A transchromosomic rat model with human chromosome 21 shows robust Down syndrome features.

Progress in earlier detection and clinical management has increased life expectancy and quality of life in people with Down syndrome (DS). However, no drug has been approved to help individuals with DS live independently and fully. Although rat models could support more robust physiological, behavioral, and toxicology analysis than mouse models during preclinical validation, no DS rat model is available as a result of technical challenges. We developed a transchromosomic rat model of DS, TcHSA21rat, which contains a freely segregating, EGFP-inserted, human chromosome 21 (HSA21) with >93% of its protein-coding genes. RNA-seq of neonatal forebrains demonstrates that TcHSA21rat expresses HSA21 genes and has an imbalance in global gene expression. Using EGFP as a marker for trisomic cells, flow cytometry analyses of peripheral blood cells from 361 adult TcHSA21rat animals show that 81% of animals retain HSA21 in >80% of cells, the criterion for a "Down syndrome karyotype" in people. TcHSA21rat exhibits learning and memory deficits and shows increased anxiety and hyperactivity. TcHSA21rat recapitulates well-characterized DS brain morphology, including smaller brain volume and reduced cerebellar size. In addition, the rat model shows reduced cerebellar foliation, which is not observed in DS mouse models. Moreover, TcHSA21rat exhibits anomalies in craniofacial morphology, heart development, husbandry, and stature. TcHSA21rat is a robust DS animal model that can facilitate DS basic research and provide a unique tool for preclinical validation to accelerate DS drug development.

Liproxstatin-1 alleviates cartilage degradation by inhibiting chondrocyte ferroptosis in the temporomandibular joint.

BGROUND INFORMATION: Ferroptosis contributes to temporomandibular joint osteoarthritis (TMJOA) lesion development and is still poorly understood. RESULTS: In this study, we used different TMJOA animal models to examine whether ferroptosis was related to disease onset in TMJOA induced by monosodium iodoacetate (MIA), IL-1ß, occlusion disorder (OD), and unilateral anterior crossbite (UAC). Immunohistochemical staining and Western blot analysis were used to detect ferroptosis- and cartilage degradation-related protein expression. Our results revealed reduced levels of the ferroptosis-related protein GPX4 in the cartilage layer, but the levels of ACSL4 and P53 were increased in the condyle. Injection of the ferroptosis inhibitor liproxstatin-1 (Lip-1) effectively decreased ACSL4, P53 and TRF expression. In vitro, IL-1ß reduced cartilage extracellular matrix expression in mandibular condylar chondrocytes (MCCs). Lip-1 maintained the morphology and function of mitochondria and ameliorated the exacerbation of lipid peroxidation and reactive oxygen species (ROS) production induced by IL-1ß. CONCLUSION: These results suggest that chondrocyte ferroptosis plays an important role in the development and progression of TMJOA. SIGNIFICANCE: Inhibiting condylar chondrocyte ferroptosis could be a promising therapeutic strategy for TMJOA.

D-A Conjugated Polymer/CdS S-Scheme Heterojunction with Enhanced Interfacial Charge Transfer for Efficient Photocatalytic Hydrogen Generation.

Owing to the improved charge separation and maximized redox capability of the system, Step-scheme (S-scheme) heterojunctions have garnered significant research attention for efficient photocatalysis of H2 evolution. In this work, an innovative linear donor-acceptor (D-A) conjugated polymer fluorene-alt-(benzo-thiophene-dione) (PFBTD) is coupled with the CdS nanosheets, forming the organic-inorganic S-scheme heterojunction. The CdS/PFBTD (CP) composite exhibits an impressed hydrogen production rate of 7.62 mmol g-1  h-1 without any co-catalysts, which is ≈14 times higher than pristine CdS. It is revealed that the outstanding photocatalytic performance is attributed to the formation of rapid electron transfer channels through the interfacial Cd─O bonding as evidenced by the density functional theory (DFT) calculations and in situ X-ray photoelectron spectroscopy (XPS) analysis. The charge transfer mechanism involved in S-scheme heterojunctions is further investigated through the photo-irradiated Kelvin probe force microscopy (KPFM) analysis. This work provides a new point of view on the mechanism of interfacial charge transfer and points out the direction of designing superior organic-inorganic S-scheme heterojunction photocatalysts.

