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Background: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. Methods and design: This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. Discussion: The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects. [ABSTRACT FROM AUTHOR]

An all-dielectric nanoantenna is expected to greatly boost the nonlinear performance owing to its large mode volume and low material loss. However, it still suffers from the relatively weak near-field enhancement and the inferior far-field directivity. In this work, by successively introducing an upper metal ring and a bottom metal film, the plasmonic resonance and the perfect electric conductor (PEC) mirror effect are employed to significantly enhance and tailor the third harmonic generation (THG) from the high-index silicon nanoantenna. Numerical results show that benefiting from both of these two metal components, not only the THG efficiency is increased by more than 1 and 3.5 orders of magnitude compared with those with only single metal component and without any metal component, respectively, but also an improved radiation directivity can be obtained. The dependences of geometric parameters are discussed as well. This work suggests a route to enhance and manipulate the nonlinear radiation by a hybrid nanoantenna and facilitates its practical applications such as biosensing and nonlinear light sources.

Abstract The pore size distribution of the catalyst layer (CL) significantly influences the effective diffusion coefficient (EDC) of the reactant gas due to the Knudsen diffusion effect in the proton exchange membrane fuel cell (PEMFC). In this study, a novel fractal method is proposed to evaluate the Knudsen diffusion based on the pore size distribution of the CL, which is then incorporated in the calculation of the EDC of oxygen in the CL. It suggests that the EDC of oxygen obtained from the proposed method considering the pore size distribution is greatly smaller than that obtained from the conventional Bruggeman correlation, hence resulting in much smaller maximum current density of PEMFC.

Objective: The objective of the study was to explore the research status and hot topics that are most studied about in Tai Chi Chuan (TCC) analgesia through a metrical and visualization analysis of the literature and provide some references for the experimental research on the analgesic effect of TCC and its clinical applications. Methods: The literature on TCC analgesia was collected from the Web of Science database, and the metrical and visualization analysis was performed using the CiteSpace. 5.6.R4 software in terms of publication outputs, countries, institutions, keywords, highly cited articles, and highly cited journals. Results: The number of annual publications gradually increased over time. The five research groups presented stable cooperative relationships and more publications. The authors ranked as top 1 were from America rather than China, which has more publications. The most common keywords were Tai Chi, randomized controlled trial, older adults, exercise, pain, low back pain, quality of life, management, etc. The literature on knee osteoarthritis and fibromyalgia had the highest citation frequency. The journals with high citation frequency included Cochrane Database System Review, Pain, and Plos One. Conclusions: Increasing attention has been paid to TCC analgesia. Randomized controlled trials, older adults, low back pain, and quality of life were found to be most studied in this field. Investigating clinical efficacy and conducting meta-analyses could be a promising direction in the future. The international cooperation and literature quality of TCC analgesia should be further strengthened.

Measurement(s) retina Technology Type(s) mass spectrometry Sample Characteristic - Organism Mus musculus Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13128044

Considering that Actinidia kolomikta bears abundant white leaves on reproductive branches during blossoming, we hypothesized that the white leaves may maintain photosynthetic capacity by adjustments of leaf anatomy and physiological regulation. To test this hypothesis, leaf anatomy, gas exchange, chlorophyll a fluorescence, and the transcriptome were examined in white leaves of A. kolomikta during flowering. The palisade and spongy mesophyll in the white leaves were thicker than those in green ones. Chloroplast development in palisade parenchyma of white leaves was abnormal, whereas spongy parenchyma of white leaves contained functional chloroplasts. The highest photosynthetic rate of white leaves was ~82% of that of green leaves over the course of the day. In addition, the maximum quantum yield of PSII (Fv/Fm) of the palisade mesophyll in white leaves was significantly lower than those of green ones, whereas Fv/Fm and quantum yield for electron transport were significantly higher in the spongy mesophyll of white leaves. Photosynthetic capacity regulation of white leaf also was attributed to upregulation or downregulation of some key genes involving in photosynthesis. Particularly, upregulation of sucrose phosphate synthase (SPS), glyeraldehyde-3-phosphate dehydrogenase (GAPDH) and RuBisCO activase (RCA) in white leaf suggested that they might be involved in regulation of sugar synthesis and Rubisco activase in maintaining photosynthetic capacity of white leaf. Conclusions: white leaves contained a thicker mesophyll layer and higher photosynthetic activity in spongy parenchyma cells than those of palisade parenchyma cells. This may compensate for the lowered photosynthetic capacity of the palisade mesophyll. Consequently, white leaves maintain a relatively high photosynthetic capacity in the field.

