Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD.

PURPOSE: To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). METHODS: The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. RESULTS: OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421-/- mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. CONCLUSIONS: OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

Supramolecular Aggregation of Carbon Nanodots.

Supramolecular aggregation has provided the archetype concept to understand the variants in an emerging systems property. Herein, we have achieved the supramolecular assembly of carbon nanodots (CDs) for the first time and employ supramolecular aggregation to understand their alteration in photophysical properties. In detail, we have employed the CDs as a block to construct the supramolecular assembly of aggregates in the CDs' antisolvent of ethanol. The CD-based aggregates exhibit complex and organized morphologies with another long-wavelength excitation-dependent emission band. The experimental results and density functional theoretical calculations reveal that the supramolecular assembly of CDs can decrease the energy gap between the ground and excited states, contributing to the new long-wavelength excitation-dependent emission. The supramolecular aggregation can be employed as one universal strategy to manipulate and understand the luminescence of CDs. These findings cast new light to build the emerging systems and understand the light emission of CDs through supramolecular chemistry.

In Situ Confining Citric Acid-Derived Carbon Dots for Full-Color Room-Temperature Phosphorescence.

Room-temperature phosphorescence has received much attention owing to its potential applications in information encryption and bioelectronics. However, the preparation of full-color single-component-derived phosphorescent materials remains a challenge. Herein, a facile in situ confining strategy is proposed to achieve full-color phosphorescent carbon dots (CDs) through rapid microwave-assisted carbonization of citric acid in NaOH. By tuning the mass ratio of citric acid and NaOH, the obtained CDs exhibit tunable phosphorescence wavelengths ranging from 483 to 635 nm and alterable lifetimes from 58 to 389 ms with a synthesis yield of up to 83.7% (>30 g per synthesis). Theoretical calculations and experimental results confirm that the formation of high-density ionic bonds between cations and CDs leads to efficient afterglow emission via the dissociation of CD arrangement, and the evolution of the aggregation state of CDs results in redshifted phosphorescence. These findings provide a strategy for the synthesis of new insights into achieving and manipulating room-temperature phosphorescent CDs, and prospect their applications in labeling and information encryption.

Improving the Performance of Poly(caprolactone)-Cellulose Acetate-Tannic Acid Tubular Scaffolds by Mussel-Inspired Coating.

Small-diameter artificial blood vessels are increasingly being used in clinical practice. However, these vessels are prone to thrombus, and it is necessary to improve blood compatibility. Surface coating is one of the commonly used methods in this regard. Inspired by the biomimicry of mussels, the use of deposition technology to obtain coating coverage on the surface of fibers has significantly piqued the interest of researchers recently. In this study, tubular scaffolds consisting of a composite of poly(caprolactone), cellulose acetate, and tannic acid (TA) were electrospun, and then the scaffolds were treated with different Fe(III) solutions (iron(III) chloride hexahydrate (FeCl3'6H2O)) to obtain four tubular scaffolds: F0, F5, F15, and F45. According to scanning electron microscopy (SEM) and field emission-SEM results, TA/Fe(III) complex is coated on the fiber of the scaffold after post-treatment; the fiber surface morphology changes with different Fe(III) concentrations. This provides designability to the performance of tubular scaffolds. The tensile strength of the F5 tubular scaffold (3.33 MPa) is higher than that of F45 (3.14 MPa), while the strain (83.9%) of the F45 tubular stent was 2.26 times that of the F5 (37.2%). In addition, cytotoxicity and antithrombotic performance were evaluated. The test results show that surface TA/Fe(III) coating treatment can affect the cytotoxicity and anticoagulation performance of the scaffold surface. The biomimetic TA/Fe(III) coating of mussels used in this study improves the performance of artificial blood vessels.

Active Control of Interface Dynamics in NASICON-Based Rechargeable Solid-State Sodium Batteries.

Severe challenges are restraining the practical application of solid-state batteries, such as the dendrite growth and unsatisfactory compatibility between solid electrolyte and electrode. Here, we propose an interface dynamic control (IDC) strategy to ensure the stable operation of NASICON-based solid-state sodium batteries. First, we introduce intergranular phase (CuO) to effectively promote the densification of Na3Zr2Si2PO12 with an optimized ionic conductivity of 1.74 × 10-3 S cm-1 at 25 °C. Moreover, the kinetically formed Na-Cu-O interlayer reveals outstanding conductive capability. The dramatically reduced interfacial area-specific resistance (70 ohm cm-2) boosts the resistance to Na dendrite growth, ensuring the excellent cycling stability of symmetric Na cells at a current density of 0.4 mA cm-2 and room temperature. All-solid-state sodium metal batteries with Na3V1.5Cr0.5(PO4)3 cathode and modified Na3Zr2Si2PO12 ceramic electrolyte reveal a high retention of 87.4% at 100 mA g-1 over 300 cycles. This work opens up a new route for the rational interface design of NASICON-structure solid electrolyte toward the application in the high energy-density and high safety electrochemical energy storage devices.

