Nitric oxide is required for lung alveolarization revealed by deficiency of argininosuccinate lyase.

Inhaled nitric oxide (NO) therapy has been reported to improve lung growth in premature newborns. However, the underlying mechanisms by which NO regulates lung development remain largely unclear. NO is enzymatically produced by three isoforms of nitric oxide synthase (NOS) enzymes. NOS knockout mice are useful tools to investigate NO function in the lung. Each single NOS knockout mouse does not show obvious lung alveolar phenotype, likely due to compensatory mechanisms. While mice lacking all three NOS isoforms display impaired lung alveolarization, implicating NO plays a pivotal role in lung alveolarization. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable of synthesizing L-arginine, the sole precursor for NOS-dependent NO synthesis. ASL is also required for channeling extracellular L-arginine into a NO-synthetic complex. Thus, ASL deficiency (ASLD) is a non-redundant model for cell-autonomous, NOS-dependent NO deficiency. Here, we assessed lung alveolarization in ASL-deficient mice. Hypomorphic deletion of Asl (AslNeo/Neo) results in decreased lung alveolarization, accompanied with reduced level of S-nitrosylation in the lung. Genetic ablation of one copy of Caveolin-1, which is a negative regulator of NO production, restores total S-nitrosylation as well as lung alveolarization in AslNeo/Neo mice. Importantly, NO supplementation could partially rescue lung alveolarization in AslNeo/Neo mice. Furthermore, endothelial-specific knockout mice (VE-Cadherin Cre; Aslflox/flox) exhibit impaired lung alveolarization at 12 weeks old, supporting an essential role of endothelial-derived NO in the enhancement of lung alveolarization. Thus, we propose that ASLD is a model to study NO-mediated lung alveolarization.

DDRGK1 is required for the proper development and maintenance of the growth plate cartilage.

Loss-of-function mutations in DDRGK1 have been shown to cause Shohat type spondyloepimetaphyseal dysplasia (SEMD). In zebrafish, loss of function of ddrgk1 leads to defects in early cartilage development. Ddrgk1-/- mice show delayed mesenchymal condensation in the limb buds and early embryonic lethality. Mechanistically, Ddrgk1 interacts with Sox9 and reduces ubiquitin-mediated proteasomal degradation of Sox9 protein. To investigate the cartilage-specific role of DDRGK1, conditional knockout mice were generated by intercrossing Prx1-Cre transgenic mice with Ddrgkfl/fl mice to delete its expression in limb mesenchymal cells. Mutant mice showed progressive severe shortening of the limbs and joint abnormalities. The growth plate showed disorganization with shortened proliferative zone and enlarged hypertrophic zone. In correlation with these findings, Sox9 and Col2a1 protein levels were decreased, while Col10a1 expression was expanded. These data demonstrate the importance of Ddrgk1 during growth plate development. In contrast, deletion of Ddrgk1 with the osteoblast-specific Osteocalcin-Cre and Leptin receptor-Cre lines did not show bone phenotypes, suggesting that the effect on limb development is cartilage-specific. To evaluate the role of DDRGK1 in cartilage postnatal homeostasis, inducible Agc1-CreERT2; Ddrgklfl/fl mice were generated. Mice in which Ddrgk1 was deleted at 3 months of age showed disorganized growth plate, with significant reduction in proteoglycan deposition. These data demonstrate a postnatal requirement for Ddrgk1 in maintaining normal growth plate morphology. Together, these findings highlight the physiological role of Ddrgk1 in the development and maintenance of the growth plate cartilage. Furthermore, these genetic mouse models recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD.

Molecular alterations due to Col5a1 haploinsufficiency in a mouse model of classic Ehlers-Danlos syndrome.

Type V collagen is a regulatory fibrillar collagen essential for type I collagen fibril nucleation and organization and its deficiency leads to structurally abnormal extracellular matrix (ECM). Haploinsufficiency of the Col5a1 gene encoding α(1) chain of type V collagen is the primary cause of classic Ehlers-Danlos syndrome (EDS). The mechanisms by which this initial insult leads to the spectrum of clinical presentation are not fully understood. Using transcriptome analysis of skin and Achilles tendons from Col5a1 haploinsufficient (Col5a1+/-) mice, we recognized molecular alterations associated with the tissue phenotypes. We identified dysregulation of ECM components including thrombospondin-1, lysyl oxidase, and lumican in the skin of Col5a1+/- mice when compared with control. We also identified upregulation of transforming growth factor ß1 (Tgf-ß) in serum and increased expression of pSmad2 in skin from Col5a1+/- mice, suggesting Tgf-ß dysregulation is a contributor to abnormal wound healing and atrophic scarring seen in classic EDS. Together, these findings support altered matrix to cell signaling as a component of the pathogenesis of the tissue phenotype in classic EDS and point out potential downstream signaling pathways that may be targeted for the treatment of this disease.

COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay.

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants in COPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures, and developmental delay of variable severity. Electron microscopy of COPB2-deficient subjects' fibroblasts showed dilated endoplasmic reticulum (ER) with granular material, prominent rough ER, and vacuoles, consistent with an intracellular trafficking defect. We studied the effect of COPB2 deficiency on collagen trafficking because of the critical role of collagen secretion in bone biology. COPB2 siRNA-treated fibroblasts showed delayed collagen secretion with retention of type I collagen in the ER and Golgi and altered distribution of Golgi markers. copb2-null zebrafish embryos showed retention of type II collagen, disorganization of the ER and Golgi, and early larval lethality. Copb2+/- mice exhibited low bone mass, and consistent with the findings in human cells and zebrafish, studies in Copb2+/- mouse fibroblasts suggest ER stress and a Golgi defect. Interestingly, ascorbic acid treatment partially rescued the zebrafish developmental phenotype and the cellular phenotype in Copb2+/- mouse fibroblasts. This work identifies a form of coatopathy due to COPB2 haploinsufficiency, explores a potential therapeutic approach for this disorder, and highlights the role of the COPI complex as a regulator of skeletal homeostasis.

Generation of a humanized mAce2 and a conditional hACE2 mouse models permissive to SARS-COV-2 infection.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2). Although the mAce2F83Y,H353K mice were susceptible to intranasal inoculation with SARS-CoV-2, they did not show gross phenotypic abnormalities. Next, we generated a Rosa26hACE2;CMV-Cre mouse line that ubiquitously expresses the human ACE2 receptor. By day 3 post infection with SARS-CoV-2, Rosa26hACE2;CMV-Cre mice showed significant weight loss, a variable degree of alveolar wall thickening and reduced survival rates. Viral load measurements confirmed inoculation in lung and brain tissues of infected Rosa26hACE2;CMV-Cre mice. The phenotypic spectrum displayed by our different mouse models translates to the broad range of clinical symptoms seen in the human patients and can serve as a resource for the community to model and explore both treatment strategies and long-term consequences of SARS-CoV-2 infection.

MDF-SA-DDI: predicting drug-drug interaction events based on multi-source drug fusion, multi-source feature fusion and transformer self-attention mechanism.

One of the main problems with the joint use of multiple drugs is that it may cause adverse drug interactions and side effects that damage the body. Therefore, it is important to predict potential drug interactions. However, most of the available prediction methods can only predict whether two drugs interact or not, whereas few methods can predict interaction events between two drugs. Accurately predicting interaction events of two drugs is more useful for researchers to study the mechanism of the interaction of two drugs. In the present study, we propose a novel method, MDF-SA-DDI, which predicts drug-drug interaction (DDI) events based on multi-source drug fusion, multi-source feature fusion and transformer self-attention mechanism. MDF-SA-DDI is mainly composed of two parts: multi-source drug fusion and multi-source feature fusion. First, we combine two drugs in four different ways and input the combined drug feature representation into four different drug fusion networks (Siamese network, convolutional neural network and two auto-encoders) to obtain the latent feature vectors of the drug pairs, in which the two auto-encoders have the same structure, and their main difference is the number of neurons in the input layer of the two auto-encoders. Then, we use transformer blocks that include self-attention mechanism to perform latent feature fusion. We conducted experiments on three different tasks with two datasets. On the small dataset, the area under the precision-recall-curve (AUPR) and F1 scores of our method on task 1 reached 0.9737 and 0.8878, respectively, which were better than the state-of-the-art method. On the large dataset, the AUPR and F1 scores of our method on task 1 reached 0.9773 and 0.9117, respectively. In task 2 and task 3 of two datasets, our method also achieved the same or better performance as the state-of-the-art method. More importantly, the case studies on five DDI events are conducted and achieved satisfactory performance. The source codes and data are available at https://github.com/ShenggengLin/MDF-SA-DDI.

