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Abstract Background Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. Methods Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. Results The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017–5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073–5.396, P = 0.033). Conclusions NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS.

Abstract The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.

TiAl composite with core-shell structure was in-situ synthesized incorporating BN nanosheets and graphene oxide into TiAl alloy using SPS, and the hot deformation behaviors were subsequently investigated on a Gleeble-1500D thermal simulation machine. The microstructural evolution and the influence of ceramic particles on hot deformation were revealed using OM, SEM, TEM, and EBSD. The results demonstrated a refined microstructure of TiAl composite induced by ceramic particles providing extra nucleation sites for DRX, contributing to lower flow stress, with peak stresses of 387 and 360 MPa for TiAl alloy and TiAl composite deformed at 1200 °C/1s−1, respectively. Moreover, dislocation slip was inhibited by ceramic particles leading to dislocation pile-up, facilitating the nucleation and growth of DRX at lamellar colony boundaries and α2/γ interfaces. Notably, the “shell” composed of TiB2 and Ti2AlN nanoparticles coordinated the deformation of lamellar colonies with different orientations, improving the hot workability of TiAl composite.

Previously we have identified that the expression number and levels of oncogenes and antioncogenes are highly positively or negatively associated with major cellular progress in a cancer cell. However, we have not defined any cellular potentials of a human tumor cell at the level of the overall gene expression. Here, we counted the overall number of expression genes and overall counts of mRNA in depth and revealed that the expression levels of mRNA were directly associated with the expression number of genes in a human tumor cell. Gene expression networks revealed steady states of tricarboxylic acid (TCA) cycle and ATP production, differentiation potentials that might be disturbed and blocked by uncertain gene expressing networks, and potential capabilities to undergo epithelial-mesenchymal transition (EMT), neurogenesis, angiogenesis, inflammatory response, immune evasion, and metastasis in a human tumor cell. Our analysis identifies unpredictable gene expression characteristics in human tumor cells. The results might profoundly influence mechanisms how a human tumor cell generates and undergoes its progresses.

Catechins, a class of phytochemicals found in various fruits and tea leaves, have garnered attention for their diverse health-promoting properties, including their potential in combating neurodegenerative diseases. Among these catechins, (−)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, has emerged as a promising therapeutic agent due to its potent antioxidant and anti-inflammatory effects. Chronic neuroinflammation and oxidative stress are key pathological mechanisms in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). EGCG has neuroprotective efficacy due to scavenging free radicals, reducing oxidative stress and attenuating neuroinflammatory processes. This review discusses the molecular mechanisms of EGCG’s anti-oxidative stress and chronic neuroinflammation, emphasizing its effects on autoimmune responses, neuroimmune system interactions, and focusing on the related effects on AD and PD. By elucidating EGCG’s mechanisms of action and its impact on neurodegenerative processes, this review underscores the potential of EGCG as a therapeutic intervention for AD, PD, and possibly other neurodegenerative diseases. Overall, EGCG emerges as a promising natural compound for combating chronic neuroinflammation and oxidative stress, offering novel avenues for neuroprotective strategies in the treatment of neurodegenerative disorders.

Abstract Background t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30–50% of patients experience drug resistance and subsequent relapse. N6-methyladenosine (m6A) is demonstrated to be involved in the development of AML. However, the regulatory mechanisms between AML1-ETO and m6A-related enzymes and the roles of dysregulated m6A modifications in the t(8;21)-leukemogenesis and chemoresistance remain elusive. Methods Chromatin immunoprecipitation, dual-luciferase reporter assay, m6A-qPCR, RNA immunoprecipitation, and RNA stability assay were used to investigate a regulatory loop between AML1-ETO and FTO, an m6A demethylase. Gain- and loss-of-function experiments both in vitro and in vivo were further performed. Transcriptome-wide RNA sequencing and m6A sequencing were conducted to identify the potential targets of FTO. Results Here we show that FTO is highly expressed in t(8;21) AML, especially in patients with primary refractory disease. The expression of FTO is positively correlated with AML1-ETO, which is attributed to a positive regulatory loop between the AML1-ETO and FTO. Mechanistically, AML1-ETO upregulates FTO expression through inhibiting the transcriptional repression of FTO mediated by PU.1. Meanwhile, FTO promotes the expression of AML1-ETO by inhibiting YTHDF2-mediated AML1-ETO mRNA decay. Inactivation of FTO significantly suppresses cell proliferation, promotes cell differentiation and renders resistant t(8;21) AML cells sensitive to Ara-C. FTO exerts functions by regulating its mRNA targets, especially IGFBP2, in an m6A-dependent manner. Regain of Ara-C tolerance is observed when IGFBP2 is overexpressed in FTO-knockdown t(8;21) AML cells. Conclusion Our work reveals a therapeutic potential of targeting AML1-ETO/FTO/IGFBP2 minicircuitry in the treatment for t(8;21) patients with resistance to Ara-C.

As the world population ages, osteoporosis, the most common disease of bone metabolism, affects more than 200 million people worldwide. The etiology is an imbalance in bone remodeling process resulting in more significant bone resorption than bone remodeling. With the advent of the osteoimmunology field, the immune system’s role in skeletal pathologies is gradually being discovered. The cytokine interferon-gamma (IFN-γ), a member of the interferon family, is an important factor in the etiology and treatment of osteoporosis because it mediates bone remodeling. This review starts with bone remodeling process and includes the cellular and key signaling pathways of bone remodeling. The effects of IFN-γ on osteoblasts, osteoclasts, and bone mass are discussed separately, while the overall effects of IFN-γ on primary and secondary osteoporosis are summarized. The net effect of IFN-γ on bone appears to be highly dependent on the environment, dose, concentration, and stage of cellular differentiation. This review focuses on the mechanisms of bone remodeling and bone immunology, with a comprehensive discussion of the relationship between IFN-γ and osteoporosis. Finding the paradoxical balance of IFN-γ in bone immunology and exploring the potential of its clinical application provide new ideas for the clinical treatment of osteoporosis and drug development.

The constant challenge in social interactions involves making informed decisions in the face of competitive and cooperative dilemmas. The decision-making process can be influenced by various factors present in the social context. According to the behavior-pattern-categorization framework of information acquisition, potential biases may develop at all stages of decision-making as information about social context is progressively entered and integrated. In this study, employing the Chicken Game, we investigated the influence of varying information levels within the behavior-pattern-categorization framework (i.e., competitiveness of behavior choice, uncertainty of behavior pattern, and sociality of category) on decision-making in the dilemma of competition and cooperation. Combined with reinforcement learning models, our findings from three experiments showed that participants exhibited basic complementary behavior, becoming less competitive against highly competitive opponents and vice versa. Notably, individuals exhibited varying adaptation rates to different levels of opponent competitiveness and fluctuations. Specifically, participants adapted slower to highly competitive opponents and faster to cooperative opponents. This asymmetric adaptation in social learning is related to the rate at which various levels of information are updated. The current study disentangles the different levels of information acquisition and highlights the asymmetric processing that can occur during the updating of information within each level.

