Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.

Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues. Notably, a single mouse EPS cell shows widespread chimeric contribution to both embryonic and extraembryonic lineages in vivo and permits generating single-EPS-cell-derived mice by tetraploid complementation. Furthermore, human EPS cells exhibit interspecies chimeric competency in mouse conceptuses. Our findings constitute a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT.

Homophily modulates double descent generalization in graph convolution networks.

Graph neural networks (GNNs) excel in modeling relational data such as biological, social, and transportation networks, but the underpinnings of their success are not well understood. Traditional complexity measures from statistical learning theory fail to account for observed phenomena like the double descent or the impact of relational semantics on generalization error. Motivated by experimental observations of "transductive" double descent in key networks and datasets, we use analytical tools from statistical physics and random matrix theory to precisely characterize generalization in simple graph convolution networks on the contextual stochastic block model. Our results illuminate the nuances of learning on homophilic versus heterophilic data and predict double descent whose existence in GNNs has been questioned by recent work. We show how risk is shaped by the interplay between the graph noise, feature noise, and the number of training labels. Our findings apply beyond stylized models, capturing qualitative trends in real-world GNNs and datasets. As a case in point, we use our analytic insights to improve performance of state-of-the-art graph convolution networks on heterophilic datasets.

Exploring the roles of noncoding RNAs in craniofacial abnormalities: A systematic review.

Congenital craniofacial abnormalities are congenital anomalies of variable expressivity and severity with a recognizable set of abnormalities, which are derived from five identifiable primordial structures. They can occur unilaterally or bilaterally and include various malformations such as cleft lip with/without palate, craniosynostosis, and craniofacial microsomia. To date, the molecular etiology of craniofacial abnormalities is largely unknown. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, circular RNAs and PIWI-interacting RNAs, function as major regulators of cellular epigenetic hallmarks via regulation of various molecular and cellular processes. Recently, aberrant expression of ncRNAs has been implicated in many diseases, including craniofacial abnormalities. Consequently, this review focuses on the role and mechanism of ncRNAs in regulating craniofacial development in the hope of providing clues to identify potential therapeutic targets.

Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

Ultrahigh Energy Storage Density and Efficiency of Lead-Free Dielectrics with Sandwich Structure.

Lead-free dielectric capacitors have attracted significant research interest for high-power applications due to their environmental benefits and ability to meet the demanding performance requirements of electronic devices. However, the development of lead-free ceramic dielectrics with outstanding energy storage performance remains a challenge. In this study, environmentally friendly ceramic dielectrics with sandwich structures are designed and fabricated to improve energy storage performance via the synergistic effect of different dielectrics. The chemical compositions of the outer and middle layers of the sandwich structure are 0.35BiFeO3 -0.65SrTiO3 and Bi0.39 Na0.36 Sr0.25 TiO3 , respectively. The experimental and theoretical simulation results demonstrate that the breakdown strength is over 700 kV cm-1 for prepare sandwich structure ceramics. As a result, an ultrahigh recoverable energy storage density of 9.05 J cm-3 and a near-ideal energy storage efficiency of 97% are simultaneously achieved under 710 kV cm-1 . Furthermore, the energy storage efficiency maintains high values (≥ 96%) within 1-100 Hz and the power density as high as 188 MW cm-3 under 400 kV cm-1 . These results indicate that the designed lead-free ceramics with a sandwich structure possess superior comprehensive energy storage performance, making them promising lead-free candidates in the energy storage field.

OsEIL2 balances rice immune responses against (hemi)biotrophic and necrotrophic pathogens via the salicylic acid and jasmonic acid synergism.

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.

Multivariate analysis compares and evaluates drought and flooding tolerances of maize germplasm.

Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological mechanisms and accurate evaluation indicators and methods of maize germplasm involved in drought and flooding stresses. The twice replicated pot experiments with 60 varieties, combined with the field validation experiment with 3 varieties, were conducted under well-watered, drought, and flooding conditions. Most varieties exhibited stronger tolerance to drought than flooding due to higher antioxidant enzyme activities, osmotic adjustment substances, and lower reactive oxygen species. In contrast, flooding stress resulted in higher levels of reactive oxygen species (particularly O2-), ascorbate peroxidase, catalase, peroxidase, and soluble sugars but lower levels of superoxide dismutase, proline, and soluble protein compared with well-watered conditions. Superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, proline, soluble sugars, and protein contents, in addition to plant height, leaf area/plant, and stem diameter, were accurate and representative indicators for evaluating maize tolerance to drought and flooding stresses and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. A total of 4 principal components were extracted, in which different principal components played a vital role in resisting different water stresses. Finally, the accuracy of the 3 varieties screened by multivariate analysis was verified in the field. This study provides insights into the different physiological mechanisms and accurate evaluation methods of maize germplasm involved in drought and flooding stresses, which could be valuable for further research and breeding.

Transcription factor LcNAC002 coregulates chlorophyll degradation and anthocyanin biosynthesis in litchi.

Chlorophyll degradation and anthocyanin biosynthesis, which often occur almost synchronously during fruit ripening, are crucial for vibrant coloration of fruits. However, the interlink point between their regulatory pathways remains largely unknown. Here, 2 litchi (Litchi chinensis Sonn.) cultivars with distinctively different coloration patterns during ripening, i.e. slow-reddening/stay-green "Feizixiao" (FZX) vs rapid-reddening/degreening "Nuomici" (NMC), were selected as the materials to study the key factors determining coloration. Litchi chinensis STAY-GREEN (LcSGR) was confirmed as the critical gene in pericarp chlorophyll loss and chloroplast breakdown during fruit ripening, as LcSGR directly interacted with pheophorbide a oxygenase (PAO), a key enzyme in chlorophyll degradation via the PAO pathway. Litchi chinensis no apical meristem (NAM), Arabidopsis transcription activation factor 1/2, and cup-shaped cotyledon 2 (LcNAC002) was identified as a positive regulator in the coloration of litchi pericarp. The expression of LcNAC002 was significantly higher in NMC than in FZX. Virus-induced gene silencing of LcNAC002 significantly decreased the expression of LcSGR as well as L. chinensis MYELOBLASTOSIS1 (LcMYB1), and inhibited chlorophyll loss and anthocyanin accumulation. A dual-luciferase reporter assay revealed that LcNAC002 significantly activates the expression of both LcSGR and LcMYB1. Furthermore, yeast-one-hybrid and electrophoretic mobility shift assay results showed that LcNAC002 directly binds to the promoters of LcSGR and LcMYB1. These findings suggest that LcNAC002 is an important ripening-related transcription factor that interlinks chlorophyll degradation and anthocyanin biosynthesis by coactivating the expression of both LcSGR and LcMYB1.

Network analysis on psychopathological symptoms, psychological measures, quality of life and COVID-19 related factors in Chinese psychiatric patients in Hong Kong.

BACKGROUND: Psychiatric patients are susceptible to adverse mental health impacts during COVID-19, but complex interplays between psychopathology and pandemic-related variables remain elusive. This study aimed to investigate concomitant associations between psychopathological symptoms, psychological measures and COVID-19 related variables in Chinese psychiatric patients during the peak of fifth pandemic wave in Hong Kong. METHODS: We employed network analysis to investigate inter-relationships among psychopathological symptoms (including depression, anxiety, post-traumatic stress disorder-like [PTSD-like] symptoms, insomnia, psychotic symptoms), cognitive complaints, health-related quality of life, loneliness, resilience and selected pandemic-related factors in 415 psychiatric outpatients between 28 March and 8 April, 2022. Network comparisons between genders, diagnosis (common mental disorders [CMD] vs. severe mental disorders [SMD]), and history of contracting COVID-19 at fifth wave were performed as exploratory analyses. RESULTS: Our results showed that anxiety represented the most central node in the network, as indicated by its highest node strength and expected influence, followed by depression and quality of life. Three comparatively strong connections between COVID-19 and psychopathological variables were observed including: fear of contagion and PTSD-like symptoms, COVID-19 stressor burden and PTSD-like symptoms, and COVID-19 stressor burden and insomnia. Network comparison tests revealed significant network structural difference between participants with history of contracting COVID-19 and those without, but showed no significant difference between genders as well as between CMD and SMD patients. CONCLUSIONS: Our findings suggest the pivotal role of anxiety in psychopathology network of psychiatric patients amidst COVID-19. Pandemic-related variables are critically associated with trauma/stress and insomnia symptoms. Future research is required to elucidate potential network structural changes between pandemic and post-COVID periods.

