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Nanoparticles (NPs) have the ability to transform poorly immunogenic tumors into activated 'hot' targets. In this study, we investigated the potential of a liposome-based nanoparticle (CRT-NP) expressing calreticulin as an in-situ vaccine to restore sensitivity to anti-CTLA4 immune checkpoint inhibitor (ICI) in CT26 colon tumors. We found that a CRT-NP with a hydrodynamic diameter of approximately 300 nm and a zeta potential of approximately +20 mV induced immunogenic cell death (ICD) in CT-26 cells in a dose-dependent manner. In the mouse model of CT26 xenograft tumors, both CRT-NP and ICI monotherapy caused moderate reductions in tumor growth compared to the untreated control group. However, the combination therapy of CRT-NP and anti-CTLA4 ICI resulted in remarkable suppression of tumor growth rates (>70%) compared to untreated mice. This combination therapy also reshaped the tumor microenvironment (TME), achieving the increased infiltration of antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages, as well as an abundance of T cells expressing granzyme B and a reduction in the population of CD4+ Foxp3 regulatory cells. Our findings indicate that CRT-NPs can effectively reverse immune resistance to anti-CTLA4 ICI therapy in mice, thereby improving the immunotherapeutic outcome in the mouse model.

Introduction: Epilepsy is a group of chronic neurological disorders characterized by seizures. Kindling, a chronic epileptic mouse model, was used to explore the epileptogenic mechanism and seek new anti-epileptics. In kindling, sub-convulsive (chemical/ electrical) stimuli were delivered repeatedly and erratically, eventually causing massive convulsions. Moreover, Morinda citrifolia (Noni) extracts are used as a remedy in ayurvedic preparations for many ailments. Noni has recently been shown to protect mice from amyloid beta-induced memory loss., Objective: This study was used to investigate the neuroprotective potential of Morinda citrifolia in mice over pentylenetetrazol (PTZ)-induced kindling seizure., Methods: Kindling was provoked by subsequent (one-day-gap) injections of PTZ (subconvulsive; 35 mg/kg; s.c.) for 29 days in mice. Following PTZ injection, convulsive behaviours were noted for 30 minutes. Open-field-test (locomotor activity), forced swimming test (depressive behaviors), elevated plus-maze, and passive avoidance tests were employed to evaluate cognition. Brain homogenate was used to estimate oxidative stress (glutathione, superoxide-dismutase, lipid-peroxidation) and acetylcholinesterase activity., Results: PTZ-provoked kindled mice displayed depressive behaviors, impaired locomotion, cognitive dysfunctions and various biochemical changes. However, treatment with Morinda citrifolia extract (500 and 1000 mg/kg, p.o) and valproic acid (200 mg/kg, p.o) before 60 min of each PTZ injection diminished kindling scores and restored behavioural, and biochemical changes., Conclusion: Our findings suggest Morinda citrifolia offered neuroprotective effects against PTZinduced kindling seizures in mice, which were established by behavioural and biochemical paradigms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this research work, a new deep learning model named VGG-COVIDNet has been proposed which can classify COVID-19 cases from normal cases over X-Rays and CT scan images of lungs. Medical practitioners use the X-Rays and CT scan images of lungs to identify whether a person is infected from COVID or not. In present times, it is very important to give real time COVID prediction with high reliability of results. Deep learning models equipped with machine learning support have been found very influential in accurate prediction of COVID or Non-COVID cases in real time. However, there are some limitations associated with the performance of these model which are model size, achieving good balance of model size and accuracy, and making a single model fitting well for both X-Ray and CT Scan image datasets. Keeping in mind these performance constraints, this new model (VGG-COVIDNet) has been proposed for real time prediction of COVID cases with good balance of model size and accuracy working well for both type of datasets (CT Scan and X-Ray). In order to control model size, an improved version of VGG-16 architecture has been proposed which contains only 13 convolutional layers and 5 fully connected layers. Multiple dropout layers have been added in the proposed architecture which can drop some percentage of features and applies random transformations to decrease the model over-fitting issue. Keeping in mind the primary goal to increase the model accuracy the proposed model has been trained on different datasets with ReLU activation function which is one of the best non-linear activation functions. Four different capacity datasets with CT scan and X-Ray images have been used to validate the performance of proposed model. The proposed model gives an overall accuracy of more than 90% on both types of input datasets i.e. X-Ray and CT Scan., (© 2023 The Author(s). Published by Elsevier B.V.)

Objective: Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed 'heat-targeted, on-demand' antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection., Methods: CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat's femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40-42 °C (∼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses., Results: CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at ∼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted., Conclusion: HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms.