The development of children’s social function is influenced by the social environment, and children also play an active role in shaping and nurturing this environment. The present study investigated the potential reciprocal dynamic impact of mothers’ mental state talk (MST) and the development of theory of mind (ToM) in children. Using a cross-sectional design, we explored the development of ToM in 3- to 5-year-old children using an unexpected location task, an unexpected content task, an appearance–reality task, and mothers’ MST during mother–child reading. The results showed the following: (1) the mothers’ MST exhibited a shift from a predilection for subjective terms (such as desires) to a preference for objective terms (such as cognitions) as their children matured; (2) the development of the children’s ToM was closely related to their mothers’ MST. The overall MST scores, as well as the different categories and referents used in MST, were closely associated with the children’s ToM development. Notably, at the age of four, a critical period emerged where the correlation between maternal MST and ToM became significantly pronounced. These findings highlight the reciprocal nature of mother–child interactions as a two-way adaptive process.

IntroductionOsteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced osteoporosis(GIOP) is the foremost form of secondary osteoporosis, extensively researched due to its prevalence.Probiotics constitute a primary bioactive component within numerous foods, offering promise as a potential biological intervention for preventing and treating osteoporosis. This study aimed to evaluate the beneficial effects of the probiotic Lactobacillus plantarum on bone health and its underlying mechanisms in a rat model of glucocorticoid dexamethasone-induced osteoporosis, using the osteoporosis treatment drug alendronate as a reference.MethodsWe examined the bone microstructure (Micro-CT and HE staining) and analyzed the gut microbiome and serum metabolome in rats.Results and discussionThe results revealed that L. plantarum treatment significantly restored parameters of bone microstructure, with elevated bone density, increased number and thickness of trabeculae, and decreased Tb.Sp. Gut microbiota sequencing results showed that probiotic treatment increased gut microbial diversity and the ratio of Firmicutes to Bacteroidota decreased. Beneficial bacteria abundance was significantly increased (Lachnospiraceae_NK4A136_group, Ruminococcus, UCG_005, Romboutsia, and Christensenellaceae_R_7_group), and harmful bacteria abundance was significantly decreased (Desulfovibrionaceae). According to the results of serum metabolomics, significant changes in serum metabolites occurred in different groups. These differential metabolites were predominantly enriched within the pathways of Pentose and Glucuronate Interconversions, as well as Propanoate Metabolism. Furthermore, treatment of L. plantarum significantly increased serum levels of Pyrazine and gamma-Glutamylcysteine, which were associated with inhibition of osteoclast formation and promoting osteoblast formation. Lactobacillus plantarum can protect rats from DEX-induced GIOP by mediating the “gut microbial-bone axis” promoting the production of beneficial bacteria and metabolites. Therefore L. plantarum is a potential candidate for the treatment of GIOP.

Abstract Background Liver ischemia/reperfusion (I/R) injury is a complex and multifactorial pathophysiological process. It is well recognized that the membrane permeability transition pore (mPTP) opening of mitochondria plays a crucial role in cell death after I/R injury. Cyclophilin D (CypD) is a critical positive regulator of mPTP. However, the effect of CypD on the pathogenesis of liver I/R injury and whether CypD is a potential therapeutic target are still unclear. Methods We constructed liver‐specific CypD knockout and AAV8‐peptidyl prolyl isomerase F (PPIF) overexpression mice. Then, a 70% liver I/R injury model was established in mice, with 90 min of ischemia and 6 h of reperfusion. The liver function was detected by the level of serum glutamic pyruvic transaminase (alanine transaminase) and glutamic oxaloacetic transaminase (aspartate aminotransferase), the liver damage score and degree of necrosis were measured by hematoxylin and eosin (H&E) staining of liver tissues. Reactive oxygen species (ROS) staining, apoptosis, and autophagy‐related molecules were used to detect apoptosis and autophagy during liver I/R. Results The liver‐specific knockout of CypD alleviated necrosis and dysfunction in liver I/R injury, by reducing the excessive production of ROS, and inhibiting cell apoptosis and autophagy. On the contrary, overexpression of CypD exacerbated I/R‐induced liver damage. Conclusion We found that the downregulation of CypD expression alleviated liver I/R injury by reducing apoptosis and autophagy through caspase‐3/Beclin1 crosstalk; in contrast, the upregulation of CypD expression aggravated liver I/R injury. Therefore, interfering with the expression of CypD seems to be a promising treatment for liver I/R injury.

Increasing evidence indicates that the addictive use of social media can have a detrimental effect on marital satisfaction, due mainly to the decrease in time and focus given to one’s spouse. However, the impact of social media use among older couples remains under-investigated, and the research that does exist relies on individual-level data that do not allow the exploration of the dynamics between the dyadic partners. Therefore, the present study focused on older adults’ use of short-video platforms, as these have been shown to be particularly addictive for older adults. A sample of 264 older couples was gathered (meanage = 68.02, SD = 8.68), and both spouses completed surveys reporting addictive use of short-video platforms, negative emotions, and marital satisfaction. Using an actor–partner interdependence model, we found an asymmetrical dyadic process in that the addictive use of short-video platforms by the wives was not only related to their own negative emotions, but also those of their spouse, as well as to decreased marital satisfaction. Meanwhile, addictive use by the husbands seemed to relate only to their own increased negative emotions, as well as to decreased marital satisfaction. Together, the findings from this study reveal dyadic dynamics with delineated pathways through which the addictive use of short-video platforms can damage older couples’ interactive processes and marital satisfaction.

This literature review explores the landscape of online teacher learning and professional development (PD) that is responsive to cultural and linguistic differences. The researchers, a diverse group of doctoral students, instructors, and teacher educators, are motivated by the need to address racial inequities and disparities exacerbated by the recent pandemic. The review aims to understand the theories and conceptual models used in responsive online teacher preparation and PD, the utilization of technology and its affordances, and the intentional targeting of specific groups for responsive teacher preparation and PD. The study followed a systematic approach, resulting in the selection of 27 articles that met the inclusion criteria. The findings highlighted the significance of socioculturally inspired theories, frameworks, and practical models in addressing inclusivity. They, in turn, influenced various tools used to reduce barriers, create online communities, enhance accessibility, and promote engagement. Accordingly, the review also revealed that to foster inclusivity, intentional efforts were required to involve teachers from minority, majority, and international communities. The implications emphasized the importance of teacher preparation and PD in establishing responsiveness, refuting deficit thinking, and capitalizing on cultural and linguistic assets. They also underscored the need for equity in the design of online teacher training and professional development. Finally, the review concluded with the various ways AI could be looped into the process.

