Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury （injury time 〉 6 months） were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury

Macrophage membrane-mediated targeted drug delivery for treatment of spinal cord injury regardless of the macrophage polarization states

Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.

The anisotropy of hexagonal close-packed iron under inner core conditions: the effect of light elements

In recent decades,global seismic observations have identified increasingly complex anisotropy of the Earth’s inner core.Numerous seismic studies have confirmed hemispherical variations in the inner core’s anisotropy.Here,based on ab initio molecular dynamics calculations,we report how the anisotropy of hexagonal close-packed(hcp)-iron,under inner core conditions,could be altered when alloyed with light elements.We find that light elements in binary allows with iron-hcp-Fe-X(X=C,O,Si,and S)-could have significant effects on density,sound velocities,and anisotropy,compared with the behavior of pure hcp-iron;the anisotropy of these binary alloys depends on combined effects of temperature and the particular alloying light element.Furthermore,the change in anisotropy strength with increasing temperature can be charted for each alloy.Alloying pure iron with some light elements such as C or O actually does not increase but decreases core anisotropy at high temperatures.But the light element S can significantly enhance the elastic anisotropy strength of hcp-Fe.

The progress of nutritional support for chronic obstructive pulmonary disease

The patients with chronic obstructive pulmonary disease (COPD) often occur weight loss and reduced muscle mass, which leads to decreased exercise capacity and vital capacity. The nutritional status is closely related to the prognosis of patients with COPD and nutritional support has played an important role in the treatment of COPD. In order to provide proper nutritional support, this article reviews the progress of nutritional support in COPD from the causes of malnutrition, energy demand assessment, assessment of nutritional risk and nutritional support methods. Moreover, this review specially reviewed the application of traditional Chinese medicine diet.

Adverse Short-Term Outcomes of Preterm Infants Born to Mothers with Preeclampsia by Doppler Cranial Ultrasound Investigation

Objective: In preeclampsia, abnormal fetal hemodynamics changes can be detected by Doppler ultrasound and predicted the perinatal outcome. But seldom studies focus on these preterm neonate’s hemodynamics changes during 72 hours after birth and the adverse short-term outcomes. The present study is planned to assess the parameters of middle cerebral arteries and associate the short-term outcome at 37 weeks early term age in pregnancies complicated by preeclampsia. Methods: A total of 114 preterm neonates were included. The Doppler cranial ultrasound was performed to bilateral middle cerebral arteries within 12 - 24 hours, 36 - 48 hours, 60 - 72 hours after birth for all the eligible study neonates. The parameters of resistive index (RI), resistive index (PI) and middle cerebral velocity (MBFV) were recorded by Doppler cranial ultrasound and 106 infants survived assessed by the Neonatal Behavioral Neurological Assessment (NBNA) at 37 weeks early term-equivalent age. Results: There were a total of 106 subjects that finally completed the NBNA examination at 37 weeks of early term-equivalent age. In the surviving infants, there were a total of 26 infants with abnormal NBNA scores, among them, 12 infants’ mothers were diagnosed with preeclampsia, accounting for up to 46.1%. In these preterm neonates, the lower velocity of bilateral middle cerebral arteries was observed in abnormal infants (p Conclusion: Velocity of middle cerebral artery is significantly abnormal in preeclampsia. The slower velocity in the 72 hours after birth, the higher associated with adverse perinatal short-term outcome.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed–1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants.

儿童保健门诊蛋白质-能量营养不良患儿病因分析

目的:探讨儿童保健门诊蛋白质-能量营养不良(PEM)病因学分布规律。方法:选择2022年1月至7月于四川大学华西第二医院儿童保健门诊部(新川)·华西儿童卓越发展中心就诊的217例PEM患儿为研究对象。根据PEM严重程度,将其分别纳入轻度PEM组(n=182)与中度PEM组(n=33)。由于重度PEM患儿例数太少(2例),未纳入分组。回顾性分析217例PEM患儿的PEM病因。采用χ^(2)检验、连续性校正χ^(2)检验或Fisher确切概率法,对轻度PEM组与中度PEM组患儿PEM病因占比进行统计学分析。轻度PEM组与中度PEM组患儿性别构成比、年龄等一般临床资料比较,差异均无统计学意义(P>0.05)。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果:①217例PEM患儿中,排名前5位PEM病因依次为:食物变态反应(FA)(135例,62.2%),小于胎龄(SGA)儿(46例,21.2%),饮食行为问题(24例,11.1%),早产儿(15例,6.9%)与反复呼吸道感染(RRTI)(6例,2.8%)。②轻度PEM组FA占比为65.4%(119/182),显著高于中度PEM组的45.5%(15/33),差异有统计学意义(χ^(2)=4.73,P=0.030)。轻度PEM组SGA儿占比为17.6%(32/182),显著低于中度PEM组的42.4%(14/33),差异亦有统计学意义(χ^(2)=10.25,P=0.001)。2组患儿饮食行为问题、早产儿、RRTI等占比分别比较,差异均无统计学意义(P>0.05)。结论:儿童保健门诊PEM患儿中,以轻、中度PEM患儿多见。导致PEM的病因中,轻度PEM组患儿PEM病因主要为FA,中度PEM组患儿以FA、SGA儿为主要PEM病因。饮食行为问题、早产儿及RRTI是导致PEM的其他病因。

