Dexterous magnetic manipulation of conductive non-magnetic objects.

Dexterous magnetic manipulation of ferromagnetic objects is well established, with three to six degrees of freedom possible depending on object geometry1. There are objects for which non-contact dexterous manipulation is desirable that do not contain an appreciable amount of ferromagnetic material but do contain electrically conductive material. Time-varying magnetic fields generate eddy currents in conductive materials2-4, with resulting forces and torques due to the interaction of the eddy currents with the magnetic field. This phenomenon has previously been used to induce drag to reduce the motion of objects as they pass through a static field5-8, or to apply force on an object in a single direction using a dynamic field9-11, but has not been used to perform the type of dexterous manipulation of conductive objects that has been demonstrated with ferromagnetic objects. Here we show that manipulation, with six degrees of freedom, of conductive objects is possible by using multiple rotating magnetic dipole fields. Using dimensional analysis12, combined with multiphysics numerical simulations and experimental verification, we characterize the forces and torques generated on a conductive sphere in a rotating magnetic dipole field. With the resulting model, we perform dexterous manipulation in simulations and physical experiments.

Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules.

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.

Association between dietary factors and breast cancer risk: a matched case-control study in Vietnam.

BACKGROUND: The role of diet in breast cancer prevention is controversial and limited in low-middle-income countries (LMICs). This study aimed to investigate the association between different dietary factors and breast cancer risk in Vietnamese women. METHODS: Three hundred seventy newly histologically confirmed breast cancer cases and 370 controls matched by 5-year age from September 2019 to March 2020 in Ho Chi Minh City were recorded dietary intake using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated using conditional logistic regression and adjusted with potential confounders. RESULTS: Compared to the lowest quartile of intake, we found that the highest intake of vegetables, fruit, soybean products, coffee, and egg significantly decreased breast cancer risk, including dark green vegetables (OR 0.46, 95% CI 0.27-0.78, ptrend=0.022), legumes (OR 0.19, 95% CI 0.08-0.44, ptrend <0.001), starchy vegetables (OR 0.37, 95% CI 0.21-0.66, ptrend=0.003), other vegetables (OR 0.46, 95% CI 0.28-0.77, ptrend=0.106), fruits (OR 0.44, 95% CI 0.26-0.74, ptrend <0.001), soybean product (OR 0.45, 95% CI 0.24-0.86, ptrend=0.311), coffee (OR 0.47, 95% CI 0.23-0.95, ptrend 0.004), and egg (OR 0.4, 95% CI 0.23-0.71, ptrend=0.002). CONCLUSION: Greater consumption of vegetables, fruit, soybean products, coffee, and eggs is associated with a lower risk of breast cancer. This study provides evidence of breast cancer prevention by increasing the intake of these dietary groups, especially in LMICs.

Seasonal Formation of Low-Sorbing Methylthiolated Arsenates Induces Arsenic Mobilization in a Minerotrophic Peatland.

Peatlands are known sinks for arsenic (As). In the present study, seasonal As mobilization was observed in an acidic, minerotrophic peatland (called Lehstenbach) in late summer, accompanied by a peak in dissolved sulfide (S(-II)). Arsenic speciation revealed the lowest seasonal porewater concentrations of arsenite and arsenate, likely due to As(III)-S-bridging to natural organic matter. Arsenic mobilization was driven by the formation of arsenite-S(-II) colloids and formation of methylthiolated arsenates (up to 59% of the sum of As species) and to a minor extent also of inorganic thioarsenates (6%-30%) and oxymethylated arsenates (5%-24%). Sorption experiments using a purified model peat, the Lehstenbach peat, natural (to mimic winter conditions) and reacted with S(-II) (to mimic late summer conditions) at acidic and neutral pH confirmed low sorption of methylthiolated arsenates. At acidic pH and in the presence of S(-II), oxymethylated arsenates were completely thiolated. This methylthiolation decreased As sorption up to 10 and 20 times compared with oxymethylated arsenates and arsenite, respectively. At neutral pH, thiolation of monomethylated arsenates was incomplete, and As could be partially retained as oxymethylated arsenates. Dimethylated arsenate was still fully thiolated and highly mobile. Misidentification of methylthiolated arsenates as oxymethylated arsenates might explain previous contradictory reports of methylation decreasing or increasing As mobility.

