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The CDKN2A gene, responsible for encoding the tumor suppressors p16(INK4A) and p14(ARF), is frequently inactivated in non-small cell lung cancer (NSCLC). Herein, an uncharacterized long non-coding RNA (lncRNA) (ENSG00000267053) on chromosome 19p13.12 was found to be overexpressed in NSCLC cells with an active, wild-type CDKN2A gene. This lncRNA, named cyclin-dependent kinase inhibitor 2A-regulated lncRNA (CyKILR), also correlated with an active WT STK11 gene, which encodes the tumor suppressor, liver kinase B1. CyKILR displayed two splice variants, CyKILRa (exon 3 included) and CyKILRb (exon 3 excluded), which are cooperatively regulated by CDKN2A and STK11 as knockdown of both tumor suppressor genes was required to induce a significant loss of exon 3 inclusion in mature CyKILR RNA. CyKILRa localized to the nucleus, and its downregulation using antisense RNA oligonucleotides enhanced cellular proliferation, migration, clonogenic survival, and tumor incidence. In contrast, CyKILRb localized to the cytoplasm, and its downregulation using small interfering RNA reduced cell proliferation, migration, clonogenic survival, and tumor incidence. Transcriptomics analyses revealed the enhancement of apoptotic pathways with concomitant suppression of key cell-cycle pathways by CyKILRa demonstrating its tumor-suppressive role. CyKILRb inhibited tumor suppressor miRNAs indicating an oncogenic nature. These findings elucidate the intricate roles of lncRNAs in cell signaling and tumorigenesis., Competing Interests: The authors declare that they have no conflicts of interest.

Objective: As a result of the coronavirus pandemic, mental health professionals have faced the challenge of helping their clients cope with pandemic-related distress on top of ongoing therapeutic issues. This article describes a telehealth-delivered peer/mutual support program for mental health professionals during the pandemic and the key themes identified by participants., Method: An interdivisional American Psychological Association task force formed a working group to identify practical ways to provide mental health professionals with direct support during the pandemic. A mutual support program, the Clinician Support Collaborative, was initiated using virtual video technology. This article describes the program and themes that emerged, including the challenges and benefits of using virtual video technology to host mutual support meetings., Results: Mutual support meetings were conducted on a weekly basis in 2020 and 2021, with mental health professionals and trainees in the Americas, Australasia, and India participating. Key themes identified included the logistical, therapeutic, and privacy concerns participants faced when shifting to telehealth, professional isolation, compassion fatigue, moral injury, burnout, stigma, disparities, and the intersection of personal/family stressors and work stressors., Conclusions: Recommendations for future use of virtual video technology to provide mutual support by and for mental health professionals are provided. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Restenosis poses a significant challenge for individuals afflicted with peripheral artery diseases, often leading to considerable morbidity and necessitating repeated interventions. The primary culprit behind the pathogenesis of restenosis is intimal hyperplasia (IH), in which the hyperproliferative and migratory vascular smooth muscle cell (VSMC) accumulate excessively in the tunica intima. 6-Phosphogluconate dehydrogenase (6PGD), sometimes referred to as PGD, is one of the critical enzymes in pentose phosphate pathway (PPP). In this study, we sought to probe whether 6PGD is aberrantly regulated in IH and contributes to VSMC phenotypic switching., Methods: We used clinical specimens of diseased human coronary arteries with IH lesions and observed robust upregulation of 6PGD at protein level in both the medial and intimal layers in comparison with healthy arterial segments., Results: 6PGD activity and protein expression were profoundly stimulated upon platelet-derived growth factor-induced VSMC phenotypic switching. Using gain-of-function (dCas9-mediated transcriptional activation) and loss-of-function (small interfering RNA-mediated) silencing, we were able to demonstrate the pathogenic role of 6PGD in driving VSMC hyperproliferation, migration, dedifferentiation, and inflammation. Finally, we conducted a rat model of balloon angioplasty in the common carotid artery, with Pluronic hydrogel-assisted perivascular delivery of Physcion , a selective 6PGD inhibitor with poor systemic bioavailability, and observed effective mitigation of IH., Conclusions: We contend that aberrant 6PGD expression and activity-indicative of a metabolic shift toward pentose phosphate pathway-could serve as a new disease-driving mechanism and, hence, an actionable target for the development of effective new therapies for IH and restenosis after endovascular interventions., Competing Interests: Supported by the 10.13039/100000002National Institutes of Health (R01HL162895 [to B.W.]) and by Veteran's Administration (VA Merit Review, BX001792 [to C.E.C.], VA Merit Review award, BX 006063 [C.E.C.], and a Senior Research Career Scientist Award, IK6BX004603 [to C.E.C.]). This work was peripherally supported by way of research cores, methodology and technology development, and software development by the 10.13039/100000002National Institutes of Health by way of P01 CA171983 (Project 1 to C.E.C.) and the R01s AI139072 (to C.E.C.) and GM137578 (to C.E.C.). The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government., (© 2024 The Author(s).)

