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Background: Patients with end-stage renal disease (ESRD) are at a higher risk of cardiovascular diseases. Intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) using optical coherence tomography (OCT) or intravascular ultrasound (IVUS) has been shown to result in better clinical outcomes than angiography guidance. Nevertheless, the clinical outcomes of IVI-guided PCI in ESRD patients remain uncertain. Objectives: This study aimed to compare the clinical outcomes of OCT- and IVUS-guided PCIs in ESRD patients and to report the trend of IVI-guided PCI in Taiwan. Methods: Patients with ESRD on maintenance dialysis, who underwent OCT- or IVUS-guided PCI from 2015 to 2021, were compared by propensity-score matching. The primary outcome was composite cardiovascular outcomes, including coronary revascularization, cardiovascular death, and acute myocardial infarction. Results: In 2021, IVI was used to guide PCIs in 27% (15,613 of 57,845) of general and 27.5% (1,754 of 6,387) of ESRD patients. Among 4,759 eligible ESRD patients, 443 and 4,316 patients underwent OCT- and IVUS-guided PCIs, respectively. After matching, the incidence of the primary outcome was comparable between the OCT and IVUS groups (42.1 [95% CI: 36.2-48.0] vs 47.6 [95% CI: 43.0-52.2] events per 100 person-years; HR: 0.88; 95% CI: 0.74-1.06). The results were similar for all components of the primary outcome and in subgroup analyses. Conclusions: The number of PCI- and IVI-guided procedures has progressively increased in the past decade in Taiwan in both the general and ESRD populations. Among ESRD patients on maintenance dialysis, the clinical outcomes were comparable between OCT- and IVUS-guided PCI.

Abstract In conventional nondispersive infrared (NDIR) gas sensors, a wide-spectrum IR source or detector must be combined with a narrowband filter to eliminate the interference of nontarget gases. Therefore, the multiplexed NDIR gas sensor requires multiple pairs of narrowband filters, which is not conducive to miniaturization and integration. Although plasmonic metamaterials or multilayer thin-film structures are widely applied in spectral absorption filters, realizing high-performance, large-area, multiband, and compact filters is rather challenging. In this study, we propose and demonstrate a narrowband meta-absorber based on a planar metal–insulator–metal (MIM) cavity with a metallic ultrathin film atop. Nearly perfect absorption of different wavelengths can be obtained by controlling the thickness of the dielectric spacer. More significantly, the proposed meta-absorber exhibits angle-dependent characteristics. The absorption spectra of different gases can be matched by changing the incident angle of the light source. We also preliminarily investigate the CO2 gas sensing capability of the meta-absorber. Afterward, we propose a tunable meta-absorber integrated with a microelectromechanical system (MEMS)-based electrothermal actuator (ETA). By applying a direct current (DC) bias voltage, the inclination angle of the meta-absorber can be controlled, and the relationship between the inclination angle and the applied voltage can be deduced theoretically. The concept of a tunable MEMS-based meta-absorber offers a new way toward highly integrated, miniaturized and energy-efficient NDIR multigas sensing systems.

Abstract Heart failure (HF) is the leading cause of death in patients with maintenance hemodialysis (MHD). Biomarkers has an important guiding role in the early diagnosis, risk stratification, and prognostic assessment of HF. Increasing studies have indicated that long non-coding RNAs (lncRNAs) have played an indispensable role in the regulatory network of HF. This study was aiming to explore the expression profiles of lncRNAs in patients treated with MHD developing heart failure. Peripheral blood mononuclear cells were isolated from 4 hemodialysis patients with reduced ejection fraction (HFrEF) and 4 hemodialysis patients with preserved ejection fraction (HFpEF), respectively. The expression profile analysis of lncRNAs was performed by using Illumina Novaseq 6000 sequencer. Quantitative real time polymerase chain reaction (qRT-PCR) was used to verify the expression of representative differentially expressed lncRNAs. Based on lncRNA-miRNA-mRNA-KEGG network analysis, the potential role of candidate lncRNAs and their association with the severity of HF were further evaluated. In total, 1,429 differentially expressed lncRNAs were found between patients with HFrEF and patients with HFpEF, of which 613 were up-regulated and 816 were down-regulated (P