DTI-MLCD: predicting drug-target interactions using multi-label learning with community detection method.

Identifying drug-target interactions (DTIs) is an important step for drug discovery and drug repositioning. To reduce the experimental cost, a large number of computational approaches have been proposed for this task. The machine learning-based models, especially binary classification models, have been developed to predict whether a drug-target pair interacts or not. However, there is still much room for improvement in the performance of current methods. Multi-label learning can overcome some difficulties caused by single-label learning in order to improve the predictive performance. The key challenge faced by multi-label learning is the exponential-sized output space, and considering label correlations can help to overcome this challenge. In this paper, we facilitate multi-label classification by introducing community detection methods for DTI prediction, named DTI-MLCD. Moreover, we updated the gold standard data set by adding 15,000 more positive DTI samples in comparison to the data set, which has widely been used by most of previously published DTI prediction methods since 2008. The proposed DTI-MLCD is applied to both data sets, demonstrating its superiority over other machine learning methods and several existing methods. The data sets and source code of this study are freely available at https://github.com/a96123155/DTI-MLCD.

NeuroPpred-Fuse: an interpretable stacking model for prediction of neuropeptides by fusing sequence information and feature selection methods.

Neuropeptides acting as signaling molecules in the nervous system of various animals play crucial roles in a wide range of physiological functions and hormone regulation behaviors. Neuropeptides offer many opportunities for the discovery of new drugs and targets for the treatment of neurological diseases. In recent years, there have been several data-driven computational predictors of various types of bioactive peptides, but the relevant work about neuropeptides is little at present. In this work, we developed an interpretable stacking model, named NeuroPpred-Fuse, for the prediction of neuropeptides through fusing a variety of sequence-derived features and feature selection methods. Specifically, we used six types of sequence-derived features to encode the peptide sequences and then combined them. In the first layer, we ensembled three base classifiers and four feature selection algorithms, which select non-redundant important features complementarily. In the second layer, the output of the first layer was merged and fed into logistic regression (LR) classifier to train the model. Moreover, we analyzed the selected features and explained the feasibility of the selected features. Experimental results show that our model achieved 90.6% accuracy and 95.8% AUC on the independent test set, outperforming the state-of-the-art models. In addition, we exhibited the distribution of selected features by these tree models and compared the results on the training set to that on the test set. These results fully showed that our model has a certain generalization ability. Therefore, we expect that our model would provide important advances in the discovery of neuropeptides as new drugs for the treatment of neurological diseases.

High-sensitivity self-powered photodetector based on an in-situ prepared CsPbBr3 microwire/InGaN heterojunction.

Low-dimensional CsPbBr3 perovskite materials have gained widespread attention, derived from their remarkable properties and potential for numerous optoelectronic applications. Herein, the sample of CsPbBr3 microwires were prepared horizontally onto n-type InGaN film substrate using an in-plane solution growth method. The resulting CsPbBr3 microwire/InGaN heterojunction allows for the achievement of a highly sensitive and broadband photodetector. Particularly for the implementation in a self-supplying manner, the best-performing photodetector can achieve a superior On/Off ratio of 4.6×105, the largest responsivity ∼ 800.0 mA/W, a maximum detectivity surpassing 4.6× 1012 Jones, and a high external quantum efficiency approaching 86.5% upon 405 nm light illumination. A rapid response time (∼ 4.48 ms/7.68 ms) was also achieved. The as-designed CsPbBr3 microwire/InGaN heterojunction device without any encapsulation exhibits superior comprehensive stability. Besides, the device featuring as a single pixel imaging unit can readily detect simple images under broadband light illumination with a high spatial resolution, acknowledging its outstanding imaging capability. The robust photodetection properties could be derived from the intense absorption of CsPbBr3 MWs and high-efficiency charge carriers transporting toward the in-situ formed CsPbBr3/InGaN heterointerface. The results may offer an available strategy for the in-situ construction of best-performing low-dimensional perovskite heterojunction optoelectronic devices.

Self-powered solar-blind detector array based on ε-Ga2O3 Schottky photodiodes for dual-mode binary UV communication.

