Digital health interventions for cervical cancer care: A systematic review and future research opportunities.

BACKGROUND: Cervical cancer is a malignancy among women worldwide, which is responsible for innumerable deaths every year. The primary objective of this review study is to offer a comprehensive and synthesized overview of the existing literature concerning digital interventions in cervical cancer care. As such, we aim to uncover prevalent research gaps and highlight prospective avenues for future investigations. METHODS: This study adopted a Systematic Literature Review (SLR) methodology where a total of 26 articles were reviewed from an initial set of 1110 articles following an inclusion-exclusion criterion. RESULTS: The review highlights a deficiency in existing studies that address awareness dissemination, screening facilitation, and treatment provision for cervical cancer. The review also reveals future research opportunities like explore innovative approaches using emerging technologies to enhance awareness campaigns and treatment accessibility, consider diverse study contexts, develop sophisticated machine learning models for screening, incorporate additional features in machine learning research, investigate the impact of treatments across different stages of cervical cancer, and create more user-friendly applications for cervical cancer care. CONCLUSIONS: The findings of this study can contribute to mitigating the adverse effects of cervical cancer and improving patient outcomes. It also highlights the untapped potential of Artificial Intelligence and Machine Learning, which could significantly impact our society.

Degradation of autotoxic chemicals and maintainence of electrical conductivity recover growth, yield and nutrient absorption of successive lettuce in recycled hydroponics.

In recycled hydroponics, successive crop cultivation by maintaining electrical conductivity (EC) suffers lower growth performance due to accumulating autotoxic root exudates. In this study, the efficiency of alternate current electro degradation (AC-ED) was evaluated for degrading allelochemicals and recovering retarded lettuce yield cultivated in EC-adjusted repeatedly used nutrient solutions. From benzoic acid (BA)-added nutrient solution, BA was completely degraded after 24 h by applying AC-ED at 551 and 940 Hz frequency with 50 and 80% electrical duty. In lettuce bioassay, fresh mass was negatively affected without the AC-ED-treated solution. Finally, lettuce seedlings were hydroponically grown in a plant factory using a half-strength Enshi nutrient solution. Culture solutions were unchanged in non-renewed solutions. Nutrient elements were supplied based on the EC (1.42 dS m-1) of culture solutions. The fresh weight of lettuce was gradually decreased in subsequent cultures. Nutrient absorption rate was reduced in non-renewed solutions though enough of all nutrient elements were available in the solution. In the final culture, the highest shoot fresh weight (SFW) was recorded in the renewed (83.0 g plant-1) solution which was similar to the AC-ED-treated solution (81.0 g plant-1) and the lowest (58.0 g plant-1) was in the non-renewed solution. By applying AC-ED, 40% lettuce yield was recovered in the EC-adjusted solution without renewing. Therefore, it is recommended that the continuous application of AC-ED with the capacity of 551 Hz and 50% duty would be applied for recovering the retarded lettuce yield cultivated with repeatedly used culture solutions in recycled hydroponics.

Chitosan-Alginate Polymeric Nanocomposites as a Potential Oral Vaccine Carrier Against Influenza Virus Infection.

Lessons from the recent COVID-19 pandemic underscore the importance of rapidly developing an efficacious vaccine and its immediate administration for prophylaxis. Oral vaccines are of particular interest, as the presence of healthcare professionals is not needed for this stress-free vaccination approach. In this study, we designed a chitosan (CH)-alginate (AL) complex carrier system encapsulating an inactivated influenza virus vaccine (A/PR/8/34, H1N1), and the efficacy of these orally administered nanocomposite vaccines was evaluated in mice. Interestingly, CH-AL complexes were able to load large doses of vaccine (≥90%) with a stable dispersion. The encapsulated vaccine was protected from gastric acid and successfully released from the nanocomposite upon exposure to conditions resembling those of the small intestines. Scanning electron microscopy of the CH-virus-AL complexes revealed that the connections between the lumps became loose and widened pores were visible on the nanocomposite's surface at pH 7.4, thereby increasing the chance of virus release into the surroundings. Orally inoculating CH-virus-AL into mice elicited higher virus-specific IgG compared to the unimmunized controls. CH-virus-AL immunization also enhanced CD4 and CD8 T cell responses while diminishing lung virus titer, inflammatory cytokine production, and body weight loss compared to the infection control group. These results suggest that chitosan-alginate polymeric nanocomposites could be promising delivery complexes for oral influenza vaccines.

