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Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease. The purpose of this study was to investigate the link between microbiota composition in important mucosal interfaces (oral, nasal, and intestinal) and PD. Sequencing was undertaken of the V4-V5 region of the 16S ribosomal RNA (rRNA) gene of the microbiome from the oral cavity, nasal cavity, and gut of 91 PD patients and 91 healthy controls. Significant differences were found in microbiota composition in the oral cavity and gut, but not the nasal cavity, between PD patients and healthy controls after adjusting for age, gender, and body mass index (BMI). More genera in the oral cavity were significantly positively correlated with clinical characteristics, such as the HAMA and HAMD rating scales. The taxa c_Clostridia, o_Clostridiales, and f_Ruminococcaceae in the gut microbiota were associated with weight and MMSE score. Furthermore, as a result of dysbiosis, there was an enrichment of ion channel-, oxidative phosphorylation-, and carbohydrate metabolism-related pathways in the oral cavity and glycolysis/gluconeogenesis- and propanoate metabolism-related pathways in the intestine. Changes in these pathways can influence metabolism and inflammation, thereby contributing to PD pathogenesis. In addition, several subnetworks containing differentially abundant microbiota in the oral cavity and gut samples from PD patients may regulate microbial composition and function in PD. Overall, our results indicate that oral and gut dysbiosis may affect PD progression and provide a basis for understanding the pathogenesis of PD and identifying potential therapeutic targets for the treatment of this disease.

BACKGROUND Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. It is known that the proliferation of PC cells is a critical process in the disease. Previous studies have failed to identify the key genes associated with PC cell proliferation, using bioinformatic analysis, genome-wide association studies, and candidate gene testing. AIM To investigate the function of the chromobox 8 (CBX8)/receptor substrate 1 (IRS1)/AKT axis in PC. METHODS A genome-wide CRISPR-Cas9 screening was performed to select genes that could facilitate PC cell proliferation. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CBX8 in PC tissues and cells. The regulatory roles of CBX8 in cell proliferation, migration, and invasion were verified by in vivo and in vitro functional assays. RESULTS CBX8 was upregulated in PC tissues and shown to drive PC cell proliferation. Higher expression of CBX8 was correlated with worse outcomes of PC patients from two independent cohorts comprising a total of 116 cases. CBX8 was also proved to serve as a promising therapeutic target for a PC xenograft model. We demonstrated that hypoxia-inducible factor (HIF)-1a induced CBX8 transcription by binding to the promoter of CBX8. CBX8 efficiently activated the PI3K/AKT signaling by upregulating insulin IRS1. CONCLUSION CBX8 is a key gene regulated by HIF-1α, and activates the IRS1/AKT pathway, which suggests that targeting CBX8 may be a promising therapeutic strategy for PC.

Atmospheric particulate matter (PM) from agricultural activities aggravates global, regional, and local air pollution. The detailed emission evaluation for major crops can be used to understand, predict, and control the release of atmospheric PM from or in agriculture. However, previous studies on sources of emissions from agricultural activities have tended to focus only on straw burning, livestock or fertilizer, etc. at a macro scale, such that there is a lack of spatial–temporal and high-resolution quantitative data on particulate emissions generated from typical farming and harvesting activities. In this study, we developed high-resolution emission inventory of atmospheric PM10 generated as a result of tilling and harvesting in China using a crop emission factor–based approach, combining agricultural, meteorological, and soil information. Temporal, spatial, and historical features of agricultural PM10 emission in China were analyzed, and an optimization methodology was proposed. The historical trends (1978–2015) for agricultural emissions have been increasing with rate of 4.3% per year for the period. The annual emissions from all agricultural operations were estimated to be 986.8kt in 2015. The contribution rate for tilling (51.0%) was higher than that for harvesting (39.0%) and planting (10.0%). The PM10 emissions at the county level were all higher by 30.5% than those at the high-resolution scale. After correction, the decreases of M2 (optimization of soil texture), M3 (optimization of soil texture and moisture), and M4 (optimization of soil texture, soil moisture, and wind speed) were 52.3%, 82.5%, and 89.6%, respectively. These results indicate the soil texture and moisture are the main factors for the decrease of emissions. The high-resolution inventory of emissions of PM10 due to farming practices and harvesting is helpful for assessing the impact of agricultural activities on regional air quality in China and providing a scientific basis for the development of pollution control measures in agriculture.

The clinical significance and regulators of IL-13Rα2 in itch and atopic dermatitis (AD) remain unclear. To identify disease-driven regulatory circuits of IL-13Rα2, transcriptomic/pathological analysis was performed in skin from patients with AD, psoriasis, healthy subjects, and murine AD model. Functionality was investigated in sensory neurons, keratinocytes and animal model, by using knockdown (KD), calcium imaging, RNA-seq, cytokine arrays, pharmacological assays, and behavioural investigations. In our study, an upregulated IL-13Rα2 expression was revealed in skin of AD patients, but not psoriasis, in a disease activity-dependent manner. In cultured human keratinocytes, IL-13 increased IL-13Rα2 transcription levels, and this were downregulated by IL-13Rα1KD. IL-13Rα2KD reduced transcription levels of EDNRA, CCL20, CCL26. In contrast, sensory neuron-derived IL-13Rα2 was upregulated by TLR2 heterodimer agonists, Pam3CSK4 and FSL-1. In a mouse cheek model, pre-administration of Pam3CSK4 and FSL-1 enhanced IL-13-elicited scratching behaviour. Consistently, in cultured sensory neurons Pam3CSK4 enhanced IL-13-elicted calcium transients, increased number of responders, and orchestrated chemerin, CCL17 and CCL22 release. These release was inhibited by IL-13Rα2KD. Collectively, IL-13 regulates keratinocyte-derived IL-13Rα2 and TLR2 to modulate neuronal IL-13Rα2, thereby promoting neurogenic inflammation and exacerbating AD and itch. Thus, the cutaneous IL-13-IL-13Rα2 and neuronal TLR2-IL-13Rα2 pathway represent important targets to treat AD and itch.

Objective: To identify serum microRNAs (miRNAs) correlated with response to neoadjuvant chemoradiation therapy (NCRT) in locally advanced rectal cancer (LARC) patients using in silico analyses and ...

