Three new lanostane triterpenoids and two new amides from Alternaria sp. with NLRP3 inflammasome inhibitory activity.

Three new lanostane triterpenoids (1-3) along with two new amides fatty compounds (4-5) were isolated from the ethyl acetate extract of a culture of the endophytic fungus Alternaria sp. gx-2. Their structures were identified by 1D and 2D NMR spectral data and HRESIMS. Compounds 1-12 were evaluated for their anti-inflammatory and tyrosinase inhibition activities. The isolated compounds did not show inhibitory activities at a concentration of 100 µM against tyrosinase, while under the concentration of 10 µM, the release of lactate dehydrogenase (LDH) inhibition rate of compound 1 was 54.45%, indicating that compound 1 had moderate anti-inflammatory activity on the activation of NLRP3 inflammasome.

Korean Developmental Screening Test for Infants and Children (K-DST): development, applications, and implications for future early childhood development interventions.

Evidence of the importance of early childhood development (ECD) has transformed child health monitoring and screening tools. Development of the Korean Developmental Screening Test for Infants and Children (K-DST) has expanded the applications of child health screening to a large number of infants and children in Korea and is contributing to the early detection of neurodevelopmental disorders and delivery of timely interventions. The previous screening tool (Korean Ages and Stages Questionnaire) raised some concerns, as its lack of consideration of the cultural background of the Korean population can lead to inaccurate or imprecise diagnoses. The K-DST, a tailored tool for Korean infants and children, is a simple and cost-efficient solution for child health monitoring and screening. This review focuses on the development and role of the K-DST in ensuring ECD. Here we review use of the K-DST for ECD screenings and discuss the best strategy for its use in other countries.

A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family / 亚洲男科学杂志(英文版)

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.

The use of drones for the delivery of diagnostic test kits and medical supplies to remote First Nations communities during Covid-19.

BACKGROUND: Health care inequity in remote and rural Indigenous communities often involves difficulty accessing health care services and supplies. Remotely Piloted Aircraft Systems, or drones, offer a potentially cost-effective method for reducing inequity by removing geographic barriers, increasing timeliness, and improving accessibility of supplies, equipment, and remote care. METHODS: We assessed the feasibility of drones for delivery of supplies, medical equipment, and medical treatment across multiple platforms, including drone fleet development and testing; payload system integration (custom fixed-mount, winch, and parachute); and medical delivery simulations (COVID-19 test kit delivery and return, delivery of personal protective equipment, and remote ultrasound delivery and testing). RESULTS: Drone operational development has led to a finalized, scalable fleet of small to large drones with functional standard operating procedures across a range of scenarios, and custom payload systems including a fixed-mount, winch-based and parachute-based system. Simulation scenarios were successful, with COVID-19 test swabs returned to the lab with no signal degradation and a remote ultrasound successfully delivered and remotely guided in the field. DISCUSSION/CONCLUSIONS: Drone-based medical delivery models offer an innovative approach to addressing longstanding issues of health care access and equity and are particularly relevant in the context of SARS-CoV-2.

Defect-rich honeycomb-like nickel cobalt sulfides on graphene through rapid microwave-induced synthesis for ultrahigh rate supercapacitors.

Nickel cobalt sulfides (NCS) are regarded as potential energy storage materials due to the versatile valent states and rich electrochemical activity, but their sluggish synthesis process and inferior rate performance hinder them from large-scale application. Herein, microwave-induced strategy has been employed for efficient synthesis of honeycomb-like NCS/graphene composites, which are explored as ultrahigh rate battery-type electrodes for supercapacitors. Due to the internal heat mechanism, the synthesis time of NCS by microwave could be shortened from hours to minutes. Density functional theory was simulated to uncover the interfacial effect between NCS and graphene, and the resulted Schottky barrier is in favor of enhancing redox activity and capacity. Ultimately, the obtained defect-rich nickel cobalt sulfides/graphene with thermal treatment (NCS/G-H) could exhibit a high specific capacitance of 1186 F g-1 at 1 A g-1 and sustain 89.8% capacity even after the increase of current density over 20 times, which is much superior to bare NCS and NCS/graphene. Furthermore, the assembled NCS/G-H hybrid supercapacitor delivers supreme energy density of 46.4 Wh kg-1, and retains outstanding long-term stability of 89.2% after 10 k cycles. These results indicate that the synthesized NCS/G-H by time-saving microwave-induced liquid process could be served as high rate materials for supercapacitors.

