Direct visualization of replication and R-loop collision using single-molecule imaging.

R-loops are three-stranded nucleic acid structures that can cause replication stress by blocking replication fork progression. However, the detailed mechanism underlying the collision of DNA replication forks and R-loops remains elusive. To investigate how R-loops induce replication stress, we use single-molecule fluorescence imaging to directly visualize the collision of replicating Phi29 DNA polymerase (Phi29 DNAp), the simplest replication system, and R-loops. We demonstrate that a single R-loop can block replication, and the blockage is more pronounced when an RNA-DNA hybrid is on the non-template strand. We show that this asymmetry results from secondary structure formation on the non-template strand, which impedes the progression of Phi29 DNAp. We also show that G-quadruplex formation on the displaced single-stranded DNA in an R-loop enhances the replication stalling. Moreover, we observe the collision between Phi29 DNAp and RNA transcripts synthesized by T7 RNA polymerase (T7 RNAp). RNA transcripts cause more stalling because of the presence of T7 RNAp. Our work provides insights into how R-loops impede DNA replication at single-molecule resolution.

ZNF212 promotes genomic integrity through direct interaction with TRAIP.

TRAIP is a key factor involved in the DNA damage response (DDR), homologous recombination (HR) and DNA interstrand crosslink (ICL) repair. However, the exact functions of TRAIP in these processes in mammalian cells are not fully understood. Here we identify the zinc finger protein 212, ZNF212, as a novel binding partner for TRAIP and find that ZNF212 colocalizes with sites of DNA damage. The recruitment of TRAIP or ZNF212 to sites of DNA damage is mutually interdependent. We show that depletion of ZNF212 causes defects in the DDR and HR-mediated repair in a manner epistatic to TRAIP. In addition, an epistatic analysis of Zfp212, the mouse homolog of human ZNF212, in mouse embryonic stem cells (mESCs), shows that it appears to act upstream of both the Neil3 and Fanconi anemia (FA) pathways of ICLs repair. We find that human ZNF212 interacted directly with NEIL3 and promotes its recruitment to ICL lesions. Collectively, our findings identify ZNF212 as a new factor involved in the DDR, HR-mediated repair and ICL repair though direct interaction with TRAIP.

Polarization-Dependent Thin Films with Biaxial Anisotropic Absorption Constructed by a Single Coating and Subsequent Topochemical Polymerization of Chromophores.

For the construction of hierarchical superstructures with biaxial anisotropic absorption, a newly synthesized diacetylene-functionalized bipyridinium is self-assembled to use an electron-accepting host for capturing and arranging guests. The formation of the donor-acceptor complex triggers an intermolecular charge transfer, leading to chromophore activation. Polarization-dependent multichroic thin films are prepared through a sequential process of single-coating, self-assembly, and topochemical polymerization of host-guest chromophores. Molecular packing structures constructed in the single-layer optical thin film possess orthogonal absorption axes for two different wavelengths. By tuning the linear polarization angle, the color of the optical thin film can be intentionally controlled. This single-layered multichroic film provides a new pathway for the development of anticounterfeiting and multiplexing encryptions.

Oxygen Vacancy-Controlled CuOx/N,Se Co-Doped Porous Carbon via Plasma-Treatment for Enhanced Electro-Reduction of Nitrate to Green Ammonia.

The electrochemical nitrate reduction reaction (NO3RR) is of significance in regards of environmentally friendly issues and green ammonia production. However, relatively low performance with a competitive hydrogen evolution reaction (HER) is a challenge to overcome for the NO3RR. In this study, oxygen vacancy-controlled copper oxide (CuOx) catalysts through a plasma treatment are successfully prepared and supported on high surface area porous carbon that are co-doped with N, Se species for its enhanced electrochemical properties. The oxygen vacancy-increased CuOx catalyst supported on the N,Se co-doped porous carbon (CuOx-H/NSePC) exhibited the highest NO3RR performance with faradaic efficiency (FE) of 87.2% and yield of 7.9 mg cm-2 h-1 for the ammonia production, representing significant enhancements of FE and ammonia yield as compared to the un-doped or the oxygen vacancy-decreased catalysts. This high performance should be attributed to a significant increase in the catalytic active sites with facilitated energetics from strategies of doping the catalytic materials and weakening the N─O bonding strength for the adsorption of NO3 - ions on the modulated oxygen vacancies. This results show a promise that co-doping of heteroatoms and regulating of oxygen vacancies can be key factors for performance enhancement, suggesting new guidelines for effective catalyst design of NO3RR.