In a dynamic environment, expectations of the future constantly change based on updated evidence and affect the dynamic allocation of attention. To further investigate the neural mechanisms underlying attentional expectancies, we employed a modified Central Cue Posner Paradigm in which the probability of cues being valid (that is, accurately indicated the upcoming target location) was manipulated. Attentional deployment to the cued location (α), which was governed by precision of predictions on previous trials, was estimated using a hierarchical Bayesian model and was included as a regressor in the analyses of electrophysiological (EEG) data. Our results revealed that before the target appeared, alpha oscillations (8∼13 Hz) for high-predictability cues (88 % valid) were significantly predicted by precision-dependent attention (α). This relationship was not observed under low-predictability conditions (69 % and 50 % valid cues). After the target appeared, precision-dependent attention (α) correlated with alpha band oscillations only in the valid cue condition and not in the invalid condition. Further analysis under conditions of significant attentional modulation by precision suggested a separate effect of cue orientation. These results provide new insights on how trial-by-trial Bayesian belief updating relates to alpha band encoding of environmentally-sensitive allocation of visual spatial attention.

The Tibet Plateau, with its extensive carbon pools, plays a pivotal role in the global carbon budget. Nevertheless, the driving factors of the carbon dioxide budget remain disputed, and the impact of freeze–thaw process on carbon release is still unclear due to the harsh climate and lack of monitoring data. To clarify the primary factors affecting the alpine meadow ecosystems and to examine the impact of freeze–thaw on carbon release, we employed the LI-8150 automated continuous measurement system. This system, in conjunction with eddy covariance meteorological data, The Boosted Regression Tree (BRT) model, and multiple stepwise regression analysis, were used to analyze the seasonal variations in carbon flux (e.g., net ecosystem carbon exchange [NEE], gross primary productivity [GPP], and ecosystem respiration [Reco]). We also investigate the carbon sources and sinks in the alpine meadow ecosystem, as well as the predominant factor of carbon flux. Our findings include: (1) the carbon sources and sinks in the alpine meadow ecosystem shift seasonally on monthly and daily scales. On a monthly scale, the ecosystem functions as a moderate carbon sink in June, July, August, and September and as a weak carbon source from October through May. (2) Overall, the alpine meadow ecosystem, located in the northeastern Qinghai Lake basin, serves as a weak carbon sink (-58.53 g C m−2 year−1). (3) Soil temperature is the primary factor driving most variations observed in NEE, Reco, and GPP, contributing 48.05 %, 78.61 %, and 65.05 %, respectively. Soil temperature, soil water dynamics influenced by freeze and thaw processes, and their interaction with plant growth collectively play a crucial role in regulating the carbon sources and sinks in ecosystems. We provide first-hand observational data for monitoring the carbon sources and sinks in the alpine meadow ecosystem of the Tibet Plateau, as well as offer future guidance for studying the carbon budget of the Tibet Plateau.

Abstract With high demands and rapid development of consumer electronics related to the Internet of Things, various methods have been developed to incorporate different indicators or sensors into packaging for inspecting the safety and quality of food products conveniently. Smart packaging technology is an effective method of monitoring the status of packaged food, thus reducing food waste and food‐borne related illnesses. Food quality can be directly detected from volatile compounds associated with food degradation and/or gas content of the modified atmosphere packaging. Flexible gas sensors based on organic/polymer functional materials have been widely explored to detect trace amounts of gases by exploiting their electrical or mechanical properties. This review first discusses the requirements of gas sensors and system integration for smart packaging. Then, the paper reviews recent advances and strategies of flexible organic/polymer‐based gas sensors and system integration for smart packaging applications. Finally, this review summarizes the challenges and opportunities of flexible gas sensors and system integration for smart packaging applications.

Psoriasis is a recurring inflammatory skin condition characterized by scaly, red patches on the skin. It affects approximately 3% of the US population and is associated with histological changes such as epidermal hyperplasia, increased blood vessel proliferation, and infiltration of leukocytes into the skin’s dermis. T cells, which are classified into various subtypes, have been found to play significant roles in immune-mediated diseases, particularly psoriasis. This paper provides a review of the different T lymphocyte subtypes and their functions in psoriasis, as well as an overview of targeted therapies for treating psoriasis.

CYP1A is the most commonly used biomarker and transgenic fish which carrying a cyp1a promoter to drive a reporter gene can be used as reliable way to monitor dioxin/dioxin-like compounds (DLCs) in the environment. Here, we cloned the cyp1a promoter of Gambusia affinis and this promoter showed stronger transcriptional activity than that of zebrafish. Then, a Tg(GAcyp1a:eGFP/Luc) transgenic zebrafish line was first constructed with the G. affinis cyp1a promoter driving eGFP expression using meganuclease I-SceI mediated transgenesis technology. The Tg(GAcyp1a:eGFP/Luc) larvae at 72 h post-fertilization (hpf) were tested by exposing to TCDD for 72 h, and induced GFP was mainly expressed in the liver with low background. The Tg(GAcyp1a:eGFP/Luc) zebrafish showed high sensitivity (limit of detection of 0.322 ng/L TCDD and 0.7 TEQ-ng/L PCDD/Fs) and specificity (insensitive to responses to PAHs and PCBs). In addition, the transgenic line showed a low detection concentration of the DLCs contaminated environmental samples (as low as 1.8 TEQ-ng/L), and the eGFP fluorescence intensity and the chemical-TEQ values were closely correlated. In conclusion, a sensitively and specifically transgenic zebrafish line was established to convenient and effective to detect DLCs in the environment.

Accurately evaluating surface water quality grade (WQG) is of great significance in improving the efficiency of regional water quality management. Based on seven main surface water quality indicators (including dissolved oxygen (DO), chemical oxygen demand (COD), permanganate index (CODMn), ammonia nitrogen (NH4+-N), fluoride (FL), total phosphorus (TP) and total nitrogen (TN)) data from 910 measuring points in Heilongjiang Province from May to August 2017, an improved Nemerow index method (IN method) based on combined weighting was constructed, and the WQG was evaluated. On this basis, the multiple linear or non-linear regression models (MLR or MNR) under different quantities of water quality indicators were established, and the prediction results were evaluated. Results show that: 1) WQG in Heilongjiang Province above grade III accounts for more than 92.6%, evaluated by the IN method; 2) The accuracy of WQG evaluated by MLR based on different quantities of water quality indicators are maintained at 77%-90% and decreases with the increase of the number of water quality indicators (N), which may be related to the selected combination of water quality indicators and key water pollutants. The accuracy is improved by 3.9%-17.4% for MNR as compared to MLR, and especially the accuracy can reach as high as 95.6% when N is 5; 3) Compare to the MLR, the MNR is less affected by the data fluctuation characteristics, and performs best when N is 5 under both the great and small data fluctuations, with an accuracy of 85% and 90%, respectively. 4) TN (0.72), NH4+-N (0.41), and CODMn (0.33) are significantly related to the WQG. COD is a key parameter affecting the stability and uncertainty of MLR and MNR. These results provide a simple and reliable method for accurately evaluating the surface WQG, which have important guiding significance for decision-makers and researchers in water environment protection and agricultural water fertilizer management in Heilongjiang Province.