Objectives: The study objectives were to measure the association among the 4 components of Society of Thoracic Surgeons antibiotic guidelines and postoperative complications in a cohort of patients undergoing valve or coronary artery bypass grafting requiring cardiopulmonary bypass., Methods: In this retrospective observational study, adult patients undergoing coronary revascularization or valvular surgery who received a Surgical Care Improvement Project-compliant antibiotic from January 1, 2016, to April 1, 2021, at a single, tertiary care hospital were included. The primary exposures were adherence to the 4 individual components of Society of Thoracic Surgeons antibiotic best practice guidelines. The association of each component and a combined metric was tested in its association with the primary outcome of postoperative infection as determined by Society of Thoracic Surgeons data abstractors, controlling for several known confounders., Results: Of the 2829 included patients, 1084 (38.3%) received care that was nonadherent to at least 1 aspect of Society of Thoracic Surgeons antibiotic guidelines. The incidence of nonadherence to the 4 individual components was 223 (7.9%) for timing of first dose, 639 (22.6%) for antibiotic choice, 164 (5.8%) for weight-based dose adjustment, and 192 (6.8%) for intraoperative redosing. In adjusted analyses, failure to adhere to first dose timing guidelines was directly associated with Society of Thoracic Surgeons-adjudicated postoperative infection (odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P = .02). Failure of weight-adjusted dosing was associated with both postoperative sepsis (odds ratio, 6.9; 95% confidence interval, 2.5-8.5; P < .01) and 30-day mortality (odds ratio, 4.3; 95% confidence interval, 1.7-11.4; P < .01). No other significant associations among the 4 Society of Thoracic Surgeons metrics individually or as a combination were observed with postoperative infection, sepsis, or 30-day mortality., Conclusions: Nonadherence to Society of Thoracic Surgeons antibiotic best practices is common. Failure of antibiotic timing and weight-adjusted dosing is associated with odds of postoperative infection, sepsis, and mortality after cardiac surgery., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke., Methods: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored., Results: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005-1.707, P = 0.046) and PaO 2 /FiO 2 on admission (OR 0.986, 95% CI 0.979-0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989-0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days., Conclusions: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO 2 /FiO 2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This overexpression has been affiliated with poor prognosis and resistance to chemotherapeutics. Consequently, FASN has come into focus as an appealing potential target for breast cancer treatment. Available FASN inhibitors, however, are unstable and have been correlated with adverse side effects., Objective: This present study aims to investigate the potential of Andrographis paniculata ethanolic crude extract (AP) as a potent FASN inhibitor in breast cancer cells., Materials & Methods: This study used MTT assay and flow cytometry analysis to measure cell viability and apoptosis following AP treatment (0-500 μg/mL). Furthermore, FASN protein expression was evaluated using immunocytochemistry whereas lipid droplet formation was quantified using Oil Red O staining. Literature-based identified AP phytochemicals were subjected to the prediction of molecular docking and ADMET properties., Results: This study demonstrated that AP significantly reduced cell viability while inducing apoptosis in breast cancer cells. In addition, for the first time, exposure to AP was demonstrated to drastically reduce intracellular FASN protein expression and lipid droplet accumulation in EMT6 and MCF-7 breast cancer cells. Docking simulation analysis demonstrated AP phytochemicals may have exerted an inhibitory effect by targeting the FASN Thioesterase (TE) domain similarly to the known FASN inhibitor, Orlistat. Moreover, all AP phytochemicals also possessed drug-likeness properties which are in accordance with Lipinski's rule of five., Conclusions: These results highlight the potential of A. paniculata ethanolic crude extract as a FASN inhibitor and hence might have the potential to be further developed as a potent chemotherapeutic drug for breast cancer treatment., Competing Interests: Conflicts of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© the Author(s).)

This study assessed the association between sociodemographic factors and post-traumatic stress symptoms (PTSS) among 18-24-year-olds during the first wave of the COVID-19 pandemic. This was a secondary analysis of data from 4508 individuals collected through an online survey conducted between June and January 2021. PTSS was measured as a dependent variable using the checklist for post-traumatic stress disorder in civilians. Age, birth sex, sexual, level of education, access to emotional and social support, and emotional distress were the independent variables. A multivariate logistic regression analysis was conducted to determine the associations between the dependent and independent variables while controlling for the country related confounding variables. Females (AOR:2.023), sexual minority individuals (AOR:1.868), those who did not disclose their sexual identify (AOR:1.476), those with poor access to emotional and social support (AOR:4.699) and individuals with no formal education (AOR:13.908), and only primary level education (AOR:4.521) had higher odds of PTSS. The study highlights the multifaceted nature of PTSS during the pandemic and suggests the importance of promoting access of young people, especially females, sexual minority individuals and those with low educational status, to emotional/social support to mitigate the probability of PTSS, especially among sexual minority individuals., (© 2024. The Author(s).)

Oxazines are an important class of compounds in oxazine ligands and medical chemistry. Here, we describe a linear-selective allylation of imines with allyl electrophiles via cross-electrophile coupling reactions, followed by cyclization with halogenated reagents, providing a new strategy to afford oxazine compounds with a tetrasubstituted carbon center. Mechanistic studies indicate that α-amino carbanion, generated by successive single-electron transfer processes, is a key intermediate for nucleophile attack on π-allylpalladium in photoredox/palladium catalysis.

Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis ( Bt ) in crop plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to Bt proteins has highlighted an urgent need for new insecticidal proteins with different modes or sites of action. We discovered a new family of insecticidal proteins from ferns. The prototype protein from Pteris species (Order Polypodiales) and variants from two other orders of ferns, Schizaeales and Ophioglossales, were effective against important lepidopteran pests of maize and soybean in diet-based assays. Transgenic maize and soybean plants producing these proteins were more resistant to insect damage than controls. We report here the crystal structure of a variant of the prototype protein to 1.98 Å resolution. Remarkably, despite being derived from plants, the structure resembles the 3-domain Cry proteins from Bt but has only two out of three of their characteristic domains, lacking the C-terminal domain which is typically required for their activities. Two of the fern proteins were effective against strains of fall armyworm that were resistant to Bt 3-domain Cry proteins Cry1Fa or Cry2A.127. This therefore represents a novel family of insecticidal proteins that have the potential to provide future tools for pest control.

Background: The aims of this study were to assess: 1) the associations among sexual activity, alcohol consumption, use of other psychoactive substances and mental health during the COVID-19 pandemic; and 2) the associations between COVID-19 preventive measures, alcohol consumption and use of psychoactive substances., Methods: This was a secondary analysis of data collected from adults in Nigeria between July and December 2020. The variables extracted included change in sexual activity, alcohol consumption and use of other psychoactive substances, COVID-19 preventive behaviors (wearing face masks, washing hands, physical distancing), anxiety, depression, post-traumatic stress disorder (PTSD) and sociodemographic variables (age, sex, education, HIV status, employment status). Multivariable logistic regressions were conducted. A model was run to regress depression, anxiety, PTSD, increased alcohol consumption, and increased use of other psychoactive substances, on increased sexual activity. In separate models, anxiety, depression, and PTSD were regressed on increased alcohol consumption and on increased use of other psychoactive substances. Finally, three models were constructed to determine the associations between increased alcohol consumption and increased use of other psychoactive substances on three separate COVID-19 preventive behaviors. All models were adjusted for sociodemographic variables., Results: Increased alcohol consumption (AOR:2.19) and increased use of other psychoactive substances (AOR: 3.71) were significantly associated with higher odds of increased sexual activity. Depression was associated with significantly higher odds of increased alcohol consumption (AOR:1.71) and increased use of other psychoactive substances (AOR:3.21). Increased alcohol consumption was associated with significantly lower odds of physical distancing (AOR:0.59)., Conclusion: There was a complex inter-relationship between mental health, sexual health, increased use of psychoactive substances. The consumption of alcohol also affected compliance with physical distancing. Further studies are needed to understand the observed relationships., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly., (© 2023. The Author(s).)