Exploring usability problems of mHealth applications developed for cervical cancer: An empirical study.

Objectives: Nowadays, mobile health applications are developed to raise awareness and facilitate screening and treatment of cervical cancer, while a very few studies have been conducted focusing on the measurement and assurance of usability and exploring the acceptable user experience of such applications. Usability issues become a crucial concern for such cervical-cancer-related applications because users with diverse backgrounds in terms of education, information technology literacy, and geographic reasons are required to access those applications. The objective of this research is to evaluate the usability of mobile health applications developed for cervical cancer patients. Methods: Two evaluation studies were conducted following the expert evaluation and a questionnaire-based user study. A total of four cervical-cancer-related applications that are focusing on the Awareness and Diagnosis theme were selected and each of the applications was evaluated by four usability experts. Then, a user study (n = 80) based on the Goal Question Metric was conducted to reveal the usability problems of four selected applications. Finally, findings of both evaluations were aggregated and analyzed. Results: Both approaches showed that all applications suffer from several usability problems while "Cervical Cancer Guide" performs better and "Cervical Cancer Tracker" showed the least in performance from the usability perspective. Again, the Goal Question Metric performs noticeably better in assessing the learnability of the applications, while the analytical heuristic evaluation performs better in identifying the issues that cause user annoyance. Conclusion: The methodology adopted and the usability problems revealed through this study can be well utilized by the information technology professionals or user interface designers for designing, evaluating, and developing the cervical-cancer-related applications with enhanced usability and user experience.

Physicochemical and functional properties of capsaicin loaded cricket protein isolate and alginate complexes.

As people become more aware of the health benefits of foods and their nutritional benefits for preventing diseases and promoting health, the demand for functional foods rich in proteins, fiber, and bioactives like capsaicin (CAP) is constantly rising. This study hypothesized that the electrostatic complexes developed by cricket protein isolate (CPI) and alginate (AL) could be utilized to encapsulate CAP, making it more water-soluble and protecting it at acidic pHs. Quantitative analysis revealed that CAP was efficiently encapsulated into the CPI-AL complexes with a maximum encapsulation efficiency of 91%, improving its aqueous solubility 45-fold. In vitro release tests showed that CAP was retained at acidic pHs (3.0 and 5.0) in CPI-AL complexes but released steadily at neutral pH (7.4), which will protect CAP in the stomach while enabling its release in the small intestine. Moreover, the antioxidant activity of CAP-CPI-AL complexes was superior to that of their individual bare equivalents. The complexes also demonstrated enhanced emulsifying capabilities and stability at acidic pHs (2.0-5.0) as the CPI fraction in the complexes increased. Our findings thus contribute to the growing body of knowledge that validates protein-polysaccharide complexation as a promising strategy for developing edible delivery systems.

Facilitating viral vector movement enhances heterologous protein production in an established plant system.

Molecular farming technology using transiently transformed Nicotiana plants offers an economical approach to the pharmaceutical industry to produce an array of protein targets including vaccine antigens and therapeutics. It can serve as a desirable alternative approach for those proteins that are challenging or too costly to produce in large quantities using other heterologous protein expression systems. However, since cost metrics are such a critical factor in selecting a production host, any system-wide modifications that can increase recombinant protein yields are key to further improving the platform and making it applicable for a wider range of target molecules. Here, we report on the development of a new approach to improve target accumulation in an established plant-based expression system that utilizes viral-based vectors to mediate transient expression in Nicotiana benthamiana. We show that by engineering the host plant to support viral vectors to spread more effectively between host cells through plasmodesmata, protein target accumulation can be increased by up to approximately 60%.

Unraveling the phase behavior of cricket protein isolate and alginate in aqueous solution.

