Efficacy of Remdesivir on Clinical Outcomes in COVID-19 Patients: A Study in a Tertiary Care Hospital in Pakistan.

Background: As of October 3, 2023, the global COVID-19 case tally exceeded 696 million, with almost 7 million fatalities. Remdesivir, approved for treatment of COVID-19 by regulatory bodies, has seen varying recommendations by the World Health Organization over time. Despite certain studies questioning its efficacy, others highlight potential benefits. The objective of this study was to gauge the impact of remdesivir on clinical outcomes in a Pakistani tertiary care hospital. Methods: An analytical cross-sectional study was conducted on 108 COVID-19 patients at Mayo Hospital Lahore between September 2020 and August 2021. Of these, 52 received remdesivir. The study employed a structured proforma for data collection, with analyses conducted using SPSS version 26, considering a p-value of less than 0.05 as statistically significant. Results: Demographic distribution between remdesivir-treated and untreated groups was similar. Significant improvement was observed in the remdesivir cohort in terms of oxygen saturation (58%), ferritin levels (58.2%), chest X-ray results (67.8%), and discharge rates (66.7%) when compared to the untreated group. Stratification based on disease severity showed that remdesivir was particularly beneficial for moderate illness cases in several parameters. Conclusion: This study suggests that remdesivir can be associated with improved outcomes, especially in patients with moderate COVID-19 severity. The data emphasizes the importance of the disease stage when considering therapeutic interventions and calls for more region-specific research to guide health responses amid diverse epidemiological landscapes.

An Amphiphilic Cell-Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9.

The discovery of safe platforms that can circumvent the endocytic pathway is of great significance for biological therapeutics that are usually degraded during endocytosis. Here we show that a self-assembled and dynamic macrocycle can passively diffuse through the cell membrane and deliver a broad range of biologics, including proteins, CRISPR Cas9, and ssDNA, directly to the cytosol while retaining their bioactivity. Cell-penetrating macrocycle CPM can be easily prepared from the room temperature condensation of diketopyrrolopyrrole lactams with diamines. We attribute the high cellular permeability of CPM to its amphiphilic nature and chameleonic properties. It adopts conformations that partially bury polar groups and expose hydrophobic side chains, thus self-assembling into micellar-like structures. Its superior fluorescence makes CPM trackable inside cells where it follows the endomembrane system. CPM outperformed commercial reagents for biologics delivery and showed high RNA knockdown efficiency of CRISPR Cas9. We envisage that this macrocycle will be an ideal starting point to design and synthesize biomimetic macrocyclic tags that can readily facilitate the interaction and uptake of biomolecules and overcome endosomal digestion.

Development of a micro-combined heat and power powered by an opposed-piston engine in building applications.

Residential homes and light commercial buildings usually require substantial heat and electricity simultaneously. A combined heat and power system enables more efficient and environmentally friendly energy usage than that achieved when heat and electricity are produced in separate processes. However, due to financial and space constraints, residential and light commercial buildings often limit the use of traditional large-scale industrial equipment. Here we develop a micro-combined heat and power system powered by an opposed-piston engine to simultaneously generate electricity and provide heat to residential homes or light commercial buildings. The developed prototype attains the maximum AC electrical efficiency of 35.2%. The electrical efficiency breaks the typical upper boundary of 30% for micro-combined heat and power systems using small internal combustion engines (i.e., <10 kW). Moreover, the developed prototype enables maximum combined electrical and thermal efficiencies greater than 93%. The prototype is optimally designed for natural gas but can also run renewable biogas and hydrogen, supporting the transition from current conventional fossil fuels to zero carbon emissions in the future. The analysis of the unit's decarbonization and cost-saving potential indicate that, except for specific locations, the developed prototype might excel in achieving decarbonization and cost savings primarily in US northern and middle climate zones.

m6A RNA methylation counteracts dark-induced leaf senescence in Arabidopsis.

