Phospho-eIF4E stimulation regulates coronavirus entry by selective expression of cell membrane-residential factors.

The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative quantitative proteomics, we found that phosphorylated eIF4E (p-eIF4E) favors the translation of selected mRNAs, and the encoded proteins are mainly involved in ECM-receptor, focal adhesion, and PI3K-Akt signaling. The current paper is focused on the relationship between p-eIF4E and the downstream host cell proteins, and their presumed effect on efficient entry of PEDV. We found that the depletion of membrane-residential factor TSPAN3, CD63, and ITGB2 significantly inhibited viral invasion of PEDV, and reduced the entry of pseudotyped particles PEDV-pp, SARS-CoV-pp, and SARS-CoV-2-pp. The specific antibodies of TSPAN3, CD63, and ITGB2 blocked the adsorption of PEDV into host cells. Moreover, we detected that eIF4E phosphorylation was increased at 1 h after PEDV infection, in accordance with the expression of TSPAN3, CD63, and ITGB2. Similar trends appeared in the intestines of piglets in the early stage of PEDV challenge. Compared with Vero cells, S209A-Vero cells in which eIF4E cannot be phosphorylated showed a decrease of invading PEDV virions. MNK kinase inhibitor blocked PEDV invasion, as well as reduced the accumulation of TSPAN3, CD63, and ITGB2. Further study showed that the ERK-MNK pathway was responsible for the regulation of PEDV-induced early phosphorylation of eIF4E. This paper demonstrates for the first time the connections among p-eIF4E stimulation and membrane-residential host factors. Our findings also enrich the understanding of the biological function of phosphorylated eIF4E during the viral life cycle.IMPORTANCEThe eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation. In our previous study, several host factors susceptible to a high level of p-eIF4E were found to be conducive to viral infection by coronavirus PEDV. The current paper is focused on cell membrane-residential factors, which are involved in signal pathways that are sensitive to phosphorylated eIF4E. We found that the ERK-MNK pathway was activated, which resulted in the stimulation of phosphorylation of eIF4E in early PEDV infection. Phospho-eIF4E promoted the viral invasion of PEDV by upregulating the expression of host factors TSPAN3, CD63, and ITGB2 at the translation level rather than at the transcription level. Moreover, TSPAN3, CD63, or ITGB2 facilitates the efficient entry of coronavirus SARS-CoV, SARS-CoV-2, and HCoV-OC43. Our findings broaden our insights into the dynamic phosphorylation of eIF4E during the viral life cycle, and provide further evidence that phosphorylated eIF4E regulates selective translation of host mRNA.

The crustacean DNA virus tegument protein VP26 binds to SNAP29 to inhibit SNARE complex assembly and autophagic degradation.

Autophagy generally functions as a cellular surveillance mechanism to combat invading viruses, but viruses have evolved various strategies to block autophagic degradation and even subvert it to promote viral propagation. White spot syndrome virus (WSSV) is the most highly pathogenic crustacean virus, but little is currently known about whether crustacean viruses such as WSSV can subvert autophagic degradation for escape. Here, we show that even though WSSV proliferation triggers the accumulation of autophagosomes, autophagic degradation is blocked in the crustacean species red claw crayfish. Interestingly, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex including CqSNAP29, CqVAMP7, and the novel autophagosome SNARE protein CqSyx12 is required for autophagic flux to restrict WSSV replication, as revealed by gene silencing experiments. Simultaneously, the expressed WSSV tegument protein VP26, which likely localizes on autophagic membrane mediated by its transmembrane region, binds the Qb-SNARE domain of CqSNAP29 to competitively inhibit the binding of CqSyx12-Qa-SNARE with CqSNAP29-Qb-SNARE; this in turn disrupts the assembly of the CqSyx12-SNAP29-VAMP7 SNARE complex, which is indispensable for the proposed fusion of autophagosomes and lysosomes. Consequently, the autophagic degradation of WSSV is likely suppressed by the expressed VP26 protein in vivo in crayfish, thus probably protecting WSSV components from degradation via the autophagosome-lysosome pathway, resulting in evasion by WSSV. Collectively, these findings highlight how a DNA virus can subvert autophagic degradation by impairing the assembly of the SNARE complex to achieve evasion, paving the way for understanding host-DNA virus interactions from an evolutionary point of view, from crustaceans to mammals.IMPORTANCEWhite spot syndrome virus (WSSV) is one of the largest animal DNA viruses in terms of its genome size and has caused huge economic losses in the farming of crustaceans such as shrimp and crayfish. Detailed knowledge of WSSV-host interactions is still lacking, particularly regarding viral escape from host immune clearance. Intriguingly, we found that the presence of WSSV-VP26 might inhibit the autophagic degradation of WSSV in vivo in the crustacean species red claw crayfish. Importantly, this study is the first to show that viral protein VP26 functions as a core factor to benefit WSSV escape by disrupting the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which is necessary for the proposed fusion of autophagosomes with lysosomes for subsequent degradation. These findings highlight a novel mechanism of DNA virus evasion by blocking SNARE complex assembly and identify viral VP26 as a key candidate for anti-WSSV targeting.

