UK5099 Inhibits the NLRP3 Inflammasome Independently of its Long-Established Target Mitochondrial Pyruvate Carrier.

Targeting NLRP3 inflammasome has been recognized as a promising therapeutic strategy for the treatment of numerous common diseases. UK5099, a long-established inhibitor of mitochondrial pyruvate carrier (MPC), is previously found to inhibit macrophage inflammatory responses independent of MPC expression. However, the mechanisms by which UK5099 inhibit inflammatory responses remain unclear. Here, it is shown that UK5099 is a potent inhibitor of the NLRP3 inflammasome in both mouse and human primary macrophages. UK5099 selectively suppresses the activation of the NLRP3 but not the NLRC4 or AIM2 inflammasomes. Of note, UK5099 retains activities on NLRP3 in macrophages devoid of MPC expression, indicating this inhibitory effect is MPC-independent. Mechanistically, UK5099 abrogates mitochondria-NLRP3 interaction and in turn inhibits the assembly of the NLRP3 inflammasome. Further, a single dose of UK5099 persistently reduces IL-1ß production in an endotoxemia mouse model. Importantly, structure modification reveals that the inhibitory activities of UK5099 on NLRP3 are unrelated to the existence of the activated double bond within the UK5099 molecule. Thus, this study uncovers a previously unknown molecular target for UK5099, which not only offers a new candidate for the treatment of NLRP3-driven diseases but also confounds its use as an MPC inhibitor in immunometabolism studies.

A transcription factor-mediated regulatory network controls fungal pathogen colonization of insect body cavities.

Successful host tissue colonization is crucial for fungal pathogens to cause mycosis and complete the infection cycle, in which fungal cells undergo a series of morphological transition-included cellular events to combat with hosts. However, many transcription factors (TFs) and their mediated networks regulating fungal pathogen colonization of host tissue are not well characterized. Here, a TF (BbHCR1)-mediated regulatory network was identified in an insect pathogenic fungus, Beauveria bassiana, that controlled insect hemocoel colonization. BbHCR1 was highly expressed in fungal cells after reaching insect hemocoel and controlled the yeast (in vivo blastospores)-to-hyphal morphological switch, evasion of immune defense response, and fungal virulence. Comparative analysis of RNA sequencing and chromatin immunoprecipitation sequencing identified a core set of BbHCR1 target genes during hemocoel colonization, in which abaA and brlA were targeted to limit the rapid switch from blastospores to hyphae and fungal virulence. Two targets encoding hypothetical proteins, HP1 and HP2, were activated and repressed by BbHCR1, respectively, which acted as a virulence factor and repressor, respectively, suggesting that BbHCR1 activated virulence factors but repressed virulence repressors during the colonization of insect hemocoel. BbHCR1 tuned the expression of two dominant hemocoel colonization-involved metabolite biosynthetic gene clusters, which linked its regulatory role in evasion of immune response. Those functions of BbHCR1 were found to be collaboratively regulated by Fus3- and Hog1-MAP kinases via phosphorylation. These findings have drawn a regulatory network in which Fus3- and Hog1-MAP kinases phosphorylate BbHCR1, which in turn controls the colonization of insect body cavities by regulating fungal morphological transition and virulence-implicated genes.IMPORTANCEFungal pathogens adopt a series of tactics for successful colonization in host tissues, which include morphological transition and the generation of toxic and immunosuppressive molecules. However, many transcription factors (TFs) and their linked pathways that regulate tissue colonization are not well characterized. Here, we identified a TF (BbHCR1)-mediated regulatory network that controls the insect fungal pathogen, Beauveria bassiana, colonization of insect hemocoel. During these processes, BbHCR1 targeted the fungal central development pathway for the control of yeast (blastospores)-to-hyphae morphological transition, activated virulence factors, repressed virulence repressors, and tuned the expression of two dominant hemocoel colonization-involved immunosuppressive and immunostimulatory metabolite biosynthetic gene clusters. The BbHCR1 regulatory function was governed by Fus3- and Hog1-MAP kinases. These findings led to a new regulatory network composed of Fus3- and Hog1-MAP kinases and BbHCR1 that control insect body cavity colonization by regulating fungal morphological transition and virulence-implicated genes.

