Major Facilitator Superfamily Domain Containing 12 Is Overexpressed in Lung Cancer and Exhibits an Oncogenic Role in Lung Adenocarcinoma Cells.

Major facilitator superfamily domain containing 12 (MFSD12) regulates lysosomal cysteine import and promotes the proliferation and survival of melanoma cells. However, the expression and function of MFSD12 in other cancers, particularly in lung cancer, remain unclear. The expression of MFSD12 across various types of cancers and corresponding control tissues was examined using TIMER. MFSD12 expression in lung adenocarcinoma (LUAD) and its correlation with distinct clinicopathological features of LUAD patients were analyzed with UALCAN. The correlation between MFSD12 expression and survival of LUAD patients was assessed using the R package, survival, and the relationship between MFSD12 expression and immune infiltration status in LUAD was investigated using CIBERSORT. In addition, MFSD12 expression was knocked down in PC9 LUAD cells and their proliferation, capacity for expansion, cell cycle, apoptosis, and migration/invasion were evaluated through CCK-8 assays, colony formation assays, 7-AAD staining, Annexin V/PI staining, and Transwell assays, respectively. The stemness of these PC9 cells was determined through Western blotting, flow cytometry, and tumor sphere formation assays. MFSD12 mRNA levels were significantly elevated in multiple types of cancers, including LUAD. MFSD12 expression was also positively correlated with cancer stage, nodal metastasis, and infiltration of various immune cells in LUAD, and high MFSD12 levels predicted poor survival among LUAD patients. Knockdown of MFSD12 in PC9 cells resulted in decreased proliferation, attenuated colony formation capacity, cell cycle arrest, elevated apoptosis, impaired migration/invasion, and reduced stemness in PC9 cells. MFSD12 is an oncogene in LUAD.

DKC1 aggravates gastric cancer cell migration and invasion through up-regulating the expression of TNFAIP6.

Gastric cancer (GC) is one hackneyed malignancy tumor accompanied by high death rate. DKC1 has been discovered to serve as a facilitator in several cancers. Additionally, it was discovered from one study that DKC1 displayed higher expression in GC tissues than in the normal tissues. Nevertheless, its role and regulatory mechanism in GC is yet to be illustrated. In this study, it was proved that DKC1 expression was upregulated in GC tissues through GEPIA and UALCAN databases. Moreover, we discovered that DKC1 exhibited higher expression in GC cells. Functional experiments testified that DKC1 accelerated cell proliferation, migration, and invasion in GC. Further investigation disclosed that the weakened cell proliferation, migration, and invasion stimulated by DKC1 knockdown can be reversed after TNFAIP6 overexpression. Lastly, through in vivo experiments, it was demonstrated that DKC1 strengthened tumor growth. In conclusion, our work uncovered that DKC1 aggravated GC cell migration and invasion through upregulating the expression of TNFAIP6. This discovery might highlight the function of DKC1 in GC treatment.

Therapeutic effects of melatonin in female mice with central precocious puberty by regulating the hypothalamic Kiss-1/Kiss1R system.

In recent years, central precocious puberty (CPP) in children is becoming more common, which seriously affects their physical and psychological health and requires finding a safe and effective treatment method. The aim of this study was to investigate the therapeutic effect of melatonin on CPP. A CPP model was established by subcutaneous injection of 300 micrograms of danazol into 5-day-old female mice, followed by treatment with melatonin and leuprolide. The vaginal opening was checked daily. Mice were weighed, gonads were weighed, gonadal index was calculated, and gonadal development was observed by hematoxylin and eosin (HE) staining. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels were measured by ELISA. By using RT-PCR and Western blotting, the mRNA and protein expression of the hypothalamus Kiss-1, Kiss-1 receptor (Kiss1R), gonadotropin-releasing hormone (GnRH), and pituitary GnRH receptor (GnRHR) were identified. The results showed that melatonin delayed vaginal opening time and reduced body weight, gonadal weight and indices in female CPP mice. Melatonin treatment prevents uterine wall thickening and ovarian luteinization in female CPP mice. Melatonin treatment reduces serum concentrations of FSH, LH, and E2 in female CPP mice. Melatonin suppressed the expressions of Kiss-1, Kiss1R and GnRH in the hypothalamus, and the expression of GnRHR in the pituitary of the female CPP mice. Our results suggest that melatonin can inhibit the hypothalamic-pituitary-gonadal (HPG) axis by down-regulating the Kiss-1/Kiss1R system, thereby treating CPP in female mice.