In this work, a solar-blind UV metal-semiconductor Schottky photodiode array is constructed by using metalorganic chemical vapor deposition grown ε-Ga2O3 thin film, possessing high-performance and self-powered characteristics, toward dual-mode (self-powered and biased modes) binary light communication. For the array unit, the responsivity, specific detectivity, and external quantum efficiency are 30.8 A/W/6.3 × 10-2 A/W, 1.51 × 104%/30.9%, 1.28 × 1014/5.4 × 1012 Jones for biased (-10 V)/self-powered operation. The rise and decay time are 0.19 and 7.96 ms at biased modes, respectively, suggesting an ability to trace fast light signal. As an array, the deviation of photocurrent is only 4.3%, highlighting the importance of accurate information communication. Through certain definition of "1/0" binary digital information, the "NY" and "IC" characters are communicated to illustrate the self-powered and biased modes by right of ASCII codes, based on the prepared ε-Ga2O3 solar-blind UV Schottky photodiode array. This work made dual-mode binary deep-UV light communication come true and may well guide the development of UV optoelectronics.

Rivaroxaban Combined with Atorvastatin Inhibits Acute Pulmonary Embolism by Promoting the Expression of NRF2/NQO1.

BACKGROUND: Atorvastatin and direct oral factor Xa inhibitors (for instance, rivaroxaban) are co-administrated in patients with atrial fibrillation. However, no studies have been conducted on the function of these two agents in acute pulmonary embolism (APE). Therefore, we investigated the effects of rivaroxaban + atorvastatin in rats with APE and explored the underlying mechanisms. METHODS: Patients with APE were enrolled, and rats with APE were generated for different regimens. The mean pulmonary arterial pressure (mPAP), heart rate, and PaO2 of APE patients and rats were measured. The plasma levels of oxidative stress- and inflammation-related factors were measured, and the expression of platelet activation markers (CD63 and CD62P) was detected. The proteins targeted by rivaroxaban and atorvastatin, the targets associated with APE, and the genes aberrantly expressed in rats with APE were intersected to obtain candidate factors. RESULTS: Rivaroxaban + atorvastatin reduced mPAP and increased PaO2 in patients and rats with APE. Rivaroxaban + atorvastatin repressed oxidative stress, inflammatory levels, and platelet activation during APE. NRF2 and NQO1 were increased in the lung of rats treated with rivaroxaban + atorvastatin. The therapeutic effect of the combination on APE rats was suppressed after NRF2 downregulation. NRF2 promoted the NQO1 transcription. NQO1 eliminated the inhibitory effect of sh-NRF2 on the combined therapy. CONCLUSION: The alleviating effect of rivaroxaban + atorvastatin administration against APE correlates with NRF2/NQO1 expression.

Exciton-polariton light-emitting diode based on a single ZnO superlattice microwire heterojunction with performance enhanced by Rh nanostructures.

One-dimensional (1D) wirelike superlattice micro/nanostructures have received considerable attention for potential applications due to their versatility and capability for modulating optical and electrical characteristics. In this study, 1D superlattice microwires (MWs), which are made of undoped ZnO and Ga-doped ZnO with periodic and alternating crystalline layers (ZnO/ZnO:Ga), were synthesized individually. Under optical excitation, a series of resonance peaks in the photoluminescence spectrum can be ascribed to polariton emission, which originates from the coupling interaction of the 1D photonic crystal and confined excitons along the wire direction. Using a p-type GaN layer as the hole transport layer, a kind of waveguide light source based on an individual ZnO/ZnO:Ga superlattice MW was proposed and constructed. By analysing the spatially resolved electroluminescence spectra, the observed multipeak was ascribed to exciton-polariton emission with a vacuum Rabi splitting of about 275 meV. Cladding with Rh nanostructures gives rise to appropriate ultraviolet plasmons, and the Rabi splitting energy of our device was enhanced up to 413 meV. The exciton-polariton properties were further examined using angle-resolved electroluminescence measurements. Therefore, individual superlattice MWs can act as optical microresonators to achieve photon-exciton coupling with a large Rabi splitting energy. The experimental results indicate that an individual ZnO/ZnO:Ga superlattice MW can be generally used in developing exciton-polariton luminescence/lasing light sources, particularly for constructing low-threshold/thresholdless lasers toward pragmatic applications.

Conjunctival sac flora and drug susceptibility analysis in normal children in East China.