Propensity score matched analysis for the safety and effectiveness of remdesivir in COVID-19 patients with renal impairment.

BACKGROUNDS: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. METHODS: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. RESULTS: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. CONCLUSION: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity.

Catabolism of 2-keto-3-deoxy-galactonate and the production of its enantiomers.

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal D-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for D-galactose catabolism. The presence of KDGal enantiomers, L-KDGal and D-KDGal, varies across these pathways. Fungal pathways generate L-KDGal through the reduction and dehydration of D-galacturonate, whereas bacterial pathways produce D-KDGal through the oxidation and dehydration of D-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that L-KDGal, identified in the bacterial catabolism of 3,6-anhydro-L-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and D- and L-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of L-KDGal and D-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers. KEY POINTS: • KDGal is a metabolic intermediate in fungal and bacterial pathways • Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal • KDGal can be used to induce pectin catabolism or produce functional materials.

The clinical availability of facial nerve enhancement in temporal bone MRI for the patients of idiopathic acute peripheral facial palsy.

PURPOSE: This study is to evaluate the duration of facial nerve enhancement in gadolinium-enhanced temporal bone MRI after the onset of acute facial palsy. METHODS: Gd-enhanced MRI imagines were examined in 13 patients with idiopathic acute facial palsy within 14 days after the onset. The degree of facial nerve function was measured according to the House-Brackmann (H-B) grading system at their first visit at outpatient clinic. The follow-up MRI was taken about 16.5 months (7-24 months) after onset of disease. The degree of facial nerve enhancement was measured with signal intensity (SI) which was quantitatively analyzed using the region-of-interest (ROI) measurements for each segment of the facial nerve. SI was statistically analyzed by comparing SI values of contralateral site and ipsilateral site using the paired t test with SPSS program. RESULTS: The gadolinium enhancement was statistically increased at labyrinthine segment and geniculate ganglion area of facial nerve at initial temporal bone MRI. The gadolinium enhancement was statistically decreased at all the segments of facial nerve except tympanic segment (p < 0.05) at follow-up MRI. CONCLUSIONS: The facial nerve enhancement in Gd-enhanced MRI images prolonged more than 21 months of the onset. The newly developed pathologic lesions of acute facial palsy especially occur at the site of labyrinthine and geniculate ganglion.

Realization of a 594 Wh kg-1 Lithium-Metal Battery Using a Lithium-Free V2 O5 Cathode with Enhanced Performances by Nanoarchitecturing.

To realize a high-energy lithium metal battery (LMB) using a high-capacity Li-free cathode, in this work, nanoplate-stacked V2 O5 with dominantly exposed (010) facets and a relatively short [010] length is proposed to be used as a cathode. The V2 O5 nanostructure can be fabricated via a modified hydrothermal method, including a Li+ crystallization inhibitor, followed by heat treatment. In particular, the enlargement of the favorable Li+ diffusion pathway in the [010] direction and the formation of a robust hierarchical nanoplate-stacked structure in the modified V2 O5 improves the electrochemical kinetics and stability; as a result, the nanoplate-stacked V2 O5 electrode exhibits a higher capacity and rate performance (258 mAh g-1 at 50 mA g-1 [0.17 C], 140 mAh g-1 at 1 A g-1 [3.4 C]) and cycling capability (79% capacity retention after 100 cycles at 0.5 C) compared to the previously reported V2 O5 nanobelt electrode. Notably, the LMB composed of Li//nanoplate-stacked V2 O5 full-cells shows high specific energy densities of 594.1 and 296.2 Wh kg-1 at 0.1 and 1.0 C, respectively, and a high Coulombic efficiency of 99.6% during 50 cycles.

