Impact of lower concentrations of dimethyl sulfoxide on cryopreservation of autologous hematopoietic stem cells: a systematic review and meta-analysis of controlled clinical studies.

BACKGROUND AIMS: Cryopreservation of hematopoietic stem cells (HSCs) is crucial for autologous transplantation, cord blood banking and other special circumstances. Dimethyl sulfoxide (DMSO) is used most commonly for cryopreserving HSC products but can cause infusional toxicities and affect cell viability and engraftment after transplant. A systematic review of controlled studies using lower concentrations of DMSO to cryopreserve HSC products in clinical transplant studies is needed to determine the effect of reducing DMSO concentrations on post-thaw cell viability, initial engraftment and adverse effects on patient health. METHODS: All studies identified in our systematic search (to July 11, 2023) examining the use of cryopreserved peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (AHCT) were included. Meta-analysis was performed to determine how varying the concentration of DMSO during cryopreservation effects post-thaw cell viability, initial engraftment and adverse effects on patient health. RESULTS: A total of 1547 studies were identified in our systematic search, with seven published articles meeting eligibility for inclusion in meta-analysis. All patients underwent AHCT using (PBSCs) to treat hematologic malignancies. The viability of CD34+ cells post thaw was greater when cryopreserved with 5% DMSO compared with 10% DMSO, with lower rates of adverse side effects in patients. DMSO concentration had minimal impact on rates of initial engraftment. Significant heterogeneity in outcome reporting was observed and the potential for bias was identified in all studies. CONCLUSIONS: Reducing the concentration of DMSO from 10% to 5% during cryopreservation of autologous PBSCs may improve cell viability and reduce DMSO-associated adverse effects in patients undergoing AHCT. Data from more studies with similar patients and standard outcome reporting are needed to increase confidence in our initial observations. PROTOCOL REGISTRATION: PROSPERO; registration number CRD42023476809 registered November 8, 2023.

Asymmetrical reproductive interference between Aedes aegypti and Aedes albopictus: Implications for coexistence.

BACKGROUND OBJECTIVES: Aedes aegypti and Aedes albopictus are two sympatric mosquito species that compete with each other for resources when their breeding habitats overlap. This study examines what happens when sympatric Ae. aegypti and Ae. albopictus mosquitoes' mate with each other and other species by looking at insemination rates, fecundity, and hatchability rate. METHODS: We performed controlled mating experiments in laboratory setting, assessing both conspecific and interspecific crosses. We measured insemination rates, egg numbers, and hatching success to examine the reproductive interference dynamics between these two distinct mosquito species. RESULTS: In the context of conspecific mating, it was observed that both female Ae. aegypti and Ae. albopictus exhibited high insemination rates, with percentages of 98% and 94% respectively. However, interspecific mating exhibited interesting asymmetries: Ae. albopictus males achieved a notable insemination success rate of 28% when mating with Ae. aegypti females, while Ae. aegypti males achieved only an 8% insemination success with Ae. albopictus females. Additionally, females that mated with interspecific males had reduced production of viable eggs compared to conspecific mating. Most notably, interspecific mating resulted in the production of infertile eggs, while conspecific mating led to successful hatching. INTERPRETATION CONCLUSION: The study reveals that Ae. aegypti and Ae. albopictus can asymmetrically interfere with each other's reproduction, causing a 'satyr' effect. This understanding of interspecific competition and reproductive interference in these mosquito species could impact their coexistence in shared breeding habitats.

Applications of Ionic Liquids in Whole-Cell and Isolated Enzyme Biocatalysis.

Ionic liquids have unique chemical properties that have fascinated scientists in many fields. The effects of adding ionic liquids to biocatalysts are many and varied. The uses of ionic liquids in biocatalysis include improved separations and phase behaviour, reduction in toxicity, and stabilization of protein structures. As the ionic liquid state of the art has progressed, concepts of what can be achieved in biocatalysis using ionic liquids have evolved and more beneficial effects have been discovered. In this review ionic liquids for whole-cell and isolated enzyme biocatalysis will be discussed with an emphasis on the latest developments, and a look to the future.

