Tetrahedral Framework Nucleic Acids Delivery of Pirfenidone for Anti-Inflammatory and Antioxidative Effects to Treat Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease, and developing an effective treatment remains a challenge. The limited therapeutic options are primarily delivered by the oral route, among which pirfenidone (PFD) improves pulmonary dysfunction and patient quality of life. However, its high dose and severe side effects (dyspepsia and systemic photosensitivity) limit its clinical value. Intratracheal aerosolization is an excellent alternative method for treating lung diseases because it increases the concentration of the drug needed to reach the focal site. Tetrahedral framework nucleic acid (tFNA) is a drug delivery system with exceptional delivery capabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using tFNA as the delivery vehicle and achieved quantitative nebulized drug delivery to the lungs via micronebulizer for lung fibrosis treatment. In vivo, Pt exhibited excellent immunomodulatory capacity and antioxidant effects. Furthermore, Pt reduced mortality, gradually restored body weight and improved lung tissue structure. Similarly, Pt also exhibited superior fibrosis inhibition in an in vitro fibrosis model, as shown by the suppression of excessive fibroblast activation and epithelial-mesenchymal transition (EMT) in epithelial cells exposed to TGF-ß1. Conclusively, Pt, a complex with tFNA as a transport system, could enrich the therapeutic regimen for IPF via intratracheal aerosolization inhalation.

Ultrasensitive optomechanical strain sensor.

We demonstrate an ultrasensitive optomechanical strain sensor based on a SiN membrane and a Fabry-Perot cavity, enabling the measurements of both static and dynamic strain by monitoring reflected light fluctuations using a single-frequency laser. The SiN membrane offers high-quality-factor mechanical resonances that are sensitive to minute strain fluctuations. The two-beam Fabry-Perot cavity is constructed to interrogate the motion state of the SiN membrane. A static strain resolution of 4.00 nɛ is achieved by measuring mechanical resonance frequency shifts of the SiN membrane. The best dynamic resolution is 4.47 pɛHz-1/2, which is close to that of the sensor using high-finesse cavity and optical frequency comb, overcoming the dependence of ultrasensitive strain sensors on narrow-linewidth laser and high-finesse cavity with frequency locking equipment. This work opens up a promising avenue for a new generation of ultrasensitive strain sensors.

Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet-induced diabetic mice.

Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high-fat-high-glucose diet (HFD)-induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD-induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate-activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet-induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.

Tunable surface plasmon resonance sensor based on graphene-coated photonic crystal fiber in terahertz.

A terahertz surface plasmon resonance (SPR) sensor is designed based on photonic crystal fiber (PCF). Graphene is selectively coated in the cladding hole of the PCF and used as plasmonic material. The coupling mechanism, loss properties, tunability, and refractive index sensing performance of the designed SPR sensor are investigated using the finite element method. The peak of the loss spectrum corresponding to the SPR frequency can be dynamically tuned by adjusting graphene's chemical potential, and a tuning sensitivity of 767.5 GHz/eV is obtained. The SPR frequency red shifts linearly with an increase in the refractive index of analyte from 1.0 to 1.5. An average frequency sensitivity of 208.14 GHz/RIU is obtained. This research provides theoretical guidance for the design of terahertz in-fiber SPR sensors and filters.

In-fiber Michelson interferometric sensor fabricated by single CO2 laser pulse.

An in-fiber Michelson interferometric sensor was presented by fabricating a concavity on the end face of a single mode fiber using a single CO2 laser pulse. Reflected beams from the bottom and air-cladding boundary of the concavity are coupled into the fiber core and superimpose to generate a two-beam in-fiber Michelson interferometer. Compared with other laser-machining methods where multiple scanning cycles with precise manipulation are needed, the proposed method is more straightforward because only a single laser pulse is used to construct the sensor. The concavity constructed by the CO2 laser is very smooth, and its shape could be controlled flexibly by changing the position of the single mode fiber and the parameters of the CO2 laser pulse, so the fringe visibilities of the proposed sensors could be more than 15 dB, which is higher than that of the most reported laser-machining in-fiber Michelson interferometers. The proposed sensor was demonstrated by measuring the temperature with a sensitivity of 11.13 pm/°C. Furthermore, the proposed device is compact (<100 µm), economical, and robust. These advantages make it a promising candidate in practical applications.

