Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.

Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extra-gustatory tissues, suggesting its additional roles in diverse physiological processes and potential therapeutic applications3. Here, we present cryo-electron microcopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A GPCRs. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis, and molecular dynamic simulations studies, illuminate the receptor's broad-spectrum ligand recognition and activation via intricate multiple ligand-binding sites. Additionally, our study uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing our knowledge underlying bitter taste perception and its broader implications in sensory biology and drug discovery.

Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

Synthesis of Ultrathin High-Entropy Oxides with Phase Controllability.

High-entropy oxides (HEOs) with an ultrathin geometric structure are especially expected to exhibit extraordinary performance in different fields. The phase structure is deemed as a key factor in determining the properties of HEOs, rendering their phase control synthesis tempting. However, the disparity in intrinsic phase structures and physicochemical properties of multiple components makes it challenging to form single-phase HEOs with the target phase. Herein, we proposed a self-lattice framework-guided strategy to realize the synthesis of ultrathin HEOs with desired phase structures, including rock-salt, spinel, perovskite, and fluorite phases. The participation of the Ga assistor was conducive to the formation of the high-entropy mixing state by decreasing the formation energy. The as-prepared ultrathin spinel HEOs were demonstrated to be an excellent catalyst with high activity and stability for the oxygen evolution reaction in water electrolysis. Our work injects new vitality into the synthesis of HEOs for advanced applications and undoubtedly expedites their phase engineering.

Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration.

The rational design of multifunctional biomaterials with hierarchical porous structure and on-demand biological activity is of great consequence for bone tissue engineering (BTE) in the contemporary world. The advanced combination of trace element cerium ions (Ce3+) with bone repair materials makes the composite material capable of promoting angiogenesis and enhancing osteoblast activity. Herein, a living and phosphorylated injectable porous hydrogel microsphere (P-GelMA-Ce@BMSCs) is constructed by microfluidic technology and coordination reaction with metal ion ligands while loaded with exogenous BMSCs. Exogenous stem cells can adhere to and proliferate on hydrogel microspheres, thus promoting cell-extracellular matrix (ECM) and cell-cell interactions. The active ingredient Ce3+ promotes the proliferation, osteogenic differentiation of rat BMSCs, and angiogenesis of endotheliocytes by promoting mineral deposition, osteogenic gene expression, and VEGF secretion. The enhancement of osteogenesis and improvement of angiogenesis of the P-GelMA-Ce scaffold is mainly associated with the activation of the Wnt/ß-catenin pathway. This study could provide novel and meaningful insights for treating bone defects with biofunctional materials on the basis of metal ions.

Intraoperative Protection of Pharyngeal Autonomic Nerves: Preventing Dysphagia After Anterior Cervical Decompression and Fusion Surgery.

OBJECTIVE: The study aims to investigate whether intraoperative protection of the pharyngeal autonomic nerve can effectively reduce the incidence of postoperative dysphagia following anterior cervical decompression and fusion surgery (ACDF). METHODS: A retrospective analysis was conducted on 130 cases that underwent ACDF from January 2018 to June 2022 at our hospital. Divided into nonautonomic neuroprotection (NANP) group and autonomic neuroprotection group based on whether receive protective measures for the pharyngeal autonomic nerve during surgery. General data were recorded and compared between the 2 groups. Postoperative outcomes were evaluated using Neck Disability Index, Japanese Orthopaedics Association (JOA) score, and JOA improvement rate. The incidence and severity of postoperative dysphagia were assessed using Bazaz dysphagia assessment criteria and swallowing-quality of life questionnaire. RESULTS: There were no significant differences in general data (P > 0.05). The average operation time and intraoperative blood loss also showed no significant differences (P > 0.05). Both groups showed significant improvements in Neck Disability Index and JOA scores at all follow-up time points compared to preoperative scores (P < 0.01). The incidence of postoperative dysphagia in the autonomic neuroprotection group was significantly lower than that in the NANP group at all follow-up time points (P < 0.05). Both group showed a significant reduction in scores 3 days postoperatively compared to preoperative scores (P < 0.01), and the NANP group also showed significant reductions in scores at 3 month and 1 year postoperative follow-up time points compared to preoperative scores (P < 0.01). CONCLUSIONS: The adoption of pharyngeal autonomic nerve protective measures during ACDF can effectively lower the probability of postoperative dysphagia.

