Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization

Significance For achieving efficient entry into host cells, viruses utilize multiple host factors for mediating the stepwise entry process. Sole expression of sodium taurocholate cotransporting polypeptide (NTCP), a cellular receptor for hepatitis B virus (HBV), is not sufficient for the efficient viral internalization into hepatocytes. Here, we identify epidermal growth factor receptor (EGFR) as a host factor that interacts with NTCP and mediates HBV internalization. Dissociation of the NTCP–EGFR interaction or functional depletion of EGFR attenuated the viral internalization to NTCP-expressing cells and infection. Our data suggest that HBV enters human hepatocytes using an intrinsic NTCP–EGFR complex as a driving force. EGFR is thus an entry cofactor required for HBV infection of the human liver. Sodium taurocholate cotransporting polypeptide (NTCP) is a host cell receptor required for hepatitis B virus (HBV) entry. However, the susceptibility of NTCP-expressing cells to HBV is diverse depending on the culture condition. Stimulation with epidermal growth factor (EGF) was found to potentiate cell susceptibility to HBV infection. Here, we show that EGF receptor (EGFR) plays a critical role in HBV virion internalization. In EGFR-knockdown cells, HBV or its preS1-specific fluorescence peptide attached to the cell surface, but its internalization was attenuated. PreS1 internalization and HBV infection could be rescued by complementation with functional EGFR. Interestingly, the HBV/preS1–NTCP complex at the cell surface was internalized concomitant with the endocytotic relocalization of EGFR. Molecular interaction between NTCP and EGFR was documented by immunoprecipitation assay. Upon dissociation from functional EGFR, NTCP no longer functioned to support viral infection, as demonstrated by either (i) the introduction of NTCP point mutation that disrupted its interaction with EGFR, (ii) the detrimental effect of decoy peptide interrupting the NTCP–EGFR interaction, or (iii) the pharmacological inactivation of EGFR. Together, these data support the crucial role of EGFR in mediating HBV–NTCP internalization into susceptible cells. EGFR thus provides a yet unidentified missing link from the cell-surface HBV–NTCP attachment to the viral invasion beyond the host cell membrane.
Page curve for fermionic Gaussian states

In a seminal paper, Page found the exact formula for the average entanglement entropy for a pure random state. We consider the analogous problem for the ensemble of pure fermionic Gaussian states, which plays a crucial role in the context of random free Hamiltonians. Using recent results from random matrix theory, we show that the average entanglement entropy of pure random fermionic Gaussian states in a subsystem of ${N}_{A}$ out of $N$ degrees of freedom is given by ${\ensuremath{\langle}{S}_{A}\ensuremath{\rangle}}_{\mathrm{G}}=(N\ensuremath{-}\frac{1}{2})\mathrm{\ensuremath{\Psi}}(2N)+(\frac{1}{4}\ensuremath{-}{N}_{A})\mathrm{\ensuremath{\Psi}}(N)+(\frac{1}{2}+{N}_{A}\ensuremath{-}N)\mathrm{\ensuremath{\Psi}}(2N\ensuremath{-}2{N}_{A})\ensuremath{-}\frac{1}{4}\mathrm{\ensuremath{\Psi}}(N\ensuremath{-}{N}_{A})\ensuremath{-}{N}_{A}$, where $\mathrm{\ensuremath{\Psi}}$ is the digamma function. Its asymptotic behavior in the thermodynamic limit is given by ${\ensuremath{\langle}{S}_{A}\ensuremath{\rangle}}_{\mathrm{G}}=N(log2\ensuremath{-}1)f+N(f\ensuremath{-}1)log(1\ensuremath{-}f)+\frac{1}{2}f+\frac{1}{4}log(1\ensuremath{-}f)\phantom{\rule{0.16em}{0ex}}+\phantom{\rule{0.16em}{0ex}}O(1/N)$, where $f={N}_{A}/N\ensuremath{\le}1/2$. Remarkably, its leading order agrees with the average over eigenstates of random quadratic Hamiltonians with number conservation, as found by \L{}yd\ifmmode \dot{z}\else \. {z}\fi{}ba, Rigol, and Vidmar. Finally, we compute the variance in the thermodynamic limit, given by the constant ${lim}_{N\ensuremath{\rightarrow}\ensuremath{\infty}}{(\mathrm{\ensuremath{\Delta}}{S}_{A})}_{\mathrm{G}}^{2}=\frac{1}{2}[f+{f}^{2}+log(1\ensuremath{-}f)]$.
Liquid vaporization actuated soft structures with active cooling and heat loss control