Abstract Background LncRNAs are critical regulators of bladder cancer (BLCA), and ferroptosis is a newly discovered cell death responsible for mediating apoptosis and tumorigenesis. The present study aims to establish a prognostic signature of differentially expressed ferroptosis-related lncRNAs (DEFRlncRNAs) and explore the DEFRlncRNA associated with NUPR1 in BLCA. Methods DEFRlncRNAs in BLCA patients were screened using univariate and multivariate Cox and LASSO regression analyses. In vitro experiments were performed to detect the regulatory effects of DEFRlncRNAs on BLCA cells. A prognostic signature of DEFRlncRNAs in BLCA was created and validated. Moreover, we used RNA-binding protein immunoprecipitation (RIP) to evaluate the correlated DEFRlncRNA with NUPR1. Results A prognostic signature involving 18 DEFRlncRNAs in BLCA was created. Overexpression of AL355353.2 or knockdown of AL136084.3 promoted apoptosis in 5637 and T24 cells in vitro. Results from Starbase database estimated that AL136084.3 was positively associated with NUPR1 (R = 0.229, p

Abstract Background This phase II randomized controlled trial tested whether the intracarotid arterial administration (ICAA) of autologous CD34 + cells to patients within 14 ± 7 days after acute ischemic stroke (IS) could be safe and further improve short- and long-term outcomes. Methods Between January 2018 and March 2022, 28 consecutive patients were equally randomly allocated to the cell-treated group (CD34 + cells/3.0 × 107/patient) or the control group (receiving optimal medical therapy). CD34 + cells were transfused into the ipsilateral brain infarct zone of cell-treated patients via the ICAA in the catheterization room. Results The results demonstrated 100% safety and success rates for the procedure, and no long-term tumorigenesis was observed in cell-treated patients. In cell-treated patients, the angiogenesis capacity of circulating endothelial progenitor cells (EPCs)/Matrigel was significantly greater after treatment than before treatment with granulocyte colony-stimulating factor (all p

Abstract The regulation of long non-coding RNAs (lncRNAs) has been implicated in the pathogenesis of sepsis-induced acute kidney injury (SI-AKI). Nevertheless, the specific roles of individual lncRNAs in this process remain unclear. This study investigated the expression of lncRNA AP001007 in lipopolysaccharide (LPS)-induced HK-2 cells and in the peripheral blood of sepsis patients. The result shows that LPS treatment downregulated the expression of AP001007 in HK-2 cells and that circulating levels of AP001007 were lower in sepsis patients. Furthermore, overexpressing AP001007 in HK-2 cells improved cell viability, mitochondrial activity, and survival when exposed to LPS. Additionally, LPS-treated HK-2 cells secreted fewer pro-inflammatory cytokines when AP001007 was overexpressed. Similar protective effects were observed in human kidney organoids (HKOs) subjected to LPS. These findings suggest that AP001007 confers protection against LPS-induced damage in HK-2 cells and HKOs, highlighting its potential as a regulator of SI-AKI.

Abstract Background Sarcopenia is typically assessed through hand grip strength, walking speed, and chair stand tests. However, it has been inadequately examined in terms of other physical fitness (PF) components in community-dwelling older adults. Thus, in this study, we explored factors influencing the risk of sarcopenia in community-dwelling older adults. In addition, we analyzed the clinicodemographic characteristics of older adults with or without sarcopenia and investigated the effect of sex on their PF. Methods This cross-sectional study included 745 older adults from a community health promotion program in Taiwan. Their clinicodemographic characteristics were recorded. PF was assessed through various tests, such as hand grip strength evaluation, 8-foot up-and-go test (8-UGT), 2-min step test, and 6-m walk test. PF and factors influencing sarcopenia risk were compared between older adults with sarcopenia (sarcopenia group) and those without it (nonsarcopenia group). A logistic regression model was performed to identify key factors associated with sarcopenia. Its predictive performance was evaluated by calculating the area under the receiver operating characteristic curve (ROC) curve. Results Regardless of sex, the sarcopenia group performed worse in almost all components of PF—for example, upper and lower limb muscular strength and endurance, cardiopulmonary fitness, and balance—than did the nonsarcopenia group. However, for men, no significant between-group difference was observed in flexibility. The logistic regression model indicated age (odds ratio [OR]: 1.107), sex (OR: 2.881), Mini Nutritional Assessment—Short Form scores (OR: 0.690), and performance in 8-UGT (OR: 1.346) as factors influencing the risk of sarcopenia. The model exhibited excellent discriminative ability in predicting sarcopenia, as indicated by an area under the curve value of 0.867 (95% confidence interval: 0.827–0.906; p