Background: COVID-19 lockdown resulted in the closure of schools with associated problems. The aim of this study was to determine the associations between depression, fear of contracting COVID-19 infection and the use of self-care measures by college students during the first wave of the COVID-19 pandemic., Methods: This was a cross-sectional study that collected data from undergraduate and postgraduate college students 18 years and older from 152 countries between June and December 2020. Study participants were recruited through crowdsourcing using various social media platforms including Facebook, Twitter, and Instagram, WhatsApp groups and emails to participants in the collaborators' networks. The dependent variables were fear of contracting COVID-19 and depression while the independent variable was students' self-care measures. Multivariable logistic regression models were conducted to assess the associations between the dependent and independent variables., Results: Of the 2840 respondents, 1305 (46.0%) had fears of contracting COVID-19 and 599 (21.1%) reported depression. The most common self-care measures were phone calls with friends/family (60.1%) and video chat (52.8%). Learning a new skill was significantly associated with higher odds of fear of contracting COVID-19 (AOR = 1.669) and lower odds of having depression (AOR = 0.684). Talking to friends/family through video chat (AOR = 0.809) was significantly associated with lower odds of feeling depressed while spending time with pets (AOR = 1.470) and taking breaks from the news/social media (AOR = 1.242) were significantly associated with higher odds of feeling depressed. Students from lower middle-income countries (AOR = 0.330) had significantly lower odds of feeling depressed than students from low-income countries., Conclusion: Self-care strategies involving social interactions were associated with less depression. Coping strategies with more cognitive demands may significantly reduce the risk of fear of COVID-19. Special attention needs to be given to students in low-income countries who have higher odds of depression during the pandemic than students from other countries., (© 2023. The Author(s).)

Group 2 innate lymphoid cells (ILC2s) cooperate with adaptive Th2 cells as key organizers of tissue type 2 immune responses, while a spectrum of innate and adaptive lymphocytes coordinate early type 3/17 immunity. Both type 2 and type 3/17 lymphocyte associated cytokines are linked to tissue fibrosis, but how their dynamic and spatial topographies may direct beneficial or pathologic organ remodelling is unclear. Here we used volumetric imaging in models of liver fibrosis, finding accumulation of periportal and fibrotic tract IL-5 + lymphocytes, predominantly ILC2s, in close proximity to expanded type 3/17 lymphocytes and IL-33 high niche fibroblasts. Ablation of IL-5 + lymphocytes worsened carbon tetrachloride-and bile duct ligation-induced liver fibrosis with increased niche IL-17A + type 3/17 lymphocytes, predominantly γδ T cells. In contrast, concurrent ablation of IL-5 + and IL-17A + lymphocytes reduced this progressive liver fibrosis, suggesting a cross-regulation of type 2 and type 3 lymphocytes at specialized fibroblast niches that tunes hepatic fibrosis.

IPD072Aa from Pseudomonas chlororaphis is a new insecticidal protein that has been shown to have high activity against western corn rootworm (WCR). IPD072 has no sequence signatures or predicted structural motifs with any known protein revealing little insight into its mode of action using bioinformatic tools. As many bacterially derived insecticidal proteins are known to act through mechanisms that lead to death of midgut cells, we evaluated whether IPD072Aa also acts by targeting the cells of WCR midgut. IPD072Aa exhibits specific binding to brush border membrane vesicles (BBMVs) prepared from WCR guts. The binding was found to occur at binding sites that are different than those recognized by Cry3A or Cry34Ab1/Cry35Ab1, proteins expressed by current maize traits that target WCR. Using fluorescence confocal microscopy, immuno-detection of IPD072Aa in longitudinal sections from whole WCR larvae that were fed IPD072Aa revealed the association of the protein with the cells that line the gut. High-resolution scanning electron microscopy of similar whole larval sections revealed the disruption of the gut lining resulting from cell death caused by IPD072Aa exposure. These data show that the insecticidal activity of IPD072Aa results from specific targeting and killing of rootworm midgut cells. IMPORTANCE Transgenic traits targeting WCR based on insecticidal proteins from Bacillus thuringiensis have proven effective in protecting maize yield in North America. High adoption has led to WCR populations that are resistant to the trait proteins. Four proteins have been developed into commercial traits, but they represent only two modes of action due to cross-resistance among three. New proteins suited for trait development are needed. IPD072Aa, identified from the bacterium Pseudomonas chlororaphis, was shown to be effective in protecting transgenic maize against WCR. To be useful, IPD072Aa must work through binding to different receptors than those utilized by current traits to reduce risk of cross-resistance and understanding its mechanism of toxicity could aid in countering resistance development. Our results show that IPD072Aa binds to receptors in WCR gut that are different than those utilized by current commercial traits and its targeted killing of midgut cells results in larval death.

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.

Background: Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia., Methods: Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis., Results: A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147)., Conclusions: Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wen, Jiang, Du, Ma, Lu, Li, Yuan, Wu, Guo, Cai, Huang, Wang and Lu.)

Objective: The study aimed to assess the association between adherence to COVID-19 preventive measures and access to media information related to COVID-19., Methods: A multi-country, cross-sectional study using an online survey was conducted from June to December 2020. The sample included 1,457 participants from Argentina, Brazil, Chile, and Mexico. The outcome variable was self-reported adherence to preventive measures (handwashing, social distancing, self-isolation, use of face masks, and working from home). The explanatory variable was self-report of following media information related to COVID-19 (watching or reading the news, following social media coverage). Multivariable logistic regression analyses were conducted to determine the associations., Results: Following information on social media was positively associated with higher odds of practicing social distancing (AOR=5.39; 95%CI: 3.93-7.30), self-isolation (AOR=1.44; 95%CI: 1.08-1.92), use of face masks (AOR=16.84; 95%CI: 10.03-28.27), handwashing (AOR=6.95; CI 95%: 4.98-9.71), and working from home (AOR=1.85; 95% CI: 1.43-2.41). Differences in the use of social media for COVID-19 information were observed among the four countries., Conclusion: Following social media was positively associated with adherence to COVID-19 preventive measures in Latin America. Social media may be effectively used for COVID-19 behaviour modification in Latin America., Competing Interests: All authors declare that there are no conflicts of interest. We acknowledge funding from the National Institutes of Health/National Institute on Aging (K01 AG064986-01) to A.L.N.