A fungal pathogen secretes a cell wall-associated ß-N-acetylhexosaminidase that is co-expressed with chitinases to contribute to infection of insects.

BACKGROUND: ß-N-acetylhexosaminidases (HEXs) are widely distributed in fungi and involved in cell wall chitin metabolism and utilization of chitin-containing substrates. However, details of the fungal pathogens-derived HEXs in the interaction with their hosts remain limited. RESULTS: An insect nutrients-induced ß-N-acetylhexosaminidase, BbHex1, was identified from the entomopathogenic fungus Beauveria bassiana, which was involved in cell wall modification and degradation of insect cuticle. BbHex1 was localized to cell wall and secreted, and displayed enzyme activity to degrade the chitinase-hydrolyzed product (GlcNAc)2. Disruption of BbHex1 resulted in a significant decrease in the level of cell wall chitin in the presence of insect nutrients and during infection of insects, with impaired ability to penetrate insect cuticle, accompanying downregulated cell wall metabolism-involved and cuticle-degrading chitinase genes. However, the opposite phenotypes were examined in the gene overexpression strain. Distinctly altered cell wall structures caused by BbHex1 mutation and overexpression led to the easy activation and evasion (respectively) of insect immune response during fungal infection. As a result, BbHex1 contributed to fungal virulence. Bioinformatics analysis revealed that promoters of some co-expressed chitinase genes with the BbHex1 promoter shared conserved transcription factors Skn7, Msn2 and Ste12, and CreA-binding motifs, implying co-regulation of those genes with BbHex1. CONCLUSION: These data support a mechanism that the fungal pathogen specifically expresses BbHex1, which is co-expressed with chitinases to modify cell wall for evasion of insect immune recognition and to degrade insect cuticle, and contributes to the fungal virulence against insects. © 2024 Society of Chemical Industry.

A network of transcription factors in complex with a regulating cell cycle cyclin orchestrates fungal oxidative stress responses.

BACKGROUND: Response to oxidative stress is universal in almost all organisms and the mitochondrial membrane protein, BbOhmm, negatively affects oxidative stress responses and virulence in the insect fungal pathogen, Beauveria bassiana. Nothing further, however, is known concerning how BbOhmm and this phenomenon is regulated. RESULTS: Three oxidative stress response regulating Zn2Cys6 transcription factors (BbOsrR1, 2, and 3) were identified and verified via chromatin immunoprecipitation (ChIP)-qPCR analysis as binding to the BbOhmm promoter region, with BbOsrR2 showing the strongest binding. Targeted gene knockout of BbOsrR1 or BbOsrR3 led to decreased BbOhmm expression and consequently increased tolerances to free radical generating compounds (H2O2 and menadione), whereas the ΔBbOsrR2 strain showed increased BbOhmm expression with concomitant decreased tolerances to these compounds. RNA and ChIP sequencing analysis revealed that BbOsrR1 directly regulated a wide range of antioxidation and transcription-associated genes, negatively affecting the expression of the BbClp1 cyclin and BbOsrR2. BbClp1 was shown to localize to the cell nucleus and negatively mediate oxidative stress responses. BbOsrR2 and BbOsrR3 were shown to feed into the Fus3-MAPK pathway in addition to regulating antioxidation and detoxification genes. Binding motifs for the three transcription factors were found to partially overlap in the promoter region of BbOhmm and other target genes. Whereas BbOsrR1 appeared to function independently, co-immunoprecipitation revealed complex formation between BbClp1, BbOsrR2, and BbOsrR3, with BbClp1 partially regulating BbOsrR2 phosphorylation. CONCLUSIONS: These findings reveal a regulatory network mediated by BbOsrR1 and the formation of a BbClp1-BbOsrR2-BbOsrR3 complex that orchestrates fungal oxidative stress responses.