Channel-assisted cervical key hole technology combined with ultrasonic bone osteotome versus posterior percutaneous endoscopic cervical foraminotomy: a clinical retrospective study.

PURPOSE: The search for more effective and safe treatment methods for cervical spondylotic radiculopathy (CSR) has led to the rapid development and increasing popularity of minimally invasive posterior cervical foraminotomy (MI-PCF). This study aims to compare two important approaches for MI-PCF surgery: the channel-assisted cervical key hole technology combined with ultrasonic bone osteotome (CKH-UBO) and posterior percutaneous endoscopic cervical foraminotomy (PPECF). METHODS: Data from patients treated with single-level CKH-UBO (n = 35) or PPECF (n = 40) were analyzed. Clinical outcomes, including visual analogue scale (VAS) scores for neck and arm pain, Neck Disability Index (NDI), and modified Macnab criteria, were assessed preoperatively, as well as at three days, three months, and one year postoperatively. RESULTS: The percentages of patients with excellent and good outcomes were 97.14% and 92.5%, respectively. The average surgical time in the CKH-UBO group was significantly shorter than in the PPECF group (p < 0.001), while the average incision length in the PPECF group was significantly smaller than in the CKH-UBO group. There were no significant differences between the two groups in terms of blood loss, hospital stay, and clinical outcomes at three days, three months, and 12 months postoperatively. CONCLUSION: CKH-UBO can achieve the same surgical outcomes as PPECF for the treatment of CSR. However, CKH-UBO saves more time but requires patients to undergo larger incisions.

Overexpression of miR-7-5p Promoted Fracture Healing Through Inhibiting LRP4 and Activating Wnt/ß-Catenin Pathway.

Background. The bone healing after fracture had a great impact on the patients' life quality. However, how miR-7-5p participated in fracture healing has not been investigated. Methods. For in vitro studies, the pre-osteoblast cell line MC3T3-E1 was obtained. The male C57BL/6 mice were purchased for in vivo experiments, and the fracture model was constructed. Cell proliferation was determined by CCK8 assay, and alkaline phosphatase (ALP) activity was measured by commercial kit. Histological status was evaluated using H&E and TRAP staining. The RNA and protein levels were detected via RT-qPCR and western blotting, respectively. Results. Overexpression of miR-7-5p increased cell viability and ALP activity in vitro. Moreover, in vivo studies consistently indicated that transfection of miR-7-5p improved the histological status and increased the proportion of TRAP-positive cells. Overexpression of miR-7-5p suppressed LRP4 expression while upregulated Wnt/ß-catenin pathway. Conclusion. MiR-7-5p decreased LRP4 level and further activated the Wnt/ß-catenin signaling, facilitating the process of fracture healing.

A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration.

The periosteum plays a vital role in the regeneration of critical-size bone defects and highly comminuted fractures, promoting the differentiation of osteoblasts, accelerating the reconstruction of the vascular network, and guiding bone tissue regeneration. However, the materials loaded with exogenous growth factors are limited by the release and activity of the elements. Therefore, the material structure must be carefully designed for the periosteal function. Here, a self-adaptive biomimetic periosteum strategy is proposed, which is a novel interpenetrating double network hydrogel consisting of diselenide-containing gelatin and calcium alginate (modified natural collagen and polysaccharide) to enhance the stability, anti-swelling, and delayed degradation of the hydrogel. The diselenide bond continuously releases nitric oxide (NO) by metabolizing endogenous nitrosated thiols (RSNO), activates the nitric oxide-cycle guanosine monophosphate (NO-cGMP) signal pathway, coordinates the coupling effect of angiogenesis and osteogenesis, and accelerates the repair of bone defects. This self-adaptive biomimetic periosteum with the interpenetrating double network structure formed by the diselenide-containing gelatin and calcium alginate has been proven to be safe and effective in repairing critical-size bone defects and is expected to provide a promising strategy for solving clinical problems.

Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

Modeling of Supercritical CO2 Adsorption for Low-Permeability Coal Seam of Huainan-Huaibei Coalfield, China.

Investigating the coal adsorption behavior on supercritical CO2 (ScCO2) is crucial for long-term CO2 geological storage. In this paper, low-permeability coal samples from the Huainan-Huaibei coalfields in China were selected. The high-pressure isothermal adsorption of CO2 was carried out at 36, 42, and 48 °C. The results of adsorption experiments were analyzed by fitting 9 types of modified adsorption models, including three different adsorption theories. Considering that different adsorption mechanisms may exist for CO2 in coal, 14 mixed adsorption models were established. The accuracy of the coefficient of determination (R2) and root-mean-square error (RMSE) for ScCO2 excess adsorption capacity was analyzed, mainly focusing on the accuracy of the key model parameters such as the adsorption phase density and the theoretical adsorption capacity. These parameters were discussed, combined with the predicted adsorption phase density of CO2 based on the intercept method. The results indicate that among the 9 types of modified adsorption considered, based on the adsorption phase density screening, the deviation of the predicted adsorption capacity from the experimental value was then considered. The Dubinin-Radushkevich (DR) model can effectively fit the adsorption behavior of CO2 at low pressure (<7.5 MPa). The Langmuir (L), Langmuir-Freundlich (LF), Extended-Langmuir (EL), and TOTH models can effectively fit the adsorption behavior of CO2 at high pressure (7.5-20 MPa), while the multimolecular layer models were unsuitable for fitting ScCO2 adsorption. The model fitting results showed that only the monomolecular layer and micropore-filled adsorption models were suitable for fitting the ScCO2 adsorption capacity. The DR-LF model best fits the adsorption data based on its key parameters of adsorption phase density and theoretical adsorption capacity. The established mixed model DR-LF fitting results showed that the CO2 in coal was dominated by microporous filling adsorption. The higher the temperature, the greater the contribution of microporous filling adsorption to the total adsorption. There still exists deviation in the adsorption phase density and theoretical adsorption capacity. The contribution percentage of different adsorption mechanisms of CO2 in coal needs to be further investigated.

Study on the Microstructure of Mg-4Zn-4Sn-1Mn-xAl As-Cast Alloys.

In this study, the microstructure of the Mg-4Zn-4Sn-1Mn-xAl (x = 0, 0.3 wt.%, denoted as ZTM441 and ZTM441-0.3Al) as-cast alloys was investigated using scanning electron microscopy (SEM), focused-ion/electron-beam (FIB) micromachining, transmission electron microscopy (TEM), and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). The analysis results revealed that the microstructure of the ZTM441 and ZTM441-0.3Al as-cast alloys both mainly consist of the α-Mg matrix, skeleton-shaped MgZn2 eutectic texture, block-shaped Mg2Sn, and Zn/Sn-rich nanoscale precipitate bands along the grain boundary and the interdendrite. Nanoscale α-Mn dispersoids formed in the grain in the ZTM441 alloy, while no α-Mn formed in the ZTM441-0.3Al alloy instead of nanoscale Al3Mn2 particles. In the ZTM441 as-cast alloy, part of the Zn element is dissolved into the α-Mn phase, and part of the Mn element is dissolved into the MgZn2 phase, but in the ZTM441-0.3Al alloy, there are no such characteristics of mutual solubility. Zn and Mn elements are easy to combine in ZTM441 as-cast alloy, while Al and Mn are easy to combine in ZTM441-0.3Al as-cast alloy. The Mg-Zn phases have not only MgZn2-type crystal structure but also Mg4Zn7- and Mg149Zn-type crystal structure in the ZTM441-0.3Al as-cast alloy. The addition of Al changes the combination of Mn and Zn, promotes the formation of Al3Mn2, and the growth of the grain.