Prevalence and correlates of depression, anxiety and trauma-like symptoms in Chinese psychiatric patients during the fifth wave of COVID-19 pandemic: a cross-sectional study in Hong Kong.

BACKGROUND: Psychiatric patients are susceptible to adverse mental health outcome during COVID-19 pandemic, but its associated factors are understudied. This observational cross-sectional study aimed to comprehensively examine prevalence and correlates of psychological distress, in terms of depression, anxiety and post-traumatic-stress-disorder (PTSD)-like symptoms, among Chinese adult psychiatric outpatients amidst the peak of fifth COVID-19 wave in Hong-Kong. METHODS: A total of 415 patients (comprising 246 patients with common-mental-disorders [CMD] and 169 with severe-mental-disorders [SMD]) and 399 demographically-matched controls without mental disorders were assessed with self-rated questionnaires between 28-March and 8-April-2022, encompassing illness profile, mental health symptoms, psychosocial measures (loneliness, resilience, coping styles) and COVID-19 related factors. Univariate and multivariable logistic regression analyses were conducted to determine variables associated with moderate-to-severe depressive, anxiety and PTSD-like symptoms among psychiatric patients. RESULTS: Our results showed that CMD patients had the greatest psychological distress relative to SMD patients and controls. Approximately 40-55% CMD patients and 25% SMD patients exhibited moderate-to-severe depression, anxiety and PTSD-like symptoms. Multivariable regression analyses revealed that female gender, lower educational attainment, single marital status, being housewife, more severe insomnia, psychotic-like symptoms and cognitive complaints, self-harm behavior, lower resilience, avoidance coping, never contracting COVID-19 infection, greater fear of contagion, and longer exposure to pandemic-related information were independently associated with depression, anxiety and/or PTSD-like symptoms in psychiatric patients. CONCLUSIONS: Our results affirm increased vulnerability of psychiatric patients toward psychological distress during pandemic. An array of identified correlates facilitates early detection of high-risk psychiatric patients for targeted strategies to minimize pandemic-related negative psychological impact.

Optimal ICSI timing on immature oocytes for low prognosis patients under the POSEIDON classification.

BACKGROUND: The optimal timing of performing ICSI on immature oocytes for POSEIDON patients is still unknown to get better early embryonic development outcomes. The purpose of this study was to implore the most appropriate time to carry out ICSI on in vitro maturation GV and MI oocytes for POSEIDON patients. METHODS: Two hundred thirty-nine immature oocytes from 163 POSEIDON patients were prospectively performed ICSI at different timings: P-ICSI (ICSI was performed on in vitro matured oocytes 4-6 h after the first polar body extrusion, N = 81), R-ICSI (ICSI was performed on in vitro matured oocytes less than 4 h after the first polar body extrusion, N = 80), and E-ICSI (ICSI was performed on in vitro matured oocytes the next day after oocytes retrieval, N = 78). Fertilization and embryonic development outcomes were collected and statistically analyzed. Mitochondria distribution of cytoplasm of in vitro matured oocytes with different time cultures after the first polar body (PB1) extrusion was stained. RESULTS: Compared to the E-ICSI group, more day 3 embryos from P-ICSI became blastocysts after sequential culture though without statistical significance (OR = 3.71, 95% CI: 0.94-14.63, P = 0.061). Compared to the E-ICSI group, more embryos from both P-ICSI and R-ICSI groups were clinically used with statistical significance (OR = 5.67, 95% CI: 2.24-14.35, P = 0.000 for P-ICSI embryos; OR = 3.23, 95% CI: 1.23-8.45, P = 0.017 for R-ICSI embryos). Compared to the E-ICSI group, transferred embryos from P-ICSI and R-ICSI had a higher implantation rate though without statistical significance (35.3% for P-ICSI embryos; 9.1% or R-ICSI embryos and 0% for E-ICSI embryos, P = 0.050). Among the three group, there were most healthy babies delivered from the P-ICSI group (5, 1 and 0 for P-ICSI, R-ICSI and E-ICSI respectively). The mitochondria in the cytoplasm of in vitro matured oocytes with a less than 4 h and 4-6 h culture after PB1 extrusion presented semiperipheral and diffused distribution patterns, respectively. CONCLUSIONS: Our results revealed P-ICSI (ICSI was performed on in vitro matured oocytes 4-6 h after the first polar body extrusion) provided the most efficient method to utilize the immaturation oocytes basing on embryos utilization and live birth outcome for low prognosis patients under the POSEIDON classification. The mitochondria distribution of the in vitro matured oocytes' cytoplasm from P-ICSI varied that from R-ICSI.