In this paper, a novel design of a 1×N multimode-interference power splitter is proposed and investigated. By using the finite difference time domain method and particle swarm optimization algorithm, our proposed 1×N optical power splitter can be optimized to realize compact size, good uniformity, low insertion loss, and broad bandwidth. To verify the effectiveness of this design, the designed 1×4 and 1×8 multimode-interference power splitters are experimentally demonstrated on an silicon-on-insulator platform. The lengths of the designed 1×4 and 1×8 power splitters are 36 μm and 47.8 μm, respectively. Experimental results show that, for the fabricated 1×4 power splitter, the uniformity ranges from 0.07 to 0.89 dB and the corresponding maximum insertion loss is 0.62 dB within a bandwidth from 1520 to 1624 nm. For the fabricated 1×8 power splitter, within a bandwidth from 1519 to 1623 nm, the uniformity varies from 0.19 to 0.83 dB and a maximum insertion loss of 0.64 dB are obtained.

To explore the distribution of stereoacuity and to examine its determinants in school-age children in Tibetan plateau, Southwest China. This is the cross-sectional part of a school-based cohort study of 7-year-old children in Lhasa, Tibet Autonomous Region, Southwest China. Children in first year of primary school were invited to undergo a comprehensive examination, including height, weight, visual acuity, cycloplegic autorefraction (1% cyclopentolate), anterior segment, cover and uncover test, and stereoacuity (Titmus Stereo Test). A total of 1833 eligible subjects were included, with a mean age of 6.82 ± 0.46 years. Mean stereoacuity was 1.78 ± 0.21 in log units (median: 60 arcsec). Children with stereoacuity equal to 40 arcsec and stereoacuity worse than 100 arcsec accounted for 29.24% and 8.18% of the cohort, respectively. Tibetan ethnicity (OR = 1.98; 95%CI, 1.30–3.03), astigmatism (OR = 1.65; 95%CI, 1.26–2.17), strabismus (OR = 2.92; 95%CI, 1.38–6.18), and amblyopia (OR = 3.77; 95%CI, 1.14–12.49) were risk factors for normal stereoacuity (= 40 arcsec). Shorter height, younger age, strabismus, and worse BCVA (P

Proliferation and apoptosis of vascular smooth muscle cells (VSMCs) are linked to intracranial aneurysm (IA) formation and progression. Long antisense noncoding RNA in the INK4 locus (ANRIL) has been reported to regulate VSMC functions in several cardiovascular diseases. However, little is known about how ANRIL influences VSMC proliferation and apoptosis during IA pathogenesis. The expression level of ANRIL in the plasma and arterial wall tissues of patients with IA was detected by real-time quantitative polymerase chain reaction. The functional role of ANRIL in the regulation of VSMC proliferation and apoptosis and its downstream regulatory mechanism were determined using Cell Counting Kit 8, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated UTP nick end labeling, western blotting, luciferase reporter assay, and RNA immunoprecipitation assay. ANRIL was downregulated in the plasma and arterial wall tissues of patients with IA, when compared with control groups. Overexpression of ANRIL significantly promoted VSMC proliferation and blocked cell apoptosis. Mechanistic studies demonstrated that ANRIL directly bound to microRNA-7 (miR-7) and that overexpression of miR-7 overturned the increased cell proliferation and decreased cell apoptosis, which was induced by ANRIL restoration. Besides, further study showed that ANRIL positively regulated fibroblast growth factor 2 (FGF2) expression via targeting miR-7. These results suggested that ANRIL affects VSMC proliferation and apoptosis via regulation of the miR-7/FGF2 pathway in IA, which provided a potential novel strategy for the treatment of IA.

Objective. The consumption of dairy is associated with decreased risk of colorectal cancer (CRC), but few studies have assessed the relationship between dairy consumption and precursors of CRC. Therefore, we performed the first meta-analysis to further evaluate this association. Methods. PubMed, Embase, Scopus, and Web of Science databases were searched through July 2020 for observational studies. Study-specific risk estimates for the highest versus lowest category were pooled using the random-effects and fixed-effects model. The methodological quality of included studies was assessed using the ROBINS-I Scale. Results. A total of 12 studies were included (3 cohort studies and 9 case-control studies). Compared with the lowest level consumption, fermented dairy products had a decreased risk of precursors of CRC in both cohort (RR = 0.92 95% CI: 0.87–0.97) and case-control studies (RR = 0.98 95% CI: 0.96–0.99). Total dairy (RR = 0.80 95% CI: 0.68–0.96) and cheese (RR = 0.96 95% CI: 0.93–0.99) consumption was inversely associated with the risk in case-control studies whereas yogurt consumption was inversely associated with the risk in cohort studies (RR = 0.91 95%CI: 0.86–0.96). No significant associations were found for consumption of total milk and non/low-fat milk. For dose-response analyses, evidence of linear association was found in total dairy and yogurt consumption. The risk decreased by 12% for an increment of 200 g/d total dairy consumption (RR = 0.88 95% CI: 0.81–0.95) and decreased by 8% for an increment of 50 g/d yogurt consumption (RR = 0.92 95% CI: 0.85–0.99). Conclusions. Fermented dairy products, specifically yogurt and cheese, were significantly associated with decreased risk of conventional and serrated precursors of colorectal cancer.

BACKGROUND Bezoars are conglomerates of indigestible foreign material that can be found in the gastrointestinal tract. Gastric ulcer, gastrointestinal perforation, and intestinal obstruction are the main complications. Acute pancreatitis secondary to bezoar is rare. Here, we present a rare case of a migratory gastric bezoar complicated by acute pancreatitis and small bowel obstruction after dissolution therapy. CASE SUMMARY A-65-year-old woman underwent gastroscopy because of epigastric pain, which revealed a huge bezoar and a gastric ulcer 10 d prior. The patient was discharged with a prescription of drinking 1 L Coca-Cola daily for 6 d, without repeat gastroscopy. However, she suddenly developed epigastric pain, nausea and vomiting for 3 d. Abdominal computed tomography (CT) revealed mild inflammation of the pancreas. Magnetic resonance cholangiopancreatography showed no abnormalities in the pancreatic duct or common bile duct. The nasogastric tube still showed drainage of more than 1.6 L of dark fluid each day after symptomatic treatment. Abdominal CT re-examination suggested intestinal obstruction. Esophagogastroduodenoscopy revealed a huge yellowish hard mass in the jejunal lumen, and we used the basket and net to fragment the bezoar. She was discharged with a good outcome. CONCLUSION Endoscopic therapy is the first choice for gastric bezoars. When mechanical disintegration cannot be achieved, timing of repeat endoscopy is important during Coca-Cola dissolution therapy.

