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.

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.

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.

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.

Shenlian (SL) Decoction, a Traditional Chinese Medicine Compound, May Ameliorate Blood Glucose via Mediating the Gut Microbiota in db/db Mice.

Shenlian (SL) decoction is a herbal formula composed of Coptis and ginseng, of which berberine and ginsenoside are the main constituents. Even though SL decoction is widely used in treating diabetes in China, the mechanism of its antidiabetes function still needs further study. Gut microbiota disorder is one of the important factors that cause diabetes. To explore the effect of SL decoction on intestinal microbiota, gut microbiota of mice was analyzed by sequencing the gut bacterial 16S rRNA V3+V4 region and metagenomics. In this study, results demonstrated that SL decoction had a better hypoglycemic effect and ß cell protection effect than either ginseng or Coptis chinensis. Alpha diversity analysis showed that all interventions with ginseng, Coptis, and SL decoction could reverse the increased diversity and richness of gut microbiota in db/db mice. PCoA analysis showed oral SL decoction significantly alters gut microbiota composition in db/db mice. 395 OTUs showed significant differences after SL treatment, of which 37 OTUs enriched by SL decoction showed a significant negative correlation with FBG, and 204 OTUs decreased by SL decoction showed a significant positive correlation with FBG. Results of KEGG analysis and metagenomic sequencing showed that SL decoction could reduce the Prevotellaceae, Rikenellaceae, and Helicobacteraceae, which were related to lipopolysaccharide biosynthesis, riboflavin metabolism, and peroxisome, respectively. It could also upregulate the abundance of Bacteroidaceae, which contributed to the metabolism of starch and sucrose as well as pentose-glucuronate interconversions. In the species level, SL decoction significantly upregulates the relative abundance of Bacteroides_acidifaciens which showed a significant negative correlation with FBG and was reported to be a potential agent for modulating metabolic disorders such as diabetes and obesity. In conclusion, SL decoction was effective in hypoglycemia and its mechanism may be related to regulating gut microbiota via upregulating Bacteroides_acidifaciens.

Targeting mTOR Signaling in Type 2 Diabetes Mellitus and Diabetes Complications.

The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM), pathological conditions and end-organ complications can be attributed to aberrant mTOR. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to the development of T2DM. This review summarizes our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in the treatment of T2DM.

ARPI, ß-AS, and UGE regulate glycyrrhizin biosynthesis in Glycyrrhiza uralensis hairy roots.

KEY MESSAGE: ARPI, ß-AS, and UGE were cloned from G. uralensis and their regulatory effects on glycyrrhizin biosynthesis were investigated. ß-AS and UGE but not ARPI positively regulate the biosynthesis of glycyrrhizin. Glycyrrhiza uralensis Fisch. has been used to treat respiratory, gastric, and liver diseases since ancient China. The most important and widely studied active component in G. uralensis is glycyrrhizin (GC). Our pervious RNA-Seq study shows that GC biosynthesis is regulated by multiple biosynthetic pathways. In this study, three target genes, ARPI, ß-AS, and UGE from different pathways were selected and their regulatory effects on GC biosynthesis were investigated using G. uralensis hairy roots. Our data show that hairy roots knocking out ARPI or UGE died soon after induction, indicating that the genes are essential for the growth of G. uralensis hairy roots. Hairy roots with ß-AS knocked out grew healthily. However, they failed to produce GC, suggesting that ß-AS is required for triterpenoid skeleton formation. Conversely, overexpression of UGE or ß-AS significantly increased the GC content, whereas overexpression of ARPI had no obvious effects on GC accumulation in G. uralensis hairy roots. Our findings demonstrate that ß-AS and UGE positively regulate the biosynthesis of GC.

Combined Transcriptomic and Metabolomic Analysis Reveals the Role of Phenylpropanoid Biosynthesis Pathway in the Salt Tolerance Process of Sophora alopecuroides.

Salt stress is the main abiotic stress that limits crop yield and agricultural development. Therefore, it is imperative to study the effects of salt stress on plants and the mechanisms through which plants respond to salt stress. In this study, we used transcriptomics and metabolomics to explore the effects of salt stress on Sophora alopecuroides. We found that salt stress incurred significant gene expression and metabolite changes at 0, 4, 24, 48, and 72 h. The integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes (DEGs) and differential metabolites (DMs) obtained in the phenylpropanoid biosynthesis pathway were significantly correlated under salt stress. Of these, 28 DEGs and seven DMs were involved in lignin synthesis and 23 DEGs and seven DMs were involved in flavonoid synthesis. Under salt stress, the expression of genes and metabolites related to lignin and flavonoid synthesis changed significantly. Lignin and flavonoids may participate in the removal of reactive oxygen species (ROS) in the root tissue of S. alopecuroides and reduced the damage caused under salt stress. Our research provides new ideas and genetic resources to study the mechanism of plant responses to salt stress and further improve the salt tolerance of plants.

Study on the Desulfurization and Regeneration Performance of Functional Deep Eutectic Solvents.

