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Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKα/β, p-NF-κB p65, NLRP3, cleaved caspase 1, and mature IL-1β occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1β pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD.

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.

Diabetic cognitive impairment is one of the common complications of type 2 diabetes, which can cause neurological and microvascular damage in the brain. Bushen Huoxue prescription (BSHX), a compound Chinese medicine, has been used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In this study, KK-Ay diabetic model mouse was administered BSHX daily for 12 weeks. Bodyweight, random blood glucose (RBG), and fasting blood glucose (FBG) were measured every 4 weeks. Triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting serum insulin (FINS), and Morris water maze were tested after 12 weeks of administration. On the day of sacrifice, the hippocampus was collected for pathological staining and advanced glycation end products (AGEs) analysis to evaluate the neuroprotective effect of BSHX. Our results showed that BSHX treatment significantly ameliorated the T2DM related insults, including the increased bodyweight, blood glucose, TG, insulin levels, AGEs, the reduced HDL-C, the impaired spatial memory, and the neurological impairment. Moreover, Western blot analysis showed that increased expression of receptors of AGEs (RAGEs), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and activation of nuclear factor-κB (NF-κB) in the hippocampus were significantly inhibited by BSHX treatment. These results indicate that BSHX can significantly ameliorate glucose and lipid metabolism dysfunction, reduce the morphological changes in hippocampus tissues, and improve the cognitive function of KK-Ay mice. These protective effects of BSHX may involve regulation of the AGEs/RAGE/NF-κB signaling pathway.

ObjectiveSince the outbreak of novel coronavirus pneumonia (COVID-19), human mobility restriction measures have raised controversies, partly due to inconsistent findings. Empirical study is urgently needed to reliably assess the causal effects of mobility restriction.MethodsOur study applied the difference-in-difference (DID) model to assess declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time, after adjusting for confounders.ResultsThe DID model showed that a continual expansion of the relative declines over time in 2020. After four weeks, population mobility declined by 54.81% (interquartile ranges, −65.50% to −43.56%). The accrued population mobility declines were associated with significant reduction of cumulative COVID-19 cases throughout six weeks (i.e., 1% decline of population mobility was associated with 0.72% (95%CI 0.50% to 0.93%) reduce of cumulative cases for one week, 1.42% two weeks, 1.69% three weeks, 1.72% four weeks,1.64% five weeks and 1.52% six weeks). The impact on weekly new cases seemed greater in the first four weeks, but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities.ConclusionPersistent population mobility restrictions are well deserved. However, a change in the degree of mobility restriction may be warranted over time, particularly after several weeks of rigorous mobility restriction. Implementation of mobility restrictions in major cities with large population sizes may be even more important.

Microstructure of Ti-28Ta powders produced by plasma rotating electrode process (PREP) was investigated by using scanning electron microscopy (SEM), optical microscopy (OM), and transmission electronic microscopy (TEM). Phase constituent of the PREP Ti-28Ta powders was analyzed by X-ray diffraction (XRD). It was found that microstructure of the PREP Ti-28Ta powders was dependent on the powder particle sizes. Predominant martensitic α”, some metastable β and trace athermal ω phases were observed in the powders with the small diameter. While, phase constituent of the PREP Ti-28Ta powders with the large particle size was predominant metastable β, some martensitic α” and trace athermal ω. With the reduction of the powder particle size, the amount of martensitic α” increased and the metastable β decreased. The martensitic α” was formed preferentially on the metastable β grain boundaries of the PREP Ti-28Ta powders. The increase of α” phase and decrease of β with reduction of the powder particle size is attributed to the increase of the volume of the grain boundaries due to the grain refinement.