Investigating Rhythmicity in App Usage to Predict Depressive Symptoms: Protocol for Personalized Framework Development and Validation Through a Countrywide Study.

BACKGROUND: Understanding a student's depressive symptoms could facilitate significantly more precise diagnosis and treatment. However, few studies have focused on depressive symptom prediction through unobtrusive systems, and these studies are limited by small sample sizes, low performance, and the requirement for higher resources. In addition, research has not explored whether statistically significant rhythms based on different app usage behavioral markers (eg, app usage sessions) exist that could be useful in finding subtle differences to predict with higher accuracy like the models based on rhythms of physiological data. OBJECTIVE: The main objective of this study is to explore whether there exist statistically significant rhythms in resource-insensitive app usage behavioral markers and predict depressive symptoms through these marker-based rhythmic features. Another objective of this study is to understand whether there is a potential link between rhythmic features and depressive symptoms. METHODS: Through a countrywide study, we collected 2952 students' raw app usage behavioral data and responses to the 9 depressive symptoms in the 9-item Patient Health Questionnaire (PHQ-9). The behavioral data were retrieved through our developed app, which was previously used in our pilot studies in Bangladesh on different research problems. To explore whether there is a rhythm based on app usage data, we will conduct a zero-amplitude test. In addition, we will develop a cosinor model for each participant to extract rhythmic parameters (eg, acrophase). In addition, to obtain a comprehensive picture of the rhythms, we will explore nonparametric rhythmic features (eg, interdaily stability). Furthermore, we will conduct regression analysis to understand the association of rhythmic features with depressive symptoms. Finally, we will develop a personalized multitask learning (MTL) framework to predict symptoms through rhythmic features. RESULTS: After applying inclusion criteria (eg, having app usage data of at least 2 days to explore rhythmicity), we kept the data of 2902 (98.31%) students for analysis, with 24.48 million app usage events, and 7 days' app usage of 2849 (98.17%) students. The students are from all 8 divisions of Bangladesh, both public and private universities (19 different universities and 52 different departments). We are analyzing the data and will publish the findings in a peer-reviewed publication. CONCLUSIONS: Having an in-depth understanding of app usage rhythms and their connection with depressive symptoms through a countrywide study can significantly help health care professionals and researchers better understand depressed students and may create possibilities for using app usage-based rhythms for intervention. In addition, the MTL framework based on app usage rhythmic features may more accurately predict depressive symptoms due to the rhythms' capability to find subtle differences. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51540.

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective.

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem-cell niches in the marrow. Stem-cell niches, in particular, can be altered by the effects of previous treatments, aging, and the paracrine effects of leukemic cells, which create inhospitable bone-marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem-cell niches can be restored to favor normal hematopoiesis may be key to reducing leukemic relapses following transplant.

A novel bivalent interaction mode underlies a non-catalytic mechanism for Pin1-mediated protein kinase C regulation.

Regulated hydrolysis of the phosphoinositide phosphatidylinositol(4,5)-bis-phosphate to diacylglycerol and inositol-1,4,5-P3 defines a major eukaryotic pathway for translation of extracellular cues to intracellular signaling circuits. Members of the lipid-activated protein kinase C isoenzyme family (PKCs) play central roles in this signaling circuit. One of the regulatory mechanisms employed to downregulate stimulated PKC activity is via a proteasome-dependent degradation pathway that is potentiated by peptidyl-prolyl isomerase Pin1. Here, we show that contrary to prevailing models, Pin1 does not regulate conventional PKC isoforms α and ßII via a canonical cis-trans isomerization of the peptidyl-prolyl bond. Rather, Pin1 acts as a PKC binding partner that controls PKC activity via sequestration of the C-terminal tail of the kinase. The high-resolution structure of full-length Pin1 complexed to the C-terminal tail of PKCßII reveals that a novel bivalent interaction mode underlies the non-catalytic mode of Pin1 action. Specifically, Pin1 adopts a conformation in which it uses the WW and PPIase domains to engage two conserved phosphorylated PKC motifs, the turn motif and hydrophobic motif, respectively. Hydrophobic motif is a non-canonical Pin1-interacting element. The structural information combined with the results of extensive binding studies and experiments in cultured cells suggest that non-catalytic mechanisms represent unappreciated modes of Pin1-mediated regulation of AGC kinases and other key enzymes/substrates.