Exploring the Effects of Various Early Hospital Feeding Approaches on Feeding Tolerance and Growth in Premature Infants.

Background: Feeding intolerance poses a significant risk of malnutrition in premature infants and may result in postnatal growth restriction, leading to irreversible damage to brain function and structure. Objective: This study aims to investigate the impact of various early hospital feeding methods on feeding tolerance and the early growth and development of premature infants. Design: A retrospective study design was adopted in this study. Setting: This study was conducted at Tongling Maternal and Child Health Hospital between January 2018 and June 2023. Participants: A total of premature, low birth-weight infants admitted to our hospital between January 2018 and June 2023 were selected for the study. The preterm infants were randomly assigned to either the experimental group (EG) or the control group (CG) using the random number table method. Interventions: The EG group received deep hydrolyzed protein formula (DHPF) milk for 1-3 weeks after opening, whereas the CG group received preterm infant formula milk continuously after the milk was opened. Primary Outcome Measures: (1) Growth and development, (2) Feeding tolerance, and (3) Incidence of complications. Results: Following 14 days of feeding, both study groups exhibited notable increases in body length, body weight, and head circumference (P < .05). These measurements were significantly higher in the EG compared to the CG (P < .05). Furthermore, the EG demonstrated a marked improvement in feeding tolerance relative to the CG (P < .01). Notably, there was no significant difference in the incidence of complications between the two groups (P > .05). Conclusions: The administration of deep hydrolyzed protein formula (DHPF) milk presents a promising strategy for enhancing the growth and development of premature infants while concurrently improving feeding tolerance. These findings underscore the potential clinical benefits of incorporating DHPF milk into neonatal care protocols.

Feeding the germline.

Nucleotides are required in order to replicate DNA in the developing germline. Here, Chi and colleagues (pp. 307-320) have used Caernohabditis elegans to identify a GLP-1-dependent checkpoint that senses food (bacterially)-supplied nucleotide levels, arresting reproductive development in the absence of sufficient nucleotide supplies.

Underutilised palm stearin as hard stock for deep-frying medium and its performance for oil uptake in instant noodles.

BACKGROUND: As a by-product of the palm oil industry, palm stearin is often overlooked despite having several beneficial properties, such as excellent stability, which is critically essential to meet the demand of the global food trend in producing safer processed food. Specifically, deep frying of food is often associated with the production of toxic compounds that could potentially migrate into the food system when oils are degraded under continuous heating. The incorporation of palm stearin is regarded as a cost-effective and efficient method to modify the fatty acid composition of oils, enhance the frying qualities and lower the degradation rate. RESULTS: This study blended 5% and 10% palm stearin into palm oil to investigate the deep-frying performance and impact on food quality. Increasing the palm stearin content improved the frying oil's oxidative and hydrolytic stability, evidenced by reduction of total polar material, free fatty acid and total oxidation value. Addition of palm stearin increased the slip melting point which improved the oil's oxidative stability but no significant increase in oil content of instant noodles was observed. Scanning electron microscopy and fluorescence microscopy showed the formation of larger pores in the noodle structure that facilitated oil retention. CONCLUSION: Blending palm stearin into frying oil enhanced the frying stability and minimally affected the oil uptake in instant noodles. This article presents the viability of blending palm stearin into frying oils to develop longer-lasting frying oils. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Overexpression of OsERF106MZ promotes parental root growth in rice seedlings by relieving the ABA-mediated inhibition of root growth under salinity stress conditions.

