Evaluation of Wetting Behaviors of Liquid Sodium on Transition Metals: An Experimental and Molecular Dynamics Simulation Study.

In sodium-cooled fast reactors, the wettability of sodium with materials is closely related to sodium-related operations and the detection accuracy of instruments and meters, so how to achieve the selection of materials with different wettability requirements is a key problem in engineering design. To meet these requirements, the wetting behaviors of liquid sodium with nine transition metals were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), and molecular dynamics (MD) simulations. The results show that metals such as zinc and gold, which react with sodium to form intermetallic compounds at the interface, exhibit superior wettability. Followed by the metals that have strong interatomic interactions even though they do not react with sodium or dissolve each other, such as cobalt, nickel and copper, while the wettability of these systems tends to be poor at low temperatures. Systems that do not react with each other or have strong interatomic affinities proved to be the most difficult to wet. Notably, metals with the closest-packed crystal structures of fcc and hcp generally have better wettability than those with a bcc structure. They can be a valuable guide for experimental research and technical control.

Effectiveness and safety of remimazolam combined with alfentanil in hysteroscopic examination: A prospective, randomized, single-blind trial.

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50). METHODS: Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon's up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination. MAIN RESULTS: The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195-0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261-1.619). CONCLUSION: In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.

Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis Amplifies In Situ Tumor Vaccination for Boosting Antitumor Immunity.

Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situ tumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situ tumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in "cold" tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situ tumor vaccines.

Prelacrimal recess approach for maxillary sinus inverted papilloma: a 15-year experience from a single center.

PURPOSE: This large retrospective, single-center, follow-up study investigated the endoscopic prelacrimal recess approach (PLRA) for treating maxillary sinus inverted papilloma (MSIP). METHODS: Between January 2007 and November 2022, patients with MSIP treated with PLRA were enrolled. Data on clinical manifestations, imaging, and surgical procedures were collected. The visual analog scale (VAS) scores for maxillofacial numbness and nasal symptoms and the SNOT-22 nasal symptom scores were statistically analyzed. RESULT: Of 122 patients (68 males and 54 females) enrolled in the study, with a mean age of 50.75 ± 12.84 years (26-80 years), 111 patients underwent PLRA, nine underwent modified PLRA, one converted to an endoscopic medial maxillectomy (EMM), and one to an endoscopic modified Denker's approach. The average follow-up was 86.60 (13-192) months, the recurrence rate was 3.28%, and 29 patients (23.77%) complained of maxillofacial numbness one month postoperatively, which disappeared in most cases one year after surgery. Five patients (4.10%) experienced mild numbness at the end of the follow-up period. Maxillary sinus ostium contracture or atresia occurred in two cases (1.64%). After surgery, the VAS nasal symptom scores improved significantly (P < 0.001). SNOT-22 indicated that the most common postoperative symptom was thick nasal discharge. CONCLUSION: PLRA is a flexible first-choice surgical treatment for maxillary sinus inverted papilloma and can be modified according to the extent of the lesion, the surgeon's experience and technique, and surgical instruments. That can help achieve complete resection and reduce recurrence and surgical complications. Upper teeth numbness, the most common postoperative complication, tends to disappear after 1 year.

AIE luminogen labeled polymeric micelles for biological imaging and chemotherapy.

In this study, an amphiphilic polymer FA-CS-DBA-CHO with aggregation-induced emission (AIE) feature was prepared by introducing 4-(diphenylamino)benzaldehyde derivative (DBA-CHO), imine bond and folic acid (FA) to the molecular structure of chitosan (CS). The amphiphilicity drove the polymer to self-assemble into micelles, and paclitaxel (PTX) could be solubilized in the hydrophobic core. Due to the excellent AIE effect, FA-CS-DBA-CHO exhibited strong cellular imaging capability. The pH-sensitive imine bond in the polymer allowed for accurate drug release in acidic environment. Both in vitro and in vivo studies demonstrated that the PTX-loaded FA-CS-DBA-CHO micelles could significantly inhibit the growth of tumor cells but without any notable toxicity. This micellar system was excellent carrier for bioimaging and chemotherapeutic drug delivery.

Correlation between ovarian follicular development and Hippo pathway in polycystic ovary syndrome.