Prevalence of overweight and obesity, dietary behaviors, and physical activities among sixth graders: a cross-sectional study in Ho Chi Minh City, Vietnam.

The prevalence of overweight and obesity among adolescents has been increasing worldwide and is a significant public health challenge. Obesity is linked to several non-communicable diseases. This study aimed to determine the prevalence of overweight and obesity based on three growth references and described physical activities and dietary patterns among sixth graders in Ho Chi Minh City (HCMC). From 2018 to 2020, a cross-sectional study was conducted on 1375 students from 16 junior high schools in HCMC. We applied Probability Proportional to Size sampling to select schools. Anthropometric measurements, pubertal status assessment, and diet and physical activity data were collected through Food Frequency and Physical Activity Questionnaires. The study revealed a high prevalence of overweight and obesity among grade 6 students, with ∼45%-56% of students classified as overweight or obese using various growth references. Moreover, most students did not meet the World Health Organization's physical activity and sedentary behavior recommendations. Most students spent <60 min/day on moderate to vigorous physical activity, and over 70% spent at least 120 min/day on sedentary activities during weekdays and weekends. The diet of the students was also imbalanced, with high intakes of protein, lipids, and carbohydrates and low consumption of fruits and vegetables. Nutritionists and policymakers should inform and encourage opportunities for healthier food and more daily activity for children, starting before the sixth-grade, so they can learn how to make healthier choices and change their behavior before they reach adolescence.

Single-Molecule Conductance of Staffanes.

We report the first conductance measurements of [n]staffane oligomers in single-molecule junctions. Our studies reveal two quantum transport characteristics unique to staffanes that emerge from their strained bicyclic structure. First, though staffanes are composed of weakly conjugated C-C σ-bonds, staffanes carry a shallower conductance decay value (ß = 0.84 ± 0.02 n-1) than alkane chain analogs (ß = 0.96 ± 0.03 n-1) when measured with the scanning tunneling microscopy break junction (STM-BJ) technique. Staffanes are more conductive than other σ-bonded organic backbones in the literature on a per atom basis. Density functional theory calculations suggest staffane backbones are effective conduits for charge transport because their significant bicyclic ring strain destabilizes the HOMO-2 energy, aligning it more closely with the Fermi energy as oligomer order increases. Second, the monostaffane is significantly lower conducting than expected. DFT calculations suggest that short monostaffanes sterically enforce insulating gauche interelectrode orientations over syn orientations. Meanwhile, [2-5]staffane wires may accommodate axial mechanical strain by "rod-bending". These findings show for the first time how bicyclic ring strain can enhance charge transmission in saturated molecular wires. These studies showcase the STM-BJ technique as a valuable tool for uncovering the stereoelectronic proclivities of molecules at material interfaces.

Direct Expression of Fluorinated Proteins in Human Cells for 19F In-Cell NMR Spectroscopy.

In-cell NMR spectroscopy is a powerful approach to study protein structure and function in the native cellular environment. It provides precious insights into the folding, maturation, interactions, and ligand binding of important pharmacological targets directly in human cells. However, its widespread application is hampered by the fact that soluble globular proteins often interact with large cellular components, causing severe line broadening in conventional heteronuclear NMR experiments. 19F NMR can overcome this issue, as fluorine atoms incorporated in proteins can be detected by simple background-free 1D NMR spectra. Here, we show that fluorinated amino acids can be easily incorporated in proteins expressed in human cells by employing a medium switch strategy. This straightforward approach allows the incorporation of different fluorinated amino acids in the protein of interest, reaching fluorination efficiencies up to 60%, as confirmed by mass spectrometry and X-ray crystallography. The versatility of the approach is shown by performing 19F in-cell NMR on several proteins, including those that would otherwise be invisible by 1H-15N in-cell NMR. We apply the approach to observe the interaction between an intracellular target, carbonic anhydrase 2, and its inhibitors, and to investigate how the formation of a complex between superoxide dismutase 1 and its chaperone CCS modulates the interaction of the chaperone subunit with the cellular environment.