Mixed-state ptychography for quantitative optical properties measurement of vector beam.

Recent advances in ptychography have extended to anisotropic specimens, but vectorial reconstruction of probes owing to polarization aliasing remains a challenge. A polarization-sensitive ptychography that enables full optical property measurement of vector light is proposed. An optimized reconstruction strategy, first calibrating the propagation direction and then performing faithful retrieval, is established. This method avoids multiple image acquisitions with various polarizer configurations and significantly improves the measurement accuracy by correlating the intensity and position of different polarization components. The capability of the proposed method to quantify anisotropic parameters of optical materials and polarization properties of vector probe is demonstrated by experiment.

The effects of pks+ Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy.

BACKGROUND AND AIM: Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients. METHODS: This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR). RESULTS: Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal-CL = 0.013, PNormal-CE = 0.042; metagenomics sequencing, PNormal-CE = 0.026) and validation cohort (PNormal-CL < 0.0001, PNormal-CE < 0.0001). Pks+ E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal-CE = 0.018; in validation cohort: PNormal-CL < 0.0001, PNormal-CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal-CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal-CE = 0.010) and through metagenomics sequencing (map 00121, PNormal-CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal-CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+ E. coli (r = 0.1895, P = 0.0012). CONCLUSIONS: E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+ E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.

Astrocyte-associated fibronectin promotes the proinflammatory phenotype of astrocytes through ß1 integrin activation.

Astrocytes are key players in neuroinflammation. In response to central nervous system (CNS) injury or disease, astrocytes undergo reactive astrogliosis, which is characterized by increased proliferation, migration, and glial fibrillary acidic protein (GFAP) expression. Activation of the transcription factor nuclear factor-κB (NF-κB) and upregulation of downstream proinflammatory mediators in reactive astrocytes induce a proinflammatory phenotype in astrocytes, thereby exacerbating neuroinflammation by establishing an inflammatory loop. In this study, we hypothesized that excessive fibronectin (FN) derived from reactive astrocytes would induce this proinflammatory phenotype in astrocytes in an autocrine manner. We exogenously treated astrocytes with monomer FN, which can be incorporated into the extracellular matrix (ECM), to mimic plasma FN extravasated through a compromised blood-brain barrier in neuroinflammation. We also induced de novo synthesis and accumulation of astrocyte-derived FN through tumor necrosis factor-α (TNF-α) stimulation. The excessive FN deposition resulting from both treatments initiated reactive astrogliosis and triggered NF-κB signaling in the cultured astrocytes. In addition, inhibition of FN accumulation in the ECM by the FN inhibitor pUR4 strongly attenuated the FN- and TNF-α-induced GFAP expression, NF-κB activation, and proinflammatory mediator production of astrocytes by interrupting FN-ß1 integrin coupling and thus the inflammatory loop. In an in vivo experiment, intrathecal injection of pUR4 considerably ameliorated FN deposition, GFAP expression, and NF-κB activation in inflamed spinal cord, suggesting the therapeutic potential of pUR4 for attenuating neuroinflammation and promoting neuronal function restoration.

Effect of a Nursing Health Education Model Based on the Rosenthal Effect on Posttraumatic Growth of Patients with a First Accidental Fracture.