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer.

Although the role of T cells in tumor immunity and modulation of the tumor microenvironment (TME) has been extensively studied, their precise involvement in gastric adenocarcinoma remains inadequately explored. In this work, we analyzed the single-cell RNA sequencing data set in GSE183904 and identified 322 T cell marker genes using the "FindAllMarkers" method of the R package "Seurat". STAD patients in the TCGA database were divided into high-risk and low-risk categories based on risk scores. The five-gene prediction signature based on T cell marker genes can predict the prognosis of gastric cancer patients with high accuracy. In the training cohort, the areas under the receiver operating characteristic (ROC) curve were 0.667, 0.73, and 0.818 at 1, 3, and 5 years. External validation of the predictive signature was also performed using multiple clinical subgroups and GEO cohorts. To help with practical application, a diagnostic model was created that shows values of 0.732, 0.752, and 0.816 for the relevant areas under the ROC curve at 1, 3, and 5 years. The T cell marker genes identified in this study may serve as potential therapeutic targets, and the developed predictive signatures and nomograms may aid in the clinical management of gastric cancer.

Brain radial enhancement pattern in patients with negative glial fibrillary acidic protein-IgG: A cases series study.

BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.

One-step synthesis of thiol-functionalized metal coordination polymers: effective and superfast removal of Hg (II) in the different matrices to ppb level.

The mercury in water bodies has posed a great threat to the environment and humans, and removing mercury and purifying wastewater has become a global environmental issue. Adopting Zn(II) coordination polymers (Zn-CPs) emerged as a new approach, however, the kind of Zn-CPs, which solely consisted of amino groups, exhibited unsatisfactory performance in capturing Hg(II) at a low level and causing the subsequent leaching of Zn(II) after adsorption. In this study, we fabricated the thiol-modified Zn-based coordination polymers (Zn-CPs-SH) through a one-step solvothermal reaction to efficiently capture Hg(II) from wastewater. Its preeminent adsorption performance could be maintained across a broad range of pH (2-7), ion strength (Cl-, SO42-, and NO3- at 0-10,000 mg/L), and dissolved organic matter (0-100 mg/L). The impressive properties, including fast kinetics (k2∼1.01 × 10-4 L/min), outstanding adsorption capacity (1278.72 mg/g, 298 K), superior selectivity (Kd∼2.3 × 104 mL/g), and excellent regeneration capability (Re = 93.54% after 5 cycles), were attributed to the ultra-abundance of adsorption sites donating from thiol groups, which was revealed by XPS analysis, DFT calculations, and molecular orbital theory. Noteworthy, the high practical application potential of Zn-CPs-SH was demonstrated by its outstanding Hg(II) removal efficiency (Re ≥ 99.10%) in various Hg(II)-spiked water matrices, e.g., tap water, river water, and industrial wastewater. Importantly, the residual Hg(II) in the treated water declined to the ppb level without any Zn(II) leaching. Overall, it is highly anticipated that the incorporation of Zn-CPs-SH would facilitate the practical implementation of highly efficient Hg(II) removal in wastewater treatment owing to its exhibiting high selective affinity, superior adsorption capacity, and enhanced efficiency.

Prognostic impact of tumor spread through air spaces for T2aN0 stage IB non-small cell lung cancer.