An Inorganic-Rich SEI Layer by the Catalyzed Reduction of LiNO3 Enabled by Surface-Abundant Hydrogen Bonding for Stable Lithium Metal Batteries.

Lithium (Li) metal anodes (LMAs) are promising anode candidates for realizing high-energy-density batteries. However, the formation of unstable solid electrolyte interphase (SEI) layers on Li metal is harmful for stable Li cycling; hence, enhancing the physical/chemical properties of SEI layers is important for stabilizing LMAs. Herein, thiourea (TU, CH4 N2 S) is introduced as a new catalyzing agent for LiNO3 reduction to form robust inorganic-rich SEI layers containing abundant Li3 N. Due to the unique molecular structure of TU, the TU molecules adsorb on the Cu electrode by forming CuS bond and simultaneously form hydrogen bonding with other hydrogen bonds accepting species such as NO3 - and TFSI- through its NH bonds, leading to their catalyzed reduction and hence the formation of inorganic-rich SEI layer with abundant Li3 N, LiF, and Li2 S/Li2 S2 . Particularly, this TU-modified SEI layer shows a lower film resistance and better uniformity compared to the electrochemically and naturally formed SEI layers, enabling planar Li growth without any other material treatments and hence improving the cyclic stability in Li/Cu half-cells and Li@Cu/LiFePO4  full-cells.

Bisphenol A modulates proliferation, apoptosis, and wound healing process of normal prostate cells: Involvement of G2/M-phase cell cycle arrest, MAPK signaling, and transcription factor-mediated MMP regulation.

Bisphenol A (BPA) is commonly used to produce epoxy resins and polycarbonate plastics. BPA is an endocrine-disrupting chemical that is leaked from the polymer and absorbed into the body to disrupt the endocrine system. Although BPA may cause cytotoxicity in the prostate, a hormone-dependent reproductive organ, its underlying mechanism has not yet been elucidated. Here, we investigated the effects of BPA on cell proliferation, apoptosis, and the wound healing process using prostate epithelial cells (RWPE-1) and stromal cells (WPMY-1). Observations revealed that BPA induced G2/M cell cycle arrest in both cell types through the ATM-CHK1/CHK2-CDC25c-CDC2 signaling pathway, and the IC50 values were estimated to be 150 µM. Furthermore, BPA was found to induce caspase-dependent apoptosis through initiator (caspase-8 and -9) and executioner (caspase-3 and -7) caspase cascades. In addition, BPA interfered with the wound healing process through inhibition of MMP-2 and - 9 expression, accompanied by reductions in the binding activities of AP-1 as well as NF-κB motifs. Phosphorylation of MAPKs was associated with the BPA-mediated toxicity of prostate cells. These results suggest that BPA exhibits prostate toxicity by inhibiting cell proliferation, inducing apoptosis, and interfering with the wound healing process. Our study provided new insights into the precise molecular mechanisms of BPA-induced toxicity in human prostate cells.

An N-Type Pseudo-Static eDRAM Macro with Reduced Access Time for High-Speed Processing-in-Memory in Intelligent Sensor Hub Applications.

This paper introduces an n-type pseudo-static gain cell (PS-nGC) embedded within dynamic random-access memory (eDRAM) for high-speed processing-in-memory (PIM) applications. The PS-nGC leverages a two-transistor (2T) gain cell and employs an n-type pseudo-static leakage compensation (n-type PSLC) circuit to significantly extend the eDRAM's retention time. The implementation of a homogeneous NMOS-based 2T gain cell not only reduces write access times but also benefits from a boosted write wordline technique. In a comparison with the previous pseudo-static gain cell design, the proposed PS-nGC exhibits improvements in write and read access times, achieving 3.27 times and 1.81 times reductions in write access time and read access time, respectively. Furthermore, the PS-nGC demonstrates versatility by accommodating a wide supply voltage range, spanning from 0.7 to 1.2 V, while maintaining an operating frequency of 667 MHz. Fabricated using a 28 nm complementary metal oxide semiconductor (CMOS) process, the prototype features an efficient active area, occupying a mere 0.284 µm2 per bitcell for the 4 kb eDRAM macro. Under various operational conditions, including different processes, voltages, and temperatures, the proposed PS-nGC of eDRAM consistently provides speedy and reliable read and write operations.

