Enhanced near-infrared optical transmission in zinc germanium phosphide crystals via precise magnesium doping.

A zinc germanium phosphorus (ZnGeP2) crystal with a chalcopyrite structure is an efficient frequency converter in the mid-infrared region. However, point defect-induced optical absorption at the pumping wavelength (near infrared region) blocked the further application of ZnGeP2. To alleviate the absorption losses caused by point defects, in situ magnesium doping compensation was presented during the ZnGeP2 bulk crystal growth process via the vertical Bridgman method. Combined with theoretical calculations, the structural distortion of the magnesium-doped ZnGeP2 crystals in different orientations was illustrated. The thermodynamic and kinetic stability of the magnesium-doped ZnGeP2 structure were demonstrated. The transmission results indicated the improvement of transmittance within a wavelength range of 1.8-2.4 µm when doped with magnesium, which revealed the powerful ability of the appropriate dopant in optimizing near-infrared optical properties. Thus, the introduction of magnesium is a practical approach to improve the transmittance performance and extend the pumping source wavelengths of ZnGeP2 crystals.

The Numerical Simulations and Experimental Study of an 8-Inch SiC Single Crystal with Reduced BPD Density.

The basal plane dislocation (BPD) density is one of the most important defects affecting the application of SiC wafers. In this study, numerical simulations and corresponding experiments were conducted to investigate the influence of cooling processes, seed-bonding methods, and graphite crucible materials on the BPD density in an 8-inch N-type 4H-SiC single crystal grown by the physical vapor transport (PVT) method. The results showed that the BPD density could be effectively reduced by increasing the cooling rate, optimizing the seed-bonding method, and adopting a graphite crucible with a similar coefficient of thermal expansion as the SiC single crystal. The BPD density in the experiments showed that a high cooling rate reduced the BPD density from 4689 cm-2 to 2925 cm-2; optimization of the seed-bonding method decreased the BPD density to 1560 cm-2. The BPD density was further reduced to 704 cm-2 through the adoption of a graphite crucible with a smaller thermal expansion coefficient.

Cell Taxonomy: a curated repository of cell types with multifaceted characterization.

Single-cell studies have delineated cellular diversity and uncovered increasing numbers of previously uncharacterized cell types in complex tissues. Thus, synthesizing growing knowledge of cellular characteristics is critical for dissecting cellular heterogeneity, developmental processes and tumorigenesis at single-cell resolution. Here, we present Cell Taxonomy (https://ngdc.cncb.ac.cn/celltaxonomy), a comprehensive and curated repository of cell types and associated cell markers encompassing a wide range of species, tissues and conditions. Combined with literature curation and data integration, the current version of Cell Taxonomy establishes a well-structured taxonomy for 3,143 cell types and houses a comprehensive collection of 26,613 associated cell markers in 257 conditions and 387 tissues across 34 species. Based on 4,299 publications and single-cell transcriptomic profiles of ∼3.5 million cells, Cell Taxonomy features multifaceted characterization for cell types and cell markers, involving quality assessment of cell markers and cell clusters, cross-species comparison, cell composition of tissues and cellular similarity based on markers. Taken together, Cell Taxonomy represents a fundamentally useful reference to systematically and accurately characterize cell types and thus lays an important foundation for deeply understanding and exploring cellular biology in diverse species.

Artesunate delays the dysfunction of age-related intestinal epithelial barrier by mitigating endoplasmic reticulum stress/unfolded protein response.

The impairment of the intestinal epithelial barrier and subsequent bacterial translocation are common in aging individuals, contributory to several local and systematic disorders. However, the underlying mechanism of the age-related degeneration has not been fully understood. In this study, we demonstrated that the intestinal KIT signaling declined and de-activated with aging, parallel with epithelial barrier dysfunction. Endoplasmic reticulum stress (ERS)/unfolded protein response (UPR) was obviously increased during aging. The ERS and its downstream IRE1α were highly activated in the aging colonic epithelium. Furthermore, by the use of Tunicamycin (Tm)-induced ERS mouse and cell models, we uncovered that the activity of the ERS/IRE1α accelerated the protein degradation of KIT via ubiquitin-proteasome pathway. The deficiency of KIT signaling further reduced the transcription of the tight junction protein Claudin-3. Of significance, Artesunate (ART) could be capable of ameliorating the detrimental effect of ERS/IRE1α, indicated by the re-gained KIT and Claudin-3 expressions and the restoration of the intestinal epithelial barrier. In conclusion, our present study provided novel evidence elucidating the ERS/IRE1α-induced loss of KIT and Claudin-3 in the aging colonic epithelium and also shed light on the protective effect of Artesunate on the intestinal epithelial barrier by blocking ERS/IRE1α activity during aging.