Longitudinal changes in bone mineral density during perimenopausal transition: the Vietnam Osteoporosis Study.

Based on the prospective cohort of the Vietnam Osteoporosis Study, we show that bone loss occurred before menopause, and that the loss accelerated in the first 5 years post-menopause. PURPOSE: To define the change in bone mineral density (BMD) among women during the menopausal transition. METHODS: The study involved 1062 women aged 40-59 who were participants of the population-based prospective Vietnam Osteoporosis Study. BMD at the femoral neck (FN), lumbar spine (LS), and whole body scan was measured by DXA. Each woman has had two BMD measurements separated by approximately 2 years, and the rate of BMD change was calculated for each woman. Multivariable linear regression models were used to quantify the association between body composition parameters and the rate of BMD change. RESULTS: At FN, there were 3 phases of BMD change: a slight decline before the age of 45-49 (average loss of 0.51%/year); a substantial decline between the ages of 49 and 54 (average loss of 1.39%/year); and then slowed down between the ages of 54 and 59 (average loss of 0.31%/year). The same trend was also observed at LS: a slight decline (- 0.56%/year) among women aged 45-49; then a significant decline between the ages of 50 and 54 (- 1.33%/year); but then slowed down at - 0.31%/year after the age of 55. Changes in BMD were not significantly associated with changes in lean mass or fat mass. CONCLUSIONS: Although bone loss occurred before menopause, the loss accelerated in the early perimenopausal transition (45-50 years of age). This finding suggests that screening for osteoporosis in women should be considered at the age of 45.

Neisseria gonorrhoeae FC428 Subclone, Vietnam, 2019-2020.

Among 114 clinical Neisseria gonorrhoeae isolates collected in Vietnam during 2019-2020, we detected 15 of subclone sequence type 13871 of the FC428 clonal complex. Fourteen sequence type 13871 isolates with mosaic penA allele 60.001 were ceftriaxone or cefixime nonsusceptible, and 3/14 were azithromycin nonsusceptible. Emergence of this subclone threatens treatment effectiveness.

Anodic Reactivity of Alkyl S-Glucosides.

A voltammetric study of a series of alkyl and aryl S-glucosides unveiled the reactivity patterns of alkyl S-glucosides toward anodic oxidation and found noteworthy differences with the trends followed by aryl derivatives. The oxidation potential of alkyl S-glucosides, estimated herein from square-wave voltammetry peak potentials (Ep), depends on the steric properties of the aglycone. Glucosides substituted with bulky groups exhibit Ep values at voltages more positive than the values of those carrying small aglycones. This relationship, observed in all analyzed alkyl series, is evidenced by good linear correlations between Ep and Taft's steric parameters (ES) of the respective alkyl substituents. Moreover, the role of the aglycone's steric properties as a primary reactivity modulator is backed by poor correlations between Ep and the radical stabilization energies (RSEs) of the aglycone-derived thiyl radicals (RS•). In contrast, aryl glucosides' Ep values exhibit excellent correlations with the aryl substituents' Hammett parameters (σ+) and the ArS• RSEs, evidencing the inherent stability of the reactive radical intermediate as the primary factor controlling aryl glucoside's electrochemical reactivity. The reactivity differences between alkyl and aryl S-glucosides also extend to the protective group's effect on Ep. Alkyl S-glucosides' reactivity proved to be more sensitive to protective group exchange.

Evaluation of genetic diversity and population structure in four indigenous duck breeds in Vietnam.

