Microencapsulation of noni fruit extract using gum arabic and maltodextrin - Optimization, stability and efficiency.

Noni fruit (Morinda citrifolia L.) has many health-supporting compounds, but its biological extracts need protection against environmental impacts for stability and efficiency. To address this, microencapsulation is an advanced technology in food applications that require optimization of coating component and temperature regime. Gum arabic (GA) and maltodextrin (MD) were suitably combined at 2:1 ratio, which showed good and stable structure as well as successful microencapsulation efficiency of the enzymatic-ultrasonic assisted noni extract. A coating density of 20 % for the GA:MD formula was with highest performance. The heat setting of spray drying was optimized at 175 and 82 °C for inlet and outlet, respectively using response surface methodology with experimental validation of maximized TFC and TSC at 88.3 and 90.3 %, respectively. Noni microencapsulated powder was assessed via a series of reliably advanced techniques such as microscopy, spectrophotometry, diffraction, and calorimetry for structural properties. Noni powder was additionally tested for storage stability, heat exposure stability, and release efficiency in pH condition and in vitro digestive tract. Promising results were obtained with at least one year storage stability, better microcapsule stability at 60 and 100 °C, quite good release at pH 7.4, and suitable release efficiency in digestive tract simulation. These properties of microencapsulated noni powder open further scalability potential and various industrial applications.

Adsorption characteristics of S-Metolachlor onto the sawdust biochar derived from Acacia auriculiformis.

The adsorption mechanism of S-Metolachlor in an aqueous solution by sawdust biochar derived from Acacia auriculiformis (SAB) was studied. SAB was manufactured at 500 °C for 4 h under oxygen-limited conditions and characterized for SEM, EDS, pHpzc, BET, and FTIR. The adsorption kinetics, isotherm, and diffusion studies of S-Metolachlor and SAB were further explored. Moreover, the effects of the solution pH were examined on the adsorption of S-Metolachlor by SAB. The BET analysis of SAB was achieved at 106.74 m2.g-1 and the solution pH did not significantly influence the S-Metolachlor adsorption. The adsorption data were fitted into a Langmuir isotherm and the PSO model. The film diffusion coefficient Df (4.93 × 10-11 to 8.17 × 10-11 m2.s-1) and the particle diffusion coefficient Dp (1.68 × 10-11 to 2.65 × 10-11 m2.s-1) were determined and the rate-limiting step of S-Metolachlor adsorption and SAB was governed by liquid film diffusion. The S-Metolachlor adsorption process onto SAB was controlled by multiple mechanisms, including pore filling, H-bonding, hydrophobic interaction, and π-π EDA interactions. H-bonding is the main interaction for the adsorption of S-Metolachlor and SAB. Conclusively, the study illustrates that biochar produced from Acacia auriculiformis sawdust possessed effective adsorption properties for S-Metolachlor herbicide.

Illuminating the breast cancer survival rates among Southeast Asian women: A systematic review and meta-analysis spanning four decades.

In Southeast Asia, breast cancer is the most prevalent cancer among women and ranks as the second leading cause of cancer-related deaths. This systematic review and meta-analysis, encompassing 27 observational cohort studies with a minimum one-year follow-up period, aimed to examine temporal trends in breast cancer survival rates. Among the subset of five out of eleven Southeast Asian nations with available data, our analysis revealed pooled survival rates of 88.8 % at 1 year, 73.8 % at 3 years, 70.8 % at 5 years, and 49.3 % at 10 years for breast cancer patients. The mean age at diagnosis was 50.77±10.07 years, with 52.81 % of patients presenting with positive lymph nodes. Notably, stages I and II remained predominant even five years post-diagnosis. Although an overall amelioration in survival rates transpired over the preceding four decades, a noticeable exception pertained to the 3-year rate, demonstrating limited improvement. These findings underscore the pressing need for enhanced research efforts, particularly in countries within the region that lack survival data, to enable accurate estimations. Furthermore, our review also emphasizes the crucial need for future comprehensive, well-designed studies to delve into the factors behind survival rate disparities in Southeast Asia and the younger age at diagnosis compared to other regions.