In order to meet the requirements for the purpose of biological implant materials, analyzes the matching requirements of the compatibility and mechanical properties of titanium foam biological; by powder metallurgy method, using TiH2 powder as raw material, using ammonium bicarbonate as pore forming agent, preparation of titanium foam. The influences of pore forming agent content and particle size, sintering temperature and holding time on the pore structure, pore distribution, pore size and compressive properties of foam titanium were discussed in detail. The results show that with the increase of the sintering temperature and prolonging holding time, titanium foam compressive yield strength and modulus increased; with the increase of the content of pore forming agent, titanium foam compression yield strength and Young's modulus decreased. The preparation of a porosity of 48% ~ 77%, pore size between 300 ~ 500 m, foam pore structure and pore size in micron level through three-dimensional pore, pore size of bio materials meet the requirements. The compressive strength is 98~186MPa, and the young's modulus is 1.6 ~ 6.8 GPa, which matches the strength and the modulus of elasticity of biological implants.

Diabetic encephalopathy (DE) is a serious complication caused by long-term cognitive impairment in diabetic patients. At present, there is no effective treatment for DE. Icariin (ICA) is a bioactive ingredient isolated from Epimedium. Previous research indicated that ICA was neuroprotective against Aβ-induced PC12 cell insult; however, the effect of ICA on an advanced glycosylation end product- (AGE-) induced neural injury model has not been studied. In this study, we investigated the neuroprotective effects of ICA on AGE-induced injury in PC12 cells. Our findings revealed that ICA could effectively protect PC12 cells from AGE-induced cell apoptosis by suppressing oxidative stress. Moreover, we observed that ICA could significantly protect against mitochondrial depolarization following AGE stimulation and inactivate the mitochondria-dependent caspase-9/3 apoptosis pathway. Most notably, we identified the direct target protein of ICA as apoptosis regulator Bax by a pulldown assay. We found that ICA could specifically target Bax protein and inhibit Bax dimer formation and migration to mitochondria. Furthermore, a siRNA knockdown experiment revealed that ICA could inhibit PC12 cell apoptosis and oxidative stress through targeting Bax. Taken together, our findings demonstrated that ICA could attenuate AGE-induced oxidative stress and mitochondrial apoptosis by specifically targeting Bax and further regulating the biological function of Bax on mitochondria.

In this study, we fabricated spherical Ti-6Al-4V powders using gas atomization. Scanning electron microscope, optical microscope, X-ray diffraction and particle size distribution were extensively performed to investigate the properties of gas-atomized Ti-6Al-4V powders. The XRD analysis shows all the gas-atomized powders are with both α and β phases. The surface of coarse powders exhibited cellular structure with equiaxed grains. However, the fine powders achieved smooth surfaces and could not be observed any crystallization. Attributed to rapid solidification, both α cell and needle-like martensite α’ phase were observed in the internal area of coarse powders, while only honeycomb cellular structure was demonstrated with refined grains in fine powders.

Neuroinflammation is a main factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease. Our previous studies indicated that the modified Wuziyanzong Prescription (MWP) can suppress neuroinflammatory responses via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. However, the anti-neuroinflammatory components of MWP remain unclear. Herein, a target-directed molecular docking fingerprint (TMDF) strategy, via integrating the chemical profiling and molecular docking approaches, was developed to identify the potential anti-neuroinflammatory components of MWP. First, as many as 120 possible structures, including 49 flavonoids, 28 phenylpropionic acids, 18 amides, 10 carotenoids, eight phenylethanoid glycosides, four lignans, two iridoids, and one triterpenoid were deduced by the source attribution and structural classification-assisted strategy. Then, their geometries were docked against five major targets of the NF-κB and MAPKs signaling cascades, including p38-α, IKKβ, ERK1, ERK2, and TRAF6. The docking results revealed diverse contributions of different components towards the protein targets. Collectively, prenylated flavonoids showed intensive or moderate anti-neuroinflammatory activities, while phenylpropanoids, amides, phenylethanoid glycosides, lignans, and triterpenoids exhibited moderate or weak anti-neuroinflammatory effects. The anti-neuroinflammatory activities of four retrieved prenylated flavonoids were tested by Western blotting assay, and the results mostly agreed with those predicted by the docking method. These gained information demonstrates that the established TMDF strategy could be a rapid and feasible methodology to investigate the potential active components in herbal compound prescriptions.