Background: The COVID-19 pandemic has induced high levels of stress. The aim of the study was to assess the relationship between emotional stress (COVID-19 related fear, anger, frustration, and loneliness) and the use of coping strategies among adults in Nigeria during the COVID-19 pandemic., Methods: Data from adults aged 18 years and above were collected through an online survey from July to December 2020. The dependent variables were COVID-19 related fear (fear of infection and infecting others with COVID-19), anger, frustration, and loneliness. The independent variables were coping strategies (use of phones to communicate with family and others, video conferencing, indoor exercises, outdoor exercises, meditation/mindfulness practices, engaging in creative activities, learning a new skill, following media coverage related to COVID-19) and alcohol consumption. Five logistic regression models were developed to identify the factors associated with each dependent variables. All models were adjusted for sociodemographic variables (age, sex at birth, and the highest level of education)., Results: Respondents who consumed alcohol, followed media coverage for COVID-19 related information, and who spoke with friends or family on the phone had higher odds of having fear of contracting COVID-19 or transmitting infection to others, and of feeling angry, frustrated, or lonely (p < 0.05). Respondents who exercised outdoors (AOR: 0.69) or learned a new skill (AOR: 0.79) had significantly lower odds of having fear of contracting COVID-19. Respondents who practiced meditation or mindfulness (AOR: 1.47) had significantly higher odds of feeling angry. Those who spoke with friends and family on the phone (AOR: 1.32) and exercised indoors (AOR: 1.23) had significantly higher odds of feeling frustrated. Those who did video conferencing (AOR: 1.41), exercised outdoors (AOR: 1.32) and engaged with creative activities (AOR: 1.25) had higher odds of feeling lonely., Conclusion: Despite the significant association between emotional stress and use of coping strategies among adults in Nigeria during the COVID-19 pandemic, it appears that coping strategies were used to ameliorate rather than prevent emotional stress. Learning new skills and exercising outdoors were used to ameliorate the fear of contracting COVID-19 in older respondents., (© 2022. The Author(s).)

Background: The aim of this study was to determine whether self-reported depression, coronavirus disease of 2019 (COVID-19) health risk profile, HIV status, and SARS-CoV-2 exposure were associated with the use of COVID-19 prevention measures., Methods: This survey collected data electronically between June 29 and December 31, 2020 from a convenient sample of 5050 adults 18 years and above living in 12 West African countries. The dependent variables were: social distancing, working remotely, difficulty obtaining face masks and difficulty washing hands often. The independent variables were self-reported depression, having a health risk for COVID-19 (high, moderate and little/no risk), living with HIV and COVID-19 status (SARS-CoV-2 positive tests, having COVID-19 symptoms but not getting tested, having a close friend who tested positive for SARS-CoV-2 and knowing someone who died from COVID-19). Four binary logistic regression models were developed to model the associations between the dependent and independent variables, adjusting for socio-demographic variables (age, gender, educational status, employment status and living status)., Results: There were 2412 (47.8%) male participants and the mean (standard deviation) age was 36.94 (11.47) years. Respondents who reported depression had higher odds of working remotely (AOR: 1.341), and having difficulty obtaining face masks (AOR: 1.923;) and washing hands often (AOR: 1.263). People living with HIV had significantly lower odds of having difficulty washing hands often (AOR: 0.483). Respondents with moderate health risk for COVID-19 had significantly higher odds of social distancing (AOR: 1.144) and those with high health risk had difficulty obtaining face masks (AOR: 1.910). Respondents who had a close friend who tested positive for SARS-CoV-2 (AOR: 1.132) and knew someone who died of COVID-19 (AOR: 1.094) had significantly higher odds of social distancing. Those who tested positive for SARS-CoV-2 had significantly lower odds of social distancing (AOR: 0.629) and working remotely (AOR: 0.713). Those who had symptoms of COVID-19 but did not get tested had significantly lower odds of social distancing (AOR: 0.783) but significantly higher odds of working remotely (AOR: 1.277)., Conclusions: The study signifies a disparity in the access to and use of COVID-19 preventative measures that is allied to the health and COVID-19 status of residents in West Africa. Present findings point to risk compensation behaviours in explaining this outcome., (© 2022. The Author(s).)

The Rad9-Rad1-Hus1 checkpoint clamp activates the DNA damage response and promotes DNA repair. DNA loading on the central channel of the Rad9-Rad1-Hus1 complex is required to execute its biological functions. Because Rad9A has the highest DNA affinity among the three subunits, we determined the domains and functional residues of human Rad9A that are critical for DNA interaction. The N-terminal globular domain (residues 1-133) had 3.7-fold better DNA binding affinity than the C-terminal globular domain (residues 134-266) of Rad9A1-266. Rad9A1-266 binds DNA 16-, 60-, and 30-fold better than Rad9A1-133, Rad9A134-266, and Rad9A94-266, respectively, indicating that different regions cooperatively contribute to DNA binding. We show that basic residues including K11, K15, R22, K78, K220, and R223 are important for DNA binding. The reductions on DNA binding of Ala substituted mutants of these basic residues show synergistic effect and are dependent on their residential Rad9A deletion constructs. Interestingly, deletion of a loop (residues 160-163) of Rad9A94-266 weakens DNA binding activity by 4.1-fold as compared to wild-type (WT) Rad9A94-266. Cellular sensitivity to genotoxin of rad9A knockout cells is restored by expressing WT-Rad9Afull. However, rad9A knockout cells expressing Rad9A mutants defective in DNA binding are more sensitive to H2O2 as compared to cells expressing WT-Rad9Afull. Only the rad9A knockout cells expressing loop-deleted Rad9A mutant are more sensitive to hydroxyurea than cells expressing WT-Rad9A. In addition, Rad9A-DNA interaction is required for DNA damage signaling activation. Our results indicate that DNA association by Rad9A is critical for maintaining cell viability and checkpoint activation under stress., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: COVID-19 affected mental health and wellbeing. Research is needed to assess its impact using validated tools. The study assessed the content validity, reliability and dimensionality of a multidimensional tool for assessing the mental health and wellbeing of adults., Methods: An online questionnaire collected data in the second half of 2020 from adults in different countries. The questionnaire included nine sections assessing: COVID-19 experience and sociodemographic profile; health and memory; pandemic stress (pandemic stress index, PSI); financial and lifestyle impact; social support; post-traumatic stress disorder (PTSD); coping strategies; self-care and HIV profile over 57 questions. Content validity was assessed (content validity index, CVI) and participants evaluated the test-retest reliability (Kappa statistic and intra-class correlation coefficient, ICC). Internal consistency of scales was assessed (Cronbach α). The dimensionality of the PSI sections and self-care strategies was assessed by multiple correspondence analysis (MCA) using all responses and SPSS. For qualitative validation, we used a semi-structured interview and NVivo was used for coding and thematic analysis., Results: The overall CVI = 0.83 with lower values for the memory items. Cronbach α for the memory items = 0.94 and ICC = 0.71. Cronbach α for PTSD items was 0.93 and ICC = 0.89. Test-retest scores varied by section. The 2-dimensions solution of MCA for the PSI behavior section explained 33.6% (precautionary measures dimension), 11.4% (response to impact dimension) and overall variance = 45%. The 2-dimensions of the PSI psychosocial impact explained 23.5% (psychosocial impact of the pandemic dimension), 8.3% (psychosocial impact of the precautionary measures of the pandemic dimension) and overall variance = 31.8%. The 2-dimensions of self-care explained 32.9% (dimension of self-care strategies by people who prefer to stay at home and avoid others), 9% (dimension of self-care strategies by outward-going people) and overall variance = 41.9%. Qualitative analysis showed that participants agreed that the multidimensional assessment assessed the effect of the pandemic and that it was better suited to the well-educated., Conclusion: The questionnaire has good content validity and can be used to assess the impact of the pandemic in cross-sectional studies especially as individual items. The PSI and self-care strategies need revision to ensure the inclusion of items with strong discrimination., (© 2022. The Author(s).)