Abstract To quantitatively analyze the number and density of macrophage-like cells (MLCs) at the vitreoretinal interface at macular region in diabetic retinopathy (DR) with and without diabetic macular edema (DME). This cross-sectional study involved 240 eyes of 146 treatment-naïve DR patients, including 151 eyes with DME. The number and density of MLCs were analyzed quantitatively using optical coherence tomography angiography (OCTA) and were compared between DME and non-DME eyes as well as proliferative DR (PDR) and non-PDR (NPDR) eyes. Correlation between MLCs density and vessel density of macular superficial capillary plexus (SCP) at macular region was evaluated. The number and density of macular MLCs were both elevated in DME group compared to non-DME group (all p

Abstract Dual-ion Li metal batteries based on non-flammable SO2-in-salt inorganic electrolytes ( Li–SO2 batteries) offer high safety and energy density. The use of cupric oxide (CuO) as a self-activating cathode material achieves a high specific capacity with cost-effective manufacturing in Li–SO2 batteries, but its cycle retention performance deteriorates owing to the significant morphological changes of the cathode active materials. Herein, we report the catalytic effect of carbonaceous materials used in the cathode material of Li–SO2 batteries, which act as templates to help recrystallize the active materials in the activation and conversion reactions. We found that the combination of oxidative-cyclized polyacrylonitrile (PAN) with N-doped carbonaceous materials and multi-yolk-shell CuO (MYS-CuO) nanoclusters as cathode active materials can significantly increase the specific capacity to 315.9 mAh g− 1 (93.8% of the theoretical value) at 0.2 C, which corresponds to an energy density of 1295 Wh kgCuO −1, with a capacity retention of 84.46% at the 200th cycle, and the cathode exhibited an atypical blossom-like morphological change.

Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer’s disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people with human immunodeficiency virus (HIV) with or without exposure to nucleoside RT inhibitors (NRTIs) using de-identified medical claims data. Eligible participants were aged ≥60 years, without pre-existing AD diagnoses, and pursued medical services in the United States from October 2015 to September 2016. Cohorts 1 (N = 46,218) and 2 (N = 32,923) had HIV. Cohort 1 had prescription claims for at least one NRTI within the exposure period; Cohort 2 did not. Cohort 3 (N = 150,819) had medical claims for the common cold without evidence of HIV or antiretroviral therapy. The cumulative incidence of new AD cases over the ensuing 2.75-year observation period was lowest in patients with NRTI exposure and highest in controls. Age- and sex-adjusted hazard ratios showed a significantly decreased risk for AD in Cohort 1 compared with Cohorts 2 (HR 0.88, p < 0.05) and 3 (HR 0.84, p < 0.05). Sub-grouping identified a decreased AD risk in patients with NRTI exposure but without protease inhibitor (PI) exposure. Prospective clinical trials and the development of next-generation agents targeting brain RTs are warranted.

Enrofloxacin (ENR) is widely used as a synthetic fluoroquinolone antibiotic for disease control in aquatic animals. ENR aptamers were screened in this study using the magnetic bead-SELEX method, and a graphene oxide fluorescent sensor was developed to detect the ENR residues in aquatic products. Firstly, ENR was conjugated to amino magnetic beads by amidation reaction, and then the aptamer sequences showing high affinity to ENR were screened step by step by using the SELEX screening method. Finally, after 10 rounds of SELEX screening, six candidate aptamers with high affinity were obtained. Among these, ENR-Apt 6 was selected based on its secondary structure features, high affinity (Kd = 35.08 nM), and high specificity to ENR. Furthermore, a fluorescent sensor was prepared using graphene oxide and ENR-Apt 6. The results showed that the linear range of the sensor could reach 600 nM (R2 = 0.986), while its optimal linear range was 1–400 nM (R2 = 0.991), with the lowest detection limit of 14.72 nM. The prepared sensor was successfully used for the detection of ENR in real samples, with a recovery range of 83.676–114.992% and a relative standard deviation < 10% for most of the samples.

Ofloxacin (OFL) is widely used in animal husbandry and aquaculture due to its low price and broad spectrum of bacterial inhibition, etc. However, it is difficult to degrade and is retained in animal-derived food products, which are hazardous to human health. In this study, a simple and efficient method was developed for the detection of OFL residues in meat products. OFL coupled with amino magnetic beads by an amination reaction was used as a stationary phase. Aptamer AWO-06, which showed high affinity and specificity for OFL, was screened using the exponential enrichment (SELEX) technique. A fluorescent biosensor was developed by using AWO-06 as a probe and graphene oxide (GO) as a quencher. The OFL detection results could be obtained within 6 min. The linear range was observed in the range of 10–300 nM of the OFL concentration, and the limit of the detection of the sensor was 0.61 nM. Furthermore, the biosensor was stored at room temperature for more than 2 months, and its performance did not change. The developed biosensor in this study is easy to operate and rapid in response, and it is suitable for on-site detection. This study provided a novel method for the detection of OFL residues in meat products.

Retrogressive thaw slumps (RTSs) are becoming more common on the Qinghai-Tibet Plateau as permafrost thaws, but the hydraulic properties of thaw slumps have not been extensively studied. To fill this knowledge gap, we used the “space-for-time substitution method” to differentiate three stages of RTSs: original grassland, collapsing, and collapsed. Our study included on-site investigations, measurements in the laboratory, and measured and simulated analyses of soil water retention curves and estimated hydrological properties. Our findings show that the measurements and simulated analyses of soil water retention were highly consistent across RTSs, indicating the accuracy of the Van Genuchten model in reproducing soil hydraulic parameters for different stages of RTSs. The original grassland stage had the highest soil water retention and content due to its high soil organic carbon (SOC) content and fine-textured micropores. In contrast, the collapsed stage had higher soil water retention and content compared to the collapsing stage, primarily due to increased proportions of soil micropores, SOC content, and lower bulk density (BD). From original grassland stage to collapsed stage, there were significant changes on the structure of each RTS site, which resulted in a decrease in SOC content and an increase in BD in general. However, the absence of soil structure and compaction led to the subsequent accumulation of organic matter, increasing SOC content. Changes in field capacity, permanent wilting point, and soil micropore distribution aligned with variations in SOC content and water content. These findings highlight the importance of managing SOC content and water content to mitigate the adverse effects of freeze-thaw cycles on soil structure and stability at different thaw collapse stages of RTSs. Effective management strategies may include incorporating organic matter, reducing soil compaction, and maintaining optimal water content. Further research is needed to determine the most suitable management practices for different soil types and environmental conditions.