BACKGROUND: Spread through air spaces (STAS) is a pattern of invasion recently identified in non-small cell lung cancer (NSCLC), with a poor prognosis. However, the predictive impact of STAS in stage IB NSCLC is not well understood. This investigation aims to assess the prognostic influence of STAS in stage IB NSCLC. METHODS: We reviewed 130 resected stage IB NSCLC between 2010 and 2015. Beyond the central tumor edge, lung parenchymal air gaps containing cancer cells were identified as STAS. In order to estimate recurrence-free survival (RFS) and overall survival (OS), Cox models and Kaplan-Meier techniques were utilized. Logistic regression analysis was employed to define the factors influencing STAS. RESULTS: Of 130 patients, 72 (55.4%) had STAS. STAS was a significant prognosticator. Kaplan-Meier method showed that STAS-positive patients had a significantly lower OS and RFS than STAS-negative patients (5-year OS, 66.5% vs. 90.4%, p = 0.02; 5-year RFS, 59.5% vs. 89.7%, p = 0.004) In a semiquantitative assessment, the RFS and OS were shorter in survival analysis when STAS increased (5-year RFS, 89.7%, no STAS, 61.8%, low STAS, 57.2%, high STAS, p = 0.013; 5-year OS, 90.4%, no STAS, 78.3%, low STAS, 57.2%, high STAS, p = 0.002). The association between STAS and poor differentiation, adenocarcinoma, and vascular invasion (p value was <0.001, 0.047, and 0.041, respectively) was statistically significant. CONCLUSIONS: The STAS is an aggressive pathological feature. RFS and OS could be significantly reduced by STAS, while it also serves as an independent predictor.

miR-218-5p and miR-320a-5p as Biomarkers for Brain Disorders: Focus on the Major Depressive Disorder and Parkinson's Disease.

Depression is one of the early and most persistent non-motor symptoms of Parkinson's disease (PD), which remains ignored, resulting in the underdiagnosis of PD. Unfortunately, scarce studies and the non-availability of diagnostic strategies cause countless complications, highlighting the need for appropriate diagnostic biomarkers. Recently, brain-enriched miRNAs regulating vital neurological functions have been proposed as potent biomarkers for therapeutic strategies. Therefore, the present study is aimed to identify the brain-enriched miR-218-5p and miR-320-5p in the serum of the Chinese depressed PD patients (n = 51) than healthy controls (n = 51) to identify their potency as biomarkers. For this purpose, depressive PD patients were recruited based on HAMA and HAMD scores and miR-218-5p and miR-320-5p and IL-6, and S100B levels were analyzed using real-time PCR (qRT-PCR) and ELISA assay, respectively. In silico analysis was performed to identify key biological pathways and hub genes involved in the psychopathology of depression in PD. Here, we found significantly downregulated miR-218-5p and miR-320-5p following higher levels of IL-6 and S100B in depressed PD patients than in control (p < 0.05). The correlation analysis revealed that both miRNAs were negatively correlated with HAMA and HAMD, and IL-6 scores, along with a positive correlation with PD duration and LEDD medication. ROC analysis showed AUC above 75% in both miRNAs in depressed PD patients, and in silico analysis revealed that both miRNA's targets regulate key neurological pathways such as axon guidance, dopaminergic synapse, and circadian rhythm. Additional analysis revealed PIK3R1, ATRX, BM1, PCDHA10, XRCC5, PPP1CB, MLLT3, CBL, PCDHA4, PLCG1, YWHAZ, CDH2, AGO3, PCDHA3, and PCDHA11 as hub-genes in PPI network. In summary, our findings show that miR-218-5p and miR-320-5p can be utilized as future biomarkers for depression in PD patients, which may aid in the early diagnosis and treatment of Parkinson's disease.

