Progressive Dual Priori Network for Generalized Breast Tumor Segmentation.

To promote the generalization ability of breast tumor segmentation models, as well as to improve the segmentation performance for breast tumors with smaller size, low-contrast and irregular shape, we propose a progressive dual priori network (PDPNet) to segment breast tumors from dynamic enhanced magnetic resonance images (DCE-MRI) acquired at different centers. The PDPNet first cropped tumor regions with a coarse-segmentation based localization module, then the breast tumor mask was progressively refined by using the weak semantic priori and cross-scale correlation prior knowledge. To validate the effectiveness of PDPNet, we compared it with several state-of-the-art methods on multi-center datasets. The results showed that, comparing against the suboptimal method, the DSC and HD95 of PDPNet were improved at least by 5.13% and 7.58% respectively on multi-center test sets. In addition, through ablations, we demonstrated that the proposed localization module can decrease the influence of normal tissues and therefore improve the generalization ability of the model. The weak semantic priors allow focusing on tumor regions to avoid missing small tumors and low-contrast tumors. The cross-scale correlation priors are beneficial for promoting the shape-aware ability for irregular tumors. Thus integrating them in a unified framework improved the multi-center breast tumor segmentation performance. The source code and open data can be accessed at https://github.com/wangli100209/PDPNet.

Comprehensive Numerical Evaluation of CO2 Huff-n-Puff in an Offshore Tight Oil Reservoir: A Case Study in Bohai Bay Area, China.

Many reports have presented that in tight formation, the flow mechanism differs from a conventional reservoir, such as molecular diffusion, Pre-Darcy flow behavior, and stress sensitivity. However, for CO2 Huff-n-Puff development, it is a challenge to synthetically research these mechanisms. Considering the above flow mechanisms and offshore engineering background, the development plan optimization becomes a key issue. In this paper, a self-developed simulator that satisfies research needs is introduced. Then, based on experimental results, the simulation is launched to analyze the effects of CO2 diffusion, Huff-n-Puff period, and permeability heterogeneity. The results indicate that molecular diffusion makes a positive contribution to the oil recovery factor. Additionally, for offshore reservoirs, limited to the development cost and CO2 facilities corrosion, when the total Huff-n-Puff time is constant, the ratio of 0.5-1.0 between the Huff period and the Puff period in every cycle performs better. Finally, the greater heterogeneity in permeability is much more favorable for the CO2 Huff-n-Puff because of more intensive transport processes in formation. These different scenarios can increase the understanding of the CO2 Huff-n-Puff in tight oil offshore reservoirs.

Successfully treatment in Lactating Women with severe acne through the combination of fire needle and photodynamic therapy:a case report.

Severe acne, characterized by cysts and nodules, can significantly impact a patient's self-image and quality of life [1]. In China, first-line treatments for severe acne typically include oral isotretinoin, topical benzoyl peroxide, and oral or topical antibiotics [2]. However, due to concerns about safety, oral isotretinoin and antibiotics are not recommended for lactating women, posing challenges in treating acne in this population and often leading to emotional distress. While photodynamic therapy has shown effectiveness in patients unwilling to take oral medications [3], treating severe acne during lactation remains a complex issue with limited research available. In this unique case, fire needle combined with photodynamic therapy was successfully utilized to address severe acne in a lactating patient. Following treatment, the patient experienced clearance of cysts, nodules, and pustules, as well as an improvement in depressive symptoms, yielding significant outcomes. Nevertheless, the efficacy and safety of this combined approach warrant further investigation through clinical trials.

Analysis of Underwater Melting Process and Leakage Plugging Performance of Phase-Change Materials.

Leakage is a high-incidence disease of embankment dams, and efficiently addressing this disease guarantees the safe operation of dams. Underwater leakage self-priming plugging technology is a new technology that utilizes the melting and solidifying characteristics of phase-change materials and the negative pressure in the leakage entry area to accurately plug the leakage. However, little is yet known about the underwater melting process of phase-change materials and how their characteristics influence the plugging effect. In this study, three kinds of phase-change materials, namely, paraffin, rosin, and stearic acid, were used to conduct underwater leakage self-priming plugging tests, observe and analyze the underwater melting process, and compare the plugging effects. The results showed that the underwater melting process of phase-change materials exhibited different plugging window periods depending on their melting points, specific heat capacities, and mobilities, which were the main factors affecting their plugging effects. In the final plugging stage, paraffin had the best plugging effect, but the material strength was low; rosin had good plugging compactness, but the fluidity performance was poor, and the material effective utilization was low; stearic acid had a low melting point but dispersed easily. Therefore, a blocking material with a suitable blocking window period can be produced by adjusting the material properties accordingly for an improved blocking effect.

