PRKDC-Mediated NHEJ May Play a Crucial Role in Aneuploidy of Chromosome 8-Driven Progression of Ovarian Cancer.

High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and hub-gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.

Engineering the Activity and Stability of the Zn-MOF Catalyst via the Interaction of Doped Zr with Zn.

Metallic atoms within metal-organic framework (MOF) materials exhibit a distinctive and adaptable coordination structure. The three-dimensional (3D) pore configuration of MOFs enables the complete exposure of metal active sites, rendering them prevalent in various catalytic reactions. In this study, zinc (Zn) atoms within Zn-based MOF materials, characterized by an abundance of valence electrons, are utilized for the transesterification of dimethyl carbonate (DMC). Additionally, the introduction of zirconium (Zr) effectively addresses the susceptibility of the MOFs' crystal structure to dissolution in organic solvents. The formulated catalyst, Zn-10%Zr-MOF(300), demonstrates remarkable catalytic performance with 91.5% DMC selectivity, 61.9% propylene carbonate (PC) conversion, and 56.6% DMC yield. Impressively, the catalyst maintains its high performance over five cycles. Results indicate that Zr interacts with Zn, forming new coordination bonds and enhancing the catalyst crystal structure stability. Moreover, electron transfer intensifies the alkalinity of the active Zn atoms, enhancing the overall catalyst performance. This research informs the development of transesterification heterogeneous catalysts and broadens the application scope of MOF catalysts.

The pivotal role of bromine in FeMnKBr/YNa catalyst for CO2 hydrogenation to light olefins.

Light olefins are key intermediates in the synthesis of petrochemicals, and the conversion of stabilized carbon dioxide to light olefins using catalysts containing halogenated elements such as chlorine is a major challenge. Building on previous reports emphasizing the toxic effects of halogen elements on catalysts, we present the synthesis of FeMnKBr/YNa catalysts. This involved the synthesis of the catalyst by melt permeation using Br-containing potassium salts, other metal nitrates and YNa zeolites. The catalyst performed well in converting syngas (H2/CO2 = 3) to light olefins with a selectivity of 56.2%, CO2 conversion of 34.4%, and CO selectivity of 13.6%. Adding Br aids in reducing the Fe phase, boosts catalyst carburization, and produces more iron carbide species. It also moderately deposits carbon on the active center's surface, enhancing active phase dispersion. Br's electronegativity mitigates the influence of K, reducing catalyst's carbon-carbon coupling ability, leading to more low-carbon olefins generation.

Precise capture of circulating endometrial cells in endometriosis.

BACKGROUND: Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM. METHODS: Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients (n = 34) hospitalized in the Peking University People's Hospital. We use the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarify the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. RESULTS: The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 µm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage. CONCLUSION: The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

Copper-Catalyzed Enantioconvergent Radical N-Alkylation of Diverse (Hetero)aromatic Amines.

The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, the bond formation relies on the interaction between nucleophile-sequestered metal complexes and radicals, limiting the nucleophile scope to sterically uncongested ones. The coupling of sterically congested nucleophiles poses a significant challenge due to difficulties in transmetalation, restricting the reaction generality. Here, we describe a probable outer-sphere nucleophilic attack mechanism that circumvents the challenging transmetalation associated with sterically congested nucleophiles. This strategy enables a general copper-catalyzed enantioconvergent radical N-alkylation of aromatic amines with secondary/tertiary alkyl halides and exhibits catalyst-controlled stereoselectivity. It accommodates diverse aromatic amines, especially bulky secondary and primary ones to deliver value-added chiral amines (>110 examples). It is expected to inspire the coupling of more nucleophiles, particularly challenging sterically congested ones, and accelerate reaction generality.

Association of sleep characteristics with cardiovascular disease risk in adults over 40 years of age: a cross-sectional survey.

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

Effect of reduction pretreatment on the structure and catalytic performance of Ir-In2O3 catalysts for CO2 hydrogenation to methanol.