Objective: To investigate the effect of a nursing health education model based on the Rosenthal effect on the posttraumatic growth of patients with a first accidental fracture. Methods: We recruited 212 patients with a first accidental fracture from February 2021 to February 2022; the patients were divided into a control group (n = 106) and an Rosenthal Group (n = 106). The control group received daily care during hospitalization, and the Rosenthal Group received treatment based on a Rosenthal effect health education model. We compared the 2 groups before and after treatment using the Chinese Posttraumatic Growth Inventory (C-PTGI), the Connor-Davidson Resilience Scale (CD-RISC), the Pittsburgh Sleep Quality Index (PSQI), a Visual Analog Scale (VAS) to assess pain, the 36-item Short Form Health Survey (SF-36) to assess quality of life, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). Results: The psychological resilience of both groups of patients improved after treatment, as assessed by C-PTGI and CD-RISC (all P < .05), and the Rosenthal Group improved more than the control group after treatment (all P < .05). The sleep quality and pain scores, as measured by PSQI and VAS, improved for both groups of patients after treatment, and the Rosenthal group improved more than the control group after treatment (all P < .05). The quality of life, as assessed by SF-36, of both groups of patients was similar before treatment (all P > .05) and improved significantly after treatment (all P < .05). The patients' depression and anxiety, as assessed by HAMA and HAMD, improved in both groups after treatment (all P < .05), and the Rosenthal group improved more than the control group after treatment (all P < .05). Conclusion: The Rosenthal effect nursing health education model promotes the posttraumatic psychological growth of patients with a first accidental fracture and enhances their psychological resilience, showing that the Rosenthal effect has important health benefits and can be promoted for clinical application to adjust a patient's psychological state.

Molecularly Tunable Heterostructured Co-Polymers Containing Electron-Deficient and -Rich Moieties for Visible-Light and Sacrificial-Agent-Free H2O2 Photosynthesis.

As an alternative to hydrogen peroxide (H2O2) production by complex anthraquinone oxidation process, photosynthesis of H2O2 from water and oxygen without sacrificial agents is highly demanded. Herein, a covalently connected molecular heterostructure is synthesized via sequential C-H arylation and Knoevenagel polymerization reactions for visible-light and sacrificial-agent-free H2O2 synthesis. The subsequent copolymerization of the electron-deficient benzodithiophene-4,8-dione (BTD) and the electron-rich biphenyl (B) and p-phenylenediacetonitrile (CN) not only expands the π-conjugated domain but also increases the molecular dipole moment, which largely promotes the separation and transfer of the photoinduced charge carriers. The optimal heterostructured BTDB-CN0.2 manifested an impressive photocatalytic H2O2 production rate of 1920 µmol g-1 h-1, which is 2.2 and 11.6 times that of BTDB and BTDCN. As revealed by the femtosecond transient absorption (fs-TA) and theoretical calculations, the linkage serves as a channel for the rapid transfer of photogenerated charge carriers, enhancing the photocatalytic efficiency. Further, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) uncovers that the oxygen reduction reaction occurs through the step one-electron pathway and the mutual conversion between C=O and C-OH with the anchoring of H+ during the catalysis favored the formation of H2O2. This work provides a novel perspective for the design of efficient organic photocatalysts.

Metformin abrogates Fusobacterium nucleatum-induced chemoresistance in colorectal cancer by inhibiting miR-361-5p/sonic hedgehog signaling-regulated stemness.

BACKGROUND: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism. METHODS: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway. RESULTS: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC. CONCLUSIONS: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Noninvasive predictive models based on lifestyle analysis and risk factors for early-onset colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We developed noninvasive predictive models for EO-CRC and investigated its risk factors. METHODS: This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs). RESULTS: All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence. CONCLUSION: We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.

Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions.

OBJECTIVE: To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. METHODS: To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed. RESULTS: A total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05). CONCLUSIONS: In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Low-Temperature-Processed Monolayer Inverse Opal SnO2 Scaffold for Efficient Perovskite Solar Cells.