Growing propensity of internet addiction among Asian college students: meta-analysis of pooled prevalence from 39 studies with over 50,000 participants.

OBJECTIVES: Rapid internet penetration and technological advancements have facilitated accessibility to internet-enabled devices globally. Since Asia lacks comprehensive data on internet addiction among college students, this review aims to estimate its pooled prevalence. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: Searches were conducted in PubMed, Scopus, CINAHL, and MEDLINE from their inception through August 2022 using terms appropriate to internet addiction and Asian countries/territorial for publications in English peer-reviewed journals. The studies included those done on current college students and provided unambiguous indicators of the threshold of internet addiction. The pooled prevalence was calculated through a random-effects meta-analysis by RStudio software, and I2 statistic was used to assess heterogeneity. The Joanna Briggs Institute critical appraisal checklist was used for quality assessment. RESULTS: Overall, between 2007 and 2021, 39 papers comprising 45 effect sizes and totaling 58,058 participants met the inclusion criteria. The pooled prevalence of internet addiction among Asian college students was 24.3% (95% confidence interval: 19.8%-29.5%, Q = 6234, df = 44, τ2 = 0.79, I2 = 99.29%), and strikingly, this percentage increased over time. A high degree of heterogeneity was seen, and no publication bias was found. CONCLUSIONS: To our knowledge, this is the first comprehensive review report on Asian college students, which found that one-fifth suffer from internet addiction. The findings emphasize the significance of multidisciplinary prevention and management strategies to mitigate the harmful effects of internet addiction. Further research is warranted to develop a standardized diagnostic tool for a more precise estimation of internet addiction among this population.

Job satisfaction of hospital pharmacists in a representative province in Mekong Delta, Vietnam.

BACKGROUND: Job satisfaction is an important factor affecting job performance and turnover of healthcare workers, especially hospital pharmacists. Nevertheless, limited studies have reported this issue in the context of Vietnam. OBJECTIVES: To help maintain the quality and size of the limited hospital pharmacy workforce in Vietnam, especially in the Mekong Delta area, this study investigated the job satisfaction of hospital pharmacists, and the associated factors, in Vinh Long province, a representative province in the central Mekong Delta. METHODS: A cross-sectional survey was conducted, recruiting hospital pharmacists working in all 17 province/district-affiliated healthcare facilities across Vinh Long province, Vietnam, between August and September 2022. RESULTS: Among the 235 survey participants (representing a response rate of 97.1%), 189 pharmacists (80.4%) reported that they were satisfied with their job. Working conditions, leadership styles, and benefits were factors found to significantly influence job satisfaction. Pharmacists who had worked in the field for 3-5 years (OR = 3.752, 95% CI = 1.036-13.595), more than 5 years (OR = 6.361, 95% CI = 2.264-17.875), did not have additional duties besides their primary responsibilities (OR = 2.046, 95% CI = 1.005-4.163), and worked in a private healthcare facility (OR = 12.021, 95% CI = 1.470-98.316), were significantly more likely to be satisfied with their job. CONCLUSIONS: Most hospital pharmacists were satisfied with their current job. To further improve job satisfaction in this population, further improvements to working conditions are necessary.

COVID-19 vaccination intention and vaccine characteristics influencing vaccination acceptance: a global survey of 17 countries.

