Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and ∼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’ blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.

The current outbreak of the beta-coronavirus (beta-Cov) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019. No specific antiviral treatments or vaccines are currently available. A recent study has reported that coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with neutrophil-specific plasma membrane rupture, and release excessive neutrophil extracellular traps (NETs) and extracellular DNAs (eDNAs). This mechanism involves the activation of NETosis, a neutrophil-specific programmed cell death, which is believed to play a crucial role in COVID-19 pathogenesis. Further progression of the disease can cause uncontrolled inflammation, leading to the initiation of cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. Herein, it is reported that DNase-I-coated melanin-like nanospheres (DNase-I pMNSs) mitigate sepsis-associated NETosis dysregulation, thereby preventing further progression of the disease. Recombinant DNase-I and poly(ethylene glycol) (PEG) are used as coatings to promote the lengthy circulation and dissolution of NET structure. The data indicate that the application of bioinspired DNase-I pMNSs reduce neutrophil counts and NETosis-related factors in the plasma of SARS-CoV-2 sepsis patients, alleviates systemic inflammation, and attenuates mortality in a septic mouse model. Altogether, the findings suggest that these nanoparticles have potential applications in the treatment of SARS-CoV-2-related illnesses and other beta-CoV-related diseases.

Conveyor fused deposition modelling (CFDM) 3D printing of graphene (GR)/polylactic acid (PLA) composite filament offers a unique capability to manufacture tailorable honeycomb structures which can be designed and optimized for specific applications. Among the various filaments that can be used for 3D printing, PLA, carbon black (CB)/PLA, and GR/PLA filaments were collected and then examined by differential scanning calorimetry (DSC), thermal gravity analysis (TGA), and Raman spectra. A stereolithography (STL) file with a 3D honeycomb structure model was prepared and transformed into a G-code file using a G-code generator. The extrusion conditions for CFDM 3D printing were controlled by infill and print speed. PLA, CB/PLA, and GR/PLA composite honeycomb samples were manufactured by 3D printing based on FDM using PLA, CB/PLA, and GR/PLA filaments. CFDM 3D printed honeycomb samples prepared by PLA, CB/PLA and GR/PLA filament were analyzed for morphology, surface resistance, electrical heating properties. For the 3D printed honeycomb structure sample using CB/PLA and GR/PLA, the optimum condition was set up 230 °C and 220 °C respectively of the printer temperature, 50 °C of bed temperature, and 30 mm/s of printer speed. Surface resistivity of honeycomb structure sample using CB/PLA and GR/PLA is about 299.0 Ω/sq and 118.0 Ω/sq. The maximum surface temperature of honeycomb structure sample using CB/PLA and GR/PLA is ca. 78.7 °C and 143.0 °C applied to 25 V.

An electro-conductive para-aramid knit was manufactured by a dip-coating in a graphene/waterborne polyurethane(WPU) composite for confirming to use as a fabric heating element applicable to a protective clothing requiring durability. The para-aramid knit was dipped in 8 wt% graphene/WPU composite solution up to five-coat cycles. As a result of electro-conductive textile by number of dip-coating cycles, the electrical, and specifically electrical heating performances were increased number of cycles from one to five. The sample with the best electrical and electrical heating performance was the five-coat sample, and to improve those properties it was hot-pressed at 100 °C, 120 °C, 140 °C and 160 °C. After hot pressing, the entire surface of the sample was filled with graphene/WPU composite and indicated smoothly surface, thus the electrical and electrical heating performance was improved than the five-coat sample. The best performance of was indicated hot-pressed at 140 °C, with a surface resistivity and capacitance of 7.5 × 104 Ω/sq and 89.4 pF, respectively. When a voltage of 50 V was applied, the surface temperature reached 54.8 °C. The five-coat sample with hot-pressed at 140 °C could be applied to a heat-resistant para-aramid knit glove with the touch screen of a mobile phone and electric heating performance.

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