Effects of regional cerebral oxygen saturation monitoring on postoperative cognitive dysfunction in older patients: a systematic review and meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is common after surgery and anesthesia, particularly in older patients. It has been reported that regional cerebral oxygen saturation (rSO2) monitoring potentially influences the occurrence of POCD. However, its role in the prevention of POCD remains controversial in older patients. Additionally, the quality of evidence on this topic is still relatively poor. METHODS: The electronic databases PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched using the indicated keywords from their inception to June 10, 2022. We limited our meta-analysis to randomized controlled trials (RCTs) that assessed the effects of rSO2 monitoring on POCD in older patients. Methodological quality and risk of bias were assessed. The primary outcome was the incidence of POCD during hospitalization. The secondary outcomes were postoperative complications and the length of hospital stay (LOS). Odds ratios (OR) and 95% confidence intervals (CI) were calculated to determine the incidence of POCD and postoperative complications. The standardized mean difference (SMD) instead of the raw mean difference and 95% CI were calculated for LOS. RESULTS: Six RCTs, involving 377 older patients, were included in this meta-analysis. The incidence of POCD ranges from 17 to 89%, with an overall prevalence of 47% in our pooled analysis. Our results demonstrated that rSO2-guided intervention could reduce the incidence of POCD in older patients undergoing non-cardiac surgery (OR, 0.44; 95% CI, 0.25 to 0.79; P = 0.006) rather than cardiac surgery (OR, 0.69; 95% CI, 0.32 to 1.52; P = 0.36). Intraoperative rSO2 monitoring was also associated with a significantly shorter LOS in older patients undergoing non-cardiac surgery (SMD, -0.93; 95% CI, -1.75 to -0.11; P = 0.03). Neither the incidence of postoperative cardiovascular (OR, 1.12; 95% CI, 0.40 to 3.17; P = 0.83) nor surgical (OR, 0.78; 95% CI, 0.35 to 1.75; P = 0.54) complications were affected by the use of rSO2 monitoring. CONCLUSION: The use of rSO2 monitoring is associated with a lower risk of POCD and a shorter LOS in older patients undergoing non-cardiac surgery. This may have the potential to prevent POCD in high-risk populations. Further large RCTs are still warranted to support these preliminary findings.

A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects.

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙-) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g-1 PcSA) and light dose (30 J cm-2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.

Dysregulated glycolysis underpins high-fat-associated endometrial decidualization impairment during early pregnancy in mice.

Pregnancy complications are more likely to occur in obese women because of defective decidualization. However, the specific mechanism of glycolysis in decidual modulation associated with obesity remains unknown. Therefore, we explored the role of glycolysis in the endometrium of obese pregnant mice during decidualization. C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. All obesity related parameters were significantly higher in the HFD mice than control. Furthermore, the HFD mice had fewer implantation sites, a smaller decidual area growth, and decreased decidualization marker protein expression than control. The HFD mice also had significantly decreased lactate production and glycolytic enzyme expression. To confirm the functional role of glycolysis during the decidual period in obese pregnant mice, we extracted endometrial stromal cells (ESCs) and treated them with oleic acid (OA) and palmitic acid (PA) to mimic a high-fat environment. Decidualization and glycolysis were significantly restricted in the OA-and PA-treated groups. Moreover, we administered a glycolytic inhibitor, 2-DG, and an agonist, pioglitazone. 2-DG treatment considerably decreased the cells' glycolysis and decidualization. However, pioglitazone treatment improved glycolysis and alleviated defective decidualization. In conclusion, obesity-induced endometrial glycolysis modifications and key glycolytic enzyme downregulation during early pregnancy might cause abnormal decidualization, leading to an unsustainable pregnancy.

From ethene to propene (ETP) on tailored silica-alumina supports with isolated Ni(ii) sites: uncovering the importance of surface nickel aluminate sites and the carbon-pool mechanism.

Catalysts with well-defined isolated Ni(ii) surface sites have been prepared on three silica-based supports. The outer shells of the support were comprised either of an amorphous aluminosilicate or amorphous alumina (AlO x ) layer - associated with a high and low density of strong Brønsted acid sites (BAS), respectively. When tested for ethene-to-propene conversion, Ni catalysts with a higher density of strong BAS demonstrate a higher initial activity and productivity to propene. On all three catalysts, the propene productivity correlates closely with the concentration of C8 aromatics, suggesting that propene may form via a carbon-pool mechanism. While all three catalysts deactivate with time on stream, the deactivation of catalysts with Ni(ii) sites on AlO x , i.e., containing surface Ni aluminate sites, is shown to be reversible by calcination (coke removal), in contrast to the deactivation of surface Ni silicate or aluminosilicate sites, which deactivate irreversibly by forming Ni nanoparticles.

[Status and Influencing Factors of Hypertension in the Elderly Aged 60 and Above in Mianyang].