TWAS Atlas: a curated knowledgebase of transcriptome-wide association studies.

Transcriptome-wide association studies (TWASs), as a practical and prevalent approach for detecting the associations between genetically regulated genes and traits, are now leading to a better understanding of the complex mechanisms of genetic variants in regulating various diseases and traits. Despite the ever-increasing TWAS outputs, there is still a lack of databases curating massive public TWAS information and knowledge. To fill this gap, here we present TWAS Atlas (https://ngdc.cncb.ac.cn/twas/), an integrated knowledgebase of TWAS findings manually curated from extensive literature. In the current implementation, TWAS Atlas collects 401,266 high-quality human gene-trait associations from 200 publications, covering 22,247 genes and 257 traits across 135 tissue types. In particular, an interactive knowledge graph of the collected gene-trait associations is constructed together with single nucleotide polymorphism (SNP)-gene associations to build up comprehensive regulatory networks at multi-omics levels. In addition, TWAS Atlas, as a user-friendly web interface, efficiently enables users to browse, search and download all association information, relevant research metadata and annotation information of interest. Taken together, TWAS Atlas is of great value for promoting the utility and availability of TWAS results in explaining the complex genetic basis as well as providing new insights for human health and disease research.

TSomVar: a tumor-only somatic and germline variant identification method with random forest.

Somatic variants act as critical players during cancer occurrence and development. Thus, an accurate and robust method to identify them is the foundation of cutting-edge cancer genome research. However, due to low accessibility and high individual-/sample-specificity of the somatic variants in tumor samples, the detection is, to date, still crammed with challenges, particularly when lacking paired normal samples as control. To solve this burning issue, we developed a tumor-only somatic and germline variant identification method (TSomVar) using the random forest algorithm established on sample-specific variant datasets derived from genotype imputation, reads-mapping level annotation and functional annotation. We trained TSomVar by using genomic variant datasets of three major cancer types: colorectal cancer, hepatocellular carcinoma and skin cutaneous melanoma. Compared with existing tumor-only somatic variant identification tools, TSomVar shows excellent performances in somatic variant detection with higher accuracy and better capability of recalling for test datasets from colorectal cancer and skin cutaneous melanoma. In addition, TSomVar is equipped with the competence of accurately identifying germline variants in tumor samples. Taken together, TSomVar will undoubtedly facilitate and revolutionize somatic variant explorations in cancer research.

Activators Confined Upconversion Nanoprobe with Near-Unity Förster Resonance Energy Transfer Efficiency for Ultrasensitive Detection.

Lanthanide-doped upconversion nanoparticles (UCNPs) as energy donors for Förster resonance energy transfer (FRET) are promising in biosensing, bioimaging, and therapeutic applications. However, traditional FRET-based UC nanoprobes show low efficiency and poor sensitivity because only partial activators in UCNPs possessing suitable distance with energy acceptors (<10 nm) can activate the FRET process. Herein, a novel excited-state energy distribution-modulated upconversion nanostructure is explored for highly efficient FRET. Integration of the optimal 4% Er3+ doped shell and 100% Yb3+ core achieves ∼4.5-fold UC enhancement compared with commonly used NaYF4:20%Yb3+,2%Er3+ nanoparticles, enabling maximum donation of excitation energy to an acceptor. The spatial confinement strategy shortens significantly the energy-transfer distance (∼4.5 nm) and thus demonstrates experimentally a 91.9% FRET efficiency inside the neutral red (NR)-conjugated NaYbF4@NaYF4:20%Yb3+,4%Er3+ nanoprobe, which greatly outperforms the NaYbF4@NaYF4:20%Yb3+,4%Er3+@SiO2@NR nanoprobe (27.7% efficiency). Theoretical FRET efficiency calculation and in situ single-nanoparticle FRET measurement further confirm the excellent energy-transfer behavior. The well-designed nanoprobe shows a much lower detection limit of 0.6 ng/mL and higher sensitivity and is superior to the reported NO2- probes. Our work provides a feasible strategy to exploit highly efficient FRET-based luminescence nanoprobes for ultrasensitive detection of analytes.

CancerSCEM: a database of single-cell expression map across various human cancers.

