Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn's disease

AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn&#x02019;s disease (CD) patients.METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort.RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and {'type':'entrez-nucleotide','attrs':{'text':'AF113016','term_id':'6642755','term_text':'AF113016'}}AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 ({'type':'entrez-nucleotide','attrs':{'text':'NR_033913','term_id':'299890801','term_text':'NR_033913'}}NR_033913, {'type':'entrez-nucleotide','attrs':{'text':'NR_038218','term_id':'333360887','term_text':'NR_038218'}}NR_038218, {'type':'entrez-nucleotide','attrs':{'text':'NR_036512','term_id':'302393555','term_text':'NR_036512'}}NR_036512, {'type':'entrez-nucleotide','attrs':{'text':'NR_049759','term_id':'388240827','term_text':'NR_049759'}}NR_049759, {'type':'entrez-nucleotide','attrs':{'text':'NR_033951','term_id':'300068996','term_text':'NR_033951'}}NR_033951, {'type':'entrez-nucleotide','attrs':{'text':'NR_045408','term_id':'354548835','term_text':'NR_045408'}}NR_045408, {'type':'entrez-nucleotide','attrs':{'text':'NR_038377','term_id':'335334999','term_text':'NR_038377'}}NR_038377 and {'type':'entrez-nucleotide','attrs':{'text':'NR_039976','term_id':'337756399','term_text':'NR_039976'}}NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network.CONCLUSION: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration.

Controlled high-density interface engineering of Fe_(3)O_(4)-FeS nanoarray for efficient hydrogen evolution

The rational design of double active sites system is vital for constructing high-efficiency iron sulfides electrocatalysts towards hydrogen evolution reaction(HER) in alkaline media. However, it remains a challenge to controllably create the high-density interface of double sites for optimal synergistic effect.Herein, we reported a simple chemical oxidation-induced surface reconfiguration strategy to obtain the interface-rich Fe_(3)O_(4)-FeS nanoarray supported on iron foam(Fe_(3)O_(4)-FeS/IF) using FeS nanosheets as precursors. The abundant Fe_(3)O_(4)-FeS interfaces could improve the dispersion of active sites and facilitate the electron transfer, leading to enhanced hydrogen evolution efficiency. And meanwhile, by altering the oxidation temperature, the content of S and O could be effectively controlled, further achieving the ratio optimization of Fe_(3)O_(4)to FeS. Synchrotron-based X-ray absorption near-edge structure, X-ray photoelectron spectroscopy and ultraviolet photoemission spectroscopy consistently confirm the changes of electronic structure and d-band center of Fe_(3)O_(4)-FeS after chemical oxidation. Consequently, Fe_(3)O_(4)-FeS/IF exhibits excellent alkaline HER activity with a low overpotential of 120.8 mV to reach 20 mA cm^(-2),and remains stable ranging from 10, 20 to 50 mA cm^(-2) for each 20 h, respectively. Therefore, the facile and controllable chemical oxidation may be an effective strategy for designing high-density interfaces of transition metal-based sulfides towards alkaline HER.

0D-2D Schottky heterostructure coupling of FeS nanosheets and Co_(9)S_(8)nanoparticles for long-term industrial-level water oxidation

The effective electron and interface/structural coupling for heterostructure electrocatalyst is the key to regulating the intrinsic activity and stability for oxygen evolution reaction(OER).Herein,a facile strategy is developed to fabricate well-dispersed zerodimensional(0D)metallic Co_(9)S_(8)nanoparticles on two-dimensional(2D)FeS nanosheets,forming FeS-Co_(9)S_(8)Schottky heterostructures with abundant heterointerfaces as OER electrocatalyst.The strong electronic coupling between FeS and Co_(9)S_(8)expedites electrons flow from Fe atoms in FeS nanosheets to Co atoms in tetrahedron sites(CoTd),thereby leading to the structural integrity of the heterostructure and the constant exposure of active sites.Operando Raman spectroscopy also indicates the Co sites in the FeS-Co_(9)S_(8)Schottky heterostructure are OER active sites.Therefore,FeS-Co_(9)S_(8)heterostructure supported by iron foam(FeS-Co_(9)S_(8)/IF)shows the remarkable activity and durability,achieving an industrial-level 500 mA·cm^(−2)current density at an overpotential of only 332 mV and maintaining for 100 h.This work demonstrates that constructing Schottky heterostructure interface with strong coupling effect may be a good strategy for excellent catalytic performances.

Effective regulation mechanisms of Fe-Ni(oxy)hydroxide:Ni-rich heteroatomic bonding(Ni–O–Fe–O–Ni)is essential

Although Fe-Ni combination performs well in transition metal-based oxygen evolution reaction(OER)electrocatalysts,there are lack of clear and general regulations mechanism to fully play the synergistic catalytic effect.Here,we made the utmost of the interaction of Fe–Ni heteroatomic pair to obtain a highly active Fe-Ni(oxy)hydroxide catalytic layer on iron foam(IF)and nickel foam(NF)by in-situ electrochemical deposition and rapid surface reconstruction,which only required 327 and 351 mV overpotential to provide a large current of 1,000 mA·cm^(−2),respectively.The results confirm that the moderate Ni-rich heteroatomic bonding(Ni–O–Fe–O–Ni)formed by adjusting the Ni/Fe ratio on the catalyst surface is important to offer predominant OER performance.Fe is a key component that enhances OER activity of Ni(O)OH,but Fe-rich structural surface formed by Fe–O–Ni–O–Fe bonding is not ideal.Finally,the remarkable oxygen evolution performance of the prepared Ni2Fe(O)OH/IF and FeNi2(O)OH/NF can be chalked up to the optimized electronic structure of Fe–Ni heteroatomic bonding,the efficient gas spillover,the fast electron transport,and nanosheet clusters morphology.In summary,our work suggests a comprehensive regulation mechanism for the construction of efficient Fe-Ni(oxy)hydroxide catalytic layer on inexpensive,stable,and self-supporting metallic material surface.