Objective To understand the prevalence and influencing factors of hypertension among the elderly aged 60 years and above in Mianyang City,Sichuan Province,so as to provide clues for targeted prevention and control of hypertension. Methods A total of 115 775 permanent residents aged 60 and above screened out from Mianyang demonstration sites from October 2017 to April 2019 were investigated by questionnaire and physical examination,and the data of personal basic information,lifestyle,body height,body weight,waist circumference,and blood pressure were collected.SPSS 22.0 was used for descriptive analysis,single factor analysis,and Logistic regression analysis. Results The prevalence rate of hypertension in the elderly aged 60 years and above in Mianyang was 50.60%.Specifically,the prevalence rates of hypertension in men and women were 50.27% and 50.85%,respectively.The prevalence rate of hypertension increased with the increase in age([Formula: see text]=370.199,P<0001).Multivariate Logistic regression analysis showed that the independent risk factors of hypertension included age of 70-79 years(OR=1.327,95%CI=1.292-1.363,P<0.001),the age of 80 years and above(OR=1.455,95%CI=1.386-1.527,P<0.001),widowhood(OR=1.343,95%CI=1.296-1.392,P<0.001),divorce(OR=1.255,95%CI=1.033-1.525,P=0.022),overweight(OR=1.431,95%CI=1.391-1.473,P<0.001),obesity(OR=2.171,95%CI=2.076-2.270,P<0.001),waist-to-height ratio>0.5(OR=1.317,95%CI=1.281-1.354,P<0.001),history of diabetes(OR=1.865,95%CI=1.791-1.941,P<0.001),history of smoking(OR=1.107,95%CI=1.068-1.148,P<0.001),and history of drinking(OR=1.950,95%CI=1.894-2.009,P<0.001).Living in urban-rural fringe areas(OR=0.628,95%CI=0.594-0.664,P<0.001),education background of junior high school and above(OR=0.942,95%CI=0.912-0.974,P<0.001),and low body weight(OR=0.785,95%CI=0.742-0.830,P<0.001) were protective factors for hypertension. Conclusions More than 50% of the elderly aged 60 years and above in Mianyang suffer from hypertension.The elderly with advanced age,widowhood,divorce,overweight,obesity,waist-to-height ratio>0.5,diabetes history,smoking history,and drinking history are the high-risk groups of hypertension.

A peptide translated from circPPP1R12A promotes the malignancy of non-small cell lung cancer cells through AKT signaling pathway.

BACKGROUND: Recent literature have indicated that the malignancy of cancer cells is modulated by hsa_circ_0000423 (named circPPP1R12A) through the way of translating protein. Herein, we investigated the role and latent mechanisms of circPPP1R12A in Non-Small Cell Lung Cancer (NSCLC). METHODS: CircPPP1R12A expression was measured by qRT-PCR. The malignancy of NSCLC was determined by CCK-8, TUNEL assay, Wound healing, Transwell and Western blotting assays. The underlying mechanisms of circPPP1R12A were confirmed by Western blotting and qRT-PCR assays. RESULTS: CircPPP1R12A expression in NSCLC tissues was higher than that of neighboring normal tissues. CircPPP1R12A showed an upregulated expression in NSCLC cells. Upregulation of circPPP1R12A could promote the cell viability of NSCLC cells and reduce the apoptosis of NSCLC cells, while it could not promote cell invasion and migration. The reduction of cell viability and apoptosis was discovered in NSCLC cells with the silencing of circPPP1R12A, but circPPP1R12A knockdown does not inhibit cell invasion and migration. There was something interesting that circPPP1R12A encoding protein circPPP1R12A-73aa was found in NSCLC cells. Mutations in circPPP1R12a-73AA might disrupt the function of circPPP1ra-73AA in A549 and H1299 cells. Next, we found that circPPP1R12A caused the increased growth of NSCLC cells by activating AKT signaling pathway. CONCLUSION: In summary, our study proved that NSCLC cell proliferation was promoted by circPPP1R12A-73aa translated from circPPP1R12A through the AKT pathway, which could throw some light on the understanding of the mechanism of NSCLC.

2D Copper(II) Metalated Metal-Organic Framework Nanocomplexes for Dual-enhanced Photodynamic Therapy and Amplified Antitumor Immunity.