TBC1D10B promotes tumor progression in colon cancer via PAK4­mediated promotion of the PI3K/AKT/mTOR pathway.

This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population.

AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.

Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota.

Ulcerative colitis (UC) is a chronic recurrent inflammatory disease affecting the rectum and colon. Numerous epidemiological studies have identified smoking as a protective factor for UC. Dysbiosis of intestinal microbiota and release of inflammatory factors are well-established characteristics associated with UC. Therefore, we have observed that nicotine exhibits the potential to ameliorate colitis symptoms in UC mice. Additionally, it exerts a regulatory effect on colonic microbiota dysbiosis by promoting the growth of beneficial bacteria while suppressing harmful bacteria. Combined in vivo and in vitro investigations demonstrate that nicotine primarily impedes the assembly of NLRP3, subsequently inhibiting downstream IL-1ß secretion.

Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

Carboxylated Hexagonal Boron Nitride/Graphene Configuration for Electrosynthesis of High-Concentration Neutral Hydrogen Peroxide.

The electrosynthesis of hydrogen peroxide (H2 O2 ) via two-electron (2e- ) oxygen (O2 ) reduction reaction (ORR) has great potential to replace the traditional energy-intensive anthraquinone process, but the design of low-cost and highly active and selective catalysts is greatly challenging for the long-term H2 O2 production under industrial relevant current density, especially under neutral electrolytes. To address this issue, this work constructed a carboxylated hexagonal boron nitride/graphene (h-BN/G) heterojunction on the commercial activated carbon through the coupling of B, N co-doping with surface oxygen groups functionalization. The champion catalyst exhibited a high 2e- ORR selectivity (>95 %), production rate (up to 13.4 mol g-1 h-1 ), and Faradaic efficiency (FE, >95 %). The long-term H2 O2 production under the high current density of 100 mA cm-2 caused the cumulative concentration as high as 2.1 wt %. The combination of in situ Raman spectra and theoretical calculation indicated that the carboxylated h-BN/G configuration promotes the adsorption of O2 and the stabilization of the key intermediates, allowing a low energy barrier for the rate-determining step of HOOH* release from the active site and thus improving the 2e- ORR performance. The fast dye degradation by using this electrochemical synthesized H2 O2 further illustrated the promising practical application.

Efficient Ternary Mn-Based Spinel Oxide with Multiple Active Sites for Oxygen Evolution Reaction Discovered via High-Throughput Screening Methods.

The discovery of more efficient and stable catalysts for oxygen evolution reaction (OER) is vital in improving the efficiency of renewable energy generation devices. Given the large numbers of possible binary and ternary metal oxide OER catalysts, high-throughput methods are necessary to accelerate the rate of discovery. Herein, Mn-based spinel oxide, Fe10 Co40 Mn50 O, is identified for the first time using high-throughput methods demonstrating remarkable catalytic activity (overpotential of 310 mV on fluorine-doped tin oxide (FTO) substrate and 237 mV on Ni foam at 10 mA cm-2 ). Using a combination of soft X-ray absorption spectroscopy and electrochemical measurements, the high catalytic activity is attributed to 1) the formation of multiple active sites in different geometric sites, tetrahedral and octahedral sites; and 2) the formation of active oxyhydroxide phase due to the strong interaction of Co2+ and Fe3+ . Structural and surface characterizations after OER show preservation of Fe10 Co40 Mn50 O surface structure highlighting its durability against irreversible redox damage on the catalytic surface. This work demonstrates the use of a high-throughput approach for the rapid identification of a new catalyst, provides a deeper understanding of catalyst design, and addresses the urgent need for a better and stable catalyst to target greener fuel.

