validated with on-site measurement datasets (3500 samples), the model exhibited excellent performance, with mean relative error (MRE) and root mean square error (RMSE) of 1.71 % and 3.63°, respectively. Compared to existing models, it was more suitable for long-term FUI inversion in various types of lakes, particularly in eutrophic regions. Subsequently, the model was applied to MODIS-500 m observations from 2000 to 2022, revealing the spatiotemporal dynamics of FUI in 180 large lakes and reservoirs (hereinafter referred to as lakes) in China. The results indicated that the long-term mean FUI in the study area was 9, with 7 and 12 in the western and eastern regions, respectively, showing a distinct spatial distribution of "blue in the west and green in the east." The mean change rate of hue angle for all lakes was -0.085°/yr, showing an overall decreasing trend. Environmental factors' relative contributions to long-term water color changes in each lake region were quantified using the multiple general linear model (GLM). Although each lake region exhibited different driving forces, they were primarily influenced by vegetation, lake surface area, and anthropogenic factors. Additionally, the seasonal types of lake water color were analyzed, with the west and east showing opposite patterns, reflecting the significant influence of topographic features and seasonal changes in climate on water color. The research results provide techniques for accurate inversion of FUI using MODIS-500 m data, while deepening the understanding of long-term water color changes in inland lakes in China.

Uncovering the Over-Smoothing Challenge in Image Super-Resolution: Entropy-Based Quantification and Contrastive Optimization.

PSNR-oriented models are a critical class of super-resolution models with applications across various fields. However, these models tend to generate over-smoothed images, a problem that has been analyzed previously from the perspectives of models or loss functions, but without taking into account the impact of data properties. In this paper, we present a novel phenomenon that we term the center-oriented optimization (COO) problem, where a model's output converges towards the center point of similar high-resolution images, rather than towards the ground truth. We demonstrate that the strength of this problem is related to the uncertainty of data, which we quantify using entropy. We prove that as the entropy of high-resolution images increases, their center point will move further away from the clean image distribution, and the model will generate over-smoothed images. Implicitly optimizing the COO problem, perceptual-driven approaches such as perceptual loss, model structure optimization, or GAN-based methods can be viewed. We propose an explicit solution to the COO problem, called Detail Enhanced Contrastive Loss (DECLoss). DECLoss utilizes the clustering property of contrastive learning to directly reduce the variance of the potential high-resolution distribution and thereby decrease the entropy. We evaluate DECLoss on multiple super-resolution benchmarks and demonstrate that it improves the perceptual quality of PSNR-oriented models. Moreover, when applied to GAN-based methods, such as RaGAN, DECLoss helps to achieve state-of-the-art performance, such as 0.093 LPIPS with 24.51 PSNR on 4× downsampled Urban100, validating the effectiveness and generalization of our approach.

Single dual-specific anti-PD-L1/TGF-ß antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma: a preclinical experimental study.

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP (anti-PD-L1/TGF-ß bispecific antibody) is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-ß) and programmed cell death ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP combinatorial chemotherapy in neoadjuvant settings significantly downstaged PDAC tumors, enhanced survival, and had a higher resectability for mice with PDAC. BiTP was high affinity binding to targets and reverse chemotherapy resistance of PDAC cells. The combination overcame immune evasion through reprogramming tumor microenvironment via increasing penetration and function of T cells, natural killer cells, and dendritic cells and decreasing the function of immunosuppression-related cells as regulatory T cells, M2 macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts. CONCLUSION: Our results suggest that the BiTP combinatorial chemotherapy is a promising neoadjuvant therapy for PDAC.

Preventing Subsidence Reoccurrence in Tianjin: New Preconsolidation Head and Safe Pumping Buffer.

Tianjin, a coastal metropolis in north China, has grappled with land subsidence for nearly a century. Yet, emerging evidence suggests a notable decrease in subsidence rates across Tianjin since 2019. This trend is primarily attributed to the importation of surface water from the Yangtze River system via the South-to-North Water Diversion Project, initiated in December 2014. Utilizing Sentinel-1A Interferometric Synthetic Aperture Radar (InSAR) data (2014-2023), this study reveals that one-third of the Tianjin plain has either halted subsidence or experienced land rebound. As a result, the deep aquifer system (~-200 to -450 m) beneath one third of the Tianjin plain has completed a consolidation cycle, leading to the establishment of new, locally specific preconsolidation heads. The identification of the newly established preconsolidation head seeks to answer a crucial question: How can we prevent the reoccurrence of subsidence in areas where it has already ceased? In essence, subsidence will stop when the local hydraulic head elevates to the new preconsolidation head (NPCH), and permanent subsidence will not be reinitiated as long as hydraulic head remains above the NPCH. The difference of the depth between current hydraulic head and the NPCH defines the safe pumping buffer (SPB). This study outlines detailed methods for identifying the NPCHs in the deep aquifer system from long-term InSAR and groundwater-level datasets. Determining NPCHs and ascertaining SPBs are crucial for estimating how much groundwater can be safely extracted without inducing permanent subsidence, and for developing sustainable strategies for long-term groundwater management and conservation.