BACKGROUND: For women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular development, proliferation of small antral follicles, and cystic follicles. The mechanism underlying its occurrence is not clear. The abnormal proliferation and development of follicles in PCOS patients is a complex process, which is affected by many factors. The objective of this study was to investigate the relationship between the Hippo pathway and follicular development in PCOS, and to further explore this relationship by using the YAP inhibitor verteporfin (VP). METHOD: 30 3-week-old BALB/C female rats were randomly divided into control group (n = 10), DHEA group (n = 10) and DHEA + VP group (n = 10). The morphology of ovary and the degree of follicular development were observed by HE staining, and the expression and location of AMH in ovarian follicles were observed by immunofluorescence. The ovarian reserve function index AMH, cell proliferation index PCNA and the ratio of Hippo pathway related proteins MST, LATS, YAP, P-YAP and P-YAP/YAP were detected by Western blot. RESULTS: After dividing 30 3-week-old female mice into control, dehydroepiandrosterone (DHEA; model of PCOS), and DHEA + VP groups, we found that the number of small follicles increased in the DHEA group compared to the control group. Additionally, in the DHEA group compared to the control group, anti-müllerian hormone (AMH; ovarian reserve index) increased, proliferating cell nuclear antigen (PCNA; cell proliferation index) decreased, and upstream (MST and LATS) and downstream (YAP and p-YAP) proteins in the Hippo pathway increased, though the p-YAP/YAP ratio decreased. VP ameliorated the increases in AMH, MST, LATS, YAP and p-YAP, but did not ameliorate the decrease in the p-YAP/YAP ratio. CONCLUSIONS: This study indicates that the increased small follicles in the ovaries and changes in ovarian reserve and cell proliferation may be closely related to Hippo pathway activation. This suggests that the Hippo pathway may be an important pathway affecting the proliferation and development of follicles and the occurrence of PCOS.

DBC1 maintains skeletal muscle integrity by enhancing myogenesis and preventing myofibre wasting.

BACKGROUND: Skeletal muscle atrophy, particularly ageing-related muscular atrophy such as sarcopenia, is a significant health concern. Despite its prevalence, the underlying mechanisms remain poorly understood, and specific approved medications are currently unavailable. Deleted in breast cancer 1 (DBC1) is a well-known regulator of senescence, metabolism or apoptosis. Recent reports suggest that DBC1 may also potentially regulate muscle function, as mice lacking DBC1 exhibit weakness and limpness. However, the function of DBC1 in skeletal muscle and its associated molecular mechanisms remain unknown, thus prompting the focus of this study. METHODS: Tibialis anterior (TA) muscle-specific DBC1 knockdown C57BL/6J male mice were generated through a single injection of 2.00 E + 11 vg of adeno-associated virus 9 delivering single-guide RNA for DBC1. Grip strength and endurance were assessed 2 months later, followed by skeletal muscle harvest. Muscle atrophy model was generated by cast immobilization of the mouse hindlimb for 2 weeks. Molecular markers of atrophy were probed in muscles upon termination. Cardiotoxin (CTX) was injected in TA muscles of DBC1 knockdown mice, and muscle regeneration was assessed by immunohistochemistry, quantitative PCR and western blotting. DBC1 knockdown C2C12 cells and myotubes were investigated using immunofluorescence staining, Seahorse, immunohistology, fluorescence-activated cell sorting and RNA-sequencing analyses. RESULTS: DBC1 knockdown in skeletal muscle of young mice led to signatures of muscle atrophy, including a 28% reduction in muscle grip force (P = 0.023), a 54.4% reduction in running distance (P = 0.002), a 14.3% reduction in muscle mass (P = 0.007) and significantly smaller myofibre cross-sectional areas (P < 0.0001). DBC1 levels decrease in age-related or limb immobilization-induced atrophic mouse muscles and overexpress DBC1-attenuated atrophic phenotypes in these mice. Muscle regeneration was hampered in mice with CTX-induced muscle injury by DBC1 knockdown, as evidenced by reductions in myofibre cross-sectional areas of regenerating myofibres with centralized nuclei (P < 0.0001), percentages of MyoG+ nuclei (P < 0.0001) and fusion index (P < 0.0001). DBC1 transcriptionally regulated mouse double minute 2 (MDM2), which mediated ubiquitination and degradation of forkhead box O3 (FOXO3). Increased FOXO3 proteins hampered myogenesis in DBC1 knockdown satellite cells by compromising around 50% of mitochondrial functions (P < 0.001) and exacerbated atrophy in DBC1 knockdown myofibres by activating the ubiquitin-proteasome and autophagy-lysosome pathways. CONCLUSIONS: DBC1 is essential in maintaining skeletal muscle integrity by protecting against myofibres wasting and enhancing muscle regeneration via FOXO3. This research highlights the significance of DBC1 for healthy skeletal muscle function and its connection to muscular atrophy.

Establishment of an immortalized cell line derived from human adenomyosis ectopic lesions.

