Turnover Intention Model: Self- Determination Theory Approach: Acces la Success

The purpose of this study is to examine and analyze the influence of mental workload and person-organization fit on turnover intention, using basic psychological needs frustration (BPNF) as the intervening variable in the hospital in Daerah Istimewa Yogyakarta. The sample of this study is vocational nurse in the hospital in Daerah Istimewa Yogyakarta. The sample is carried out through survey from 153 respondents, which is processed using Structural Equation Modeling (SEM) method. This study finds that mental workload does not have direct influence on turnover intention, but it is mediated (full mediation) by need for competence frustration and need for relatedness frustration. Person-organization fit has a positive influence on need for autonomy frustration. However, person-organization fit does not have an influence on turnover intention, and basic psychological needs does not mediate the relationship of these variables. This study also found that the category of mental workload is quite low, person-organization fit is low, basic psychological needs frustration is quite low, and turnover intention is low. Nurse has the extrinsic motivation of identified regulation, thus hospital leaders should bring their motivation from identified regulation to intrinsic motivation, through internalization by establishing supportive work environment, namely Islamic spiritual workplace (ISW), with basic psychological needs supporting in each of its dimension. This study is expected to be a reference for practitioners in human resource management, especially regarding human resource retention function through the implementation of ISW. ISW contributes to lower mental workload, the increase of person-organization fit, establishment of basic psychological need satisfaction, as well as the decrease of basic psychological needs frustration and turnover intention.

HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway.

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a specific interaction with the PEDV S protein, and positive regulation of PEDV infection was validated by knockdown and overexpression tests. Further studies verified the role of HSPA5 in viral attachment and internalization. In addition, we found that HSPA5 interacts with S proteins through its nucleotide-binding structural domain (NBD) and that polyclonal antibodies can block viral infection. In detail, HSPA5 was found to be involved in viral trafficking via the endo-/lysosomal pathway. Inhibition of HSPA5 activity during internalization would reduce the subcellular colocalization of PEDV with lysosomes in the endo-/lysosomal pathway. Together, these findings show that HSPA5 is a novel PEDV potential target for the creation of therapeutic drugs. IMPORTANCE PEDV infection causes severe piglet mortality and threatens the global pig industry. However, the complex invasion mechanism of PEDV makes its prevention and control difficult. Here, we determined that HSPA5 is a novel target for PEDV which interacts with its S protein and is involved in viral attachment and internalization, influencing its transport via the endo-/lysosomal pathway. Our work extends knowledge about the relationship between the PEDV S and host proteins and provides a new therapeutic target against PEDV infection.

Human Adenovirus Type 26 Infection Mediated by αvß3 Integrin Is Caveolin-1-Dependent.

Human adenovirus type 26 (HAdV26) has been recognized as a promising platform for vaccine vector development, and very recently vaccine against COVID-19 based on HAdV26 was authorized for emergency use. Nevertheless, basic biology of this virus, namely, pathway which HAdV26 uses to enter the cell, is still insufficiently known. We have shown here that HAdV26 infection of human epithelial cells expressing low amount of αvß3 integrin involves clathrin and is caveolin-1-independent, while HAdV26 infection of cells with high amount of αvß3 integrin does not involve clathrin but is caveolin-1-dependent. Thus, this study demonstrates that caveolin-1 is limiting factor in αvß3 integrin-mediated HAdV26 infection. Regardless of αvß3 integrin expression, HAdV26 infection involves dynamin-2. Our data provide for the first-time description of HAdV26 cell entry pathway, hence increase our knowledge of HAdV26 infection. Knowing that functionality of adenovirus vector is influenced by its cell entry pathway and intracellular trafficking, our results will contribute to better understanding of HAdV26 immunogenicity and antigen presentation when used as vaccine vector. IMPORTANCE In order to fulfill its role as a vector, adenovirus needs to successfully deliver its DNA genome to the host nucleus, a process highly influenced by adenovirus intracellular translocation. Thus, cell entry pathway and intracellular trafficking determine functionality of human adenovirus-based vectors. Endocytosis of HAdV26, currently extensively studied as a vaccine vector, has not been described so far. We present here that HAdV26 infection of human epithelial cells with high expression of αvß3 integrin, one of the putative HAdV26 receptors, is caveolin-1- and partially dynamin-2-dependent. Since caveolin containing domains provide a unique environment for specific signaling events and participate in inflammatory signaling one can imagine that directing HAdV26 cell entry toward caveolin-1-mediate pathway might play role in immunogenicity of this virus. Therefore, our results contribute to better understanding of HAdV26 infection pathway, hence, can be helpful in explaining induction of immune response and antigen presentation by HAdV26-based vaccine vector.