Soft robotic systems that are inspired by nature utilize soft materials to perform various tasks in diverse environments. One promising method to control their movement is by utilizing liquid vaporization. In most cases, liquid with high vapor pressure is injected into hollow cavities inside the elastomer. Heating the system vaporizes the liquid, and the structure is inflated by the generated gas. However, there is a significant time lag between powering the system and structural actuation due to the slow increase in temperature that is exacerbated by heat loss. Simply using materials with low thermal conductivity can improve actuation, but the reduced heat loss concurrently increases cooling time during the reversing process. Furthermore, underwater actuation through vaporization remains a challenge, since heat loss becomes even more significant. To address these issues, this study aims to develop a system that can actively control heat loss to enhance both actuation and cooling while performing consistently even in extreme environments. First, double-walled structures were fabricated with silicone elastomer to drastically lower thermal conductivity. Next, a thermoelectric device was installed on the bottom layer to heat and cool the sealed liquid by reversing current flow. The low thermal conductivity of the double-walled structure enhanced actuation performance, while actively cooling the system with the thermoelectric device accelerated the reversing process. Structures with single- and double-layered walls were tested underwater to validate their performance. Finite element models verified the effects of wall designs on heat transfer and structural mechanics. Demonstration of enhanced reversible actuation of the system was performed using a soft anemone-like structure operated underwater.
Soil Salinity Type Effects on the Relationship between the Electrical Conductivity and Salt Content for 1:5 Soil-to-Water Extract

Soil salinity severely affects soil ecosystem quality and crop production in semi-arid and arid regions. A vast quantity of data on soil salinity has been collected by research organizations of the Commonwealth of Independent States (CIS, formerly USSR) and many other countries over the last 70 years, but using them in the current international network (irrigation and reclamation strategy) is complicated. This is because in the CIS countries salinity was expressed by total soluble salts as a percentage on a dry-weight basis (total soluble salts, TSS, %) and eight salinity types (chemistry) determined by the ratios of the anions and cations (Cl−, SO42−, HCO3−, and Na+, Ca2+, Mg2+) in diluted soil water extract (soil/water = 1:5) without assessing electrical conductivity (EC). Measuring the EC (1:5) is more convenient, yet EC is not only affected by the concentration but also characteristics of the ions and the salinity chemistry. The objective of this study was to examine the relationship between EC and TSS of soils in a diluted extract (1:5) for eight classic salinity types. We analyzed extracts (1:5) of 1100 samples of a clayey soil (0–20 cm) collected from cultivated semi-arid and arid regions for EC, TSS, soluble cations (Na+, Ca2+, Mg2+), and anions (HCO3−, Cl−, SO42−). Results revealed that (i) the variation in the proportional relationships (R2 ≥ 0.91–0.98) between EC (0.12–5.6 dS m−1) and TSS (0.05–2.5%) could be related to salinity type, and (ii) the proportionality coefficient of the relationships (2.2 2–3.16) decreased in the following order of salinity type: SO4 < Cl(SO4)–HCO3 < Cl(HCO3)–SO4 < SO4 (HCO3)–Cl < Cl. The findings suggest that once the salinity type of the soil is established, EC (1:5) values can be safely used for the evaluation of the soil salinity degree in the irrigated land in the context of sustainable soil and crop management.
ADOPTION OF SOCIAL MEDIA MARKETING AMONG AGROPRENEURS IN PENINSULAR MALAYSIA