Metamaterials with active tunability of electromagnetic response have attracted much attention due to their flexibility and applicability in a wide range of optoelectronic applications. In this study, a mid-infrared (MIR) H-shaped metamaterial absorber (HMA) with high tunability is proposed. The structure of HMA is composed of one longitudinal and two transverse metal bars, forming an H-shaped resonator. By varying structural parameters, the HMA achieves perfect triple-band absorption. The resonant intensities of first and second resonances can be modulated linearly at the wavelength of 5.3 μm, while the resonant intensity of third resonance can be kept as stable at the wavelength of 7.3 μm. By moving the transverse metal bar, the maximum tuning range of resonance is 290 nm. Due to the non-rotationally symmetric configuration of HMA, it exhibits polarization-dependence characteristic. HMA exhibits the switchable function from triple-resonance to double-resonance. These results prove that the proposed HMA can be used for applications in gas sensing, polarization controlling, and IR filtering fields.

Herba Siegesbeckiae (HS) has been traditionally used for managing cardio- and cerebro-vascular diseases. Our previous study demonstrated that HS ameliorates myocardial ischemia/reperfusion (I/R) injury. Also, the differentially expressed proteins between HS and I/R groups were shown to be displayed as UCHL5 and were mainly enriched in the NLRP3 inflammasome pathway. However, further elucidation is required concerning the effective subfractions, constituents, and HS influence on the UCHL5/NLRP3 pathway. A co-immunoprecipitation assay and UCHL5 overexpression in cardiomyocyte explores were used to determine the interaction between UCHL5 and NLRP3 during myocardial I/R. The water extracts of HS were subjected to column chromatography using a macroporous adsorption resin. Four HS subfractions (HS-A [H 2 O elution], HS-B [20% ethanol elution], HS-C [50% ethanol elution], and HS-D [95% ethanol elution]) were obtained in this study. HS-C exhibited the most significant protective effect against myocardial I/R and improved I/R injury in vivo . HS-C markedly restrained the expression of UCHL5 and NLRP3 and resisted the role of UCHL5/NLRP3 in the pathogenesis of I/R. Eleven main constituents of HS-C were identified, among which kirenol best displayed anti-I/R injury activity and binding energy. Kirenol accounted for 62.4% of HS-C. Thus, HS-C effectively protected against myocardial I/R injury, which was attributed to mitigation of the UCHL5/NLRP3 pathway and kirenol was identified as the core active constituent.

Abstract cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions.

Background: Breast cancer-related lymphedema (BCRL) is one of the debilitating complications after breast cancer treatment. Several forms of patient-reported outcome measures (PROMs) were developed to evaluate the severity of BCRL based on the patients’ perspective. LYMPH-Q Upper Extremity Module is a newly developed questionnaire for BCRL. This study aimed to demonstrate the process of translation and cultural adaption from English to Mandarin Chinese. Methods and results: The translation process followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines for the translation and cultural adaption of PROM. The process included four steps: forward translation, back translation, back translation review, and patient interviews. In total, five patients with BCRL were recruited for patient interviews.The forward translation step involved two professional translators whose native language was Mandarin Chinese. A reconciled translated version was produced. In the back translation step, the reconciled translated version in Mandarin Chinese was sent to another professional translator whose native language was English. The back-translated version in English was sent back to the developer of LYMPH-Q for review. In this step, 22 items were revised. In the final step of patient interviews, 15 items were revised based on the patients’ feedback. Conclusion: The development of Mandarin Chinese version of LYMPH-Q Upper Extremity Module and its utilization in conjunction with the existing objective measures could provide a more well-rounded picture of the status of patients with BCRL worldwide.