Purpose The previous analysis of systematic reviews and meta-analyses have illustrated that obstructive sleep apnea (OSA) is correlated with multiple health outcomes. In the present research, our main aim was to execute an umbrella review to assess the available evidence for the associations between OSA and health outcomes. Methods Herein, a meta-analysis of previous observational investigations that have reported associations between OSA and health outcomes in all human populations and settings was performed. We used these studies to execute an umbrella review of available meta-analyses and systematic reviews. Results Sixty-six articles comprising 136 unique outcomes were enrolled in this analysis. Of the 136 unique outcomes, 111 unique outcomes had significant associations (p Conclusion Among the 66 meta-analyses exploring 136 unique outcomes, only 7 statistically significant outcomes were rated as high quality of evidence. OSA may correlate with an increased risk of coronary revascularization after PCI, postoperative respiratory failure, steatosis, ALT elevation, MS, psoriasis, and Parkinson’s disease.

The development of electrochemiluminescence (ECL) emitters remains a great research interest in ECL analysis. Herein, luminol-doped polymer dots (L-Pdots) and diethylamine-coupled Pdots (N-Pdots) were synthesized to design a both potential- and color-resolved ECL strategy. L-Pdots showed the maximum ECL emission at 450 nm in the presence of hydrogen peroxide at +0.6 V, while the maximum emission of N-Pdots was at 675 nm under +1.0 V. This strategy was conveniently used to construct a novel ECL array imaging method for high-throughput detection of two microRNAs (miRNAs). The array was prepared with the mixture of L-Pdots and N-Pdots that were covalently modified with quencher-labeled DNAs, respectively, to recognize the corresponding miRNAs. Upon the addition of duplex-specific nuclease, the DNAs hybridized with miRNAs were digested to release the quenchers and miRNAs, which led to the ECL recovery of Pdots and target-cyclic signal amplification. By imaging the array at +0.6 and +1.0 V and using miRNA-21 and miRNA-205 as the analytes, the blue and red channel images could be extracted to quantify these miRNAs with detection limits of 2.5 and 3.1 pM, respectively. This work provides a new family member of potential- or color-resolved ECL emitters and successfully realizes the simultaneous and high-throughput sensing of multiplex miRNAs.

To compare the differences between cycloplegic and noncycloplegic refraction as well as associated factors in grade one students of primary schools, and explore the effectiveness of noncycloplegic refraction for refractive error screening.Cross-sectional study.A school-based study of 1856 students was conducted in Lhasa, Tibetan Plateau, China. Cycloplegia was achieved with two drops of 1% cyclopentolate and 1 drop of Mydrin P at a 5-min interval. Autorefraction was performed under both cycloplegic and noncycloplegic conditions. Bland-Altman analysis, receiver operating characteristic curve analysis, univariate and multiple linear regression models were used for analysis.Of the 1856 children enrolled, 1830 (98.60%) completed all procedures. The average age was 6.83 ± 0.46 years. 965 (52.73%) children were boys and 1737 (94.92%) were Tibetan. Overall, there was a significant difference between cycloplegic and noncycloplegic SE of 0.90 ± 0.76D (P 0.001). However, the intra-class coefficient correlation (ICC) for cylinder between these two methods was high (ICC = 0.941, 95% CI, 0.935-0.946). Larger differences between cycloplegic and noncycloplegic SE were associated with hyperopic RE and higher cylindrical value (P 0.001). The prevalence of myopia, emmetropia and hyperopia with and without cycloplegia was (3.93% vs 14.59%), (9.95% vs 45.8%) and (86.21% vs 39.56%), respectively. Myopia, emmetropia and hyperopia based on noncycloplegic refraction was defined as SE ≤ - 0.625D, - 0.625 SE ≤ 0D, and SE 0D, respectively.Lack of cycloplegia leads to underestimation of hyperopia, with overestimation of myopia and emmetropia. Larger hyperopic refraction exhibited greater difference between cycloplegic and noncycloplegic refraction.

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over the world, has a generally poor prognosis, and its progression is positively correlated with the density of blood vessels. Recently, tumor-associated macrophages (TAMs) were proven to be beneficial for angiogenesis, but their mechanism of action remains unclear. Our study indicated that M2 macrophages were positively correlated with the microvessel density (MVD) of PDAC tissues, and M2 macrophage-derived exosomes (MDEs) could promote the angiogenesis of mouse aortic endothelial cells (MAECs) in vitro. At the same time, the M2 MDEs could also promote the growth of subcutaneous tumors and increase the vascular density of mice. Moreover, we also found that miR-155-5p and miR-221-5p levels in the M2 MDEs were higher than those in M0 MDEs, and they could be transferred into MAECs, as demonstrated by RNA sequencing (RNA-seq) and qPCR analysis. Our data confirmed the interaction between TAMs and the angiogenesis of PDAC by exosomes. Additionally, targeting the exosomal miRNAs derived from TAMs might provide diagnostic and therapeutic strategies for PDAC.

Objective To evaluate the efficacy and safety of intravenous immunoglobulin G (IVIG) in infants with ABO hemolytic disease of the newborn (HDN). Methods Infants with moderate-to-severe ABO HDN during early neonatal period ( Results Forty-six patients were classified into the IVIG group and 68 other patients were classified into the phototherapy only group. There was no significant difference in duration of phototherapy, hospitalization periods, needs for exchange transfusion, transfusions, and incidence of bilirubin-induced neurological sequelae between these two groups (P = 0.20, 0.27, 0.65, 0.47, 0.78, respectively). Conclusion It seems unnecessary to expose neonates to IVIG in moderate-to-severe ABO HDN when the available data show no appreciable benefits.

Imbalances in trace element concentrations in the blood as a result of poor nutrition may affect the development of coronary heart disease. To study the relationship between zinc ion concentration in the peripheral blood and coronary heart disease, we performed multiple logistic regression and hierarchical analyses on blood measurements of 3541 patients. The experimental group comprised 1253 patients diagnosed with coronary heart disease, and the control group included 2288 healthy patients. The zinc ion concentrations were measured by a color rendering method, and the results were analyzed using SPSS software. Fifteen laboratory quality evaluation samples from the Clinical Laboratory Center of the Chinese Ministry of Health were selected for analysis. The mean values and average bias were calculated. The estimated qualified judgment standard was

Copper halide Cs3Cu2X5 (X = Cl, Br, I) nanocrystals (NCs) have become a research hotspot in recent years. Compared with perovskite NCs, they have a large Stokes shift with a self-absorption-free effect and convenient solution processability, which endows them with potential applications in high-resolution flexible X-ray imaging and ultraviolet detection. However, the synthesis of Cs3Cu2I5 NCs is limited to the hot-injection method, which needs tedious operation procedures. Here, a one-pot fabrication strategy was designed based on the principle of chemical potential and thermodynamic equilibrium to achieve the mass production of Cs3Cu2I5 NCs. With the assistance of I−, Cs3Cu2I5 NCs were successfully fabricated with a reaction yield of about 70%, with the emission peak located at 445 nm and a high photoluminescence quantum yield (PLQY) of 72.6%. By scaling up the initial reaction volume tenfold, we successfully demonstrated mass production. Furthermore, Cs3Cu2Br5 and Cs3Cu2Cl5 NCs were also fabricated using this approach, indicating the versatility of this method. This strategy effectively optimizes the experimental process and cost, providing convenience for subsequent research based on this kind of material, such as optical electronic devices, ion-doping studies and so on.