Four deep eutectic solvents (DESs) were synthesized, and 5-30% polyethylenimine (PEI) was added to make functional DESs (FDESs) for dynamic absorption experiments of hydrogen sulfide. The synthesized FDESs were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and nuclear magnetic resonance. The results demonstrated the successful synthesis of FDESs. The interaction between H2S and the FDESs was discussed at a molecular level via the quantum chemical calculations. It was noticed that FDESs prefer chemisorption on H2S. In this work, the 25% PEI/FDES@EG showed the highest desulfurization performance. The effects of H2S concentration and temperature on the desulfurization performance were investigated. It was found that a relatively low temperature (30 °C) was favorable for the absorption of H2S. The 25% PEI/FDES@EG could remove H2S efficiently over a low H2S concentration. Moisture played an important role in the FDES desulfurization system. The absorption/desorption cycle experiment indicated that the FDESs retain their good regeneration performance for at least five times.

Intrinsic and Synaptic Properties Shaping Diverse Behaviors of Neural Dynamics.

The majority of neurons in the neuronal system of the brain have a complex morphological structure, which diversifies the dynamics of neurons. In the granular layer of the cerebellum, there exists a unique cell type, the unipolar brush cell (UBC), that serves as an important relay cell for transferring information from outside mossy fibers to downstream granule cells. The distinguishing feature of the UBC is that it has a simple morphology, with only one short dendritic brush connected to its soma. Based on experimental evidence showing that UBCs exhibit a variety of dynamic behaviors, here we develop two simple models, one with a few detailed ion channels for simulation and the other one as a two-variable dynamical system for theoretical analysis, to characterize the intrinsic dynamics of UBCs. The reasonable values of the key channel parameters of the models can be determined by analysis of the stability of the resting membrane potential and the rebound firing properties of UBCs. Considered together with a large variety of synaptic dynamics installed on UBCs, we show that the simple-structured UBCs, as relay cells, can extend the range of dynamics and information from input mossy fibers to granule cells with low-frequency resonance and transfer stereotyped inputs to diverse amplitudes and phases of the output for downstream granule cells. These results suggest that neuronal computation, embedded within intrinsic ion channels and the diverse synaptic properties of single neurons without sophisticated morphology, can shape a large variety of dynamic behaviors to enhance the computational ability of local neuronal circuits.

Plasma-catalytic degradation of ciprofloxacin in aqueous solution over different MnO2 nanocrystals in a dielectric barrier discharge system.

The α-MnO2, ß-MnO2 and γ-MnO2 samples were prepared by the hydrothermal method and were used for the degradation of ciprofloxacin (CIP) wastewater in a combined DBD-catalytic process. The physical and chemical properties of the samples were systematically studied by several analytical techniques including BET, XRD, SEM, HRTEM, XPS, and H2-TPR. The combination of DBD with α-MnO2 showed the highest CIP degradation efficiency, and the efficiency could reach 93.1% after 50 min, which was 10.8% and 18.1% higher, respectively, than those of ß-MnO2 and γ-MnO2 catalysts in the plasma-catalytic system. According to the model of response surface methodology, the contribution of key experimental parameters on the CIP degradation decreased in the order: peak voltage > air flow rate > initial concentration > initial pH. The optimum operating parameters were peak voltage 17 kV, air flow rate 2.5 L min-1, an initial concentration 5 mg L-1 and an initial pH 6.9. The quenching experiments of active species showed that OH and O2- were critical to the CIP degradation. The generated O3 might be adsorbed by the α-MnO2 catalyst and resulted in more OH generation. The intermediate products of CIP degradation in DBD+α-MnO2 system were analyzed by LC-MS, and three possible degradation pathways were proposed. This research provides an insight into the use of the crystallographic structures in discharge plasma system for antibiotics in water.

Synthesis of γ-Lactones by TBAI-Promoted Intermolecular Carboesterification of Carboxylic Acids with Alkenes and Alcohols.

A novel tetrabutylammonium iodide (TBAI)-promoted three-component reaction of carboxylic acid with alkene and alcohol has been developed, which represents facile and straightforward access to polysubstituted γ-lactone skeletons in moderate-to-good yields. This methodology is distinguished by the use of a commercial catalyst and readily available starting materials, wide substrate scope, and operational simplicity. Mechanistic studies suggested that this transformation went through a radical process.

Overcoming the Anatomical and Physiological Barriers in Topical Eye Surface Medication Using a Peptide-Decorated Polymeric Micelle.

The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.

Self-assembled peptido-nanomicelles as an engineered formulation for synergy-enhanced combinational SDT, PDT and chemotherapy to nasopharyngeal carcinoma.

A formulation of self-assembled peptido-nanomicelles has been developed for a combinational treatment of SDT, PDT and chemotherapy to nasopharyngeal carcinoma. In vitro cellular tests and in vivo mice therapy proved effective for targeted tumor growth inhibition. These merits provided a novel approach to non-invasive cancer treatments.