Social media has become one of the main platforms for businesses around the world to markettheir products or services. However, some entrepreneurs still feel doubtful whether social mediamarketing is effective enough compared to the traditional marketing on seeking attention fromtheir targeted audience based on the different generation. Besides, people still think that socialmedia is used as the medium for people around the world to socialize with everyone instead ofmarketing their product or services, especially agro-based products. Entrepreneurs also did not usesocial media marketing because they do not have the sufficient knowledge on how to fully utilizethe social media to market their product. This will hinder them from using social media marketingin their business because they might need more time and assistance to learn how to employ socialmedia marketing. Thus, the main objective of this study is to investigate the adoption of socialmedia marketing among agropreneurs in Peninsular Malaysia. Primary data was collected usingstructured questionnaire via online survey. The questionnaire have been distributed through socialmedia platforms and e-mailed to the targeted respondents using purposive sampling method. Atotal of 113 respondents from 12 states in Peninsular Malaysia was successfully participated inthis study. Data collected was analyzed using descriptive analysis, chi-square analysis and factoranalysis. The results of this study indicated that the adoption level of social media marketingamong agropreneurs in Peninsular Malaysia is on the medium high level and the highest socialmedia platform adopted is Facebook. Besides that, the results of chi-square analysis showed thatrespondent’s demographic and business profile including gender, age, education level and typesof agro-based business operated has an association with the adoption of social media marketingamong agropreneurs. The results of factor analysis discovered four factors that influencingadoption of social media marketing among agropreneurs namely; perceived usefulness, socialinfluence, perceived ease of use and facilitating conditions. Hence, entrepreneurs that alreadyadopted social media marketing should cooperate and create an association of online agropreneursto encourage other entrepreneurs so that they start adopting social media marketing.
Direct Cobamide Remodeling via Additional Function of Cobamide Biosynthesis Protein CobS from Vibrio cholerae

Cobamides are widespread cofactors that mediate metabolic interactions in complex microbial communities. Few studies directly examine cobamide profiles, but several have shown that mammalian gastrointestinal tracts are rich in cobamide analogs. ABSTRACT Vitamin B12 belongs to a family of structurally diverse cofactors with over a dozen natural analogs, collectively referred to as cobamides. Most bacteria encode cobamide-dependent enzymes, many of which can only utilize a subset of cobamide analogs. Some bacteria employ a mechanism called cobamide remodeling, a process in which cobamides are converted into other analogs to ensure that compatible cobamides are available in the cell. Here, we characterize an additional pathway for cobamide remodeling that is distinct from the previously characterized ones. Cobamide synthase (CobS) is an enzyme required for cobamide biosynthesis that attaches the lower ligand moiety in which the base varies between analogs. In a heterologous model system, we previously showed that Vibrio cholerae CobS (VcCobS) unexpectedly conferred remodeling activity in addition to performing the known cobamide biosynthesis reaction. Here, we show that additional Vibrio species perform the same remodeling reaction, and we further characterize VcCobS-mediated remodeling using bacterial genetics and in vitro assays. We demonstrate that VcCobS acts upon the cobamide pseudocobalamin directly to remodel it, a mechanism which differs from the known remodeling pathways in which cobamides are first cleaved into biosynthetic intermediates. This suggests that some CobS homologs have the additional function of cobamide remodeling, and we propose the term “direct remodeling” for this process. This characterization of yet another pathway for remodeling suggests that cobamide profiles are highly dynamic in polymicrobial environments, with remodeling pathways conferring a competitive advantage. IMPORTANCE Cobamides are widespread cofactors that mediate metabolic interactions in complex microbial communities. Few studies directly examine cobamide profiles, but several have shown that mammalian gastrointestinal tracts are rich in cobamide analogs. Studies of intestinal bacteria, including beneficial commensals and pathogens, show variation in the ability to produce and utilize different cobamides. Some bacteria can convert imported cobamides into compatible analogs in a process called remodeling. Recent discoveries of additional cobamide remodeling pathways, including this work, suggest that remodeling is an important factor in cobamide dynamics. Characterization of such pathways is critical in understanding cobamide flux and nutrient cross-feeding in polymicrobial communities, and it facilitates the establishment of microbiome manipulation strategies via modulation of cobamide profiles.
Realization of Osteolysis, Angiogenesis, Immunosuppression, and Drug Resistance by Extracellular Vesicles: Roles of RNAs and Proteins in Their Cargoes and of Ectonucleotidases of the Immunosuppressive Adenosinergic Noncanonical Pathway in the Bone Marrow Niche of Multiple Myeloma