Purpose: This study aimed to determine the efficacy of the dexamethasone (DEX) intravitreal implant for the regression of macular edema and the improvement of best-corrected visual acuity (BCVA) after the removal of idiopathic epiretinal membrane (ERM).Methods: This prospective randomized controlled trial recruited 81 patients with idiopathic ERM. These patients all underwent 25-gauge pars plana vitrectomy combined with ERM and internal limiting membrane peeling surgery. Among them, 41 eyes in the DEX group received additional DEX implants and 40 in the non-DEX group did not. Outcomes including central retinal thickness (CRT), BCVA, and intraocular pressure were measured 1 and 3 months after surgery.Results: The DEX group had thinner CRTs compared to the non-DEX group at 1 month postoperatively (p

Objective: The present study aimed to determine the effect-site concentration of remifentanil of 90% (EC90) for smooth emergence in patients with a video DLT (VDLT) under sevoflurane-maintained general anesthesia and to investigate whether the EC90 was affected by epidural anesthesia. Methods: One hundred and twenty patients who underwent video-assisted thoracic surgery (VATS) were enrolled. Patients received either general anesthesia combined with epidural anesthesia (PEA group, n = 60) or general anesthesia (GA group, n = 60). The primary outcome was the EC90 for smooth emergence in both groups. The secondary outcomes were intraoperative emergence, smooth emergence, recovery, and hemodynamic profiles in both groups. Result: The EC90 values for smooth emergence in patients using VDLT were 3.5 ng/ml (95% confidence interval [CI], 3.3–4.4 ng/ml) in the PEA group and 2.7 ng/ml (95% CI, 2.5–3.2 ng/ml) in the GA group. The total amount of remifentanil infusion during emergency was significantly higher in the PEA group (164.6 ± 47.9 μg) than in the GA group (127.1 ± 30.4 μg) (P

The gene expression networks of a single cell can be used to reveal cell type- and condition-specific patterns that account for cell states, cell identity, and its responses to environmental changes. We applied single cell sequencing datasets to define mRNA patterns and visualized potential cellular capacities among hepatocellular cancer cells. The expressing numbers and levels of genes were highly heterogenous among the cancer cells. The cellular characteristics were dependent strongly on the expressing numbers and levels of genes, especially oncogenes and anti-oncogenes, in an individual cancer cell. The transcriptional activations of oncogenes and anti-oncogenes were strongly linked to inherent multiple cellular programs, some of which oppose and contend against other processes, in a cancer cell. The gene expression networks of multiple cellular programs proliferation, differentiation, apoptosis, autophagy, epithelial-mesenchymal transition, ATP production, and neurogenesis coexisted in an individual cancer cell. The findings give rise a hypothesis that a cancer cell expresses balanced combinations of genes and undergoes a given biological process by rapidly transmuting gene expressing networks.

Abstract This study aimed to investigate the correlation between the severity of photoreceptor damage and the level of anti-retina antibodies (ARAs) in aqueous humor, including recoverin, CA II and enolase-α IgG antibody of macular edema patients. Aqueous humor samples were collected from macular edema patients and from cataract patients. Patients were divided into three groups according to the severity of discontinuity of ellipsoid zone (EZ) shown on optical coherence tomography (OCT) imaging: cataract patients with intact EZ, macular edema patients with mild EZ damage, and macular edema patients with severe EZ damage. The level of ARAs was determined with enzyme-linked immunosorbent assay (ELISA). The correlation between the level of ARAs and the degree of photoreceptor damage was analyzed. The level of ARAs of the intact EZ group was significantly lower than that in the severely damaged group (P

Abstract Background To compare the efficacy and safety of preoperative intravitreal injections of ranibizumab and conbercept in Chinese proliferative diabetic retinopathy (PDR) patients. Methods This prospective randomized controlled trial enrolled 90 eyes of 80 patients with PDR. Forty-four eyes of 40 patients that received intravitreal ranibizumab (IVR) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVR group. Forty-six eyes of 40 patients that received intravitreal conbercept (IVC) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVC group. Intraoperative and postoperative indices were assessed for further comparison between the two groups. Results There were no statistically significant differences in all surgery indices, including intraoperative indices (surgery time, P = 0.225; intraoperative bleeding, P = 0.808; endodiathermy use, P = 0.693; incidence of iatrogenic retinal breaks, P = 0.740; relaxing retinotomy, P = 0.682; retinal reattachment, P = 0.682 and silicone oil tamponade, P = 0.814) and postoperative indices (postoperative vitreous hemorrhage (VH), P = 0.808; neovascular glaucoma (NVG), P = 0.964; recurrent retinal detachment, P = 0.531; postoperative fibrovascular proliferation progression, P = 0.682 and reoperation, P = 0.955) between the two groups. There were no statistically significant differences in best-corrected visual acuity (BCVA) at each follow-up visit (P = 0.939, 0.669, 0.741 and 0.717, respectively) or in central retinal thickness (CRT) (P = 0.976, 0.699, 0.551 and 0.686, respectively). As for safety profile, both groups had no ocular or system adverse events during the observation period. Conclusions IVR and IVC as a pretreatment of vitrectomy had similar efficacy and safety profile for Chinese PDR patients. Trial registration: Registered at ClinicalTrials.gov ( NCT05414149 ).

The heterogeneity of fibroblasts in normal colon mucosa and colorectal cancer (CRC) is examined using single cell data, showing their potential function in normal gut homeostasis and in CRC.

Abstract Background To compare swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC). Methods SS-OCTA and ICGA images of 39 eyes with symptomatic CSC were collected and aligned. Spatial overlap of the annotations of the coarse granulated high reflective area on choriocapillary OCTA and the hyperfluorescence area on mid-phase ICGA was calculated according to the Jaccard index (JI). SS-OCTA findings of fellow eyes and changes in SS-OCTA abnormalities during the follow-up were also analyzed. Results Three main types of abnormalities in choriocapillaris SS-OCTA images were found: type A, coarse granulated high reflective area (39 eyes [100%]); type B, roundish dark halo around Type A (32 eyes [82.1%]); and type C, coarse granulated low reflective area (39 eyes [100%]). The mean JI of type A on SS-OCTA and the hyperfluorescence area on ICGA were 0.55 ± 0.15 for grader 1 and 0.49 ± 0.15 for grader 2. The mean area of type A abnormalities on SS-OCTA and hyperfluorescence on ICGA was 3.976 (IQR, 2.139–8.168) and 3.043 (IQR, 1.408–4.909) mm2 (P = 0.199). The areas of type A, B and C abnormalities on SS-OCTA after laser treatment or observation were 3.36mm2 (IQR, 2.399–9.312), 2.9mm2 (IQR, 2.15–3.7), and 0.19mm2 (IQR, 0.08–0.23), respectively, which was smaller than those in the baseline (7.311mm2 (IQR 3.788–11.209), P

Tryptophan (Trp) is an essential amino acid that can be metabolized via endogenous and exogenous pathways, including the Kynurenine Pathway, the 5-Hydroxyindole Pathway (also the Serotonin pathway), and the Microbial pathway. Of these, the Microbial Trp metabolic pathways in the gut have recently been extensively studied for their production of bioactive molecules. The gut microbiota plays an important role in host metabolism and immunity, and microbial Trp metabolites can influence the development and progression of various diseases, including inflammatory, cardiovascular diseases, neurological diseases, metabolic diseases, and cancer, by mediating the body’s immunity. This review briefly outlines the crosstalk between gut microorganisms and Trp metabolism in the body, starting from the three metabolic pathways of Trp. The mechanisms by which microbial Trp metabolites act on organism immunity are summarized, and the potential implications for disease prevention and treatment are highlighted.