BACKGROUND: The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines present a dilemma in vaccination choices, which may result in individuals refusing a particular COVID-19 vaccine offered, hence presenting a threat to immunisation coverage and reaching herd immunity. The study aimed to assess global COVID-19 vaccination intention, vaccine characteristics influencing vaccination acceptance and desirable vaccine characteristics influencing the choice of vaccines. METHODS: An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 countries worldwide. Proportions and the corresponding 95% confidence intervals (CI) of COVID-19 vaccine acceptance and vaccine characteristics influencing vaccination acceptance were generated and compared across countries and regions. Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy. RESULTS: Of the 19,714 responses received, 90.4% (95% CI 81.8-95.3) reported likely or extremely likely to receive COVID-19 vaccine. A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia (96.4%), China (95.3%) and Norway (95.3%), while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan (34.6%), the U.S. (29.4%) and Iran (27.9%). Males, those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy. Less than two-thirds (59.7%; 95% CI 58.4-61.0) reported only being willing to accept a vaccine with an effectiveness of more than 90%, and 74.5% (95% CI 73.4-75.5) said they would accept a COVID-19 vaccine with minor adverse reactions. A total of 21.0% (95% CI 20.0-22.0) reported not accepting an mRNA vaccine and 51.8% (95% CI 50.3-53.1) reported that they would only accept a COVID-19 vaccine from a specific country-of-origin. Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology. The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries. The foremost important vaccine characteristic influencing vaccine choice is adverse reactions (40.6%; 95% CI 39.3-41.9) of a vaccine and effectiveness threshold (35.1%; 95% CI 33.9-36.4). CONCLUSIONS: The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efficient plan for the delivery of interventions dynamically tailored to the local population.

A Phase I Dose-Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies.

PURPOSE: As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically "cold" cancers, which are intrinsically insensitive to immunotherapy, as well as in "hot/warm" metastatic cancers that are, atypical of such cancers, resistant to immunotherapy. PATIENTS AND METHODS: In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400-640 mg/m2) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1-2, while the latter was administered on day 8 of cycles 1-4. Response was assessed using immune-related RECIST and retreatment was allowed, if deemed beneficial, after completion of cycle 4 or at progression. RESULTS: Twenty-two patients were enrolled, of whom 21 were evaluable, encompassing castration-resistant prostate cancer (n = 11), pancreatic cancer (n = 7), immunotherapy-resistant melanoma (n = 2), and human papillomavirus-negative head and neck cancer (n = 1). Drug-related hematologic toxicities, rash, fever, nausea, vomiting, and elevation of liver enzymes were observed in > 10% of patients. The most common drug-related grade 3 adverse event was alanine aminotransferase elevation (33.3%). Two patients discontinued ipilimumab and 4 required evofosfamide deescalation due to toxicity. Of 18 patients with measurable disease at baseline, 3 (16.7%) achieved partial response and 12 (66.7%) achieved stable disease. The best responses were observed at 560 mg/m2 evofosfamide. Preexisting immune gene signatures predicted response to therapy, while hypermetabolic tumors predicted progression. Responders also showed improved peripheral T-cell proliferation and increased intratumoral T-cell infiltration into hypoxia. CONCLUSIONS: No new or unexpected safety signals were observed from combining evofosfamide and ipilimumab, and evidence of therapeutic activity was noted.

X chromosome regulation: diverse patterns in development, tissues and disease.

Genes on the mammalian X chromosome are present in one copy in males and two copies in females. The complex mechanisms that regulate the X chromosome lead to evolutionary and physiological variability in gene expression between species, the sexes, individuals, developmental stages, tissues and cell types. In early development, delayed and incomplete X chromosome inactivation (XCI) in some species causes variability in gene expression. Additional diversity stems from escape from XCI and from mosaicism or XCI skewing in females. This causes sex-specific differences that manifest as differential gene expression and associated phenotypes. Furthermore, the complexity and diversity of X dosage regulation affect the severity of diseases caused by X-linked mutations.

Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.

The Rhox cluster on the mouse X chromosome contains reproduction-related homeobox genes expressed in a sexually dimorphic manner. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Consistent with other homeobox genes, Rhox6 and 9 are in bivalent domains prior to embryonic stem cell differentiation and thus poised for activation. In female mouse ES cells, KDM6A is specifically recruited to Rhox6 and 9 for gene activation, a process inhibited by Kdm6a knockdown in a dose-dependent manner. In contrast, KDM6A occupancy at Rhox6 and 9 is low in male ES cells and knockdown has no effect on expression. In mouse ovary where Rhox6 and 9 remain highly expressed, KDM6A occupancy strongly correlates with expression. Our study implicates Kdm6a, a gene that escapes X inactivation, in the regulation of genes important in reproduction, suggesting that KDM6A may play a role in the etiology of developmental and reproduction-related effects of X chromosome anomalies.