Dual-Function of Cation-Doping to Activate Cationic and Anionic Redox in a Mn-Based Sodium-Layered Oxide Cathode.

Recently, sodium-ion batteries have shown great potential for energy storage owing to their favorable electrochemical properties and intrinsic cost performance, which fuels the research and development of Mn-based layered oxides as promising sodium-ion cathodes. However, the undesirable structural evolution and oxygen redox impose great challenge on the cycling stability and rate capability of such cathodes. In this work, it is reported that Fe and Al can effectively tailor the Na2/3 Mn2/3 Fe1/6 Al1/6 O2 to trigger a stable cationic and anionic redox behavior. In situ X-ray diffraction analysis confirms the retention of a stable P2 phase upon cycling, and density functional theory results demonstrate that Al3+ doping can strengthen the covalency of MnO bond. The Na2/3 Mn2/3 Fe1/6 Al1/6 O2 cathode can retain 90% of its initial capacity within the voltage range of 2.0-4.2 V versus Na+ /Na at 200 mA g-1 after 100 cycles. Moreover, ex situ X-ray photoelectron spectroscopy reveals that the specific capacity can be replenished by the synergistic reactions between Fe3+ /Fe4+ /Fe3+ and O2- /(O2 )n - pairs within the voltage range of 4.0-4.4 V versus Na+ /Na, which is also elucidated by theoretical calculation.

Solid-State Na Metal Batteries with Superior Cycling Stability Enabled by Ferroelectric Enhanced Na/Na3 Zr2 Si2 PO12 Interface.

Solid-state metal batteries are attracting unprecedented concern because of their high energy density and safety. However, their service life, especially at high specific density, is hindered by the undesirable reversibility of metal anodes, owing to the inhomogeneous ion distribution and awkward charge transfer dynamics at the electrode/electrolyte interface. In this work, it is well demonstrated that ferroelectric phase BaTiO3 reinforced Na3 Zr2 Si2 PO12 ceramic electrolyte can deconcentrate the distribution of charge transfer and self-accelerate Na+ migration at the Na/Na3 Zr2 Si2 PO12 interface upon cycling, realizing a compact Na deposition morphology together with a high critical current density (1.05 mA cm-2 at ambient conditions). Assembled symmetric cells based on the proposed composite electrolyte render stable cycling up to 1000 h at 0.3 mA cm-2 . Specifically, the all solid-state sodium metal batteries paired with Na3 V1.5 Cr0.5 (PO4 )3 cathode material can deliver a capacity of 95 mAh g-1 at 100 mA g-1 and maintain 84.4% of the initial capacity after 400 cycles. This excellent electrochemical performance clearly confirm the feasibility of the introduction of ferroelectric BaTiO3 to suppress the dendrite nucleation and Na propagation within ceramic electrolyte. This research offers new insight into the rational design of inorganic electrolyte, revealing dendrite-free and long-term all-solid-state sodium batteries.

Chemoenzymatic Isolation and Characterization of High Purity Mammalian Melanin.

Although melanin is one of the most ubiquitous polymers in living systems, our understanding of its molecular structure, biosynthesis and biophysical properties has been limited to only a small number of organisms other than humans. This is in part due to the difficulty associated with isolating pure melanin. While purification methods exist, they typically involve harsh treatments with strong acid/base conditions combined with elevated temperatures that can lead to the polymer backbone degradation. To be successful, a viable isolation method must deliver a selective, yet complete degradation of non-melanin biopolymers as well as remove small molecule metabolites that are not integrative to the melanin backbone. Here, we demonstrate the use of chemoenzymatic processing guided by fluorescent probes for the purification and isolation of native mammalian melanin without significant induction of chemical degradation. This multi-step purification-tracking methodology enables quantitative isolation of pure melanin from mammalian tissue for spectroscopic characterization.

Heat-Stimuli Shape Memory Effect of Poly (ε-Caprolactone)-Cellulose Acetate Composite Tubular Scaffolds.