Simple Summary Multiple myeloma (MM) is a disease that extensively involves bone, and angiogenesis and immunosuppression are important processes in the development of MM. Proteasome inhibitors and immunomodulatory drugs remarkably improve the survival of MM patients. However, MM is still an incurable disease that rapidly becomes resistant to these drugs. There is robust evidence that extracellular vesicles (EVs) contribute to cancer metastasis. Osteoclasts, in addition to immunosuppressive cells in the bone marrow (BM), are key players in osteolysis and immunosuppression. BM stromal cells and MM cells secrete EVs through which they communicate with each other: EVs, in fact, contain proteins, small RNAs, and long non-coding RNAs that mediate this communication and contribute to angiogenesis, osteolysis, and cancer dissemination and drug resistance. Ectoenzymes are expressed in myeloma cells, osteoclasts, and stromal cells and produce immunosuppressive adenosine. Recently, an antibody targeting CD38, an ectoenzyme, has been shown to improve the survival of patients with MM. Thus, understanding the properties of EV and ectoenzymes will help elucidate key processes of MM development. Abstract Angiogenesis and immunosuppression promote multiple myeloma (MM) development, and osteolysis is a primary feature of MM. Although immunomodulatory drugs and proteasome inhibitors (PIs) markedly improve the survival of patients with MM, this disease remains incurable. In the bone marrow niche, a chain of ectoenzymes, including CD38, produce immunosuppressive adenosine, inhibiting T cell proliferation as well as immunosuppressive cells. Therefore, anti-CD38 antibodies targeting myeloma cells have the potential to restore T cell responses to myeloma cells. Meanwhile extracellular vesicles (EVs) containing microRNAs, proteins such as cytokines and chemokines, long noncoding RNAs, and PIWI-interacting RNAs have been shown to act as communication tools in myeloma cell/microenvironment interactions. Via EVs, mesenchymal stem cells allow myeloma cell dissemination and confer PI resistance, whereas myeloma cells promote angiogenesis, myeloid-derived suppressor cell proliferation, and osteoclast differentiation and inhibit osteoblast differentiation. In this review, to understand key processes of MM development involving communication between myeloma cells and other cells in the tumor microenvironment, EV cargo and the non-canonical adenosinergic pathway are introduced, and ectoenzymes and EVs are discussed as potential druggable targets for the treatment of MM patients.
The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel variant of concern (VOC) designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and shown to enhance infectivity in vitro and decrease antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both strains exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most body weight loss among all 3 lineages. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three strains. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the upper respiratory tract (URT) but not in the lungs. In multi-virus in-vivo competition experiments, we found that epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the URT gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) variants in hamsters. These results demonstrate enhanced virulence and high relative fitness of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) strain. Author Summary In the last 12 months new variants of SARS-CoV-2 have arisen in the UK, South Africa, Brazil, India, and California. New SARS-CoV-2 variants will continue to emerge for the foreseeable future in the human population and the potential for these new variants to produce severe disease and evade vaccines needs to be understood. In this study, we used the hamster model to determine the epsilon (B.1.427/429) SARS-CoV-2 strains that emerged in California in late 2020 cause more severe disease and infected hamsters have higher viral loads in the upper respiratory tract compared to the prior B.1 (614G) strain. These findings are consistent with human clinical data and help explain the emergence and rapid spread of this strain in early 2021.
Isolation and Characterization of Novel Lytic Phages Infecting Multidrug-Resistant Escherichia coli

