The clinical characteristics of non-cystic fibrosis bronchiectasis patients with positive serum tumor markers: a retrospective study.

BACKGROUND: Serum tumor markers (STM), extensively used for the diagnosis, monitoring and prognostic assessment of tumors, can be increased in some non-malignant lung diseases. To date, there is a paucity of studies regarding the clinical characteristics of non-cystic fibrosis bronchiectasis patients with positive STMs. OBJECTIVE: To investigate the clinical characteristics and indicators of bronchiectasis with positive STMs. METHODS: The clinical data of 377 bronchiectasis patients was retrospectively collected from January 2017 to December 2019 from Beijing Chaoyang Hospital. Patients were divided into the STM negative group, the single STM positive group and the ≥2 STMs positive group according to the number of the positive STMs. The clinical characteristics are described and compared separately. The multivariate logistic regression analysis model was used to investigate the indicators regarding positive STMs. RESULTS: Patients in the ≥2 STMs positive group were older (P = 0.015), had higher mMRC scores (P < 0.001) and developed higher fever (P = 0.027). Additionally, these patients also had lower Albumin/Globulin Ratio (A/G), albumin (ALB), prealbumin (PAB) (P < 0.001, P < 0.001, P < 0.001, respectively) and higher CRP, ESR and Fbg (P < 0.001, P < 0.001 and P < 0.001, respectively). Age (OR 1.022, 95%CI 1.003-1.042; P = 0.026) and the number of affected lobes (OR 1.443, 95%CI 1.233-1.690; P < 0.001) were independently associated with one and ≥ 2 positive STMs in bronchiectasis patients. CONCLUSION: The ≥2 positive STMs are associated with a higher inflammation status and severer radiologic manifestations in bronchiectasis patients.

Electrostatic Self-Assembly Enabling Integrated Bulk and Interfacial Sodium Storage in 3D Titania-Graphene Hybrid.

Room-temperature sodium-ion batteries have attracted increased attention for energy storage due to the natural abundance of sodium. However, it remains a huge challenge to develop versatile electrode materials with favorable properties, which requires smart structure design and good mechanistic understanding. Herein, we reported a general and scalable approach to synthesize three-dimensional (3D) titania-graphene hybrid via electrostatic-interaction-induced self-assembly. Synchrotron X-ray probe, transmission electron microscopy, and computational modeling revealed that the strong interaction between titania and graphene through comparably strong van der Waals forces not only facilitates bulk Na+ intercalation but also enhances the interfacial sodium storage. As a result, the titania-graphene hybrid exhibits exceptional long-term cycle stability up to 5000 cycles, and ultrahigh rate capability up to 20 C for sodium storage. Furthermore, density function theory calculation indicated that the interfacial Li+, K+, Mg2+, and Al3+ storage can be enhanced as well. The proposed general strategy opens up new avenues to create versatile materials for advanced battery systems.

Insights into the Distinct Lithiation/Sodiation of Porous Cobalt Oxide by in Operando Synchrotron X-ray Techniques and Ab Initio Molecular Dynamics Simulations.

Sodium-ion batteries (SIBs) have been considered as one of the promising power source candidates for the stationary storage industries owing to the much lower cost of sodium than lithium. It is well-known that the electrode materials largely determine the energy density of the battery systems. However, recent discoveries on the electrode materials showed that most of them present distinct lithium and sodium storage performance, which is not yet well understood. In this work, we performed a comparative understanding on the structural changes of porous cobalt oxide during its electrochemical lithiation and sodiation process by in operando synchrotron small angel X-ray scattering, X-ray diffraction, and X-ray absorption spectroscopy. It was found that compared to the lithiation process, the porous cobalt oxide undergoes less pore structure changes, oxidation state, and local structure changes as well as crystal structure evolution during its sodiation process, which is attributed to the intrinsic low sodiation activity of cobalt oxide as evidenced by ab initio molecular dynamics simulations. Moreover, it was indicated that the sodiation activity of metal sulfides is higher than that of metal oxides, indicating a better candidate for SIBs. Such understanding is crucial for future design and improvement of high-performance electrode materials for SIBs.

