Metformin Preserves β-Cell Compensation in Insulin Secretion and Mass Expansion in Prediabetic Nile Rats

Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic β-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and β-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on β-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human β-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on β-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited β-cell glucose-stimulated insulin secretion in vitro, stimulation of β-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, β-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress β-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on β-cell function or cell mass and, instead, early metformin treatment may help protect β-cells from exhaustion and decompensation.     

Preliminary Structural Data Revealed That the SARS-CoV-2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity

The evolution of new SARS-CoV-2 variants around the globe has made the COVID-19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor-binding motif (RBM) of the receptor-binding domain (RBD) spike glycoprotein, i. e. L452R-E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R-E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic-stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural-dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS-CoV-2 variants.     

Opportunities,Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19 †

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with Δ⁹-tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19.     

Far-red-emitting YAl3(BO3)4:Cr3+ phosphors with excellent thermal stability and high luminescent yield for plant growth LEDs

Phosphors-converted LEDs (pc-LEDs) are excellent artificial light sources for indoor plant cultivation, in which the far-red-emitting component (700−780 nm) plays an important role in regulating the photomorphogenesis of plants. Accordingly, highly efficient and thermally stable far-red-emitting phosphors are indispensable for developing high-performance plant cultivation pc-LEDs. Herein, far-red-emitting YAl₃(BO₃)₄:Cr³⁺ (YAB:Cr³⁺) phosphors were synthesized by solid-state reaction, and their photoluminescence characteristics, thermal quenching, quantum yield (QY), and application in pc-LEDs were systematically investigated. The YAB:Cr³⁺ phosphor has an intense broadband absorption to the blue light, simultaneously exhibiting the sharp-line ²E emission and the broadband ⁴ T₂ emission of Cr³⁺ with a QY of ~86.7%. The far-red broadband emissions of YAB:Cr³⁺ centered at ~735 nm show a high resemblance to the active-state (P_FR) absorption of plant phytochrome. Moreover, the YAB:Cr³⁺ phosphor shows the thermally enhanced luminescence at temperatures of 303−393 K and the near-zero thermal quenching up to 423 K. The anomalous thermal enhancement is attributed to the temperature-dependent repopulation between ²E and ⁴ T₂ states. Finally, a pc-LED device was fabricated with the YAB:Cr³⁺ phosphor and blue chip, exhibiting the light out power of ~50.6 mW and energy conversion efficiency of ~17.4% at 100 mA drive current, respectively. The exceptional PL features including suitable excitation/emission wavelengths, suppressed thermal quenching and high QY make YAB:Cr³⁺ phosphors very promising for applications in plant growth pc-LEDs.     

致密砂岩油藏能量补充方式评价及优化

针对致密砂岩油藏大规模体积压裂开发后能量补充困难的问题,利用自主设计制作的大型人造三维岩心物理模型和物理模拟实验舱,开展致密砂岩油藏能量补充方式优化研究。实验结果表明:致密砂岩油藏压裂开发过程中,地层能量损耗严重,采取注水或注气的方式可有效进行能量补充;地层中裂缝规模越大,越有利于原油渗流,后续补充能量的传播范围越广,有助于进一步提高原油采收率;从提高驱油效率和扩大波及系数方面优选吞吐渗吸介质,CO₂均优于活性水,CO₂吞吐开发在矿场试验中取得了显著的增油效果,因此,CO₂吞吐作为一种有效的能量补充方式在致密油开发中展现了良好的应用前景。该文分析了致密砂岩储层水平井压裂开发的渗流规律,优选出致密砂岩储层大规模压裂开发后最佳渗吸介质,可为致密砂岩油藏开发设计提供重要的理论依据。     

Single Cell Bioprinting with Ultrashort Laser Pulses

Tissue engineering requires the precise positioning of mammalian cells and biomaterials on substrate surfaces or in preprocessed scaffolds. Although the development of 2D and 3D bioprinting technologies has made substantial progress in recent years, precise, cell-friendly, easy to use, and fast technologies for selecting and positioning mammalian cells with single cell precision are still in need. A new laser-based bioprinting approach is therefore presented, which allows the selection of individual cells from complex cell mixtures based on morphology or fluorescence and their transfer onto a 2D target substrate or a preprocessed 3D scaffold with single cell precision and high cell viability (93–99% cell survival, depending on cell type and substrate). In addition to precise cell positioning, this approach can also be used for the generation of 3D structures by transferring and depositing multiple hydrogel droplets. By further automating and combining this approach with other 3D printing technologies, such as two-photon stereolithography, it has a high potential of becoming a fast and versatile technology for the 2D and 3D bioprinting of mammalian cells with single cell resolution.     