The immunosuppressive tumor microenvironment (TME) poses tremendous challenges for efficient immunotherapy. Smart nanomedicine is designed to modulate immunosuppressive TMEs based on the combination of dual-enhanced photodynamic therapy (PDT) triggered immunogenic cell death (ICD) and relieved hypoxic microenvironment. Copper(II) metalated metal-organic framework nanosheets (Cu-TCPP(Al)) are the foundation of the nanomedicine, and platinum nanoparticles (Pt NPs) and folate are subsequently introduced onto the Cu-TCPP(Al) surface (Cu-TCPP(Al)-Pt-FA). Upon targeted cellular uptake, intracellular GSH concentration is decreased because of the specific adsorption between GSH and CuII; meanwhile, Pt NPs possess catalase-like activity, which can continuously depose intracellular H2O2 to O2 to alleviate the hypoxic TME. The two factors synergistically improve the ROS concentration for dual-enhanced PDT. The highly toxic ROS can correspondingly cause amplified oxidative stress and then trigger the ICD. The ICD process stimulates antigen-presenting cells and activates the systemic antitumor immune response. Furthermore, the relieved hypoxic TME increases the infiltration of cytotoxic T lymphocytes (CTLs) at the tumor site, which can promote the transformation of the immunosuppressive M2 macrophage to immunoactive M1 phenotype. The easily prepared yet versatile nanomedicine possesses an excellent antitumor effect with the cooperation of dual-enhanced PDT and immunotherapy.

Impairment of endometrial decidual reaction in early pregnant mice fed with high fat diet.

OBJECTIVE: To investigate the effect of obesity induced by high fat diet on decidual reaction of endometrium in mice, and the effect of high fat treatment on decidual reaction of endometrial stromal cells. METHODS: Twelve 4-week-old healthy C57BL/6J female mice were randomly divided into high fat diet group and control group with 6 mice in each group. They were fed with high fat diet (22 kJ/g) or normal diet (16 kJ/g) for 12 weeks, respectively. The body weight of mice was measured every week. After feeding for 12 weeks, the body length and width of mice were measured, and the levels of fasting serum triglyceride and total cholesterol were determined. Then the mice were mated with healthy C57BL/6J male mice, and the uterine tissues were collected on the seventh day of pregnancy. The decidual cells and collagen fibers in mouse endometrium was observed by HE staining and Masson staining respectively. The expression of decidual reaction related proteins in mouse endometrium were detected by immunohistochemistry and Western blotting. Mouse endometrial stromal cells (mESCs) were isolated and treated with the oleic acid and palmitic acid in vitro, and the decidual reaction was induced with estradiol and progesterone. The accumulation of lipid droplets in mESCs was observed by oil red O and Bodipy staining. The cytoskeleton of mESCs was observed by phalloidin staining. The levels of decidual reaction related genes and proteins were detected by real-time fluorescence quantitative PCR and Western blotting. RESULTS: After feeding for 12 weeks, the body weight of mice in the high fat group was significantly higher than that in the control group ( P<0.01), and there was no significant difference in body length between two groups ( P>0.05), but the body width of mice in the high fat group was significantly larger than that in the control group ( P<0.01), and the levels of serum triglyceride and total cholesterol were significantly higher than those in the control group (Both P<0.05). The number of embryo implantation in the high fat group was significantly less than that in the control group ( P<0.01). The differentiation of mESCs to decidual cells in high fat group was slow and abnormal. The expression levels of decidual reaction markers bone morphogenetic protein (BMP)2 and homeobox A10 (HOXA10) were lower than those in the control group, and there was significant difference in the expression level of HOXA10 ( P<0.01). The results of oil red O and Bodipy staining in mESCs showed that after high fat treatment, the accumulation of lipid droplets increased significantly, phalloidin staining showed abnormal cytoskeleton morphology. The expression levels of decidual reaction related genes dtprp, HOXA10 and proteins BMP2, HOXA10 and cyclooxygenase (COX)2 were significantly lower than those in the control group ( P<0.05). CONCLUSION: Obesity induced by high fat diet and high fat treatment can impair the decidual reaction of endometrium and endometrial stromal cells in mice.

Deep Learning-Based CT Imaging in the Diagnosis of Treatment Effect of Pulmonary Nodules and Radiofrequency Ablation.