Doing good or looking good: how socially responsible human resource management practices influence employees' CSR-specific performance

PurposeThis study examines whether, how and when socially responsible human resource management (SRHRM) practices increase employees' in-role and extra-role corporate social responsibility (CSR) performance.Design/methodology/approachThis study uses data from 422 employees of 68 companies.FindingsSRHRM improves employees' in-role CSR-specific performance via impression management motivation and enhance extra-role CSR-specific performance via prosocial motivation. Moral identity symbolization strengthens the relationship between SRHRM and impression management motivation, and moral identity internalization reinforces the relationship between SRHRM and prosocial motivation. The authors also propose mediated moderation models.Practical implicationsThis study indicates that company can adopt SRHRM practices to improve employees' in-role and extra-role CSR-specific performance.Originality/valueThis study reveals how and when SRHRM practices influence employees' CSR-specific performance and sheds light on the social impacts of SRHRM.

Radiologic and Endoscopic Treatment for a Disconnected Pancreatic Duct Syndrome Associated to Percutaneous Pancreatic Fistula: Achieving the "Internalization of the Fistula"

Background and aim: A 40-year-old male was referred to our institute for the management of a percutaneous pancreatic fistula after acute pancreatitis due to SARS-COV2 infection. He developed a peripancreatic collection(PPC) which was percutaneously drained due to infection. After the resolution of PPC, a percutaneous leakage of the main pancreatic duct (MPD) was observed, so he underwent Endoscopic Retrograde ColangioPancreatography(ERCP) with biliary plus pancreatic sphincterotomy and placement of both pancreatic and biliary stent without resolution of the leak. Material(s) and Method(s): Then he was referred to our institution, where initial management included ERCP with placement of two trans-papillary pancreatic stents and the removal of percutaneous catheter, but the fistula kept to drain. Result(s): A multidisciplinary-board decided to perform a rendezvous with interventional radiology to facilitate an endoscopic ultrasound(EUS) trans-gastric drainage of the pancreatic area draining in the percutaneous fistula. Conclusion(s): The procedure included an initial ERCP with replacement of the two pancreatic stents while the radiologist places percutaneously a guidewire through the fistula to the pancreatic point of leakage into MPD. After that, EUS identified the point in which the percutaneous guidewire was getting into the MPD and a trans-gastric EUS-guided insertion of a guidewire achieved the MPD through a 19-Gauge needle. The latter guidewire crossed the percutaneous fistula and came out. At that point, a dilation up to 10 mm was performed to create a trans-gastric pancreatic fistula. The next step was to insert percutaneously a double pigtail(10 Fr) releasing the distal side into the stomach and the proximal side into the main pancreatic duct in order to stabilize the neo-fistula. Another trans-gastric plastic stent was endoscopically placed through the pancreato-gastric neo-fistula. At the end, injection of contrast dye through the percutaneous fistula showed a complete drainage into stomach. In conclusion, the procedure achieved the complete exclusion and resolution of the pancreatic-cutaneous fistula.Copyright © 2023. Editrice Gastroenterologica Italiana S.r.l.