This study characterized genetic diversity and population structure of four indigenous Vietnamese duck breeds and an exotic breed for setting the conservation priority. A total of 200 samples from four duck breeds (Sincheng, Minhhuong, Muongchieng and Bauben) and an exotic breed (Supermeat) were genotyped for fifteen microsatellite markers. The average number of alleles per locus was 14.07. A moderate genetic diversity was observed for indigenous breeds as mean of observed and expected heterozygosity as Ho = 0.50 and He = 0.57, respectively. The Bauben had the lowest values of Ho (0.41) and He (0.48) while Sincheng had the highest values of Ho (0.6) and He (0.69), respectively. The inbreeding coefficients (FIS) ranged from 0.12 to 0.16, and all breeds were significantly under heterozygote deficit. Nei's genetic distance was the shortest between Minhhuong and Muongkhieng. The discriminant analysis of principal components of studied breeds resulted in four genetic clusters. The Minhhuong and Muongkhieng breeds joined the same genetic cluster while other breeds had their own clusters. These results indicated that the possibility to combine Minhhuong and Muongkhieng for reducing the cost of conservation and suggested that conservation of the Bauben should be prioritized to avoid inbreeding depression and genetic drift.

Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma.

The neural transcription factor SOX11 is usually highly expressed in typical mantle cell lymphoma (MCL), but it is absent in the more indolent form of MCL. Despite being an important diagnostic marker for this hard-to-treat malignancy, the mechanisms of aberrant SOX11 expression are largely unknown. Herein, we describe 2 modes of SOX11 regulation by the cell-cycle regulator cyclin D1 (CCND1) and the signal transducer and activator of transcription 3 (STAT3). We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac). Increased H3K9/14Ac and SOX11 expression was also observed after histone deacetylase 1 (HDAC1) or HDAC2 was depleted by RNA interference or inhibited by the HDAC inhibitor vorinostat. Mechanistically, we showed that CCND1 interacted with and sequestered HDAC1 and HDAC2 from the SOX11 locus, leading to SOX11 upregulation. Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts. Functionally, inactivation of STAT3 by inhibiting the upstream Janus kinase (JAK) 1 or JAK2 or by STAT3 knockdown was found to increase SOX11 expression, whereas interleukin-21 (IL-21)-induced STAT3 activation or overexpression of the constitutively active form of STAT3 decreased SOX11 expression. In addition, targeting SOX11 directly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11+ MCL cells. Collectively, we demonstrate the involvement of CCND1 and STAT3 in the regulation of SOX11 expression, providing new insights and therapeutic implications in MCL.

Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996-2015): a population-based study.

BACKGROUND: The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. METHODS: A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996-2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. RESULTS: In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996-2000 (95% confidence interval [95% CI]: 2.2-2.6) to 7.5 per 100,000 during 2011-2015 (95% CI: 7.3-7.9), corresponded to an overall APC of 8.7 (95% CI 7.6-9.9). The APC in men and women was 6.2 (95% CI: 4.2-8.2) and 9.2 (95% CI: 8.0-10.4), respectively. The incidence rate in the < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3-12.0)). CONCLUSIONS: There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.

B-cell receptor-mediated NFATc1 activation induces IL-10/STAT3/PD-L1 signaling in diffuse large B-cell lymphoma.

Knowledge of programmed death ligand 1 (PD-L1) expression and its regulation in B-cell lymphoma cells is limited. Investigating mechanisms that control PD-L1 expression in B-cell lymphoma cells might identify biomarkers that predict the efficacy of immunotherapy with anti-programmed death-1/PD-L1 antibodies. In addition, identification of mechanisms that regulate PD-L1 may identify molecules that can be targeted to improve the clinical efficacy of immune checkpoint inhibitors. In this study, we used proteomic approaches and patient-derived B-cell lymphoma cell lines to investigate mechanisms that regulate PD-L1 expression. We found that PD-L1 expression, particularly in nongerminal center B cell-derived diffuse large B-cell lymphoma (DLBCL), is controlled and regulated by several interactive signaling pathways, including the B-cell receptor (BCR) and JAK2/STAT3 signaling pathways. We found that that BCR-mediated NFATc1 activation upregulates IL-10 chemokine expression in PD-L1+ B-cell lymphoma cells. Released IL-10 activates the JAK2/STAT3 pathway, leading to STAT3-induced PD-L1 expression. IL-10 antagonist antibody abrogates IL-10/STAT3 signaling and PD-L1 protein expression. We also found that BCR pathway inhibition by BTK inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3 activation, thereby inhibiting IL-10 and PD-L1 expression. Finally, we validated the PD-L1 signaling network in 2 primary DLBCL cohorts consisting of 428 and 350 cases and showed significant correlations among IL-10, STAT3, and PD-L1. Thus, our findings reveal a complex signaling network regulating PD-L1 expression in B-cell lymphoma cells and suggest that PD-L1 expression can be modulated by small molecule inhibitors to potentiate immunotherapies.