Because adenomyosis (AM) ectopic primary cells are hard to come by, have a short lifespan, and the characteristics that alter over time, their utility in AM research is constrained. This study aimed to establish a line of immortalized human adenomyosis ectopic cell (ihAMEC) to change this situation. Primary cells were obtained from AM ectopic lesion tissue and then infected with Simian Vacuolating Virus 40 Tag (SV40 T) lentivirus and screened to establish immortalized cells. We verified the main features and found that the ihAMEC could be cultured for more than 50 generations and the proliferation ability of ihAMEC was more active than that of primary cells. The cytoskeleton and cell types of ihAMEC were similar to primary cells and maintained a normal karyotype. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins, and estrogen/progesterone receptors in ihAMEC was similar to the expression seen in primary cells. In addition, the response of ihAMEC under estrogen treatment and Lipopolysaccharide intervention is similar to primary cells. The clonogenic ability of ihAMEC was lower than tumor cells and did not form tumors in tumorigenicity assays. Thus, ihAMEC can be used as in vitro cellular model for pathogenesis and drug development studies regarding AM.

Accuracy of antibiotic concentrations in drug dispensing in neonates: a laboratory-based study.

BACKGROUND: Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates. METHODS: Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy. RESULTS: The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.

Fabrication of Zn-Air Battery with High Output Capacity Under Ultra-Large Current.

Zn-air battery (ZAB) is advocated as a more viable option in the new-energy technology. However, the limited-output capacity at a high current density impedes the driving range in power batteries substantially. Here, a novel heterojunction-based graphdiyne (GDY) and Ag29Cu7 alloy quantum dots (Ag29Cu7 QDs/GDY) for constructing a high-performance aqueous ZAB are fabricated. The as-fabricated ZAB achieves discharge at up to 100 mA cm-2 (the highest value ever reported) along with a remarkable output specific capacity of 786.2 mAh g-1 Zn , which is mainly benefitted from the binary-synergistic effect toward a stable triple-phase interface for air electrode induced by the Ag29Cu7 QDs and GDY in harsh base, together with the decreasing reaction energy barrier and polarization. The results outperform the superior reports discharging at low current and will bring breakthrough progress toward the practical applications of ZAB on large power supply facilities.

Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning.

MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

Upregulation of eIF2α by m6A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m6A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m6A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.

The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents.

Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.

Whole exome sequencing and transcriptome analysis in two unrelated patients with novel SET mutations.

The human SET nuclear proto-oncogene (SET) gene is a protein-coding gene that encodes proteins that affects chromatin remodeling and gene transcription. Mutations in the SET gene have been reported to cause intellectual disability (ID) and epilepsy. In this study, we collected and analyzed clinical, genetic, and transcript features of two unrelated Chinese patients with ID. Both patients were characterized by moderate intellectual disability. Whole-exome sequencing identified two novel heterozygous mutations in the SET gene: NM_001122821.1:c.532-3 T > A and NM_001122821.1:c.3 G > C (p.0?). Additionally, RNA sequencing revealed widespread dysregulation of genes involved in NF-kB signaling and neuronal system in these two patients. To our knowledge, this is the first report of SET mutations causing ID in the Chinese population, broadening the genetic and ethnic spectrum of SET-related disorders and highlighting the importance of screening for SET gene variants.

Sulfur dioxide-releasing polymeric micelles based on modified hyaluronic acid for combined cancer therapy.

In this study, an amphiphilic polymer mPEG-HA(SA)-DNs was designed and synthesized to fabricate a multifunctional micellar system to enhance the therapeutic efficacy and reduce the toxic effect of paclitaxel (PTX). The polymer was prepared by introducing mPEG, stearic acid (SA) and 2,4-dinitrobenzenesulfonic acid (DNs) to the backbone of hyaluronic acid (HA). With above modifications, the fabricated micelles could encapsulate PTX in the core with high drug loading. The optimized PTX-loaded micelles had a mean size of 158.3 nm. Upon the effect of mPEG, the mPEG-HA(SA)-DNs micelles reduced the non-specific protein adsorption. In vitro drug release study revealed the excellent glutathione (GSH)-triggered PTX release behavior of the micelles. Moreover, GSH could trigger the detachment of DNs segment from mPEG-HA(SA)-DNs, and result in the release of SO2. In vitro and in vivo antitumor efficacy studies demonstrated that the PTX-loaded mPEG-HA(SA)-DNs micelles exhibited outstanding tumor suppression effect. The micelles would be potential carriers for combination cancer therapy by SO2 and PTX.

Critical miRNAs in regulating pulmonary hypertension: A focus on Signaling pathways and therapeutic Targets.