Small molecule RAF265 as an antiviral therapy acts against HSV-1 by regulating cytoskeleton rearrangement and cellular translation machinery.

Host-targeting antivirals (HTAs) have received increasing attention for their potential as broad-spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost- and time- efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus-1 (HSV-1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B-RAF V600E, reduced viral loads of HSV-1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV-1.

Bacterial communities associated with mushrooms in the Qinghai-Tibet Plateau are shaped by soil parameters.

Fungi capable of producing fruit bodies are essential food and medicine resources. Despite recent advances in the study of microbial communities in mycorrhizospheres, little is known about the bacterial communities contained in fruit bodies. Using high-throughput sequencing, we investigated the bacterial communities in four species of mushrooms located on the alpine meadow and saline-alkali soil of the Qinghai-Tibet Plateau (QTP). Proteobacteria (51.7% on average) and Actinobacteria (28.2% on average) were the dominant phyla in all of the sampled fairy ring fruit bodies, and Acidobacteria (27.5% on average) and Proteobacteria (25.7% on average) dominated their adjacent soils. For the Agria. Bitorquis, Actinobacteria was the dominant phylum in its fruit body (67.5% on average) and adjacent soils (65.9% on average). The alpha diversity (i.e., Chao1, Shannon, Richness, and Simpson indexes) of the bacterial communities in the fruit bodies were significantly lower than those in the soil samples. All of the fungi shared more than half of their bacterial phyla and 16.2% of their total operational taxonomic units (OTUs) with their adjacent soil. Moreover, NH4+ and pH were the key factors associated with bacterial communities in the fruit bodies and soils, respectively. These results indicate that the fungi tend to create a unique niche that selects for specific members of the bacterial community. Using culture-dependent methods, we also isolated 27 bacterial species belonging to three phyla and five classes from fruit bodies and soils. The strains isolated will be useful for future research on interactions between mushroom-forming fungi and their bacterial endosymbionts.

Oral administration of Synechococcus sp. PCC7942 trans-vp19 and trans-vp (19+28) genes improve the immune and antioxidant capacity in Procambarus clarkii under white spot syndrome virus stress.

This study aimed to evaluate antioxidant capacity and protection from white spot syndrome virus (WSSV) challenge of Procambarus clarkii fed trans-vp19 and trans-vp (19 + 28) genes of Synechococcus sp. PCC7942 (Syn7942). P. clarkii were fed transgenic cyanobacteria continuously for 7 days, and then infected with WSSV after 12 h starvation. The daily mortality in each group was measured for 10 days and hepatopancreas and muscle of P. clarkii were examined for enzymes phenoloxidase (PO) activity, catalase (CAT) activity, glutathione peroxidase (GSH-px) activity, and malondialdehyde (MDA) concentration after immunization and viral challenge at different times. Compared with the WSSV-infected crayfish in positive control group (challenge and no vaccination) and wild type group (challenge, feeding wild-type Syn7942), vp19 group (challenge, feeding Syn7942 trans-vp19 gene) and vp (19 + 28) group [challenge, feeding Syn7942 trans-vp (19 + 28) genes] significantly improved the survival rate from 0% to 60% and 56.7%, respectively. Consistently, significantly greater PO, CAT, and GSH-px activity and significantly lower MDA concentration in the vp19 and vp (19 + 28) groups compared to the control group. These results demonstrate that the trans-vp19 and trans-vp (19 + 28) gene of Syn7942 significantly facilitated the immune and antioxidant capacity of crayfish. Therefore, the trans-vp19 and trans-vp (19 + 28) genes of Syn7942 could provide protection for crayfish as an anti-WSSV oral medication.

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Combining nanotechnology with monoclonal antibody drugs for rheumatoid arthritis treatments.

Rheumatoid arthritis (RA) is a systemic immune disease characterized by synovial inflammation. Patients with RA commonly experience significant damage to their hand and foot joints, which can lead to joint deformities and even disability. Traditional treatments have several clinical drawbacks, including unclear pharmacological mechanisms and serious side effects. However, the emergence of antibody drugs offers a promising approach to overcome these limitations by specifically targeting interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and other cytokines that are closely related to the onset of RA. This approach reduces the incidence of adverse effects and contributes to significant therapeutic outcomes. Furthermore, combining these antibody drugs with drug delivery nanosystems (DDSs) can improve their tissue accumulation and bioavailability.Herein, we provide a summary of the pathogenesis of RA, the available antibody drugs and DDSs that improve the efficacy of these drugs. However, several challenges need to be addressed in their clinical applications, including patient compliance, stability, immunogenicity, immunosupression, target and synergistic effects. We propose strategies to overcome these limitations. In summary, we are optimistic about the prospects of treating RA with antibody drugs, given their specific targeting mechanisms and the potential benefits of combining them with DDSs.

