High performance TM-pass polarizer using multimode Bragg grating waveguide.

A novel ultra-broadband TM-pass polarizer with high polarization extinction ratio (PER) and low reflection has been proposed and demonstrated by utilizing multimode Bragg grating waveguide (MBGW) and two tapered waveguides. By optimizing the period of the MBGW, the injected TE0 mode is coupled into the backward TE2 mode and effectively leaked into the cladding. Meanwhile, the injected TM0 mode propagates through the polarizer without any negative impact. The operation bandwidth can be significantly expanded by cascading multiple MBGW structures, each of which operates at a different central Bragg wavelength. The simulation results indicate that the designed polarizer can achieve an insertion loss (IL) below 0.24 dB and a PER above 39 dB simultaneously across a bandwidth of 300 nm (1400 nm∼1700nm), while the reflected signal is below -9.1 dB. The experiment results demonstrate that the fabricated polarizer can realize an IL below 0.56 dB and a PER above 33 dB in a 160 nm bandwidth ranging from 1470 nm to 1630 nm. Due to limitations in the equipment used, measurements for other wavelength ranges are not conducted. With these merits, the proposed device would find significant applications in optical communication systems.

Nanocavity in hollow sandwiched catalysts as substrate regulator for boosting hydrodeoxygenation of biomass-derived carbonyl compounds.

Hydrodeoxygenation of oxygen-rich molecules toward hydrocarbons is attractive yet challenging in the sustainable biomass upgrading. The typical supported metal catalysts often display unstable catalytic performances owing to the migration and aggregation of metal nanoparticles (NPs) into large sizes under harsh conditions. Here, we develop a crystal growth and post-synthetic etching method to construct hollow chromium terephthalate MIL-101 (named as HoMIL-101) with one layer of sandwiched Ru NPs as robust catalysts. Impressively, HoMIL-101@Ru@MIL-101 exhibits the excellent activity and stability for hydrodeoxygenation of biomass-derived levulinic acid to gamma-valerolactone under 50°C and 1-megapascal H2, and its activity is about six times of solid sandwich counterparts, outperforming the state-of-the-art heterogeneous catalysts. Control experiments and theoretical simulation clearly indicate that the enrichment of levulinic acid and H2 by nanocavity as substrate regulator enables self-regulating the backwash of both substrates toward Ru NPs sandwiched in MIL-101 shells for promoting reaction with respect to solid counterparts, thus leading to the substantially enhanced performance.

Gastroretentive Raft Forming System for Enhancing Therapeutic Effect of Drug-Loaded Hollow Mesoporous Silica on Gastric Ulcers.

Gastric ulcers are characterized by damage to the stomach lining and are often triggered by substances such as ethanol and non-steroidal anti-inflammatory drugs. Patchouli alcohol (PA) has demonstrated effectiveness in treating gastric ulcers through antioxidative and anti-inflammatory effects. However, the water insolubility of PA and rapid gastric emptying cause low drug concentration and poor absorption in the stomach, resulting in limited treatment efficacy of PA. This study develops an oral gastroretentive raft forming system (GRFDDS) containing the aminated hollow mesoporous silica nanoparticles (NH2-HMSN) for PA delivery. The application of NH2-HMSN can enhance PA-loading capacity and water dispersibility, promoting bio-adhesion to the gastric mucosa and sustained drug release. The incorporation of PA-loaded NH2-HMSN (NH2-HMSN-PA) into GRFDDS can facilitate gastric drug retention and achieve long action, thereby improving therapeutic effects. The results reveal that NH2-HMSN-PA protects the gastric mucosa damage by inhibiting NLRP3-mediated pyroptosis. The GRFDDS, optimized through orthogonal design, demonstrates the gastric retention capacity and sustained drug release, exhibiting significant therapy efficacy in an ethanol-induced acute gastric ulcers model and an aspirin-induced chronic gastric ulcers model through antioxidation, anti-pyroptosis, and anti-inflammation. This study provides a potential strategy for enhancing druggability of insoluble natural compounds and therapeutic management of gastric ulcers.

C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 contributes to GA-mediated growth and flowering by interaction with DELLA proteins.