Abstract Simultaneously activating metal and lattice oxygen sites to construct a compatible multi-mechanism catalysis is expected for the oxygen evolution reaction (OER) by providing highly available active sites and mediate catalytic activity/stability, but significant challenges remain. Herein, Fe and S dually modulated NiFe oxyhydroxide (R-NiFeOOH@SO4) is conceived by complete reconstruction of NiMoO4·xH2O@Fe,S during OER, and achieves compatible adsorbate evolution mechanism and lattice oxygen oxidation mechanism with simultaneously optimized metal/oxygen sites, as substantiated by in situ spectroscopy/mass spectrometry and chemical probe. Further theoretical analyses reveal that Fe promotes the OER kinetics under adsorbate evolution mechanism, while S excites the lattice oxygen activity under lattice oxygen oxidation mechanism, featuring upshifted O 2p band centers, enlarged d-d Coulomb interaction, weakened metal-oxygen bond and optimized intermediate adsorption free energy. Benefiting from the compatible multi-mechanism, R-NiFeOOH@SO4 only requires overpotentials of 251 ± 5/291 ± 1 mV to drive current densities of 100/500 mA cm−2 in alkaline media, with robust stability for over 300 h. This work provides insights in understanding the OER mechanism to better design high-performance OER catalysts.

Abstract Introduction Hypercholesterolemia is associated with increased inflammation and impaired serotonin neurotransmission, potentially contributing to depressive symptoms. However, the role of statins, particularly pitavastatin, in modulating serotonin transporter (SERT) function within this context remains underexplored. This study aimed to investigate whether pitavastatin counteracts the neurobiological effects of hypercholesterolemia. Methods Low-density lipoprotein receptor knockout (LDLR−/−) mice on a C57BL/6 background were assigned to three groups: a control group fed a standard chow diet, a group fed a high-fat diet (HFD), and a third group fed a high-fat diet supplemented with pitavastatin (HFD + Pita). We evaluated the effects of HFD with or without pitavastatin on lipid profiles, inflammatory markers, and SERT availability using small-animal positron emission tomography (PET) scans with the radioligand 4-[18F]-ADAM over a 20-week period. Results Pitavastatin treatment in HFD-fed mice significantly reduced both total cholesterol and LDL cholesterol levels in HFD-fed mice compared to those on HFD alone. Elevated inflammatory markers such as IL-1α, MCP-1/CCL2, and TNF-α in HFD mice were notably decreased in the HFD + Pita group. PET scans showed reduced SERT availability in the brains of HFD mice; however, pitavastatin improved this in brain regions associated with mood regulation, suggesting enhanced serotonin neurotransmission. Additionally, the sucrose preference test showed a trend towards increased preference in the HFD + Pita group compared to the HFD group, indicating a potential reduction in depressive-like behavior. Conclusion Our findings demonstrate that pitavastatin not only lowers cholesterol and reduces inflammation but also enhances SERT availability, suggesting a potential role in alleviating depressive symptoms associated with hypercholesterolemia. These results highlight the multifaceted benefits of pitavastatin, extending beyond its lipid-lowering effects to potentially improving mood regulation and neurotransmitter function.

Abstract We propose a meta-emitter based on micro-electro-mechanical system (MEMS) technology. The main structure of the meta-emitter unit cell is composed of four symmetrically split crosses of Au and SiO2 bilayer cantilevers. By changing the size of the cantilevers, this MEMS-based meta-emitter can realize the tunable perfect absorption, and the absorption spectrum is within the longwave infrared (LWIR) wavelength from 8.90 to 11.90 µm. When the surface temperature of the meta-emitter rises, the electrothermal actuation mechanism is performed through the different thermal expansion coefficient (TEC) of the bilayer cantilevers. Therefore, the cantilevers will be bent downward and the bending height of the cantilevers decreases linearly. In such case, the peak value of thermal radiation power can be tuned from the wavelength of 9.52 µm to 10.48 µm when the temperature of meta-emitter is increased from 293 to 1290 K. This proposed MEMS-based meta-emitter is an excellent LWIR light source and has potential application prospects in gas sensing, infrared spectroscopy analysis, medical care and so on.