Divergent Synthesis of Sulfur-Containing Bridged Cyclobutanes by Lewis Acid Catalyzed Formal Cycloadditions of Pyridinium 1,4-Zwitterionic Thiolates and Bicyclobutanes.

Bridged cyclobutanes and sulfur heterocycles are currently under intense investigation as building blocks for pharmaceutical drug design. Two formal cycloaddition modes involving bicyclobutanes (BCBs) and pyridinium 1,4-zwitterionic thiolate derivatives were described to rapidly expand the chemical space of sulfur-containing bridged cyclobutanes. By using Ni(ClO4)2 as the catalyst, an uncommon higher-order (5+3) cycloaddition of BCBs with quinolinium 1,4-zwitterionic thiolate was achieved with broad substrate scope under mild reaction conditions. Furthermore, the first Lewis acid-catalyzed asymmetric polar (5+3) cycloaddition of BCB with pyridazinium 1,4-zwitterionic thiolate was accomplished. In contrast, pyridinium 1,4-zwitterionic thiolates undergo an Sc(OTf)3-catalyzed formal (3+3) reaction with BCBs to generate thia-norpinene products, which represent the initial instance of synthesizing 2-thiabicyclo[3.1.1]heptanes (thia-BCHeps) from BCBs. Moreover, we have successfully used this (3+3) protocol to rapidly prepare thia-BCHeps-substituted analogues of the bioactive molecule Pitofenone. Density functional theory (DFT) computations imply that kinetic factors govern the (5+3) cycloaddition reaction between BCB and quinolinium 1,4-zwitterionic thiolate, whereas the (3+3) reaction involving pyridinium 1,4-zwitterionic thiolates is under thermodynamic control.

Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway.

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.

The role of macrophage-derived Exosomes in reversing peritoneal fibrosis: Insights from Astragaloside IV.

BACKGROUND: Peritoneal dialysis (PD) is a successful renal replacement therapy for end-stage renal disease. Long-term PD causes mesothelial-mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs), leading to peritoneal fibrosis (PF), which reduces the efficiency of PD. Macrophages are thought to play a role in the onset and perpetuation of peritoneal injury. However, the mechanisms by which macrophages-PMCs communication regulates peritoneal fibrosis are not fully understood resulting in a lack of disease-modifying drugs. Astragaloside IV (AS-IV) possessed anti-fibrotic effect towards PF in PD whereas the mechanistic effect of AS-IV in PD is unknown. METHODS: The primary macrophages were extracted and treated with LPS or AS-IV, then co-cultured with primary PMCs in transwell plates. The macrophage-derived exosomes were extracted and purified by differential centrifugation, then co-cultured with primary PMCs. Small RNA-seq was used to detect differential miRNAs in exosomes, and then KEGG analysis and q-PCR were performed for validation. In vivo PD rat models were established by inducing with high-glucose peritoneal dialysis fluid and different concentrations of AS-IV and exosomes were intraperitoneal injection. Through qRT-PCR, western blotting, and luciferase reporting, candidate proteins and pathways were validated in vivo and in vitro. The functions of the validated pathways were further investigated using the mimic or inhibition strategy. PF and inflammatory situations were assessed. RESULTS: We found AS-IV reversed the MMT of PMCs caused by LPS-stimulated macrophages and the improving effect was mediated by macrophage-derived exosomes in vitro. We also demonstrated that AS-IV significantly reduced the MMT of PMCs in vitro or PF in a rat PD model via regulating exosome-contained miR-204-5p which targets Foxc1/ß-catenin signaling pathway. CONCLUSION: AS-IV attenuates macrophage-derived exosomes induced fibrosis in PD through the miR-204-5p/Foxc1 pathway.

Switching between the [2π+2σ] and Hetero-[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles.

The exploration of the complex chemical diversity of bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over the past two decades. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S-BCOs) and highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid-catalyzed formal cycloaddition of bicyclobutanes (BCBs) and 3-benzylideneindoline-2-thione derivatives have been established. The first hetero-(4+3) cycloaddition of BCBs, catalyzed by Zn(OTf)2, was achieved with a broad substrate scope under mild conditions. In contrast, the less electrophilic BCB ester undergoes a Sc(OTf)3-catalyzed [2π+2σ] reaction with 1,1,2-trisubstituted alkenes, yielding BCHs with a spirocyclic quaternary carbon center. Control experiments and preliminary theoretical calculations suggest that the diastereoselective [2π+2σ] product formation may involve a concerted cycloaddition between a zwitterionic intermediate and E-1,1,2-trisubstituted alkenes. Additionally, the hetero-(4+3) cycloaddition may involve a concerted nucleophilic ring-opening mechanism.