Background: This study determined if non-communicable disease status, HIV status, COVID-19 status and co-habiting were associated with COVID-19 test status in sub-Saharan Africa., Methods: Data of 5945 respondents age 18-years-old and above from 31 countries in sub-Saharan Africa collected through an online survey conducted between June and December 2020, were extracted. The dependent variable was COVID-19 status (testing positive for COVID-19 and having symptoms of COVID-19 but not getting tested). The independent variables were non-communicable disease status (hypertension, diabetes, cancer, heart conditions, respiratory conditions, depression), HIV positive status, COVID-19 status (knowing a close friend who tested positive for COVID-19 and someone who died from COVID-19) and co-habiting (yes/no). Two binary logistic regression models developed to determine associations between the dependent and independent variables were adjusted for age, sex, employment, sub region and educational status., Results: Having a close friend who tested positive for COVID-19 (AOR:6.747), knowing someone who died from COVID-19 infection (AOR:1.732), and living with other people (AOR:1.512) were significantly associated with higher odds of testing positive for COVID-19 infection, while living with HIV was associated with significantly lower odds of testing positive for COVID-19 infection (AOR:0.284). Also, respondents with respiratory conditions (AOR:2.487), self-reported depression (AOR:1.901), those who had a close friend who tested positive for COVID-19 infection (AOR:2.562) and who knew someone who died from COVID-19 infection (AOR:1.811) had significantly higher odds of having symptoms of COVID-19 infection but not getting tested., Conclusion: Non-communicable diseases seem not to increase the risk for COVID-19 positive test while cohabiting seems to reduce this risk. The likelihood that those who know someone who tested positive to or who died from COVID-19 not getting tested when symptomatic suggests there is poor contact tracing in the region. People with respiratory conditions and depression need support to get tested for COVID-19., (© 2022. The Author(s).)

Acute myocardial infarction (AMI) is one of the main causes of death in the world, and the incidence of AMI is increasing in the young population. Drug-coated balloon (DCB) has become an effective concept for the treatment of in-stent restenosis, small vessel disease, bifurcation lesions, high blood risk conditions, and even de novo large vessel disease. To ensure whether DCB can play an alternative role in AMI, we conducted a comprehensive meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of DCB in the treatment of AMI. Electronic databases were searched for RCTs that compared DCB with stent for AMI. The primary outcome was major adverse cardiac events (MACEs), the secondary outcome was late lumen loss (LLL). RevMan 5.3 software and RStudio software were used for data analysis. Five RCTs involving 528 patients with 6-12 months of follow-up were included. There was no significant difference in the incidence of MACEs between DCB group and stent group (RR, 0.85; 95% CI 0.42 to 1.74; P = 0.66). Lower LLL was shown in DCB group (WMD, - 0.29; 95% CI - 0.46 to - 0.12; P < 0.001). This meta-analysis of RCT showed that DCB might provide a promising way on AMI compared with stents. Rigorous patients' selection and adequate predilation of culprit lesions are necessary to optimize results and prevent bailout stent implantation.PROSPERO registration number: CRD42020214333., (© 2022. The Author(s).)

Background: The COVID-19 pandemic has created multiple mental health challenges. Many residents in South Africa face pre-existing elevated levels of stress and the pandemic may have had varying impacts on sub-populations. The aims of this study were to determine: 1) the factors associated with post-traumatic stress symptoms (PTSS) and 2) sex differences in the factors associated with PTSS in adults residing in South Africa during the COVID-19 pandemic., Methods: Study participants aged 18 years and above, were recruited for this cross-sectional study through an online survey implemented from June 29, 2020 to December 31, 2020. The outcome variable was PTSS; explanatory variables were sex at birth, COVID-19 status, social isolation and access to emotional support. Confounders considered were age, education level completed and current work status. Logistic regressions were used to determine the association between the outcome and explanatory variables after adjusting for confounders., Outcomes: There were 489 respondents. Among all respondents, those who were older (AOR: 0.97; 95% CI: 0.95 - 0.99) and had access to emotional support from family and relatives (AOR: 0.27; 95% CI: 0.14 - 0.53) had significantly lower odds of PTSS. Respondents who felt socially isolated had higher odds of PTSS (AOR: 1.17; 95% CI: 1.08 - 1.27). Females had higher PTSS scores and higher odds of PTSS compared to males (AOR: 2.18; 95% CI: 1.41-3.39). Females (AOR: 0.27; 95% CI: 0.08 - 0.95) and males (AOR: 0.26; 95% CI: 0.11, 0.59) who had access to emotional support had significantly lower odds of PTSS than those who had no support. Females (AOR: 1.15; 95% CI: 1.04 -1.27) and males (AOR: 1.19; 95% CI: 0.11, 0.59) who felt socially isolated had higher odds of PTSS compared to those who did not feel socially isolated., Interpretation: Compared to males, females had higher scores and higher odds of reporting PTSS during the COVID-19 pandemic. Access to emotional support ameliorated the odds of having PTSS for both sexes, while feeling socially isolated worsened the odds for both sexes., (© 2022. The Author(s).)