With solution-processability, low-temperature proper energy level and superior stability, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is one common hole-transport material for the quantum dot light-emitting diode (QLED) application. However, the conductivity of the traditional PEDOT:PSS is very low, which has an adverse effect on QLED devices. Herein, one surface-annealing method for the PEDOT:PSS film to exchange their original composition and surface morphology is proposed. The advantage of this approach lies in the fact that the conductivity of the PEDOT:PSS film annealed with toluene (1.25 S cm−1) and ethylene glycol (EG, 10.52 S cm−1) are obviously improved compared with the air-annealing method (0.13 S cm−1). The difference is that the EG-washed PEDOT:PSS film shows a relatively rough surface with more PEDOT domains, whereas the toluene treated PEDOT:PSS film can promote the formation of a smooth, PSS-dominated surface and change the PEDOT chain structure from coiled to linear, thus, the conductivity of the PEDOT:PSS film is enhanced. As a result, the QLED device achieves a maximum luminance of 31 140 cd m−2 and power efficiency of 13.4 lm W−1, showing 48% and 25% enhancements, respectively, compared to the control device. This work provides an efficient approach for improving of perovskite QLED performance.

In this study, a blue fluorescent material Sr3Y(BO3)3:Bi3+ was synthesized by the high temperature solid-state reaction method. The corresponding structural characteristics, concentration and temperature dependent luminescence characteristics of Sr3Y(BO3)3:Bi3+ and the LED device performances were systematically studied. At different excitation wavelengths in the range of 340–375 nm, the photoluminescence (PL) region can be adjusted from green (CIE: (0.2524, 0.4063); Peak: 511 nm) to blue (CIE: (0.1936, 0.1236); Peak: 415 nm). The best excitation peaked at ∼370 nm, which well matches with the emission of a commercial near-ultraviolet (NUV) light-emitting diode (LED) chip. The thermal quenching experiment was performed, and the activation energy was calculated as 0.23 eV. At high temperature, the Sr2.55Y(BO3)3:0.45Bi3+ phosphor presented good thermal stability (79.99% of RT emission intensity at 420 K). LED devices (chip: 370 nm) using the Sr2.55Y(BO3)3:0.45Bi3+ phosphor as a fluorescent material showed excellent electroluminescence performance. Under a driving current of 20 mA, the devices showed CIE coordinates of (0.3842, 0.3980), a correlated color temperature (CCT) of 4053 K and a high color rendering index (Ra) of 91.6. This work demonstrates that Sr3Y(BO3)3:Bi3+ is a promising NUV excited blue fluorescent material which shows advantage in white light-emitting diodes for solid-state lighting.

In this paper, a design of a silicon mode (de)multiplexer based on cascaded counter-tapered couplers is proposed and investigated. By using the particle swarm optimization algorithm and finite difference time domain method, structural parameters of each counter-tapered coupler in our proposed mode (de)multiplexer are optimized so that high conversion efficiencies can be obtained and coupling lengths can be significantly shortened. The coupling lengths of counter-tapered couplers in the proposed silicon four-mode (de)multiplexer operating in transverse-electric polarization are 8 μm, 9 μm, and 10 μm. The corresponding conversion efficiencies are respectively 98.98%, 99.98%, and 98.68%. Experimental results show that, the fabricated device exhibits a demultiplexed crosstalk of -32.76 dB, -27.10 dB, -32.45 dB, or -33.29 dB at 1550 nm wavelength, when the fundamental transverse-electric mode is respectively launched into the ports Input0, Input1, Input2, or Input3. The measured demultiplexed crosstalk is less than -15.15 dB from 1525 to 1596 nm and lower than -18.12 dB from 1525 to 1561 nm.

Background: Lupus nephritis (LN) is the most severe organ manifestations of systemic lupus erythematosus (SLE). Although increased knowledge of the disease pathogenesis has improved treatment options, outcomes have plateaued as current immunosuppressive therapies have failed to prevent disease relapse in more than half of treated patients. Thus, there is still an urgent need for novel therapy. Mesenchymal stem cells (MSCs) possess a potently immunosuppressive regulation on immune responses, and intravenous transplantation of MSCs ameliorates disease symptoms and has emerged as a potential beneficial therapy for LN. The objective of this review is to discuss the defective functions of MSCs in LN patients and the application of MSCs in the treatment of both LN animal models and patients. Summary: Bone marrow MSCs from SLE patients exhibit impaired capabilities of migration, differentiation, and immune regulation and display senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and patients with LN by inducing regulatory immune cells and suppressing Th1, Th17, T follicular helper cell, and B-cell responses. In addition, MSCs can home to the kidney and integrate into tubular cells and differentiate into mesangial cells. Key Messages: The efficacy of MSCs in the LN treatment remains to be confirmed, and future advances from stem cell science can be expected to pinpoint significant MSC subpopulations, as well as specific mechanisms of action, leading the way to the use of more potent stimulated or primed pretreated MSCs to treat LN.

Bi-Doped nitridated germanate glasses covering the whole NIR region from 800–1600 nm have attracted considerable attention due to their potential application in tunable fiber lasers and optical amplifiers. However, it remains challenging to regulate the luminescence behaviour of Bi because of the coexistence of multi-centers in the glasses. Here, we successfully regulated multi Bi NIR centers to obtain a flatter and ultra-broadband emission in nitridated germanate glasses. By varying the alkaline earth metal fluorides from MgF2 to BaF2, the glass structures were gradually depolymerized. A looser glass network, on one hand, promoted Bi in lower valences to be oxidized into Bi2+ and Bi3+, thus reducing the NIR emission intensity at ∼1150 and ∼1260 nm; on the other hand, it also enhanced the energy transfer from Bi+ to Bi0, which resulted in a relatively flatter emission band. In addition, the depolymerised glass structure could facilitate more nitride bonds, which are favorable for dispersing and stabilizing the new Bi NIR active centers related to germanate for ∼930 and ∼1490 nm emission. This investigation offers an efficient way to manipulate the multi-center luminescence behaviour of Bi in nitridated germanate glasses, and is beneficial to understand the mechanism of Bi NIR emission centers in glasses.