With the proliferating studies of human cancers by single-cell RNA sequencing technique (scRNA-seq), cellular heterogeneity, immune landscape and pathogenesis within diverse cancers have been uncovered successively. The exponential explosion of massive cancer scRNA-seq datasets in the past decade are calling for a burning demand to be integrated and processed for essential investigations in tumor microenvironment of various cancer types. To fill this gap, we developed a database of Cancer Single-cell Expression Map (CancerSCEM, https://ngdc.cncb.ac.cn/cancerscem), particularly focusing on a variety of human cancers. To date, CancerSCE version 1.0 consists of 208 cancer samples across 28 studies and 20 human cancer types. A series of uniformly and multiscale analyses for each sample were performed, including accurate cell type annotation, functional gene expressions, cell interaction network, survival analysis and etc. Plus, we visualized CancerSCEM as a user-friendly web interface for users to browse, search, online analyze and download all the metadata as well as analytical results. More importantly and unprecedentedly, the newly-constructed comprehensive online analyzing platform in CancerSCEM integrates seven analyze functions, where investigators can interactively perform cancer scRNA-seq analyses. In all, CancerSCEM paves an informative and practical way to facilitate human cancer studies, and also provides insights into clinical therapy assessments.

Low threshold lasing emissions from a single upconversion nanocrystal.

Cross-relaxation among neighboring emitters normally causes self-quenching and limits the brightness of luminescence. However, in nanomaterials, cross-relaxation could be well-controlled and employed for increasing the luminescence efficiency at specific wavelengths. Here we report that cross-relaxation can modulate both the brightness of single upconversion nanoparticles and the threshold to reach population inversion, and both are critical factors in producing the ultra-low threshold lasing emissions in a micro cavity laser. By homogenously coating a 5-µm cavity with a single layer of nanoparticles, we demonstrate that doping Tm3+ ions at 2% can facilitate the electron accumulation at the intermediate state of 3H4 level and efficiently decrease the lasing threshold by more than one order of magnitude. As a result, we demonstrate up-converted lasing emissions with an ultralow threshold of continuous-wave excitation of ~150 W/cm2 achieved at room temperature. A single nanoparticle can lase with a full width at half-maximum as narrow as ~0.45 nm.

Dual-Mode Upconversion Nanoprobe Enables Broad-Range Thermometry from Cryogenic to Room Temperature.

Noncontact optical thermometers based on the luminescence intensity ratio of two thermally coupled energy levels, exhibiting high sensitivity, excellent accuracy, fast response, and low environment dependence, have attracted great interests in scientific research, life activities, and industrial manufacturing processes. However, the use of optical thermometers in extreme atmospheres (below 150 K) is usually limited by the required large temperature activation because of the relatively big energy difference (200 cm-1 ≤ ΔE ≤ 2000 cm-1). Here, we propose a strategy to alleviate the ultralow temperature-sensing problem by exploiting and utilizing the near-infrared (NIR) thermally coupled Stark sublevels of Tm3+ (3H4|0 → 3H6/3H4|1 → 3H6, ΔE ≈ 300 cm-1) that is much sensitive to minimal temperature variation, especially at ultralow temperatures because of the tiny energy difference. The integration of ultralow temperature-sensitive Tm3+ ions and room-temperature-sensitive Er3+ ions in an ultrasmall α-NaYbF4:Tm3+@CaF2@NaYF4:Yb3+/Er3+@CaF2 core/multishell nanoparticle (∼15 nm) as a dual-mode upconversion luminescent nanoprobe enables the broad-range temperature detection from 10 to 295 K. This structure induces ∼14 times NIR emission and ∼sixfold green upconversion luminescence output in comparison with the α-NaYbF4:Tm3+ core and α-NaYbF4:Tm3+@CaF2@NaYF4:Yb3+/Er3+ core/shell/shell nanoparticles. The maximum absolute and relative sensitivities of this dual-mode temperature sensor reach 0.67% and 3.06% K-1, respectively, showing the advantage of the concurrent utilization of the Tm3+ NIR 801/820 nm band ratio and the typical Er3+ visible 521/538 nm band ratio for a wide-range temperature-sensing purpose. This work provides a promising strategy to develop accurate and effective, contactless broad-range/ultralow temperature sensors.

Genetic polymorphisms of IL17A, TLR4 and P2RX7 and associations with the risk of chronic obstructive pulmonary disease.