Long-term prognosis of culotte versus different crush strategies in management of unprotected left main bifurcation coronary lesions: A meta-analysis.

OBJECTIVE: To assess the long-term clinical effects of Culotte and different Crush techniques in the treatment of unprotected left main bifurcation coronary lesions to determine the best percutaneous coronary intervention strategy. METHODS: The systematic review and meta-analysis comprised search on PubMed, Embase, Cochrane Library, WanFang Data and the China National Knowledge Infrastructure literature databases to locate randomised controlled trials and cohort studies published in Chinese and/or English language till June 2021 and comprised application of Culotte and Crush stenting techniques for percutaneous coronary intervention in patients with unprotected left main bifurcation coronary lesions. The selected studies were analysed for quality, publication bias and heterogeneity. RESULTS: Of the 197 studies located, 8(4.06%) were subjected to meta-analysis. The incidence of major adverse cardiac events in the Mixed-Crush group was higher than the Culotte group (p=0.02), which, in turn, was higher than the Double Kiss Crush group (p<0.0001), The incidence of target lesion revascularisation in the Culotte group was significantly higher than Double Kiss Crush group (p<0.001). The incidence of myocardial infarction in the Culotte group was higher than the Double Kiss Crush group (p=0.04). The incidence of cardiogenic death in the Double Kiss Crush group was similar to that in the Culotte group (p=0.32). CONCLUSIONS: Patients in the Double Kiss Crush group had the most long-term benefits, while those receivingg Mixed Crush had the least long-term benefits.

Targeting AMPK Signaling in the Liver: Implications for Obesity and Type 2 Diabetes Mellitus.

Obesity and type 2 diabetes mellitus (T2DM), as common metabolic diseases, are pathologically characterized by overnutrition and insulin resistance (IR), which subsequently lead to glucose and lipid metabolism disorders. The liver, a major metabolic organ of the body, integrates hormone and metabolic signals to regulate the synthesis of lipids and glucose as well as their transport to peripheral tissues, hence playing an essential role in the development of obesity and T2DM. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a central regulator involved in cellular and organismal metabolism in eukaryotes, which activates processes that produce ATP and diminishes its consumption. In addition, AMPK also regulates mitochondrial homeostasis and promotes autophagy, both of which are associated with the pathogenesis of IR. Therefore, increasing AMPK activity is considered a promising therapeutic strategy to prevent obesity and T2DM. In this review, we summarize the role of hepatic AMPK in obesity and T2DM and the potential of using AMPK activators as therapeutics for metabolic disorders.

Multicomponent Composite Membrane with Three-Phase Interface Heterostructure as Photocatalyst for Organic Dye Removal.

A multicomponent composite membrane (P-S-T/C) with three-phase interface heterostructure is ingeniously designed. A polydopamine (PDA)-modified conductive carbon fiber cloth (CFC) is used as the substrate. Activated poly(vinylidene fluoride) (PVDF) with titanium dioxide (TiO2) and a silicon dioxide (SiO2) aerogel are electrospun as the top layer. The three-phase interface heterostructure was formed by TiO2, conductive CFC, and the SiO2 aerogel. Its photocatalytic performance is validated by photodegradation of organic dyes in a low-oxygen (O2) water environment. On combining with the capillary condensation of a bilayer structure, P-S-T/C exhibits excellent removal capability for anionic and cationic dyes. Moreover, P-S-T/C exhibits excellent stability and recyclability under simulated sunlight. The mechanism study indicates that the separated photogenerated carriers diffuse to the composite membrane surface rapidly on the three-phase interface of P-S-T/C. The abundant O2 adsorbed on the porous SiO2 aerogel surface acts as an electron (e-)-trapping agent, which can also decrease the work function of the composite materials. Superoxide radicals (•O2 -) play a dominant role in the reaction of photodegradation supported by a free radical-trapping experiment. This work paves a way to design a membrane with photocatalytic performance by constructing the interface heterostructure.