Recently, the development and application of lane line departure warning systems have been in the market. For any of the systems, the key part of lane line tracking, lane line identification, or lane line departure warning is whether it can accurately and quickly detect lane lines. Since 1990s, they have been studied and implemented for the situations defined by the good viewing conditions and the clear lane markings on road. After then, the accuracy for particular situations, the robustness for a wide range of scenarios, time efficiency and integration into higher-order tasks define visual lane line detection and tracking as a continuing research subject. At present, these kinds of lane marking line detection methods based on machine vision and image processing can be divided into two categories: the traditional image processing and semantic segmentation (includes deep learning) methods. The former mainly involves feature-based and model-based steps, and which can be classified into similarity- and discontinuity-based ones; and the model-based step includes different parametric straight line, curve or pattern models. The semantic segmentation includes different machine learning, neural network and deep learning methods, which is the new trend for the research and application of lane line departure warning systems. This paper describes and analyzes the lane line departure warning systems, image processing algorithms and semantic segmentation methods for lane line detection.

To examine the role of individual race/ethnicity and community racial/ethnic mix on the type of opioid-related emergency department (ED) visits in Florida. The study identifies opioid-related ED visits that involved heroin, non-heroin poisoning, and opioid use disorder (OUD) from the first quarter of 2010 to the second quarter of 2018 in Florida. The trend is depicted by patients’ race/ethnicity and racial/ethnic mix of residential communities. Combined with zip code tabulation area data, the study builds a multilevel model and examines how individual-level and community-level covariates relate to the type of opioid-related ED visits. While opioid-related ED visit rate was highest among white patients, majority-black communities caught up with the majority-white communities in the visit rate. The multilevel model results suggest that the likelihood of an opioid-related ED visit involving heroin, non-heroin poisoning, or OUD differed by patient race/ethnicity as well as community racial/ethnic mix. Opioid-related ED visits among minority patients were more likely to involve non-heroin poisoning than non-Hispanic white patients, whereas patients from minority-dominant communities were more likely to involve heroin poisoning than from majority-white communities. However, community racial/ethnic mix was not significantly or less significantly associated with the likelihood of involving OUD ED visits. The study highlights the heterogeneity of the opioid overdose problem across racial/ethnic patients and communities with different racial/ethnic mixes. Future policies may consider the effect of living in different racial/ethnic mixed communities in addition to individual race/ethnicity.

With the maturity of neural network theory, it provides new ideas and methods for the prediction and analysis of stock market investment. The purpose of this paper is to improve the accuracy of stock market investment prediction, we build neural network model and genetic algorithm model, study the law of stock market operation, and improve the effectiveness of neural network and genetic algorithm. Through the empirical research, it is found that the neural network model can make up for the shortcomings of the traditional algorithm through the optimization of genetic algorithm.

Context Aaptamine is a potent ocean-derived non-traditional drug candidate against human cancers. However, the underlying molecular mechanisms governing aaptamine-mediated repression of lung cancer cells remain largely undefined. Objective To examine the inhibitory effect of aaptamine on proliferation and progression of non-small cell lung carcinoma (NSCLC) and dissect the potential mechanisms involved in its anticancer functions. Materials and methods In vitro assays of cell proliferation, cell cycle analysis, clonal formation, apoptosis and migration were performed to examine the inhibitory effects of aaptamine (8, 16 and 32 μg/mL) on NSCLC cells. The expression levels of proteins were analysed using western blotting analysis when cells were treated with a single drug or a combination treatment for 48 h. Results Aaptamine significantly inhibited A549 and H1299 cells proliferation with IC50 values of 13.91 and 10.47 μg/mL. At the concentrations of 16 and 32 μg/mL, aaptamine significantly reduced capacities in clonogenicity, enhanced cellular apoptosis and decreased the motile and invasive cellular phenotype. In addition, aaptamine arrested cell cycle at G1 phase via selectively abating cell cycle regulation drivers (CDK2/4 and Cyclin D1/E). Western blotting results showed that aaptamine attenuated the protein expression of MMP-7, MMP-9 and upregulated the expression of cleaved-PARP and cleaved-caspase 3. Moreover, aaptamine inhibited PI3K/AKT/GSK3β signalling cascades through specifically degrading the phosphorylated AKT and GSK3β. Discussion and conclusions Aaptamine retarded the proliferation and invasion of NSCLC cells by selectively targeting the pathway PI3K/AKT/GSK3β suggesting it as a potential chemotherapeutic agent for repressing tumorigenesis and progression of NSCLC in humans.

O2O (Online to Offline) services enable customers to place orders online and receive products/services offline. In addition to traditional in-house drivers, the emergence of crowd-sourced drivers p...

Aims: The present study was designed to evaluate whether the expression of the suppressor of cytokine signaling 3 (SOCS3) gene could serve as a biomarker to predict the risk of acute myocardial inf...

Background Overactive bladder is defined as “urgency, with or without urge incontinence, usually with frequency and nocturia”. Electroacupuncture may be a safe and an effective alternative therapy for overactive bladder, but the evidence is limited. Methods We will conduct a three-arm, non-inferiority, multi-centre randomized controlled clinical trial. A total of 420 patients with moderate and severe overactive bladder will be randomly assigned to one of three groups: the electroacupuncture group (N = 140), sham electroacupuncture group (N = 140), and solifenacin group (N = 140). The primary outcome will be the change in the overactive bladder symptom score from baseline to the end of the 12-week treatment. The secondary outcomes will include the proportion of participants with a decrease in the overactive bladder symptom score ≥ 3 at weeks 4, 8, 12, 20, and 32; the change in average 24 h values of urination, nocturnal urination, urgency incontinence and urgency episodes from baseline to weeks 4, 8, 12, 20 and 32, and so forth. The adverse events will be recorded. Statistical analysis will include covariance analysis, nonparametric tests and descriptive statistics. Discussion This study will answer the question of whether electroacupuncture is effective and non-inferior to solifenacin for improving the symptoms of overactive bladder patients. Trial registration Chinese clinical trial registry (ChiCTR1800019928).

Accurate link latency information is essential for various traffic engineering problems, such as routing design and network diagnosis. However, due to the routing constraints, link latency measurement is still a challenging problem in hybrid software-defined networks (SDNs) and little literature has been found in this field. Due to cost, a hybrid SDN composed of conventional routers and SDN switches will exist for some time to come, which shows the necessity and the urgency to address this problem. In this paper, we investigate this link latency measurement problem in two different scenarios: 1) the conventional routers can only support the shortest path routing protocol, and 2) the conventional routers can support source routing protocol. For both of these scenarios, we show how to deploy a minimum number of monitors and how to construct measurement paths between monitors to measure all the link latencies. Several algorithms are presented to solve these problems and the evaluations on different topologies prove the superiority of the proposed methods.