Nanostructured Black Phosphorus/Ketjenblack-Multiwalled Carbon Nanotubes Composite as High Performance Anode Material for Sodium-Ion Batteries.

Sodium-ion batteries are promising alternatives to lithium-ion batteries for large-scale applications. However, the low capacity and poor rate capability of existing anodes for sodium-ion batteries are bottlenecks for future developments. Here, we report a high performance nanostructured anode material for sodium-ion batteries that is fabricated by high energy ball milling to form black phosphorus/Ketjenblack-multiwalled carbon nanotubes (BPC) composite. With this strategy, the BPC composite with a high phosphorus content (70 wt %) could deliver a very high initial Coulombic efficiency (>90%) and high specific capacity with excellent cyclability at high rate of charge/discharge (∼1700 mAh g(-1) after 100 cycles at 1.3 A g(-1) based on the mass of P). In situ electrochemical impedance spectroscopy, synchrotron high energy X-ray diffraction, ex situ small/wide-angle X-ray scattering, high resolution transmission electronic microscopy, and nuclear magnetic resonance were further used to unravel its superior sodium storage performance. The scientific findings gained in this work are expected to serve as a guide for future design on high performance anode material for sodium-ion batteries.

Insight into the Capacity Fading Mechanism of Amorphous Se2S5 Confined in Micro/Mesoporous Carbon Matrix in Ether-Based Electrolytes.

In contrast to the stable cycle performance of space confined Se-based cathodes for lithium batteries in carbonate-based electrolytes, their common capacity fading in ether-based electrolytes has been paid less attention and not yet well-addressed so far. In this work, the lithiation/delithiation of amorphous Se2S5 confined in micro/mesoporous carbon (Se2S5/MPC) cathode was investigated by in situ X-ray near edge absorption spectroscopy (XANES) and theoretical calculations. The Se2S5/MPC composite was synthesized by a modified vaporization-condensation method to ensure a good encapsulation of Se2S5 into the pores of MPC host. In situ XANES results illustrated that the lithiation/delithiation reversibility of Se component was gradually decreased in ether-based electrolytes, leading to an aggravated formation of long-chain polyselenides during cycling and further capacity decay. Moreover, ab initio calculations revealed that the binding energy of polyselenides (Li2Sen) with carbon host is in an order of Li2Se6 > Li2Se4 > Li2Se. The insights into the failure mechanism of Se-based cathode gain in this work are expected to serve as a guide for future design on high performance Se-based cathodes.

COPD Assessment Test and risk of readmission in patients with bronchiectasis: a prospective cohort study.

Introduction: Readmission following bronchiectasis exacerbation is a common and challenging clinical problem and few simple predictive tools exist. The COPD Assessment Test (CAT) is an easy-to-use questionnaire. This study aims to evaluate the predictive value of CAT scores in determining the risk of readmission in patients with bronchiectasis exacerbation. Methods: We conducted a prospective cohort study in 106 bronchiectasis patients admitted with exacerbation. All patients completed the CAT at admission and at discharge. Patients were followed-up for 12 months to collect data on readmission. The area under the curve was used to measure the predictive value of CAT at admission, CAT at discharge and change in CAT for readmission due to bronchiectasis exacerbation. Results: 46 patients were readmitted for bronchiectasis exacerbation within 12 months. High CAT at admission was an independent risk factor for readmission within 12 months in patients with acute exacerbation of bronchiectasis (hazard ratio 3.201, 95% CI 1.065-9.624; p<0.038) after adjustment for confounding variables. The cut-off value of CAT at admission and CAT at discharge to predict 12-month readmission in patients with acute exacerbation of bronchiectasis was 23.5 (sensitivity 62.2%, specificity 83.6%) and 15.5 (sensitivity 52.2%, specificity 87.0%). Conclusions: CAT at admission is a strong predictor of readmission in patients with bronchiectasis exacerbation.

Chemical composition and microbiota changes across musk secretion stages of forest musk deer.