Case report: Report of a rare encounter: metastasis of renal cell carcinoma to the thyroid.

Renal cell carcinoma (RCC) is the most common renal tumor, with lung, bone, and liver being the primary sites of metastasis. Thyroid metastasis, on the other hand, is relatively uncommon. Metastatic tumors in the thyroid gland typically manifest as multiple or isolated nodules, which can be easily overlooked due to the lack of specific clinical and imaging features. However, the identification of thyroid metastasis suggests the presence of systemic metastasis and is indicative of a poor prognosis for patients. In this paper, we present two cases of thyroid metastasis following nephrectomy, with the objective of enhancing understanding among medical community regarding the diagnosis and treatment of thyroid metastasis originating from renal cell carcinoma. By raising awareness about this phenomenon, we emphasize the importance of early detection and diagnosis to improve patient prognoses. The implementation of standardized treatment protocols at the earliest possible stage is also emphasized. Through this research, we aim to contribute to the early identification and management of thyroid metastasis in patients with renal cell carcinoma, ultimately leading to improved outcomes.

Curcumin-polydopamine nanoparticles alleviate ferroptosis by iron chelation and inhibition of oxidative stress damage.

Ferroptosis, characterized by elevated iron levels and lipid peroxidation (LPO), is a recently identified regulatory mechanism of cell death. Its substantial involvement in ischemic tissue injury, neurodegenerative disorders, and cancer positions ferroptosis inhibition as a promising strategy for managing these diverse diseases. In this study, we introduce curcumin-polydopamine nanoparticles (Cur-PDA NPs) as an innovative ferroptosis inhibitor. Cur-PDA NPs demonstrate remarkable efficacy in chelating both Fe2+ and Fe3+in vitro along with scavenging free radicals. Cur-PDA NPs were found to efficiently mitigate reactive oxygen species, reduce Fe2+ accumulation, suppress LPO, and rejuvenate mitochondrial function in PC12 cells. Thus, these NPs can act as potent therapeutic agents against ferroptosis, primarily via iron chelation and reduction of oxidative stress.

Bioinspired Slippery Surfaces for Liquid Manipulation from Tiny Droplet to Bulk Fluid.

Slippery surfaces, which originate in nature with special wettability, have attracted considerable attention in both fundamental research and practical applications in a variety of fields due to their unique characteristics of superlow liquid friction and adhesion. Although research on bioinspired slippery surfaces is still in its infancy, it is a rapidly growing and enormously promising field. Herein, a systematic review of recent progress in bioinspired slippery surfaces, beginning with a brief introduction of several typical creatures with slippery property in nature, is presented. Subsequently,this review gives a detailed discussion on the basic concepts of the wetting, friction, and drag from micro- and macro-aspects and focuses on the underlying slippery mechanism. Next, the state-of-the-art developments in three categories of slippery surfaces of air-trapped, liquid-infused, and liquid-like slippery surfaces, including materials, design principles, and preparation methods, are summarized and the emerging applications are highlighted. Finally, the current challenges and future prospects of various slippery surfaces are addressed.

Two new jatrophane diterpenoids from Euphorbia helioscopia with activity towards autophagic flux.

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.

Carbene-Catalyzed [4+2] Cycloaddition of Cyclobutenones and Isatins for Quick Access to Chiral Chlorine-Containing Spirocyclic δ-Lactones.

Here we report a carbene-catalyzed enantio- and diastereoselective [4+2] cycloaddition reaction of cyclobutenones with isatins for the quick and efficient synthesis of spirocyclic δ-lactones bearing a chiral chlorine. A broad range of substrates with various substitution patterns proceed smoothly in this reaction, with the spirooxindole δ-lactone products afforded in generally good to excellent yields and optical purities under mild reaction conditions.

Corner- and edge-mode enhancement of near-field radiative heat transfer.