Gibberellic acid (GA) plays a central role in many plant developmental processes and is crucial for crop improvement. DELLA proteins, the core suppressors in the GA signaling pathway, are degraded by GA via the 26S proteasomal pathway to release the GA response. However, little is known about the phosphorylation-mediated regulation of DELLA proteins. In this study, we combined GA response assays with protein-protein interaction analysis to infer the connection between Arabidopsis thaliana DELLAs and the C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 (CPL3), a phosphatase involved in the dephosphorylation of RNA polymerase II. We show that CPL3 directly interacts with DELLA proteins and promotes DELLA protein stability by inhibiting its degradation by the 26S proteasome. Consequently, CPL3 negatively modulates multiple GA-mediated processes of plant development, including hypocotyl elongation, flowering time, and anthocyanin accumulation. Taken together, our findings demonstrate that CPL3 serves as a novel regulator that could improve DELLA stability and thereby participate in GA signaling transduction.

Redox homeostasis in cardiac fibrosis: Focus on metal ion metabolism.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

Bioinspired carbon nanotube-based nanofluidic ionic transistor with ultrahigh switching capabilities for logic circuits.

The voltage-gated ion channels, also known as ionic transistors, play substantial roles in biological systems and ion-ion selective separation. However, implementing the ultrafast switchable capabilities and polarity switching of ionic transistors remains a challenge. Here, we report a nanofluidic ionic transistor based on carbon nanotubes, which exhibits an on/off ratio of 104 at operational gate voltage as low as 1 V. By controlling the morphology of carbon nanotubes, both unipolar and ambipolar ionic transistors are realized, and their on/off ratio can be further improved by introducing an Al2O3 dielectric layer. Meanwhile, this ionic transistor enables the polarity switching between p-type and n-type by controlled surface properties of carbon nanotubes. The implementation of constructing ionic circuits based on ionic transistors is demonstrated, which enables the creation of NOT, NAND, and NOR logic gates. The ionic transistors are expected to have profound implications for low-energy consumption computing devices and brain-machine interfacing.

Structuring Cu Membrane Electrode for Maximizing Ethylene Yield from CO2 Electroreduction.

Electrocatalytic ethylene (C2H4) evolution from CO2 reduction is an intriguing route to mitigate both the energy and environmental crises; however, to acquire industrially relevant high productivity and selectivity at low energy cost remains to be challenging. Membrane assembly electrode has shown great prospect and tailoring its architecture for maximizing C2H4 yield at minimum voltage with long-term stability becomes critical. Here a freestanding Cu membrane cathode is designed and constructed by electrochemically depositing mesoporous Cu film on Cu foam to simultaneously manage CO2, electron, water, and product transport, which shows an extraordinary C2H4 Faradaic efficiency of 85.6% with a full cell power conversion efficiency of 33% at a current density of 368 mA cm-2, heading the techno-economic viability for electrocatalytic C2H4 production.

Iatrogenic Pseudoaneurysm with Acute Arterial Thrombosis in Multiple Branches of the Lower Limbs Treated by Ultrasound-guided Thrombin Injection: A Case Report.

INTRODUCTION: With the development of vascular intervention, pseudoaneurysm complications are increasing. Ultrasound-guided thrombin injection (UGTI) is currently the treatment of choice for pseudoaneurysm, but the pharmacological properties of thrombin may trigger acute thrombosis within the vessel lumen. Despite a very low incidence, this type of primary arterial thrombosis is a serious complication of UGTI, and cases involving multiple branches of the lower limb arteries are particularly rare. CASE PRESENTATION: Here, we report a case of a 65-year-old male who underwent UGTI for the treatment of an iatrogenic pseudoaneurysm of the femoral artery complicated by acute thrombosis of multiple arteries in the lower limbs, and the patient ultimately underwent a successful thrombectomy. CONCLUSION: We reviewed the case and analyzed the possible etiologic causes, providing a reference for future clinical work.

Epigenetic signatures in cardiac fibrosis: Focusing on noncoding RNA regulators as the gatekeepers of cardiac fibroblast identity.