Forest musk deer is the most important animal for natural musk production, and the musk composition changes periodically during musk secretion, accompanied by variation in the com-position of deer-symbiotic bacteria. GC-MS and 16S rRNA sequencing were conducted in this study, the dynamic changes to correlated chemical composition and the microbiota across musk secretion periods (prime musk secretion period, vigorous musk secretion period and late musk secretion period) were investigated by integrating its serum testosterone level in different mating states. Results showed that the testosterone level, musk composition and microbiota changed with annual cycle of musk secretion and affected by its mating state. Muscone and the testosterone level peaked at vigorous musk secretion period, and the microbiota of this stage was distinct from the other 2 periods. Actinobacteria, Firmicutes and Proteobacteria were dominant bacteria across musk secretion period. PICRUSt analysis demonstrated that bacteria were ubiquitous in musk pod and involved in the metabolism of antibiotics and terpenoids in musk. "Carbohydrates and amino acids," "fatty acids and CoA" and "secretion of metabolites" were enriched at 3 periods, respectively. Pseudomonas, Corynebacterium, Clostridium, Sulfuricurvum were potential biomarkers across musk secretion. This study provides a more comprehensive understanding of genetic mechanism during musk secretion, emphasizing the importance of Actinobacteria and Corynebacterium in the synthesis of muscone and etiocholanone during musk secretion, which required further validation.

A population-based cohort study for presence of ulceration among cutaneous malignant melanoma subgroups of patients.

Background: Observational studies suggest that ulceration is considered to be a negative prognostic factor for cutaneous melanoma. However, the impact of ulceration over different subgroups (e.g. AJCC Stage, thickness level) are controversial and its true causal effect on survival is lack of studies in the view of treating ulceration as an exposure. Objective: To explore the true causal effect of ulceration on melanoma's survival by adopting a combination of methods to discover proper adjustment set and confirming its correctness through a variety of means. Methods: A minimal sufficient adjustment set (MSAS) was found using directed acyclic graphs (DAG) to adjust the effect of causality. Sensitivity analysis was conducted to diagnose potential confounders in addition to MSAS. Cox models were built to analyze the causality in-depth and the model was validated using a novel method. Lastly, stratified effects of ulceration were examined to illustrate its impact within subgroups. Results: Hazard ratio (HR) of ulceration after adjustment by MSAS variables was 1.99 (95% CI=1.88-2.09). The sensitivity analysis of propensity score matching and E-value both demonstrated that variables other than MSAS do not have great influence on ulceration and MSS relationship. The HR of ulceration in AJCC Stage, thickness level, invasion level and tumor extension were all monotonically decreased from 5.76 to 1.57, 4.03 to 1.78, 2.75 to 1.78 and 2.65 to 1.71 respectively. Conclusion: Ulceration in all subgroups were shown to have a significantly negative impact on MSS and its magnitude of effect was monotonically decreased as the disease progressed. The true effect of ulceration can be adjusted by MSAS and its correctness was validated through a variety of approaches.

Sevoflurane-Induced Neurotoxicity in the Developing Hippocampus via HIPK2/AKT/mTOR Signaling.

Sevoflurane (Sev) is a widely used inhalational anesthetic for general anesthesia in children. Previous studies have confirmed that multiple exposures to inhaled anesthetic can induce long-term neurotoxicity in newborn mice. However, the underlying mechanisms remain elusive. In this study, we investigated the role of homeodomain interacting protein kinase 2 (HIPK2), a stress activating kinase involved in neural survival and synaptic plasticity, and its underlying mechanism in sevoflurane-induced neurotoxicity. Empirical study showed that neuronal apoptosis was elevated after exposure to sevoflurane. Meanwhile, up-regulation of HIPK2 and AKT/mTOR signaling was observed in primary hippocampal neurons and hippocampus in mice upon anesthetic exposure. A64, antagonist of HIPK2, could significantly reduce increased apoptosis and activation of AKT/mTOR induced by sevoflurane. AKT antagonist MK2206 partially alleviated neuronal apoptosis without affecting the expression of HIPK2. Experimental results demonstrated a crucial role of HIPK2/AKT/mTOR signaling in neurotoxicity of sevoflurane. Thus, HIPK2/AKT/mTOR signaling can serve as a potential target for the protection of inhalation anesthesia-induced cytotoxicity in the future.