In2O3 has been found a promising application in CO2 hydrogenation to methanol, which is beneficial to the utilization of CO2. The oxygen vacancy (Ov) site is identified as the catalytic active center of this reaction. However, there remains a great challenge to understand the relations between the state of oxygen species in In2O3 and the catalytic performance for CO2 hydrogenation to methanol. In the present work, we compare the properties of multiple In2O3 and Ir-promoted In2O3 (Ir-In2O3) catalysts with different Ir loadings and after being pretreated under different reduction temperatures. The CO2 conversion rate of Ir-In2O3 is more promoted than that of pure In2O3. With only a small amount of Ir loading, the highly dispersed Ir species on In2O3 increase the concentration of Ov sites and enhance the activity. By finely tuning the catalyst structure, Ir-In2O3 with an Ir loading of 0.16 wt.% and pre-reduction treatment under 300°C exhibits the highest methanol yield of 146 mgCH3OH/(gcat·hr). Characterizations of Raman, electron paramagnetic resonance, X-ray photoelectron spectroscopy, CO2-temperature programmed desorption and CO2-pulse adsorption for the catalysts confirm that more Ov sites can be generated under higher reduction temperature, which will induce a facile CO2 adsorption and desorption cycle. Higher performance for methanol production requires an adequate dynamic balance among the surface oxygen atoms and vacancies, which guides us to find more suitable conditions for catalyst pretreatment and reaction.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

ECM1 promotes migration and invasion in endometriosis.

Extracellular matrix protein 1 (ECM1) is a glycoprotein that may be a key player in tumorigenesis and tumor progression. However, knowledge regarding the role of ECM1 in endometriosis (EM) is still lacking. Microarray analyses were performed to compare the mRNA expression patterns between paired EU tissues and ectopic endometrial (EC) tissues (n = 4) from EM patients. ECM1 expression was significantly increased in the eutopic endometrial (EU) tissues than paired EC tissues of endometriotic patients and normal endometrial (NE) tissues of controls without EM. Blocking ECM1 with siRNA attenuated the migration and invasion of hEM15A cells and modified the distribution of the F-actin cytoskeleton. We conducted microarray analyses and bioinformatics analyses to investigate the differentially expressed genes (DEGs) and related pathways regulated by ECM1. A total of 161 DEGs between the siECM1 and the negative control (siNC) treatments were identified, consisting of 79 downregulated genes and 82 upregulated genes. Enriched DEGs were associated with 9 gene ontology (GO) terms. Moreover, a protein-protein interaction (PPI) network was constructed for the hub genes and modules. Radixin (RDX) was the second most downregulated gene in the siECM1 group compared with the siNC group. ECM1 knockdown significantly decreased the expression of RDX, RhoC, ROCK1, N-cadherin and ß-catenin but not ROCK2. ECM1 showed high tissue-specific expression in EU tissues from EM patients, and may contribute to the migration, invasion and reorganization of the F-actin cytoskeleton in eutopic endometrial stromal cells via the RhoC/ROCK1 signaling pathway in EM.

Construction and evaluation of novel self-assembled nanoparticles of Herpetospermum caudigerum Wall / 药学学报

It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

Immunization with Embryonic Stem Cells/Induced Pluripotent Stem Cells Induces Effective Immunity against Ovarian Tumor-Initiating Cells in Mice.