Evacuation navigation in emergencies such as fires is one of the most important operational considerations for a building. The large and complicated interior spaces, as well as the intensive popula...

Background Radiotherapy plays an important role in multidisciplinary treatment of esophageal squamous cell carcinoma (ESCC). However, the long term prognosis, relapse and metastasis of patients who received radiotherapy with different radiotherapy technique and fractions were unclear. The objective of the present study was to investigate the correlation of them. Methods Six prospective studies were conducted in succession including 475 locally advanced ESCC patients received two-dimensional (2D) and three-dimensional (3D) radiotherapy with late course accelerated hyperfractionated fraction (LCAF) and continuous accelerated hyperfractionated fraction (CAHF). Overall survival was analyzed using the Kaplan-Meier method. Research regarding the incidence of Grade 3 or higher acute radiation-related toxicity was conducted. Details of relapse and metastasis were also investigated. Results The median follow-up time was 57.5 months. The overall incidence of failure was 49%. No significant survival difference was observed in both LACF vs. CAHF and 2DRT vs. 3DRT groups (P=0.55 and 0.64, respectively). Fewer incidences of acute toxicities were observed in ESCC patients treated with 3DRT compared with those treated with 2DRT (P

This study aims to evaluate the cost-benefit of vaccination services, mostly partial series administration, provided by a mobile clinic program (MCP) in Houston for children of transient and low-income families. The study included 469 patients who visited the mobile clinics on regular service days in 2 study periods in 2014 and 836 patients who attended vaccination events in the summer of 2014. The benefit of partial series vaccination was estimated based on vaccine efficacy/effectiveness data. Our conservative cost-benefit estimates show that, compared with office-based settings, every dollar spent on vaccination by the MCP would result in $0.9 societal cost averted as an incremental benefit in regular service days and $3.7 during vaccination-only events. To further improve the cost-benefit of vaccination services in the MCP, decision-makers and stakeholders may consider improving work efficiency during regular service days or hosting more vaccination events.

Chronic itch poses major health care and economic burdens worldwide. In 2013, B‐type natriuretic peptide (BNP) was identified as an itch‐selective neuropeptide and shown to be both necessary and sufficient to produce itch behaviour in mice. Since then, mechanistic studies of itch have increased, not only at central levels of the spinal relay of itch signalling but also in the periphery and skin. In this review, we have critically analysed recent findings from complementary pharmacological and physiological approaches, combined with genetic strategies to examine the role of BNP in itch transduction and modulation of other pruritic proteins. Additionally, potential targets and possible strategies against BNP signalling are discussed for developing novel therapeutics in itch. Overall, we aim to provide insights into drug development by altering BNP signalling to modulate disease symptoms in chronic itch, including conditions for which no approved treatment exists.

Abtract Background Despite the high risk and economic burden of influenza-related diseases, about one-third of adults aged 65 and older still forego annual influenza vaccination. Mass media, as a leading source of health information for the public, can influence and promote health behaviors, such as vaccination. However, empirical evidence on the effect of media coverage on influenza vaccination uptake remains limited. Objective We examine the impact of media coverage by month on influenza vaccination among the elderly. Methods This study exploits variation in the number of influenza-related news reports by month and across seasons and examines its impact on vaccine uptake in a linear probability model with state fixed effects and seasonable random effects. We combine individual-level influenza vaccination data from the Behavioral Risk Factor Surveillance System (BRFSS), 2010-2017, and media coverage data from the NewsBank database along with several other data sources including weather data from the Global Historical Climatology Network and data on the influenza season from FluView from the Centers for Disease Control and Prevention. Results Our main results indicate every 100 additional media reports about influenza published in October were associated with an increase in the vaccination uptake rate among those aged 65+ of 0.3 percentage points. This association holds in January, but not in November or December. It was more pronounced in late-peak seasons and in seasons where the vaccine was highly effective. Conclusion This study provides suggestive evidence that variation in the number of media reports is associated with variation in influenza vaccination uptake.

Hierarchical Modulation (HM) is quite efficient for multimedia broadcast in wireless networks. It exploits the wireless broadcast advantage and allows a transmission to reach different users with various qualities. However, existing HM related schemes are based on specially designed hardware, leading to extra hardware and deployment cost in practice. As a remedy for this, we design and implement a software-based HM scheme, named as SoftHM. By carefully tuning the Physical Layer input of a packet (a sequence of “0” or “1” bits, known as PHY payload), a transmitter simply broadcasts the packet with a single rate (e.g., 54Mbps, the highest rate in 802.11g WLAN), while diverse receivers can decode and extract different amount of information (with different reception rate, e.g., 12Mbps or 54Mbps) from it based on their link qualities. Reverse engineering techniques are adopted so that SoftHM works in a plug-in mode, offering it high potentials for wireless systems without any changes in existing modulation and coding modules. We implement SoftHM based on Universal Software Radio Peripheral (USRP) B210 and Commercial of the Shelf (COTS) Wi-Fi devices. Both rigorous analysis on its performance and comprehensive implementation-based experiments show that compared with the traditional time-sharing approach, to support low-quality users with the same bandwidth, high-quality users in SoftHM achieve 111.1% to 616.7% higher throughput. Likewise, to serve high-quality users with the same bandwidth, low quality users in softHM achieve 176.9% to 390.9% higher throughput.

A switchable polarization beam splitter utilizing GST-on-silicon waveguides is introduced and comprehensively investigated in this paper. Based on the phase matching and mode hybridization, structural parameters of the presented device are optimized by using the particle swarm optimization algorithm and finite difference time domain method, so that the output fundamental transverse-electric (TE0) and transverse-magnetic (TM0) modes can be switched by controlling the phase state of GST and the device exhibits broad bandwidth, low crosstalk, and high polarization extinction ratio. For the designed device with the amorphous GST, the crosstalk is lower than −23.40 dB and the polarization extinction ratio is larger than 21.35 dB over the C-band. In the case of the crystalline GST, within the C-band, the crosstalk of less than −27.37 dB and the polarization extinction ratio of greater than 21.37 dB are achieved.