Progressive NO2 Sensors with Rapid Alarm and Persistent Memory-Type Responses for Wide-Range Sensing Using Antimony Triselenide Nanoflakes

Antimony triselenide (Sb₂Se₃) nanoflake-based nitrogen dioxide (NO₂) sensors exhibit a progressive bifunctional gas-sensing performance, with a rapid alarm for hazardous highly concentrated gases, and an advanced memory-type function for low-concentration (<1 ppm) monitoring repeated under potentially fatal exposure. Rectangular and cuboid shaped Sb₂Se₃ nanoflakes, comprising van der Waals planes with large surface areas and covalent bond planes with small areas, can rapidly detect a wide range of NO₂ gas concentrations from 0.1 to 100 ppm. These Sb₂Se₃ nanoflakes are found to be suitable for physisorption-based gas sensing owing to their anisotropic quasi-2D crystal structure with extremely enlarged van der Waals planes, where they are humidity-insensitive and consequently exhibit an extremely stable baseline current. The Sb₂Se₃ nanoflake sensor exhibits a room-temperature/low-voltage operation, which is noticeable owing to its low energy consumption and rapid response even under a NO₂ gas flow of only 1 ppm. As a result, the Sb₂Se₃ nanoflake sensor is suitable for the development of a rapid alarm system. Furthermore, the persistent gas-sensing conductivity of the sensor with a slow decaying current can enable the development of a progressive memory-type sensor that retains the previous signal under irregular gas injection at low concentrations.     

Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Graphene-Based Heterostructure Composite Sensing Materials for Detection of Nitrogen-Containing Harmful Gases

Graphene-based heterostructure composite is a new type of advanced sensing material that includes composites of graphene with noble metals/metal oxides/metal sulfides/polymers and organic ligands. Exerting the synergistic effect of graphene and noble metals/metal oxides/metal sulfides/polymers and organic ligands is a new way to design advanced gas sensors for nitrogen-containing gas species including NH₃ and NO₂ to solve the problems such as poor stability, high working temperature, poor recovery, and poor selectivity. Different fabrication methods of graphene-based heterostructure composite are extensively studied, enabling massive progress in developing chemiresistive-type sensors for detecting the nitrogen-containing gas species. With the components of noble metals/metal oxides/metal sulfides/polymers and organic ligands which are composited with graphene, each material has its attractive and unique electrical properties. Consequently, the corresponding composite formed with graphene has different sensing characteristics. Furthermore, working ambient gas and response type can affect gas-sensitive characteristic parameters of graphene-based heterostructure composite sensing materials. Moreover, it requires particular attention in studying gas sensing mechanism of graphene-based heterostructure composite sensing materials for nitrogen-containing gas species. This review focuses on related scientific issues such as material synthesis methods, sensing performance, and gas sensing mechanism to discuss the technical challenges and several perspectives.     

Boosted 2D graphene nanosheets by organic-inorganic hybrid cross-linker for an efficient and stable supercapacitor

Using covalent graphene derivatives in energy storage applications is promising. From this view, covalently cross-linked graphene oxide (GO) nanosheets are designed using polyoligomeric silsesquioxanes-propyl-NH₂ (POPN). Then, by incorporating cobalt sulfide nanoparticles into the porous scaffold, a high-value nanocomposite is formed. In a typical three-electrode cell, this nanocomposite declared substantial specific capacity of 454 and 438 Fg^-1 using cyclic voltammetry (CV) and charge-discharge (GCD) assessments. The device is assembled via two identical electrodes containing RGO-SiO₃-NH2-poss-NH2-SiO₃-RGO/cobalt sulfide (RGO-Si-POPN-Si-RGO/CoS₂). Utilizing CV and GCD methods, specific capacitances of 328 and 315 Fg^-1 are realized at a sweep rate and current density of 2 mVs^?1 and 0.5 Ag^-1, respectively. The device presents desirable energy density of 18.5 Whkg^?1 at the power density of 325 Wkg^-1. More impressively, around 97.9% of the specific capacitance is retained after 5000 charge-discharge cycles. The results confirm exceptional capacitive capabilities and super stability of the nanocomposite suitable for practical systems.