This study uses bibliometric techniques to explore the international knowledge base on climate change education (CCE), which considers education as crucial for addressing the climate emergency through fostering climate-literate citizens. Analyzing two decades of scientific literature on CCE, we identify evolving considerations, foci, trends, and recommendations, examining a total of 1,264 articles published between 2000 and 2022 in educational-related fields in Web of Science. Using bibliometric techniques, we assessed research trends, author co-citations and journal citations to reveal an evolving publication landscape, including shifts in locations of productive researchers, influential articles, and leading journals publishing CCE studies. Bibliometric techniques help to identify the intellectual knowledge structure and inter-journal referencing, encompassing Theoretical Basis of CCE, Psychology of CCE and Communication, Climate Change within Socioscientific Issues, Conceptions of Climate Change, and Epistemology in CCE. Based on the trends, association networks, limitations and gaps revealed by this analysis, we conclude with suggestions for future research.

Chenopodium formosanum (CF) is a species endemic to Taiwan that is rich in both nutrients and antioxidants. Although the seeds of CF have long been considered valuable sources of antioxidants, no studies have yet examined the levels of antioxidant in CF leaves or these leaves’ optimal extraction methods. In this study, Response Surface Methodology (RSM) was applied to determine the optimal conditions for promoting total phenolic content (TPC), total flavonoid content (TFC), di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) radical scavenging, 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and ferric reducing ability of plasma (FRAP). Results showed that the concentration of ethanol had a major effect on TPC, DPPH radical scavenging, ABTS radical scavenging, and FRAP, whereas temperature had a major effect on TFC. The final optimized results for 100 mL ethanol solution to extract 1 g CF leaves determined using RSM were 141.26 µg gallic acid equivalents/mL for TPC, 158.09 µg quercetin equivalents/mL for TFC, 92.85% for DPPH radical scavenging, 50.49% for ABTS radical scavenging, and 26.85 µg vitamin C equivalents/mL for FRAP. RSM employed in this study revealed that CF leaves, similar to CF seeds, are a potent source of antioxidants.

This study utilized the Taguchi method to optimize the conditions for the hydrothermal extraction of γ-aminobutyric acid (GABA) from fermented mulberry leaves (FMLs) and evaluated the antioxidant capacity of FML extract powder (EP). Four extraction factors—the leaves-to-water ratio, temperature, duration, and pH—were considered, and a series of experiments were conducted in accordance with a Taguchi design. The results indicated that the optimal hydrothermal extraction conditions were a leaves-to-water ratio of 1:10, temperature of 100 °C, duration of 15 min, and pH of 4. Under these conditions, the GABA content of an FML infusion was 75.04 mg GABA/g EP. Further analysis revealed that the pH had the strongest impact on GABA extraction, with the corresponding signal/noise ratio ranging from 27.36 to 31.60. Additionally, experimental results for antioxidant capacity showed that the total phenolic and flavonoid content of the EP were 12.94 mg gallic acid equivalent/g EP and 81.77 mg quercetin equivalent/g EP, respectively. The IC50 values for ABTS and DPPH free-radical-scavenging ability were 0.58 mg/mL and 0.20 mg/mL, respectively. The reducing power of the EP was 81.69 mg vitamin C equivalent/g EP. These findings provide an important foundation for further applications of FMLs.