Small-diameter artery disease is the most common clinical occurrence, necessitating the development of small-diameter artificial blood vessels. In this study, seven types of poly(-caprolactone)-cellulose acetate (PCL-CA) composite nanofiber membranes were prepared with different proportions of PCL and CA. The adhesion and growth of Mc3t3-e1 cells were considered to confirm the in vitro cytocompatibility of PCL-CA membranes. A smooth stainless-steel mandrel with a diameter of 4 mm was used to roll up the prepared nanofiber membranes to produce the tubular scaffold with 50 °C hot water. The tubular scaffolds were subjected to axial and circumferential tensile tests. The mechanical performance of the PCL-CA tubular scaffold could be improved by increasing the layers. In addition, the burst pressure (BP) of the tubular scaffolds was increased with the layers, and the BPs of six-layer (2380 ± 36.8 mmHg) and eight-layer (3720 ± 80.5 mmHg) tubular scaffolds were much higher than that of the human saphenous vein (2000 mmHg). The compression shape memory performances of the PCL-CA tubular scaffold with different layers were also investigated to simulate and analyze the contraction and expansion of tubular scaffolds. The experimental results showed that the compression strain of the tubular scaffold in the diameter direction reached 35%, and the ultimate shape recovery rate reached 87%. However, the shape fixity rate and shape recovery rate increased, demonstrating that the optimum number of layers can improve the compression shape memory performance of the tubular scaffold. The results of this study, including comprehensive morphological and mechanical properties and cytocompatibility, indicated the potential applicability of PCL-CA tubular scaffolds as tissue engineering grafts.

A Nanocluster [Ag307Cl62(SPhtBu)110]: Chloride Intercalation, Specific Electronic State, and Superstability.

The controlling synthesis of novel nanoclusters of noble metals (Au, Ag) and the determination of their atomically precise structures provide opportunities for investigating their specific properties and applications. Here we report a novel silver nanocluster [Ag307Cl62(SPhtBu)110] (Ag307) whose structure is determined by X-ray single crystal diffraction. The structure analysis shows that nanocluster Ag307 contains a Ag167 core, a surface shell of [Ag140Cl2S110], and a Cl60 intermediate layer located between Ag167 and [Ag140Cl2S110]. It is a first example that such many chlorides are intercalated into a Ag nanocluster. Chlorides are released in situ from solvent CHCl3. Nanocluster Ag307 exhibits superstability. Differential pulse voltammetry experiment reveals that Ag307 has continuous charging/discharging behavior with a capacitance value of 1.39 aF, while the Ag307 has a surface plasmonic feature. These characteristics show that Ag307 is of metallic behavior. However, its electron paramagnetic resonance (EPR) spectra display a spin magnetic behavior which could be originated from the unpassivated dangling bonds of surface atoms. The direct capture of EPR signals can be attributed to the Cl- intercalating layer which partly suppresses the electronic interactions between core and surface atoms, resulting in the relatively independent electronic states for core and surface atoms.

Unraveling the Structure and Function of Melanin through Synthesis.

Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial. Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation. Generally, melanin is classified into five types-eumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelanin-based on the various chemical precursors used in their biosynthesis. Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified. Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins. In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melanin-based materials, while the synthetic analogues of other melanins have received far less attention. In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine. We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure-function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials.

Semiconductor-based selective emitter with a sharp cutoff for thermophotovoltaic energy conversion.

A semiconductor emitter can possibly achieve a sharp cutoff wavelength due to its intrinsic bandgap absorption and almost zero sub-bandgap emission without doping. A germanium-wafer-based selective emitter with front-side antireflection and backside metal coating is studied here for thermophotovoltaic (TPV) energy conversion. Optical simulation predicts the spectral emittance above 0.9 in the wavelengths from 1 to 1.85 µm and below 0.2 in the sub-bandgap range with a sharp cutoff around the bandgap, indicating superior spectral selectivity behavior. This is confirmed by excellent agreement with indirectly measured spectral emittance of the fabricated Ge-based selective emitter sample. Furthermore, the TPV efficiency by pairing the Ge-based selective emitter with a GaSb cell is theoretically analyzed at different temperatures. This Letter facilitates the development of the semiconductor-based selective emitters for enhancing TPV performance.