Pulmonary hypertension (PH) is complex disease as a result of obstructive pulmonary arterial remodeling, which in turn results in elevated pulmonary arterial pressure (PAP) and subsequent right ventricular heart failure, eventually leading to premature death. However, there is still a lack of a diagnostic blood-based biomarker and therapeutic target for PH. Because of the difficulty of diagnosis, new and more easily accessible prevention and treatment strategy are being explored. New target and diagnosis biomarkers should also allow for early diagnosis. In biology, miRNAs are short endogenous RNA molecules that are not coding. It is known that miRNAs can regulate gene expression and affect a variety of biological processes. Besides, miRNAs have been proven to be a crucial factor in PH pathogenesis. miRNAs have various effects on pulmonary vascular remodeling and are expressed differentially in various pulmonary vascular cells. Nowadays, it has been shown to be critical in the functions of different miRNAs in the pathogenesis of PH. Therefore, clarifying the mechanism of miRNAs regulating pulmonary vascular remodeling is of great importance to explore new therapeutic targets of PH and improve the survival qualify and time of patients. This review is focused on the role, mechanism, and potential therapeutic targets of miRNAs in PH and puts forward possible clinical treatment strategies.

Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review.

Granulomatous polyangiitis (GPA) is a rare systemic autoimmune vasculitis disease that is highly correlated with anti-neutrophil cytoplasmic antibodies (ANCAs). It was formerly called as "Wegener's granulomatosis." The clinical manifestations are diverse, mainly involving the upper respiratory tract, lungs, and kidneys, and this disease can involve the brain parenchyma as an isolated solid mass. Only one case has been reported thus far. To provide further information on this rare case, we report a case of GPA involving the fourth ventricle and review the relevant literature. A 32-year-old Chinese female developed fever, cough, and shortness of breath for 20 days. An 80 mm × 80 mm skin ulcer was seen on the right lower limb. CT showed multiple large patches of increased density in both lungs. The patient's serological ANCA was positive. Later, the patient developed dizziness and headache. Magnetic resonance imaging of the head showed a mass of approximately 21 mm × 24 mm in the fourth ventricle. The patient had a craniotomy for mass resection, and macroscopically, the mass was gray-red and measured 25 mm × 20 mm × 20 mm, was soft, had local hemorrhage and necrosis, and had no capsule. The main microscopic features included necrotizing granulomatous vasculitis, the patient's immunohistochemistry was positive for CD68 and negative for glial fibrillary acidic protein, and the acid-fast staining and hexaamine silver staining were negative. Combined with the clinical history, serology, and imaging, the pathological diagnosis was GPA in the fourth ventricle. The patient was switched to rituximab combined with steroid therapy because she did not tolerate cyclophosphamide. After 5 months of follow-up, the patient's lung lesions and skin ulcers had completely improved, but the brain lesions had further progressed. When a patient has multiple system diseases, abnormal clinical manifestations, and positive serological ANCAs, a diagnosis of GPA should be carefully considered, and biopsies of easy-to-access sites should be performed. If the patient's histopathological manifestations include vasculitis, granuloma, and necrosis, a diagnosis of GPA is more likely. If a patient subsequently develops an intraventricular mass, the clinicians should consider a diagnosis of GPA, which can rarely involve the cerebral ventricle to avoid an unnecessary biopsy or surgical treatment of intracranial lesions. When a patient is intolerant to the traditional treatment drug cyclophosphamide and needs to be switched to rituximab, the treatment effect of intracerebral lesions is not ideal; therefore, the treatment of lesions involving GPA in the ventricle is worthy of further exploration.

Promoting sensitive colorimetric detection of hydroquinone and Hg2+ via ZIF-8 dispersion enhanced oxidase-mimicking activity of MnO2 nanozyme.

Reducing the agglomeration and improving the dispersibility in water of two-dimensional (2D) nanozymes is one of the effective ways to improve their enzyme-like activity. In this work, we propose a method by constructing zeolitic imidazolate framework-8 (ZIF-8)-dispersed 2D manganese-based nanozymes to achieve the specific regulated improvement of oxidase-mimicking activity. By in-situ growth of manganese oxides nanosheets of MnO2(1), MnO2(2) and Mn3O4 on the surface of ZIF-8, the corresponding nanocomposites of ZIF-8 @MnO2(1), ZIF-8 @MnO2(2), and ZIF-8 @Mn3O4 were prepared at room temperature. The Michaelis-Menton constant measurements indicated that ZIF-8 @MnO2(1) exhibits best substrate affinity and fastest reaction rate for 3,3',5,5'-tetramethylbenzidine (TMB). The ZIF-8 @MnO2(1)-TMB system was exploited to detection of trace hydroquinone (HQ) based on the reducibility of phenolic hydroxyl groups. In addition, by employing the fact that the cysteine (Cys) with the excellent antioxidant capacity can bind the Hg2+ based on the formation of "S-Hg2+" bonds, the ZIF-8 @MnO2(1)-TMB-Cys system was applied to detection of Hg2+ with high sensitivity and selectivity. Our findings not only provide a better understanding of the relationship between dispersion of nanozyme and enzyme-like activity, but also provide a general method for the detection of environmental pollutants using nanozymes.