BACKGROUND: Roots are essential for plant growth and have a variety of functions, such as anchoring the plant to the ground, absorbing water and nutrients from the soil, and sensing abiotic stresses, among others. OsERF106MZ is a salinity-induced gene that is expressed in germinating seeds and rice seedling roots. However, the roles of OsERF106MZ in root growth remain poorly understood. RESULTS: Histochemical staining to examine ß-glucuronidase (GUS) activity in transgenic rice seedlings harboring OsERF106MZp::GUS indicated that OsERF106MZ is mainly expressed in the root exodermis, sclerenchyma layer, and vascular system. OsERF106MZ overexpression in rice seedlings leads to an increase in primary root (PR) length. The phytohormone abscisic acid (ABA) is thought to act as a hidden architect of root system structure. The expression of the ABA biosynthetic gene OsAO3 is downregulated in OsERF106MZ-overexpressing roots under normal conditions, while the expression of OsNPC3, an AtNPC4 homolog involved in ABA sensitivity, is reduced in OsERF106MZ-overexpressing roots under both normal and NaCl-treated conditions. Under normal conditions, OsERF106MZ-overexpressing roots show a significantly reduced ABA level; moreover, exogenous application of 1.0 µM ABA can suppress OsERF106MZ-mediated root growth promotion. Additionally, OsERF106MZ-overexpressing roots display less sensitivity to ABA-mediated root growth inhibition when treated with 5.0 µM ABA under normal conditions or exposed to NaCl-treated conditions. Furthermore, chromatin immunoprecipitation (ChIP)-qPCR and luciferase (LUC) reporter assays showed that OsERF106MZ can bind directly to the sequence containing the GCC box in the promoter region of the OsAO3 gene and repress the expression of OsAO3. CONCLUSIONS: OsERF106MZ may play a role in maintaining root growth for resource uptake when rice seeds germinate under salinity stress by alleviating ABA-mediated root growth inhibition.

Synergistic Optimization of Energy Storage Density of PYN-Based Antiferroelectric Ceramics by Composition Design and Microstructure Engineering.

PbYb0.5 Nb0.5 O3 (PYN)-based ceramics, featured by their ultra-high phase-switching field and low sintering temperature (950 °C), are of great potential in exploiting dielectric ceramics with high energy storage density and low preparation cost. However, due to insufficient breakdown strength (BDS), their complete polarization-electric field (P-E) loops are difficult to be obtained. Here, to fully reveal their potential in energy storage, synergistic optimization strategy of composition design with Ba2+ substitution and microstructure engineering via hot-pressing (HP) are adopted in this work. With 2 mol% Ba2+ doping, a recoverable energy storage density (Wrec ) of 10.10 J cm-3 and a discharge energy density (Wdis ) of 8.51 J cm-3 can be obtained, supporting the superior current density (CD ) of 1391.97 A cm-2 and the outstanding power density (PD ) of 417.59 MW cm-2 . In situ characterization methods are utilized here to reveal the unique movement of the B-site ions of PYN-based ceramics under electric field, which is the key factor of the ultra-high phase-switching field. It is also confirmed that microstructure engineering can refine the grain of ceramics and improve BDS. This work strongly demonstrates the potential of PYN-based ceramics in energy storage field and plays a guiding role in the follow-up research.

Enantioselective Access to Chiral 2,5-Diketopiperazines via Stereogenic-at-Cobalt(III)-Catalyzed Ugi-4CRs/Cyclization Sequences.

An asymmetric synthesis of chiral 2,5-diketopiperazines by the Ugi-4CR/cyclization is exhibited. The employment of catalytic anionic chiral Co(III) complexes delivered α-propiolyl aminoamides in high yields with excellent enantioselectivities (31 examples, up to 95% ee). The following treatment of Ugi-adducts with PPh3 leads to chiral 2,5-DKPs without significant loss of enantioselectivities (26 examples, up to 91% ee).

Nontarget Chemical Composition of Surface Waters May Reflect Ecosystem Processes More than Discrete Source Contributions.