PURPOSE: To investigate the distribution characteristics of conjunctival sac flora and assess the susceptibility of commonly used topical antimicrobial agents in normal children under the age of 18 in East China. METHODS: In 2019, a study was conducted at Qingdao Eye Hospital of Shandong First Medical University to analyze the microorganism cultures of conjunctival sac in 1258 normal children (2516 eyes; average age, 6.21 ± 3.78 years) in East China. Exclusion criteria included children with ocular surface diseases and those who had used any topical antimicrobial agents recently. The microorganism species in the conjunctival sac were analyzed using the M-38A protocol (microdilution method; investigators read the minimum inhibitory concentration [MIC] values) by the Clinical and Laboratory Standards Institute to determine drug susceptibility. RESULTS: The incidence of conjunctival sac microorganism in children was 32.87% (827/2516), a total of 541 cases (male 293, female 248). Children with conjunctival sac flora in a single eye were 255 and in both eyes were 286 (no statistical difference, P > 0.05). The concordance rate of children with binocular conjunctival sac flora was 32.16% (174/541; male 84, female 90). A total of 42 species of bacteria were detected. Children with Gram-positive cocci accounted for the highest proportion, 91.54% (757/827). The top three bacteria with the highest detection rates were Staphylococcus epidermidis (S. epidermidis; 52.12%), Streptococcus (12.09%), and Staphylococcus aureus (S. aureus; 10.76%). Streptococcus mitis (5.20%) accounted for the highest proportion of Streptococcus.S. epidermidis had the highest proportion in all age groups and was positively correlated with age (r = 0.89, P = 0.03). Before six years of age, the streptococcal proportion(mainly S. mitis) was greater than that of Staphylococcus aureus. The drug susceptibility analysis showed that S. epidermidis was most sensitive to gatifloxacin (98.61%), while it had the highest resistance rate to erythrocin (87.94%). S. aureus had the highest susceptibility to moxifloxacin (100%). Streptococcus was most sensitive to moxifloxacin (96.97%) and had the highest resistance rate to tobramycin (92.93%). CONCLUSIONS: Conjunctival sac flora in children was dominated by Gram-positive cocci, mainly S. epidermidis, S. aureus, and Streptococcus. S. epidermidis increased with age; the proportion of Streptococcus was higher than S. aureus among children aged 0-6 years. The typical conjunctiva sac flora was generally sensitive to quinolones, such as moxifloxacin and gatifloxacin; Streptococcus displayed high resistance to tobramycin antibiotics; and the female children had higher resistance to tobramycin than the male children.

A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is an inborn error of cationic amino acid (arginine, lysine, ornithine) transport caused by biallelic pathogenic variants in SLC7A7, which encodes the light subunit of the y+LAT1 transporter. Treatments for the complications of LPI, including growth failure, renal disease, pulmonary alveolar proteinosis, autoimmune disorders and osteoporosis, are limited. Given the early lethality of the only published global Slc7a7 knockout mouse model, a viable animal model to investigate global SLC7A7 deficiency is needed. Hence, we generated two mouse models with global Slc7a7 deficiency (Slc7a7em1Lbu/em1Lbu; Slc7a7Lbu/Lbu and Slc7a7em1(IMPC)Bay/em1(IMPC)Bay; Slc7a7Bay/Bay) using CRISPR/Cas9 technology by introducing a deletion of exons 3 and 4. Perinatal lethality was observed in Slc7a7Lbu/Lbu and Slc7a7Bay/Bay mice on the C57BL/6 and C57BL/6NJ inbred genetic backgrounds, respectively. We noted improved survival of Slc7a7Lbu/Lbu mice on the 129 Sv/Ev × C57BL/6 F2 background, but postnatal growth failure occurred. Consistent with human LPI, these Slc7a7Lbu/Lbu mice exhibited reduced plasma and increased urinary concentrations of the cationic amino acids. Histopathological assessment revealed loss of brush border and lipid vacuolation in the renal cortex of Slc7a7Lbu/Lbu mice, which combined with aminoaciduria suggests proximal tubular dysfunction. Micro-computed tomography of L4 vertebrae and skeletal radiographs showed delayed skeletal development and suggested decreased mineralization in Slc7a7Lbu/Lbu mice, respectively. In addition to delayed skeletal development and delayed development in the kidneys, the lungs and liver were observed based on histopathological assessment. Overall, our Slc7a7Lbu/Lbu mouse model on the F2 mixed background recapitulates multiple human LPI phenotypes and may be useful for future studies of LPI pathology.