The Bbotf1 Zn(â ¡)2Cys6 transcription factor contributes to antioxidant response, fatty acid assimilation, peroxisome proliferation and infection cycles in insect pathogenic fungus Beauveria bassiana.

The abilities to withstand oxidation and assimilate fatty acids are critical for successful infection by many pathogenic fungi. Here, we characterized a Zn(II)2Cys6 transcription factor Bbotf1 in the insect pathogenic fungus Beauveria bassiana, which links oxidative response and fatty acid assimilation via regulating peroxisome proliferation. The null mutant ΔBbotf1 showed impaired resistance to oxidants, accompanied by decreased activities of antioxidant enzymes including CATs, PODs and SODs, and down-regulated expression of many antioxidation-associated genes under oxidative stress condition. Meanwhile, Bbotf1 acts as an activator to regulate fatty acid assimilation, lipid and iron homeostasis as well as peroxisome proliferation and localization, and the expressions of some critical genes related to glyoxylate cycle and peroxins were down-regulated in ΔBbotf1 in presence of oleic acid. In addition, ΔBbotf1 was more sensitive to osmotic stressors, CFW, SDS and LDS. Insect bioassays revealed that insignificant changes in virulence were seen between the null mutant and parent strain when conidia produced on CZP plates were used for topical application. However, propagules recovered from cadavers killed by ΔBbotf1 exhibited impaired virulence as compared with counterparts of the parent strain. These data offer a novel insight into fine-tuned aspects of Bbotf1 concerning multi-stress responses, lipid catabolism and infection cycles.

Fungal co-expression network analyses identify pathogen gene modules associated with host insect invasion.

The broad host range fungal insect pathogen, Beauveria bassiana, has been commercialized as an alternative to chemical insecticides for pest control worldwide. B. bassiana represents a unique model system with which to examine host-pathogen interactions, and a wide range of genes and processes have been studied. However, significant aspects of virulence, particularly on the genomic scale, remain poorly studied. Here, we have combined available transcriptomes with three newly generated data sets for a combined total analysis of 76 deep-sequenced samples covering growth, development, stress responses, and infection during the life cycle of B. bassiana. Co-expression network analyses resulted in the identification of gene modules enriched during two critical stages of the infection process, namely (i) cuticle penetration and (ii) in vivo hyphal body (dimorphic transition) growth capable of avoiding innate and humoral immune defenses. These analyses identify unique signatures of metabolism, signaling, secondary metabolite production, host defense suppression, membrane reorganization, effector production, and secretion for each stage, including genetic regulators and epigenetic patterns. These data provide a comprehensive framework for understanding and probing fungal adaptations to its pathogenic life cycle and expand the candidate repertoire for continued dissection of the host-pathogen interaction. IMPORTANCE Insect fungal pathogens have evolved unique strategies for overcoming host structural and immunological defenses that span from the sclerotized cuticle to innate and humoral cellular responses. Two critical stages of the infection process involve (i) cuticle penetration and (ii) immune evasion within the insect hemocoel. A set of 76 global transcriptomic data for B. bassiana that include the cuticle penetration and hemocoel growth stages were analyzed for patterns (gene modules) of expression, yielding unique insights into these different life stages. These analyses integrate gene networks involved in fungal development, stress response and pathogenesis to further the systematic understanding of the global processes integral to the unique adaptation employed by fungal pathogens of insects.

Insect fungal pathogens secrete a cell wall-associated glucanase that acts to help avoid recognition by the host immune system.

