Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

Together with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163⁺ CD206⁺ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.     

Niche adaptation and genome expansion in the chlorophyll d-producing cyanobacterium Acaryochloris marina

Acaryochloris marina is a unique cyanobacterium that is able to produce chlorophyll d as its primary photosynthetic pigment and thus efficiently use far-red light for photosynthesis. Acaryochloris species have been isolated from marine environments in association with other oxygenic phototrophs, which may have driven the niche-filling introduction of chlorophyll d. To investigate these unique adaptations, we have sequenced the complete genome of A. marina. The DNA content of A. marina is composed of 8.3 million base pairs, which is among the largest bacterial genomes sequenced thus far. This large array of genomic data is distributed into nine single-copy plasmids that code for >25% of the putative ORFs. Heavy duplication of genes related to DNA repair and recombination (primarily recA) and transposable elements could account for genetic mobility and genome expansion. We discuss points of interest for the biosynthesis of the unusual pigments chlorophyll d and α-carotene and genes responsible for previously studied phycobilin aggregates. Our analysis also reveals that A. marina carries a unique complement of genes for these phycobiliproteins in relation to those coding for antenna proteins related to those in Prochlorococcus species. The global replacement of major photosynthetic pigments appears to have incurred only minimal specializations in reaction center proteins to accommodate these alternate pigments. These features clearly show that the genus Acaryochloris is a fitting candidate for understanding genome expansion, gene acquisition, ecological adaptation, and photosystem modification in the cyanobacteria.     

Anomalous functional connectivity within the default-mode network in treatment-naive patients possessing first-episode major depressive disorder

Background and Objective:Previous studies have shown that the default-mode network (DMN) has a substantial role in patients with major depressive disorder (MDD). However, there is a shortage of information regarding variations in the functional connectivity (FC) of the DMN of treatment-naive patients with first-episode MDD. The present study aims to explore the FC of the DMN in such patients.Methods:The study population consisted of 33 patients and 35 controls, paired regarding age, gender, education level, and health condition. Depression severity was assessed through the Hamilton Depression Scale (HAM-D), and subjects underwent evaluation during the resting-state through functional magnetic resonance imaging (rs-fMRI). To assess the result, we used FC and ICA. We used Spearman''s correlation test to detect potential correlations between anomalous FC and severity of HAM-D scores.Results:We have found a decreased FC in the left medial orbitofrontal gyrus (MOFG) and right marginal gyrus (SMG) in depressive patients compared to controls. There was a negative correlation between abnormal FC in the right SMG and HAM-D scores. We have not found any increase in FC of the DMN in treatment-naive, first-episode of MDD patients.Conclusions:Our study provided evidence of a negative correlation between abnormal FC in the DMN and severity of depression symptoms measured by HAM-D in treatment-naive MDD patients. This finding could shed some light on the relevance of DMN for understanding the pathophysiology of cognitive impairment in MDD.     

Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects

ObjectivesPolymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.MethodsAn open-label, single-dose clinical trial was conducted in healthy Chinese subjects. Polymyxin B (sulphate) was administered intravenously at 0.75 or 1.5 mg/kg (n = 10 per dose, 5 males and 5 females) to examine the safety and pharmacokinetics.ResultsOne female subject in the 1.5-mg/kg group discontinued due to abdominal pain during administration. The most frequently reported adverse events were perioral paraesthesia, dizziness, and numbness of extremities (7/10 subjects in the 0.75-mg/kg group, all subjects in the 1.5-mg/kg group). All neurotoxicity-related events dissipated without treatment within a maximum of 23 h. Notably, abdominal pain (3/5) and vulvar pruritus (2/5), colpitis (2/5) or abnormal uterine bleeding (1/5) were reported in female subjects receiving the 1.5-mg/kg dose. In the 0.75-mg/kg group, the total clearance, volume of distribution and half-life of polymyxin B were 0.028±0.002 L/h/kg, 0.219±0.023 L/kg and 5.44±0.741 h, respectively; similar values were observed in the 1.5-mg/kg group. Urinary recovery was 3.7 ± 1.1% and 8.1 ± 1.3% in the 0.75- and 1.5-mg/kg groups, respectively. Population pharmacokinetics of polymyxin B was consistent with a three-compartment model. The clearance and distribution of the central compartment were 0.027 L/h/kg and 0.071 L/kg, respectively.ConclusionsThis study is the first to examine the safety and pharmacokinetics of polymyxin B in healthy subjects. Our results highlight that acute toxicity is a dose-limiting factor for intravenous polymyxin B.     