Density functional theory, molecular docking and bioassay studies on (S)-2-hydroxy-N-(2S,3S,4R,E)-1,3,4 trihydroxyicos-16-en-2-yl)tricosanamide.

A novel indigoferamide-A, earlier isolated from the seeds of Indigofera heterantha Wall was characterized using density functional theory, molecular docking and bioassays studies. Density functional theory calculations were performed at B3LYP/6-31G(d,p) to gain geometric insight of the compound. Conformational analyses have been performed around three important dihedral angles to explore the lowest energy structure and conformer. The simulated vibrational spectrum of the compound at B3LYP/6-31G(d,p) was scaled with two scaling factors, and the scaled harmonic vibrations shows nice correlation with the experimental values. 1H and 13C NMR chemical shifts were calculated using Cramer's re-parameterized function W04 at 6- 31G(d,p) basis set. Several conformers lying within 2 kcal mol-1 of the minimum energy conformer were considered; however, the chemical shifts were not significantly different among these conformers. The Gaussian averaged theoretical 1H and 13C chemical shifts correlate nicely with the experimental data. Electronic properties such as band gap, ionization potential and electron affinities were also simulated for the first time, however, no comparison could be made with the experiment. The compound was also screened for urease, antiglycation activities and the theoretical explanation of the results is provided based on molecular docking simulations.

Microporous 2D NiCoFe phosphate nanosheets supported on Ni foam for efficient overall water splitting in alkaline media.

The development of high-performance non-precious electrocatalysts for both H2 and O2 evolution reactions (HER and OER activities) and overall water splitting is highly desirable but remains a grand challenge. Herein, we report a facile method to synthesize ultrathin, amorphous, porous, oxygen and defect enriched NiCoFe phosphate nanosheets (NSs). Owing to their microporous confinement in a 2D orientation, which can reduce the ion transport resistance during electrochemical processes, and defect enriched structure with higher electrochemically active surface area, these NiCoFe phosphate porous nanosheets supported on nickel foam (NiCoFe phosphate NSs/NF) facilitate the diffusion of gaseous products (H2 and O2) and exhibit remarkable catalytic performance and outstanding stability for both HER, OER and overall water splitting in an alkaline electrolyte (1.0 M KOH). For the OER electrocatalyst, 2D NiCoFe phosphate NSs/NF was oxidized to NiCoFe oxides/hydroxides on the catalyst surface and exhibited remarkable OER activity with a low overpotential of only 240 mV needed to reach a current density of 10 mA cm-2. For HER, 2D NiCoFe phosphate NSs/NF afforded a current density of 10 mA cm-2 at a low overpotential of only -231 mV. Furthermore, employing 2D NiCoFe phosphate NSs/NF as the electrocatalyst for both the anode and the cathode, a water splitting electrolyzer was able to reach 10 mA cm-2 at a cell voltage of 1.52 V with robust durability. Various characterization techniques indicated that the long term stability and the activity for overall water splitting are due to the porosity, the electrochemically active constituents, and synergistic effects. This work could be inspiring in the design of Earth abundant and highly efficient electrocatalysts for overall water splitting, especially for OER.

Trimetallic PtCoFe Alloy Monolayer Superlattices as Bifunctional Oxygen-Reduction and Ethanol-Oxidation Electrocatalysts.

A synthesis strategy for the preparation of trimetallic PtCoFe alloy nanoparticle superlattices is reported. Trimetallic PtCoFe alloy monolayer array of nanoparticle superlattices with a large density of high index facets and platinum-rich surface are successfully prepared by coreduction of metal precursors in formamide solvent. The concentration of cetyl trimethyl ammonium bromide plays a vital role for the formation of a monolayer array of nanoparticle superlattices, while the size of nanoparticles is determined by NaI. The prepared monolayer array of nanoparticle superlattices is the superior catalyst for oxygen reduction reaction as well as for ethanol oxidation owing to their specific structural and compositional characteristics.

Diplomatic and operational adaptations to global health programmes in post-conflict settings: contributions of monitoring and evaluation systems to health sector development and 'nation-building' in South Sudan.