Micro-electro-mechanical system (MEMS) is once proposed in 1970s and evolving rapidly. Current researchers are seeking for better designs and better applications for MEMS actuators. This work presents an electrostatic driven dual-axis scanning micromirror, i.e., two-dimensional (2D) scanning micromirror with mirror size of 500 μm × 500 μm. The scanning mirror is implemented by using bulk micromachining process on silicon on insulator (SOI) substrate, which is compatible with present complementary metal oxide semiconductor (CMOS) manufacturing technology. The scanning frequency of the slow axis and the fast axis is 4.87 kHz and 31.15 kHz, respectively. The impact factors of the dimensions of comb fingers and torsion beams are analyzed and discussed in this study. Under the driving voltage difference of 100 volts and 70 volts, the deviation angle is 4.57° × 13.08°. Therefore, a simple design of a dual-axis MEMS scanning micromirror is proposed, which can be precisely controlled without additional complex sensors or circuits.

In this work, an actively tunable terahertz metamaterial (TTM) is proposed to realize variable optical attenuation and sensing applications. The unit cell of TTM is composed of H-shaped resonator (HSR) and C-shaped resonator (CSR). The resonant frequency can be tuned from 0.60 THz to 0.82 THz and show an analog electromagnetically induced transparency (EIT) phenomenon. By adjusting the geometry parameters of HSR and CSR, the enhanced quality (Q) factor is obtained from 2 to 14. Moreover, the CSR can be rotated from 0° to 90° to show the potential in the variable optical attenuator (VOA) application. The resonant intensity at 0.60 THz can be gradually decreased and then disappeared eventually when the CSR rotated from 0° to 90° in TE mode. While the resonant intensity at 0.60 THz can be gradually increased and then reach maximum value from 0° to 90° in TM mode. To demonstrate the proposed TTM can be used for the environmental sensing application, the TTM is exposed on the ambient environment with different refractive indexes from 1.0 to 2.2. The maximum sensitivity is 67 GHz. This work offers a novel approach for the THz metamaterial using for the VOA, optical switching, and sensing applications.

Background: Hepatosteatosis is a common condition that can lead to cirrhosis and liver cancer. Galectin-3 (GAL-3) has been implicated in liver fibrosis and inflammation. Objectives: The purpose of this study was to investigate the association between GAL-3 and hepatosteatosis. Design: This study is a retrospective secondary analysis of data from a community health screening program. Methods: A total of 766 participants were included in the final analysis. Hepatosteatosis was diagnosed using ultrasonography, and GAL-3 levels were measured using enzyme-linked immunosorbent assay. Logistic regression analysis was used to examine the association between GAL-3 levels and the presence of hepatosteatosis, adjusting for age, sex, and other potential confounding factors. Results: The prevalence of moderate-to-severe hepatosteatosis in the study population was 31.5%. The participants with hepatosteatosis had a significantly higher mean level of GAL-3 compared to those without hepatosteatosis (16.6 ± 7.3 vs 13.5 ± 7.3 ng/ml; p 1 and GAL-3 >14.4 ng/ml was associated with a significantly increased risk (aOR 3.37, 95% CI: 1.90–5.99, p

Abstract Coronary artery disease (CAD) such as acute myocardial infarction (MI) share several common risk factors with cancers, and each disease may influence the prognosis of the other. Recently, acute MI was demonstrated to accelerate the outgrowth of preexisting breast cancer cells but the risk of breast cancer after MI remains unclear. This study aimed to investigate the association between acute MI and a subsequent diagnosis of breast cancer. Female patients with and without a history of acute MI were identified from nationwide databases in Taiwan. Patients with a diagnosis of cancer, MI or CAD prior to the study period were excluded. After reducing confounding through inverse probability of treatment weighting, we compared the incidence of newly diagnosed breast cancer between patients with a history of acute MI and those without. As a result, a total of 66,445 female patients were obtained, including 15,263 patients with a history of acute MI and 51,182 patients without. The incidences of breast cancer during follow-up were 1.93 (95% confidence interval [CI] 1.78–2.09) and 1.80 (95% CI 1.67–1.93) per 1,000 person-years for patients with and without a history of acute MI, respectively. The hazard ratio (HR) was 1.05 (95% CI 0.78–1.41, P = 0.756). In subgroup analysis, breast cancer risk was significantly associated with acute MI in patients using antidiabetic drugs (HR 1.27; 95% CI 1.02–1.58) and in low to moderate urbanization levels (HR 1.28; 95% CI 1.06–1.53). In conclusion, the risk of newly diagnosed breast cancer was not increased in patients with acute MI when compared to general population without MI or CAD.