Domestic violence in developing countries: An evidence from Bangladesh

Women all over the world face a multitude of issues daily. Unfortunately, one of the most common and tragic concerns that women face, especially those in third world countries, is domestic violence. This research paper has tried to find out and analyze the trend of domestic violence during this current period of lockdown and social distancing measures, which the COVID-19 pandemic has necessitated. During our investigations, a few variables intrigued us;these variables do not lead to a simple, uncomplicated conclusion on the occurrence of domestic violence. On the contrary, the pool of 350 respondents (especially from urban areas), which include homemakers and working women alike, education was one such variable that played a pivotal role in preventing domestic violence. Another variable was the effect of social stigma;because many women have internalized the impact of spousal and familial abuse, most of them find it incredibly difficult, if not impossible, to speak up about the struggles they face. We have made use of logistic regression models to verify the independent variables and their validity.

Tight junction protein occludin is an internalization factor for SARS-CoV-2 infection and mediates virus cell-to-cell transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads efficiently by spike-mediated, direct cell-to-cell transmission. However, the underlying mechanism is poorly understood. Herein, we demonstrate that the tight junction protein occludin (OCLN) is critical to this process. SARS-CoV-2 infection alters OCLN distribution and expression and causes syncytium formation that leads to viral spread. OCLN knockdown fails to alter SARS-CoV-2 binding but significantly lowers internalization, syncytium formation, and transmission. OCLN overexpression also has no effect on virus binding but enhances virus internalization, cell-to-cell transmission, and replication. OCLN directly interacts with the SARS-CoV-2 spike, and the endosomal entry pathway is involved in OCLN-mediated cell-to-cell fusion rather than in the cell surface entry pathway. All SARS-CoV-2 strains tested (prototypic, alpha, beta, gamma, delta, kappa, and omicron) are dependent on OCLN for cell-to-cell transmission, although the extent of syncytium formation differs between strains. We conclude that SARS-CoV-2 utilizes OCLN as an internalization factor for cell-to-cell transmission.

Cellular Senescence and COVID-19

Older adults are at a higher risk of developing serious illness and mortality from COVID-19. Among a multitude of factors, cellular senescence associated with ageing, obesity, cardiovascular diseases, and diabetes seems to be statistically correlated with severe SARS-CoV-2 infections and mortality. Surface proteins such as vimentin and CD26 that are differentially ex-pressed on senescent cells seem important for SARS-CoV-2 attachment and internalization. Potential therapeutic agents against this novel virus also exhibit senolytic and anti-inflammatory actions, implicating that their beneficial effects could, in part, be attributed to their senescent cell removal and the associated inflammatory phenotype neutralizing properties. Elucidating the underlying molecular mechanisms that connect cellular senescence and severity of SARS-CoV-2 infection might help direct towards development of effective therapeutics for elderly patients of COVID-19.Copyright © 2021 Bentham Science Publishers.

Undergraduate students and the COVID-19 pandemic: A look-back at first-year constructs of psychological adjustment, implications for clinicians and college administrators

The COVID-19 pandemic created significant challenges for college students and for the clinicians and college administrators who work with students. To better understand the challenges, we evaluated the impact of pandemic disruptions on the psychological adjustment of 1,062 undergraduate students during the first academic year of the pandemic (fall semester 2020, spring semester 2021). Adjustment (American Psychiatric Association [APA], 2013) and the theory of planned behavior (TPB;Ajzen, 1985, 1991) were used as conceptual references for the study. Students completed an online survey with items reflecting their concerns about the pandemic (The Healthy Minds Network [HMN], 2020);items comparing their prepandemic mental status to their current mental status (HMN, 2020);and standardized assessments of anxiety, depression, and personality (APA, n.d.). Comparisons were made between students living (a) on the college campus in a dormitory;(b) off campus within commuting distance to the college;and (c) away from the college in another city, state, or country. Consistent with other peer-reviewed studies, our students showed adjustment challenges and a decline in functional behavior (e.g., Chirikov et al., 2020). Two principal components reflecting adjustment and the TPB were identified: internalized concerns about the pandemic, and externalized responses to the pandemic. Students, regardless of living situation, reported higher levels of internalized psychological distress. Students living on campus showed more externalized adjustment challenges including an increase in alcohol and substance use, and a decline in academic performance. Recommendations focused on reducing risk factors and increasing protective and healthy lifestyle practices at college administration and clinical levels. (PsycInfo Database Record (c) 2023 APA, all rights reserved) Impact Statement Undergraduate college students had difficulty adjusting to pandemic disruptions as measured by changes in anxiety, depression, loneliness, psychological distress, alcohol and substance use, and academic performance. Younger students, living on campus, were more challenged than their peers who were not living on campus. Recommendations focused on reducing risk factors and increasing protective and healthy lifestyle practices at college administration and clinical levels. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Analyzing Impact of Technology-Facilitated Knowledge Creation on Student Satisfaction in Distance Learning Education