Senescence is an important physiological process which directly affects many agronomic traits in plants. Senescence induces chlorophyll degradation, phytohormone changes, cellular structure damage, and altered gene regulation. Although these physiological outputs are well defined, the molecular mechanisms employed are not known. Using dark-induced leaf senescence (DILS) as the experimental system, we investigated the role of N6-methyladenosine (m6A) mRNA methylation during senescence in Arabidopsis (Arabidopsis thaliana). Plants compromised in m6A machinery components like METHYLTRANSFERASE A (mta mutant) and VIRILIZER1 (vir-1 mutant) showed an enhanced DILS phenotype. This was accompanied by compromised chloroplast and photosynthesis performance in mta as well as accumulation of senescence-promoting camalexin and phytohormone jasmonic acid after dark treatment. m6A levels increased during DILS and destabilized senescence-related transcripts thereby preventing premature aging. Due to inefficient decay, senescence-related transcripts like ORESARA1 (ORE1), SENESCENCE-ASSOCIATED GENE 21 (SAG21), NAC-like, activated by AP3/PI (NAP), and NONYELLOWING 1 (NYE1) over-accumulated in mta thereby causing accelerated senescence during DILS. Overall, our data propose that m6A modification is involved in regulating the biological response to senescence in plants, providing targets for engineering stress tolerance of crops.

Oral health behind the bars: oral health seeking behavior among jail prisoners at central jail of Peshawar, Pakistan: a cross-sectional study.

BACKGROUND: The oral health care-seeking behavior among prison inmates is an overlooked area, often leading to deteriorating general health due to the prisoners' limited awareness of oral hygiene practices. It is crucial to address this issue and understand the factors associated with oral healthcare-seeking behavior in prisons. OBJECTIVE: To assess the oral healthcare-seeking behavior of prison inmates at Central Prisoner Jail, Peshawar Pakistan and to look the factors associated with their dental care utilization. MATERIAL AND METHODS: This cross-sectional study was conducted at Central Prisoner Jail, Peshawar Khyber Pakhtunkhwa, Pakistan from November 2021 to April 2022. A consecutive sampling technique was used to collect data from both convicted and under-trial prisoners by using a pre-tested WHO Basic Oral Health Survey 2013 tool. Our outcome variable was "Visit to a dentist in the last 12 months (Never/Once or more than one visit). Chi-square test was used to determine univariate association with other explanatory variables while multivariable logistic regression was performed to adjust for potential confounders. RESULT: A total of 225 participants were recruited to the study with a mean (SD) age of 32.9(11.4). More than two-thirds of 200(88.9%) of the participants were males. One-third of the sample never visited the dentist75(33.3). Participants who completed college/university education and never visited the dentist in the last 12 months constituted a smaller proportion (17.6%) compared to those who visited the dentist once or more than once n = 28(82.4%, p-value = 0.003). Individuals who were using toothbrushes were most frequently visiting the dentist n = 130(72.6%=p value = 0.001) as compared to never visitors. Multivariate logistic regression analysis revealed that Participants who experienced teeth pain or discomfort had 0.42 times lower odds of visiting the dentist compared to those who did not experience any pain or discomfort [AOR 0.42 (95% CI 0.17-0.80), p = 0.04]. Similarly, Participants who do not use any denture have 4.06 times higher odds[AOR 4.06(95% CI 1.76-9.36), p = 0.001] of visiting the dentist compared to those who use a denture. CONCLUSION: Our result demonstrates that those prisoners who were experiencing tooth pain or discomfort and not using dentures were the strong predictors with lower dental visit frequency to seek oral health care.

Linker histone H1 modulates defense priming and immunity in plants.