Fungal insect pathogens have evolved diverse mechanisms to evade host immune recognition and defense responses. However, identification of fungal factors involved in host immune evasion during cuticular penetration and subsequent hemocoel colonization remains limited. Here, we report that the entomopathogenic fungus Beauveria bassiana expresses an endo-ß-1,3-glucanase (BbEng1) that functions in helping cells evade insect immune recognition/ responses. BbEng1 was specifically expressed during infection, in response to host cuticle and hemolymph, and in the presence of osmotic or oxidative stress. BbEng1 was localized to the fungal cell surface/ cell wall, where it acts to remodel the cell wall pathogen associated molecular patterns (PAMPs) that can trigger host defenses, thus facilitating fungal cell evasion of host immune defenses. BbEng1 was secreted where it could bind to fungal cells. Cell wall ß-1,3-glucan levels were unchanged in ΔBbEng1 cells derived from in vitro growth media, but was elevated in hyphal bodies, whereas glucan levels were reduced in most cell types derived from the BbEng1 overexpressing strain (BbEng1OE). The BbEng1OE strain proliferated more rapidly in the host hemocoel and displayed higher virulence as compared to the wild type parent. Overexpression of their respective Eng1 homologs or of BbEng1 in the insect fungal pathogens, Metarhizium robertsii and M. acridum also resulted in increased virulence. Our data support a mechanism by which BbEng1 helps the fungal pathogen to evade host immune surveillance by decreasing cell wall glucan PAMPs, promoting successful fungal mycosis.

Sterol Regulatory Element-Binding Protein, BbSre1, Controls Oxidative Stress Response, Peroxisome Division, and Lipid Homeostasis in an Insect Fungal Pathogen.

Sterol regulatory element-binding protein, Sre1, regulates sterol biosynthesis, lipid metabolism, hypoxia adaptation, and virulence in some fungi, even though its roles are varied in fungal species. However, few studies report its other functions in fungi. Here, we report novel roles of Sre1 homolog, BbSre1, in the insect fungal pathogen, Beauveria bassiana, that regulates oxidative stress response, peroxisome division, and redox homeostasis. The gene disruption stain showed increased sensitivity to oxidative stress, which was in line with oxidative stress-induced-BbSre1 nuclear import and control of antioxidant and detoxification-involved genes. The gene mutation also inhibited peroxisome division, affected redox homeostasis, and impaired lipid/fatty acid metabolism and sterol biosynthesis, which was verified by downregulation of their associated genes. These data broaden our understanding of role of Sre1, which regulates peroxisome division, antioxidant, and detoxification-involved genes for control of redox homeostasis and oxidative stress response that links to lipid/fatty acid metabolism and sterol biosynthesis.

Fus3/Kss1-MAP kinase and Ste12-like control distinct biocontrol-traits besides regulation of insect cuticle penetration via phosphorylation cascade in a filamentous fungal pathogen.

BACKGROUND: Homolog of the yeast Fus3/Kss1 mitogen-activated protein kinase (MAPK) pathway and its target transcription factor, Ste12-like, are involved in penetration of host cuticle/pathogenicity in many ascomycete pathogens. However, details of their interaction during fungal infection, as well as their controlled other virulence-associated traits, are unclear. RESULTS: Ste12-like (BbSte12) and Fus3/Kss1 MAPK homolog (Bbmpk1) interacted in nucleus, and phosphorylation of BbSte12 by Bbmpk1 was essential for penetration of insect cuticle in an insect fungal pathogen, Beauveria bassiana. However, some distinct biocontrol-traits were found to be mediated by Ste12 and Bbmpk1. In contrast to ΔBbmpk1 colony that grew more rapid than wild-type strain, inactivation of BbSte12 resulted in the opposite phenotype, which was consistent with their different proliferation rates in insect hemocoel after direct injection of conidia bypass the cuticle. Reduced conidial yield with decreased hydrophobicity was examined in both mutants, however they displayed distinct conidiogenesis, accompanying with differently altered cell cycle, distinct hyphal branching and septum formation. Moreover, ΔBbmpk1 showed increased tolerance to oxidative agent, whereas the opposite phenotype was seen for ΔBbSte12 strain. RNA sequencing analysis revealed that Bbmpk1 controlled 356 genes depending on BbSte12 during cuticle penetration, but 1077 and 584 genes were independently controlled by Bbmpk1 and BbSte12. CONCLUSION: BbSte12 and Bbmpk1 separately participate in additional pathways for control of conidiation, growth and hyphal differentiation, as well as oxidative stress response besides regulating cuticle penetration via phosphorylation cascade. © 2023 Society of Chemical Industry.

