10†µm-Level TiNb2 O7 Secondary Particles for Fast-Charging Lithium-Ion Batteries.

TiNb2 O7 with Wadsley-Roth phase delivers double theoretical specific capacity and similar working potential in comparison to spinel Li4 Ti5 O12 , the commercial high-rate anode material, and thus can enable much higher energy density of lithium-ion batteries. However, the inter-particle resistance within the high-mass-loading TiNb2 O7 electrode would impede the capacity release for practical application, especially under fast-charging conditions. Herein, 10-20 µm-size carbon-coated TiNb2 O7 secondary particle (SP-TiNb2 O7 ) consisting of initial micro-scale TiNb2 O7 particles (MP-TiNb2 O7 ) was fabricated. The high crystallinity of active material could enable fast-charge diffusion and electrochemical reaction rate within particles, and the small number of stacking layers of SP-TiNb2 O7 could reduce the large inter-particle resistance that regular particle electrode often possess and achieve high compaction density of electrodes with high mass loading. The investigation on materials structure and electrochemical reaction kinetics verified the advances of the as-fabricated SP-TiNb2 O7 in achieving superior electrochemical performance. The SP-TiNb2 O7 exhibited high reversible capacity of 292.7 mAh g-1 in the potential range of 1-3 V (Li+ /Li) at 0.1 C, delivering high-capacity release of 94.3 %, and high capacity retention of 86 % at 0.5 C for 250 cycles in half cell configuration. Particularly, the advances of such an anode were verified in practical 5 Ah-level laminated full pouch cell. The as-assembled LiFePO4 ||TiNb2 O7 full cell exhibited a high capacity of 5.08 Ah at high charging rate of 6 C (77.9 % of that at 0.2 C of 6.52 Ah), as well as an ultralow capacity decay rate of 0.0352 % for 250 cycles at 1 C, suggesting the great potential for practical fast-charging lithium-ion batteries.

MicroRNA-200a-3p Is a Positive Regulator in Cardiac Hypertrophy Through Directly Targeting WDR1 as Well as Modulating PTEN/PI3K/AKT/CREB/WDR1 Signaling.

Cardiac hypertrophy is an adaptive expansion of the myocardium due to the overloaded stress of heart. Recently, emerging studies have drawn a conclusion that microRNAs (miRNAs) are involved in myocardial hypertrophy and even heart failure. To figure out the role of microRNA-200a-3p (miR-200a-3p) in cardiac hypertrophy, the in vitro cardiac hypertrophy model was established in H9c2 cells using angiotensin II (Ang-II) as previously described. First of all, we observed a significant increase of miR-200a-3p expression in Ang-II-induced hypertrophic H9c2 cells. Moreover, inhibition of miR-200a-3p dramatically reversed the Ang-II-upregulated expression of hypertrophic markers (atrial natriuretic peptide, brain natriuretic peptide, and ß-MHC) and the expanded cell surface area in H9c2 cells. In addition, our results indicated that miR-200a-3p directly targeted both WDR1 and phosphatase and tensin homolog (PTEN). In this regard, miR-200a-3p further activated PI3K/AKT/CREB pathway so as to intensify its negative regulation on WDR1. At length, WDR1 silence, PTEN inhibitor, and PI3K activator recovered the repressive effect of miR-200a-3p suppression on the development of cardiac hypertrophy. Jointly, our study suggested that miR-200a-3p facilitated cardiac hypertrophy by not only directly targeting WDR1 but also through modulating PTEN/PI3K/AKT/CREB/WDR1 signaling, therefore proving novel downstream molecular pathway of miR-200a-3p in cardiac hypertrophy.

Upscale production of ethyl (S)-4-chloro-3-hydroxybutanoate by using carbonyl reductase coupled with glucose dehydrogenase in aqueous-organic solvent system.