High Detectivity of PbS Films Deposited on Quartz Substrates: The Role of Enhanced Photogenerated Carrier Separation.

PbS films grown on quartz substrates by the chemical bath deposition method were annealed in an O2 atmosphere to investigate the role of oxygen in the sensitization process at different annealing temperatures. The average grain size of the PbS films gradually increased as the annealing temperature increased from 400 °C to 700 °C. At an annealing temperature of 650 °C, the photoresponsivity and detectivity reached 1.67 A W-1 and 1.22 × 1010 cm Hz1/2 W-1, respectively. The role of oxides in the sensitization process was analyzed in combination with X-ray diffraction and scanning electron microscopy results, and a three-dimensional network model of the sensitization mechanism of PbS films was proposed. During the annealing process, O functioned as a p-type impurity, forming p+-type PbS layers with high hole concentrations on the surface and between the PbS grains. As annealing proceeds, the p+-type PbS layers at the grain boundaries interconnect to form a three-dimensional network structure of hole transport channels, while the unoxidized p-type PbS layers act as electron transport channels. Under bias, photogenerated electron-hole pairs were efficiently separated by the formed p+-p charge separation junction, thereby reducing electron-hole recombination and facilitating a higher infrared response.

Clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of II° lumbar isthmic spondylolisthesis: A retrospective cohort study.

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is not suitable for high-grade isthmic spondylolisthesis, whether MIS-TLIF can treat II° lumbar isthmic spondylolisthesis (IS) is still controversial. This retrospective cohort study compared the clinical efficacy of MIS-TLIF and open transforaminal lumbar interbody fusion (OPEN-TLIF) in the treatment of II° lumbar IS. From January 2017 to January 2023, 101 patients with II° lumbar IS were diagnosed in our hospital and underwent surgical treatment, of which 53 received MIS-TLIF surgery and 48 received OPEN-TLIF surgery. The operation time, blood loss and surgical complications were compared between the 2 groups. The pain, function, reduction rate and fusion rate of the patients were evaluated during follow-up. The amount of intraoperative blood loss, postoperative drainage, and postoperative hospital stay in the MIS-TLIF group were significantly lower than those in the OPEN-TLIF group were (P < .01). In the MIS-TLIF group, there were 1 case of dural sac injury and 3 cases of lower limb paralysis. The complication rate of MIS-TLIF was lower than the OPEN-TLIF group (P = .032). In the visual analog scale score of low back pain, the MIS-TLIF group was lower than the OPEN-TLIF group after operation and at the last follow-up. There were no significant differences in postoperative leg pain score, slippage rate, and fusion rate between the 2 groups. Compared with OPEN-TLIF, MIS-TLIF has the advantages of better low back pain relief, less trauma, less bleeding and faster recovery, and is worthy of clinical promotion.

Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3-Energized and Microenvironment-Modulated Hydrogel Microspheres to Impede Osteoarthritis.

Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3-TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM). Molecular mechanical investigations disclose that SIRT3-induced chondroprotection depended on the repression of mitochondrial apoptosis (mtApoptosis) and the activation of mitophagy. Inspired by the high-level matrix proteinases and reactive oxygen species (ROS) in the OA environment, by anchoring gelatin methacrylate (GelMA) and benzenediboronic acid (PBA) to hyaluronic acid methacrylate (HAMA) with microfluidic technology, a dual-responsive hydrogel microsphere laden with DMY is tactfully fabricated and named as DMY@HAMA-GelMA-PBA (DMY@HGP). In vivo injection of DMY@HGP ameliorated cartilage abrasion and subchondral bone sclerosis, as well as promoted motor function recovery in post-traumatic OA (PTOA) model via recouping endogenous mtApoptosis and mitophagy balance. Overall, this study unveils a novel mitochondrial dynamic-oriented strategy, holding great promise for the precision treatment of OA.