Metal-polyphenol polymer modified polydopamine for chemo-photothermal therapy.

Chemotherapy combined with photothermal therapy (PTT) is a new way to improve the curative effect of cancer treatment. Here, we developed a multifunctional nanoparticle, namely PTX@mPDA@Fe-GA with the loading of a chemotherapeutic drug paclitaxel (PTX) for targeted and synergistic chemotherapy/photothermal therapy in lung cancer. Fe-gallic acid (Fe-GA) was coated on the surface of mesoporous polydopamine (mPDA) nanoparticles, and then the PTX was placed in the mesopores. The drug release of the loaded PTX exhibited pH- and thermal-dual responsive manner. Both mPDA and Fe-GA have high photothermal conversion ability and play a role in photothermal therapy. In addition, the results revealed that mPDA@Fe-GA had excellent biocompatibility and low hemolysis rate. The PTX-loaded mPDA@Fe-GA not only has excellent killing effect on lung cancer cells (A549) in vitro, but also can significantly suppress the growth of A549 subcutaneous tumor in nude mice. In a nutshell, the developed multifunctional nanoparticles integrate photothermal therapy and efficient chemotherapeutic drug delivery, providing new therapeutic ideas in the fight against lung cancer.

The AreA Nitrogen Catabolite Repression Activator Balances Fungal Nutrient Utilization and Virulence in the Insect Fungal Pathogen Beauveria bassiana.

In many fungi, the AreA GATA-type transcription factor mediates nitrogen catabolite repression affecting fungal development and, where applicable, virulence. Here, we investigated the functions of AreA in the fungal entomopathogen and plant endophyte Beauveria bassiana using knockdown of gene expression. The antiAreA mutants were impaired in nitrogen utilization and showed increased sensitivities to osmotic stressors but increased tolerances to oxidative/hypoxia stresses. Repression of BbAreA caused overall minimal effects on fungal virulence. The minor effects on virulence appeared to be due in part to competing secondary effects where host defense phenoloxidase activity was significantly decreased, but production of the fungal metabolite oosporein was increased and hyphal body development was impaired. Knockdown of BbAreA expression also resulted in impairment in ability of the fungus to associate with host plants. These data implicate that BbAreA likely acts as a regulator to balance fungal nutrient utilization, pathogenicity, and mutualism, facilitating the fungal occupation of host niches.

A novel transcription factor negatively regulates antioxidant response, cell wall integrity and virulence in the fungal insect pathogen, Beauveria bassiana.

Genomic data have identified a class of fungal specific transcription factors (FsTFs) that are thought to regulate unique aspects of fungal gene expression, although the functions of many of these proteins remain unknown. Here, a novel FsTF (BbStf1), which features a leucine zipper dimerization domain and a fungal transcription factor regulatory middle homology region, was characterized in Beauveria bassiana, a filamentous insect fungal pathogen. Transcriptional activation and nuclear localization were experimentally confirmed for BbStf1. Disruption of Bbstf1 resulted in increased tolerance to oxidative stress and cell wall perturbation, accompanied by increased peroxidase (POD) and superoxide dismutase (SOD) activities and ratio of reduced/oxidized glutathione (GSH/GSSG), and by thickened cell wall and altered composition. Gene expression profile analysis revealed that transcription patterns of antioxidant enzyme and cell wall integrity-involved genes were altered in the ∆Bbstf1, including some BbStf1-targeted genes clarified with evidence. The ∆Bbstf1 strain displayed greater virulence to Galleria mellonella in the bioassays through both topical infection and intrahaemocoel injection due to more rapid proliferation in the haemocoel as compared to the wild-type strain. Altogether, BbStf1 acts as a negative regulator of antioxidant response, cell wall integrity and virulence in B. bassiana.

Multifunctional role of a fungal pathogen-secreted laccase 2 in evasion of insect immune defense.