Background: Multiple facets of the pandemic can be a source of fear, depression, anxiety and can cause changes in sleep patterns. The aim of this study was to identify health profiles and the COVID-19 pandemic related factors associated with fear, depression, anxiety and changes in sleep pattern in adults in Nigeria., Methods: The data for this analysis was extracted from a cross-sectional online survey that collected information about mental health and well-ness from a convenience sample of adults 18 years and above resident in Nigeria from July to December 2020. Study participants were asked to complete an anonymous, closed-ended online questionnaire that solicited information on sociodemographic profile, health profiles (high, moderate and low COVID-19 infection risk profile) including HIV status, COVID-19 status, and self-reported experiences of fear, anxiety, depression and changes in sleep patterns., Results: In total, 4,439 participants with mean age of 38.3 (±11.6) years responded to the survey. Factors associated with higher odds of having COVID-19 related fear were health risk ( p < 0.05); living with HIV (AOR: 3.88; 95% CI: 3.22-4.69); having COVID-19 symptoms but not tested (AOR: 1.61; 95% CI: 1.30-1.99); having a friend who tested positive to COVID-19 (AOR: 1.28; 95% CI: 1.07-1.53) and knowing someone who died from COVID-19 (AOR: 1.43; 95% CI: 1.24-1.65). The odds of feeling anxious was significantly higher for those with moderate or low health risk profile ( p < 0.05); living with HIV (AOR: 1.64; 95% CI: 1.32-2.04); had a friend who tested positive for COVID-19 (AOR: 1.35; 95% CI: 1.08-1.68) or knew someone who died from COVID-19 (AOR: 1.53; 95% CI: 1.28-1.84). The odds of feeling depressed was significantly higher for those with health risk profile ( p < 0.05); living with HIV (AOR: 2.49; 95% CI: 1.89-3.28); and respondents who had COVID-19 symptoms but had not taken a test (AOR: 1.41; 95% CI: 1.02-1.94). Factors associated with higher odds of having sleep pattern changes were having moderate and low health risk profiles ( p < 0.05)., Conclusion: The study findings suggest that the pandemic may cause fear, anxiety, depression and changes in sleep patterns differently for people with different health profile, HIV status and COVID-19 status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Folayan, Ibigbami, Brown, El Tantawi, Aly, Ezechi, Abeldaño, Ara, Ayanore, Ellakany, Gaffar, Al-Khanati, Idigbe, Jafer, Khan, Khalid, Lawal, Lusher, Nzimande, Popoola, Quadri, Roque, Al-Tammemi, Yousaf, Virtanen, Zuñiga, Ndembi, Nkengasong and Nguyen.)

The aim of the study was to assess if there were significant differences in the adoption of COVID-19 risk preventive behaviors and experience of food insecurity by people living with and without HIV in Nigeria. This was a cross-sectional study that recruited a convenience sample of 4471 (20.5% HIV positive) adults in Nigeria. Binary logistic regression analysis was conducted to test the associations between the explanatory variable (HIV positive and non-positive status) and the outcome variables-COVID-19 related behavior changes (physical distancing, isolation/quarantine, working remotely) and food insecurity (hungry but did not eat, cut the size of meals/skip meals) controlling for age, sex at birth, COVID-19 status, and medical status of respondents. Significantly fewer people living with HIV (PLWH) reported a positive COVID-19 test result; and had lower odds of practicing COVID-19 risk preventive behaviors. In comparison with those living without HIV, PLWH had higher odds of cutting meal sizes as a food security measure (AOR: 3.18; 95% CI 2.60-3.88) and lower odds of being hungry and not eating (AOR: 0.24; 95% CI 0.20-0.30). In conclusion, associations between HIV status, COVID-19 preventive behaviors and food security are highly complex and warrant further in-depth to unravel the incongruities identified., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The education sector experienced substantial impacts during the COVID-19 pandemic resulting from worldwide restrictions., Purpose: To examine differences in the sleep patterns, sexual activity, screen use, and food intake of students and non-students during the COVID-19 pandemic., Methods: This was a global cross-sectional study conducted in the second half of 2020 using multiple social media platforms to recruit study participants globally. A close-ended questionnaire was administered anonymously in English, French, Spanish, Portuguese, and Arabic to adults ages 18 and older. The outcome variables considered in analyses were changes in sleep pattern, sexual activity, screen use, and food intake. The explanatory variable was student status categorized as students vs. non-student. T-test, chi-square, and Mann Whitney U tests were used to assess differences between student and non-student populations. One logistic regression model was built for each outcome variable. Country of residence and country income level were included in the adjusted models., Results: There were 17,008 participants of which 3,793 (22.3%) were students. Of the total sample, 4,889 (28.7%) reported changes in sleep, 4,642 (31.8%) reported increases in sexual activity, 10,278 (70.7%) reported increases in screen use, and 5,662 (40.2%) reported increases in food intake during the pandemic. Compared to non-students, students had significantly higher odds of reporting changes in sleep (AOR = 1.52), increases in sexual activity (AOR = 1.79), and increases in screen use (AOR = 1.36) but lower odds of reporting increase in food intake (AOR = 0.87)., Conclusion: Students displayed higher risk of experiencing changes in sleep, sexual behavior, and screen use during the COVID-19 pandemic. This has the potential to lead to broader adverse effects on students' overall wellbeing. The findings and implications raise further obligations on the education sector to put extra-curricular support systems in place that address COVID-19 related behavior changes that have the potential to adversely impact students' wellbeing., Competing Interests: The authors have declared that no competing interests exist.

Background: Nigeria is a country with high risk for traumatic incidences, now aggravated by the COVID-19 pandemic. This study aimed to identify differences in COVID-19 related post-traumatic stress symptoms (PTSS) among people living and not living with HIV; to assess whether PTSS were associated with COVID-19 pandemic-related anger, loneliness, social isolation, and social support; and to determine the association between PTSS and use of COVID-19 prevention strategies., Methods: The data of the 3761 respondents for this analysis was extracted from a cross-sectional online survey that collected information about mental health and wellness from a convenience sample of adults, 18 years and above, in Nigeria from July to December 2020. Information was collected on the study's dependent variable (PTSS), independent variables (self-reported COVID-19, HIV status, use of COVID-19 prevention strategies, perception of social isolation, access to emotional support, feelings of anger and loneliness), and potential confounder (age, sex at birth, employment status). A binary logistic regression model tested the associations between independent and dependent variables., Results: Nearly half (47.5%) of the respondents had PTSS. People who had symptoms but were not tested (AOR = 2.20), felt socially isolated (AOR = 1.16), angry (AOR = 2.64), or lonely (AOR = 2.19) had significantly greater odds of reporting PTSS (p < 0.001). People living with HIV (AOR = 0.39), those who wore masks (AOR = 0.62) and those who had emotional support (AOR = 0.63), had lower odds of reporting PTSS (p < .05)., Conclusion: The present study identified some multifaceted relationships between post-traumatic stress, HIV status, facemask use, anger, loneliness, social isolation, and access to emotional support during this protracted COVID-19 pandemic. These findings have implications for the future health of those affected, particularly for individuals living in Nigeria. Public health education should be incorporated in programs targeting prevention and prompt diagnosis and treatment for post-traumatic stress disorder at the community level., (© 2022. The Author(s).)