Neutrophil extracellular traps (NETs) that are produced in the tumour microenvironment (TME) have been suggested to play an essential role in the dissemination of metastatic cancer under multiple infectious and inflammatory conditions. However, the functions of NETs in promoting non-small cell lung cancer (NSCLC) metastasis and the underlying mechanisms remain incompletely understood. Here, we found that NETs promoted NSCLC cell invasion and migration by inducing epithelial to mesenchymal transition (EMT). To explore how NETs contribute to NSCLC metastasis, microarrays were performed to identify substantial numbers of long noncoding RNAs (lncRNAs) and mRNAs that were differentially expressed in NSCLC cells after stimulation with NETs. Interestingly, we observed that the expression of lncRNA MIR503HG was downregulated after NETs stimulation, and ectopic MIR503HG expression reversed the metastasis-promoting effect of NETs in vitro and in vivo. Notably, bioinformatics analysis revealed that differentially expressed genes were involved in the NOD-like receptor and NF-κB signalling pathways that are associated with inflammation. NETs facilitated EMT and thereby contributed to NSCLC metastasis by activating the NF-κB/NOD-like receptor protein 3 (NLRP3) signalling pathway. Further studies revealed that MIR503HG inhibited NETs-triggered NSCLC cell metastasis in an NF-κB/NLRP3-dependent manner, as overexpression of NF-κB or NLRP3 impaired the suppressive effect of MIR503HG on NETs-induced cancer cell metastasis. Together, these results show that NETs activate the NF-κB/NLRP3 pathway by downregulating MIR503HG expression to promote EMT and NSCLC metastasis. Targeting the formation of NETs may be a novel therapeutic strategy for treating NSCLC metastasis.

To investigate the potential role of apple polyphenol extract (APE) in the prevention and alleviation of circadian rhythm disturbances, eighty male C57BL/6 mice fed a high-fat diet (HFD) were randomized into four groups: 24 h ad libitum feeding (AL), 12 h restricted nighttime feeding (NF) or daytime feeding (DF), and daytime feeding with APE intragastric administration (DF-APE). Five weeks later, the mice were sacrificed at 6 h intervals over 24 h. Disrupted fluctuations in serum lipid profiles and hormones, along with desynchronization of circadian clock genes and metabolic genes were observed after daytime HFD feeding. However, APE treatment improved hepatic steatosis and recovered circadian rhythms of Cry1/2, and genes Acc and Hsl related to lipid synthesis and hydrolysis of cholesteryl esters, and Cyp7a1 in bile acid synthesis. In conclusion, the present study provides new evidence revealing that the circadian clock might be a novel target for APE to regulate metabolic homeostasis.

Introduction Shift workers are at an increased risk of developing obesity and type 2 diabetes. Eating and sleeping out of synchronisation with endogenous circadian rhythms causes weight gain, hyperglycaemia and insulin resistance. Interventions that promote weight loss and reduce the metabolic consequences of eating at night are needed for night shift workers. The aim of this study is to examine the effects of three weight loss strategies on weight loss and insulin resistance (HOMA-IR) in night shift workers.Methods and analysis A multisite 18-month, three-arm randomised controlled trial comparing three weight loss strategies; continuous energy restriction; and two intermittent fasting strategies whereby participants will fast for 2 days per week (5:2); either during the day (5:2D) or during the night shift (5:2N). Participants will be randomised to a weight loss strategy for 24 weeks (weight loss phase) and followed up 12 months later (maintenance phase). The primary outcomes are weight loss and a change in HOMA-IR. Secondary outcomes include changes in glucose, insulin, blood lipids, body composition, waist circumference, physical activity and quality of life. Assessments will be conducted at baseline, 24 weeks (primary endpoint) and 18 months (12-month follow-up). The intervention will be delivered by research dietitians via a combination of face-to-face and telehealth consultations. Mixed-effect models will be used to identify changes in dependent outcomes (weight and HOMA-IR) with predictor variables of outcomes of group, time and group–time interaction, following an intention-to-treat approach.Ethics and dissemination The study protocol was approved by Monash Health Human Research Ethics Committee (RES 19-0000-462A) and registered with Monash University Human Research Ethics Committee. Ethical approval has also been obtained from the University of South Australia (HREC ID: 202379) and Ambulance Victoria Research Committee (R19-037). Results from this trial will be disseminated via conference presentations, peer-reviewed journals and student theses.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN-12619001035112).

