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Transarterial radioembolization (TARE) is a local radionuclide therapy and is successfully used in hepatocellular carcinoma (HCC) treatment. Radioactive microspheres have been widely studied for TARE. Preparation of ideal radioactive microspheres is significant for clinical research and patient treatment. In this study, we have designed a novel multifunctional microsphere, i.e., polydopamine (PDA)-coated 177Lu-radiolabeled silica microspheres (MS) denoted as 177Lu-MS@PDA, which can be used for TARE and photothermal therapy (PTT). The radiostability of 177Lu-MS@PDA was significantly improved by coating 177Lu-MS with PDA. In addition, the coating of PDA makes microspheres have excellent photothermal performance. MicroSPECT/CT images showed that 177Lu-MS@PDA was accurately embolized and remained in the tumor during the observation time. At the time, it also showed that 177Lu-MS@PDA was very stable in vivo. Furthermore, the anti-tumor results demonstrated that TARE combined with PTT of 177Lu-MS@PDA can significantly inhibit tumor growth without obvious side effects. 177Lu-MS@PDA holds great potential as a promising radioactive microsphere for HCC.

During tandem hot rolling (THR), the rolling force plays an important role in strip shape control, but the influence mechanism of the rolling force on the strip shape is still currently unclear. This paper proposes a novel 3D multi-stand coupled thermo-mechanical finite element (FE) model for the THR developed employing a segmentation modelling strategy and data transfer technologies. This developed FE model has been validated by industrial experiments. Besides, the effects of rolling force on the strip shape (including strip crown and flatness) in the THR have been quantitatively studied. Results show that the strip crown increases with the rolling force at each stand, while the regulation efficiency of rolling force on the strip crown decreases continuously from (Finish stand 1) F1 to (Finish stand 7) F7, which is attributed to the significant increase in strip plastic rigidity from F1 to F7. Furthermore, lateral metal flow and strip plastic rigidity have a coupled effect on the regulation efficiency of rolling force on the strip flatness; more precisely, the regulation efficiency is mainly affected by the lateral metal flow in the upstream stand, while it is mainly influenced by the strip plastic rigidity in the downstream stand. These findings not only throw light on the influence mechanism of rolling force on the strip shape, but also offer a way to control and improve the strip shape by employing reasonable rolling force during industrial production.

Oceanic mesoscale eddies (with scale 101–102km) and their submesoscale fine structures (with scale 100–101km) can effectively induce vertical motions and bring nutrients into the oceanic euphotic layer, which leaves abundant footprints on the ocean surface chlorophyll distributions and have the potential to promote primary productivity of oceanic ecosystem. In return, these surface chlorophyll footprints observed by ocean color satellites can serve as a useful tool to reveal the spatial structures of mesoscale eddies and their submesoscale fine structures. By combining artificial intelligence (AI) algorithms to develop a series of identification strategies for typical surface chlorophyll patterns around mesoscale eddies, we find that over 20% of mesoscale eddy observations exhibit identifiable typical chlorophyll patterns, which tends to regulate an increase of the surface chlorophyll concentration within the corresponding eddies, especially enhancing by about 30% in nutrient‐restricted subtropical regions compared with the background values. Based on their geometric features, typical chlorophyll patterns are primarily classified as Core, Spiral, Tail, Ring, Loop, and Eye respectively by clustering algorithm. Further spatial‐spectral analysis found that the typical patterns on eddies exhibit a much steeper wave‐number spectral slope about −3, compared to the non‐typical distributions on eddies and the non‐eddy background distribution (about −2.7–−2.2). This implies that the occurrence of different typical chlorophyll patterns may correspond to specific mesoscale and submesoscale dynamic processes. Mesoscale eddies and their submesoscale fine structures collectively play non‐negligible roles in sustaining nutrient supply and promoting productivity in the oceanic euphotic layer. Although submesoscale processes are believed to result in ageostrophic motions and allow forward oceanic energy cascade, the resolutions of traditional in‐situ ocean measurements and satellite altimetry observations are typically too coarse to resolve them. In this paper, we elaborate on artificial intelligence (AI) techniques to develop a series of typical surface chlorophyll pattern identification strategies. The AI framework automatically identified six types of typical chlorophyll patterns of mesoscale eddy, in the context of the generally comparable geometric characteristics that are potentially reflected from their underlined oceanic dynamics. Over 20% mesoscale eddy observations tend to exhibit identifiable typical chlorophyll patterns, which leads to a remarkable increase of surface chlorophyll concentration. The wave‐number spectrum of eddy‐induced typical patterns exhibit a significantly steeper slope, in comparison of the non‐typical distributions on eddies and the non‐eddy background distribution. Our results may help to establish parameterizations for the submesoscale processes of mesoscale eddies, or provide an observational baseline to verify high‐resolution physical‐biogeochemical coupled oceanic numerical models, or even improve the model simulations of oceanic primary productivity and carbon fixation capacity. Six types of typical chlorophyll patterns on mesoscale eddies and their submesoscale fine‐structures are identified globally by artificial intelligence (AI) methodThe typical patterns tend to substantially enhance chlorophyll concentration of the corresponding eddiesThe wave‐number spectral slope of the typical chlorophyll pattern is significantly different from the background value Six types of typical chlorophyll patterns on mesoscale eddies and their submesoscale fine‐structures are identified globally by artificial intelligence (AI) method The typical patterns tend to substantially enhance chlorophyll concentration of the corresponding eddies The wave‐number spectral slope of the typical chlorophyll pattern is significantly different from the background value