Novel research synergized by Chinese medicine pattern classification in rheumatoid arthritis

Clinical Rheumatology -     

Layer-by-layer assembled polyaniline/carbon nanomaterial-coated cellulosic aerogel electrodes for high-capacitance supercapacitor applications

Traditional layer-by-layer (LbL) assembled electrodes are mostly multilayer composites formed on two-dimensional membrane materials. In this case, the electroactive material cannot enter the interior of the substrate. With porous aerogels as the substrate, the LbL assembly of the electroactive material into the three-dimensional aerogel skeleton can be realised, greatly improving the utilisation and the electrochemical performance of the electroactive material. To create a promising aerogel electrode for high-performance energy storage devices, we herein report an aerogel based on wood pulp fibre (WPF) and cellulose nanocrystals (CNC), for use as a porous substrate for LbL assembly of nanostructural polyaniline (PANI) and graphene oxide (GO) or carboxylic multi-walled carbon nanotubes (CMCNT). Owing to the uniformly distributed multilayer nanoarchitecture, interpenetrating channels, and hydrophilic character of the cellulosic aerogel substrate, the produced electrodes of (PANI/CMCNT)₁₀ and (PANI/CMCNT)₁₀ both display high specific capacitances, favourable capacitance retention, good cycling stabilities, and structural flexibility. In the three-electrode test, their gravimetric specific capacitances are as high as 716.62 and 636.63 F g⁻¹, respectively. In addition, the assembled symmetric supercapacitors show good areal specific capacitances (1.95 and 1.49 F cm⁻²) in addition to high areal specific energies (168.64 and 113.57 mW h cm⁻², respectively). These results demonstrate that the integration of the LbL-assembled electroactive materials and porous cellulosic aerogel substrate can be a promising strategy to design high-efficiency green energy storage devices.

Cellulosic aerogel was used as a porous lightweight substrate to layer-by-layer assembly polyaniline and carbon nanomaterials for high capacitance supercapacitor applications.     

中国慢性病前瞻性研究:10个项目地区成年人肺功能指标水平和气流受限现患率的差异分析

目的 描述中国慢性病前瞻性研究(CKB)10个地区人群肺功能指标水平和气流受限现患率的地区差异。方法 剔除基线调查时肺功能指标异常个体后,分析10个地区512 495名30～79岁调查对象肺功能指标水平(FEV₁和FVC)和气流受限(分别采用GOLD标准和LLN标准进行判断)现患率的地区差异。结果 10个地区男性的FEV₁(2.66 L)和FVC(3.16 L)均高于女性(1.99 L和2.35 L);河南和哈尔滨人群FEV₁和FVC高于其他地区。基于GOLD标准的气流受限现患率:男性(5.13%)高于女性(3.75%);农村人群高于城市(男性:6.32% vs. 3.47%;女性:4.26% vs. 2.97%);四川人群现患率最高(男性为13.34%,女性为10.70%),其次是苏州、河南和湖南。基于LLN标准的气流受限现患率(男性为6.93%,女性为6.29%)略高于GOLD标准,但地区差异近似。结论 CKB的10个地区人群无论在肺功能指标水平和气流受限现患率上均存在明显的地区差异。     

中国1995－2012年双生子出生体重变化趋势分析

目的 描述分析中国双生子出生体重变化趋势。方法 使用中国双生子登记系统在中国8个省份收集的1995-2012年出生的双生子人群(共10 827对),采用病例回顾方法分析出生体重各指标情况和变化趋势。结果 调整性别、卵型、出生地区后,出生年份每推迟5年,双生子出生体重平均值降低0.01 kg(P=0.041).随着时间变化,双生子优势方出生体重、劣势方出生体重均不同程度地降低,出生体重相对差与出生体重不一致率在2007年以后有升高趋势。结论 1995-2012年中国双生子出生体重呈下降趋势,出生体重不一致率逐渐上升。考虑到出生体重不一致与某些不良健康结局的风险存在关联,应对双生子出生体重不一致予以重视。     

中国10个地区成年人食物摄入频率特征差异的分析

目的 描述中国慢性病前瞻性研究(CKB)项目10个地区人群食物摄入频率特征的地区差异。方法 CKB项目于2004－2008年在城市和农村各5个地区募集自愿参加的30～79岁常住居民进入队列并完成基线调查。本研究分析10个项目地区中512 891名30～79岁队列成员12组食物的摄入频率,描述各食物组摄入频率特征的地区差异。结果 南方城市(99.0%)和南方农村(99.9%)人群每天摄入的谷类食物以大米为主,北方农村(99.0%)和北方城市如青岛(88.4%)人群则以面食为主。河南人群每天摄入杂粮人群比例最高(98.8%)。甘肃人群每天摄入新鲜蔬菜比例最低(74.0%)。在南方城市人群每天摄入新鲜水果、腌制蔬菜、肉类及其制品比例高于农村地区,北方也存在相同现象。北方城市(37.1%)和农村(14.6%)人群每天摄入蛋类及其制品高于南方城市(6.5%)和农村(6.9%)。北方城市地区人群每天摄入豆制品、乳类及其制品比例最高,其中哈尔滨人群每天摄入豆制品比例最高(10.0%),青岛人群每天摄入乳类及其制品比例最高(34.3%)。结论 CKB项目研究人群谷类食物、蛋类及其制品、豆制品摄入频率存在南北差异,肉类及其制品、家禽及其制品、水产/海产品、新鲜水果、腌制蔬菜、乳类及其制品摄入频率存在城乡差异。