Urinary tract infections affect approximately 150 million people annually. The current antibiotic resistance crisis demands the development of novel therapeutic alternatives. ABSTRACT Urinary tract infections (UTIs) are the second most frequent bacterial infections worldwide, with Escherichia coli being the main causative agent. The increase of antibiotic-resistance determinants among isolates from clinical samples, including UTIs, makes the development of novel therapeutic strategies a necessity. In this context, the use of bacteriophages as a therapeutic alternative has been proposed, due to their ability to efficiently kill bacteria. In this work, we isolated and characterized three novel bacteriophages, microbes laboratory phage 1 (MLP1), MLP2, and MLP3, belonging to the Chaseviridae, Myoviridae, and Podoviridae families, respectively. These phages efficiently infect and kill laboratory reference strains and multidrug-resistant clinical E. coli isolates from patients with diagnosed UTIs. Interestingly, these phages are also able to infect intestinal pathogenic Escherichia coli strains, such as enteroaggregative E. coli and diffusely adherent E. coli. Our data show that the MLP phages recognize different regions of the lipopolysaccharide (LPS) molecule, an important virulence factor in bacteria that is also highly variable among different E. coli strains. Altogether, our results suggest that these phages may represent an interesting alternative for the treatment of antibiotic-resistant E. coli. IMPORTANCE Urinary tract infections affect approximately 150 million people annually. The current antibiotic resistance crisis demands the development of novel therapeutic alternatives. Our results show that three novel phages, MLP1, MLP2, and MLP3 are able to infect both laboratory and multidrug-resistant clinical isolates of Escherichia coli. Since these phages (i) efficiently kill antibiotic-resistant clinical isolates of uropathogenic Escherichia coli (UPEC), (ii) recognize different portions of the LPS molecule, and (iii) are able to efficiently infect intestinal pathogenic Escherichia coli hosts, we believe that these novel phages are good candidates to be used as a therapeutic alternative to treat antibiotic-resistant E. coli strains generating urinary tract and/or intestinal infections.
Dynamic Expression of EpCAM in Primary and Metastatic Lung Cancer Is Controlled by Both Genetic and Epigenetic Mechanisms

Simple Summary Epithelial cell adhesion molecule (EpCAM) is a tumor marker widely used in both basic studies and clinics. However, our study demonstrates that EpCAM expression is strongly upregulated by gene amplification and promoter hypomethylation in primary lung tumors, but severely downregulated by epigenetic repression (including promoter hypermethylation and histone deacetylation), tumor-associated macrophages (TAMs), and TAMs-derived TGFβ in metastatic lung tumors. DNMT inhibitor 5-aza-dC, HDAC inhibitor MS-275, and TGFβ neutralizing antibody are able to restore EpCAM expression in highly metastatic lung cancer cells. These findings disclose that multiple mechanisms contribute to the dynamic expression patterns of EpCAM in primary and metastatic lung tumors, redefining the application of EpCAM as a biomarker in tumor cell identification and isolation in specific cancers and clinical stages. Abstract Although great progress has been achieved in cancer treatment in the past decades, lung cancer remains the leading cause of cancer death, which is partially caused by the fact that most lung cancers are diagnosed at advanced stages. To improve the sensitivity and specificity of lung cancer diagnosis, the underlying mechanisms of current diagnosis methods are in urgent need to be explored. Herein, we find that the expression of EpCAM, the widely used molecular marker for tumor cell characterization and isolation, is strongly upregulated in primary lung tumors, which is caused by both gene amplification and promoter hypomethylation. In contrast, EpCAM expression is severely repressed in metastatic lung tumors, which can be reversed by epigenetic drugs, DNMT inhibitor 5-aza-dC and HDAC inhibitor MS-275. Moreover, tumor-associated macrophages (TAMs) impede EpCAM expression probably through TGFβ-induced EMT signaling. These findings unveil the dynamic expression patterns of EpCAM and differential roles of epigenetic modification in EpCAM expression in primary and metastatic lung tumors, providing novel insights into tumor cell isolation and lung cancer diagnosis.