Characteristics, Prognosis, and Competing Risk Nomograms of Cutaneous Malignant Melanoma: Evidence for Pigmentary Disorders.

Purpose: Cutaneous malignant melanoma (CMM) always presents as a complex disease process with poor prognosis. The objective of the present study was to explore the influence of solitary or multiple cancers on the prognosis of patients with CMM to better understand the landscape of CMM. Methods: We reviewed the records of CMM patients between 2004 and 2015 from the Surveillance, Epidemiology, and End Results Program. The cumulative incidence function was used to represent the probabilities of death. A novel causal inference method was leveraged to explore the risk difference to death between different types of CMM, and nomograms were built based on competing risk models. Results: The analysis cohort contained 165,043 patients with CMM as the first primary malignancy. Patients with recurrent CMM and multiple primary tumors had similar overall survival status (p = 0.064), while their demographics and cause-specific death demonstrated different characteristics than those of patients with solitary CMM (p < 0.001), whose mean survival times are 75.4 and 77.3 months and 66.2 months, respectively. Causal inference was further applied to unveil the risk difference of solitary and multiple tumors in subgroups, which was significantly different from the total population (p < 0.05), and vulnerable groups with high risk of death were identified. The established competing risk nomograms had a concordance index >0.6 on predicting the probabilities of death of CMM or other cancers individually across types of CMM. Conclusion: Patients with different types of CMM had different prognostic characteristics and different risk of cause-specific death. The results of this study are of great significance in identifying the high risk of cause-specific death, enabling targeted intervention in the early period at both the population and individual levels.

New progress in the study of germline susceptibility genes of myeloid neoplasms.

In 2016, the World Health Organization incorporated 'myeloid neoplasms with germline predisposition' into its classification of tumors of hematopoietic and lymphoid tissues, revealing the important role of germline mutations in certain myeloid neoplasms, particularly myelodysplastic syndrome and acute myeloid leukemia. The awareness of germline susceptibility has increased, and some patients with myeloid neoplasms present with a preexisting disorder or organ dysfunction. In such cases, mutations in genes including CCAAT enhancer binding protein α (CEBPA), DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41), RUNX family transcription factor 1 (RUNX1), GATA binding protein 2 (GATA2), Janus kinase 2 (JAK2) and ETS variant transcription factor 6 (ETV6) have been recognized. Moreover, with the application of advanced technologies and reports of more cases, additional germline mutations associated with myeloid neoplasms have been identified and provide insights into the formation, prognosis and therapy of myeloid neoplasms. The present review discusses the well-known CEBPA, DDX41, RUNX1, GATA2, JAK2 and ETV6 germline mutations, and other mutations including those of lymphocyte adapter protein/SH2B adapter protein 3 and duplications of autophagy related 2B, GSK3B interacting protein αnd RB binding protein 6, ubiquitin ligase, that remain to be confirmed or explored. Recommendations for the management of diseases associated with germline mutations are also provided.

Long Non-coding RNA and mRNA Profile of Liver Tissue During Four Developmental Stages in the Chicken.

The liver is the major organ of lipid biosynthesis in the chicken. In laying hens, the liver synthesizes most of the yolk precursors and transports them to developing follicles to produce eggs. However, a systematic investigation of the long non-coding RNA (lncRNA) and mRNA transcriptome in liver across developmental stages is needed. Here, we constructed 12 RNA libraries from liver tissue during four developmental stages: juvenile (day 60), sexual maturity (day 133), peak laying (day 220), and broodiness (day 400). A total of 16,930 putative lncRNAs and 18,260 mRNAs were identified. More than half (53.70%) of the lncRNAs were intergenic lncRNAs. The temporal expression pattern showed that lncRNAs were more restricted than mRNAs. We identified numerous differentially expressed lncRNAs and mRNAs by pairwise comparison between the four developmental stages and found that VTG2, RBP, and a novel protein-coding gene were differentially expressed in all stages. Time-series analysis showed that the modules with upregulated genes were involved in lipid metabolism processes. Co-expression networks suggested functional relatedness between mRNAs and lncRNAs; the DE-lncRNAs were mainly involved in lipid biosynthesis and metabolism processes. We showed that the liver transcriptome varies across different developmental stages. Our results improve our understanding of the molecular mechanisms underlying liver development in chickens.