Monitoring and evaluation (M&E) systems are an essential element of functioning and accountable global health programmes. In post-conflict settings, the role of M&E systems is also critical to ensure that health services are being delivered to those populations and regions most in need. Given the inherent challenges of health service delivery in such environments, a range of both diplomatic and operational adaptations to M&E procedures are necessary. Using the '12 components' of a functioning M&E system as a conceptual and analytical framework, we observed and reviewed the key challenges to M&E systems in South Sudan as part of a broader review of United Nations Development Programme (UNDP) activities supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria. Based on additional interview-based reviews and analyses of M&E activities, a list of adaptations to standardized M&E procedures in response to post-conflict environmental challenges was developed. The study concludes that development and implementation of M&E systems in post-conflict environments requires extensive adaptations to conventional procedures. Flexible and adaptable as well as 'diplomatically sensitized' M&E systems are considered to be essential to the successful completion of M&E-related activities, and may also contribute to broader international relations, 'nation-building', and peace-keeping goals.

Discriminating hepatocellular carcinoma from metastatic carcinoma on fine-needle aspiration biopsy of the liver: the utility of immunocytochemical panel.

The cytomorphologic features of hepatocellular carcinoma (HCC) in fine-needle aspiration (FNA) biopsy are well described. However, correctly diagnosing HCC on cytologic features alone and differentiating it from metastatic adenocarcinoma (MAC) remains a challenge. Studies have recommended the use of various immunocytochemical (ICC) stains to aid in the diagnosis and distinction of these tumors with variable success rates. In this study, we evaluated a panel of seven ICC stains, HepPar1, glypican-3, polyclonal and monoclonal carcinoembryonic antigen (pCEA, mCEA), MOC-31, CK7, and CK20, in 42 FNA cases of HCC and 48 FNA cases of MAC. The aim was to identify the most sensitive and specific markers and the best panel for accurate diagnosis. Overall, 38 of 42 HCC and 44/48 MAC tumors were correctly identified by a panel of four markers, CK7, MOC-31, HepPar1, and glypica-3, with accuracy rate of 90.5 and 91.7%, respectively. In the HCC group, glypican-3 was most sensitive and detected in 34/42 (81%), whereas HepPar1 and pCEA were less sensitive and detected in 30/42 (71.4%) and 21/42 (50%), respectively. In the MAC group, MOC-31 was most sensitive and detected in 38/48 (79.2%), followed by CK7 in 20/48 (41.7%). Stepwise logistic regression analysis showed that a panel of glypican-3, HepPar1, MOC-31, and CK7 is most helpful in diagnosing and accurately differentiating HCC from MAC on FNA biopsies of the liver. We conclude that a panel of HepPar1, glypican-3, MOC-31, and CK7 accurately and statistically significantly differentiates these two malignancies (P < 0.05).

Comparison of Thin-Prep and cell block preparation for the evaluation of Thyroid epithelial lesions on fine needle aspiration biopsy.

BACKGROUND: The objective of this study was to compare the utility of Thin-Prep (TP) cytologic preparation with that of Cell Block (CB) preparation in the diagnosis of thyroid lesions, mainly follicular epithelial lesions, by fine needle aspiration biopsy (FNAB). Feasibility of using the TP slides for immunocytochemical stains is also discussed. METHODS: A total of 126 consecutive cases of thyroid FNAB with TP slides and 128 consecutive cases of thyroid FNAB with CB slides were reviewed blindly by two cytopathologists. The presence of colloid, follicular cells, macrophages and lymphocytes/plasma cells were recorded and scored 0-4 on each case based on TP or CB slide review. The cytologic diagnoses were grouped as follows: cyst, colloid nodule, colloid nodule with cystic change, chronic thyroiditis, atypical/neoplastic and non-diagnostic. RESULTS: The TP slides had higher diagnostic rate than CB slides. The diagnostic yield was 68% of the TP slides whereas only 24% of the CB slides were diagnostic. Also, only 4 atypical/neoplastic lesions were diagnosed on the TP slides and the corresponding direct smears, while 5 cases of atypical/neoplastic lesions were diagnosed on the smears but could not be diagnosed on the corresponding CB slides. Additionally, the TP slides revealed cytologic features that were not observed on the direct traditional smears of the same case. CONCLUSION: In thyroid FNAB cases, TP slide preparation is superior to CB slide preparation and is more likely to have greater cellularity for diagnosis and detect atypical/neoplastic thyroid lesions, particularly those of follicular cell origin. Furthermore, TP slides appear to detect helpful diagnostic cytologic features and should be considered complementary to, rather than replacing, direct smears.