Although Covid-19 cases are continuing to decrease, the practice of online learning has become common in education. Many education institutions have online classes besides face-to-face classes. However, many research reported several problems in distance learning practice mainly because of the limitation of interactive conversation and learning activities and finally lead to an ineffective knowledge creation process. It is reported that in a distance learning setting during the pandemic, the motivation and participation rate decreased while the absence and dropout rates increased. Knowledge conversion is a term to reflect the acquisition of new know-how or tacit knowledge from the learning activities. Currently, various technology vendor keeps making innovations to solve this problem, and available technologies that can be utilized to support distance learning education are increasing. Therefore, this paper aims to know the impact of the knowledge creation process on student satisfaction and explain how to utilize technologies throughout the knowledge creation chain. Based on the statistical analysis it is found that the knowledge creation process that is represented using the SECI model simultaneously has a significant positive effect on student satisfaction. This means all phases in SECI (socialization, externalization, combination, and internalization) are simultaneously able to improve student satisfaction. However, partially, only socialization and internalization that has a significant positive impact on student satisfaction, which indicates these two factors partially could lead to better student satisfaction if it is planned and managed appropriately. This paper also constructs a matrix that helps education practitioners choose the right technology for each knowledge creation phase. © 2022 IEEE.

"Thin and muscular": A cross-sectional mixed methods study of people's descriptions of health

As weight status is frequently associated with health and the COVID-19 pandemic has raised attention to weight status, we used a cross-sectional mixed-methods design to explore how weight status or body size is described when defining health. We recruited 288 participants who were 18 years and older and living in the United States to complete a study about health and health behaviors during the pandemic. First, we used directed content analysis to explore if and how weight status/body size is described when asked to define health. Next, we used intensity sampling and a constant comparison approach to assess whether descriptions of health differed by diagnosis of a chronic disease, sex, and weight bias internalization. Seventy percent (n = 202) of participants described an aspect of weight, body size, or shape when defining health, the majority of which (65%) indicated someone could be unhealthy due to their weight or size. Only 29% (n = 84) of participants implied or directly stated a person could be healthy regardless of weight or size. There were no significant differences in the description of health by chronic disease status or weight bias internalization. Women included health behaviors more frequently than men. Our findings indicate that weight was inextricably linked with health among most adults in the United States. To promote health and reduce the damaging effects of weight stigma, it is imperative that preventive interventions and policies include weight-inclusive messages that underscore the importance of the multiple indicators of health, beyond weight and size. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The TGEV Membrane Protein Interacts with HSC70 To Direct Virus Internalization through Clathrin-Mediated Endocytosis.