Organic-inorganic halide perovskite solar cells (PSCs) have attracted tremendous attention in the photovoltaic field due to their excellent optical properties and simple fabrication process. However, the recombination of photogenerated electron-hole pairs at the interface severely affects the power conversion efficiency (PCE) of the PSCs. Herein, a monolayer of inverse opal SnO2 (IO-SnO2 ) is synthesized via a template-assisted method and used as a scaffold for perovskite layer (PSK). The porous IO-SnO2 scaffold increases the contact area and shortens the transport distance between the electron transport layer (ETL) and PSK. Ultraviolet photoelectron spectroscopy and Kelvin probe force microscopy results indicate that the built-in electric field is enhanced with IO-SnO2 scaffold, strengthening the driving force for charge separation. Femtosecond transient absorption spectroscopy measurements reveal that the IO-SnO2 scaffold facilitates interfacial electron transfer from PSK to ETL. Based on the above superiorities, the IO-SnO2 -based PSCs exhibit boosted PCE and device stability compared with the pristine PSCs. This work provides insights into the development of novel scaffold layers for high-performance PSCs.

The association between essential trace element mixture and cognitive function in Chinese community-dwelling older adults.

BACKGROUND: The evidence about the effect of essential trace element (ETE) mixture on cognitive function amongst older adults is limited. This study aims to evaluate the associations of single ETEs and ETE mixture with cognitive function using a representative sample of community-dwelling older adults in China. METHODS: A total of 3814 older adults were included in the study. Urinary concentrations of selenium (Se), vanadium (V), cobalt (Co), strontium (Sr), and molybdenum (Mo) were detected by inductively coupled plasma mass spectrometry. Cognitive function in older adults was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Linear regression and Bayesian kernel machine regression (BKMR) were performed to explore the associations of single ETEs and ETE mixture with cognitive function, respectively. RESULTS: Linear regression showed that urinary levels of Se and V were positively associated with MMSE scores in the adjusted single-element models. BKMR also showed marginally positive associations of Se and V with MMSE scores. Moreover, higher urinary levels of ETE mixture were significantly associated with increased MMSE scores in a dose-response pattern, and Se was the most important contributor within the mixture. Both Se and V demonstrated positive additive effects on the associations of other ETEs with MMSE scores, whereas Co had a negative additive effect. CONCLUSIONS: V and Se are positively associated with cognitive function, individually and as a mixture. ETE mixture exhibits a linear dose-response association with improved cognitive function, with Se being the most important component within the mixture. Mixture analyses rather than single ETE analyses may provide a real-world perspective on the relationship between ETE mixture and cognitive function. Further cohort studies are needed to clarify the association of multiple ETEs with cognitive function.

In situ Irradiated XPS Investigation on S-Scheme TiO2 @ZnIn2 S4 Photocatalyst for Efficient Photocatalytic CO2 Reduction.

Reasonable design of efficient hierarchical photocatalysts has gained significant attention. Herein, a step-scheme (S-scheme) core-shell TiO2 @ZnIn2 S4 heterojunction is designed for photocatalytic CO2 reduction. The optimized sample exhibits much higher CO2 photoreduction conversion rates (the sum yield of CO, CH3 OH, and CH4 ) than the blank control, i.e., ZnIn2 S4 and TiO2 . The improved photocatalytic performance can be attributed to the inhibited recombination of photogenerated charge carriers induced by S-scheme heterojunction. The improvement is also attributed to the large specific surface areas and abundant active sites. Meanwhile, S-scheme photogenerated charge transfer mechanism is testified by in situ irradiated X-ray photoelectron spectroscopy, work function calculation, and electron paramagnetic resonance measurements. This work provides an effective strategy for designing highly efficient heterojunction photocatalysts for conversion of solar fuels.

Core-Shell Structured C@SiO2 Hollow Spheres Decorated with Nickel Nanoparticles as Anode Materials for Lithium-Ion Batteries.

Silicon oxide is regarded as a promising anode material for lithium-ion batteries owing to high theoretical capacity, abundant reserve, and environmental friendliness. Large volumetric variations during the discharging/charging and intrinsically poor electrical conductivity, however, severely hinder its application. Herein, a core-shell structured composite is constructed by hollow carbon spheres and SiO2 nanosheets decorated with nickel nanoparticles (Ni-SiO2 /C HS). Hollow carbon spheres, as mesoporous cores, not only significantly facilitate the electron transfer but also prominently enhance the mechanical robustness of anode materials, which separately improves the rate performance and the cyclic durability. Besides, ultrathin SiO2 nanosheets, as hierarchical shells, provide abundant electrochemical active surface for capacity increment. Moreover, nickel nanoparticles boost the transport capacity of electrons in SiO2 nanosheets. Such a unique architecture of Ni-SiO2 /C HS guarantees an enhanced discharge capacity (712 mAh g-1 at 0.1 A g-1 ) and prolonged cyclic durability (352 mAh g-1 at 1.0 A g-1 after 500 cycles). The present work offers a possibility for silica-based anode materials in the application of next-generation lithium-ion batteries.