We investigated the association between genetic polymorphisms of IL17A, TLR4 and P2RX7 genes and chronic obstructive pulmonary disease (COPD) in a Han population. We performed a case-control study with 152 COPD subjects from the Third People's Hospital of Nantong in 2015. Healthy controls were selected from a group of people attending the physical examination and were frequency-matched to the cases by sex and age. Genotyping was performed using TaqMan allelic discrimination technology. A logistic regression model was used to calculated odds ratios (OR) and 95% confidence intervals (CI). After Bonferroni correction, polymorphisms rs2275913 and rs763780 in the IL17A gene, rs10759932 and rs2737190 in the TLR4 gene, and rs1718119 in the P2RX7 gene were significantly associated with altered risk for COPD. Individuals carrying rs2275913 allele A had a reduced risk (OR 0.62; 95% CI: 0.46-0.86). Individuals carrying rs763780 allele C had an increased risk (OR 1.96; 95% CI: 1.29-2.98). Individuals carrying rs10759932 allele C had a reduced risk (OR 0.49; 95% CI: 0.34-0.73). Individuals carrying rs2737190 allele G had a reduced risk (OR 0.51; 95% CI: 0.37-0.71). Individuals carrying rs1718119 allele A had a reduced risk (OR 0.69; 95% CI: 0.45-1.06).Genetic polymorphisms in IL17A, TLR4 and P2RX7 genes were significantly associated with altered risks for COPD.

A single-cell analysis platform for electrochemiluminescent detection of platelets adhesion to endothelial cells based on Au@DL-ZnCQDs nanoprobes.

A novel single-cell analysis platform (SCA) was developed for the investigation of platelets adhesion to single human umbilical vein endothelial cell (HUVEC) via using the adhesion molecule (E-selectin) on the damaged HUVEC as the marker site, and integrating electrochemiluminescence (ECL) with the ultrasensitive Au@DL-ZnCQDs nanoprobes. The Au@DL-ZnCQDs nanocomposite, a kind of double layer zinc-coadsorbed carbon quantum dot (ZnCQDs) core-shell nanoprobe, was firstly constructed by using gold nanoparticles (AuNPs) as the core to load with ZnCQDs and then the citrate-modified silver nanoparticles (AgNPs) as the bridge to link AuNPs-ZnCQDs with ZnCQDs to form the core-shell with double layer ZnCQDs (DL-ZnCQDs) nanoprobe, revealed a 10-fold signal amplification. The H2O2-induced oxidative damage HUVECs were utilized as the cellular model on which anti-E-selectin functionalized nanoprobes specially recognized E-selectin, the SCA showed that the ECL signals decreased with platelets adhesion to single HUVEC. The proposed SCA could effectively and dynamically monitor the adhesion between single HUVEC and platelets in the absence and presence of collagen activation, moreover, be able to quantitatively detect the number of platelets adhesion to single HUVEC, and show a good analytical performance with linear range from 1 to 15 platelets. In contrast, the HUVEC was down-regulated the expression of adhesion molecules by treating with quercetin inhibitor, and the SCA also exhibited the feasibility for analysis of platelets adhesion to single HUVEC. Therefore, the single-cell analysis platform provided a novel and promising protocol for analysis of the single intercellular adhesion, and it will be beneficial to elucidate the pathogenesis of cardiovascular diseases.

Enhancing dye-sensitized solar cell efficiency through broadband near-infrared upconverting nanoparticles.

The inability to utilize near infrared (NIR) light has posed a stringent limitation for the efficiencies of most single-junction photovoltaic cells such as dye-sensitized solar cells (DSSCs). Here, we describe a strategy to alleviate the NIR light harvesting problem by upconverting non-responsive NIR light in a broad spectral range (over 190 nm, 670-860 nm) to narrow solar-cell-responsive visible emissions through incorporated dye-sensitized upconversion nanoparticles (DSUCNPs). Unlike typically reported UCNPs with narrow and low NIR absorption, the organic dyes (IR783) anchored on the DSUCNP surface were able to harvest NIR photons broadly and efficiently, and then transfer the harvested energy to the inorganic UCNPs (typically reported), entailing an efficient visible upconversion. We show that the incorporation of DSUCNPs into the TiO2 photoanode of a DSSC is able to elevate its efficiency from 7.573% to 8.568%, enhancing the power conversion efficiency by about 13.1%. We quantified that among the relative efficiency increase, 7.1% arose from the contribution of broad-band upconversion in DSUCNPs (about ∼3.4 times higher than the highest previously reported value of ∼2.1%), and 6.0% mainly from the scattering effect of DSUCNPs. Our strategy has immediate implications for the use of DSUCNPs to improve the performance of other types of photovoltaic devices.

Pleurotus nebrodensis polysaccharide(PN50G) evokes A549 cell apoptosis by the ROS/AMPK/PI3K/AKT/mTOR pathway to suppress tumor growth.