Coronavirus membrane protein is a major component of the viral envelope and plays a central role in the viral life cycle. Studies of the coronavirus membrane protein (M) have mainly focused on its role in viral assembly and budding, but whether M protein is involved in the initial stage of viral replication remains unclear. In this study, eight proteins in transmissible gastroenteritis virus (TGEV)-infected cells coimmunoprecipitated with monoclonal antibodies (MAb) against M protein in PK-15 cells, heat shock cognate protein 70 (HSC70), and clathrin were identified by matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry (MALDI-TOF MS). Further studies demonstrated that HSC70 and TGEV M colocalized on the cell surface in early stages of TGEV infection; specifically, HSC70 bound M protein through its substrate-binding domain (SBD) and preincubation of TGEV with anti-M serum to block the interaction of M and HSC70 reduced the internalization of TGEV, thus demonstrating that the M-HSC70 interaction mediates the internalization of TGEV. Remarkably, the process of internalization was dependent on clathrin-mediated endocytosis (CME) in PK-15 cells. Furthermore, inhibition of the ATPase activity of HSC70 reduced the efficiency of CME. Collectively, our results indicated that HSC70 is a newly identified host factor involved in TGEV infection. Taken together, our findings clearly illustrate a novel role for TGEV M protein in the viral life cycle and present a unique strategy used by HSC70 to promote TGEV infection in which the interaction with M protein directs viral internalization. These studies provide new insights into the life cycle of coronaviruses. IMPORTANCE TGEV is the causative agent of porcine diarrhea, a viral disease that economically affects the pig industry in many countries. However, the molecular mechanisms underlying viral replication remain incompletely understood. Here, we provide evidence of a previously undescribed role of M protein in viral replication during early stages. We also identified HSC70 as a new host factor affecting TGEV infection. We demonstrate that the interaction between M and HSC70 directs TGEV internalization in a manner dependent on CME, thus revealing a novel mechanism for TGEV replication. We believe that this study may change our understanding of the first steps of infection of cells with coronavirus. This study should facilitate the development of anti-TGEV therapeutic agents by targeting the host factors and may provide a new strategy for the control of porcine diarrhea.

Transferrin Receptor Protein 1 Cooperates with mGluR2 To Mediate the Internalization of Rabies Virus and SARS-CoV-2.

Identification of bona fide functional receptors and elucidation of the mechanism of receptor-mediated virus entry are important to reveal targets for developing therapeutics against rabies virus (RABV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our previous studies suggest that metabotropic glutamate receptor subtype 2 (mGluR2) functions as an entry receptor for RABV in vitro, and is an important internalization factor for SARS-CoV-2 in vitro and in vivo. Here, we demonstrate that mGluR2 facilitates RABV internalization in vitro and infection in vivo. We found that transferrin receptor 1 (TfR1) interacts with mGluR2 and internalizes with mGluR2 and RABV in the same clathrin-coated pit. Knockdown of TfR1 blocks agonist-triggered internalization of mGluR2. Importantly, TfR1 also interacts with the SARS-CoV-2 spike protein and is important for SARS-CoV-2 internalization. Our findings identify a novel axis (mGluR2-TfR1 axis) used by RABV and SARS-CoV-2 for entry, and reveal TfR1 as a potential target for therapeutics against RABV and SARS-CoV-2. IMPORTANCE We previously found that metabotropic glutamate receptor subtype 2 (mGluR2) is an entry receptor for RABV in vitro, and an important internalization factor for SARS-CoV-2 in vitro and in vivo. However, whether mGluR2 is required for RABV infection in vivo was unknown. In addition, how mGluR2 mediates the internalization of RABV and SARS-CoV-2 needed to be resolved. Here, we found that mGluR2 gene knockout mice survived a lethal challenge with RABV. To our knowledge, mGluR2 is the first host factor to be definitively shown to play an important role in RABV street virus infection in vivo. We further found that transferrin receptor protein 1 (TfR1) directly interacts and cooperates with mGluR2 to regulate the endocytosis of RABV and SARS-CoV-2. Our study identifies a novel axis (mGluR2-TfR1 axis) used by RABV and SARS-CoV-2 for entry and opens a new door for the development of therapeutics against RABV and SARS-CoV-2.

Phytochemicals Against SARS-COV-2 Infection

Natural Product Communications Special Collection "Phytochemicals against SARS-COV-2 Infection" accepted 13 manuscripts, represented by 2 reviews, 9 original articles, and 1 letter to the editor. These deal with the use of traditional medicines, the use of network pharmacology, and docking studies to identify active compounds with prominent binding to various receptors responsible for internalization and replication, such as ACE2, S-protein, Mpro, PLpro, RdRp, and NSP15 endoribonuclease, as well as the possible use of phytochemicals against virus-associated inflammation. Copyright © The Author(s) 2023.