Intergranular Shielding for Ultrafine-Grained Mo-Doped Ni-Rich Li[Ni0.96 Co0.04 ]O2 Cathode for Li-Ion Batteries with High Energy Density and Long Life.

Deploying Ni-enriched (Ni≥95 %) layered cathodes for high energy-density lithium-ion batteries (LIBs) requires resolving a series of technical challenges. Among them, the structural weaknesses of the cathode, vigorous reactivity of the labile Ni4+ ion species, gas evolution and associated cell swelling, and thermal instability issues are critical obstacles that must be solved. Herein, we propose an intuitive strategy that can effectively ameliorate the degradation of an extremely high-Ni-layered cathode, the construction of ultrafine-scale microstructure and subsequent intergranular shielding of grains. The formation of ultrafine grains in the Ni-enriched Li[Ni0.96 Co0.04 ]O2 (NC96) cathode, achieved by impeding particle coarsening during cathode calcination, noticeably improved the mechanical durability and electrochemical performance of the cathode. However, the buildup of the strain-resistant microstructure in Mo-doped NC96 concurrently increased the cathode-electrolyte contact area at the secondary particle surface, which adversely accelerated parasitic reactions with the electrolyte. The intergranular protection of the refined microstructure resolved the remaining chemical instability of the Mo-doped NC96 cathode by forming an F-induced coating layer, effectively alleviating structural degradation and gas generation, thereby extending the battery's lifespan. The proposed strategies synergistically improved the structural and chemical durability of the NC96 cathode, satisfying the energy density, life cycle performance, and safety requirements for next-generation LIBs.

Pseudo-Static Gain Cell of Embedded DRAM for Processing-in-Memory in Intelligent IoT Sensor Nodes.

This paper presents a pseudo-static gain cell (PS-GC) with extended retention time for an embedded dynamic random-access memory (eDRAM) macro for analog processing-in-memory (PIM). The proposed eDRAM cell consists of a two-transistor (2T) gain cell with a pseudo-static leakage compensation that maintains stored data without charge loss issue. Hence, the PS-GC can offer unlimited retention time in the same manner as static RAM (SRAM). Due to the extended retention time, bulky capacitors in conventional eDRAM are no longer needed, thereby, improving the area efficiency of eDRAM-based analog PIMs. The active leakage compensation of the PS-GC can effectively hold stored data even in a deep-submicron process that show significant leakage current. Therefore, the PS-GC can accelerate write-access time and read-access time without concern of increased leakage current. The proposed gain cell and its 64 × 64 eDRAM macro were implemented in a 28 nm CMOS process. The bitcell of the proposed gain cell has 0.79- and 0.58-times the area of those of 6T SRAM and 8T STAM, respectively. The post-layout simulation results demonstrate that the eDRAM maintains the pseudo-static operation with unlimited retention time successfully under wide range variations of process, voltage and temperature. At the operating frequency of 667 MHz, the eDRAM macro achieved an operating voltage range from 0.9 to 1.2 V and operating temperature range from -25 to 85 °C regardless of the process variation. The post-layout simulated write-access time and read-access time were below 0.3 ns at an operating temperature of 85 °C. The PS-GC consumes a static power of 2.2 nW/bit at an operating temperature of 25 °C.

Discovery of substituted indole derivatives as allosteric inhibitors of m6 A-RNA methyltransferase, METTL3-14 complex.

m6 A RNA methyltransferase (METTL3-14) catalyzes the methylation of adenosine in mRNA and plays important roles in mRNA functions, and it has been implicated in the progression of multiple cancers, including acute myeloid leukemia (AML). In this study, we describe the discovery of the first allosteric inhibitor of the METTL3-14 complex based on structure-activity relationship (SAR) and optimization studies of the hit compound, 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic acid (CDIBA). Compound 43n was optimized throughout the modifications of 4 different regions of the structure, and it displayed potent enzyme inhibitory activity of the METTL3-14 complex (IC50  = 2.81 µM) and an antiproliferative effect in the AML cell lines by suppressing the m6 A level of mRNA. The inhibition mechanism and binding mode of 43n were based on the interaction of the reversible and noncompetitive inhibitory profile at the allosteric site along with selectivity for the METTL3-14 complex relative to each subunit enzyme or truncated complex enzyme.

Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP.

Attenuating the expression of immediate early (IE) proteins is essential for controlling the lytic replication of human cytomegalovirus (HCMV). The human microRNAs (hsa-miRs), miR-200b-3p and miR-200c-3p, have been identified to bind the 3'-untranslated region (3'-UTR) of the mRNA encoding IE proteins. However, whether hsa-miRs can reduce IE72 expression and HCMV viral load or exhibit a crosstalk with the host cellular signaling machinery, most importantly the NF-κB cascade, has not been evaluated. In this study, argonaute-crosslinking and immunoprecipitation-seq revealed that miR-200b-3p and miR-200c-3p bind the 3'-UTR of UL123, which is a gene that encodes IE72. The binding of these miRNAs to the 3'-UTR of UL123 was verified in transfected cells stably expressing GFP. We used miR-200b-3p/miR-200c-3p mimics to counteract the downregulation of these miRNA after acute HCMV infection. This resulted in reduced IE72/IE86 expression and HCMV VL during lytic infection. We determined that IE72/IE86 alone can inhibit the phosphorylation of RelA/p65 at the Ser536 residue and that p-Ser536 RelA/p65 binds to the major IE promoter/enhancer (MIEP). The upregulation of miR-200b-3p and miR-200c-3p resulted in the phosphorylation of RelA/p65 at Ser536 through the downregulation of IE, and the binding of the resultant p-Ser536 RelA/p65 to MIEP resulted in a decreased production of pro-inflammatory cytokines. Overall, miR-200b-3p and miR-200c-3p-together with p-Ser536 RelA/p65-can prevent lytic HCMV replication during acute and latent infection.

Structural insights into novel mechanisms of inhibition of the major ß-carbonic anhydrase CafB from the pathogenic fungus Aspergillus fumigatus.

In fungi the ß-class of carbonic anhydrases (ß-CAs) are zinc metalloenzymes that are essential for growth, survival, differentiation, and virulence. Aspergillus fumigatus is the most important pathogen responsible for invasive aspergillosis and possesses two major ß-CAs, CafA and CafB. Recently we reported the biochemical characterization and 1.8 Å crystal structure of CafA. Here, we report a crystallographic analysis of CafB revealing the mechanism of enzyme catalysis and establish the relationship of this enzyme to other ß-CAs. While CafA has a typical open conformation, CafB, when exposed to acidic pH and/or an oxidative environment, has a novel type of active site in which a disulfide bond is formed between two zinc-ligating cysteines, expelling the zinc ion and stabilizing the inactive form of the enzyme. Based on the structural data, we generated an oxidation-resistant mutant (Y159A) of CafB. The crystal structure of the mutant under reducing conditions retains a catalytic zinc at the expected position, tetrahedrally coordinated by three residues (C57, H113 and C116) and an aspartic acid (D59), and replacing the zinc-bound water molecule in the closed form. Furthermore, the active site of CafB crystals grown under zinc-limiting conditions has a novel conformation in which the solvent-exposed catalytic cysteine (C116) is flipped out of the metal coordination sphere, facilitating release of the zinc ion. Taken together, our results suggest that A. fumigatus use sophisticated activity-inhibiting strategies to enhance its survival during infection.

Comparing axon regeneration in male and female mice after peripheral nerve injury.