It is well established that near-field radiative heat transfer (NFRHT) can exceed Planck's blackbody limit1 by orders of magnitude owing to the tunnelling of evanescent electromagnetic frustrated and surface modes2-4, as has been demonstrated experimentally for NFRHT between two large parallel surfaces5-7 and between two subwavelength membranes8,9. However, although nanostructures can also sustain a much richer variety of localized electromagnetic modes at their corners and edges10,11, the contributions of such additional modes to further enhancing NFRHT remain unexplored. Here we demonstrate both theoretically and experimentally a physical mechanism of NFRHT mediated by the corner and edge modes, and show that it can dominate the NFRHT in the 'dual nanoscale regime' in which both the thickness of the emitter and receiver, and their gap spacing, are much smaller than the thermal photon wavelengths. For two coplanar 20-nm-thick silicon carbide membranes separated by a 100-nm vacuum gap, the NFRHT coefficient at room temperature is both predicted and measured to be 830 W m-2 K-1, which is 5.5 times larger than that for two infinite silicon carbide surfaces separated by the same gap, and 1,400 times larger than the corresponding blackbody limit accounting for the geometric view factor between two coplanar membranes. This enhancement is dominated by the electromagnetic corner and edge modes, which account for 81% of the NFRHT between the silicon carbide membranes. These findings are important for future NFRHT applications in thermal management and energy conversion.

Zn-based batteries for sustainable energy storage: strategies and mechanisms.

Batteries play a pivotal role in various electrochemical energy storage systems, functioning as essential components to enhance energy utilization efficiency and expedite the realization of energy and environmental sustainability. Zn-based batteries have attracted increasing attention as a promising alternative to lithium-ion batteries owing to their cost effectiveness, enhanced intrinsic safety, and favorable electrochemical performance. In this context, substantial endeavors have been dedicated to crafting and advancing high-performance Zn-based batteries. However, some challenges, including limited discharging capacity, low operating voltage, low energy density, short cycle life, and complicated energy storage mechanism, need to be addressed in order to render large-scale practical applications. In this review, we comprehensively present recent advances in designing high-performance Zn-based batteries and in elucidating energy storage mechanisms. First, various redox mechanisms in Zn-based batteries are systematically summarized, including insertion-type, conversion-type, coordination-type, and catalysis-type mechanisms. Subsequently, the design strategies aiming at enhancing the electrochemical performance of Zn-based batteries are underscored, focusing on several aspects, including output voltage, capacity, energy density, and cycle life. Finally, challenges and future prospects of Zn-based batteries are discussed.

Development of a hydroxypropyl methyl cellulose/polyacrylic acid interpolymer complex formulated buccal mucosa adhesive film to facilitate the delivery of insulin for diabetes treatment.

Buccal mucosa administration is a promising method for insulin (INS) delivery with good compliance. However, buccal mucosa delivery systems still face challenges of long-term mucosal adhesion, sustained drug release, and mucosal drug penetration. To address these issues, a double-layer film consisting of a hydroxypropyl methylcellulose/polyacrylic acid interpolymer complex (IPC)-formulated mucoadhesive layer and an ethylcellulose (EC)-formulated waterproof backing layer (IPC/EC film) was designed. Protamine (PTM) and INS were co-loaded in the mucoadhesive layer of the IPC/EC film (PTM-INS-IPC/EC film). In ex vivo studies with porcine buccal mucosa, this film exhibited robust adhesion, with an adhesion force of 120.2 ±â€¯20.3 N/m2 and an adhesion duration of 491 ±â€¯45 min. PTM has been shown to facilitate INS mucosal transfer. Pharmacokinetic studies indicated that the PTM-INS-IPC/EC film significantly improved the absorption of INS, exhibiting a 1.45 and 2.24-fold increase in the area under the concentration-time curve (AUC0-∞) compared to the INS-IPC/EC film and free INS, respectively. Moreover, the PTM-INS-IPC/EC film effectively stabilized the blood glucose levels of type 1 diabetes mellitus (T1DM) rats with post oral glucose administration, maintaining lower glucose levels for approximately 8 h. Hence, the PTM-INS-IPC/EC film provides a promising noninvasive INS delivery system for diabetes treatment.

Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis.

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for colon cancer therapy.

Immune checkpoint blockade therapy provides a new strategy for tumor treatment; however, the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects. Herein, we reported a lipid/PLGA nanocomplex (RDCM) co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase (IDO) inhibitor 1MT to improve immunotherapy of colon cancer. Arginine-glycine-aspartic acid (RGD) as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol (PEG), and programmed cell death-ligand 1 (PD-L1) peptide inhibitor DPPA (sequence: CPLGVRGK-GGG-d(NYSKPTDRQYHF)) was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker. The Ce6 and 1MT were encapsulated in PLGA nanoparticles. The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes. When the nanocomplexes were delivered to tumor, DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding. RGD facilitated the cellular internalization of nanocomplexes via avß3 integrin. Strong immunogenic cell death was induced by 1O2 generated from Ce6 irradiation under 660 nm laser. 1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment. The RDCM facilitated the maturation of dendritic cells, inhibited the activity of IDO, and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice, triggering a robust immunological memory effect, thus effectively preventing tumor metastasis. The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.