(S)-4-chloro-3-hydroxybutanoate ((S)-CHBE) is an important chiral intermediate to synthesize the side chain of cholesterol-lowering drug atorvastatin. To biosynthesize the (S)-CHBE, a recombinant Escherichia coli harboring the carbonyl reductase and glucose dehydrogenase was successfully constructed. The recombinant E. coli was cultured in a 500-L fermentor; after induction and expression, the enzyme activity and cell biomass were increased to 23,661.65 U/L and 13.90 g DCW/L which was 3.24 and 2.60-folds compared with those in the 50 L fermentor. The biocatalytic process for the synthesis of (S)-CHBE in an aqueous-organic solvent system was constructed and optimized with a substrate fed-batch strategy. The ethyl 4-chloro-3-oxobutanoate concentration reached to 1.7 M, and the (S)-CHBE with yield of 97.2 % and enantiomeric excess (e.e.) of 99 % was obtained after 4-h reaction in a 50-L reactor. In this study, the space-time yield and space-time yield per gram of biomass (dry cell weight, DCW) were 413.17 mM/h and 27.55 mM/h/g DCW for (S)-CHBE production, respectively, which were the highest values as compared to previous reports. Finally, (S)-CHBE was extracted from the reaction mixture with 82 % of yield and 95 % of purity. This study paved the foundation for the upscale production of (S)-CHBE by biocatalysis method.

CD32 Expression by CD4+ T and CD8+ T Lymphocytes Is Increased in Patients with Chronic Hepatitis B Virus Infection.

FcγR is expressed by many immune cells and plays an important role in the immune response to hepatitis B virus (HBV) infection. CD32 belongs to the FcγR family. This study aimed to observe changes in CD32 expression by CD4+ T and CD8+ T lymphocytes in chronic HBV infection patients and evaluate the clinical utility of CD4+ T and CD8+ T CD32 expression to assess the severity of liver injury in chronic HBV-infected patients. A total of 68 chronic HBV patients and 40 healthy individuals were recruited, and the median fluorescence intensity (MFI) of CD32 expression on CD4+ T, CD8+ T lymphocytes was measured using flow cytometry and the CD4+ T, CD8+ T CD32 index was calculated. The reactivity of the healthy individual lymphocytes to mixed patients' plasma containing HBV was observed. Finally, the correlation between CD4+ T, CD8+ T lymphocytes CD32 MFI and liver function indicator levels was analyzed. The CD4+ T, CD8+ T CD32 MFI and index were significantly elevated in HBV patient groups than in normal control group (p < 0.001, for all). Furthermore, the CD32 MFI of healthy persons' CD4+ T and CD8+ T lymphocytes were remarkably increased when stimulated with mixed patients' plasma containing high HBV copies (p < 0.001; P < 0.001). More importantly, in HBV patients, there was a significant positive correlation between CD4+ T, CD8+ T CD32 MFI and the level of serum aspartate aminotransferase (p < 0.05, p < 0.05). In conclusion, the increased expression of CD32 on CD4+ T and CD8+ T lymphocytes might be potential promising biomarkers for the severity of liver function impairment in chronic HBV patients.

The effects of fructose diphosphate on routine coagulation tests in vitro.

To evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration of 0, 1, 2, 3, 4, 5, 6, 10, 15, 20, 25, 30 and 35 mg/mL of drug. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FBG) and thrombin time (TT) of samples were analyzed with blood coagulation analyzers from four different manufacturers(Sysmex, Stago, SEKISUI and Werfen) and their corresponding reagents, respectively. Before the experiment, we also observed whether there were significant differences in coagulation test results of different lots of reagents produced by each manufacturer. At the same time as the four routine clotting tests, the Sysmex blood coagulation analyzer and its proprietary analysis software were used to detect the change of maximum platelet aggregation rate in platelet-rich plasma after adding FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL). The results of PT, aPTT and TT showed a FDP (0-35 mg/mL) concentration-dependent increase and a FBG concentration-dependent decrease. The degree of change (increase or decrease) varied depending on the assay system, with PT and aPTT being more affected by the Sysmex blood coagulation testing instrument reagent system and less affected by CEKISUI, TT less affected by CEKISUI and more affected by Stago, and FBG less affected by Stago and more affected by Sysmex. The results of PT, aPTT and TT were statistically positively correlated with their FDP concentrations, while FBG was negatively correlated. The correlation coefficients between FDP and the coagulation testing systems of Sysmex, Stago, Werfen and SEKISUI were 0.975, 0.988, 0.967, 0.986 for PT, and 0.993, 0.989, 0.990 and 0.962 for aPTT, 0.994, 0.960, 0.977 and 0.982 for TT, - 0.990, - 0.983, - 0.989 and - 0.954 for FBG, respectively. Different concentrations of FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL) had different effects on the maximum aggregation rate of platelet induced by the agonists of adenosine diphosphate (ADP, 5 µmol/L), arachidonic acid (Ara, 1 mmol/L), collagen (Col, 2.5 µg/mL) and epinephrine (Epi,10 µmol/L), but the overall downward trend was consistent, that is, with the increase of FDP concentration, the platelet aggregation rate decreased significantly. Our experimental study demonstrated a possible effect of FDP on the assays of coagulation and Platelet aggregation, which may arise because the drug interferes with the coagulation and platelet aggregation detection system, or it may affect our in vivo coagulation system and Platelet aggregation function, the real mechanism of which remains to be further verified and studied.