Mammalian X upregulation is associated with enhanced transcription initiation, RNA half-life, and MOF-mediated H4K16 acetylation.

X upregulation in mammals increases levels of expressed X-linked transcripts to compensate for autosomal biallelic expression. Here, we present molecular mechanisms that enhance X expression at transcriptional and posttranscriptional levels. Active mouse X-linked promoters are enriched in the initiation form of RNA polymerase II (PolII-S5p) and in specific histone marks, including histone H4 acetylated at lysine 16 (H4K16ac) and histone variant H2AZ. The H4K16 acetyltransferase males absent on the first (MOF), known to mediate the Drosophila X upregulation, is also enriched on the mammalian X. Depletion of MOF or male-specific lethal 1 (MSL1) in mouse ES cells causes a specific decrease in PolII-S5p and in expression of a subset of X-linked genes. Analyses of RNA half-life data sets show increased stability of mammalian X-linked transcripts. Both ancestral X-linked genes, defined as those conserved on chicken autosomes, and newly acquired X-linked genes are upregulated by similar mechanisms but to a different extent, suggesting that subsets of genes are distinctly regulated depending on their evolutionary history.

Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.

Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed 'Ohno's hypothesis'). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics. We obtained new, independent RNA-seq data, measured RNA polymerase distribution and reanalyzed published expression data in mammals, C. elegans and Drosophila. Our analyses, which take into account the skewed gene content of the X chromosome, support the hypothesis of upregulation of expressed X-linked genes to balance expression of the genome.

Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X.

In Mus spretus, the chloride channel 4 gene Clcn4-2 is X-linked and dosage compensated by X up-regulation and X inactivation, while in the closely related mouse species Mus musculus, Clcn4-2 has been translocated to chromosome 7. We sequenced Clcn4-2 in M. spretus and identified the breakpoints of the evolutionary translocation in the Mus lineage. Genetic and epigenetic differences were observed between the 5'ends of the autosomal and X-linked loci. Remarkably, Clcn4-2 introns have been truncated on chromosome 7 in M. musculus as compared with the X-linked loci from seven other eutherian mammals. Intron sequences specifically preserved in the X-linked loci were significantly enriched in AT-rich oligomers. Genome-wide analyses showed an overall enrichment in AT motifs unique to the eutherian X (except for genes that escape X inactivation), suggesting a role for these motifs in regulation of the X chromosome.

Dosage regulation of the active X chromosome in human triploid cells.

In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence-based and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s). To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81-0.84) in triploid cells with one active X and higher (1.32-1.4) in triploid cells with two active X's. Thus, overall X-linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset ( approximately 7%) of genes had expression levels apparently proportional to the number of autosomal sets.

High expression of the mammalian X chromosome in brain.

Divergence between the sex chromosomes has led to loss and differentiation of Y-linked genes and haplo-insufficiency for X-linked genes in males. A mechanism of dosage compensation, for which we recently found evidence in mammals, evolved to restore a balanced expression of the genome by doubling the transcriptional output from the X chromosome. X inactivation would then serve to avoid hyper-transcription of X-linked genes in females by silencing one X chromosome. We also found that, compared to the rest of the genome, the X chromosome contains an excess of genes highly expressed in brain tissues. The exceptionally important role of the X chromosome in brain function, evident from the prevalence of X-linked forms of mental retardation, is discussed in view of sex chromosome regulation and evolution and sexual reproduction.

Dosage compensation of the active X chromosome in mammals.