Background: Mass screening and treatment (MSaT) aims at reducing the spread of malaria in communities by identifying and treating infected persons regardless of the symptoms. This study was conducted to identify and treat asymptomatic cases using MSaT approaches in the community., Methods: Three rounds of MSaT using cluster combination approaches were carried out during September 2018 to December 2019 to identify and treat asymptomatic malaria cases in the community. All individuals who were present in the household were screened using RDT irrespective of malaria related symptoms. Simultaneously thick and thin blood smear and blood spot were collected for further analysis using microscopy and diagnostic PCR done in a subset of the samples., Results: Logistic regression analysis revealed that asymptomatic malaria cases significantly less among the older age groups compared with < 5 years children (OR ranged between 0.52 and 0.61; p < 0.05), lowest in cluster 4 (OR = 0.01; p < 0.0001); during third round of MSaT survey (OR = 0.11; p < 0.0001) and significantly higher in moderate to high endemic areas (OR = 88.30; p < 0.0001)., Conclusion: Over the three rounds of MSaT, the number of asymptomatic cases were significantly less in the older age groups, and during third round. Similarly, the asymptomatic cases were significantly less in the low endemic area with API < 1 (cluster four). Therefore, the malaria elimination programme may consider the MSaT strategy to identify asymptomatic cases that would be otherwise missed by routine fever based surveillance. This MSaT strategy would help accomplish the malaria elimination goal in an expedited manner., (© 2022. The Author(s).)

Background: Low-density malaria infections (LDMI) are defined as infections that are missed by the rapid diagnostic test (RDT) and/or microscopy which can lead to continued transmission and poses a challenge in malaria elimination efforts. This study was conducted to investigate the prevalence of LDMI in febrile cases using species-specific nested Polymerase Chain Reaction (PCR) tests in the Malaria Elimination Demonstration Project, where routine diagnosis was conducted using RDT., Methods: Every 10th fever case from a cross-sectional community based fever surveillance was tested with RDT, microscopy and nested PCR. Parasite DNA was isolated from the filter paper using Chelex based method. Molecular diagnosis by nested PCR was performed targeting 18SrRNA gene for Plasmodium species., Results: The prevalence of malaria was 2.50% (436/17405) diagnosed by PCR, 1.13% (196/17405) by RDT, and 0.68% (118/ 17,405) by microscopy. Amongst 17,405 febrile samples, the prevalence of LDMI was 1.51% (263/17405) (95% CI 1.33-1.70), which were missed by conventional methods. Logistic regression analysis revealed that illness during summer season [OR = 1.90 (p < 0.05)] and cases screened within three days of febrile illness [OR = 5.27 (p < 0.001)] were the statistically significant predictors of LDMI., Conclusion: The prevalence of malaria among febrile cases using PCR was 2.50% (436/17405) as compared to 1.13% (196/17405) by RDT. Higher number of the LDMI cases were found in subjects with ≤ 3 days mean duration of reported fever, which was statistically significant (p < 0.001). This observation suggests that an early detection of malaria with a more sensitive diagnostic method or repeat testing of the all negative cases may be useful for curtailing malaria transmission. Therefore, malaria elimination programme would benefit from using more sensitive and specific diagnostic methods, such as PCR., (© 2022. The Author(s).)

The COVID-19 pandemics caused an unprecedented mortality, distress, and globally poses a challenge to mental resilience. To our knowledge, this is the first study that aimed to investigate the psychological distress among the adult general population across 13 countries. This cross-sectional study was conducted through online survey by recruiting 7091 respondents. Psychological distress was evaluated with COVID-19 Peritraumatic Distress Index (CPDI). The crude prevalence of psychological distress due to COVID-19 is highest in Vietnam, followed by Egypt, and Bangladesh. Through Multivariate Logistic Regression Analysis, the respondents from Vietnam holds the highest level of distress, while the respondents from Sri Lanka holds the lowest level of distress with reference to Nepal.Female respondents had higher odds of having reported psychological distress, and those with tertiary education were less likely to report psychological distress compared to those with lower level of education. The findings indicate that psychological distress is varies across different countries. Therefore, different countries should continue the surveillance on psychological consequences through the COVID-19 pandemic to monitor the burden and to prepare for the targeted mental health support interventions according to the need. The coping strategies and social support should be provided especially to the lower educational attainment group., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Introduction: Previous studies conducted on the psychological impact of infectious outbreaks have found heavy psychological burdens among general population with more severe affect in the current pandemic. The main aim of this study is to examine the level of psychological distress during COVID-19 in Bangladesh and explore factors associated with higher psychological distress., Methods: An internet-based, cross-sectional survey was conducted from March to April 2020 in Bangladesh among adults 18 years old and above using structured online questionnaires distributed through emails and other social media throughout Bangladesh with an overall response rate of 34%. Modified version of the Covid19 peritraumatic distress index (CPDI) was used to measure distress. Univariate and Bivariate analysis was used to estimate prevalence of CPDI symptoms and test for the associations between CPDI and the exposure variables. Logistic regression analyses were used to estimate the odds ratios of our outcome variable by exposure variables., Results: Overall, 44.3% of respondents were suffering from mild to moderate distress and 9.5% were suffering from severe distress. Female respondents were 2.435 times more likely to suffer from CPDI mild to severe distress than males. As compared to Dhaka and Mymensing region of Bangladesh, odds of distress was 1.945 times more in Chittagong/Sylhet region (p-value = 0.035)., Conclusion: Large proportion of adult population in Bangladesh are experiencing psychological distress, with level of distress varies by different symptoms and predictors. This study suggest the need to develop comprehensive crisis prevention system including epidemiological monitoring, screening, and referral with targeted intervention to reduce psychological distress., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Author(s).)