PPARα/γ signaling pathways are involved in Chlamydia pneumoniae-induced foam cell formation via upregulation of SR-A1 and ACAT1 and downregulation of ABCA1/G1.

Chlamydia pneumoniae (Cpn) has been reported to be involved in the pathogenesis of early atherosclerosis by inducing macrophage-derived foam cell formation in the presence of low-density lipoprotein (LDL). However, the biochemical mechanisms underlying Cpn-induced foam cell formation are still not fully elucidated. The present study showed that in LDL-treated THP-1-derived macrophages, Cpn not only upregulated the expression of scavenger receptor A1 (SR-A1) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), but it also downregulated the expression of ATP binding cassette transporters (ABCA1 and ABCG1) at both the mRNA and protein levels. These processes facilitated cholesterol accumulation and promoted macrophage-derived foam cell formation. Treatment with the peroxisome proliferator-activated receptor (PPAR)-γ agonist rosiglitazone or the PPARα agonist fenofibrate decreased the number of foam cells induced by Cpn, while the PPARγ antagonist GW9662, the PPARα antagonist MK886, or PPARα/γ siRNAs enhanced the effect of Cpn on foam cell formation and gene expression of SR-A1, ACAT1, and ABCA1/G1. Moreover, the PPARγ agonist rosiglitazone reversed the downregulation of CD36 by Cpn, while PPARγ siRNA and the PPARγ inhibitor GW9662 further suppressed CD36 expression. However, the PPARα agonist, inhibitor, and siRNA all showed no effect on CD36 expression. In conclusion, the PPARα and PPARγ pathways are both involved in Cpn-induced macrophage-derived foam cell formation by upregulating SR-A1 and ACAT1 and downregulating ABCA1/G1 expression.

RTEF-1 Inhibits Vascular Smooth Muscle Cell Calcification through Regulating Wnt/ß-Catenin Signaling Pathway.

Vascular calcification (VC) is highly prevailing in cardiovascular disease, diabetes mellitus, and chronic kidney disease and, when present, is associated with cardiovascular events and mortality. The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is regarded as the foundation for mediating VC. Related transcriptional enhancer factor (RTEF-1), also named as transcriptional enhanced associate domain (TEAD) 4 or transcriptional enhancer factor-3 (TEF-3), is a nuclear transcriptional factor with a potent effect on cardiovascular diseases, apart from its oncogenic role in the canonical Hippo pathway. However, the role and mechanism of RTEF-1 in VC, particularly in calcification of VSMCs, are poorly understood. Our results showed that RTEF-1 was reduced in calcified VSMCs. RTEF-1 significantly ameliorated ß-glycerophosphate (ß-GP)-induced VSMCs calcification, as detected by alizarin red staining and calcium content assay. Also, RTEF-1 reduced alkaline phosphatase (ALP) activity and decreased expressions of osteoblast markers such as Osteocalcin and Runt-related transcription factor-2 (Runx2), but increased expression of contractile protein, including SM α-actin (α-SMA). Additionally, RTEF-1 inhibited ß-GP-activated Wnt/ß-catenin pathway which plays a critical role in calcification and osteogenic differentiation of VSMCs. Specifically, RTEF-1 reduced the levels of Wnt3a, p-ß-catenin (Ser675), glycogen synthase kinase-3ß (GSK-3ß), and p-GSK-3ß (Ser9), but increased the levels of p-ß-catenin (Ser33/37). Also, RTEF-1 increased the ratio of p-ß-catenin (Ser33/37) to ß-catenin proteins and decreased the ratio of p-GSK-3ß (Ser9) to GSK-3ß protein. LiCl, a Wnt/ß-catenin signaling activator, was observed to reverse the protective effect of RTEF-1 overexpression on VSMCs calcification induced by ß-GP. Accordingly, Dickkopf-1 (Dkk1), a Wnt antagonist, attenuated the role of RTEF-1 deficiency in ß-GP-induced VSMCs calcification. Taken together, we concluded that RTEF-1 ameliorated ß-GP-induced calcification and osteoblastic differentiation of VSMCs by inhibiting Wnt/ß-catenin signaling pathway.