Monosomy of the X chromosome owing to divergence between the sex chromosomes leads to dosage compensation mechanisms to restore balanced expression between the X and the autosomes. In Drosophila melanogaster, upregulation of the male X leads to dosage compensation. It has been hypothesized that mammals likewise upregulate their active X chromosome. Together with X inactivation, this mechanism would maintain balanced expression between the X chromosome and autosomes and between the sexes. Here, we show that doubling of the global expression level of the X chromosome leads to dosage compensation in somatic tissues from several mammalian species. X-linked genes are highly expressed in brain tissues, consistent with a role in cognitive functions. Furthermore, the X chromosome is expressed but not upregulated in spermatids and secondary oocytes, preserving balanced expression of the genome in these haploid cells. Upon fertilization, upregulation of the active X must occur to achieve the observed dosage compensation in early embryos.

Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpG methylation during early development.

Escape from X inactivation results in expression of genes embedded within inactive chromatin, suggesting the existence of boundary elements between domains. We report that the 5' end of Jarid1c, a mouse escape gene adjacent to an inactivated gene, binds CTCF, displays high levels of histone H3 acetylation, and functions as a CTCF-dependent chromatin insulator. CpG island methylation at Jarid1c was very low during development and virtually absent at the CTCF sites, signifying that CTCF may influence DNA methylation and chromatin modifications. CTCF binding sites were also present at the 5' end of two other escape genes, mouse Eif2s3x and human EIF2S3, each adjacent to an inactivated gene, but not at genes embedded within large escape domains. Thus, CTCF was specifically bound to transition regions, suggesting a role in maintaining both X inactivation and escape domains. Furthermore, the evolution of X chromosome domains appears to be associated with repositioning of chromatin boundary elements.

The complete genome sequence of the avian pathogen Mycoplasma gallisepticum strain R(low).

The complete genome of Mycoplasma gallisepticum strain R(low) has been sequenced. The genome is composed of 996,422 bp with an overall G+C content of 31 mol%. It contains 742 putative coding DNA sequences (CDSs), representing a 91 % coding density. Function has been assigned to 469 of the CDSs, while 150 encode conserved hypothetical proteins and 123 remain as unique hypothetical proteins. The genome contains two copies of the rRNA genes and 33 tRNA genes. The origin of replication has been localized based on sequence analysis in the region of the dnaA gene. The vlhA family (previously termed pMGA) contains 43 genes distributed among five loci containing 8, 2, 9, 12 and 12 genes. This family of genes constitutes 10.4% (103 kb) of the total genome. Two CDSs were identified immediately downstream of gapA and crmA encoding proteins that share homology to cytadhesins GapA and CrmA. Based on motif analysis it is predicted that 80 genes encode lipoproteins and 149 proteins contain multiple transmembrane domains. The authors have identified 75 proteins putatively involved in transport of biomolecules, 12 transposases, and a number of potential virulence factors. The completion of this sequence has spawned multiple projects directed at defining the biological basis of M. gallisepticum.

Detection of Staphylococcus aureus enterotoxin B at femtomolar levels with a miniature integrated two-channel surface plasmon resonance (SPR) sensor.

Surface plasmon resonance (SPR) biosensors offer the capability for continuous real-time monitoring. The commercial instruments available have been large in size, expensive, and not amenable to field applications. We report here an SPR sensor system based on a prototype two-channel system similar to the single channel Spreeta devices. This system is an ideal candidate for field use. The two-channel design provides a reference channel to compensate for bulk refractive index (RI), non-specific binding and temperature variations. The SPR software includes a calibration function that normalizes the response from both channels, thus enabling accurate referencing. In addition, a temperature-controlled enclosure utilizing a thermo-electric module based on the Peltier effect provides the temperature stability necessary for accurate measurements of RI. The complete SPR sensor system can be powered by a 12V battery. Pre-functionalized, disposable, gold-coated thin glass slides provide easily renewable sensor elements for the system. Staphylococcus aureus enterotoxin B (SEB), a small protein toxin was directly detectable at sub-nanomolar levels and with amplification at femtomolar levels. A regeneration procedure for the sensor surface allowed for over 60 direct detection cycles in a 1-month period.