Gut Microbiome of Chinese Forest Musk Deer Examined across Gender and Age.

Animal gut microbiota begins to colonize after birth and is functionally indispensable for maintaining the health of the host. It has been reported that gender and age influence the composition of the intestinal microbiome. However, the effects of gender and age on the intestinal microorganism of forest musk deer (FMD) remain unclear. The aim of this study was to establish the relationship between the structure and composition of fecal microbiota of male and female forest musk deer with age. Here, Illumina Miseq 300PE sequencing platform targeting 16S rRNA V3-V4 hypervariable region applied to define the fecal microbiota of male and female FMD with two age groups, juvenile (age 1-2 years) and adult (age 4-10 years). Alpha diversity index did not show significant difference in bacterial diversity between the males and females or among age groups. The intestinal microbiota of FMD was dominated by three phyla, the Firmicutes, Proteobacteria and Bacteroidetes regardless of gender and different ages. Higher proportions of Proteobacteria were found in adult male and juvenile female individuals. The composition of Bacteroidetes was stable with the gender and age of FMD. Interestingly, the relative abundance of genera Clostridiales and Bacteroidales were higher in the juvenile FMD. Conversely, proportions of Pseudomonas and Lachnospiraceae were abundant in the adult FMD. Higher proportions of Ruminococcaceae, Dore, and 5-7N15 were found in the juvenile male groups. They may reflect the different immune resistance of male and female individuals at different stages of development. This study explored the fecal microbiota composition of forest musk deer in relation to gender and age, which may provide an effective strategy for developing intestinal microecological preparations and potential musk deer breeding.

Characterizing the microbiota in gastrointestinal tract segments of Rhabdophis subminiatus: Dynamic changes and functional predictions.

The gut microbiota helps the host to absorb nutrients and generate immune responses that can affect host behavior, development, reproduction, and overall health. However, in most of the previous studies, microbiota was sampled mainly using feces and intestinal contents from mammals but not from wild reptiles. Here, we described the bacterial profile from five different gastrointestinal tract (GIT) segments (esophagus, stomach, small intestine, large intestine, and cloaca) of three wild Rhabdophis subminiatus using 16S rRNA V4 hypervariable amplicon sequencing. Forty-seven bacterial phyla were found in the entire GIT, of which Proteobacteria, Firmicutes, and Bacteroidetes were predominant. The results showed a significant difference in microbial diversity between the upper GIT segments (esophagus and stomach) and lower GIT segments (large intestine and cloaca). An obvious dynamic distribution of Fusobacteria and Bacteroidetes was observed, which mainly existed in the lower GIT segments. Conversely, the distribution of Tenericutes was mainly observed in the upper GIT. We also predicted the microbial functions in the different GIT segments, which showed that microbiota in each segments played an important role in higher membrane transport and carbohydrate and amino acid metabolism. Microbes in the small intestine were also mainly involved in disease-related systems, while in the large intestine, they were associated with membrane transport and carbohydrate metabolism. This is the first study to investigate the distribution of the gut microbiota and to predict the microbial function in R. subminiatus. The composition of the gut microbiota certainly reflects the diet and the living environment of the host. Furthermore, these findings provide vital evidence for the diagnosis and treatment of gut diseases in snakes and offer a direction for a model of energy budget research.

Isolation, primary culture, and morphological characterization of gland epithelium from forest musk deer (Moschus berezovskii).