An assessment of genetic diversity and population structures of fifteen Vietnamese indigenous pig breeds for supporting the decision making on conservation strategies.

The study aimed to characterize genetic diversity, genetic clusters, and phylogenetic relationships of 15 Vietnamese indigenous pig breeds across the country for supporting the decision making of the conservation strategies. For this purpose, 638 samples from the breeds together with two wild pig breeds and an exotic breed were genotyped with 19 microsatellite markers recommended from FAO/ISAG for diversity studies. The higher genetic diversity was observed for indigenous breeds (mean He = 0.67) and wild breeds (mean He = 0.74); the indigenous CoAluoi breed compared the out-breed Landrace (He = 0.59). Fifteen percent of the genetic variation came from differences among breeds. The unrooted neighbor-joining dendrogram obtained from Nei's genetic distances showed three nodes with 100% supported bootstrap values. The first node included the three indigenous breeds (Hung, LungPu, and MuongKhuong), the second node included the indigenous BaXuyen and the exotic Landrace, and the third node included the two wild Thailand and Vietnam pig breeds. The discriminant analysis of principal component (DAPC) of 18 studied breeds resulted in 12 genetic clusters. Unlike the other indigenous breeds, the BaXuyen was in the same genetic cluster with the exotic Landrace-which agreed with the 100% bootstrap value of their node-so the BaXuyen should not be conserved. The five indigenous pig breeds-Huong, VanPa, Soc, ChuProng, and CoAluoi-were assigned to their own clusters, which agreed with the low supported bootstrap values of their nodes. These five breeds should be in the high conservation priority. Finally, the 9 indigenous pig breeds (MuongKhuong, LungPu, Hung, TapNa, MongCai, HaLang, Lung, Meo, and Ban breeds) formed four genetic admixture structures. These results suggest the conservation strategies should be built based on from five to nine pig groups thus reducing the cost of conservation whereas still remaining the genetic diversity of the studied breeds.

Interleukin-1 receptor associated kinase (IRAK)-M -mediated type 2 microglia polarization ameliorates the severity of experimental autoimmune encephalomyelitis (EAE).

Toll-like receptor 4 (TLR4) play a key role in activating the innate immune system during pathogen recognition. In the pathogenesis of multiple sclerosis (MS), activated TLR4 together with myeloid differentiation primary response gene 88 (MyD88) produce an inflammatory microenvironment that promotes the differentiation of microglia into the M1 phenotype, who plays a key role in the pathogenesis of MS. Interleukin-1 receptor-associated kinase (IRAK)-M is specifically expressed in microglia in central nervous system (CNS) and act as a negative regulator of TLR4-MyD88 signaling pathway. Moreover, previous studies have shown that IRAK-M promotes the differentiation of type 2 microglia; however, its role in MS has not been explored. In the present study, we demonstrated that IRAK-M expression is elevated during EAE, and IRAK-M-/- mice significantly accelerated course and increased severity of disease, accompanied by a visible increase of the M1 microglia infiltrated. In conclusion, these data indicates that IRAK-M significantly improves EAE onset through down-regulation of the TLR4-MyD88 signaling pathway, which finally leads to differentiation of M2 phenotype in the microglia. Our study suggests that IRAK-M may be a potential therapeutic target for the treatment of MS.

AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma.

AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found that high levels of p-AKT nuclear expression, observed in 24.3% of the study cohort, were associated with significantly worse progression-free survival and Myc and Bcl-2 overexpression. However, multivariate analysis indicated that AKT hyperactivation was not an independent factor. miRNA profiling analysis demonstrated that 63 miRNAs directly or indirectly related to the phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway were differentially expressed between DLBCLs with high and low p-AKT nuclear expression. We further targeted AKT signaling using a highly selective AKT inhibitor MK-2206 in 26 representative DLBCL cell lines and delineated signaling alterations using a reverse-phase protein array. MK-2206 treatment inhibited lymphoma cell viability, and MK-2206 sensitivity correlated with AKT activation status in DLBCL cells. On MK-2206 treatment, p-AKT levels and downstream targets of AKT signaling were significantly decreased, likely because of the decreased feedback repression; Rictor and phosphatidylinositol 3-kinase expression and other compensatory pathways were also induced. This study demonstrates the clinical and therapeutic implications of AKT hyperactivation in DLBCL and suggests that AKT inhibitors need to be combined with other targeted agents for DLBCL to achieve optimal clinical efficacy.

Comparison of the microdrop and minimum volume cooling methods for vitrification of porcine in vitro-produced zygotes and blastocysts after equilibration in low concentrations of cryoprotectant agents.

We compared the efficacy of the microdrop and minimum volume cooling (MVC) methods for the vitrification of in vitro-produced porcine zygotes and blastocysts after equilibration in low concentrations of cryoprotectant agents. Zygotes and blastocysts were equilibrated in 2% (v/v) ethylene glycol and 2% (v/v) propylene glycol for 13-15 min. Then, they were vitrified in a medium comprised of 17.5% ethylene glycol, 17.5% propylene glycol, 0.3 M sucrose, and 50 mg/ml polyvinylpyrrolidone either by either dropping them directly into liquid nitrogen (microdrop method) or placing them on Cryotop sheets in a minimum volume of medium and plunging into liquid nitrogen (MVC method). Both zygotes and blastocysts were successfully vitrified. For the vitrification of zygotes, the MVC and microdrop methods were equally effective; however, for blastocyst vitrification, MVC was superior. For both methods, the vitrification of zygotes produced higher-quality embryos than the vitrification of blastocysts.

Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence.

Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions. To address this aim, a search of the literature was conducted using Pubmed, Google Scholar, and the Cochrane Database. In total, 239 unique articles were screened, and the 22 preclinical studies that met the a priori inclusion/exclusion criteria were summarized, including the study aims, sample (size, groups, species, strain, sex, age/weight), TBI model, therapeutic details (preparation, dose, route, duration), key findings, and conclusions. The evidence from these 22 studies was analyzed to draw comparisons across studies, identify remaining gaps, and suggest future directions. Taken together, the published evidence suggests that MEL has neuroprotective properties via a number of mechanisms with few toxic effects reported. Notably, available evidence is largely based on data from adult male rats and, to a lesser extent, mice. Few studies collected data beyond a few days of the initial injury, necessitating additional longer-term studies. Other future directions include diversification of samples to include female animals, pediatric and geriatric animals, and transgenic strains.

High-Throughput Screening and Prediction Model Building for Novel Hemozoin Inhibitors Using Physicochemical Properties.

It is essential to continue the search for novel antimalarial drugs due to the current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. An in vitro colorimetric high-throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9,600 structurally diverse compounds. The physicochemical properties of positive hits and randomly selected compounds were extracted from the ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i.e., traditional multivariate logistic regression and Bayesian model averaging. Our results showed that a total of 224 positive-hit compounds exhibited the ability to inhibit hemozoin formation, with 50% inhibitory concentrations (IC50s) ranging from 3.1 µM to 199.5 µM. The best model according to traditional multivariate logistic regression included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and number of atoms of hydrogen, while the best model according to Bayesian model averaging included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and index of refraction. Both models had a good discriminatory power, with area under the curve values of 0.736 and 0.781 for the traditional multivariate model and Bayesian model averaging, respectively. In conclusion, the prediction models can be a new, useful, and cost-effective approach for the first screen of hemozoin inhibition-based antimalarial drug discovery.