The western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, is considered one of the most economically important pests of maize ( Zea mays L.) in the United States (U.S.) Corn Belt with costs of management and yield losses exceeding USD ~1-2 billion annually. WCR management has proven challenging given the ability of this insect to evolve resistance to multiple management strategies including synthetic insecticides, cultural practices, and plant-incorporated protectants, generating a constant need to develop new management tools. One of the most recent developments is maize expressing double-stranded hairpin RNA structures targeting housekeeping genes, which triggers an RNA interference (RNAi) response and eventually leads to insect death. Following the first description of in planta RNAi in 2007, traits targeting multiple genes have been explored. In June 2017, the U.S. Environmental Protection Agency approved the first in planta RNAi product against insects for commercial use. This product expresses a dsRNA targeting the WCR snf7 gene in combination with Bt proteins (Cry3Bb1 and Cry34Ab1/Cry35Ab1) to improve trait durability and will be introduced for commercial use in 2022.

Telomeres consist of special features and proteins to protect the ends of each chromosome from deterioration and fusion. The telomeric DNA repeats are highly susceptible to oxidative damage that can accelerate telomere shortening and affect telomere integrity. Several DNA repair factors including MYH/MUTYH DNA glycosylase, its interacting partners Rad9/Rad1/Hus1 checkpoint clamp, and SIRT6 aging regulator, are associated with the telomeres. MYH prevents C:G to A:T mutation by removing adenine mispaired with a frequent oxidative DNA lesion, 8-oxoguanine. Here, we show that hMYH knockout (KO) human HEK-293T cells are more sensitive to H 2 O 2 treatment, have higher levels of DNA strand breaks and shorter telomeres than the control hMYH +/+ cells. SIRT6 foci increase at both the global genome and at telomeric regions in H 2 O 2 -treated hMYH +/+ cells. However, in untreated hMYH KO HEK-293T cells, SIRT6 foci only increase at the global genome, but not at the telomeric regions. In addition, the hMYH KO HEK-293T cells have increased extra-chromosomal and intra-chromosomal telomeres compared to the control cells, even in the absence of H 2 O 2 treatment. After H 2 O 2 treatment, the frequency of extra-chromosomal telomeres increased in control HEK-293T cells. Remarkably, in H 2 O 2 -treated hMYH KO cells, the frequencies of extra-chromosomal telomeres, intra-chromosomal telomeres, and telomere fusions are further increased. We further found that the sensitivity to H 2 O 2 and shortened telomeres of hMYH KO cells, are restored by expressing wild-type hMYH, and partially rescued by expressing hMYH Q324H mutant (defective in Hus1 interaction only), but not by expressing hMYH V315A mutant (defective in both SIRT6 and Hus1 interactions). Thus, MYH interactions with SIRT6 and Hus1 are critical for maintaining cell viability and telomeric stability. Therefore, the failure to coordinate 8-oxoG repair is detrimental to telomere integrity.

Objectives: Danzhi Jiangtang capsule (DJC) is widely used for preventing and treating diabetic cardiomyopathy (DCM). However, the underlying mechanisms of the anti-inflammatory and antiapoptotic activities are unclear., Methods: In the in vivo diabetic cardiomyopathy rat model, cardiac function was measured through echocardiography, histological changes in the myocardium were visualized using HE staining, and cardiomyocyte apoptosis was detected using TUNEL. The serum levels of anti-inflammatory cytokines were detected using ELISA. Finally, TLR4, MyD88, and NF-κB mRNA expressions were analyzed using RT-qPCR. In the in vitro experiments, the apoptosis rate of the H9c2 cells was detected using FCM; moreover, TLR4, MyD88 and NF-κB mRNA expressions were measured using RT-qPCR and related protein levels were investigated using Western blotting., Results: In vivo, DJC effectively improved cardiac function, alleviated the pathological changes, and reduced the apoptosis rate. Moreover, DJC reduced TNF-α, IL-1β, and IL-6 activities, with significant inhibition of the TLR4, MyD88 and NF-κB p65 mRNA expression. Moreover, in vitro , DJC effectively inhibited high-glucose-induced H9c2 apoptosis-an effect similar to that for TAK242. Finally, both the DJC and TAK242 considerably reduced TLR4, MyD88, NF-κB, Bax, and caspase-3 protein expression but increased that of BCL-2., Conclusions: DJC prevented the overactivation of the TLR4/MyD88/NF-κB signaling pathway and regulate cardiomyocyte apoptosis against DCM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Actinomycosis is a rare indolent infectious disease with nonspecific clinical presentations that delay diagnosis. Although actinomycosis is thought to be more prevalent in developing countries, data from developing countries are scarce. This study aimed to profile actinomycosis in developing countries and identify how it differed from profiles of developed countries., Methods: Patients fulfilling the inclusion criteria for actinomycosis from Nanfang Hospital in southern China between January 1999 and December 2018 were retrospectively analyzed. We described clinical characteristics, diagnostic procedures, differential diagnosis, and management of actinomycosis of clinical significance., Results: Thirty‑one patients were included in this study. The disease was diagnosed predominately in the orocervicofacial (n = 14), cardiothoracic (n = 11), abdominopelvic (n = 5), and soft tissue (n = 1) regions. Diagnosis was obtained by either histopathology (n = 29, 94%) or microbiology (n = 2, 6%). Only one-third of patients presented with general symptoms, such as fever and weight loss. Ten were lost during follow-up, and the median duration of antibiotic use was 93.5 days (interquartile range 28-300), whereas the median follow-up time was 34 months (interquartile range 9-132). Ten patients receiving complete resection of the lesion were cured without postoperative use of antibiotics. Only one patient relapsed during the follow-up period., Conclusions: Actinomycosis is a rare disease even in developing countries, and both misdiagnosis and missed diagnosis are common. Diagnosis was often delayed and was obtained postoperatively from histopathology in developing countries. Hence, clinicians should be aware of this disease in patients with high risk factors. In the future, specific molecular methods may help to improve early diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

An online survey was conducted to identify factors associated with financial insecurity, food insecurity and poor quality of daily lives of adults in Nigeria during the first wave of the COVID-19 pandemic. The associations between the outcome (experience of financial loss, changes in food intake and impact of the pandemic on daily lives) and the explanatory (age, sex, education level, anxiety, depression, HIV status) variables were determined using logistic regression analysis. Of the 4439 respondents, 2487 (56.0%) were financially insecure, 907 (20.4%) decreased food intake and 4029 (90.8%) had their daily life negatively impacted. Males (AOR:0.84), people who felt depressed (AOR:0.62) and people living with HIV -PLHIV- (AOR:0.70) had significantly lower odds of financial insecurity. Older respondents (AOR:1.01) had significantly higher odds of financial insecurity. Those depressed (AOR:0.62) and PLHIV (AOR:0.55) had significantly lower odds of reporting decreased food intake. Respondents who felt anxious (AOR:0.07), depressed (AOR: 0.48) and who were PLHIV (AOR:0.68) had significantly lower odds of reporting a negative impact of the pandemic on their daily lives. We concluded the study findings may reflect a complex relationship between financial insecurity, food insecurity, poor quality of life, mental health, and socioeconomic status of adults living in Nigeria during the COVID-19 pandemic.

