The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin.

A cytosolic role for the histone methyltransferase Ezh2 in regulating lymphocyte activation has been suggested, but the molecular mechanisms underpinning this extranuclear function have remained unclear. Here we found that Ezh2 regulated the integrin signaling and adhesion dynamics of neutrophils and dendritic cells (DCs). Ezh2 deficiency impaired the integrin-dependent transendothelial migration of innate leukocytes and restricted disease progression in an animal model of multiple sclerosis. Direct methylation of talin, a key regulatory molecule in cell migration, by Ezh2 disrupted the binding of talin to F-actin and thereby promoted the turnover of adhesion structures. This regulatory effect was abolished by targeted disruption of the interactions of Ezh2 with the cytoskeletal-reorganization effector Vav1. Our studies reveal an unforeseen extranuclear function for Ezh2 in regulating adhesion dynamics, with implications for leukocyte migration, immune responses and potentially pathogenic processes.

Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice.

IMPORTANCE: Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality.

Enhancing light extraction efficiency of the inclined-sidewall-shaped DUV micro-LED array by hybridizing a nanopatterned sapphire substrate and an air-cavity reflector.

In this work, we hybridize an air cavity reflector and a nanopatterned sapphire substrate (NPSS) for making an inclined-sidewall-shaped deep ultraviolet micro light-emitting diode (DUV micro-LED) array to enhance the light extraction efficiency (LEE). A cost-effective hybrid photolithography process involving positive and negative photoresist (PR) is explored to fabricate air-cavity reflectors. The experimental results demonstrate a 9.88% increase in the optical power for the DUV micro-LED array with a bottom air-cavity reflector when compared with the conventional DUV micro-LED array with only a sidewall metal reflector. The bottom air-cavity reflector significantly contributes to the reduction of the light absorption and provides more escape paths for light, which in turn increases the LEE. Our investigations also report that such a designed air-cavity reflector exhibits a more pronounced impact on small-size micro-LED arrays, because more photons can propagate into escape cones by experiencing fewer scattering events from the air-cavity structure. Furthermore, the NPSS can enlarge the escape cone and serve as scattering centers to eliminate the waveguiding effect, which further enables the improved LEE for the DUV micro-LED array with an air-cavity reflector.

On the origin of the enhanced light extraction efficiency of DUV LED by using inclined sidewalls.

It is known that light extraction efficiency (LEE) for AlGaN-based deep ultraviolet (DUV) light-emitting diodes (LEDs) can be enhanced by using an inclined sidewall of mesa. However, the reported optimal inclined angles are different. In this work, to explore the origin for enhancing the LEE of DUV LED by using inclined sidewalls, we investigate the effect of an inclined sidewall angle on the LEE for AlGaN-based DUV LEDs with different mesa diameters by using ray tracing. It is found that when compared to large-size DUV LEDs with inclined sidewall, the LEE of small-size DUV LEDs with inclined sidewall is enhanced from both the bottom and side surfaces due to the reduced scattering length and material absorption. Additionally, the optimal inclined sidewall angle is recommended within the range of 25°-65°, and the optimal angle for DUV LEDs decreases as the chip size increases. It can be attributed to the fact that there are two scattering mechanisms for the inclined sidewall. For smaller chip sizes, most of the light is directly scattered into escape cones by the inclined sidewall, resulting in a larger optimal angle. For larger chip sizes, the light firstly experiences total internal reflections by the out-light plane and then is scattered into escape cones by the inclined sidewalls, leading to a smaller optimal angle.

Enhanced light extraction efficiency for the inclined-sidewall-shaped AlGaN-based DUV LED by using an omni-directional reflector with a thin hybrid dielectric layer.

In this Letter, an omni-directional reflector (ODR) with a thin hybrid dielectric layer (hybrid-ODR) is proposed to enhance the light extraction efficiency (LEE) for inclined-sidewall-shaped AlGaN-based deep ultraviolet light-emitting diode (DUV LED) by inserting a thin diamond with high refraction index into a conventional Al/Al2O3-based ODR. The three-dimensional finite-difference time-domain (3D FDTD) simulation results show that the LEE of TM-polarized light for the DUV LED with hybrid-ODR is enhanced by 18.5% compared with Al/Al2O3-based ODR. It is because the diamond can transform the evanescent wave in Al2O3 into the propagating light wave in diamond, thereby preventing effective excitation of the surface plasmon polariton (SPP) on the surface of the metal Al. Moreover, the Brewster's angle effect causes the TM-polarized light in diamond to propagate effectively into AlGaN. Furthermore, decreasing the total thickness of the dielectric layer also improves the scattering effect of the inclined sidewall. However, the utilization of hybrid-ODR results in a slight reduction in the LEE for transverse electric (TE) polarized light because the light is confined to the diamond layer and eventually absorbed by the metal Al.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Magnetic navigation-assisted colonoscopic enteral tube placement in swine (with video): a preliminary study.

BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.

Sucurchalasins A and B, Sulfur-Containing Heterodimers of a Cytochalasan and a Macrolide from the Endophytic Fungus Aspergillus spelaeus GDGJ-286.

Two sulfur-containing heterodimers of a cytochalasan and a macrolide, sucurchalasins A and B (1 and 2), and four known cytochalasan monomers (3-6), as well as four known macrolide derivatives (7-10), were obtained from the endophytic fungus Aspergillus spelaeus GDGJ-286. Sucurchalasins A and B (1 and 2) are the first cytochalasan heterodimers formed via a thioether bridge between cytochalasan and curvularin macrolide units. Their structures were elucidated by detailed analysis of NMR, LC-MS/MS, and X-ray crystallography. In bioassays, 1 and 2 exhibited cytotoxic effects on A2780 cells, with IC50 values of 3.9 and 8.3 µM, respectively. They also showed antibacterial activities against E. faecalis and B. subtilis with MIC values of 3.1 and 6.3 µg/mL, respectively.

Relationships among protozoa, bacteria and fungi in polycyclic aromatic hydrocarbon-contaminated soils.

Soil bacterial and fungal communities play key roles in the degradation of organic contaminants, and their structure and function are regulated by bottom-up and top-down factors. Microbial ecological effects of polycyclic aromatic hydrocarbons (PAHs) and trophic interactions among protozoa and bacteria/fungi in PAH-polluted soils have yet to be determined. We investigated the trophic interactions and structure of the microbiome in PAH-contaminated wasteland and farmland soils. The results indicated that the total concentration of the 16 PAHs (∑PAHs) was significantly correlated with the Shannon index, NMDS1 and the relative abundances of bacteria, fungi and protozoa (e.g., Pseudofungi) in the microbiome. Structural equation modelling and linear fitting demonstrated cascading relationships among PAHs, protozoan and bacterial/fungal communities in terms of abundance and diversity. Notably, individual PAHs were significantly correlated with microbe-grazing protozoa at the genus level, and the abundances of these organisms were significantly correlated with those of PAH-degrading bacteria and fungi. Bipartite networks and linear fitting indicated that protozoa indirectly modulate PAH degradation by regulating PAH-degrading bacterial and fungal communities. Therefore, protozoa might be involved in regulating the microbial degradation of PAHs by predation in contaminated soil.

Cytotoxic withanolides from the leaves of Datura stramonium L.

Six novel withanolides, along with nine known related compounds were isolated from the leaves of Datura stramonium L. The structures and absolute configurations of the new withanolides were elucidated by employing various spectral techniques and comparing them with those previously reported in the literature. In addition, four withanlides demonstrated interesting cytotoxic activity on LN229 cells with IC50 <20 µM.

Computational and Experimental Comparison of Molecularly Imprinted Polymers Prepared by Different Functional Monomers-Quantitative Parameters Defined Based on Molecular Dynamics Simulation.

BACKGROUND: In recent years, the advancement of computational chemistry has offered new insights into the rational design of molecularly imprinted polymers (MIPs). From this aspect, our study tried to give quantitative parameters for evaluating imprinting efficiency and exploring the formation mechanism of MIPs by combining simulation and experiments. METHODS: The pre-polymerization system of sulfadimethoxine (SDM) was investigated using a combination of quantum chemical (QC) calculations and molecular dynamics (MD) simulations. MIPs were prepared on the surface of silica gel by a surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP). RESULTS: The results of the QC calculations showed that carboxylic monomers exhibited higher bonding energies with template molecules than carboxylic ester monomers. MD simulations confirmed the hydrogen bonding sites predicted by QC calculations. Furthermore, it was observed that only two molecules of monomers could bind up to one molecule of SDM, even when the functional monomer ratio was up to 10. Two quantitative parameters, namely, the effective binding number (EBN) and the maximum hydrogen bond number (HBNMax), were defined. Higher values of EBN and HBNMax indicated a higher effective binding efficiency. Hydrogen bond occupancies and RDF analysis were performed to analyze the hydrogen bond formation between the template and the monomer from different perspectives. Furthermore, under the influence of the EBN and collision probability of the template and the monomers, the experimental results show that the optimal molar ratio of template to monomer is 1:3. CONCLUSIONS: The method of monomer screening presented in this study can be extended to future investigations of pre-polymerization systems involving different templates and monomers.

A PCB image segmentation model based on rotational X-ray computed laminography imaging.