Nanocomposite of Conducting Polymer and Li Metal for Rechargeable High Energy Density Batteries.

The structure and electrochemical performance of lithium (Li) metal degrade quickly owing to its hostless nature and high reactivity, hindering its practical application in rechargeable high energy density batteries. In order to enhance the electrochemical reversibility of metallic Li, we designed a Li/Li2S-poly(acrylonitrile) (LSPAN) composite foil via a facile mechanical kneading approach using metallic Li and sulfurized poly(acrylonitrile) as the raw materials. The uniformly dispersed Li2S-poly(acrylonitrile) (Li2S-PAN) in a metallic Li matrix buffered the volume change on cycling, and its high Li ion conductivity enabled fast Li ion diffusion behavior of the composite electrode. As expected, the LSPAN electrode showed reduced voltage polarization, enhanced rate capability, and prolonged cycle life compared with the pure Li electrode. It exhibited stable cycling for 600 h with a symmetric cell configuration at 1 mA cm-2 and 1 mA h cm-2, far outperforming the pure metallic Li counterpart (400 h). Also, the LiCoO2||LSPAN full cells with a cathode mass loading of ∼16 mg cm-2 worked stably for 100 cycles at 0.5 C with a high capacity retention of 96.5%, while the LiCoO2||Li full cells quickly failed within only 50 cycles.

Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18.

The ongoing global pandemic of COVID-19 disease, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly infect lung epithelial cells, and spread mainly through respiratory droplets. However, recent studies showed potential intestinal infection of SARS-CoV-2, implicated the possibility that the intestinal infection of SARS-CoV-2 may correlate with the dysbiosis of gut microbiota, as well as the severity of COVID-19 symptoms. Here, we investigated the alteration of the gut microbiota in COVID-19 patients, as well as analyzed the correlation between the altered microbes and the levels of intestinal inflammatory cytokine IL-18, which was reported to be elevated in the serum of in COVID-19 patients. Comparing with healthy controls or seasonal flu patients, the gut microbiota showed significantly reduced diversity, with increased opportunistic pathogens in COVID-19 patients. Also, IL-18 level was higher in the fecal samples of COVID-19 patients than in those of either healthy controls or seasonal flu patients. Moreover, the IL-18 levels were even higher in the fecal supernatants obtained from COVID-19 patients that tested positive for SARS-CoV-2 RNA than those that tested negative in fecal samples. These results indicate that changes in gut microbiota composition might contribute to SARS-CoV-2-induced production of inflammatory cytokines in the intestine and potentially also to the onset of a cytokine storm.

Serum beta2-microglobulin levels are highly associated with the risk of acute ischemic stroke.

Inflammation is considered an important mechanism of cell death or survival after ischemic stroke. As an important marker of inflammation, the role of ß2-microglobulin (ß2M) in acute ischemic stroke is unclear. We investigated the relationship between serum ß2M and the risk of acute ischemic stroke (AIS). Patients with AIS (202 cases), intracerebral hemorrhage (ICH, 41 cases), and healthy controls (253 cases) were recruited. Clinical and biochemical characteristics were collected. We used three binary logistic regression models to evaluate the correlation of ß2M with the risk of AIS. Furthermore, we investigated the relationship between serum ß2M and the National Institute of Health Stroke Scale (NIHSS) score, the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) subtypes, and the Essen Stroke Risk Score (ESRS) in patients with AIS. Our results showed that serum ß2M levels in patients with AIS were much higher than those in patients with ICH and in the control subjects. Individuals with higher levels of ß2M had higher odds of AIS. Moreover, serum ß2M levels were significantly and positively correlated with ESRS. In addition, the levels of ß2M were varied with different subgroups of AIS (TOAST classification). Serum ß2M is highly associated with the risk of AIS.