Single-Cell Profiling Uncovers the Roles of Endometrial Fibrosis and Microenvironmental Changes in Adenomyosis.

Purpose: Adenomyosis (AM) is a common benign uterine disorder that has deleterious effects on women's health. However, the pathogenesis of AM is not clearly understood. We aimed to investigate the pathophysiological changes and molecular mechanism in AM. Methods: Single-cell RNA sequencing (scRNA-seq) was employed to construct a transcriptomic atlas of various cell subsets from the ectopic endometrium (EC) and eutopic endometrium (EM) of one AM patient and evaluate differential expression. The Cell Ranger software pipeline (version 4.0.0) was applied to conduct sample demultiplexing, barcode processing and mapping reads to the reference genome (human GRCh38). Different cell types were classified with markers with the "FindAllMarkers" function, and differential gene expression analysis was performed with Seurat software in R. The findings were confirmed by Reverse Transcription Real-Time PCR using samples from three AM patients. Results: We identified nine cell types: endothelial cells, epithelial cells, myoepithelial cells, smooth muscle cells, fibroblasts, lymphocytes, mast cells, macrophages and unknown cells. A number of differentially expressed genes, including CLO4A1, MMP1, TPM2 and CXCL8, were identified from all cell types. Functional enrichment showed that aberrant gene expression in fibroblasts and immune cells was related to fibrosis-associated terms, such as extracellular matrix dysregulation, focal adhesion and the PI3K-Akt signaling pathway. We also identified fibroblast subtypes and determined a potential developmental trajectory related to AM. In addition, we identified increased cell-cell communication patterns in EC, highlighting the imbalanced microenvironment in AM progression. Conclusion: Our results support the theory of endometrial-myometrial interface disruption for AM, and repeated tissue injury and repair could lead to increased fibrosis in the endometrium. Therefore, the present study reveals the association between fibrosis, the microenvironment, and AM pathogenesis. This study provides insight into the molecular mechanisms regulating AM progression.

Effects of NM23 transfection of human gastric carcinoma cells in mice.

Gastric carcinoma is a frequent malignant tumor worldwide. NM23 plays an important role in pathological processes, including in the occurrence and development of tumors. The purpose of this study is to examine the effect of NM23 transfection of human gastric carcinoma cells (BGC-823) on growth and metastases of BGC-823 abdominal cancer xenografts in nude mice. BGC-823 cells were transfected with an adenovirus vector for NM23 (NM23-OE), transfected with an empty vector (NC), or were not transfected (Ctrl). Eighteen female BALB/c-nu mice were randomly divided into three groups (six per group) according to the type of BGC-823 cells administered by intraperitoneal injection. After 2 weeks, necropsies of mice were performed, abdominal circumferences were measured, and abdominal cavities were searched by ultrasound. In order to observe the xenografts in nude mice, there were gross macroscopic observations and microscopic observations. In addition, immunohistochemical analysis and western blot of NM23 were also performed. Green fluorescence in the NM23-OE and NC cells indicated successful transfection. The multiplicity of infection is 80%. A comparison of the three groups of mice indicated the NM23-OE group had positive conditions (abdominal circumferences: 81.83 ± 2.40 mm), but the other groups had negative conditions and enlarged abdomens (NC: 90.83 ± 2.32 mm; Ctrl: 92.67 ± 2.07 mm). Ultrasound observations confirmed large tumors in the NC and Ctrl groups, but did not find in the NM23-OE group. There were no obvious ascites in the NM23-OE group, but the cytological examination of ascites exfoliation in NC and Ctrl groups indicated that there were large and deep-stained gastric carcinoma cells. Tumor expression of NM23 was greater in the NM23-OE group than in the NC and Ctrl groups (both p < 0.05). In conclusion, transfection of BCG-823 cells with NM23 rather than an empty vector (NC) or no vector (Ctrl) led to reduced growth and metastases of abdominal cancer xenografts in nude mice.