Cytosolic and Nucleosolic Calcium-Regulated Molecular Networks in Response to Long-Term Treatment with Abscisic Acid and Methyl Jasmonate in Arabidopsis thaliana.

Calcium acts as a universal secondary messenger that transfers developmental cues and stress signals for gene expression and adaptive growth. A prior study showed that abiotic stresses induce mutually independent cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic Ca2+ ([Ca2+]nuc) increases in Arabidopsis thaliana root cells. However, gene expression networks deciphering [Ca2+]cyt and [Ca2+]nuc signalling pathways remain elusive. Here, using transgenic A. thaliana to selectively impair abscisic acid (ABA)- or methyl jasmonate (MeJA)-induced [Ca2+]cyt and [Ca2+]nuc increases, we identified [Ca2+]cyt- and [Ca2+]nuc-regulated ABA- or MeJA-responsive genes with a genome oligo-array. Gene co-expression network analysis revealed four Ca2+ signal-decoding genes, CAM1, CIPK8, GAD1, and CPN20, as hub genes co-expressed with Ca2+-regulated hormone-responsive genes and hormone signalling genes. Luciferase complementation imaging assays showed interactions among CAM1, CIPK8, and GAD1; they also showed interactions with several proteins encoded by Ca2+-regulated hormone-responsive genes. Furthermore, CAM1 and CIPK8 were required for MeJA-induced stomatal closure; they were associated with ABA-inhibited seed germination. Quantitative reverse transcription polymerase chain reaction analysis showed the unique expression pattern of [Ca2+]-regulated hormone-responsive genes in cam1, cipk8, and gad1. This comprehensive understanding of distinct Ca2+ and hormonal signalling will allow the application of approaches to uncover novel molecular foundations for responses to developmental and stress signals in plants.

Isoliquiritigenin alleviates diabetic symptoms via activating AMPK and inhibiting mTORC1 signaling in diet-induced diabetic mice.

PURPOSE: To determine the effects of isoliquiritigenin (ISL), a chalcone compound isolated from licorice, on type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: 8-week-old C7BL/6 mice were used to establish the T2DM animal model by feeding with high-fat-high-glucose diet (HFD) combined with intraperitoneal injection of streptozotocin. The animals were treated with ISL for 3 weeks. Blood glucose levels, oral glucose tolerance, and insulin tolerance were examined, serum parameters were determined, histologic sections were prepared, activities of enzymes related to glucolipid metabolism were analyzed, and the mitochondrial function was investigated to evaluate effects of ISL on metabolism. The underlying mechanisms of ISL alleviating insulin resistance and restoring metabolic homeostasis were analyzed in HepG2 and INS-1 cells. RESULTS: ISL exhibits a potent activity in relieving hyperglycemia of type 2 diabetic mice. It alleviates insulin resistance and restores metabolic homeostasis without obvious adversary effects in HFD-induced diabetic mice. The metabolic benefits of ISL treatment include promoting hepatic glycogenesis, inhibiting hepatic lipogenesis, reducing hepatic steatosis, and sensitizing insulin signaling. Mechanistically, ISL activates adenosine monophosphate-activated protein kinase (AMPK) and inhibits mammalian target of rapamycin complex 1 (mTORC1). It also suppresses mitochondrial function and reduces ATP production. CONCLUSION: Our findings demonstrate that ISL is able to significantly reduce blood glucose level and alleviate insulin resistance without obvious side effects in diabetic mice, hence uncovering a great potential of ISL as a novel drug candidate in prevention and treatment of T2DM.