The associative phase behavior of cricket protein isolate (CPI) and sodium alginate (AL) in aqueous solutions was explored using turbidimetry, methylene blue spectroscopy, zeta potentiometry, dynamic light scattering, and confocal microscopy as a function of pH, biopolymer ratio, total biopolymer concentration (CT), and ionic strength. When both biopolymers had net-negative charges, soluble complexes formed between pH 6.0 and 8.0, however when both biopolymers had opposing net charges, insoluble complexes formed as complex coacervates below pH 5.5, defined as pHφ1, followed by precipitates below another critical pH 3.0 (pHp). Increasing the CPI:AL weight ratio or CT facilitated complex formation, and the addition of salts (NaCl/KCl) had a salt-enhancement and salt-reduction impact at low and high salt concentrations, respectively. Ionic interactions between oppositely charged CPI and AL were mainly responsible for the formation of their insoluble complexes, while hydrogen bonding and hydrophobic interactions also played significant roles.

Curcumin-Loaded Human Serum Albumin Nanoparticles Prevent Parkinson's Disease-like Symptoms in C. elegans.

Parkinson's disease is one of the most common degenerative disorders and is characterized by observable motor dysfunction and the loss of dopaminergic neurons. In this study, we fabricated curcumin nanoparticles using human serum albumin as a nanocarrier. Encapsulating curcumin is beneficial to improving its aqueous solubility and bioavailability. The curcumin-loaded HSA nanoparticles were acquired in the particle size and at the zeta potential of 200 nm and -10 mV, respectively. The curcumin-loaded human serum albumin nanoparticles ameliorated Parkinson's disease features in the C. elegans model, including body movement, basal slowing response, and the degeneration of dopaminergic neurons. These results suggest that curcumin nanoparticles have potential as a medicinal nanomaterial for preventing the progression of Parkinson's disease.

Production of active Exendin-4 in Nicotiana benthamiana and its application in treatment of type-2 diabetics.

GLP-1 (Glucagon-like peptide-1) is a peptide that stimulates insulin secretion from the ß-cell for glycemic control of the plasma blood glucose level. Its mimetic exenatide (synthetic Exendin-4) with a longer half-life of approximately 3.3-4 h is widely used in clinical application to treat diabetes. Currently, exenatide is chemically synthesized. In this study, we report that the GLP-1 analogue recombinant Exendin-4 (Exdn-4) can be produced at a high level in Nicotiana benthamiana, with an estimated yield of 50.0 µg/g fresh biomass. For high-level expression, we generated a recombinant gene, B:GB1:ddCBD1m:8xHis : Exendin-4 (BGC : Exdn-4), for the production of Exendin-4 using various domains such as the BiP signal peptide, the GB1 domain (B1 domain of streptococcal G protein), a double cellulose binding domain 1 (CBD1), and 8 His residues (8xHis) to the N-terminus of Exendin-4. GB1 was used to increase the expression, whereas double CBD1 and 8xHis were included as affinity tags for easy purification using MCC beads and Ni2+-NTA resin, respectively. BGC : Exdn-4 was purified by single-step purification to near homogeneity using both Ni2+-NTA resin and microcrystalline cellulose (MCC) beads. Moreover, Exdn-4 without any extra residues was produced from BGC : Exdn-4 bound onto MCC beads by treating with enterokinase. Plant-produced Exdn-4 (Exendin-4) was as effective as chemically synthesized Exendin-4 in glucose-induced insulin secretion (GIIS) from mouse MIN6m9 cells a pancreatic beta cell line.

Dual targeting smart drug delivery system for multimodal synergistic combination cancer therapy with reduced cardiotoxicity.

This study first reports the development of a smart drug delivery system (DDS) for multimodal synergistic cancer therapy combining chemo-photothermal-starvation approaches. A magnetic photothermal agent was synthesized by preparing iron oxide (IO) nanoparticles (NPs) with covalently attached indocyanine green (ICG) and glucose oxidase (GOx) (ICGOx@IO). Synthesized ICGOx@IO NPs were co-encapsulated with doxorubicin (Dox) and EGCG ((-)-epigallocatechin-3-gallate) inside PLGA (poly(lactic-co-glycolic acid)) NPs using multiple emulsion solvent evaporation method. Such formulation gave the advantage of triggered drug release by near-infrared (NIR) laser irradiation (808 nm at 1 W/cm2). RGD peptide was attached to the surface of PLGA NPs and the final hydrodynamic size was around 210 nm. Dual targeting by peptide and 240 mT external magnet significantly improved cellular uptake. Cellular uptake was observed using FACS, electron and optical microscopy. Dual targeting along with laser irradiation could reduce in vitro cell viability by 90 ± 2% (Dox-equivalent dose: 10 µg/ml) and complete tumor ablation was achieved in vivo due to synergetic therapeutic effect. Another attractive feature of the DDS was the significant reduction of cardiotoxicity of doxorubicin by EGCG. This new platform is thus expected to hold strong promise for future multimodal combination therapy of cancers. STATEMENT OF SIGNIFICANCE: Doxorubicin is one of the most studied and effective chemotherapeutic agents whose application is hindered due to its cardiotoxicity. In this study, we used (-)-Epigallocatechin-3-gallate (EGCG) to overcome that limitation. However, drug delivery to tumor sites with no/minimum accumulation in healthy organs is always challenging. Although peptide-based targeting is very popular, the effectiveness of receptor/ligand binding active targeting is sometimes questioned which motivated us to apply dual targeting approach. Multimodal therapies can exhibit synergistic effects and subsequently reduce the required dose of drug over monotherapy. We aimed to achieve chemo-photothermal-starvation combination therapy in this study and such achievement is yet to be reported. Our developed system also has the advantage of triggered drug release by near-infrared (NIR) laser irradiation.