Linker H1 histones play an important role in animal and human pathogenesis, but their function in plant immunity is poorly understood. Here, we analyzed mutants of the three canonical variants of Arabidopsis H1 histones, namely H1.1, H1.2 and H1.3. We observed that double h1.1h1.2 and triple h1.1h1.2h1.3 (3h1) mutants were resistant to Pseudomonas syringae and Botrytis cinerea infections. Transcriptome analysis of 3h1 mutant plants showed H1s play a key role in regulating the expression of early and late defense genes upon pathogen challenge. Moreover, 3h1 mutant plants showed enhanced production of reactive oxygen species and activation of mitogen activated protein kinases upon pathogen-associated molecular pattern (PAMP) treatment. However, 3h1 mutant plants were insensitive to priming with flg22, a well-known bacterial PAMP which induces enhanced resistance in WT plants. The defective defense response in 3h1 upon priming was correlated with altered DNA methylation and reduced global H3K56ac levels. Our data place H1 as a molecular gatekeeper in governing dynamic changes in the chromatin landscape of defense genes during plant pathogen interaction.

Histone modifications and DNA methylation act cooperatively in regulating symbiosis genes in the sea anemone Aiptasia.

BACKGROUND: The symbiotic relationship between cnidarians and dinoflagellates is one of the most widespread endosymbiosis in our oceans and provides the ecological basis of coral reef ecosystems. Although many studies have been undertaken to unravel the molecular mechanisms underlying these symbioses, we still know little about the epigenetic mechanisms that control the transcriptional responses to symbiosis. RESULTS: Here, we used the model organism Exaiptasia diaphana to study the genome-wide patterns and putative functions of the histone modifications H3K27ac, H3K4me3, H3K9ac, H3K36me3, and H3K27me3 in symbiosis. While we find that their functions are generally conserved, we observed that colocalization of more than one modification and or DNA methylation correlated with significantly higher gene expression, suggesting a cooperative action of histone modifications and DNA methylation in promoting gene expression. Analysis of symbiosis genes revealed that activating histone modifications predominantly associated with symbiosis-induced genes involved in glucose metabolism, nitrogen transport, amino acid biosynthesis, and organism growth while symbiosis-suppressed genes were involved in catabolic processes. CONCLUSIONS: Our results provide new insights into the mechanisms of prominent histone modifications and their interaction with DNA methylation in regulating symbiosis in cnidarians.

A Novel Sustainable Process for Multilayer Graphene Synthesis Using CO2 from Ambient Air.

Graphene produced by different methods can present varying physicochemical properties and quality, resulting in a wide range of applications. The implementation of a novel method to synthesize graphene requires characterizations to determine the relevant physicochemical and functional properties for its tailored application. We present a novel method for multilayer graphene synthesis using atmospheric carbon dioxide with characterization. Synthesis begins with carbon dioxide sequestered from air by monoethanolamine dissolution and released into an enclosed vessel. Magnesium is ignited in the presence of the concentrated carbon dioxide, resulting in the formation of graphene flakes. These flakes are separated and enhanced by washing with hydrochloric acid and exfoliation by ammonium sulfate, which is then cycled through a tumble blender and filtrated. Raman spectroscopic characterization, FTIR spectroscopic characterization, XPS spectroscopic characterization, SEM imaging, and TEM imaging indicated that the graphene has fifteen layers with some remnant oxygen-possessing and nitrogen-possessing functional groups. The multilayer graphene flake possessed particle sizes ranging from 2 µm to 80 µm in diameter. BET analysis measured the surface area of the multilayer graphene particles as 330 m2/g, and the pore size distribution indicated about 51% of the pores as having diameters from 0.8 nm to 5 nm. This study demonstrates a novel and scalable method to synthesize multilayer graphene using CO2 from ambient air at 1 g/kWh electricity, potentially allowing for multilayer graphene production by the ton. The approach creates opportunities to synthesize multilayer graphene particles with defined properties through a careful control of the synthesis parameters for tailored applications.

Dataset of ultralow temperature refrigeration for COVID 19 vaccine distribution solution.