Aims: To determine the bioactive components of Hedyotis Diffusae Herba (HDH) and the targets in treating lupus nephritis (LN), and so as to elucidate the protective mechanism of HDH against LN.Methods and results: An aggregate of 147 drug targets and 162 LN targets were obtained from online databases, with 23 overlapped targets being determined as potential therapeutic targets of HDH against LN. Through centrality analysis, TNF, VEGFA and JUN were screened as core targets. And the bindings of TNF with stigmasterol, TNF with quercetin, and VEGFA with quercetin were further validated by molecular docking. By conducting Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses for drug targets, disease targets and the shared targets, TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway, etc., were found in all these three lists, indicating the potential mechanism of HDH in the treatment of LN.Conclusion: HDH may ameliorate the renal injury in LN by targeting multi-targets and multi-pathways, including TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway and so on, which provided novel insights into further researches of the drug discovery in LN.

Psoriasis vulgaris (PV) is a common inflammatory skin disorder with immune imbalance contributing to its pathology. It has been reported that auranofin, a known anti-rheumatic drug, has the therapeutic effects on inflammatory diseases. However, the effects and underlying mechanisms of auranofin on PV have not been reported. Here, we showed that auranofin significantly attenuated the mixture of five proinflammatory cytokines (termed as M5) induced hyperproliferation and inflammation in HaCaT cells, a kind of human immortalized keratinocyte cell line. Topical administration of auranofin markedly alleviated the imiquimod (IMQ)-induced mouse psoriatic dermatitis both in appearance and in pathology. The psoriasis area and severity index (PASI) score, acanthosis, dermal infiltrated inflammatory cells and Ki-67 expression were improved obviously. The results of RNA-sequencing from both M5-induced HaCaT cells and IMQ-treated mouse dermatitis showed that auranofin could regulate inflammation-related signaling pathway. Meanwhile, we observed that fatty acid 2-hydroxylase (FA2H), a key molecule in lipid metabolism, was significantly increased after auraonfin treatment in both M5-induced HaCaT cells and IMQ-treated mouse skin. Knockdown of FA2H in HaCaT cells remarkably inhibited cell apoptosis, increased cell proliferation and the expression profiles of inflammatory-related genes, whereas FA2H overexpression had opposite effect. In conclusion, auranofin notably alleviated IMQ-induced psoriasis-like skin inflammation, which might be mediated by increasing FA2H expression, suggesting its potential to be a novel strategy for psoriasis treatment.

Background: This study aimed to analyze clinical and multimodal imaging characteristics of acute macular neuroretinopathy (AMN) post-recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: Retrospective observational study. Medical records and multimodal imaging of 12 AMN eyes of eight patients (six female and two male) with recent SARS-CoV-2 infection were retrospectively analyzed. Results: Four patients (50%) presented with bilateral AMN. Fundus ophthalmoscopy revealed a reddish-brown lesion around the macula, and two eyes had cotton-wool spots at the posterior pole. Three eyes showed mild hypo-autofluorescence. All FFA images (7 eyes) showed no abnormal signs. On OCT scans, all eyes showed outer nuclear layer (ONL) thinning, 8 eyes (66.7%) showed ONL hyperreflectivity, 5 eyes (41.7%) showed outer plexiform layer (OPL) hyperreflectivity, 8 eyes (66.7%) showed interdigitation zone (IZ) disruption, 11 eyes (91.6%) showed ellipsoid zone (EZ) disruption, 2 eyes (16.7%) showed cotton-wool spots and inner plexiform layer (IPL) hyperreflectivity, 1 eye (8.3%) had intraretinal cyst and 1 eye (8.3%) had inner nuclear layer (INL) thinning. Persistent scotoma, ONL hyperreflectivity and IZ/EZ disruption as well as recovery of OPL hyperreflectivity were reported after follow-up in three cases. Conclusions: AMN post-SARS-CoV-2 mostly affected young females and could present unilaterally or bilaterally. Dark lesions on IR reflectance and outer retinal hyperreflectivity on OCT are useful in diagnosing AMN. OPL/ONL hyperreflectivity on OCT could disappear after follow-up, but ONL thinning and IZ/EZ could persist.

Spinel is a precious stone with a long history. In ancient societies spinel was considered to be an imitation of ruby. With the depletion of ruby mineral resources, gem—grade spinel has attracted more and more attention from consumers. In the last decade, as the popularity of spinel in the global colored gem market continues to rise, plenty of domestic and foreign jewelry brands have launched spinel based jewelry. This study takes spinels from Burma, Vietnam, Sri Lanka, and Tanzania as its research objects and performs a series of tests to obtain their gemological characteristics, spectral characteristics, and chemical composition, with the aim of comparing the differences between spinels with different colors from different areas and exploring the chromogenic mechanism of spinels. Only Burmese red spinels have a typical Cr spectrum. The types of inclusions and the contents of trace elements are the main differences between spinels from the four areas. Burmese spinel is characterized by an octahedral negative crystal filled with dolomite or a mixture of dolomite and calcite. Magnesite is present in Sri Lankan spinels, and dolomite is present in Tanzanian spinel. Dislocation systems and the presence of titanite and talc inclusions are strongly indicative features of Vietnamese spinel. Sri Lankan spinel is characterized by abundant gas–liquid inclusions, such as the beaded healing fissure. The trace element contents of the four areas are different. Burmese spinel is poor in Fe and Zn (Fe: 135.68–3925 ppm; Zn: 338.58–1312 ppm), while Burmese red spinel is rich in Cr (up to 7387 ppm). Vietnamese spinel is rich in Fe (3669.63–19,425 ppm) and poor in Ti content (3+ and V3+, showing a wide absorption band centered at 400 nm and 550 nm. Fe plays a dominant role in purple spinels. The purple spinel is colored by Fe3+ and Fe2+.

Type 2 diabetes (T2D) is a commonly diagnosed condition that has been extensively studied. The composition and activity of gut microbes, as well as the metabolites they produce (such as short-chain fatty acids, lipopolysaccharides, trimethylamine N-oxide, and bile acids) can significantly impact diabetes development. Treatment options, including medication, can enhance the gut microbiome and its metabolites, and even reverse intestinal epithelial dysfunction. Both animal and human studies have demonstrated the role of microbiota metabolites in influencing diabetes, as well as their complex chemical interactions with signaling molecules. This article focuses on the importance of microbiota metabolites in type 2 diabetes and provides an overview of various pharmacological and dietary components that can serve as therapeutic tools for reducing the risk of developing diabetes. A deeper understanding of the link between gut microbial metabolites and T2D will enhance our knowledge of the disease and may offer new treatment approaches. Although many animal studies have investigated the palliative and attenuating effects of gut microbial metabolites on T2D, few have established a complete cure. Therefore, conducting more systematic studies in the future is necessary.

