Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various cancers. The aim of this study was to determinate the prognostic value of the neutrophil ...lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) in patients with esophageal squamous cell carcinoma (ESCC).
Preoperative NLR and PLR were evaluated in 483 patients undergoing esophagectomy for ESCC from January 2005 to December 2008. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC) curves were also plotted to verify the accuracy of NLR and PLR for survival prediction.
High preoperative NLR (≥3.5 versus < 3.5, P = 0.039) and PLR (≥150 versus < 150, P < 0.001) were significantly associated with poor overall survival in multivariate analysis. However, our study demonstrated a better discrimination for the PLR in terms of hazard ratio(HR) than the NLR (HR = 1.840 versus HR = 1.339). Patients with NLR ≥3.5 had significantly poorer overall survival compared to NLR <3.5 (35.4% versus 57.7%, P < 0.001). Patients with PLR ≥150 also had significantly poorer overall survival compared to patients with PLR <150 (32.7% versus 63.5%, P < 0.001). The area under the curve (AUC) was 0.658 (95% confidence interval (CI): 0.610 to 0.706, P < 0.001) for NLR and 0.708 (95% CI: 0.662 to 0.754, P < 0.001) for PLR, indicating that PLR was superior to NLR as a predictive factor in ESCC.
Preoperative NLR and PLR were significant predictors of overall survival in patients with ESCC. However, PLR is superior to NLR as a predictive factor in patients with ESCC.
The molecular mechanism underlying brain regeneration in vertebrates remains elusive. We performed spatial enhanced resolution omics sequencing (Stereo-seq) to capture spatially resolved single-cell ...transcriptomes of axolotl telencephalon sections during development and regeneration. Annotated cell types exhibited distinct spatial distribution, molecular features, and functions. We identified an injury-induced ependymoglial cell cluster at the wound site as a progenitor cell population for the potential replenishment of lost neurons, through a cell state transition process resembling neurogenesis during development. Transcriptome comparisons indicated that these induced cells may originate from local resident ependymoglial cells. We further uncovered spatially defined neurons at the lesion site that may regress to an immature neuron–like state. Our work establishes spatial transcriptome profiles of an anamniote tetrapod brain and decodes potential neurogenesis from ependymoglial cells for development and regeneration, thus providing mechanistic insights into vertebrate brain regeneration.
Trade-offs in brain development
Salamander brains share some, but not all, structures with the mammalian brain. They also have greater capacity to regenerate in response to damage. Three groups now come together with single-cell transcriptomics analyses that set the salamander brain in evolutionary context (see the Perspective by Faltine-Gonzalez and Kebschull). By comparing salamander brains with those of lizard, turtle, and mouse, Woych
et al
. track the evolutionary innovations that gave rise to the mammalian six-layered neocortex, which salamanders do not have. Lust
et al
. take a close look at why the axolotl brain is so much more capable of regeneration than is the mammalian brain. Finally, Wei
et al
. compare the developmental and regenerative processes in the axolotl brain. —PJH
Developmental and regenerative processes in the axolotl brain are revealed by single-cell analyses.
INTRODUCTION
Brain regeneration requires the coordination of complex responses in a time- and region-specific manner. Identifying the cell types and molecules involved in this process would advance our understanding of brain regeneration and provide potential targets for regenerative medicine research. However, progress in this field has been hampered by the limited regeneration capacity of the mammalian brain and an incomplete mechanistic understanding of the regeneration process at both the cellular and molecular levels. Axolotls (
Ambystoma mexicanum
) can regenerate damaged appendages and multiple internal organs, including the brain. Therefore, axolotls may serve as a model for studying brain regeneration.
RATIONALE
If we are to understand the mechanism of brain regeneration, we need research tools that can achieve large-scale data acquisition and analyses to simultaneously decode complex cellular and molecular responses. It also seemed to us that a comparison between brain regeneration and developmental processes would help to provide new insights into the nature of brain regeneration. Accordingly, we removed a small portion of the lateral pallium region of the axolotl left telencephalon and collected tissue samples at multiple stages during regeneration. In parallel, we collected tissue samples of the axolotl telencephalon at multiple developmental stages. We then used high-definition and large-field Stereo-seq (spatial enhanced resolution omics sequencing) technology to generate spatial transcriptomic data from sections that covered both hemispheres of the axolotl telencephalon at single-cell resolution. Analyses of cell type annotation, cell spatial organization, gene activity dynamics, and cell state transition were performed for a mechanistic investigation of injury-induced regeneration compared to these cell attributes during development.
RESULTS
With the use of Stereo-seq, we generated a group of spatial transcriptomic data of telencephalon sections that covered six developmental and seven injury-induced regenerative stages. The data at single-cell resolution enabled us to identify 33 cell types present during development and 28 cell types involved in regeneration, including different types of excitatory and inhibitory neurons, and several ependymoglial cell subtypes. For development, our data revealed a primitive type of ependymoglial cells that may give rise to three subgroups of adult ependymoglial cells localized in separate areas of the ventricular zone, with different molecular features and potentially different functions. For regeneration, we discovered a subpopulation of ependymoglial cells that may originate from local resident ependymoglial cells activated by injury. This population of progenitor cells may then proliferate to cover the wound area and subsequently replenish lost neurons through a state transition to intermediate progenitors, immature neurons, and eventually mature neurons. When comparing cellular and molecular dynamics of the axolotl telencephalon between development and regeneration, we found that injury-induced ependymoglial cells were similar to developmental-specific ependymoglial cells in terms of their transcriptome state. We also observed that regeneration of the axolotl telencephalon exhibited neurogenesis patterns similar to those seen in development in molecular cascades and the potential cell lineage transition, which suggests that brain regeneration partially recapitulates the development process.