THE WORLD HEALTH ORGANIZATION: THE COVID-19 PANDEMIC AND TRANSNATIONAL LAW

The reflections made in this writing, bring to discussion the importance of transnational law, in the face of the occurrence of the current pandemic. From this, considerations are made about the transnational law produced by the WHO against Covid-19. Also, an analysis is made of the central categories and their relationship with the prefix ‘trans-' and transnational law. Subsequently, the WHO is discussed, its emergence and performance in the elaboration of a transnational legal framework to be considered when internalizing its guidelines by each Member State. In the context of final considerations, it is emphasized, in addition to the importance that should be attributed to transnational law that the work of the WHO, as a transnational actor, practices materialized acts such as transnational law, both in terms of guidance and in connection with public health matters. The methodology used was based on the inductive method, using the bibliographic research.

Spatial and temporal distances in a virtual global world: Lessons from the COVID-19 pandemic.

The experience of COVID-19 prompted us to rethink the imperatives of distance for the organization of value-creating activities globally. We advance a conceptualization of distance as representing separation in both space and time and posit that these distance dimensions represent different kinds of separation and require varied theoretical attention. We delineate the intrinsic qualities of spatial and temporal distances and theorize the impact of this extended conceptualization of distance on major tenets of international business theory and their predictions regarding the patterns of international business activity. We illustrate the ways by which varying configurations of spatial and temporal distances serve different value-creating activities and draw their implications for countries' global integration. We advance a call for more attention to time and temporal distance and their impact on the ways firms organize their value-creating activities in an increasingly virtual world.

L'expérience de COVID-19 nous a incités à repenser les impératifs de la distance pour l'organisation d'activités créatrices de valeur au niveau mondial. Nous conceptualisons la distance comme un construit représentant la séparation à la fois dans l'espace et dans le temps, et postulons que ces dimensions de la distance représentent différents types de séparation et nécessitent une attention théorique variée. Nous spécifions les qualités intrinsèques des distances temporelles et spatiales, et théorisons l'impact de cette conceptualisation étendue de la distance sur les principaux principes de la théorie des affaires internationales et leurs prédictions en matière de configurations d'activité en commerce international. Nous illustrons les façons dont diverses configurations de distances spatiales et temporelles servent différentes activités créatrices de valeur, et élaborons les implications pour l'intégration mondiale des pays. Nous appelons à accorder davantage d'attention au temps et à la distance temporelle, ainsi qu'à leur impact sur la manière dont les entreprises organisent leurs activités créatrices de valeur dans un monde de plus en plus virtuel.

La experiencia de COVID-19 nos instó repensar los imperativos de la distancia para la organización de actividades de creación de valor a nivel mundial. Avanzamos una conceptualización de la distancia como representación de la separación tanto en el espacio como en el tiempo y planteamos que estas dimensiones de la distancia representan diferentes tipos de separación y requieren una atención teórica variada. Delineamos las cualidades intrínsecas de las distancias espaciales y temporales y teorizamos el impacto de esta conceptualización ampliada de la distancia en los principales postulados de la teoría de los negocios internacionales y sus predicciones en relación con los patrones de la actividad de negocios internacionales. Ilustramos el modo en que las distintas configuraciones de las distancias espaciales y temporales sirven para diferentes actividades de creación de valor y extraemos sus implicaciones para la integración global de los países. Hacemos un llamamiento para que se preste más atención a la distancia temporal y al tiempo y a su impacto en la forma en que las empresas organizan sus actividades de creación de valor en un mundo cada vez más virtual.