Cardiac fibroblasts play a pivotal role in cardiac fibrosis by transformation of fibroblasts into myofibroblasts, which synthesis and secrete a large number of extracellular matrix proteins. Ultimately, this will lead to cardiac wall stiffness and impaired cardiac performance. The epigenetic regulation and fate reprogramming of cardiac fibroblasts has been advanced considerably in recent decades. Non coding RNAs (microRNAs, lncRNAs, circRNAs) regulate the functions and behaviors of cardiac fibroblasts, including proliferation, migration, phenotypic transformation, inflammation, pyroptosis, apoptosis, autophagy, which can provide the basis for novel targeted therapeutic treatments that abrogate activation and inflammation of cardiac fibroblasts, induce different death pathways in cardiac fibroblasts, or make it sensitive to established pathogenic cells targeted cytotoxic agents and biotherapy. This review summarizes our current knowledge in this field of ncRNAs function in epigenetic regulation and fate determination of cardiac fibroblasts as well as the details of signaling pathways contribute to cardiac fibrosis. Moreover, we will comment on the emerging landscape of lncRNAs and circRNAs function in regulating signal transduction pathways, gene translation processes and post-translational regulation of gene expression in cardiac fibroblast. In the end, the prospect of cardiac fibroblasts targeted therapy for cardiac fibrosis based on ncRNAs is discussed.

Characteristics of deceleration capacity and deceleration runs in vasovagal syncope.

PURPOSE: Increased vagal activity plays a prominent role in vasovagal syncope (VVS). The aim of this study was to characterize vagal function in VVS by evaluating the heart rate (HR) deceleration capacity (DC) and the HR deceleration runs (DRs) in patients with VVS between attacks. METHODS: A total of 188 consecutive VVS patients were enrolled in the study, of whom 129 had positive head-up tilt test (HUTT); 132 healthy participants were enrolled as controls. DC, DRs (DR2, i.e., episodes of 2 consecutive beat-to-beat HR decelerations), and the sum of DR8-10 (very long DR [VLDR]) were calculated using 24-h electrograms. Clinical characteristics, DC, and DRs were compared among syncope groups and controls. RESULTS: Patients with VVS had higher DC (10.63 ± 2.1 vs. 6.58 ± 1.7 ms; P < 0.001) and lower minimum HR and DR6-10 than controls. No significant differences in DC or DR6-10 were found between the patients with positive and those with negative HUTT results. In multivariate logistic regression analysis, minimum HR ≥ 40 bpm (odds ratio [OR] 0.408, 95% confidence interval [CI] 0.167-0.989; P = 0.048), daytime DC ≥ 7.37 ms (OR 3.040, 95% CI 1.220-7.576; P = 0.013), and VLDR ≥ 0.046% (OR 0.306, 95% CI 0.138-0.679; P = 0.004) were demonstrated to be risk factors significantly associated with VVS. CONCLUSION: Compared to healthy controls, patients with VVS demonstrated distinct HR deceleration profiles between attacks, including overall higher DC and lower DR6-10.

Erratum: Author correction to "Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles" [Acta Pharmaceutica Sinica B 12 (2022) 1523-1533].

[This corrects the article DOI: 10.1016/j.apsb.2021.09.004.].

WTAP boosts lipid oxidation and induces diabetic cardiac fibrosis by enhancing AR methylation.

Dysregulated lipid metabolism occurs in pathological processes characterized by cell proliferation and migration. Nonetheless, the mechanism of increased mitochondrial lipid oxidation is poorly appreciated in diabetic cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. Herein, increased WTAP expression promotes cardiac fibroblast proliferation and migration, contributing to diabetic cardiac fibrosis. Knockdown of WTAP suppresses mitochondrial lipid oxidation, fibroblast proliferation and migration to ameliorate diabetic cardiac fibrosis. Mechanistically, WTAP-mediated m6A methylation of AR induced its degradation, dependent on YTHDF2. Additionally, AR directly interacts with mitochondrial lipid oxidation enzyme Decr1; overexpression of AR-suppressed Decr1-mediates mitochondrial lipid oxidation, inhibiting cardiac fibroblast proliferation and migration. Knockdown of AR produced the opposite effect. Clinically, increased WTAP and YTHDF2 levels correlate with decreased AR expression in human DCM heart tissue. We describe a mechanism wherein WTAP boosts higher mitochondrial lipid oxidation, cardiac fibroblast proliferation, and migration by enhancing AR methylation in a YTHDF2-dependent manner.

Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/ß-Catenin Pathway.

The most prevalent type of alopecia is androgenetic alopecia (AGA), which has a high prevalence but no effective treatment. Elevated dihydrotestosterone (DHT) level in the balding area was usually thought to be critical in the pathophysiology of AGA. The canonical Wnt/ß-catenin signaling pathway plays a key role in promoting hair follicle development and sustaining the hair follicle cycle. Adipose-derived stem cell exosomes (ADSC-Exos) are widely used in the field of regenerative medicine due to the advantages of being cell free and immune privileged. Still, few studies have reported the therapeutic effect on hair disorders. As a result, we sought to understand how ADSC-Exos affected hair growth and explore the possibility that ADSC-Exos could counteract the hair-growth-inhibiting effects of DHT. This research using human hair follicle organs, in vitro dermal papilla cells, and in vivo animal models showed that ADSC-Exos not only encouraged healthy hair growth but also counteracted the inhibitory effects of DHT on hair growth. Additionally, we discovered that ADSC-Exos increased Ser9 phosphorylated glycogen synthase kinase-3ß levels and facilitated nuclear translocation of ß-catenin, which may have been blocked by the specific Wnt/ß-catenin signaling pathway inhibitor dickkopf-related protein 1. Our findings suggested that ADSC-Exos are essential for hair regeneration, which is anticipated to open up new therapeutic possibilities for clinical alopecia, particularly for the treatment of AGA.

Anomalous Mechanical and Electrical Interplay in a Covalent Organic Framework Monolayer Membrane.

Ion transport through nanoconfinement, driven by both electrical and mechanical forces, has drawn ever-increasing attention, due to its high similarity to stress-sensitive ion channels in biological systems. Previous studies have reported only pressure-induced enhancement in ion conductance in low-permeable systems such as nanotubes, nanoslits, or single nanopores. This enhancement is generally explained by the ion accumulation caused by the capacitive effect in low-permeable systems. Here, we fabricate a highly permeable COF monolayer membrane to investigate ion transport behavior driven by both electrical and mechanical forces. Our results show an anomalous conductance reduction activated by external mechanical force, which is contrary to the capacitive effect-dominated conductance enhancement observed in low-permeable nanopores or channels. Through simulations, we uncovered a distinct electrical-mechanical interplay mechanism that depends on the relative rate between the ion diffusion from the boundary layer to the membrane surface and the ion transport through the membrane. The high pore density of the COF monolayer membrane reduces the charge accumulation caused by the capacitive effect, resulting in fewer accumulated ions near the membrane surface. Additionally, the high membrane permeability greatly accelerates the dissipation of the accumulated ions under mechanical pressure, weakening the effect of the capacitive layer on the streaming current. As a result, the ions accumulated on the electrodes, rather than in the capacitive layer, dominating the streaming current and giving rise to a distinct electrical-mechanical interplay mechanism compared to that in low-permeable nanopores or channels. Our study provides new insights into the interplay between electrical and mechanical forces in ultra-permeable systems.

Epigenetic hallmarks in pulmonary fibrosis: New advances and perspectives.

Epigenetics indicates that certain phenotypes of an organism can undergo heritable changes in the absence of changes in the genetic DNA sequence. Many studies have shown that epigenetic patterns play an important role in the lung and lung diseases. Pulmonary fibrosis (PF) is also a type of lung disease. PF is an end-stage change of a large group of lung diseases, characterized by fibroblast proliferation and massive accumulation of extracellular matrix, accompanied by inflammatory injury and histological destruction, that is, structural abnormalities caused by abnormal repair of normal alveolar tissue. It causes loss of lung function in patients with multiple complex diseases, leading to respiratory failure and subsequent death. However, current treatment options for IPF are very limited and no drugs have been shown to significantly prolong the survival of patients. Therefore, based on a systematic understanding of the disease mechanisms of PF, this review integrates the role of epigenetics in the development and course of PF, describes preventive and potential therapeutic targets for PF, and provides a theoretical basis for further exploration of the mechanisms of PF.