Laccases are widely present in bacteria, fungi, plants and invertebrates and involved in a variety of physiological functions. Here, we report that Beauveria bassiana, an economic important entomopathogenic fungus, secretes a laccase 2 (BbLac2) during infection that detoxifies insect immune response-generated reactive oxygen species (ROS) and interferes with host immune phenoloxidase (PO) activation. BbLac2 is expressed in fungal cells during proliferation in the insect haemocoel and can be found to distribute on the surface of haemolymph-derived in vivo fungal hyphal bodies or be secreted. Targeted gene-knockout of BbLac2 increased fungal sensitivity to oxidative stress, decreased virulence to insect, and increased host PO activity. Strains overexpressing BbLac2 showed increased virulence, with reduced host PO activity and lowered ROS levels in infected insects. In vitro assays revealed that BbLac2 could eliminate ROS and oxidize PO substrates (phenols), verifying the enzymatic functioning of the protein in detoxification of cytotoxic ROS and interference with the PO cascade. Moreover, BbLac2 acted as a cell surface protein that masked pathogen associated molecular patterns (PAMPs), enabling the pathogen to evade immune recognition. Our data suggest a multifunctional role for fungal pathogen-secreted laccase 2 in evasion of insect immune defenses.

Epidemiology and Outcomes of Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: A Multicenter Retrospective Study.

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). However, the epidemiological features and outcomes of AKI among COVID-19 patients with ARDS are unknown. METHODS: We retrospectively recruited consecutive adult COVID-19 patients who were diagnosed with ARDS according to Berlin definition from 13 designated intensive care units in the city of Wuhan, China. Potential risk factors of AKI as well as the relation between AKI and in-hospital mortality were investigated. RESULTS: A total of 275 COVID-19 patients with ARDS were included in the study, and 49.5% of them developed AKI during their hospital stay. In comparison with patients without AKI, patients who developed AKI were older, tended to have chronic kidney disease, had higher Sepsis-Related Organ Failure Assessment score on day 1, and were more likely to receive invasive ventilation and develop acute organ dysfunction. Multivariate analysis showed that age, history of chronic kidney disease, neutrophil-to-lymphocyte ratio, and albumin level were independently associated with the occurrence of AKI. Importantly, increasing AKI severity was associated with increased in-hospital mortality when adjusted for other potential variables: odds ratio of stage 1 = 5.374 (95% CI: 2.147-13.452; p < 0.001), stage 2 = 6.216 (95% CI: 2.011-19.210; p = 0.002), and stage 3 = 34.033 (95% CI: 9.723-119.129; p < 0.001). CONCLUSION: In this multicenter retrospective study, we found that nearly half of COVID-19 patients with ARDS experienced AKI during their hospital stay. The coexistence of AKI significantly increased the mortality of these patients.

Pest management via endophytic colonization of tobacco seedlings by the insect fungal pathogen Beauveria bassiana.

BACKGROUND: It has been suggested that entomopathogenic fungi can be introduced into plants as endophytes potentially leading to insect control. Here, we sought to identify specific strains of the insect pathogenic fungus, Beauveria bassiana that would form endophytic associations with tobacco (Nicotiana benthamiana) benefitting host plant growth and/or resistance against insect pests and pathogens. RESULTS: Tobacco seeds were inoculated with six different B. bassiana strains and entophytic colonization, plant growth, and resistance to pathogens and insect pests were evaluated over a 50 day-period. Although all the strains could colonize seedlings, 90% seedling colonization was seen for four strains. Fungal cells could be detected in stems more readily than in leaf and root tissues. Colonization by B. bassiana boosted plant growth with an increased photosynthetic rate, chlorophyll content, and stomatal and trichome density seen in fungal treated plants. Tobacco seedlings colonized by specific B. bassiana strains displayed significantly increased tolerance/resistance against bacterial and fungal pathogens. B. bassiana-colonized seedlings also displayed higher resistance to aphids (Myzus persicae) as compared to untreated controls. Colonization by B. bassiana was shown to trigger both of the salicylic acid (SA) and jasmonate acid (JA) defense pathways, but SA pathway was upregulated much more than JA pathway for some of the tested strains. CONCLUSION: Specific strains of B. bassiana can be introduced into host plants as endophytes, resulting in promotion of host plant growth, increased resistance to microbial pathogens, and/or increased resistance to insect pests. © 2020 Society of Chemical Industry.