Silencing HIF-1α aggravates non-alcoholic fatty liver disease in vitro through inhibiting PPAR-α/ANGPTL4 singling pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an aberrant lipid metabolism disease. Hypoxia inducible factor-1 (HIF-1α) is a transcription factor which plays an important part in adapting lower oxygen condition. Here, we aimed to clarify the relationship between HIF-1α and NAFLD. METHODS: HepG2 cells was stimulated by oleic acid (OA) and palmitic acid (PA) to establish in vitro model of NAFLD. The expression of lipid metabolism-related genes, the binding of PPARα to HIF-1α promoter, the lipid deposition, and oxidative stress were detected by qRT-PCR, western blot, Chip assay, Oil Red O staining and ELISA assays, respectively. RESULTS: HIF-1α silence promoted lipid accumulation in NAFLD cells, accompanying by the significantly increased contents of TG (triglyceride) and ApoB (apolipoprotein B). In HepG2 cells treated with OA/PA, the expression of lipid metabolism-related genes and proteins, including APOE, A2m, TNFRSF11B, LDLr, and SREBP2, and the intracellular lipid deposition were up-regulated and further aggravated after silencing HIF-1α. In addition, the loss of HIF-1α could remarkably elevate MDA contents while inhibit the activities of beneficial antioxidant enzymes SOD and GSH-Px to activate oxidative stress, and promote the secretion of pro-inflammatory IL-6 and TNF-α to aggravate inflammation in NDFLD cells. PPARα positively bound to HIF-1α promoter. The silence of PPARα aggravated lipid deposition under normal or hypoxic environment in NAFLD cells. In addition, PPAR-α silence could decrease the expression of HIF-1α and ANGPTL4 in NAFLD cell model; moreover, the expression of APOE, A2m and TNFRSF11B and the production of TG and MDA were increased by PPAR-α suppression. CONCLUSION: HIF-1α plays a crucial role in the regulation of lipid metabolism through activating PPAR-α/ANGPTL4 signaling pathway in NAFLD.

Eco-efficiency evaluation model: a case study of the Yangtze River Economic Belt.

After the concept of ecological efficiency (eco-efficiency) was put forward and constantly supplemented, it generally refers to the maximization of economic benefits with minimum energy consumption and environmental damage. In a new eco-efficiency model proposed by this paper, the input indexes take into account the consumption of capital, human, resources and energy, and the environmental load caused by them. The output indexes take into account GDP, income, and tax revenue. An optimal weighted cross-evaluation efficiency (OWCE) model based on data standardization is proposed, by improving the traditional data envelopment models of CCR and BCC. The OWCE model not only objectively weights but also unifies the comparison scale, and facilitates the establishment of the super-efficiency decomposition model, which is conducive to further exploring the reasons for the difference of eco-efficiency in various regions. Empirically, the eco-efficiencies of 11 provinces (municipalities) along the Yangtze River Economic Belt (YREB) were analyzed based on the data from 2008 to 2019. The results show that there has been a serious imbalance in the 11 provinces, showing a trend of high in the east and low in the west, although the eco-efficiency has been improving continuously in the past 10 years. Shanghai, Zhejiang, and Jiangsu, which are located in the traditional Yangtze River lower delta region, are the top in terms of eco-efficiency, among which Shanghai ranks the first place with absolute advantage, and also is far ahead in sub-efficiencies of basic input, energy consumption, capital and human input, and environmental cost. Geographical location, especially whether it is close to the ocean, and the length of river flow have a certain positive impact on eco-efficiency. Through in-depth analysis, high-energy consumption, high pollution, and low economic output are the main reasons for low eco-efficiency in the middle and upper reaches of the Yangtze River.

Selenomelanin: An Abiotic Selenium Analogue of Pheomelanin.

Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.

Actuation Characteristics and Mechanism of Electroactive Plasticized Thermoplastic Polyurethane.

As interesting alternatives, electroactive actuators based on plasticized thermoplastic polyurethane (TPU) have shown their potential in developing soft robotics due to the large bending deformation, fast response, and good durability, especially their designable properties. Understanding the actuation mechanism is essential for controlling soft actuators as well as developing novel ones. In this work, the behaviors of the plasticizer and TPU membranes in electric fields were investigated and observed in situ by a microscope, showing that the plasticizer molecules migrated toward the anode of the actuator. It is found that there was a very thin plasticizer-rich layer formed in the material because of the accumulation of negatively charged plasticizer molecules, basing on the results of electrochemical impedance measurement and space charge measurement. This further led to a lower Young's modulus but an internal electric field with a higher density in this layer, resulting in the deformation of the actuator. Furthermore, based on the actuation mechanism, some actuation characteristics of the developed soft actuators were clarified. The maximum deflection of these actuators increased with the number of cycle tests, and in each cycle test, the deflection quickly reached the maximum value and then gradually decreased. It is believed that these characteristics are strongly related to the behaviors of plasticizer molecules, which were investigated accordingly.