Most COVID-19 vaccines require temperature control for transportation and storage. Two types of vaccine have been developed by manufacturers (Pfizer and Moderna). Both vaccines are based on mRNA and lipid nanoparticles requiring low temperature storage. The Pfizer vaccine requires ultra-low temperature storage (-80 °C to -60 °C), while the Moderna vaccine requires -30 °C storage. However, the last stage of distribution is quite challenging, especially for rural or suburban areas, where local towns, pharmacy chains and hospitals may not have the infrastructure required to store the vaccine at the required temperature. In addition, there is limited data available to address ancillary challenges of the distribution framework for both transportation and storage stages, including safety concerns due to human exposure to large amounts of CO2 from dry-ice sublimation, issues due to the pressure increase caused by dry-ice sublimation, and the potential issue caused by non-uniform cryogenic temperatures. As such, there is a need for test dataset to assist the development of a quick, effective, secure, and safe solution to mitigate the challenges faced by vaccine distribution logistics.

Ethylene involvement in the regulation of heat stress tolerance in plants.

Because of the rise in global temperature, heat stress has become a major concern for crop production. Heat stress deteriorates plant productivity and alters phenological and physiological responses that aid in precise monitoring and sensing of mild-to-severe transient heat stress. Plants have evolved several sophisticated mechanisms including hormone-signaling pathways to sense heat stimuli and acquire heat stress tolerance. In response to heat stress, ethylene, a gaseous hormone, is produced which is indispensable for plant growth and development and tolerance to various abiotic stresses including heat stress. The manipulation of ethylene in developing heat stress tolerance targeting ethylene biosynthesis and signaling pathways has brought promising out comes. Conversely increased ethylene biosynthesis and signaling seem to exhibit inhibitory effects in plant growth responses from primitive to maturity stages. This review mainly focuses on the recent studies of ethylene involvement in plant responses to heat stress and its functional regulation, and molecular mechanism underlying the plant responses in the mitigation of heat-induced damages. Furthermore, this review also describes the crosstalk between ethylene and other signaling molecules under heat stress and approaches to improve heat stress tolerance in plants.

COVID 19 vaccine distribution solution to the last mile challenge: Experimental and simulation studies of ultra-low temperature refrigeration system.

Most COVID-19 vaccines require ambient temperature control for transportation and storage. Both Pfizer and Moderna vaccines are based on mRNA and lipid nanoparticles requiring low temperature storage. The Pfizer vaccine requires ultra-low temperature storage (between -80 °C and -60 °C), while the Moderna vaccine requires -30 °C storage. Pfizer has designed a reusable package for transportation and storage that can keep the vaccine at the target temperature for 10 days. However, the last stage of distribution is quite challenging, especially for rural or suburban areas, where local towns, pharmacy chains and hospitals may not have the infrastructure required to store the vaccine. Also, the need for a large amount of ultra-low temperature refrigeration equipment in a short time period creates tremendous pressure on the equipment suppliers. In addition, there is limited data available to address ancillary challenges of the distribution framework for both transportation and storage stages. As such, there is a need for a quick, effective, secure, and safe solution to mitigate the challenges faced by vaccine distribution logistics. The study proposes an effective, secure, and safe ultra-low temperature refrigeration solution to resolve the vaccine distribution last mile challenge. The approach is to utilize commercially available products, such as refrigeration container units, and retrofit them to meet the vaccine storage temperature requirement. Both experimental and simulation studies are conducted to evaluate the technical merits of this solution with the ability to control temperature at -30 °C or -70 °C as part of the last mile supply chain for vaccine candidates.

Structural, Thermal, and Mechanical Characterization of a Thermally Conductive Polymer Composite for Heat Exchanger Applications.

Polymer composites are being considered for numerous thermal applications because of their inherent benefits, such as light weight, corrosion resistance, and reduced cost. In this work, the microstructural, thermal, and mechanical properties of a 3D printed polymer composite with high thermal conductivity are examined using multiple characterization techniques. Infrared spectroscopy and X-ray diffraction reveal that the composite contains a polyphenylene sulfide matrix with graphitic fillers, which is responsible for the high thermal conductivity. Furthermore, differential scanning calorimetry determines that the glass transition and melting point of the composite are 87.6 °C and 285.6 °C, respectively. Thermogravimetric analysis reveals that the composite is thermally stable up to ~400 °C. Creep tests are performed at different isotherms to evaluate the long-term performance of the composite. The creep result indicates that the composite can maintain mechanical integrity when used below its glass transition temperature. Nanoindentation tests reveal that modulus and hardness of the composite is not significantly influenced by heating or creep conditions. These findings indicate that the composite is potentially suitable for heat exchanger applications.