A young male with chronic nonproductive cough diagnosed with blastomycosis in China: a case report.

BACKGROUND: Blastomycosis is a fungal infectious disease prevalent in North America and rarely reported in Asia. Misdiagnosis of malignancy and other infectious diseases were reported. CASE PRESENTATION: A 24-years-old male patient presented with chronic non-productive cough of 4 months duration. He had been diagnosed with Mycobacterium tuberculosis infection and lung malignancy elsewhere and presented to us as the symptoms persisted. We offered him the biopsy under endobronchial ultrasound-guide sheath-transbronchial lung biopsy and sample specimen were sent for next generation sequencing analysis, returned as Blastomyces Dermatitidis infection. The patient was treated by itraconazole for 6 months, his symptoms decreased significantly and the CT scan showed resolution of the lesion. CONCLUSION: We shared a case of blastomycosis with delayed and difficult diagnosis and reviewed the knowledge regarding differential diagnosis and next generation sequencing technologies.

Association between chest CT features and clinical course of Coronavirus Disease 2019.

PURPOSE: This retrospective study aims to illustrate the radiographic characteristics of Coronavirus Disease 2019 and the correlation with the clinical course. METHODS: 195 hospitalized patients confirmed as Coronavirus Disease 2019 at First Hospital of Changsha, Hunan Province from December 31, 2019 to February 20, 2020 were enrolled. Chest computed tomography scan, clinical data and laboratory tests results were collected accordingly. Variable characteristics were recorded, radiographic evolution and outcome were analyzed along with the time course. Representative laboratory tests results were analyzed based on the image findings. RESULTS: Majority of the patients showed bilateral (73.8%), multiple lobes involvements (75.9%), peripheral distribution (83.1%), ground-glass opacification (41.0%), increased vascular margins (63.1%), long axis parallelism (55.9%), patchy ground-glass opacities beneath the pleura (51.3%) and consolidation (45.6%). According to the repeated radiology analysis, patients of improving/stable group tended to have younger age compared with worsening group (45.3 ± 15.0 VS. 59.3 ± 13.5, P = 0.001). Based on the laboratory test results, patients with positive image findings shared elder age, 46.0 (35.0-60.0)VS.31.0 (12.0-37.0) P < 0.001, and higher chance developing fever(P < 0.05); higher level of lymphocytes, C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase; lower level of white blood cells, neutrophil and albumin(P < 0.001). CONCLUSIONS: There are several specific image changes along with the disease progression may be helpful in early recognition and differential diagnosis of Coronavirus Disease 2019. Comprehensive assessments of both imaging feature and laboratory test results may offer an intact knowledge of Coronavirus Disease 2019.

Upside-down InAs/InAs1-xSbx type-II superlattice-based nBn mid-infrared photodetectors with an AlGaAsSb quaternary alloy barrier.

Ga-free InAs/InAsSb type-II superlattices (T2SLs) are emerging as candidate materials for high temperature operation of mid-infrared photodetectors, which are critical for infrared technology with an aim to provide low-cost and compact detection systems. In this work, by utilizing upside-down device structure, a closely lattice-matched Al0.83Ga0.17AsSb quaternary alloy as electron barrier was pre-grown before the growth of InAs/InAsSb T2SLs absorber in a nBn device. Based on this design, we have demonstrated 5-µm cut-off mid-wavelength infrared (MWIR) photodetectors that exhibited a dark current density of 1.55 × 10-4 A/cm2 at an operation bias 400mV at 150K. A saturated quantum efficiency at ∼4.0 µm reaches 37.5% with a 2 µm absorber and the peak responsivity reaches 1.2 A/W, which yields a peak specific detectivity as high as ∼1.82 × 1011 cm·H z1/2/W at a forward bias of 400mV.