ETU-Net: efficient Transformer and convolutional U-style connected attention segmentation network applied to endoscopic image of epistaxis.

Epistaxis is a typical presentation in the otolaryngology and emergency department. When compressive therapy fails, directive nasal cautery is necessary, which strongly recommended operating under the nasal endoscope if it is possible. Limited by the operator's clinical experience, complications such as recurrence, nasal ulcer, and septum perforation may occur due to insufficient or excessive cautery. At present, deep learning technology is widely used in the medical field because of its accurate and efficient recognition ability, but it is still blank in the research of epistaxis. In this work, we first gathered and retrieved the Nasal Bleeding dataset, which was annotated and confirmed by many clinical specialists, filling a void in this sector. Second, we created ETU-Net, a deep learning model that smartly integrated the excellent performance of attention convolution with Transformer, overcoming the traditional model's difficulties in capturing contextual feature information and insufficient sequence modeling skills in picture segmentation. On the Nasal Bleeding dataset, our proposed model outperforms all others models that we tested. The segmentation recognition index, Intersection over Union, and F1-Score were 94.57 and 97.15%. Ultimately, we summarized effective ways of combining artificial intelligence with medical treatment and tested it on multiple general datasets to prove its feasibility. The results show that our method has good domain adaptability and has a cutting-edge reference for future medical technology development.

A Monolayer High-Entropy Layered Hydroxide Frame for Efficient Oxygen Evolution Reaction.

High-entropy materials with tailored geometric and elemental compositions provide a guideline for designing advanced electrocatalysts. Layered double hydroxides (LDHs) are the most efficient oxygen evolution reaction (OER) catalyst. However, due to the huge difference in ionic solubility product, an extremely strong alkali environment is necessary to prepare high-entropy layered hydroxides (HELHs), which results in an uncontrollable structure, poor stability, and scarce active sites. Here, a universal synthesis of monolayer HELH frame in a mild environment is presented, regardless of the solubility product limit. Mild reaction conditions allow this study to precisely control the fine structure and elemental composition of the final product. Consequently, the surface area of the HELHs is up to 380.5 m2  g-1 . The current density of 100 mA cm-2 is achieved in 1 m KOH at an overpotential of 259 mV, and, after 1000 h operation at the current density of 20 mA cm-2 , the catalytic performance shows no obvious deterioration. The high-entropy engineering and fine nanostructure control open opportunities to solve the problems of low intrinsic activity, very few active sites, instability, and low conductance during OER for LDH catalysts.

Liquid metal for high-entropy alloy nanoparticles synthesis.

High-entropy alloy nanoparticles (HEA-NPs) show great potential as functional materials1-3. However, thus far, the realized high-entropy alloys have been restricted to palettes of similar elements, which greatly hinders the material design, property optimization and mechanistic exploration for different applications4,5. Herein, we discovered that liquid metal endowing negative mixing enthalpy with other elements could provide a stable thermodynamic condition and act as a desirable dynamic mixing reservoir, thus realizing the synthesis of HEA-NPs with a diverse range of metal elements in mild reaction conditions. The involved elements have a wide range of atomic radii (1.24-1.97 Å) and melting points (303-3,683 K). We also realized the precisely fabricated structures of nanoparticles via mixing enthalpy tuning. Moreover, the real-time conversion process (that is, from liquid metal to crystalline HEA-NPs) is captured in situ, which confirmed a dynamic fission-fusion behaviour during the alloying process.

The clinicopathological and immunohistochemical features of breast carcinomas with signet-ring-cell differentiation.

BACKGROUND: This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin. METHODS: A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People's Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis. RESULTS: Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic. CONCLUSION: We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study.