Axons in the adult mammalian central nervous system fail to regenerate after injury. By contrast, spontaneous axon regeneration occurs in the peripheral nervous system (PNS) due to a supportive PNS environment and an increase in the intrinsic growth potential induced by injury via cooperative activation of multifaceted biological pathways. This study compared axon regeneration and injury responses in C57BL/6 male and female mice after sciatic nerve crush (SNC) injury. The extent of axon regeneration in vivo was indistinguishable in male and female mice when observed at 3 days after SNC injury, and primary dorsal root ganglion (DRG) neurons from injured, male and female mice extended axons to a similar length. Moreover, the induction of selected regeneration-associated genes (RAGs), such as Atf3, Sprr1a, Gap43, Sox11, Jun, Gadd45a, and Smad1 were comparable in male and female DRGs when assessed by quantitative real-time reverse transcription polymerase chain reaction. Furthermore, the RNA-seq analysis of male and female DRGs revealed that differentially expressed genes (DEGs) in SNC groups compared to sham-operated groups included many common genes associated with neurite outgrowth. However, we also found that a large number of genes in the DEGs were sex dependent, implicating the involvement of distinct gene regulatory network in the two sexes following peripheral nerve injury. In conclusion, we found that male and female mice mounted a comparable axon regeneration response and many RAGs were commonly induced in response to SNC. However, given that many DEGs were sex-dependently expressed, future studies are needed to investigate whether they contribute to peripheral axon regeneration, and if so, to what extent.

Magnetic-field enhanced modulation transfer spectroscopy: theory and experiment.

We herein present a theoretical and experimental study on magnetic-field enhanced modulation transfer spectroscopy (MTS) for the 5S1/2 (F = 1) → 5P3/2 (F' = 0, 1, and 2) transitions of 87Rb atoms. The density matrix equations are solved numerically to obtain the MTS spectra and an excellent agreement is found between the experimental and calculated results. In particular, the enhancement of the MTS signal for the F = 1 → F' = 0 transition in the presence of the magnetic field is directly verified based on the comparison of the results calculated by neglecting with those calculated including the Zeeman coherences in the F = 1 ground state. The unexpected behaviors of the F = 1 → F' = 1 transition are also examined.

Transglutaminase 2 mediates lung inflammation and remodeling by transforming growth factor beta 1 via alveolar macrophage modulation.

Transforming growth factor beta 1 (TGF-ß1) induces pulmonary fibrosis by enhancing epithelial apoptosis and affects the enzymatic activity of transglutaminase 2 (TG2). The aim of this study was to determine the role of TG2 in TGF-ß1-induced lung remodeling and alveolar macrophage modulation. We characterized the in vivo effects of TGF-ß1 and TG2 on lung inflammation, fibrosis, and macrophage activity using transgenic C57BL/6 mice with wild and null TG2 loci. The effect of TG2 inhibition on in vitro TGF-ß1-stimulated alveolar macrophages was assessed through mRNA analysis. TG2 was remarkably upregulated in the lungs of TGF-ß1 transgenic (TGF-ß1 Tg) mice, especially in alveolar macrophages and epithelial cells. In the absence of TG2, TGF-ß1-induced inflammation was suppressed, decreasing the number of macrophages in the bronchoalveolar lavage fluid. In addition, the alveolar destruction and peribronchial fibrosis induced by TGF-ß1 overexpression were significantly reduced, which correlated with decreases in the expression of fibroblast growth factor and matrix metallopeptidase 12, respectively. However, TG2 deficiency did not compromise the phagocytic activity of alveolar macrophages in TGF-ß1 Tg mice. At the same time, TG2 contributed to the regulation of TGF-ß1-induced macrophage activation. Inhibition of TG2 did not affect the TGF-ß1-induced expression of CD86, an M1 marker, in macrophages, but it did reverse the TGF-ß1-induced expression of CD206. This result suggests that TG2 mediates TGF-ß1-induced M2-like polarization but does not contribute to TGF-ß1-induced M1 polarization. In conclusion, TG2 regulates macrophage modulation and plays an important role in TGF-ß1-induced lung inflammation, destruction, and fibrosis.

Emergent procedures for oropharyngeal bleeding during the COVID-19 pandemic: Protection of medical staff.

During an ongoing pandemic of COVID-19, controlling the oropharyngeal bleeding, such as post-tonsillectomy hemorrhage, with cauterization is considered a very vulnerable procedure for medical staff because of high probability of exposure to aerosolized secretion. The authors aimed to introduce an appropriate treatment protocol for oropharyngeal bleeding that provides first aid to patients while protecting medical staff at high-risk of infection such as COVID-19.