Hot workability of a forged beta gamma Ti–44Al–6Nb–1Mo-0.3 (B, Y, La, Ce) alloy was studied on a Gleeble-3800 thermal simulation machine under variable conditions. The flow stress and microstructural evolution were analyzed carefully after deformed at variable conditions (deformed to different strains holding 30s then continue to deform to ε = 0.6; deformed to ε = 0.2 holding 5s, 10s, 60s, 120s respectively, and then continue to deform to ε = 0.6). All true stress–strain curves showed typical work hardening and flow softening features indicating that dynamic recrystallization (DRX) was the dominating softening mechanism under variable hot deformation conditions. Lamellar colonies transformed into γ phase through DRX under normal continuous deformation conditions, which was because that the γ-DRX and B2-DRX were triggered at all stage. However, the γ→α phase transformation (PT) was observed when the discontinuous two-step deformation was carried out. The deformation residual stress was significantly reduced with the appearance and growth of α phase. The results show that uniform equiaxed DRX grains can be obtained by increasing of strain and holding time at the first stage during two-step hot deformation.

Summary: DOPEY2 has been shown to be associated with Down syndrome and PCDH7 might be involved in Rett syndrome and MECP2 duplication syndrome. The mechanism how both proteins play roles in these syndromes are largely unknown. Here, we show that Dopey2 and Pcdh7 balance the proliferation and differentiation of neural stem cells and progenitors during embryonic neurogenesis to generate proper size and architecture of zebrafish brains. Dopey2 and Pcdh7 mutually restricted expression of each other in zebrafish embryos. Dopey2 was responsible for the proliferation of neural stem cells/progenitors, whereas Pcdh7 was responsible for the differentiation of neural stem cells/progenitors. Both proteins were shown to orchestrate the proper development and arrangement of neural cells in zebrafish embryonic brains. The results provide an insight into mechanisms to understand how the embryonic brain is constituted and how developmental defects occur in the brains of patients with Down syndrome, Rett syndrome, or MECP2 duplication syndrome.

Abstract Background Autologous platelet concentrate has been widely used to encourage the regeneration of hard and soft tissues. Up to now, there are three generations of autologous platelet concentrates. Many studies have shown that the three autologous concentrates have different effects, but the specific diversities have not been studied. The purpose of this study was to explore and compare the effects of platelet-rich fibrin, concentrated growth factor and platelet-poor plasma on the healing of tooth extraction sockets in New Zealand rabbits. Methods A total of 24 healthy male New Zealand white rabbits aged 8–12 weeks were selected. The experimental animals were randomly divided into four groups: three experimental groups were respectively implanted with PPP, CGF and PRF gel after bilateral mandibular anterior teeth were extracted, and the control group did not implant any material. The alveolar bone of the mandibular anterior region was taken at 2, 4 and 8 weeks after operation. The height and width of the extraction wound were detected by CBCT, the growth of the new bone was observed by HE and Masson staining, and the expression of osteogenic genes was detected by real-time PCR. Data were analyzed using IBM SPSS statistical package 22.0. Results The radiological results showed that alveolar bone resorption in all groups gradually increased over time. However, the experimental groups showed lower amounts of bone resorption. The histological results showed that new bone formation was observed in all groups. Over time, the new bone trabeculae of the CGF group became closely aligned while those in the PPP and PRF groups remained scattered. PCR results showed that the expression of BMP-2 and ALP was higher in the experimental groups than the control group. Conclusion In conclusion, the application of PRF, CGF and PPP in tooth extraction sockets effectively promoted bone regeneration. CGF showed more effective bone induction and tissue regeneration ability in the long term.

Purpose: To determine if MRI features and molecular subtype influence the detectability of breast cancers on MRI in high-risk patients. Methods and Materials: Breast cancers in a high-risk population of 104 patients were diagnosed following MRI describing a BI-RADS 4–5 lesion. MRI characteristics at the time of diagnosis were compared with previous MRI, where a BI-RADS 1–2–3 lesion was described. Results: There were 77 false-negative MRIs. A total of 51 cancers were overlooked and 26 were misinterpreted. There was no association found between MRI characteristics, the receptor type and the frequency of missed cancers. The main factors for misinterpreted lesions were multiple breast lesions, prior biopsy/surgery and long-term stability. Lesions were mostly overlooked because of their small size and high background parenchymal enhancement. Among missed lesions, 50% of those with plateau kinetics on initial MRI changed for washout kinetics, and 65% of initially progressively enhancing lesions then showed plateau or washout kinetics. There were more basal-like tumours in BRCA1 carriers (50%) than in non-carriers (13%), p = 0.0001, OR = 6.714, 95% CI = [2.058–21.910]. The proportion of missed cancers was lower in BRCA carriers (59%) versus non-carriers (79%), p < 0.05, OR = 2.621, 95% CI = [1.02–6.74]. Conclusions: MRI characteristics or molecular subtype do not influence breast cancer detectability. Lesions in a post-surgical breast should be assessed with caution. Long-term stability does not rule out malignancy and multimodality evaluation is of added value. Lowering the biopsy threshold for lesions with an interval change in kinetics for a type 2 or 3 curve should be considered. There was a higher rate of interval cancers in BRCA 1 patients attributed to lesions more aggressive in nature.

A drug carrier usually refers to a tool that can carry the effective ingredients of drugs into the human body. The drug-controlled release system prepared by a new drug carrier can allow the gradual release of the drug in the human body at a stable rate, thus decreasing the frequency of administration and reducing the toxicity and side effects thereof; however, existing drug carriers generally have problems such as low drug loading, poor biocompatibility, stability, and specificity, each of which could be improved. Calcium carbonate can be used as a sustained-release carrier of active substances, with good biocompatibility, biodegradability, low cost, easy preparation, and broad application prospects. This paper reviews the synthesis and structural characteristics of calcium carbonate carrier materials and the related research progress of calcium carbonate as a controlled release carrier for therapeutic drugs, providing a reference for promoting the research and application of calcium carbonate as a drug carrier.

Biodiesel is considered a potential substitute for fossil diesel because of its unique environmentally friendly and renewable advantages. The efficient and durable heterogeneous catalysts are vital to greenly and efficiently drive the biodiesel production process. The ionic liquid-functionalized materials, possessing the characteristics of both homogeneous and heterogeneous catalysts, are one of the promising substitutions for conventional homogeneous acid/base catalysts for producing biodiesel. This mini-review focuses on recent advances in supported acid/base ionic liquids to synthesize ionic liquid-functionalized materials for producing biodiesel. The methods of immobilizing ionic liquids on supports were summarized. The merits and demerits of various supports were discussed. The catalytic activities of the ionic liquid-functionalized materials for biodiesel production were reviewed. Finally, we proposed the challenges and future development direction in this area.