BACKGROUND: The rapid development of industrialization in printed circuit board (PCB) warrants more complexity and integrity, which entails an essential procedure of PCB inspection. X-ray computed laminography (CL) enables inspection of arbitrary regions for large-sized flat objects with high resolution. PCB inspection based on CL imaging is worthy of exploration. OBJECTIVE: This work aims to extract PCB circuit layer information based on CL imaging through image segmentation technique. METHODS: In this work, an effective and applicable segmentation model for PCB CL images is established for the first time. The model comprises two components, with one integrating edge diffusion and l0 smoothing to filter CL images with aliasing artifacts, and the other being the fuzzy energy-based active contour model driven by local pre-fitting energy to segment the filtered images. RESULT: The proposed model is able to suppress aliasing artifacts in the PCB CL images and has good performance on images of different circuit layers. CONCLUSIONS: Results of the simulation experiment reveal that the method is capable of accurate segmentation under ideal scanning condition. Testing of different PCBs and comparison of different segmentation methods authenticate the applicability and superiority of the model.

Revealing Mitochondrion-Lysosome Dynamic Interactions and pH Variations in Live Cells with a pH-Sensitive Fluorescent Probe.

Mitochondrion-lysosome interactions have garnered significant attention in recent research. Numerous studies have shown that mitochondrion-lysosome interactions, including mitochondrion-lysosome contact (MLC) and mitophagy, are involved in various biological processes and pathological conditions. Single fluorescent probes are termed a pivotal chemical tool in unraveling the intricate spatiotemporal interorganelle interplay in live cells. However, current chemical tools are insufficient to deeply understand mitochondrion-lysosome dynamic interactions and related diseases, Moreover, the rational design of mitochondrion-lysosome dual-targeting fluorescent probes is intractable. Herein, we designed and synthesized a pH-sensitive fluorescent probe called INSA, which could simultaneously light up mitochondria (red emission) and lysosomes (green emission) for their internal pH differences. Employing INSA, we successfully recorded long-term dynamic interactions between lysosomes and mitochondria. More importantly, the increasing mitochondrion-lysosome interactions in ferroptotic cells were also revealed by INSA. Further, we observed pH variations in mitochondria and lysosomes during ferroptosis for the first time. In brief, this work not only introduced a pH-sensitive fluorescent probe INSA for the disclosure of the mitochondrion-lysosome dynamic interplays but also pioneered the visualization of the organellar pH alternation in a specific disease model.

Hydrogen inhalation therapy regulates lactic acid metabolism following subarachnoid hemorrhage through the HIF-1α pathway.

The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.

Carrier-envelope-phase-dependent below-threshold harmonic generation in few-cycle mid-infrared laser fields.

We theoretically study the dependence of below-threshold harmonic generation (BTHG) of atoms on the carrier-envelope phase (CEP) driven by few-cycle mid-infrared laser pulses. The BTHG spectra can be accurately and efficiently calculated by solving the three-dimensional time-dependent Schrödinger equation using the time-dependent generalized pseudospectral method. We present the BTHG spectra as a function of the laser-field CEP. CEP-dependent enhancement or suppression occurred at low laser field intensities owing to the changes in the resonant effects associated with multiple quantum trajectories. However, the BTHG of atoms driven by high laser intensities is insensitive to the CEP. The synchrosqueezing time-frequency transform of the BTHG and extended semiclassical analysis are performed to elucidate the underlying physical mechanism.

Suppressing optical crosstalk for GaN/InGaN based flip-chip micro light-emitting diodes by using an air-cavity patterned sapphire substrate as a light filter.

In this work, by using three-dimensional finite-difference time-domain (3D FDTD) method, the effect of conventional nano-patterned sapphire substrate (NPSS) on the optical crosstalk and the light extraction efficiency (LEE) for InGaN/GaN-based flip-chip micro light-emitting diodes (µ-LEDs) are systematically studied. We find that the conventional NPSS is not suitable for µ-LEDs. It is because the inclined mesa sidewall for µ-LEDs possesses a good scattering effect for µ-LEDs, but the introduced conventional NPSS causes part of the light be off escape cone between sapphire and air and become the guided light. To suppress the guided light and improve the optical crosstalk, a thick air layer between the n-GaN layer and the sapphire substrate can be used as a light filter to prevent the guided light from propagating into the sapphire. However, in reality, it is challenging to make the aforementioned air layer from point of fabrication view. Therefore, we propose the air-cavity patterned sapphire substrate (AC-PSS) as the light filter. Our results show that the crosstalk ratio can be decreased to the value even lower than 10%. The LEE can also be enhanced simultaneously due to combination effects of the filtering effect of the AC-PSS and the scattering effect of the inclined mesa sidewall.