As one of the most common cancers in the world, hepatocellular carcinoma (HCC) has become a major threat to human health. Radioembolization is a first-line option for the treatment of HCC, especially when other conventional treatments fail or there exist some relative contraindications. Herein, we developed a facile and efficient method for preparing 177Lu-microspheres potentially useful for precise radioembolization therapy of HCC. The radiolabeling efficiency of 177Lu-microspheres was as high as 96.8% ± 0.5%, and the radiolabeling process did not alter the morphology of the mother microspheres. The SPECT/CT studies enabled by the unique emissions of 177Lu suggested that almost no 177Lu ion loaded by the microspheres was released over more than 32 d in vivo, which led to remarkable inhibition effect on the growth of HepG2 tumors subcutaneously transplanted in mice. The current approach may thus offer promising 177Lu-microspheres for clinical radioembolization of HCC.

ABSTRACTMacroautophagy/autophagy is known to be important for intracellular quality control in the lens. GJA8 is a major gap junction protein in vertebrate lenses. Mutations in GJA8cause cataracts in humans. The well-known cataractogenesis mechanism is that mutated GJA8 leads to abnormal assembly of gap junctions, resulting in defects in intercellular communication among lens cells. In this study, we observed that ablation of Gja8b (a homolog of mammalian GJA8) in zebrafish led to severe defects in organelle degradation, an important cause of cataractogenesis in developing lens. The role of autophagy in organelle degradation in lens remains disputable. Intriguingly, we also observed that ablation of Gja8b induced deficient autophagy in the lens. More importantly, in vivotreatment of zebrafish with rapamycin, an autophagy activator that inhibits MAPK/JNK and MTORC1 signaling, stimulated autophagy in the lens and relieved the defects in organelle degradation, resulting in the mitigation of cataracts in gja8bmutant zebrafish. Conversely, inhibition of autophagy by treatment with the chemical reagent 3-MA blocked these recovery effects, suggesting the important roles of autophagy in organelle degradation in the lens in gja8bmutant zebrafish. Further studies in HLE cells revealed that GJA8 interacted with ATG proteins. Overexpression of GJA8 stimulated autophagy in HLE cells. These data suggest an unrecognized cataractogenesis mechanism caused by ablation of Gja8b and a potential treatment for cataracts by stimulating autophagy in the lens.Abbreviations:3-MA: 3-methyladenine; ATG: autophagy related; AV: autophagic vacuoles; Dpf: days post fertilization; GJA1: gap junction protein alpha 1; GJA3: gap junction protein alpha 3; GJA8: gap junction protein alpha 8; Hpf: hours post fertilization; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; WT: wild type.

Cucumber (Cucumis sativusL.) is a widely cultivated crop with rich germplasm resources, holding significant nutritional value. It also serves as an important model for studying epidermal cell fate and sex determination. Cucumbers are covered with multicellular and unbranched trichomes, including a specific type called spines found on the surface of the fruit. The presence and density of these fruit spines determine the visual quality of cucumber fruits. However, the key regulatory genes and mechanisms underlying cucumber fruit spine development remain poorly understood. In this study, we identified a WUSCHEL-related homeobox (WOX) family gene CsWOX3, which functioned as a typical transcriptional repressor and played a negative role in fruit spine development. Spatial–temporal expression analysis revealed that CsWOX3exhibited a relatively high expression level in the cucumber female floral organs, particularly in the fruit exocarp. Knockout of CsWOX3using CRISPR/Cas9 resulted in a significant 2-to-3-fold increase in the diameter of fruit spines base, while overexpression led to a 17% decrease in the diameter compared to the wild-type. A SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factor CsSPL15 could directly bind and activate the expression of CsWOX3, thereby suppressing the expression of downstream auxin-related genes, such as CsARF18. Additionally, the RING-finger type E3 ubiquitin ligase CsMIEL1-like interacted with the HD domain of CsWOX3, which might result in the ubiquitination and subsequent alteration in protein stability of CsWOX3. Collectively, our study uncovered a WOX transcription factor CsWOX3and elucidated its expression pattern and biological function. This discovery enhances our comprehension of the molecular mechanism governing cucumber fruit spine morphogenesis.