Gamma radiation application to rice: Reduced glycemic index in relation to modified carbohydrate observed in FTIR spectra.

This study was conducted with a popular, low price Bangladesh rice variety BRRI Dhan 29 with a view to possible carbohydrate modification targeting lower glycemic index using gamma radiation application. Irradiation process (5 and 10 â€‹kGy â€‹at a dose rate of 9.74kGy/h) altered amylose content, amylose/amylopectin ratio, swelling power, and solubility index. FTIR spectroscopy confirmed the changed molecular structures due to radiation application. Treatment with a dose of 5 and 10kGy caused increased amylose and amylose/amylopectin ratio significantly (p â€‹< â€‹0.02). The highest amylose content was found in 10 â€‹kGy irradiated rice (30.20%) compared to unirradiated one (17.27%). Gamma radiation caused decreased swelling and increased water solubility in rice powder. These features of carbohydrate amendment in irradiated rice lead to reduced glycemic index as investigated with the in vivo experiments. Therefore, this study suggests gamma-irradiated rice (10kGy) is beneficial for diabetic subjects keeping lower blood glucose levels.

Delineating the interaction mechanism of glabridin and ovalbumin by spectroscopic and molecular docking techniques.

The interaction between ovalbumin (OVA) and isoflavonoid glabridin (GB) was investigated using spectroscopic and molecular docking techniques. Fluorescence spectroscopy revealed that GB was bound to OVA mainly due to hydrogen bonding and hydrophobic forces. FT-IR spectroscopy showed that the combination of GB and OVA resulted in a decrease in the ß-sheet content of OVA and an increase in the α-helix and extended-chain content. All these experimental results were supported and clarified by molecular docking simulations. GB binding was able to inhibit chemical denaturant-induced structural changes in OVA as observed by intrinsic tryptophan and ANS fluorescence. Moreover, GB-OVA complex increased the aqueous solubility of GB by about 4.45 times at pH 7.0. These results provided insights into the interaction between GB and OVA that contributes to the utilization of GB in the food and pharmaceutical industries.

Overexpression and Purification of Gracilariopsis chorda Carbonic Anhydrase (GcCAα3) in Nicotiana benthamiana, and Its Immobilization and Use in CO2 Hydration Reactions.

Carbonic anhydrase (CA; EC 4.2.2.1) is a Zn-binding metalloenzyme that catalyzes the reversible hydration of CO2. Recently, CAs have gained a great deal of attention as biocatalysts for capturing CO2 from industrial flue gases owing to their extremely fast reaction rates and simple reaction mechanism. However, their general application for this purpose requires improvements to stability at high temperature and under in vitro conditions, and reductions in production and scale-up costs. In the present study, we developed a strategy for producing GcCAα3, a CA isoform from the red alga Gracilariopsis chorda, in Nicotiana benthamiana. To achieve high-level expression and facile purification of GcCAα3, we designed various constructs by incorporating various domains such as translation-enhancing M domain, SUMO domain and cellulose-binding domain CBM3. Of these constructs, MC-GcCAα3 that had the M and CBM3 domains was expressed at high levels in N. benthamiana via agroinfiltration with a yield of 1.0 g/kg fresh weight. The recombinant protein was targeted to the endoplasmic reticulum (ER) for high-level accumulation in plants. Specific and tight CBM3-mediated binding of recombinant GcCAα3 proteins to microcrystalline cellulose beads served as a means for both protein purification from total plant extracts and protein immobilization to a solid surface for increased stability, facilitating multiple rounds of use in CO2 hydration reactions.