Evolutionary and functional analysis of two-component system in chickpea reveals CaRR13, a TypeB RR, as positive regulator of symbiosis.

The critical role of cytokinin in early nodulation in legumes is well known. In our study, exogenous cytokinin application to roots of the important crop legume, chickpea (Cicer arietinum L.), led to the formation of pseudo-nodules even in the absence of rhizobia. Hence, a genome-wide analysis of the cytokinin signalling, two-component system (TCS) genes, was conducted in chickpea, Medicago and Cajanus cajan. The integrated phylogenetic, evolutionary and expression analysis of the TCS genes was carried out, which revealed that histidine kinases (HKs) were highly conserved, whereas there was diversification leading to neofunctionalization at the level of response regulators (RRs) especially the TypeB RRs. Further, the functional role of the CaHKs in nodulation was established by complementation of the sln1Δ mutant of yeast and cre1 mutants of (Medicago) which led to restoration of the nodule-deficient phenotype. Additionally, the highest expressing TypeB RR of chickpea, CaRR13, was functionally characterized. Its localization in the nucleus and its Y1H assay-based interaction with the promoter of the early nodulation gene CaNSP2 indicated its role as a transcription factor regulating early nodulation. Overexpression, RNAi lines and complementation of cre1 mutants with CaRR13 revealed its critical involvement as an important signalling molecule regulating early events of nodule organogenesis in chickpea.

Predictors of Disease Severity in Adult Covid-19 Patients Admitted in Mayo Hospital, Lahore, Pakistan.

OBJECTIVE: To assess disease severity, based on clinical presentation and laboratory investigations. STUDY DESIGN:  Observational study. PLACE AND DURATION OF STUDY: COVID-19 Isolation Unit of Mayo Hospital, Lahore from 15th March to 31st May, 2020. METHODOLOGY: Four hundred and forty-five COVID-19 RT-PCR positive patients of either gender in age group of 18-80 years, admitted in isolation wards, high dependency units (HDUs) and intensive care units (ICUs) of the Hospital, were selected for the study via simple random sampling. Clinical presentations and laboratory investigations were recorded for all patients. Kruskal-Wallis test, Pearson Chi-square test, boxplots and ROC curve were used to analyse the data. A p-value ≤0.05 was considered statistically significant. RESULTS: Out of the 445 cases, a male predominance 286 (64.3%) was observed with majority of patients 324 (72.8%) having mild disease, 73 (16.4%) moderate, 25 (5.6%) severe and 23 (5.2%) having critical disease. D-dimer was considered to be the best discriminatory marker to assess disease severity with an overall accuracy of 92.1%. CONCLUSION: Fever, sore throat, shortness of breath, body aches, abdominal pain, anosmia and aguesia were the predominant symptoms in majority of patients belonging to different categories based on disease severity. Inflammatory markers like D-dimers and ferritin levels determined the overall disease severity with a high accuracy. Key Words: Disease severity, Clinical presentation, Laboratory investigations, RT-PCR.

Gas-Phase Temperature Mapping of Evaporating Microdroplets.