Radionuclides for cancer theranostic have confronted problems such as limitation in real-time visualization and unsatisfactory therapeutic effect sacrificed by the nonspecific distribution. Nanoscale metal–organic frameworks (nMOFs) have been widely used in biomedical applications including cancer imaging and drug delivery. However, there have been rare reports utilizing nMOFs as a single nanoplatform to label various radionuclides for tumor imaging and radioisotope therapy (RIT). In this work, we developed polyethylene glycol (PEG) modified zirconium-based nMOFs (PCN-224) with favorable size, water solubility and biocompatibility. Interestingly, without the help of chelating agents, metal radionuclides (technetium-99 m/99mTc, lutetium-177/177Lu) could be efficiently labeled onto nMOFs viachelating with the porphyrin structure and iodine-125 (125I) viachemical substitution of hydrogen in the benzene ring. The radionuclide-labeled PCN-PEG nanoparticles all exhibit excellent radiolabeling stability in different solutions. In accordance with the fluorescence imaging of mice injected with PCN-PEG, SPECT/CT imaging illustrates strong tumor accumulation of 99mTc-PCN-PEG. Moreover, 177Lu-PCN-PEG significantly inhibited the growth of tumor without inducing any perceptible toxicity to the treated mice. Hence, the radionuclide-delivery nanoplatform based on nMOFs would provide more opportunities for precise tumor theranostics and expand the biomedical applications of MOF nanomaterials.

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. Methods: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. Results: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. Conclusion: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.

To overcome the drawbacks of traditional therapy for corneal neovascularization (CNV), we evaluated the efficacy of polyethylene glycol (PEG)-conjugated APRPG peptide modified dexamethasone (Dex), a novel nano-prodrug (Dex-PEG-APRPG, DPA).

Mitochondrial malfunction and autophagy defects are often concurrent phenomena associated with neurodegeneration. We show that Miga, a mitochondrial outer-membrane protein that regulates endoplasmic reticulum-mitochondrial contact sites (ERMCSs), is required for autophagy. Loss of Miga results in an accumulation of autophagy markers and substrates, whereas PI3P and Syx17 levels are reduced. Further experiments indicated that the fusion between autophagosomes and lysosomes is defective in Migamutants. Miga binds to Atg14 and Uvrag; concordantly, Miga overexpression results in Atg14 and Uvrag recruitment to mitochondria. The heightened PI3K activity induced by Miga requires Uvrag, whereas Miga-mediated stabilization of Syx17 is dependent on Atg14. Miga-regulated ERMCSs are critical for PI3P formation but are not essential for the stabilization of Syx17. In summary, we identify a mitochondrial protein that regulates autophagy by recruiting two alternative components of the PI3K complex present at the ERMCSs.

Immunohistochemistry (IHC) plays an important role in target protein analysis. However, many researchers analyze IHC images by five/three-tier manual ranking methods based on stained area and density. Such manual scoring might be biased by the antibody amount, counterstaining density, overall brightness, and most importantly, researchers' ranking experience. The potential lack of reliability in manual approach drives us to develop an automatic tool to quantitatively analyze IHC, which can also be used for immunocytochemistry (ICC). We applied a “color deconvolution” method based on an red-green-blue (RGB) color vector matching the color of desired immunochemistry agent, 3,3′-diaminobenzidine (DAB) with haematoxylin in this case, to acquire pseudo-color images. Subsequently, Density, the product of integrating the single pixel staining density by area stained, is used as an index of immunostaining. We observed a strong correlation between the results by our automatic method and the manual scoring from experienced researchers, demonstrating the utility of this method in IHC and ICC. For IHC analysis, five-tier ranking based on density (n = 161) shows a high Spearman's coefficient (rho) of 0.80 (P < 0.0001) with the annotation given by two experienced scientists. However, the rho between experienced and inexperienced researchers' annotation (n = 154) is only 0.66 (P < 0.0001). In immunocytochemistry, the rho between density and experienced researchers' annotation is 0.80 (n = 44, P < 0.0001). In conclusion, our method can rank multiple protein targets in immunohistochemistry and may be also used in immunochemistry.