Anti-Parkinson's Disease Function of Dioscin-Zein-Carboxymethyl Cellulose Nanocomplex in Caenorhabditis elegans.

Nanosized dioscin-loaded zein-CMC (DZC) complex comprising dioscin (glycoside saponin), zein (corn protein), and carboxymethyl cellulose (CMC) is fabricated through anti-solvent coprecipitation. The optimized ratio of zein to CMC for the homogenous complexation is 5:1, and DZC maintains its stability in a wide range of pH (3.0-8.0) and ionic strength (0-50 mm NaCl). No biological toxicity of DZC is found in Caenorhabditis elegans with a normal lifespan and body size. Parkinson's disease (PD) is characterized by the loss of dopamine (DA) and dopaminergic neurons. In cat-2 mutant with defective biosynthesis of DA, DZC-fed animals show intact DA behaviors including basal slowing response (≈60%) and alcohol avoidance (≈80%). Such DA promotional effects are a result of the enhanced expression/activation of DA transporter, DAT-1 in DA neurons. Taken together, DZC has a potential for preventing PD as an oral-administered drugs and supplements.

Effect of dye and temperature on the physico-mechanical properties of jute/PP and jute/LLDPE based composites.

Jute fabrics and unidirectional jute fiber reinforced polypropylene (PP) and linear low density polyethylene (LLDPE) based composites were prepared successfully by compression molding technique. The unidirectional jute fiber was treated with Reactive Orange HB® and Deep Blue LW® dye to investigate physico-mechanical properties. The Reactive Orange HB® treated composites showed relatively better mechanical properties than the Deep Blue LW® treated composites. The jute fiber-based composites showed higher mechanical properties than that of jute-based fabrics. The polypropylene-based composites showed better mechanical properties than that of LLDPE. The variations of mechanical properties were also observed. The highest mechanical properties were at -18 °C and lowest at 50 °C. Water absorbent, SEM and FT-IR analysis of the composite was also carried out.

Molecular Mechanism of the Specificity of Protein Import into Chloroplasts and Mitochondria in Plant Cells.

Plants possess both types of endosymbiotic organelles, chloroplasts and mitochondria. Transit peptides and presequences function as signal sequences for specific import into chloroplasts and mitochondria, respectively. However, how these highly similar signal sequences confer the protein import specificity remains elusive. Here, we show that mitochondrial- or chloroplast-specific import involves two distinct steps, specificity determination and translocation across envelopes, which are mediated by the N-terminal regions and functionally interchangeable C-terminal regions, respectively, of transit peptides and presequences. A domain harboring multiple-arginine and hydrophobic sequence motifs in the N-terminal regions of presequences was identified as the mitochondrial specificity factor. The presence of this domain and the absence of arginine residues in the N-terminal regions of otherwise common targeting signals confers specificity of protein import into mitochondria and chloroplasts, respectively. AtToc159, a chloroplast import receptor, also contributes to determining chloroplast import specificity. We propose that common ancestral sequences were functionalized into mitochondrial- and chloroplast-specific signal sequences by the presence and absence, respectively, of multiple-arginine and hydrophobic sequence motifs in the N-terminal region.

Expression of seven carbonic anhydrases in red alga Gracilariopsis chorda and their subcellular localization in a heterologous system, Arabidopsis thaliana.

KEY MESSAGE: Red alga, Gracilariopsis chorda, contains seven carbonic anhydrases that can be grouped into α-, ß- and γ-classes. Carbonic anhydrases (CAHs) are metalloenzymes that catalyze the reversible hydration of CO2. These enzymes are present in all living organisms and play roles in various cellular processes, including photosynthesis. In this study, we identified seven CAH genes (GcCAHs) from the genome sequence of the red alga Gracilariopsis chorda and characterized them at the molecular, cellular and biochemical levels. Based on sequence analysis, these seven isoforms were categorized into four α-class, one ß-class, and two γ-class isoforms. RNA sequencing revealed that of the seven CAHs isoforms, six genes were expressed in G. chorda in light at room temperature. In silico analysis revealed that these seven isoforms localized to multiple subcellular locations such as the ER, mitochondria and cytosol. When expressed as green fluorescent protein fusions in protoplasts of Arabidopsis thaliana leaf cells, these seven isoforms showed multiple localization patterns. The four α-class GcCAHs with an N-terminal hydrophobic leader sequence localized to the ER and two of them were further targeted to the vacuole. GcCAHß1 with no noticeable signal sequence localized to the cytosol. The two γ-class GcCAHs also localized to the cytosol, despite the presence of a predicted presequence. Based on these results, we propose that the red alga G. chorda also employs multiple CAH isoforms for various cellular processes such as photosynthesis.