A experiência do COVID-19 nos levou a repensar os imperativos de distância para a organização de atividades de criação de valor globalmente. Avançamos uma conceituação de distância como representação de separação tanto em espaço quanto em tempo e postulamos que essas dimensões de distância representam diferentes tipos de separação e requerem atenção teórica distinta. Delineamos as qualidades intrínsecas das distâncias espaciais e temporais e teorizamos o impacto dessa conceituação estendida de distância nos principais pilares da teoria em negócios internacionais e suas previsões a respeito dos padrões de atividade em negócios internacionais. Ilustramos formas pelas quais distintas configurações de distâncias espaciais e temporais atendem a diferentes atividades de criação de valor e descrevemos suas implicações para a integração global de países. Propomos um apelo por maior atenção a tempo e distância temporal e seu impacto nas maneiras pelas quais empresas organizam suas atividades de criação de valor em um mundo cada vez mais virtual.

Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process.

Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals.

Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by N-Acetylcysteine Irrespective of the Oxidoreductive Environment.

The binding of SARS-CoV-2 spikes to the cell receptor angiotensin-converting enzyme 2 (ACE2) is a crucial target both in the prevention and in the therapy of COVID-19. We explored the involvement of oxidoreductive mechanisms by investigating the effects of oxidants and antioxidants on virus uptake by ACE2-expressing cells of human origin (ACE2-HEK293). The cell uptake of pseudoviruses carrying the envelope of either Delta or Omicron variants of SARS-CoV-2 was evaluated by means of a cytofluorimetric approach. The thiol N-acetyl-L-cysteine (NAC) inhibited the uptake of both variants in a reproducible and dose-dependent fashion. Ascorbic acid showed modest effects. In contrast, neither hydrogen peroxide (H2O2) nor a system-generating reactive oxygen species (ROS), which play an important role in the intracellular alterations produced by SARS-CoV-2, were able to affect the ability of either Delta or Omicron SARS-CoV-2 pseudoviruses to be internalized into ACE2-expressing cells. In addition, neither H2O2 nor the ROS generating system interfered with the ability of NAC to inhibit that mechanism. Moreover, based on previous studies, a preventive pharmacological approach with NAC would have the advantage of decreasing the risk of developing COVID-19, irrespective of its variants, and at the same time other respiratory viral infections and associated comorbidities.

Angiotensin converting enzyme 2 in the gastrointestinal tract: binding with coronavirus and its consequences

Introduction: Angiotensin converting enzyme 2 (ACE2) is expressed in several cell types in the body including the gastrointestinal (GI) epithelium. Objective:To provide an overview of the normal distribution of ACE2 in the GI tract, altered ACE2 expression notably in coronavirus infection and its consequences. Materials and Methods: Pubmed and google scholar were searched using the key words ACE2 paired with GI tract, intestinal permeabilty, gut microbiota, inflammatory bowel disease. Results and Discussion: ACE2 is highly expressed in the ileum and colon in human being as well as in rodents. In this current situation of COVID-19 pandemic, downregulation of ACE2 has been reported due to internalization of the ACE2-virus complex within the cells. Although researches are still in infancy in this topic, altered luminal microbiota, increased intestinal permeability, higher level of inflammatory markers and deficient nutrient transport has been reported due to altered ACE2 expression. Conclusion:Altered expression of ACE2 has the possibility to hamper normal physiological function of the GI tract and might affect GI disease progression and prognosis.

Absorption Capacity and Development of Photocatalyst Green Ceramic Products with Moderation of Green Environment for Sustainability Performance of Developing Industries

Business Sustainability is closely related to the green environment and of the products produced, photocatalyst is one of the strategies in caring for the green environment. The benefits of this product are a very important opportunity for small business actors where ceramic SMEs have never developed photocatalyst green products. This study uses SEM-PLS analysis, with SmartPLS software as a processing tool where data is obtained from 300 business actors developing green products (photocatalysts) spread across Indonesia;data collection is carried out directly using questionnaires with stratified purposive sampling method and obtained research samples totaling 200 SMEs. This research shows that the development of green products can be a perfect mediation in bridging the absorption capacity and business sustainability. The development of green products encourages the spirit of obtaining information, interpretation, internalization and facilities by SMEs so as to provide increased productivity, increase production quality, increase environmental friendliness and more dissemination to the green product market. However, the green environment cannot drive the sustainable performance of SMEs because it is not fully understood that the green environment is driving its products but rather to market needs and profit targets and existing market needs.