AfIP-1A/1B is a two-component insecticidal protein identified from the soil bacterium Alcaligenes faecalis that has high activity against western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). Previous results revealed that AfIP-1A/1B is cross-resistant to the binary protein from Bacillus thuringiensis (Bt), Cry34Ab1/Cry35Ab1 (also known as Gpp34Ab1/Tpp35Ab1; Crickmore et al., 2020), which was attributed to shared binding sites in WCR gut tissue (Yalpani et al., 2017). To better understand the interaction of AfIP-1A/1B with its receptor, we have systematically evaluated the binding of these proteins with WCR brush border membrane vesicles (BBMVs). Our findings show that AfIP-1A binds directly to BBMVs, while AfIP-1B does not; AfIP-1B binding only occurred in the presence of AfIP-1A which was accompanied by the presence of stable, high molecular weight oligomers of AfIP-1B observed on denaturing protein gels. Additionally, we show that AfIP-1A/1B forms pores in artificial lipid membranes. Finally, binding of AfIP-1A/1B was found to be reduced in BBMVs from Cry34Ab1/Cry35Ab1-resistant WCR where Cry34Ab1/Cry35Ab1 binding was also reduced. The reduced binding of both proteins is consistent with recognition of a shared receptor that has been altered in the resistant strain. The coordination of AfIP-1B binding by AfIP-1A, the similar structures between AfIP-1A and Cry34Ab1, along with their shared binding sites and cross-resistance, suggest a similar role for AfIP1A and Cry34Ab1 in receptor recognition and docking site for their cognate partners, AfIP-1B and Cry35Ab1, respectively., (Copyright © 2021. Published by Elsevier Inc.)

Objective: In this commentary, we suggest that the unprecedented global impact of the COVID-19 pandemic provides a compelling reason for researchers to stretch beyond usual limits and find new ways to engage in global collaborations., Methods: We point to data that have emerged on the mental health and economic consequences of the pandemic to illustrate the extent to which these common issues cross national borders. There is high likelihood that these burdens will continue to persist long after the pandemic is declared "over.", Results: We urge researchers, particularly those from countries with higher income economies, to share resources to increase international collaborative research efforts. We present a case study of an ongoing project and offer some lessons learned for individual investigators., Conclusion: Global problems require global solutions. The COVID-19 pandemic is a global crisis that should prompt researchers to engage in science and research across national borders., Competing Interests: Conflict of Interest Disclosure Statement The authors have no conflicts to disclose.

A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound 3 was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of 3 -Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA. Interaction studies showed that 3 may bind to both G-tetrad and the lateral loop near the 5'-end. The intracellular colocalization with BG4 and competition studies with BRACO19 reveal that 3 may interact with G4-structures. Moreover, 3 reduces the telomere length and downregulates hTERC and hTERT mRNA expression in HeLa cells. The cytotoxicity of 3 against cancer cells (IC 50 = 12.7-16.2 μM) was found to be generally higher than noncancer cells (IC 50 = 52.3 μM). The findings may support that the ligand is telomere G4-DNA specific and may provide meaningful insights for anticancer drug design.

Objective: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis., Methods: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course., Results: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results., Conclusions: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

Purpose: In an effort to protect health care workers at the beginning and end of oral and maxillofacial surgeries, we describe a negative-pressure intubation hood (NPIH) designed to reduce the risk aerosol exposure from fiberoptic intubation (FOI) and extubation. This design is especially important during the Coronavirus disease 2019 era, as it provides greater protection from Severe Acute Respiratory Syndrome-Coronavirus-2 during FOI and extubation, which are some of the most high-risk, aerosol generating procedures of oral and maxillofacial surgery cases., Materials and Methods: This article describes the step-by-step process of assembling a NPIH for FOI using various supplies found commonly in hospitals and surrounding community retail stores, which include transparent medical dressings, equipment covers, intravenous pole clips, polyvinylchloride pipes and adaptors, copper pipe, and a Buffalo smoke evacuator. We then discuss how to create access ports for the anesthesiologist to insert their arms and FOI instrumentation and provide a demonstration of us using the hood with a manikin on an operating room table., Results: This study successfully demonstrates a novel technique for performing FOI in a NIPH assembled from basic supplies found commonly among hospital and community retail stores., Conclusions: This NIPH for FOI is easily made and adaptable to operating room tables, and provides protection against aerosols generated from FOI and subsequent extubation during oral and maxillofacial surgeries., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

In the base excision repair pathway, MYH/MUTYH DNA glycosylase prevents mutations by removing adenine mispaired with 8-oxoG, a frequent oxidative lesion. MYH glycosylase activity is enhanced by Rad9-Rad1-Hus1 (9-1-1) checkpoint clamp and SIRT6 histone/protein deacetylase. Here, we show that MYH, SIRT6, and 9-1-1 are recruited to confined oxidatively damaged regions on telomeres in mammalian cells. Using different knockout cells, we show that SIRT6 responds to damaged telomeres very early, and then recruits MYH and Hus1 following oxidative stress. However, the recruitment of Hus1 to damaged telomeres is partially dependent on SIRT6. The catalytic activities of SIRT6 are not important for SIRT6 response but are essential for MYH recruitment to damaged telomeres. Compared to wild-type MYH, the recruitment of hMYH V315A mutant (defective in both SIRT6 and Hus1 interactions), but not hMYH Q324H mutant (defective in Hus1 interaction only), to damaged telomeres is severely reduced. The formation of MYH/SIRT6/9-1-1 complex is of biological significance as interrupting their interactions can increase cell's sensitivity to H 2 O 2 and/or elevate cellular 8-oxoG levels after H 2 O 2 treatment. Our results establish that SIRT6 acts as an early sensor of BER enzymes and both SIRT6 and 9-1-1 serve critical roles in DNA repair to maintain telomere integrity.