Prolines in Transit Peptides Are Crucial for Efficient Preprotein Translocation into Chloroplasts.

Chloroplasts import many preproteins that can be classified based on their physicochemical properties. The cleavable N-terminal transit peptide (TP) of chloroplast preproteins contains all the information required for import into chloroplasts through Toc/Tic translocons. The question of whether and how the physicochemical properties of preproteins affect TP-mediated import into chloroplasts has not been elucidated. Here, we present evidence that Pro residues in TP mediate efficient translocation through the chloroplast envelope membranes for proteins containing transmembrane domains (TMDs) or proteins prone to aggregation. By contrast, the translocation of soluble proteins through the chloroplast envelope membranes is less dependent on TP prolines. Proless TPs failed to mediate protein translocation into chloroplasts; instead, these mutant TPs led to protein mistargeting to the chloroplast envelope membranes or nonspecific protein aggregation during import into chloroplasts. The mistargeting of TMD-containing proteins caused by Pro-less TPs in wild-type protoplasts was mimicked by wild-type TPs in hsp93-V protoplasts, in which preprotein translocation is compromised. We propose that the physicochemical properties of chloroplast proteins affect protein translocation through the chloroplast envelope, and prolines in TP have a crucial role in the efficient translocation of TMD-containing proteins.

Evolution of rubisco complex small subunit transit peptides from algae to plants.

Chloroplasts evolved from a free-living cyanobacterium acquired by the ancestor of all photosynthetic eukaryotes, including algae and plants, through a single endosymbiotic event. During endosymbiotic conversion, the majority of genes in the endosymbiont were transferred to the host nucleus and many of the proteins encoded by these genes must therefore be transported into the chloroplast after translation in the cytosol. Chloroplast-targeted proteins contain a targeting signal, named the transit peptide (TP), at the N-terminus. However, the evolution of TPs is not well understood. In this study, TPs from RbcS (rubisco small subunit) were compared between lower and higher eukaryotes. Chlamydomonas reinhardtii RbcS (CrRbcS) TP was non-functional in Arabidopsis. However, inclusion of a critical sequence motif, FP-RK, from Arabidopsis thaliana RbcS (AtRbcS) TP allowed CrRbcS TP to deliver proteins into plant chloroplasts. The position of the FP-RK motif in CrRbcS TP was critical for function. The QMMVW sequence motif in CrRbcS TP was crucial for its transport activity in plants. CrRbcS TPs containing additional plant motifs remained functional in C. reinhardtii. These results suggest that TPs evolved by acquiring additional sequence motifs to support protein targeting to chloroplasts during evolution of land plants from algae.

Deciphering the interactions of fish gelatine and hyaluronic acid in aqueous solutions.

The interactions of fish gelatine (FG) with hyaluronic acid (HA) are studied in an aqueous environment at 25°C by turbidimetric titration, confocal scanning laser microscopy, dynamic light scattering, zeta potentiometry, spectrophotometry with methylene blue, and construction of state diagrams. FG forms soluble complexes with HA above a boundary pH (pHφ1), where both biopolymers are net-negatively charged, but develop insoluble complexes as liquid-state complex coacervates below pHφ1, where the two biopolymers are oppositely charged. The insoluble complexes are continuously aggregated with further acid titration, followed by immediate visible phase-separation when another boundary pH (pHp) is reached. The complex formation is mainly driven by electrostatic attractions rather than hydrogen bonding or hydrophobic interactions. The complex formation is promoted by increasing FG-to-HA weight ratio or total biopolymer concentration, or at a low ionic strength, but significantly suppressed in the presence of high ionic strength.