Biocatalytic Generation of o-Quinone Imines in the Synthesis of 1,4-Benzoxazines and Its Comparative Green Chemistry Metrics.

1,4-Benzoxazines are important motifs in many pharmaceuticals and can be formed by a reaction sequence involving the oxidation of o-aminophenols to their corresponding quinone imine followed by an in situ inverse electron demand Diels-Alder (IEDDA) cycloaddition with a suitable dienophile. Reported herein is the development of a reaction sequence that employs horseradish peroxidase to catalyze the oxidation of the aminophenols prior to the IEDDA as a more sustainable alternative to the use of conventional stoichiometric oxidants. The synthesis of 10 example benzoxazines is demonstrated in this "one-pot, two-step" procedure with yields between 42% and 92%. The green chemistry metrics, including the E-factor and generalized reaction mass efficiency, for this biocatalytic reaction were compared against the conventional chemical approach. It was found that the reported biocatalytic route was approximately twice as green by these measures.

Infant and young child feeding practices and associated socioeconomic and demographic factors among children aged 6-23 months in Ghana: Findings from Ghana Multiple Indicator Cluster Survey, 2017-2018.

BACKGROUND: Association between poor infant and young child feeding (IYCF) practices and malnutrition in infants and young children (IYC) is well established. Furthermore, appropriate IYCF practices are important during the first 1,000 days of life to ensure optimal health and development. Understanding IYCF practices and associated socioeconomic and demographic factors will inform interventions to achieve the UN 2030 Sustainable Development Goal (SDG) target to end malnutrition in all forms. OBJECTIVE: This study estimates the prevalence of Minimum Dietary Diversity (MDD), Minimum Meal Frequency (MMF), and Minimum Acceptable Diet (MAD), and examines their association with socioeconomic and demographic characteristics among children aged 6-23 months in Ghana. METHOD: We used data from the Ghana Multiple Indicator Cluster Survey 6 (GMICS6) conducted in 2017-18. Participants were recruited through multi-stage stratified cluster sampling. Information on caregiver's self-reported breastfeeding status and 24-hour dietary recall of foods IYC were fed with were collected through face-to-face interviews. We estimated the prevalence of MDD, MMF and MAD with a 95% confidence interval (CI). We investigated the socioeconomic and demographic determinants of MDD, MMF and MAD using univariate and multivariable logistic regression analyses. FINDINGS: Among 2,585 IYC aged 6-23 months, MDD, MMF and MAD were estimated as 25.46%, 32.82% and 11.72% respectively. Age of the IYC, educational status of the mothers/primary caregivers, and resident regions were found to have positive associations with MDD, MMF and MAD. In addition, the richest household wealth index and urban area of residence were found to have significant positive associations with MDD. CONCLUSION: We report a low prevalence of MDD, MMF and MAD. Efforts to improve IYCF practices among children aged 6-23 months in Ghana should focus on multi-sectorial approaches including increasing access to formal education, income-generating activities and addressing regional and rural-urban inequity.

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of hematopoietic stem cells.

Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a stem cell agonist in AA2P and optimize a series of stem cell agonist cocktails (SCACs) to help promote robust expansion of human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention and function of immature HSPC. We show that AA2P-mediated HSPC expansion is driven through DNA demethylation leading to enhanced expression of AXL and GAS6. Further, we demonstrate that GAS6 enhances the serial engraftment activity of HSPCs and show that the GAS6/AXL pathway is critical for robust HSPC expansion.

Biological and computational studies provide insights into Caesalphinia digyna Rottler stems.