CONCLUSION
Our spatial transcriptomic data highlight the cellular and molecular features of the axolotl telencephalon during development and injury-induced regeneration. Further characterization of the activation and functional regulation of ependymoglial cells may yield insights for improving the regenerative capability of mammalian brains. Our single-cell spatial transcriptome of the axolotl telencephalon, a tetrapod vertebrate, also provides data useful for further research in developmental, regenerative, and evolutionary brain biology. All data are accessible in an interactive database (
https://db.cngb.org/stomics/artista
).
Development and regeneration of axolotl telencephalon.
The spatially resolved single-cell transcriptome of the adult axolotl telencephalon as determined by Stereo-seq analyses (left). Upon brain injury in the highlighted lateral pallium region of the left hemisphere, a neural progenitor subpopulation at the wound site was rapidly induced and subsequently replenished lost neurons (bottom right) through a process that partially resembles neurogenesis during development (top right).
CREDIT: YUNZHI YANG, BGI
Summary Background A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody ...persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. Methods We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6–35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov , number NCT01508247. Findings 10 245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1–96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2–90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). Interpretation EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. Funding China's 12–5 National Major Infectious Disease Program, Beijing Vigoo Biological.
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral ...organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
Electrochromic technology offers exciting opportunities for smart applications such as energy‐saving and interactive systems. However, achieving dual‐band regulation together with the multicolor ...function is still an unmet challenge for electrochromic devices. Herein, an ingenious electrochromic strategy based on reversible manganese oxide (MnO2) electrodeposition, different from traditional ion intercalation/deintercalation‐type electrochromic materials is proposed. Such a deposition/dissolution‐based MnO2 brings an intriguing electrochromic feature of dual‐band regulation for the ultraviolet (UV) and visible lights with high optical modulation (93.2% and 93.6% at 400 and 550 nm, respectively) and remarkable optical memory. Moreover, a demonstrative smart window assembled by MnO2 and Cu electrodes delivers the electrochromic properties of effective dual‐band regulation accompanied by multicolor changes (transparent, yellow, and brown). The robust redox deposition/dissolution process endows the MnO2‐based electrochromic device with excellent rate capability and an areal capacity of 570 mAh m−2 at 0.1 mA cm−2. It is believed that the metal oxide‐based reversible electrodeposition strategy would be an attractive and promising electrochromic technology and provide a train of thought for the development of multifunctional electrochromic devices and applications.
A novel electrochromic strategy based on reversible manganese oxide (MnO2) electrodeposition is demonstrated, in which the robust deposition/dissolution process endows the MnO2‐based device with selective dual‐band regulation in ultraviolet–visible regions, remarkable optical memory, multicolor changes (transparent, yellow, and brown), in addition to high rate capability and superior energy storage capacity.
This paper is concerned with the optimal identification problem of dynamical systems in which only quantized output observations are available under the assumption of fixed thresholds and bounded ...persistent excitations. Based on a time-varying projection, a weighted Quasi-Newton type projection (WQNP) algorithm is proposed. With some mild conditions on the weight coefficients, the algorithm is proved to be mean square and almost surely convergent, and the convergence rate can be the reciprocal of the number of observations, which is the same order as the optimal estimate under accurate measurements. Furthermore, inspired by the structure of the Cramér–Rao lower bound, an information-based identification (IBID) algorithm is constructed with an adaptive design about weight coefficients of the WQNP algorithm, where the weight coefficients are related to the parameter estimates which leads to the essential difficulty of algorithm analysis. Beyond the convergence properties, this paper demonstrates that the IBID algorithm tends asymptotically to the Cramér–Rao lower bound, and hence is asymptotically efficient. A numerical example is simulated to show the effectiveness of the proposed algorithms.
Lymphopenia is a useful predictive factor in several cancers. The aim of this study was to determine the prognostic value of lymphopenia in patients with esophageal squamous cell carcinoma (ESCC).A ...retrospective analysis of 307 consecutive patients who had undergone esophagectomy for ESCC was conducted. In our study, a lymphocyte count (LC) of fewer than 1.0 Giga/L was defined as lymphopenia. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analyses were performed to evaluate the prognostic factors. Receiver operating characteristic (ROC) curve was also plotted to verify the accuracy of LC for CSS prediction.The mean LC was 1.55 ± 0.64 Giga/L (range 0.4-3.7 Giga/L). The incidence of lymphopenia (LC < 1.0 Giga/L) was 16.6% (51/307). Patients with lymphopenia (LC < 1.0 Giga/L) had a significantly shorter 5-year CSS (21.6% vs 43.8%, P = 0.004). On multivariate analysis, lymphopenia (LC < 1.0 Giga/L) was an independent prognostic factor in patients with ESCC (P = 0.013). Lymphopenia had a hazard ratio (HR) of 1.579 95% confidence interval (CI): 1.100-2.265 for CSS. ROC curve demonstrated that lymphopenia (LC < 1.0 Giga/L) predicts survival with a sensitivity of 86.2% and a specificity of 27.2%. Lymphopenia (LC < 1.0 Giga/L) is still an independent predictive factor for long-term survival in patients with ESCC.