Electron-hole plasma Fabry-Perot lasing in a Ga-incorporated ZnO microbelt via Ag nanoparticle deposition.

In this work, individual ZnO via Ga-doped (ZnO:Ga) microbelts with excellent crystallinity and smooth facets can enable the realization of lateral microresonator Fabry-Perot (F-P) microlasers, and the F-P lasing action originates from excitonic state. Interestingly, introducing Ag nanoparticles (AgNPs) deposited on the microbelt can increase F-P lasing characteristics containing a lower threshold and enhanced lasing output. Especially for the large size AgNPs (the diameter d is approximately 200 nm), the lasing features also exhibit a significant redshift of each lasing peak and an observable broadening of the spectral line width with an increase of the excitation fluence. And the remarkable lasing characteristics are belonging to the electron-hole plasma (EHP) luminescence. The behavior and dynamics of the stimulated radiation in an AgNPs@ZnO:Ga microbelt are studied, suggesting the Mott-transition from the excitonic state to EHP state that is responsible for the F-P lasing. These features can be attributed to the working mechanism that the hot electrons created by the large size AgNPs through nonradiative decay can fill the conduction band of nearby ZnO:Ga, leading to a downward shift of the conduction band edge. This novel filling influence can facilitate bandgap renormalization and result in EHP emission. The results provide a comprehensive understanding of the transition between excitonic and EHP states in the stimulated emission process. More importantly, it also can provide new scheme to developing high efficiency and ultra-low threshold microlasing diodes.

Interface engineering enhanced near-infrared electroluminescence in an n-ZnO microwire/p-GaAs heterojunction.

Interface engineering in the fabrication of low-dimensional optoelectronic devices has been highlighted in recent decades to enhance device characteristics such as reducing leakage current, optimizing charge transport, and modulating the energy-band structure. In this paper, we report a dielectric interface approach to realize one-dimensional (1D) wire near-infrared light-emitting devices with high brightness and enhanced emission efficiency. The light-emitting diode is composed of a zinc oxide microwire covered by a silver nanolayer (Ag@ZnO MW), magnesium oxide (MgO) buffer layer, and p-type gallium arsenide (GaAs) substrate. In the device structure, the insertion of a MgO dielectric layer in the n-ZnO MW/p-GaAs heterojunction can be used to modulate the device features, such as changing the charge transport properties, reducing the leakage current and engineering the band alignment. Furthermore, the cladding of the Ag nanolayer on the ZnO MW can optimize the junction interface quality, thus reducing the turn-on voltage and increasing the current injection and electroluminescence (EL) efficiency. The combination of MgO buffer layer and Ag nanolayer cladding can be utilized to achieve modulating the carrier recombination path, interfacial engineering of heterojunction with optimized band alignment and electronic structure in these carefully designed emission devices. Besides, the enhanced near-infrared EL and improved physical contact were also obtained. The study of current transport modulation and energy-band engineering proposes an original and efficient route for improving the device performances of 1D wire-type heterojunction light sources.

Electrically driven whispering-gallery-mode microlasers in an n-MgO@ZnO:Ga microwire/p-GaN heterojunction.

In emerging miniaturized applications, semiconductor micro/nanostructures laser devices have drawn great public attentions of late years. The device performances of micro/nanostructured microlasers are highly restricted to the different reflective conditions at various side surfaces of microresonators and junction interface quality. In this study, an electrically driven whispering-gallery-mode (WGM) microlaser composed of a Ga-doped ZnO microwire covered by a MgO layer (MgO@ZnO:Ga MW) and a p-type GaN substrate is illustrated experimentally. Incorporating a MgO layer on the side surfaces of ZnO:Ga MWs can be used to reduce light leakage along the sharp edges and the ZnO:Ga/GaN interface. This buffer layer incorporation also enables engineering the energy band alignment of n-ZnO:Ga/p-GaN heterojunction and manipulating the current transport properties. The as-constructed n-MgO@ZnO:Ga MW/p-GaN heterojunction device can emit at an ultraviolet wavelength of 375.5 nm and a linewidth of about 25.5 nm, achieving the excitonic-related recombination in the ZnO:Ga MW. The broadband spectrum collapsed into a series of sharp peaks upon continuous-wave (CW) operation of electrical pumping, especially for operating current above 15.2 mA. The dominant emission line was centered at 378.5 nm, and the line width narrowed to approximately 0.95 nm. These sharp peaks emerged from the spontaneous emission spectrum and had an average spacing of approximately 5.5 nm, following the WGM cavity modes. The results highlight the significance of interfacial engineering for optimizing the performance of low-dimensional heterostructured devices and shed light on developing future miniaturized microlasers.