This work proposes an intelligent video processing architecture for bandwidth-efficient edge-cloud video streaming. On receiving the bandwidth-saving low-quality video streaming in compressed format, the proposed architecture can perform direct DNN-based video enhancement, e.g., super-resolution and motion-compensated frame interpolation (MCFI), on streams. By utilizing the metadata motion vectors and residuals extracted from the encoded video, our workflow will significantly eliminate the unnecessary pixels being processed by the video-enhancing DNNs, and greatly promote the execution efficiency. The evaluation results on popular datasets show that our architecture can reduce the edge-side processing latency of video-enhancing DNNs by 90% compared to the traditional flow while producing accurate and high-quality videos on edge.

Background Decreased best corrected visual acuity among children should be treated early in life, and vision screening in schoolchildren is an efficient and feasible selection for developing countries. Thus, the screening accuracy of different visual acuity tests is the key point for making vision screening strategies. The present study aims to explore the screening accuracy of uncorrected visual acuity (UCVA) and pin-hole corrected visual acuity (PCVA) using different vision chart in the detection of decreased best-corrected visual acuity (BCVA) among schoolchildren. Methods Grade one primary schoolchildren in urban Lhasa with data of UCVA using tumbling E chart (UCVAE), PCVA using tumbling E chart (PCVAE), UCVA using Lea Symbols chart (UCVAL), PCVA using Lea Symbols chart (PCVAL) and BCVA using Lea Symbols chart were reviewed. Decreased BCVA was defined as BCVA≤20/32(≥0.2 logMAR). Difference, reliability, and diagnostic parameters in the detection of decreased BCVA of different visual acuity results were analyzed. Results Overall, 1672 children aged 6.58 ± 0.44 years fulfilling the criteria. The prevalence of decreased BCVA was 6.8%. Although no significant differences were found between UCVAE vs UCVAL (p = .84, paired t-test) as well as PCVAE vs PCVAL (p = .24), the ICC between them was low (0.68 and 0.57, respectively). The average difference between BCVA and UCVAE, UCVAL, PCVAE, PCVAL was logMAR -0.08 (− 0.37, 0.21), − 0.08 (− 0.29, 0.17), − 0.05 (− 0.30, 0.19), − 0.06 (− 0.23, 0.12) using Bland–Altman method. The area under the receiver operating characteristic curve of UCVAE, PCVAE, UCVAL, PCVAL for the detection of decreased BCVA was 0.78 (0.73, 0.84), 0.76 (0.71, 0.82), 0.95 (0.94, 0.96), 0.93 (0.91, 0.95), respectively. Conclusion Pinhole does not increase the screening accuracy of detecting decreased BCVA in grade one primary schoolchildren. Visual acuity test using Lea Symbols is more efficient than Tumbling E in the screening of that age. Trial registration Data were maily from the Lhasa Childhood Eye Study which has finished the clinical registration on (ChiCTR1900026693).

BackgroundSquamous cell cancers in the hypopharynx (HP) and cervical esophagus (CE) are different diseases with different staging systems and treatment approaches. Pharyngoesophageal junction (PEJ) tumor involves both the hypopharynx and the cervical esophagus simultaneously, but few reports focused on PEJ tumors. This study aimed to clarify clinical characteristics and the treatment approaches of PEJ tumors.Patients and MethodsA total of 222 patients with squamous cell carcinoma in the HP, PEJ, and CE were collected between January 2008 and June 2018 in Fudan University Shanghai Cancer Center. We compared different lymph node metastatic patterns of three diseases above and the survival of different tumor locations, different lymph node metastasis, and different radiotherapy approaches.ResultsFor HP, PEJ, and CE cancer, the upper and middle cervical lymph node metastatic rates were 85.7%, 47.1%, and 5.8%, respectively; the lower cervical lymph node metastatic rates were 36.7%, 42.9%, and 35.0%, respectively; and the mediastinal lymph node metastatic rates were 2.0%, 72.9%, and 80.6%, respectively. The 3-year overall survival rates were 69.5% in the HP group, 52.0% in the PEJ group, and 69.6% in the CE group (p = 0.024). No survival differences were found between the involved-field-irradiation and elective-node-irradiation subgroups among PEJ tumors (p = 0.717 for OS and p = 0.454 for PFS, respectively).ConclusionHP cancers had a high prevalence in all cervical lymph node metastases, while CE cancers had a lower prevalence in the cervical and mediastinal lymph node metastases. PEJ cancer had the combined metastatic patterns of both HP and CE cancers. Involved field irradiation was feasible in chemoradiotherapy for PEJ cancers.

Background Early and effective ocular screening may help to eliminate treatable eye disorders. The Lhasa Childhood Eye Study (LCES) revealed the particular prevalence of refractive error and visual impairment in grade one schoolchildren (starting age of 6 years old) in Lhasa. Methods This is a cross-sectional part of school-based cohort study. One thousand nine hundred forty-three children were enrolled (median age, 6.78 years, range, 5.89 to 10.32). Each child underwent general and ocular examinations, including logarithm of the minimum angle of resolution (logMAR) visual acuity, cycloplegic autorefraction, and slit-lamp biomicroscopy evaluation. Multivariate and correlation analyses were performed to evaluate the association between refractive error with gender and ethnics. Results The prevalence of visual impairment (logMAR visual acuity ≥0.3 in the better-seeing eye) of uncorrected, presenting and best-corrected visual acuity (BCVA) was 12.2, 11.7 and 2.7%, respectively. Refractive error presented in 177 (78.0%) out of 227 children with bilateral visual impairment. Myopia (spherical equivalent refractor [SER] ≤ − 0.50 diopter [D] in either eye) was present in 4.7% children when measured after cycloplegic autorefraction. Hyperopia (SER ≥ + 2.00 D) affected 12.1% children. Hyperopia was significantly associated with female gender (P Conclusion The Lhasa Childhood Eye Study is the first school-based cohort study to reveal the prevalence and pattern of refractive error and visual impairment in Lhasa. Effective strategies such as corrective spectacles should be considered to alleviate treatable visual impairment.