PurposeTo identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical applicationMethodsThis case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups.ResultMean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA.ConclusionThis is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.

BackgroundCurrently, longitudinal studies on frailty are in an early stage, particularly in low- and middle-income countries. Only one study was conducted in Hong Kong to examine age-period-cohort effects on the prevalence of frailty among Chinese older adults.ObjectivesThis study aims to shed light on the prevalence trajectory of frailty among older adults in mainland China through the APC model and to analyze the effects of age, period, and cohort on the prevalence trajectory.MethodsThe sample for this study was older adults aged 65–109 years old from the 2002 to 2014 Chinese Longitudinal Healthy Longevity Survey (CLHLS). Frailty status was measured by Rockwood FI. An age-period-cohort model was used to describe the effects of age, period, and cohort on the prevalence trajectory of frailty.ResultsThe prevalence of frailty among Chinese older adults changed significantly with age, period, and cohort. Furthermore, the effect of age was much stronger than the effect of period and cohort. The prevalence of frailty in the 101–103 and 104–106 age groups was 8.998 (95% CI 13.667–5.924) and 8.699 (95% CI 13.037–5.805) times higher than the in the 65–67 age group, respectively. The sensitivity analysis based on Fried's frailty phenotype showed similar results, confirming the robustness of our findings.ConclusionAll of the age effect reflecting the individual aging process, period effect reflecting change in the social environment, and birth cohort effect reflecting different generations could influence the prevalence of frailty at the population level. In contrast, the age effect was the main effect.

BackgroundLung adenocarcinoma (LUAD) is the most common type of Non-small-cell lung cancer (NSCLC). Distant metastasis of lung adenocarcinoma reduces the survival rate. we aim to develop a nomogram in order to predict the survival of patients with metastatic lung adenocarcinoma.MethodsWe retrospectively collected patients who were initially diagnosed as metastatic LUAD from 2010 to 2015 from SEER database. Based on the multivariate and univariate Cox regression analysis of the training cohorts, independent prognostic factors were assessed. The nomogram prediction model was then constructed based on these prognostic factors to predict the overall survival at 12, 24 and 36 months after surgery. Nomogram were identified and calibrated by c-index, time-dependent receiver operating characteristic curve (time-dependent AUC) and calibration curve. Decision curve analysis (DCA) was used to quantify the net benefit of the nomogram at different threshold probabilities, and to better compare with the TNM staging system, we calculated the c-index of this nomogram as well as the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI).ResultA total of 1102 patients with metastatic LUAD who met the requirements were included for analysis. They were randomly divided into 774 in the training cohorts and 328 in the validation cohorts. As can be seen from the calibration plots, the predicted nomogram and the actual observations in both of the training and validation cohorts were generally consistent. The time dependent AUC values of 12 months, 24 months and 36 months were 0.707, 0.674 and 0.686 in the training cohorts and 0.690, 0.680 and 0.688 in the verification cohorts, respectively. C-indexes for the training and validation cohorts were 0.653 (95%CI 0.626-0.68)and 0.663 (95%CI 0.626-1), respectively. NRI and IDI show that the model is more clinical applicable than the existing staging system. In addition, our risk scoring system based on Kaplan Meier (K-M) survival curve can accurately divide patients into three hierarchy risk groups.ConclusionThis has led to the development and validation of a prognostic nomogram to assist clinicians in determining the prognosis of patients with metastatic lung adenocarcinoma after primary site surgery.

BackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.ResultsOA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.ConclusionsWe developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy.

Abstract Under adverse conditions, such as sustained or chronic hyperglycemia or hyperlipidemia, ROS (reactive oxygen species) or/and ER-stress (endoplasmic reticulum stress) will be induced in pancreatic β cells. ROS or ER-stress damages β-cells even leads to apoptosis. Previously we found ROS or ER-stress resulted in JNK activation in β cells and overexpressing NR4A1 in MIN6 cells reduced JNK activation via modulating cbl-b expression and subsequent degrading the upstream JNK kinase (MKK4). To search other possible mechanisms, we found the mRNA level and protein level of MKP7 (a phosphatase for phospho-JNK) were dramatic reduced in pancreatic β cells in the islets from NR4A1 KO mice compared with that from wild type mice. To confirm what we found in animals, we applied pancreatic β cells (MIN6 cells) and found that the expression of MKP7 was increased in NR4A1-overexpression MIN6 cells. We further found that knocking down the expression of MKP7 increased the p-JNK level in pancreatic β cells upon treatment with TG or H2O2. After that, we figured out that NR4A1 did enhance the transactivation of the MKP7 promoter by physical association with two putative binding sites. In sum, NR4A1 attenuates JNK phosphorylation incurred by ER-stress or ROS partially via enhancing MKP7 expression, potentially decreases pancreatic β cell apoptosis induced by ROS or ER-stress. Our finding provides a clue for diabetes prevention.

Abstract Background Systemic sclerosis (SSc) is a multisystem rheumatic disease. Orofacial manifestations are commonly in SSc but maybe usually ignored and overshadowed by other systemic complications. Multiple comparative studies have been conducted to investigate the possible links between SSc and oral manifestations. The present study aimed to investigate the oral health status in patients with SSc. Methods Pubmed, Embase, Web of Science, and Scopus were searched up to July 2020. Following outcomes were evaluated: Probing depth (PD), Attachment loss (AL), Bleeding on probing (BOP), Number or percentage of Sites with PD ≥ 4 mm, Prevalence of periodontitis, Number of teeth, Decayed Teeth, Missing teeth, Filled teeth, DMFT index, and the interincisal distance. Newcastle-Ottawa Scale (NOS) were applied for quality assessment. The statistical analysis was processed using the software STATA. Results 11 eligible studies were included. The maximum interincisor distance was significantly restricted in SSc patients (SMD − 1.061; 95 %CI [− 1.546, − 0.576]; Z = 4.29, P = 0.000).The prevalence of Periodontitis (OR 7.007; 95 %CI [3.529, 13.915]; Z = 5.56, P = 0.000), PD (SMD 3.101; 95 %CI [1.374, 4.829]; Z = 3.52, P = 0.000), AL(SMD 2.584; 95 %CI [0.321, 4.846]; Z = 2.24, P = 0.025), sites with PD ≥ 4mm (SMD 2.071 ; 95 %CI [0.267, 3.875]; Z = 2.25, P = 0.024) and the number of decayed teeth (SMD, 0.186; 95 %CI [0.007, 0.365]; Z = 2.04, P = 0.041) were increased significantly in SSc population in comparison with the controls. Conclusions SSc patients have limited mouth opening, higher periodontitis prevalence, and worse periodontal status, as well as an increased number of decayed teeth. Routinely oral hygiene instruction and initial periodontal treatment is recommended for SSc patients.