Research of epithelial cells in musk gland is lacking. There are no good characterized epithelial cell lines that can provide complementary in vitro models for in vivo research. We successfully cultivated epithelial cells of musk gland for the first time. The protocol described here produces epithelial cell lines from the mature secreting musk gland. Based on morphological observation, epithelial cells of musk gland were isolated and cultured in vitro. After the third passage, the musk gland-derived cells were filled with many lipid droplets and proliferated well. We used gas chromatography and mass spectrometry to explore the chemical composition of lipid droplets in the musk gland-derived cells. The main components of secreted lipid droplet were alkanes, esters, amines, alcohols, ketones, organic acids, and aldehydes. Muscone, which is the main active compound of musk, was not found. This is a new attempt in the field of animal musk to obtain naturally secreted animal musk in vitro by cloning specialized cells. In conclusion, this study provides a reference at the cellular level to further analyze the biology and physiology of the musk gland epithelium and secretion mechanism of musk deer.

A Comparison of Genetic Diversity of COX-III Gene in Lowland Chickens and Tibetan Chickens.

To obtain a full understanding of the genetic diversity of the cytochrome oxidase III gene (COX-III) and its association with high altitude adaptation in Tibetan chickens, we sequenced COX-III in 12 chicken populations (155 Tibetan chickens and 145 other domestic chickens). We identified a total of 11 single nucleotide polymorphisms (SNPs) and 12 haplotypes (Ha1-Ha12). Low genetic diversity (haplotype diversity = 0.531 ± 0.087, nucleotide diversity = 0.00125) was detected for COX-III, and haplotype diversity of Tibetan chicken populations (0.750 ± 0.018) was markedly higher than lowland chicken populations (0.570 ± 0.028). Obvious genetic differentiation (nucleotide divergence = 0.092~0.339) and conspicuous gene communication (gene flow = 0.33~32.22) among 12 populations suggested that Tianfu black-bone fowl (white feather) was possibly introduced from Tibetan chicken. SNP m.10587 T>C affects the specific functions of the COX enzyme. Haplotype Ha3 was found in Tibetan chickens, and SNP m.10115G>A caused an amino acid substitution (Val62Ile) associated with phospholipid binding, while mutations m.10017C>A and m.10555G>A and the previously reported SNP m.10065T>C reduced the hydropathy index to some extent. Together, this indicates that the mitochondrial membrane is more hydrophobic in Tibetan chickens.

Revisiting the Corrosion of the Aluminum Current Collector in Lithium-Ion Batteries.

The corrosion of aluminum current collectors and the oxidation of solvents at a relatively high potential have been widely investigated with an aim to stabilize the electrochemical performance of lithium-ion batteries using such components. The corrosion behavior of aluminum current collectors was revisited using a home-build high-precision electrochemical measurement system, and the impact of electrolyte components and the surface protection layer on aluminum foil was systematically studied. The electrochemical results showed that the corrosion of aluminum foil was triggered by the electrochemical oxidation of solvent molecules, like ethylene carbonate, at a relative high potential. The organic radical cations generated from the electrochemical oxidation are energetically unstable and readily undergo a deprotonation reaction that generates protons and promotes the dissolution of Al3+ from the aluminum foil. This new reaction mechanism can also shed light on the dissolution of transitional metal at high potentials.

The musk chemical composition and microbiota of Chinese forest musk deer males.

Male musk deer secrete musk from the musk gland located between their naval and genitals. Unmated male forest musk deer generate a greater amount of musk than mated males, potentially allowing them to attract a greater number of females. In this study, we used gas chromatography and mass spectrometry (GC/MS) to explore musk chemical composition of the musk pods of captive mated and unmated sexually mature Chinese forest musk deer and used next-generation sequencing to intensively survey the bacterial communities within them. Analysis of the chemical composition of the musk showed that unmated males have more muscone and cholesterol. Features of the musk16S rRNA gene showed that mated Chinese forest musk deer have both a greater Shannon diversity (p < 0.01) and a greater number of estimated operational taxonomic units than unmated ones; many bacterial genera were overrepresented in unmated Chinese forest musk deer males. Members of these genera might be involved in musk odor fermentation. PICRUSt analysis revealed that metabolic pathways such as aldosterone-regulated sodium reabsorption, metabolism of terpenoids and polyketides, flavone and flavonol biosynthesis, and isoflavonoid biosynthesis were enriched in the musk of unmated Chinese forest musk deer males.