Association of stress hyperglycemia with clinical outcomes in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention: a cohort study.

BACKGROUND: In recent years, several studies have demonstrated that stress hyperglycemia is significantly associated with poor prognosis in patients diagnosed with acute coronary syndrome (ACS). In the present study, we aimed to investigate the potential associations between various markers of stress hyperglycemia, such as admission blood glucose (ABG), fasting blood sugar (FBS), and stress hyperglycemia ratio (SHR) with different definitions, and the occurrence of adverse cardiovascular events in patients diagnosed with ST-elevation myocardial infarction (STEMI) who have undergone percutaneous coronary intervention (PCI). METHODS: Our study enrolled a total of 1099 patients diagnosed with STEMI who underwent PCI from 2016 to 2021. The primary outcomes of this study were in-hospital death and all-cause mortality. RESULTS: Stress hyperglycemia was associated with a higher incidence of in-hospital death (ABG OR: 1.27 95% CI 1.19-1.36; FBS OR: 1.25 95% CI 1.16-1.35; SHR1 OR: 1.61 95% CI 1.21-2.14; SHR2 OR: 1.57, 95%CI 1.22-2.01; SHR3 OR: 1.59, 95%CI 1.24-2.05) and all-cause mortality (ABG HR: 1.10, 95% CI 1.07-1.14; FBS HR: 1.12, 95 CI 1.07-1.17; SHR1 HR: 1.19 95% CI 1.03-1.39; SHR2 HR: 1.28, 95%CI 1.14-1.44; SHR3 HR: 1.29, 95%CI 1.14-1.45) after adjusting for ischemic time, age, gender, BMI, hypertension, hyperlipidemia, diabetes mellitus (DM), current smoking history, chronic kidney disease (CKD), previous history of coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), stroke, cancer, culprit vessel, multi-vessel disease. These associations exhibited a non-linear, J-shaped pattern, wherein the risk significantly increased when the ABG and FBS levels exceeded 5mmol/L. Moreover, the inflection point for SHR was estimated to be 1.2. CONCLUSIONS: Stress hyperglycemia was significantly associated with an increased risk of in-hospital death and all-cause mortality in STEMI patients treated with PCI. Stress hyperglycemia should be considered a high-risk prognostic marker in all STEMI patients, regardless of with or without diabetes.

Fabricating and investigating a beveled mesa with a specific inclination angle to improve electrical and optical performances for GaN-based micro-light-emitting diodes.

In this Letter, beveled mesas for 30 × 30 µm2 GaN-based micro-light-emitting diodes (µLEDs) with different inclination angles are designed, fabricated, and measured. We find that µLED with a mesa inclination angle of 28° has the lowest internal quantum efficiency (IQE) and the highest injection current density at which the peak IQE is obtained. This is due to the increased quantum confined Stark effect (QCSE) at the mesa edge. The increased QCSE results from the strong electric field coupling effect. Instead of radiative recombination, more nonradiative recombination and leakage current will be generated in the sidewall regions. Besides, the smallest angle (28°) also produces the lowest light extraction efficiency (LEE), which arises from the optical loss caused by the sidewall reflection at the beveled surface sides. Therefore, the inclination angle for the beveled mesa has to be increased to 52° and 61° by using Ni and SiO2 as hard masks, respectively. Experimental and numerical results show that the external quantum efficiency (EQE) and the optical power can be enhanced for the fabricated devices. Meanwhile, the reduced surface recombination rate also decreases the leakage current.

New chromones from the roots of Saposhnikovia divaricata (Turcz.) Schischk with anti-inflammatory activity.

Fifteen new chromones, sadivamones A-E (1-5), cimifugin monoacetate (6), sadivamones F-N (7-15), together with fifteen known chromones (16-30), were isolated from the ethyl acetate portions of 70% ethanol extract of Saposhnikovia divaricata (Turcz.) Schischk roots. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. Meanwhile, LPS induced RAW264.7 inflammatory cell model was used to determine the potential anti-inflammatory activity of all the isolated compounds in vitro. The results showed that compounds 2, 8, 12-13, 18, 20-22, 24, and 27 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. To determine the signaling pathways involved in the suppression of NO production by compounds 8, 12 and 13, we investigated ERK and c-Jun N-terminal protein kinase (JNK) expression by western blot analysis. Further mechanistic studies demonstrated that compounds 12 and 13 inhibited the phosphorylation of ERK and the activation of ERK and JNK signaling in RAW264.7 cells via MAPK signaling pathways. Taken together, compounds 12 and 13 may be valuable candidates for the treatment of inflammatory diseases.

MethHC 2.0: information repository of DNA methylation and gene expression in human cancer.

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.