Caesalpinia digyna (Rottl.) (Family: Fabaceae) is an essential medicinal plant for it's conventional uses against a kind of human disorders. This research aims to investigate the antidiarrheal, antibacterial and antifungal properties of the methanol extract of the stems extracts of the C. digyna (MECD). The in vivo antidiarrheal activity of the stem extracts were evaluated by using castor oil-induced diarrhea, castor oil-induced enteropooling and charcoal induced intestinal transit in mice model. Besides, in vitro antimicrobial potentiality of MECD was investigated by the disc diffusion method. In silico activity of the isolated compounds were performed by Schrödinger-Maestro (Version 11.1) software. In addition, The ADME/T analysis and PASS prediction were implemented by using pass online tools. In the antidiarrheal investigation, the MECD exhibited a notable inhibition rate in all test approaches which were statistically significant (p < 0.05, p < 0.1, p < 0.01). MECD 400 mg/kg showed the maximum antidiarrheal potency in all the test methods. In vitro antimicrobial analysis unveiled that, MECD revealed higher potentiality against almost all pathogens and indicates dose-dependent activity against almost all the bacteria and fungi. In the case of in silico evaluation of anti-diarrheal, anti-bacterial and anti-fungal activity, all three isolated compounds met the pre-conditions of Lipinski's five rules for drug discovery. Pass predicted study also employed for all compounds. However, The chemical constituents of the C. digyna can be a potent source of anti-diarrheal, anti-bacterial and anti-fungal medicine and further modification and simulation studies are required to establish the effectiveness of bioactive compounds.

Molecular genetic and biochemical characterization of a putative family of zinc metalloproteins in Caenorhabditis elegans.

Four highly similar genes (W08E12.2, W08E12.3, W08E12.4 and W08E12.5) which are consecutively aligned on chromosome IV of the C. elegans genome are predicted to code for small (120-141aa) yet cysteine rich (18-19 cysteines) proteins. Cloning and sequencing of the genomic regions of the isoforms confirmed the presence and order of all genes. The generation of transgenic worms strains with an integrated single copy or extrachromosomal multi-copy PW08E12.3;W08E12.4::GFP uncovered that W08E12.3 and W08E12.4 are constitutively expressed in the pharynx and significantly induced in worms exposed to 100 µM Zn. Knockdown by RNAi did not have a marked consequence on reproductive performance nor was a Zn-dependent effect on nematode growth observed. However, RNAi of these genes led to an accumulation of Zn in the intestinal cells. W08E12.3 was recombinantly expressed in E. coli and the purified protein was shown to be able to bind up to 6.5 Zn molecules at neutral pH. Zn-binding was acid-labile and the apo protein was observed at pH < 4.3. This characterization suggests W08E12.2, W08E12.3, W08E12.4 and W08E12.5 belong to a family of putative Metalloproteins which, akin to metallothioneins, may play an important role in Zn-sensing, homeostasis and/or detoxification.

Prevalence and experiences of intimate partner violence against women with disabilities in Bangladesh: results of an explanatory sequential mixed-method study.

This study was aimed to estimate the prevalence of intimate partner violence (IPV) in a sample of 226 women with disabilities living in four different districts of Bangladesh. It also explored the physical and psychological suffering of women experiencing violence and their various coping strategies. A cross-sectional survey was carried out with 226 women with disabilities to measure the prevalence of IPV, and 16 in-depth interviews were conducted to document in detail the experiences of violence encountered by the abused women. Among the 226 women interviewed in the survey, about 84% reported ever having experienced at least one act of emotional abuse, physical, or sexual violence from their partner during their lifetime. Women who were older (aged above 32 years), separated, and members of economic/savings group were more likely to report ever having experienced any IPV than women with disabilities who were younger (aged 32 years and less), married, and not members of economic/savings group. Most of the women experiencing violence reported sufferings from physical and psychological problems. Of all the women who experienced violence, less than half (45%) reported seeking support to minimize or avoid violence experiences. However, seeking support from informal network such as family and relatives was commonly reported by many (81.4%) of them. Study findings suggest that women with disabilities who possess poor socio-economic status coupled with economic dependency on husbands' income and wide-spread social stigma against disability make them vulnerable to IPV. Future interventions to address IPV against women with disabilities should include building community knowledge of disability and IPV, countering the pervasive social stigma against disabilities, and improving the socio-economic conditions of women with disabilities through education and employment.