Dynamically regulated electroluminescence via strain engineering.

Dynamic regulation of the light-emission wavelength has important scientific significance for developing new electroluminescent devices and expanding the application scope to the fields of lighting, display, sensing, and human-machine interaction. In this work, an electroluminescent device with a dynamically tunable emission wavelength is achieved based on the piezoresistive effect. The tunable range can reach up to 12 nm as the external strain increases from 0% to 0.148%. Also, the luminescence mechanism of the device is systematically analyzed, and is shown to be mainly due to the transition of electrons in the ground state to the excitation state caused by thermal tunneling excitation with the participation of multi-phonons. The shift of the emission wavelength originates from the narrowing of the energy band structure under the tensile strain and the change of the crystal field around the defect centers. This work provides a new, to the best of our knowledge, strategy for the development of wavelength-tunable light-emitting devices.

Resilience, coping style, and COVID-19 stress: effects on the quality of life in frontline health care workers.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P<0.001), whereas, working in confirmed case wards, COVID-19 stress, and passive coping were negatively correlated with the QOL (P<0.001). Resilience and the active coping were negatively correlated with COVID-19 stress (P<0.001). Resilience, coping style,and COVID-19 stressaccounted for 32%, 13%, and 8% of the variance in predicting the Global QOL, respectively. In conclusion, working in confirmed COVID-19 case wards and COVID-19 stress impaired the QOL in HCWs. Psychological intervention to improve the resilience and coping style, and reduce COVID-19 stress are important in improving the QOL and mental health of HCWs.

Prognostic analysis of Yes-associated protein 1 in patients with colorectal cancer. A systematic review and meta-analsysis.

BACKGROUND: Colorectal cancer (CRC) is the most common carcinoma worldwide, but a lack of effective prognostic markers limits the clinical diagnosis and treatment. Yes-associated protein 1 (YAP1) is an effector of the HIPPO-pathway, which plays a critical role in cancer development and prognosis, including CRC. However, previous reports have suggested that it plays a dual role in CRC. METHODS: A meta-analysis using RevMan software 5.4 and Stata 14.0 was performed to evaluate the relationship between YAP1 and clinical outcomes of CRC, after searching for eligible studies from the PubMed, Web of Science and Embase databases. Online datasets GEPIA and LOGpc were also used to calculate survival results and compare with the meta-analysis results. Besides, "DESeq" packages was used for expression analysis of YAP1 from TCGA dataset. RESULTS: YAP1 was over expression in the tissue of cancers comparing to normal tissues in patients with CRC from TCGA database (p=0.000164) and GEPIA database. A total of 10 studies involving 2305 patients from literatures were selected. Pooled HR indicated that over-expression of YAP1 was associated with poor clinical outcomes (HR=1.70, 95% CI: 1.28-2.26, p=0.0003). Subgroup analysis showed a clear correlation between over-expression of YAP1 and worse survival rate in Chinese patients (HR=1.94, 95% CI: 1.40-2.69, p=0.0001), nuclear YAP1 over-expression (HR=2.07, 95% CI: 1.29-3.31, p=0.003), 60 months follow-up duration (HR=1.89, 95% CI: 1.30-2.73, p=0.0008), IHC test (HR=1.65, 95% CI: 1.17-2.33, p=0.005), IHC combined with other tests (HR=1.77, 95% CI: 1.13-2.77, p=0.01) and multivariate analysis (HR=1.70, 95% CI: 1.24-2.31, p=0.0009). Nevertheless, disease-free survival (DFS) did not show significant result in the patients with CRC in our meta-analysis (HR=1.38, 95% CI: 0.51-3.75, p=0.52) as well as in the GEPIA and LOGpc databases. Meanwhile, YAP1 over-expression was also significantly associated with worse overall survival (OS) in GSE17536, GSE40967, GSE29623 and GSE71187. CONCLUSION: YAP1 over-expression is common in CRC tissues. Over-expression of YAP1 in CRC patients, particularly in the nucleus, might be related to shorter OS, maybe in the early stages. YAP1 could serve as a potential predictor of poor prognosis in CRC.