We investigated environmental, landscape, and microbial factors that could structure the spatiotemporal variability in the nontarget chemical composition of four riverine systems in the Oregon Coast Range, USA. We hypothesized that the nontarget chemical composition in river water would be structured by broad-scale landscape gradients in each watershed. Instead, only a weak relationship existed between the nontarget chemical composition and land cover gradients. Overall, the effects of microbial communities and environmental variables on chemical composition were nearly twice as large as those of the landscape, and much of the influence of environmental variables on the chemical composition was mediated through the microbial community (i.e., environment affects microbes, which affect chemicals). Therefore, we found little evidence to support our hypothesis that chemical spatiotemporal variability was related to broad-scale landscape gradients. Instead, we found qualitative and quantitative evidence to suggest that chemical spatiotemporal variability of these rivers is controlled by changes in microbial and seasonal hydrologic processes. While the contributions of discrete chemical sources are undeniable, water chemistry is undoubtedly impacted by broad-scale continuous sources. Our results suggest that diagnostic chemical signatures can be developed to monitor ecosystem processes, which are otherwise challenging or impossible to study with existing off-the-shelf sensors.

Research evaluating the effectiveness of dementia interventions in low- and middle-income countries: A systematic mapping of 340 randomised controlled trials.

OBJECTIVES: More people with dementia live in low- and middle-income countries (LMICs) than in high-income countries, but best-practice care recommendations are often based on studies from high-income countries. We aimed to map the available evidence on dementia interventions in LMICs. METHODS: We systematically mapped available evidence on interventions that aimed to improve the lives of people with dementia or mild cognitive impairment (MCI) and/or their carers in LMICs (registered on PROSPERO: CRD42018106206). We included randomised controlled trials (RCTs) published between 2008 and 2018. We searched 11 electronic academic and grey literature databases (MEDLINE, EMBASE, PsycINFO, CINAHL Plus, Global Health, World Health Organization Global Index Medicus, Virtual Health Library, Cochrane CENTRAL, Social Care Online, BASE, MODEM Toolkit) and examined the number and characteristics of RCTs according to intervention type. We used the Cochrane risk of bias 2.0 tool to assess the risk of bias. RESULTS: We included 340 RCTs with 29,882 (median, 68) participants, published 2008-2018. Over two-thirds of the studies were conducted in China (n = 237, 69.7%). Ten LMICs accounted for 95.9% of included RCTs. The largest category of interventions was Traditional Chinese Medicine (n = 149, 43.8%), followed by Western medicine pharmaceuticals (n = 109, 32.1%), supplements (n = 43, 12.6%), and structured therapeutic psychosocial interventions (n = 37, 10.9%). Overall risk of bias was judged to be high for 201 RCTs (59.1%), moderate for 136 (40.0%), and low for 3 (0.9%). CONCLUSIONS: Evidence-generation on interventions for people with dementia or MCI and/or their carers in LMICs is concentrated in just a few countries, with no RCTs reported in the vast majority of LMICs. The body of evidence is skewed towards selected interventions and overall subject to high risk of bias. There is a need for a more coordinated approach to robust evidence-generation for LMICs.

Discovery of pterostilbene analogs as novel NLRP3 inflammasome inhibitors for potential treatment of DSS-induced colitis in mice.

The pterostilbene skeleton is a promising chemical scaffold that exerts anti-inflammatory, anti-depressant, and anti-tumor effects. In this study, we aim to reduce in vivo and in vitro toxicity of compound 32 (preliminary work) and maintain its biological activity. A series of novel pterostilbene derivatives (D1-D43) were designed and synthesized, and their anti-inflammatory activities were screened. All compounds were screened to evaluate their inhibitory effect on LPS/Nigericin-induced IL-1ß production and pyroptosis. The structure-activity relationships was deduced, and finally 1-((E)-4-(2-ethoxyethoxy)styryl)-3,5-dimethoxy-2-((E)-2-nitrovinyl)benzene (D22) was found to be a low-toxic compound with most potent inhibitory efficacy (against IL-1ß: IC50 = 2.41 µM). Preliminary mechanism studies showed that compound D22 may affect the assembly of NLRP3 inflammasome by targeting NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasome. The in vivo anti-inflammatory activity indicated that compound D22 had significant therapeutic effects on DSS-induced mouse acute colitis models.