外泌体:连接机械力感应和肝癌发生的纽带

Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer,and the third leading cause of cancer-related mortality worldwide.This disease is intimately related to mechanical stress.Most HCCs develop in the context of liver fibrosis or cirrhosis,accompanied by increased stiffness.

Elastic properties of disordered binary hcp-Fe alloys under high pressure: Effects of light elements

The effects of light elements on the elastic properties of disordered binary hcp-Fe alloys were investigated at high pressures using plane-wave density functional theory combined with the Monte Carlo special quasi-random structure method.We found that the increase in the O content in hcp-Fe had a more pronounced effect on the sound velocity than Si,S,and C.The longitudinal wave velocity was decreased by∼6%with 2%O content,which was a much greater decrease than the values of 0.6%and 2%induced by the same content of Si and S,respectively,under high pressures.Compared with the other three light elements,the longitudinal wave velocity of the Fe-C alloy exhibited the most gradual decreasing with increasing C content.In addition,the effects of different O and S contents on the anisotropy of hcp-Fe alloys strongly depended on the variation in pressure,whereas the pressure only slightly affected the anisotropy of Fe-Si alloy systems.

Degradation of kanamycin from production wastewater with high-concentration organic matrices by hydrothermal treatment

It is known that many kinds of fermentative antibiotics can be removed by temperatureenhanced hydrolysis from production wastewater based on their easy-to-hydrolyze characteristics.However,a few aminoglycosides are hard to hydrolyze below 100℃ because of their stability expressed by high molecular energy gap(E).Herein,removal of hard-to-hydrolyze kanamycin residue from production wastewater by hydrothermal treatment at subcritical temperatures was investigated.The results showed the reaction temperature had a significant impact on kanamycin degradation.The degradation half-life(t1/2)was shortened by 87.17-fold when the hydrothermal treatment temperature was increased from 100℃ to 180℃.The t1/2 of kanamycin in the N2 process was extended by 1.08-1.34-fold compared to that of the corresponding air process at reaction temperatures of 140-180℃,indicating that the reactions during hydrothermal treatment process mainly include oxidation and hydrolysis.However,the contribution of hydrolysis was calculated as 75%-98%,which showed hydrolysis played a major role during the process,providing possibilities for the removal of kanamycin from production wastewaters with high-concentration organic matrices.Five transformation products with lower antibacterial activity than kanamycin were identified using UPLC-QTOF-MS analysis.More importantly,hydrothermal treatment could remove 97.9%of antibacterial activity(kanamycin EQ,1,109 mg/L)from actual production wastewater with CODCr around 100,000 mg/L.Furthermore,the methane production yield in anaerobic inhibition tests could be increased about 2.3 times by adopting the hydrothermal pretreatment.Therefore,it is concluded that hydrothermal treatment as a pretreatment technology is an efficient method for removing high-concentration hard-to-hydrolyze antibiotic residues from wastewater with high-concentration organic matrices.

First-principles study of structural, elastic, and electronic properties of CeB6 under pressure

We performed a first-principles study of the electronic, elastic, and thermal properties of the rareearth hexaboride CeB6 using the local density approximation （LDA） in consideration of the effective onsite Coulomb parameter Ueff. To systemically evaluate the effect of Ueff on the structure of the material, the dependences of the lattice parameter a0 and bulk modulus B on Ueff were examined in the framework of the LDA＋U and GGA（PBE）＋U scheme. We obtained a lattice constant a0, elastic constants Cij, and a bulk modulus B at 0 K and 0 GPa that were in good agreement with the experimental results and other theoretical findings. We focused on the electronic structure by analyzing the variation of the density of states with different Ueff values and pressures, which indicates the metallic characteristic of CeB6. Interestingly, the effect of high pressure was similar to that of increasing Ueff, as the peaks at the bottom of the conduction band moved to the high-energy region in both cases. The elastic constants Cij, bulk modulus B, shear modulus G, Young＇s modulus E, shear-sound velocity Vs, and longitudinal-sound velocity VL were calculated from 0 to 120 GPa. Additionally, the Debye temperature D and elastic Debye temperature E were systematically calculated using the thermodynamic methods in the range of 0-100 GPa. This research may provide a comprehensive understanding of the Kondo compound CeB6 and similar rare-earth hexaborides.