New aspects of the epigenetic regulation of EMT related to pulmonary fibrosis.

Pulmonary fibrosis is a chronic and progressive fibrotic disease that results in impaired gas exchange, ventilation, and eventual death. The pro-fibrotic environment is instigated by various factors, leading to the transformation of epithelial cells into myofibroblasts and/or fibroblasts that trigger fibrosis. Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in the pathogenesis of pulmonary fibrosis. Epigenetic regulation of tissue-stromal crosstalk involving DNA methylation, histone modifications, non-coding RNA, and chromatin remodeling plays a key role in the control of EMT. The review investigates the epigenetic regulation of EMT and its significance in pulmonary fibrosis.

Crosstalk between oxidative stress and epigenetic marks: New roles and therapeutic implications in cardiac fibrosis.

With the in-depth investigation of cardiac fibrosis, oxidative stress (OS) has been recognized as a significant pathophysiological pathway involved in cardiac remodeling and progression. OS is a condition characterized by the disruption of equilibrium between reactive oxygen species (ROS) produced by the organism and the antioxidant defense system, resulting in adverse effects on the structure and function of the heart. The accumulation of reactive substances beyond cellular thresholds disrupts the normal physiology of both cardiomyocytes and non-cardiomyocytes, leading to OS, inflammation, hypertrophy, and cardiac fibrosis. Furthermore, cardiac OS also modulates several crucial genes involved in maintaining cellular homeostasis, including those associated with mitochondrial biogenesis, injury, and antioxidant defense, which are inevitably associated with concurrent epigenetic changes. Multiple studies have demonstrated the crucial role of epigenetic modifications in regulating cardiac OS. Consequently, modulating OS through targeted epigenetic modifications emerges as a potentially promising therapeutic strategy for managing cardiac fibrosis. This article provides a new review of current research on this subject and proposes that epigenetics may improve OS-induced cardiac fibrosis.

Glycolytic reprogramming in organ fibrosis: New dynamics of the epigenetic landscape.

Accumulating evidence has shown that aerobic glycolysis is essential for the establishment and maintenance of the fibrotic phenotype, so treatments targeting glycolytic reprogramming may become an important strategy to reduce fibrosis. Here, we reviewed current evidence on the glycolytic reprogramming in organ fibrosis, new dynamics of the epigenetic landscape. Epigenetic regulation of the expression of specific genes involved mediates glycolytic reprogramming, thereby affecting fibrosis progression. A comprehensive understanding of the interplay between aerobic glycolysis and epigenetics holds great promise for the treatment and intervention of fibrotic diseases. This article aims to comprehensively review the effect of aerobic glycolysis on organ fibrosis, and to elucidate the relevant epigenetic mechanisms of glycolytic reprogramming in different organs.

METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation.

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of mitochondrial fission is not well appreciated in cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. We investigated the causes and consequences of mitochondrial fission in cardiac fibrosis using cultured cells, animal models, and clinical samples. Increased METTL3 expression caused excessive mitochondrial fission, resulting in the proliferation and migration of cardiac fibroblasts that lead to cardiac fibrosis. Knockdown of METTL3 suppressed mitochondrial fission, inhibiting fibroblast proliferation and migration for ameliorating cardiac fibrosis. Elevated METTL3 and N6-methyladenosine (m6A) levels were associated with low expression of long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation of GAS5 induced its degradation, dependent of YTHDF2. GAS5 could interact with mitochondrial fission marker Drp1 directly; overexpression of GAS5 suppressed Drp1-mediated mitochondrial fission, inhibiting cardiac fibroblast proliferation and migration. Knockdown of GAS5 produced the opposite effect. Clinically, increased METTL3 and YTHDF2 levels corresponded with decreased GAS5 expression, increased m6A mRNA content and mitochondrial fission, and increased cardiac fibrosis in human heart tissue with atrial fibrillation. We describe a novel mechanism wherein METTL3 boosts mitochondrial fission, cardiac fibroblast proliferation, and fibroblast migration: METTL3 catalyzes m6A methylation of GAS5 methylation in a YTHDF2-dependent manner. Our findings provide insight into the development of preventative measures for cardiac fibrosis.