A Discrete Tetrahedral Indium Cage as an Efficient Heterogeneous Catalyst for the Fixation of CO2 and the Strecker Reaction of Ketones.

A discrete tetrahedral indium cage, {[In12(µ3-OH)4(HCO2)24(tcma)4]} (In12-GL), was synthesized solvothermally by the reaction of indium nitrate with the tripodal tricarboxylic acid ligand N,N,N-tris{(2'-carboxy[1,1'-biphenyl]-4-yl)methyl}methylammonium chloride ([H3tcma]+Cl). This cage consists of four trimeric units [In3(µ3-OH)(µ2-CO2)3(µ2-HCO2)3] and four [tcma]2- ligands, which all perform as 3-connection nodes to bridge each other, resulting in a tetrahedral cage structure. The trimeric unit [In3(µ3-OH)(µ2-CO2)3(µ2-HCO2)3] is observed for the first time in the family of In-based metal-organic structures and can be considered as an evolution of a 6-connected [In3(µ3-O)(µ2-CO2)6] unit. Each In3+ is terminally coordinated by a µ1-HCO2 group. This cage contains potential Lewis acidic/basic active sites endowed by In3+ ions as Lewis acidic sites and the uncoordinated oxygen atoms of µ1-HCO2 moieties as Lewis basic sites and was explored as an effective heterogeneous catalyst in the cycloaddition of CO2 with epoxides and the Strecker reaction for amino nitriles. These catalytic reactions were deduced to happen on the surface of the In12-GL cage.

Optical characterization and modeling of nanoporous gold absorbers fabricated by thin-film dealloying.

This work studies the optical reflectance of nanoporous gold (NPG) thin films of varying pore volume fraction (PVF) synthesized by chemical dealloying of Ag-Au alloy precursors. The fabricated samples are characterized by scanning electron microscopy, and spectral hemispherical reflectance is measured with an integrating sphere. The effective isotropic optical constants of NPG with varying PVF are modeled for the wavelength range from 0.4 to 1.6 µm using the Bruggeman effective medium theory. As the thickness of the NPG thin films is more than ten times larger than the effective penetration depth, the spectral reflectance is simply modeled with the Fresnel coefficients at the interface of air and semi-infinite NPG with different incident angles and polarizations. Consistent with the modeling results, the optical measurement data shows that the spectral normal reflectance of NPG significantly decreases with larger PVF values in the near-infrared regime. On the other hand, the reflectance increases greatly only within visible range at larger oblique angles for transverse-electric polarized waves compared to transverse-magnetic waves. Moreover, the NPG samples demonstrate good thermal stability from room temperature up to 100 °C with little changes in the temperature-dependent spectral hemispherical reflectance.

Risk factors and clinical features of deterioration in COVID-19 patients in Zhejiang, China: a single-centre, retrospective study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection. METHODS: A retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration. RESULTS: One hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36-58] vs [51-70], P = 0.0001); sex (49% vs 77.6%, P = 0.0031); Body Mass Index (BMI) ([21.53-25.51] vs [23.28-27.01], P = 0.0339); hypertension (17.6% vs 57.1%, P < 0.0001); IL-6 ([6.42-30.46] vs [16.2-81.71], P = 0.0001); IL-10 ([2.16-5.82] vs [4.35-9.63], P < 0.0001); T lymphocyte count ([305-1178] vs [167.5-440], P = 0.0001); B lymphocyte count ([91-213] vs [54.5-163.5], P = 0.0001); white blood cell count ([3.9-7.6] vs [5.5-13.6], P = 0.0002); D2 dimer ([172-836] vs [408-953], P = 0.005), PCT ([0.03-0.07] vs [0.04-0.15], P = 0.0039); CRP ([3.8-27.9] vs [17.3-58.9], P < 0.0001); AST ([16, 29] vs [18, 42], P = 0.0484); artificial liver therapy (2% vs 16.3%, P = 0.0148); and glucocorticoid therapy (64.7% vs 98%, P < 0.0001) were associated with the severity of the disease. Age and weight were independent risk factors for disease severity. CONCLUSION: Deterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and artificial liver therapy, when necessary, may help reduce mortality in critically ill patients.

Sheng Mai San protects H9C2 cells against hyperglycemia-induced apoptosis.

BACKGROUND: Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. METHODS: HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 µg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. RESULTS: SMS treatments at 25, 50, 100 µg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 µg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 µg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. CONCLUSION: SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.