Tunable Magnetic Properties in Sr2FeReO6 Double-Perovskite.

Double-perovskite oxides have attracted recent attention due to their attractive functionalities and application potential. In this paper, we demonstrate the effect of dual controls, i.e., the deposition pressure of oxygen (PO2) and lattice mismatch (ε), on tuning magnetic properties in epitaxial double-perovskite Sr2FeReO6 films. In a nearly lattice matched Sr2FeReO6/SrTiO3 film, the ferrimagnetic-to-paramagnetic phase transition occurs when PO2 is reduced to 30 mTorr, probably due to the formation of Re4+ ions that replace the stoichiometric Re5+ to cause disorders of B-site ions. On the other hand, a large compressive strain or tensile strain shifts this critical PO2 to below 1 mTorr or above 40 mTorr, respectively. The observations can be attributed to the modulation of B-site ordering by epitaxial strain through affecting elemental valence. Our results provide a feasible way to expand the functional tunability of magnetic double-perovskite oxides that hold great promise for spintronic devices.

Coordination-Adaptive Polydentate Pseudorotaxane Ligand for Capturing Multiple Uranyl Species.

The propensity of uranyl for hydrolysis in aqueous environments prevents precise control of uranyl species in the scenarios of on-demand separation and tailored synthesis. Herein, using cucurbit[7]uril (CB[7]) as the macrocyclic molecule and 4,4'-bipyridine-N,N'-dioxide (DPO) as the string molecule, we propose a new kind of multidentate pseudorotaxane ligand, DPO@CB[7] for capturing uranyl species at different pH's. With the aprotic nature of DPO for metal coordination, the coordination ability of the DPO@CB[7] ligand is less affected by pH and can work in a wide range of pH's. Furthermore, by adaptive uranyl coordination, this aprotic pseudorotaxane ligand achieves effective recognition for different uranyl species ranging from monomeric to tetrameric originating from hydrolysis at varying pH's, and four novel uranyl-rotaxane compounds (URC1-4) are successfully obtained. Single-crystal X-ray diffraction analysis reveals that the DPO@CB[7] ligand coordinates with uranyl centers from monomeric to tetrameric in four different modes, as a result of structural flexibility of the DPO@CB[7] pseudorotaxane ligand. A detailed discussion for conformation flexibility of the DPO@CB[7] ligand has been conducted on the position changes of the DPO ligand trapped in the CB[7], which thus reveals good adaptivity of DPO@CB[7] that is noncovalently bonded as a supramolecular motif. In addition, characterization of the physicochemical properties of URC1 and URC2 with high phase purity, including powder X-ray diffraction (PXRD), infrared spectroscopy (IR), thermogravimetric analysis (TGA), and luminescence properties, are also provided. This work provides a good case of an adaptive pseudorotaxane ligand for the recognition and capture of different uranyl species and will bring valuable hints to the design of multifunctional supramolecular ligands for actinide separation in the future.

Synthesis of Trapen Ligand-Based U(IV) and Th(IV) 2-Phosphaethynolate Complexes and Comparison of Covalency with Corresponding Ti(IV) Analogues.

The involvement of the 2-phosphaethynolate anion species with ambident nucleophilic properties serves as an essential protocol for synthesizing oxygen-bound or phosphorus-bound complexes. This work mainly describes the synthesis and characterization of U, Th, and Ti phosphaethynolate complexes featuring a preferential O-coordination fashion. Among these complexes, the first examples of a Ti(IV)-OCP complex 3A, Th(IV)-OCP complex 3B, and U(IV)-OCP complex 3C were assembled by a salt metathesis reaction between M(TrapenTMS)(Cl) (M = Ti, Th, U) and NaOCP(dioxane)2.5 and were all crystallographically characterized. The structural similarity of this series of phosphaethynolate complexes allows us to compare the bonding properties of d- and f-block elements in the corresponding compounds. The well-established density functional theory (DFT) computational method was employed to explore the electronic structures and covalency in M-O bonding, and the results showed a consistent pattern. The calculation result showed that 2-phosphaethynolate complexes exhibited the covalency trend of U-O > Th-O > Ti-O due to the involvement of 5f orbitals.