Ginsenoside 3β-O-Glc-DM(C3DM) Enhances the Antitumor Activity of Taxol on Lewis Lung Cancer by Targeting the Interleukin-6/Jak2/STAT3 and Interleukin-6/AKT Signaling Pathways

Objective:Nonsmall-cell lung cancer(NSCLC)is an aggressive,highly chemoresistant disease.Taxol is an effective chemotherapeutic drug widely used for the treatment of NSCLC.However,the clinical use of Taxol is limited due to the occurrence of adverse side effects under high therapeutic doses.Therefore,it is desirable to explore combination therapy to reduce the dose of chemotherapeutic drugs and achieve excellent outcomes.A biosynthetic ginsenoside,3-O-β-D-glucopyranosyl-dammar-24-ene-3β,20 S-diol(3β-O-Glc-DM,C3 DM)is obtained from microbial fermentation by metabolic engineering.Based on previous study findings,we aimed to explore the mechanism of combination therapy with C3 DM and Taxol and its increasing antitumor effect on Lewis lung cancer(LLC)in this study.Materials and Methods:A thiazolyl blue tetrazolium bromide(MTT)assay was performed to evaluate cell viability;the apoptotic effect was studied using cell apoptosis assay.The Lewis tumor xenograft experiment was performed to determine the effects of C3 DM combined with Taxol on tumor growth in vivo,and western blotting was performed to analyze protein expressions.Results:C3 DM effectively inhibited the proliferation of NSCLC cells.Moreover,C3 DM increased the antiproliferative activity of Taxol and significantly enhanced cell apoptosis induced by Taxol in Lewis lung cancer cells.C3 DM alone also suppressed Lewis tumor growth and enhanced the antitumor activity of Taxol in vivo.Western blot analysis revealed that the effects of the antiproliferation and apoptosis induction of C3 DM treatment alone or in combination with Taxol on Lewis lung cancer were mediated by inhibiting the interleukin-6(IL-6)/Jak2/STAT3 and IL-6/AKT signaling pathways.Conclusions:The results showed that C3 DM has the potential to be used in combination therapy with Taxol against NSCLC.

The Antitumor Activity and Mechanism of MCL3 in G422 Glioblastoma

Objective:Parthenolide(PTL)induces anti-tumor effects via the nuclear factor kappa B(NF-κB)signaling pathway.MCL3,a PTL derivative,is a sesquiterpene lactone synthesized by the rearrangement and subsequent oxidation of PTL.The aim of this study was to elucidate the antitumor activity and mechanism of action of MCL3 in glioblastoma(GBM).Materials and Methods:The effects of MCL3 on G422 cell proliferation,apoptosis,invasion,and angiogenesis in vitro were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,flow cytometry,the cell invasion,and tube formation assays.The subcutaneously transplanted G422 xenograft model was used to detect the effect of MCL3 on tumor growth in vivo.Pathological changes were analyzed by immunohistochemical staining.The effects of MCL3 on NF-κB and Stat3 transcriptional activities were examined using a dual-luciferase reporter assay.Protein levels related to the NF-κB/interleukin(IL)-6/Stat3 signaling pathway were determined using western blot analysis.Results:MCL3 inhibited GBM cell proliferation,invasion,and angiogenesis in a concentration-dependent manner.Moreover,MCL3 decreased the transcriptional activities of NF-κB and Stat3.MCL3 suppressed tumor growth in the subcutaneously transplanted G422 xenograft model,while the inhibition rate was 79%in tumor weight at 40.0 mg/kg.MCL3 blocked the NF-κB/IL-6/Stat3 signaling pathway in G422 cells and tumor tissues,resulting in the downregulation of Stat3 target genes related to apoptosis,invasion,etc.,Conclusion:The results show that MCL3 might inhibit G422 GBM growth partly due to the inhibition of the NF-κB/IL-6/Stat3 signaling pathway.

Role of endothelial cells in the regulation of mechanical microenvironment on tumor progression

Majority of cancer patients die from cancer metastases.The physical stimulation produced by microenvironment regulates invasive behavior of cancer cells.Blood vessel is one of the“pathways”for cancer to metastasize,in which tumor cells need to cross the endothelial barrier for intravasation and extravasation.Tumor vessels are arranged in untraditional hierarchies and characterized with rupture,bend,swell and high permeability that are beneficial to intravasation of cancer cell.Abnormal vessels are accompanied with uneven blood flow,increased compression and interstitial fluid pressure.Meanwhile,excessive proliferation of tumor leads to low oxygen pressure in solid tumor.The aberrant tumor mechanical microenvironment changes the biochemical and mechanical signal transduction of endothelial cells and participates in tumor progression.Many current researches focus on how chemical signals regulate endothelial cell function while the role of physical cues is unclear.In this review,the role of endothelial cells in the regulation of shear stress,intercellular force,extracellular matrix and pressure on tumor progression is summarized.