Pharmacokinetic and Pharmacodynamic Efficacies of Continuous versus Intermittent Administration of Meropenem in Patients with Severe Sepsis and Septic Shock： A Prospective Randomized Pilot Study

Background： The antibiotic meropenem is commonly administered pharmacokinetic, clinical, and bacteriological efficacies of continuous patients. n patients with severe sepsis and septic shock. We compared the infusion of meropenem versus internaittent administration in such Methods： Patients admitted to the Intensive Care Unit （ICU） with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous （n = 25） or intermittent groups 01 = 25）. The continuous group received a loading dose of 0.5 g of meropenem lbllowed by a continuous infusion of 3 g/day： the intermittent group received an initial dose of 1.5 g lbllowed by 1 g lbr every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations tbr the first and third dosing periods （steady state） were also measured. Results： Clinical success was similar in both the continuous （64%） and intermittent （56%） groups （P = 0.564）： the rates of microbiological eradication and superinfection （81.8% vs. 66.7% [P = 0.255] and 4% vs. 16% [P 0.157], respectively） showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group （7.6 vs. 9.4 days; P = 0.035）, where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first （Cmax： 19.8 mg/L vs. 51.8 mg/L, P = 0.000; Cmin： 11.2 mg/L vs. 0.5 nag/L, P = 0.000） and third dosing periods （Cmax： 12.5 mg/L vs. 46.4 rag/L, P = 0.000; Cmin： 11.4 mg/L vs. 0.6 rag/L, P = 0.000）. For medium-susceptibility pathogens, continuous inthsion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group- Conclusions： Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous inthsion may be more optimal against imermediate-susceptibility pathogens.

Microwave-assisted molybdenum-nickel alloy for efficient water electrolysis under large current density through spillover and Fe doping

The development of high-efficiency electrocatalysts for overall water splitting under large current density is significant and challenging.Herein,a high-performing Fe-doped MoNi alloy catalyst(M-H-MoNiFe-50)abundant with flower-like nanorods assemblies has been prepared by high-pressure microwave reaction and hydrogen reduction.Firstly,Fe doped NiMoO_(4) precursor(M-MoNiFe-50)was synthesized by microwave fast heating,ensuring the robustness of nanorods,which owns larger area and improved catalytic activity than that by conventional hydrothermal method.Secondly,M-MoNiFe-50 was reduced in H_(2)/Ar to fabricate Fe-incorporated MoNi_(4) alloys(M-H-MoNiFe-50),greatly enhancing the conductivity and facilitating hydrogen/oxygen spillover.The final M-H-MoNiFe-50 exhibits remarkable activity for alkaline/acidic hydrogen evolution reaction and oxygen evolution reaction with low overpotential of 208(alkaline),254(acid)and 347 mV at 1,000 mA·cm^(−2).Moreover,an alkaline water electrolyzer is established using M-H-MoNiFe-50 as anode and cathode,generating a current density of 100 mA·cm^(−2) at 1.58 V with encouraging durability of 50 h at 1,000 mA·cm^(−2).The extraordinary water splitting performance can be chalked up to the large surface area,favorable charge transfer,modified electron distribution,intrinsic robustness as well as an efficient gas spillover of M-H-MoNiFe-50.The final electrocatalyst has great prospects for practical application and confirms the significance of Fe doping,microwave method and spillover effect for catalytic performance improvement.

Anxiolytic Effect of Increased NREM Sleep after Acute Social Defeat Stress in Mice

Social defeat stress(SDS)plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression.Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS.However,the effect of acute SDS on sleep/wake behavior in mice varies between studies.In addition,whether sleep changes in response to stress contribute to anxiety is not well established.Here,we first investigated the effects of acute SDS on sleep/wake states in the active period in mice.Our results showed that total sleep time(time in rapid eyemovement[REM]and non-REM[NREM]sleep)increased in the active period after acute SDS.NREM sleep increased mainly during the first 3 h after SDS,while REM sleep increased at a later time.Then,we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS.Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state,while in mice with ad libitum sleep the anxiety rapidly faded away.Altogether,our findings suggest an anxiolytic effect of NREM sleep,and indicate a potential therapeutic strategy for anxiety.

Hollow Fe_(4)C/FeP Nanoboxes with Heterostructure and Carbon Armor for Efficient and Stable Hydrogen Evolution

The heterojunction interfacial modulation of FeP is an effective strategy to regulate the intrinsic activity and stability, which is a major challenge to promote the industrial application of FeP-based electrocatalysts. Herein, hollow Fe_(4)C/FeP box with heterojunction interface and carbon armor is successfully synthesized, which can expose numerous active sites and protect catalyst from corrosion. Electrochemical measurements show that Fe_(4)C/FeP exhibits excellent hydrogen evolution activity and stability. It only needs 180 mV to achieve the current density of 10 mA cm^(-2). The high-activity may be due to the synergistic effects of porous framework, graphitic carbon coating and heterojunction structure of FeC and FeP, which optimize the electronic structure and accelerates electron transfer. In addition, the target catalyst can withstand 5000 cycles of CV testing without significant change in properties. The excellent stability may be attributed to the graphitic carbon coating as the armor that can prevent the catalyst from corrosion of electrolyte. This work may provide a synthetic approach to produce a series of carbon-coated and heterojunction structure of transition metal phosphides for water splitting.