Cancer stem cells (CSCs) express pluripotent markers and share many features with normal pluripotent stem cells. It is possible that immunity induced by embryonic stem cells (ESCs) and induced pluripotent stem cells- (IPSCs-) based vaccines may selectively target CSCs. In our study, cells expressing the pluripotent marker CD133 in the murine ovarian cancer cell-line ID8 were isolated and identified as CSCs. We investigated the preventive efficacy of ESCs and IPSCs-based vaccines against the development of ovarian cancer in vivo and evaluated the humoral and cellular immunities targeting CSCs in vitro. Our study showed that preimmunization with both mouse-derived embryonic stem cells (mESCs) and mouse-induced pluripotent stem cells (mIPSCs) lysates, combined with an immunostimulatory adjuvant CpG, elicited strong humoral and cellular responses. These responses effectively suppressed the development of CSC-derived tumors. Immune sera collected from mESCs and mIPSCs-vaccinated mice contained antibodies that were capable of selectively targeting CSCs, resulting in the lysis of CSCs in the presence of complement. Cytotoxic T-lymphocytes generated from splenocytes of mESCs and mIPSCs-vaccinated hosts could secrete interferon- (IFN-) γ in response to CSCs and kill CSCs in vitro. These findings indicate that vaccines based on mESCs and mIPSCs can elicit effective antitumor immunities. These immunities are related to the conferring of humoral and cellular responses that directly target CSCs.

Biogenic Selenium Nanoparticles Synthesized Using Alginate Oligosaccharides Attenuate Heat Stress-Induced Impairment of Breast Meat Quality via Regulating Oxidative Stress, Metabolome and Ferroptosis in Broilers.

Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss (p < 0.05), freezing loss (p < 0.001), and shear force (p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, ß-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways (p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle (p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT, GPX1, GPX3, heme oxygenase-1 (HO-1), masculoaponeurotic fibrosarcoma G (MafG), MafK, selenoprotein W (SELENOW), SELENOK, ferritin heavy polypeptide-1 (FTH1), Ferroportin 1 (Fpn1), and nuclear factor erythroid 2-related factor 2 (Nrf2) (p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 (Keap1) and prostaglandin-endoperoxide Synthase 2 (PTGS2) expression (p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers.

Biogenic Selenium Nanoparticles Synthesized with Alginate Oligosaccharides Alleviate Heat Stress-Induced Oxidative Damage to Organs in Broilers through Activating Nrf2-Mediated Anti-Oxidation and Anti-Ferroptosis Pathways.

Selenium (Se) is an essential trace element for maintaining health due to its ideal antioxidant properties. We previously prepared a new type of biogenic selenium nanoparticles based on alginate oligosaccharides (SeNPs-AOS), and this study aimed to investigate the protective effects of SeNPs-AOS (Se particle size = 80 nm, Se content = 8%) on organ health in broilers challenged with HS. A total of 192 21-day-old Arbor Acres broilers were randomly divided into four groups according to a 2 × 2 experimental design, including a thermoneutral zone group (TN, raised under 23 ± 1.5 °C); TN + SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (HS, raised under 33 ± 2 °C for 10 h/day); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). There were six replicates in each group (eight broilers per replicate). The results showed that SeNPs-AOS improved the splenic histomorphology, enhanced the activity of catalase (CAT) and glutathione peroxidase (GSH-Px) of the spleen, as well as upregulating the splenic mRNA expression of antioxidant-related genes in broilers under HS. In addition, SeNPs-AOS reversed the pathological changes in bursa caused by HS increased the activity of GST, GSH-Px, and CAT and upregulated the mRNA expression of Nrf2 and antioxidant-related genes in the bursa of heat-stressed broilers. In addition, dietary SeNPs-AOS improved the hepatic damage, increased the activity of GSH-Px in the liver, and upregulated the mRNA expression of antioxidant-related genes while downregulating the Keap1 gene expression of the liver in broilers during HS. Moreover, dietary SeNPs-AOS upregulated the anti-ferroptosis-related genes expression of liver in broilers under HS. In conclusion, dietary SeNPs-AOS could relieve HS-induced oxidative damage to the spleen, bursa of Fabricius and liver in broilers by upregulating the Nrf2-mediated antioxidant gene expression and SeNPs-AOS could also upregulate the expression of hepatic Nrf2-related anti-ferroptosis genes in heat-stressed broilers. These findings are beneficial for the development of new nano-antioxidants in broilers.