A combined experimental and theoretical investigation of Ag-Pt sub-nanometer clusters as heterogeneous catalysts in the CO→CO 2 reaction (COox) is presented. Ag 9 Pt 2 and Ag 9 Pt 3 clusters are size-selected in the gas phase, deposited on an ultrathin amorphous alumina support, and tested as catalysts experimentally under realistic conditions and by first-principles simulations at realistic coverage. In situ GISAXS/TPRx demonstrates that the clusters do not sinter or deactivate even after prolonged exposure to reactants at high temperature, and present comparable, extremely high COox catalytic efficiency. Such high activity and stability are ascribed to a synergic role of Ag and Pt in ultranano-aggregates, in which Pt anchors the clusters to the support and binds and activates two CO molecules, while Ag binds and activates O 2 , and Ag/Pt surface proximity disfavors poisoning by CO or oxidized species., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Adsorption of pre-formed Agn clusters for n = 1 - 8 on a graphite substrate is studied within the density functional theory employing the vdW-DF2 functional to treat dispersion interactions. Top sites above surface layer carbon atoms turn out to be most favorable for a Ag adatom, in agreement with experimental observations. The same feature is observed for clusters of almost all sizes which have the lowest energies when the Ag atoms are positioned over top sites. Most gas phase isomers retain their structures over the substrate, though a couple of them undergo significant distortions. Energetics of the adsorption can be understood in terms of a competition between energy cost of disturbing Ag-Ag bonds in the cluster and energy gain from Ag-C interactions at the surface. Ag3 turns out to be an exceptional candidate in this regard that undergoes significant structural distortion and has only two of the Ag atoms close to surface C atoms in its lowest energy structure.

Single Cr, Mn, Fe, Co and Ni doped Al clusters having up to 12 Al atoms are studied using density functional methods. The global minima of structure for all the clusters are identified, and their relative stability and electronic and magnetic properties are studied. FeAl4 and CoAl3 are found to have enhanced stability and aromatic behavior. In contrast to binary transition metal alkali and transition metal alkaline earth clusters, spherical shell models cannot describe the electronic structure of transition metal aluminum clusters.

Objectives: This study aims to investigate the role of different factors associated with exposure to second-hand smoke (SHS) in the workplace and home in the urban and rural areas of India., Design: Secondary analysis of the data from the Global Adult Tobacco Survey conducted in 2009-2010., Setting and Participants: Data were analysed from 32 738 rural and 23 202 urban non-smokers at home and 4809 rural and 6227 urban non-smokers in the workplace in India., Outcomes and Methods: We used two measures of SHS: exposure to SHS at home and exposure to SHS in the workplace. SHS exposure at home is estimated for non-smokers who reported anyone smoking inside his/her home. Exposure to SHS in the workplace is estimated for non-smokers who reported anyone smoking in the workplace in the past 30 days before the survey. Statistical techniques such as χ(2) test, logistic regression and discriminant function analysis were used., Results: The results showed that SHS exposure in the workplace and home is higher in the rural areas than in the urban areas. As compared with men, women are significantly more likely to be exposed to SHS at home (OR=1.20, 95% CI 1.10 to 1.30) in the rural areas, and less likely at the workplace in the urban areas (OR=0.49, 95% CI 0.40 to 0.59). Education and region are significant predictors of exposure levels to SHS at home and the workplace in the rural and urban areas. The knowledge of number of smoking-related hazards significantly discriminates the SHS exposure in the rural workplace. SHS exposure at home is most affected by region in the rural areas and education in the urban areas., Conclusions: The factors which affect SHS exposure differ in the rural and urban areas of India. The study concludes that the risk of getting exposed to SHS at home and the workplace among non-smokers is higher in the rural areas of the country.

Impact of supplemental UV-B (sUV-B) has been investigated on photosynthetic pigments, antioxidative enzymes, metabolites, and protein profiling of radish plants under realistic field conditions. Exposure of sUV-B leads to oxidative damage in plants. However, plants possess a number of UV-protection mechanisms including a stimulation of antioxidant defense system. It caused alteration in reactive oxygen species metabolism primarily by decreasing catalase activity vis-à-vis enhanced activities of other enzymatic (superoxide dismutase, ascorbate peroxidase, and glutathione reductase) and non-enzymatic (ascorbic acid) antioxidants. Qualitative analysis of samples also showed significant reductions in photosynthetic pigments and protein content. After sUV-B exposure, protein profile showed differences mainly at eight points--126.8, 84.8, 71.9, 61.5, 47.8, 40.6, 38.9, and 17.5 kDa, whereas protein(s) of 38.9 kDa showed increment. Results of the present investigation clearly showed the adverse effect of sUV-B on total biomass at final harvest.