The potential impact of six antibiotics (chlortetracycline, tetracycline and tylosin; sulfamethoxazole, sulfamethazine and trimethoprim) on plant growth and soil quality was studied by using seed ...germination test on filter paper and plant growth test in soil, soil respiration and phosphatase activity tests. The phytotoxic effects varied between the antibiotics and between plant species (sweet oat, rice and cucumber). Rice was most sensitive to sulfamethoxazole with the EC10 value of 0.1
mg/L. The antibiotics tested inhibited soil phosphatase activity during the 22 days' incubation. Significant effects on soil respiration were found for the two sulfonamides (sulfamethoxazole and sulfamethazine) and trimethoprim, whereas little effects were observed for the two tetracyclines and tylosin. The effective concentrations (EC10 values) for soil respiration in the first 2 days were 7
mg/kg for sulfamethoxazole, 13
mg/kg for sulfamethazine and 20
mg/kg for trimethoprim. Antibiotic residues in manure and soils may affect soil microbial and enzyme activities.
Terrestrial ecotoxicological effects of antibiotics are related to their sorption and degradation behavior in soil.
•Systematically analyze the relationships between 18 SNPs and the age at onset (AAO) of PD.•To most of these SNPs, their relationships with AAO of PD have not been studied before.•This is the first ...report of the association between DYRK1A or MS4A6A gene with AAO of PD.•The effect of DYRK1A and MS4A6A gene in AD indicates the possibility that AD and PD share common pathways.
Parkinson’s disease (PD) is known as the most common neurodegenerative disease after Alzheimer’s disease (AD). The precise pathogenic mechanism of PD remains unclear, but genetic and environmental factors are widely recognized to be associated with it. Although many associated genes have been discovered, they account for only a few PD patients. Recently, there are growing evidences indicating that patients with PD and AD share similarities in clinical features, pathology and genetic risks. However, no study has been conducted on the relations between AD associated genes and age at onset (AAO) of PD. In this study, we have detected 14 single nucleotide polymorphisms (SNPs) in 9 AD genome wide association studies top hit genes and 4 SNPs in 4 PD-cognitive impairment related genes among 297 Chinese PD patients. Through the linear regression analysis, we identified the significant associations of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier AAO in PD patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD. This is the first report of significant associations of DYRK1A and MS4A6A SNPs and the AAO of PD. On account of their effects both in AD and PD, it is indicated that AD and PD possibly share some common pathways.
The Kuroshio intrusion plays a vitally important role in carrying nutrients to marginal seas. However, the key mechanism leading to the Kuroshio intrusion remains unclear. In this study we postulate ...a mechanism: when the Kuroshio runs onto steep topography northeast of Taiwan, the strong inertia gives rise to upwelling over topography, leading to a left‐hand spiral in the stratified ocean. This is called the topographic beta spiral, which is a major player regulating the Kuroshio intrusion; this spiral can be inferred from hydrographic surveys. In the world oceans, the topographic beta spirals can be induced by upwelling generated by strong currents running onto steep topography. This is a vital mechanism regulating onshore intruding flow and the cross‐shelf transport of energy and nutrients from the Kuroshio Current to the East China Sea. This topographic beta spiral reveals a long‐term missing link between the oceanic general circulation theory and shelf dynamic theory.
Key Points
A “topographic beta spiral” is proposed to explain the observed subsurface‐to‐bottom horizontally turning Kuroshio branch currents northeast of Taiwan
This is a vital mechanism regulating the cross‐shelf transport of energy/nutrients from the Kuroshio Current to marginal seas in oceans
The “topographic beta spiral” can be used as a diagnostic tool in revealing boundary current intrusions/bifurcations in the world ocean
Plain Language Summary
The water and material exchange between global ocean and marginal sea is attracting immense research interest because it significantly influences the coastal hydrodynamic environment and ecosystem. We first report the topographic beta spiral inferred from observations, which is generated by strong upwelling induced when strong western boundary current runs onto steep topography in coastal sea. We postulate that this mechanism plays a vital role in regulating intrusion/bifurcation of western boundary currents. This mechanism may be at work in many places in the world oceans; thus, it can be used as a clue in predicting the intrusion path and the bifurcation pattern of strong boundary currents. Similar to Ekman spiral, topographic beta spiral is one kind of very important and common spirals in the world oceans. In some cases, topographic beta spiral suggests that the intruding water mass originates from the deep water of western boundary current rather than surface water. Since temperature, oxygen and nutrients in the deep water are significantly different to the shelf water, this intruding water can influence coastal ecosystem and hypoxia.
PDF