Virus Dynamics and Decay in Evaporating Human Saliva Droplets on Fomites.

The transmission of most respiratory pathogens, including SARS-CoV-2, occurs via virus-containing respiratory droplets, and thus, factors that affect virus viability in droplet residues on surfaces are of critical medical and public health importance. Relative humidity (RH) is known to play a role in virus survival, with a U-shaped relationship between RH and virus viability. The mechanisms affecting virus viability in droplet residues, however, are unclear. This study examines the structure and evaporation dynamics of virus-containing saliva droplets on fomites and their impact on virus viability using four model viruses: vesicular stomatitis virus, herpes simplex virus 1, Newcastle disease virus, and coronavirus HCoV-OC43. The results support the hypothesis that the direct contact of antiviral proteins and virions within the "coffee ring" region of the droplet residue gives rise to the observed U-shaped relationship between virus viability and RH. Viruses survive much better at low and high RH, and their viability is substantially reduced at intermediate RH. A phenomenological theory explaining this phenomenon and a quantitative model analyzing and correlating the experimentally measured virus survivability are developed on the basis of the observations. The mechanisms by which RH affects virus viability are explored. At intermediate RH, antiviral proteins have optimal influence on virions because of their largest contact time and overlap area, which leads to the lowest level of virus activity.

A primary cardiac schwannoma of the right ventricle: a case report and literature review.

BACKGROUND: Primary cardiac schwannoma remains extremely rare and difficult to distinguish from other myocardial tumours. We report a case of cardiac schwannoma that occurred in the lateral wall of the right ventricle and grew in the myocardial walls. It is the third case of schwannoma that occurred in the free wall of the right ventricle. Moreover, we reviewed and summarised the literature for cases involving benign cardiac schwannomas. CASE PRESENTATION: We present a case of a 64-year-old woman who presented to our centre with syncope for 1-2 min. Echocardiogram and contrast-enhanced computed tomography subsequently revealed a 2.9 × 1.9 cm homogeneous mass originating from the anterior wall of the right ventricle. The patient underwent thoracotomy to resect the mass, which was pathologically verified as Schwann cell tumour. CONCLUSIONS: This is a rare case added to the limited existing literature on cardiac schwannoma. Comprehensive analysis of various imaging examinations is helpful to determine the extent of the tumour. Complete surgical resection is recommended for similar cases involving cardiac schwannomas, especially when the patient has related symptoms. Patients generally have a good prognosis. The pathogenesis of cardiac schwannoma needs further research in order to prevent and manage this rare lesion.

Disturbance of serum lipid metabolites and potential biomarkers in the Bleomycin model of pulmonary fibrosis in young mice.

BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking. METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms. RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools. CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.

Formation of halonitromethanes from methylamine in the presence of bromide during UV/Cl2 disinfection.

The UV/Cl2 process is commonly used to achieve a multiple-barrier disinfection and maintain residuals. The study chose methylamine as a precursor to study the formation of high-toxic halonitromethanes (HNMs) in the presence of bromide ions (Br-) during UV/Cl2 disinfection. The maximum yield of HNMs increased first and then decreased with increasing concentration of Br-. An excessively high concentration of Br- induced the maximum yield of HNMs in advance. The maximum bromine incorporation factor (BIF) increased, while the maximum bromine utilization factor (BUF) decreased with the increase of Br- concentration. The maximum yield of HNMs decreased as pH value increased from 6.0 to 8.0 due to the deprotonation process. The BUF value remained relatively higher under an acidic condition, while pH value had no evident influence on the BIF value. The maximum yield of HNMs and value of BUF maximized at a Cl2:Br- ratio of 12.5, whereas the BIF value remained relatively higher at low Cl2:Br- ratios (2.5 and 5). The amino group in methylamine was first halogenated, and then released into solution as inorganic nitrogen by the rupture of C-N bond or transformed to nitro group by oxidation and elimination pathways. The maximum yield of HNMs in real waters was higher than that in pure water due to the high content of dissolved organic carbon. Two real waters were sampled to verify the law of HNMs formation. This study helps to understand the HNMs formation (especially brominated species) when the UV/Cl2 process is adopted as a disinfection technique.