Evaporation is a ubiquitous and complex phenomenon of importance to many natural and industrial systems. Evaporation occurs when molecules near the free interface overcome intermolecular attractions with the bulk liquid. As molecules escape the liquid phase, heat is removed, causing evaporative cooling. The influence of evaporative cooling on inducing a temperature difference with the surrounding atmosphere as well as within the liquid is poorly understood. Here, we develop a technique to overcome past difficulties encountered during the study of heterogeneous droplet evaporation by coupling a piezo-driven droplet generation mechanism to a controlled micro-thermocouple to probe microdroplet evaporation. The technique allowed us to probe the gas-phase temperature distribution using a micro-thermocouple (50 µm) in the vicinity of the liquid-vapor interface with high spatial (±10 µm) and temporal (±100 ms) resolution. We experimentally map the temperature gradient formed surrounding sessile water droplets having varying curvature dictated by the apparent advancing contact angle (100° ≲ θ ≲ 165°). The experiments were carried out at temperatures below and above ambient for a range of fixed droplet radii (130 µm ≲ R ≲ 330 µm). Our results provide a primary validation of the centuries-old theoretical framework underpinning heterogeneous droplet evaporation mediated by the working fluid, substrate, and gas thermophysical properties, droplet apparent contact angle, and droplet size. We show that microscale droplets residing on low-thermal-conductivity substrates such as glass absorb up to 8× more heat from the surrounding gas compared to droplets residing on high-thermal-conductivity substrates such as copper. Our work not only develops an experimental understanding of the heat transfer mechanisms governing droplet evaporation but also presents a powerful platform for the study and characterization of liquid-vapor transport at curved interfaces wetting and nonwetting advanced functional surfaces.

Moisture affinity of HDPE/phase-change material composites for thermal energy storage applications.

Moisture adsoprtion can degrade the structural integrity of thermal energy storage devices and can negatively impact the capacity and charging/discharging behaviour. Steady-state and transient experiments are conducted at various operating temperatures to evaluate the moisture affinity of organic phase-change material (PCM) shape stabilized with high-density polyethylene (HDPE).

Hybrid hollow silica particles: synthesis and comparison of properties with pristine particles.

In the past decade, interest in hollow silica particles has grown tremendously because of their applications in diverse fields such as thermal insulation, drug delivery, battery cathodes, catalysis, and functional coatings. Herein, we demonstrate a strategy to synthesize hybrid hollow silica particles having shells made of either polymer-silica or carbon-silica. Hybrid shells were characterized using electron microscopy. The effect of hybrid shell type on particle properties such as thermal and moisture absorption was also investigated.

Low cost and scalable method for modifying surfaces of hollow particles from hydrophilic to hydrophobic.

Hydrophobic hollow silica particles are desirable for several applications such as hydrophobic coatings, thermal insulation, and thermally resistant insulative paints. However, converting hydrophilic particles into hydrophobic particles without compromising their structural integrity is challenging. In this work, we present a low cost strategy to modify the surface of hollow silica particles from hydrophilic to hydrophobic without compromising their structural integrity.

Genome invasion by a hypomethylated satellite repeat in Australian crucifer Ballantinia antipoda.

Repetitive sequences are ubiquitous components of all eukaryotic genomes. They contribute to genome evolution and the regulation of gene transcription. However, the uncontrolled activity of repetitive sequences can negatively affect genome functions and stability. Therefore, repetitive DNAs are embedded in a highly repressive heterochromatic environment in plant cell nuclei. Here, we analyzed the sequence, composition and the epigenetic makeup of peculiar non-pericentromeric heterochromatic segments in the genome of the Australian crucifer Ballantinia antipoda. By the combination of high throughput sequencing, graph-based clustering and cytogenetics, we found that the heterochromatic segments consist of a mixture of unique sequences and an A-T-rich 174 bp satellite repeat (BaSAT1). BaSAT1 occupies about 10% of the B. antipoda nuclear genome in >250 000 copies. Unlike many other highly repetitive sequences, BaSAT1 repeats are hypomethylated; this contrasts with the normal patterns of DNA methylation in the B. antipoda genome. Detailed analysis of several copies revealed that these non-methylated BaSAT1 repeats were also devoid of heterochromatic histone H3K9me2 methylation. However, the factors decisive for the methylation status of BaSAT1 repeats remain currently unknown. In summary, we show that even highly repetitive sequences can exist as hypomethylated in the plant nuclear genome.