Serum ß2-Microglobulin Is Closely Associated With the Recurrence Risk and 3-Month Outcome of Acute Ischemic Stroke.

Background and Purpose: Inflammation plays a significant role in the pathogenesis of acute ischemic stroke (AIS). The role of ß2-microglobulin (ß2M) as a potential initiator of the inflammatory response in AIS is unclear. The purpose of this study was to analyze the relationship of serum ß2M with the recurrence risk and 3-month outcome of AIS. Methods: A total of 205 patients with AIS were recruited, and their clinical and biochemical characteristics were collected. All patients were followed up for 3 months after stroke onset, and the occurrence of death or major disability at 3 months after onset was the outcome of interest in this study. We evaluated the association of serum ß2M levels with the National Institute of Health Stroke Scale (NIHSS) scores, modified Rankin Scale (mRS) scores, and Essen Stroke Risk Score (ESRS) values in patients with AIS. Then, we used receiver operating curve analysis to calculate the optimal cutoff value for discriminating outcomes in patients with AIS and a binary logistic regression model to evaluate the risk factors for a poor outcome after AIS. Results: Our results showed that serum ß2M levels were significantly and positively correlated with ESRS values (r = 0.176, P < 0.001) and mRS scores (r = 0.402, P < 0.001), but the levels of ß2M were not correlated with NIHSS scores (r = 0.080, P = 0.255) or with infarct volume (r = 0.013, P = 0.859). In a further study, we found that 121 patients (59.02%) had poor outcomes. The optimal ß2M cutoff to predict the 3-month outcome of AIS in this study was 1.865 mg/l, and ß2M was independently associated with a poor outcome at 3 months (OR = 3.325, 95% confidence interval: 1.089~10.148). Conclusions: In conclusion, we inferred that serum ß2M was positively associated with the recurrence risk and 3-month outcome of AIS, but it did not appear to be directly related to the severity of AIS or the size of the infarct at admission.

Costunolide ameliorates lipoteichoic acid-induced acute lung injury via attenuating MAPK signaling pathway.

Lipoteichoic acid (LTA)-induced acute lung injury (ALI) is an experimental model for mimicking Gram-positive bacteria-induced pneumonia that is a refractory disease with lack of effective medicines. Here, we reported that costunolide, a sesquiterpene lactone, ameliorated LTA-induced ALI. Costunolide treatment reduced LTA-induced neutrophil lung infiltration, cytokine and chemokine production (TNF-α, IL-6 and KC), and pulmonary edema. In response to LTA challenge, treatment with costunolide resulted less iNOS expression and produced less inflammatory cytokines in bone marrow derived macrophages (BMDMs). Pretreatment with costunolide also attenuated the LTA-induced the phosphorylation of p38 MAPK and ERK in BMDMs. Furthermore, costunolide treatment reduced the phosphorylation of TAK1 and inhibited the interaction of TAK1 with Tab1. In conclusion, we have demonstrated that costunolide protects against LTA-induced ALI via inhibiting TAK1-mediated MAPK signaling pathway, and our studies suggest that costunolide is a promising agent for treatment of Gram-positive bacteria-mediated pneumonia.

Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke.

Increasing evidences have demonstrated that inflammation is involved in the mechanisms of acute ischemic stroke (AIS). As an important and easy-to-measure inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) shows a high association with mortality in patients with stroke in recent studies. In this study, we evaluated the prognostic role of NLR in patients with AIS. One hundred forty-three patients with AIS were enrolled. Clinical data were collected and the NLR was calculated from the admission blood work. The patients were followed up for 3 months after stroke onset. The occurrence of death and the major disability at 3 months after onset were end points in this study. Modified Rankin Scale score ≥3 was considered as poor outcome. In this study, 75 patients (52%) had poor outcome. We used binary logistic regression model to evaluate risk factor for poor outcome of AIS and found that the NLR was independently associated with the poor outcome of 3 months (P < 0.001). The optimal cutoff value for NLR as a predictor for 3-month outcome was 2.995. Therefore, in our study, high NLRs inversely predicted 3-month outcome in patients with AIS.