Since the strong antineoplastic potential against A549 cells of Pleurotus nebrodensis polysaccharide (PN50G) in vitro has been proven previously, the definitive mechanism of PN50G-induced apoptosis in A549 cells in vivo was further investigated. All the results indicated that PN50G significantly suppressed tumor growth in A549 tumor-bearing mice. Tumor cells treated with PN50G were arrested in the G0/G1 phase, and marked changes in the expression of cell cycle-related proteins, including cyclin D1, cyclin A and cyclin B1, were observed. Moreover, western blotting analysis indicated that PN50G triggered the mitochondrial apoptotic pathway, for an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3 and PRPP in A549 tumor cells were observed. And the decrease in the expression of the translation related protein P70S6K was observed, because PN50G activated AMPK phosphorylation, but inhibited PI3K/AKT phosphorylation and suppressed the activation of the mammalian target of rapamycin (mTOR) induced by PN50G. In vivo imaging was performed on tumor-bearing mice, and the results indicated that PN50G significantly increased the intracellular levels of reactive oxygen species (ROS). Furthermore, it indicated that PN50G promoted the protein expression of Beclin 1 and LC-3 in a dose-dependent manner. All the results suggested that PN50G-mediated apoptosis and autophagy of A549 tumor cells in vivo mainly involved in the mitochondrial pathway and the AMPK/PI3K/mTOR pathway.

Synthesis of Upconversion ß-NaYF4:Nd3+/Yb3+/Er3+ Particles with Enhanced Luminescent Intensity through Control of Morphology and Phase.

Hexagonal NaYF4:Nd3+/Yb3+/Er3+ microcrystals and nanocrystals with well-defined morphologies and sizes have been synthesized via a hydrothermal route. The rational control of initial reaction conditions can not only result in upconversion (UC) micro and nanocrystals with varying morphologies, but also can produce enhanced and tailored upconversion emissions from the Yb3+/Er3+ ion pairs sensitized by the Nd3+ ions. The increase of reaction time converts the phase of NaYF4:Nd3+/Yb3+/Er3+ particles from the cubic to the hexagonal structure. The added amount of oleic acid plays a critical role in the shape evolution of the final products due to their preferential attachment to some crystal planes. The adjustment of the molar ratio of F-/Ln3+ can range the morphologies of the ß-NaYF4:Nd3+/Yb3+/Er3+ microcrystals from spheres to nanorods. When excited by 808 nm infrared laser, ß-NaYF4:Nd3+/Yb3+/Er3+ microplates exhibit a much stronger UC emission intensity than particles with other morphologies. This phase- and morphology-dependent UC emission holds promise for applications in photonic devices and biological studies.

Enhancing Solar Cell Efficiency Using Photon Upconversion Materials.

Photovoltaic cells are able to convert sunlight into electricity, providing enough of the most abundant and cleanest energy to cover our energy needs. However, the efficiency of current photovoltaics is significantly impeded by the transmission loss of sub-band-gap photons. Photon upconversion is a promising route to circumvent this problem by converting these transmitted sub-band-gap photons into above-band-gap light, where solar cells typically have high quantum efficiency. Here, we summarize recent progress on varying types of efficient upconversion materials as well as their outstanding uses in a series of solar cells, including silicon solar cells (crystalline and amorphous), gallium arsenide (GaAs) solar cells, dye-sensitized solar cells, and other types of solar cells. The challenge and prospect of upconversion materials for photovoltaic applications are also discussed.

Xiaoqinglong granules as add-on therapy for asthma: latent class analysis of symptom predictors of response.

Xiaoqinglong granules (XQLG) has been shown to be an effective therapy in asthma animal models. We reviewed the literature and conducted this study to assess the impact of XQLG as an add-on therapy to treatment with fluticasone/salmeterol (seretide) in adult patients with mild-to-moderate, persistent asthma. A total of 178 patients were randomly assigned to receive XQLG and seretide or seretide plus placebo for 90 days. Asthma control was assessed by asthma control test (ACT), symptoms scores, FEV(1), and PEF. Baseline patient-reported Chinese medicine (CM)-specific symptoms were analyzed to determine whether the symptoms may be possible indicators of treatment response by conducting latent class analysis (LCA). There was no statistically significant difference in ACT score between two groups. In the subset of 70 patients with symptoms defined by CM criteria, XQLG add-on therapy was found to significantly increase the levels of asthma control according to global initiative for asthma (GINA) guidelines (P = 0.0329). There was no significant difference in another subset of 100 patients with relatively low levels of the above-mentioned symptoms (P = 0.1291). Results of LCA suggest that patients with the six typical symptoms defined in CM may benefit from XQLG.