Signal intensity ratio of draining vein on silent MR angiography as an indicator of high-flow arteriovenous shunt in brain arteriovenous malformation.

OBJECTIVES: To evaluate whether the signal intensity ratio (rSI) of the draining vein on silent MR angiography is correlated with arteriovenous (A-V) transit time on digital subtraction angiography (DSA), thereby identifying high-flow A-V shunt in brain arteriovenous malformation (BAVM), and to analyze whether the rSI and the characteristic of draining veins on silent MRA are associated with hemorrhage presentation. METHODS: Eighty-one draining veins of 46 participants with BAVM (mean age 33.2 ± 16.9 years) who underwent silent MRA and DSA were evaluated retrospectively. The correlation between the rSI of the draining vein on silent MRA and A-V transit time on DSA was examined. The AUC-ROC was obtained to evaluate the performance of the rSI in determining the presence of high-flow A-V shunt. The characteristics of draining veins with the maximum rSI (rSImax) were further compared between the hemorrhagic and non-hemorrhagic untreated BAVM. RESULTS: The rSI of each draining vein on silent MRA was significantly correlated with A-V transit time from DSA (r = -0.81, p < .001). The AUC-ROC was 0.89 for using the rSI to determine the presence of high-flow A-V shunt. A cut-off rSI value of 1.09 yielded a sensitivity of 82.4% and a specificity of 82.8%. The draining vein with rSImax and no ectasia was significantly more observed in the hemorrhagic group (p = 0.045). CONCLUSIONS: The rSI of the draining vein on silent MRA is significantly correlated with A-V transit time on DSA, and it can be used as an indicator of high-flow A-V shunt in BAVM. KEY POINTS: • The signal intensity ratio (rSI) of the draining vein on silent MRA significantly correlated with arteriovenous (A-V) transit time of brain arteriovenous malformation (BAVM) on digital subtraction angiography (DSA). • The area under the receiver operating characteristic curve (AUC) was 0.89 for using the rSI of draining veins to determine high-flow A-V shunt. • Draining veins with maximum rSI and no ectasia were significantly more observed in the hemorrhagic group of BAVM (p = 0.045).

Influence of calcination temperature on photocatalytic H2O2productivity of hierarchical porous ZnO microspheres.

Photocatalytic production of H2O2from water and atmospheric oxygen has been recognized as a green and sustainable chemical process, due to the abundance of raw materials and sustainable solar energy. Herein, flower-like hierarchical ZnO microspheres were prepared by hydrothermal method followed by calcination at different temperatures, and their photocatalytic performance in H2O2production was examined under simulated sunlight irradiation. The calcination temperature plays a vital role in the structure, morphology, and surface area of the final ZnO products as well as their optical and electrochemical properties, which are determining factors in their photocatalytic activity. The ZnO calcined at 300 °C (Zn-300) exhibits the highest activity and optimal stability, showing productivity of 2793µmol l-1within 60 min of irradiation, which was 6.5 times higher than that of uncalcined ZnO precursor. The remarkable photocatalytic activity is attributed to enhanced light utilization, large surface area, abundant exposed active sites, improved separation efficiency, and prolonged carrier lifespan. Moreover, the results from cycling experiments indicate the as-prepared ZnO samples exhibit good stability and long-time performance. This work provides useful information for the preparation of hierarchical ZnO photocatalysts.