Abstract Background Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIP L . Methods Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIP L in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia. Results Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIP L relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products. Conclusions A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.

Abstract Background Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. Methods Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. Results It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. Conclusions Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Abstract Background Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. Purpose The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. Study design and methods Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. Results In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. Conclusion ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

Abstract Peptidoglycan (PG) sacculi surround the cytoplasmic membrane, maintaining cell integrity by withstanding internal turgor pressure. During cell growth, PG endopeptidases cleave the crosslinks of the fully closed sacculi, allowing for the incorporation of new glycan strands and expansion of the peptidoglycan mesh. Outer-membrane-anchored NlpI associates with hydrolases and synthases near PG synthesis complexes, facilitating spatially close PG hydrolysis. Here, we present the structure of adaptor NlpI in complex with the endopeptidase MepS, revealing atomic details of how NlpI recruits multiple MepS molecules and subsequently influences PG expansion. NlpI binding elicits a disorder-to-order transition in the intrinsically disordered N-terminal of MepS, concomitantly promoting the dimerization of monomeric MepS. This results in the alignment of two asymmetric MepS dimers respectively located on the two opposite sides of the dimerization interface of NlpI, thus enhancing MepS activity in PG hydrolysis. Notably, the protein level of MepS is primarily modulated by the tail-specific protease Prc, which is known to interact with NlpI. The structure of the Prc-NlpI-MepS complex demonstrates that NlpI brings together MepS and Prc, leading to the efficient MepS degradation by Prc. Collectively, our results provide structural insights into the NlpI-enabled avidity effect of cellular endopeptidases and NlpI-directed MepS degradation by Prc.

Background: Central venous catheterization (CVC) is a critical clinical procedure. To avoid complications, possessing good knowledge regarding the CVC care bundle and skills for the proper insertion and maintenance of CVC are important. Objectives: To evaluate the effectiveness of an educational intervention and the use of an interactive response system in enhancing the CVC bundle care and insertion skills of medical students undergoing critical care medicine training. Materials and Methods: Sixth-year medical students (equivalent to fourth-year students in the United States) engaged in didactic lessons, interactive demonstrations, and simulator training facilitated by a CVC team comprising three thoracic and two vascular surgeons (all with a minimum 5 years of experience in central venous access) during their intensive care unit (ICU) rotation. Self-reported knowledge and confidence levels were assessed using pre-and posttests administered through the Zuvio App, an interactive response system. Results: A total of 60 students underwent the educational intervention, of which 54 completed the pretest and 40 completed the posttest. In the posttest, significant improvement was found in the CVC bundle care competency and understanding (P = 0.002), preprocedural preparation (P = 0.002), insertion procedures (P = 0.004), complications (P = 0.003), and insertion depth decisions (P = 0.001). Staff and students reported that assessment and interaction via the Zuvio App were valuable, practical, and feasible in a clinical setting, providing trainees with an individual competency portfolio of receiving precise medical education. Conclusions: Integrating the training provided by a specialized team with an interactive response system enhanced the knowledge and competency level in CVC insertion among medical students in this study.

Abstract Spider silk is a promising material with great potential in biomedical applications due to its incredible mechanical properties and resistance to degradation of commercially available bacterial strains. However, little is known about the bacterial communities that may inhabit spider webs and how these microorganisms interact with spider silk. In this study, we exposed two exopolysaccharide-secreting bacteria, isolated from webs of an orb spider, to major ampullate (MA) silk from host spiders. The naturally occurring lipid and glycoprotein surface layers of MA silk were experimentally removed to further probe the interaction between bacteria and silk. Extensibility of major ampullate silk produced by Triconephila clavata that was exposed to either Microbacterium sp. or Novosphigobium sp. was significantly higher than that of silk that was not exposed to bacteria (differed by 58.7%). This strain-enhancing effect was not observed when the lipid and glycoprotein surface layers of MA silks were removed. The presence of exopolysaccharides was detected through NMR from MA silks exposed to these two bacteria but not from those without exposure. Here we report for the first time that exopolysaccharide-secreting bacteria inhabiting spider webs can enhance extensibility of host MA silks and silk surface layers play a vital role in mediating such effects.