Objective: Findings from previous observational studies on the association between red meat intake and risk of rheumatoid arthritis (RA) are inconsistent. Therefore, we aimed to evaluate the impact of red meat intake on the incidence of RA by meta-analysis.Methods: PubMed and Web of Science were searched for eligible observational studies regarding the association between red meat intake and the risk of RA until June 30, 2021. Risk estimates with corresponding 95% confidence interval (95% CI) were pooled. Subgroup analysis and meta-regression analysis were performed to explore the potential sources of heterogeneity. Sensitivity analysis and publication bias test were also carried out.Results: A total of eleven studies were selected, involving 4 cohort studies with 5 203 identified cases from 349 776 individuals and 7 case-control studies with 3 762 cases and 6 856 controls. The pooled risk estimate of RA risk was 0.94 (95% CI: 0.77 to 1.15) for ever versus non/occasional red meat intake, while high dose of red meat intake increased the risk of RA (OR: 1.26, 95% CI: 1.07 to 1.50) in the categorical meta-analysis. Dose-response meta-analysis suggested a non-linear dose-response relationship between red meat intake and RA (P=0.028). Red meat intake was found to be a risk factor of RA when the dose ranged from 96 to 166 g/day.Conclusion: High dose of red meat intake could increase the risk of RA. Mechanistic studies are warranted to clarify the aetiologic pathways through which high dose of red meat intake may promote RA.

Objective Studies have published the association between the expression of matrix metalloproteinases (MMPs) and the outcome of cervical cancer. However, the prognostic value in cervical cancer remains controversial. This meta-analysis was conducted to evaluate the prognostic functions of MMP expression in cervical cancer. Methods A comprehensive search of PubMed, Embase, and Web of Science databases was conducted to identify the eligible studies according to defined selection and excluding criteria and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Fixed and random effects models were evaluated through the hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the overall survival (OS), recurrence-free survival (RFS), and progress-free survival (PFS). Results A total of 18 eligible studies including 1967 patients were analyzed for prognostic value. Totally 16 selected studies including 21 tests were relevant to the cervical cancer OS, 4 studies focused on RFS, and 1 study on PFS. The combined pooled HRs and 95% CIs of OS were calculated with random-effects models (HR = 1.64, 95% CI = 1.01–2.65, P = .000). In the subgroup analysis for OS, there was no heterogeneity in MMP-2 (I2 = .0%, P = .880), MMP-1 (I2 = .0%, P = .587), and MMP-14 (I2 = 28.3%, P = .248). In MMP-7 and MMP-9, the heterogeneities were obvious (I2 = 99.2% ( P = .000) and I2 = 77.9% ( P = .000), respectively). The pooled HRs and 95% CIs of RFS were calculated with fixed-effects models (HR = 2.22, 95% CI = 1.38–3.58, P = .001) and PFS (HR = 2.29, 95% CI = 1.14–4.58, P = .035). Conclusions The results indicated that MMP overexpression was associated with shorter OS and RFS in cervical cancer patients. It suggested that MMP overexpression might be a poor prognostic marker in cervical cancer. Research Registry Registration Number: reviewregistry 1159.

Modern tourism plays an increasingly important economic role in regional development. However, in the practice of regional economic development, there is often a lag in economic development where the tourism industry is prosperous. We explored the potential impact of the development level of informatization on the coupling and coordination relationship between the tourism industry and regional economic development. Using provincial panel data from 2008 to 2017, we constructed a spatial Dubin model for empirical research. We established an evaluation model for the coupling and coordination relationship between tourism and regional economic development based on the establishment of evaluation models and indicator systems for informatization, tourism, and regional economic development. The results show that improvements to informatization generally promoted the coupling and coordination of tourism and regional economic development. Informatization not only improved the coupling and coordination of tourism and economic development in the region but also had significant spatial spillover effects. In addition to the influencing factors at the information level, the advantages of tourism resources and the level of economic development on the whole also helped to improve the degree of coupling and coordination, while the widening of the income gap between urban and rural areas hindered coordinated development. Further discussion shows that informatization will affect the degree of coupling and coordination between the tourism industry and regional economic development by influencing the level of institutional environment. The findings highlight the need to focus on diversified development of the regional tourism industry and economy while improving the level of informatization and strengthening cross-regional cooperation during informatization. The conclusions contribute to improving the coordinated development of regional tourism and regional economy and provide a scientific basis for the development of informatization and the formulation of tourism and economic policies.

We read the Rong’s paper [1] with great interest. In this article, a total of 53 acquired pure red cell aplasia (PRCA) patients, including 30 idiopathic PRCA and 23 secondary PRCA patients, were re...

Increasing evidence suggests that triggering receptor expressed on myeloid cells 2 (TREM2) is implicated in the pathophysiology of neuroinflammation. The aim here was to investigate the neuroprotective role of TREM2 and its regulatory mechanism after subarachnoid hemorrhage (SAH). TREM2 siRNA was administered to measure the detrimental role of TREM2 in mediating microglial polarization in vivo and in vitro after experimental SAH. The relationship between Toll-like receptor 4 (TLR4) signaling and TREM2 was further explored. The soluble TREM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The results showed that TREM2 mainly located in the microglia and presented a markedly delayed elevation after SAH. TREM2 knockdown triggered increased pro-inflammatory productions, aggravated microglial activities, and further exacerbated neurological dysfunction after SAH. Significantly, TLR4 knockout increased the expression of TREM2, accompanied by ameliorated neuroinflammation and improved neurological function. Corresponding to different clinical Hunt–Hess grades, obviously enhanced accumulation of soluble TREM2 was detected in the CSF of patients with SAH. TREM2 played a pivotal role in mediating microglial polarization after SAH, and the neuroprotective effect of TREM2 might be potentially suppressed by the hyperactive TLR4 in the early phase of SAH. Pharmacological targeting of TREM2 may be a promising strategy for SAH therapy.

• Background• It is not currently known whether free fatty acids can be used as predictors for the prognosis of patients with acute ST-segment elevation myocardial infarction. The results of many studies on the correlation between free fatty acids and the prognosis of patients with acute myocardial infarction are inconsistent. The purpose of this clinical study is to determine the predictive effect of different free fatty acids in the plasma on cardiovascular events within the 12 months after a patient suffers an acute ST-segment elevation myocardial infarction.• Methods• This study is a prospective, observational, single-center cohort study. After enrollment, all participants will receive standard treatment and will be tested for 31 kinds of plasma free fatty acids. The patients will be followed up 2, 6, and 12 months after discharge. The primary endpoint is the compound cardiovascular events from onset to 12 months, including the cumulative incidence of all-cause death, heart failure, or coronary revascularization events. According to the power and sample size calculation, it will be necessary to enroll 747 patients in this study. After follow-up, data will be collected and analyzed to explore the predictive effect of different free fatty acids in plasma on the prognosis of acute elevated ST-segment myocardial infarction, and the risk factors of the endpoint events within 12 months.• Discussion• This study will provide new insightful evidence of serum indicators indicating the 12-month cardiovascular events of acute ST-segment elevation myocardial infarction.Trial registration: This study was retrospectively registrated at Chinese Clinical Trail Registry (https://www.chictr.org.cn/) on 14th July,2021. Registration number: ChiCTR2100048731.