To study the effect of computerized tomography (CT) images based on deep learning algorithms on the diagnosis of pulmonary nodules and the effect of radiofrequency ablation (RFA), the U-shaped fully convolutional neural network (FCNN) (U-Net) was enhanced. The convolutional neural network (CNN) algorithm was compared with the U-Net algorithm, and segmentation performances were analyzed. Then, it was applied to the CT image diagnosis of 110 lung cancer patients admitted to hospital. The patients in the observation group (55 cases) were diagnosed based on the improved U-Net algorithm, while those in the control group (55 cases) were diagnosed by traditional methods and then treated with RFA. The Dice coefficient (0.8753) and intersection over union (IOU) (0.8788) obtained by the proposed algorithm were remarkably higher than the Dice coefficient (0.7212) and IOU (0.7231) obtained by the CNN algorithm, and the differences were considerable (P < 0.05). The boundary of the pulmonary nodule can be segmented more accurately by the proposed algorithm, which had the segmentation result closest to the gold standard among the three algorithms. The diagnostic accuracy of the pulmonary nodule in the observation group (95.3%) was superior to that of the control group (90.7%). The long diameter, volume, and maximum area of the pulmonary nodule of the observation group were significantly higher than those of the control group, with substantial differences (P < 0.05). Patients were reexamined after one, three, and six months of treatment, and 71 patients (64.55%) had complete remission, 32 patients (29.10%) had partial remission, 6 patients (5.45%) had stable disease, and 1 patient (0.90%) had disease progression. The remission rate (complete remission + partial remission) was 93.65%. The improved U-NET algorithm had good image segmentation performance and ideal segmentation effect. It can clearly display the shape of pulmonary nodules, locate the lesions, and accurately evaluate the therapeutic effect of RFA, which had clinical application value.

TfR Aptamer Enhanced Blood-Brain Barrier Penetration of Biomimetic Nanocomplexes for Intracellular Transglutaminase 2 Imaging and Silencing in Glioma.

Engineering a versatile nanocomplex integrating effective penetration of the blood-brain barrier (BBB), accurate diagnosis, and boosting therapy has always been an intractable challenge in glioblastoma multiforme (GBM). Herein, biomimetic nanocomplexes (TMPsM) for single intracellular transglutaminase 2 (TG2)-triggered self-assembly imaging and RNAi therapy for GBM are subtly developed. To prove the concept, transferrin receptor (TfR) aptamer-modified brain metastatic tumor cell membrane is prepared as the shell for dual BBB targeting capability and prolonged blood retention time. Upon targeting entering into GBM, hollow MnO2 is decomposed to release KKGKGQQ-tetraphenylethene (Pep-TPE) and siRNA. Owing to TG2 dependence, the non-emissive Pep-TPE would be self-aggregated to induce the emission turn-on in GBM that contain overexpressed TG2. The resulting aggregation-induced emission fluorescence imaging with a high signal-to-noise ratio can achieve the precise localization of the tumor and dynamic detection of TG2 activity, thereby allowing the GBM accurate diagnosis. Notably, the TG2 can be silenced by the released siRNA to cause cell apoptosis and increase chemotherapeutic sensitivity, ultimately realizing excellent antitumor efficacy. In vitro and in vivo results demonstrate that the as-prepared TMPsM indeed possess superior BBB penetration, precise diagnosis, and effective therapy of GBM. The proposed strategy may pioneer a new path for the theranostics of brain tumors.

Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.

Deubiquitinating enzymes (DUBs) are a group of proteases that are important for maintaining cell homeostasis by regulating the balance between ubiquitination and deubiquitination. As the only known metalloproteinase family of DUBs, JAB1/MPN/Mov34 metalloenzymes (JAMMs) are specifically associated with tumorigenesis and immunological and inflammatory diseases at multiple levels. The far smaller numbers and distinct catalytic mechanism of JAMMs render them attractive drug targets. Currently, several JAMM inhibitors have been successfully developed and have shown promising therapeutic efficacy. To gain greater insight into JAMMs, in this review, we focus on several key proteins in this family, including AMSH, AMSH-LP, BRCC36, Rpn11, and CSN5, and emphatically discuss their structural basis, diverse functions, catalytic mechanism, and current reported inhibitors targeting JAMMs. These advances set the stage for the exploitation of JAMMs as a target for the treatment of various diseases.