Viral vectors are agents enabling gene transfer and genome editing and have widespread utility across the healthcare and biotechnology sectors. In January 2023, the International Bureau for Weights and Measures’ Consultative Committee for Amount of Substance (CCQM) held a workshop on Metrology for Viral systems as molecular tools. The workshop brought together international leaders from across regulatory, industry, government science, and metrology sectors to better understand key challenges for the community: Exploring current limitations in the measurement of virus-derived, virus-based, and virus-like systems in terms of quantification and characterisation; surveying the state-of-the-art in analytical methods and reference material provision for these entities; and initiating a dialog for the strategic development and implementation of suitable standardisation approaches for this sector. This article presents the workshop background and rationale, presentation summaries, conclusions, and recommendations.

Fatty infiltration of the rotator cuff muscles is very common following rotator cuff tears and is one of the most important factors in determining treatment. Current clinical practice relies on subjective evaluation of fatty infiltration through categorical scoring based on the Goutallier classification system. The Dixon magnetic resonance imaging (MRI) sequence provides flexibility in selecting echo times for water–fat separation. The Dixon method, therefore, has the potential to provide robust and high-quality fat quantification that allows for more accurate calculation of fat fraction (%Fat) of the rotator cuff muscles than the Goutallier classification system. However, significant variance exists in sequencing and post-processing methodology within the recent application of Dixon sequences to quantify rotator cuff fatty infiltration. In this paper, we conducted a systematic review to synthesize the relevant literature utilizing Dixon sequencing for the quantification of rotator cuff fatty infiltration. The literature search was extracted from 1094 articles, with 12 studies included in the final review. Regardless of the varying sequencing pattern and post-processing techniques among studies, the findings suggest the Dixon method is reliable for quantitatively calculating the fat fraction of the rotator cuff muscles, even at very low levels of fatty infiltration. In addition, a quantitative difference in fat fraction was observed between participants with different degrees of tear vs. those without any shoulder pathologies. Multi-point Dixon imaging has the potential to be utilized clinically to objectively quantify fatty infiltration and may lead to improved clinical decision making for patients with rotator cuff tears.

Background Herpes zoster (HZ) is the reactivation of varicella zoster virus predominantly affecting individuals aged over 50 years. Dementia is a prevalent age-related condition. The association between HZ and dementia was under dispute. Objectives The objective of this study was to evaluate the evidence on the association of HZ with dementia. Methods We conducted a systematic review and meta-analysis to evaluate the risk of dementia in individuals with a history of HZ compared to those without such a history. We searched PubMed, Embase, Medline, and Cochrane Library for studies published up to February 24, 2024. The risk of bias of studies was examined by the Newcastle–Ottawa Scale. A random effects model meta-analysis was performed to calculate the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI). Subgroup analyses on Alzheimer’s disease (AD), vascular dementia (VD), and cranial nerve involvement of HZ were executed. We used the GRADE methodology to assess the certainty of evidence. Results We included seven cohorts and two case–control studies involving 3,550,251 subjects. The risk of bias of included studies was generally low. The meta-analysis found no association of HZ with dementia (pooled HR 1.00, 95% CI 0.94–1.07 for cohort studies; pooled OR 1.05, 95% CI 0.84–1.30 for case-control studies), with the certainty of evidence being very low. Subgroup analyses for AD, VD, and cranial never HZ also revealed no significant differences (pooled HR being 0.99, 95% CI 0.89–1.09; 1.04, 95% CI 0.85–1.27; and 1.36, 95% CI 0.76–2.43, respectively). Conclusion The current evidence does not support an association of HZ with dementia.