Retrospective Analysis of Death Cases of Oral Diphenidol Hydrochloride Poisoning.

OBJECTIVES: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths. METHODS: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected. RESULTS: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied. CONCLUSIONS: Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS: This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.

A mosaic karyotype of 45,X/46,X,psu idic(Y)(q12) in a ten-year-old boy: integrating high-throughput sequencing with cytogenetic technique for precise diagnosis and genetic counselling.

BACKGROUND: Isodicentric Y chromosome (idic(Y)) is the most commonly reported aberration of the human Y chromosome, which is an important cause of abnormal sexual development. The breakpoints of isodicentric Y chromosome mostly occurred in Yq11.2 and Yp11.3, however, the breakpoints in Yq12 are relatively rare. CASE PRESENTATION: We described a 10-year-old boy presenting hypospadias, micropenis and short stature, as well as unilateral cryptorchidism without normal testicular seminiferous tubules structure by biopsy. Whole exome sequencing didn't find any pathogenic/likely pathogenic variants related to phenotypes of this patient. Copy number variation sequencing showed the duplication of whole Y chromosome. Subsequently, karyotyping and FISH analyses demonstrated his genetic diagnosis was mosaic 45,X[8]/46,X,psu idic(Y)(q12)[32], with the breakpoint in Yq12. CONCLUSIONS: Our case proved that it would be beneficial to integrate high-throughput sequencing with cytogenetic technique for precise diagnosis, treatment and genetic counselling.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

TREPH: A Plug-In Topological Layer for Graph Neural Networks.

Topological Data Analysis (TDA) is an approach to analyzing the shape of data using techniques from algebraic topology. The staple of TDA is Persistent Homology (PH). Recent years have seen a trend of combining PH and Graph Neural Networks (GNNs) in an end-to-end manner to capture topological features from graph data. Though effective, these methods are limited by the shortcomings of PH: incomplete topological information and irregular output format. Extended Persistent Homology (EPH), as a variant of PH, addresses these problems elegantly. In this paper, we propose a plug-in topological layer for GNNs, termed Topological Representation with Extended Persistent Homology (TREPH). Taking advantage of the uniformity of EPH, a novel aggregation mechanism is designed to collate topological features of different dimensions to the local positions determining their living processes. The proposed layer is provably differentiable and more expressive than PH-based representations, which in turn is strictly stronger than message-passing GNNs in expressive power. Experiments on real-world graph classification tasks demonstrate the competitiveness of TREPH compared with the state-of-the-art approaches.

Separation, characterization and anti-psoriasis effect of self-assembled nanoparticles from Shaoyao Gancao Decoction / 中国中药杂志

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.

Locally Fluorinated Electrolyte Medium Layer for High-Performance Anode-Free Li-Metal Batteries.

Low cycling Coulombic efficiency (CE) and messy Li dendrite growth problems have greatly hindered the development of anode-free Li-metal batteries (AFLBs). Thus, functional electrolytes for uniform lithium deposition and lithium/electrolyte side reaction suppression are desired. Here, we report a locally fluorinated electrolyte (LFE) medium layer surrounding Cu foils to tailor the chemical compositions of the solid-electrolyte interphase (SEI) in AFLBs for inhibiting the immoderate Li dendrite growth and to suppress the interfacial reaction. This LFE consists of highly concentrated LiTFSI dissolved in a fluoroethylene carbonate and/or succinonitrile plastic mixture. The CE of Cu||LiNi0.8Co0.1Mn0.1O2 (NCM811) AFLB increased to a high level of 99% as envisaged, and the cycling ability was also highly improved. These improvements are facilitated by the formation of a uniform, dense, and LiF-rich SEI. LiF possesses high interfacial energy at the LiF/Li interface, resulting in a more uniform Li deposition process as proved by density functional theory (DFT) calculation results. This work provides a simple yet utility tech for the enhancement of future high-energy-density AFLBs.