Integrin beta- like 1 (ITGBL1), an extracellular matrix protein, plays an oncogenic role in diverse forms of cancers. To this end, we examined the importance of ITGBL1 in gastric cancer (GC). The upregulated expression of ITGBL1 in GC was associated with a poor prognosis. Moreover, upregulation of ITGBL1 enhanced cell mobility while silencing it exerted an opposite effect. Up-regulation of ITGBL1 significantly promoted phosphorylation of Akt, decreased the ratio of phosphorylated Akt in AGS/ITGBL1-shRNA and N87/ITGBL1-shRNA cells, enhanced cell mobility and proliferation. Silencing ITGBL1 had an opposite effect on Akt phosphorylation, cell mobility, and proliferation. These findings show that ITGBL1 regulates mobility and proliferation of GC likely through activation of Akt signaling.

Abstract Background Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. Methods Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. Results AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. Conclusions Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.

Liquiritigenin (LG), isoliquiritigenin (Iso-LG), together with their respective glycoside derivatives liquiritin (LN) and isoliquiritin (Iso-LN), are the main active flavonoids of Glycyrrhiza uralensis, which is arguably the most widely used medicinal plant with enormous demand on the market, including Chinese medicine prescriptions, preparations, health care products and even food. Pharmacological studies have shown that these ingredients have broad medicinal value, including anti-cancer and anti-inflammatory effects. Although the biosynthetic pathway of glycyrrhizin, a triterpenoid component from G. uralensis, has been fully analyzed, little attention has been paid to the biosynthesis of the flavonoids of this plant. To obtain the enzyme-coding genes responsible for the biosynthesis of LN, analysis and screening were carried out by combining genome and comparative transcriptome database searches of G. uralensis and homologous genes of known flavonoid biosynthesis pathways. The catalytic functions of candidate genes were determined by in vitro or in vivo characterization. This work characterized the complete biosynthetic pathway of LN and achieved the de novo biosynthesis of liquiritin in Saccharomyces cerevisiae using endogenous yeast metabolites as precursors and cofactors for the first time, which provides a possibility for the economical and sustainable production and application of G. uralensis flavonoids through synthetic biology. KEY WORDS: Glycyrrhiza uralensis, Liquiritin, Isoliquiritin, Liquiritigenin, Isoliquiritigenin, Heterologous synthesis, Saccharomyces cerevisiae

Abstract Background Introgression of chromatin from Secale species into common wheat has for decades been a successful strategy for controlling the wheat diseases. The wild Secale species, Secale africanum Stapf., is a valuable source for resistance to foliar disease of wheat. A wheat-S. africanum chromosome 6Rafr substitution line displayed resistance to both powdery mildew and stripe rust at the adult-plant stage. Results Wheat-S. africanum chromosome 6Rafr deletion and translocation lines were produced and identified by sequential non-denaturing fluorescence in situ hybridization (ND-FISH) using multiple Oligo-based probes. Different ND-FISH patterns were observed between S. cereale 6R and S. africanum 6Rafr. With reference to the physical map of the draft genome sequence of rye inbred line Lo7, a comprehensive PCR marker analysis indicated that insertions and deletions had occurred by random exchange between chromosomes 6R and 6Rafr. A survey of the wheat- S. africanum 6Rafr lines for disease resistance indicated that a powdery mildew resistance gene(s) was present on the long arm of 6Rafr at FL0.85–1.00, and that a stripe rust resistance gene(s) was located in the terminal region of 6RafrS at FL0.95–1.00. The wheat-S. africanum 6Rafr introgression lines also displayed superior agronomic traits, indicating that the chromosome 6Rafr may have little linkage drag in the wheat background. Conclusions The combination of molecular and cytogenetic methods allowed to precisely identify the chromosome rearrangements in wheat- S. africanum 6Rafr substitution, deletion and translocation lines, and compare the structural difference between chromosomes 6R and 6Rafr. The wheat- S. africanum 6Rafr lines containing gene(s) for powdery mildew and stripe rust resistance could be used as novel germplasm for wheat breeding by chromosome engineering.

This article presents a standalone cloud detection algorithm over the land (CDL) for microwave humidity sounder-2 (MWHS-2), which is characterized by the first operational satellite sensor measuring 118.75 GHz. The CDL is based on the advanced machine learning algorithm gradient boosting decision tree, which achieves the state-of-the-art performance on tabular data with high accuracy, fast training speed, great generalization ability, and weight factor ranking of predictors (or features). Given that the new-generation weather radar of China (CINRAD) provides improved cloud information with extensive temporal-spatial coverage, the observations from CINRAD are used to train the algorithm in this study. There are four groups of radiometric information employed to evaluate the CDL: all frequency ranges from MWHS-2 (all-algorithm), the humidity channels near 183.31 GHz (hum-algorithm), the temperature channels near 118.75 GHz (tem-algorithm), and the window channels at 89 and 150 GHz (win-algorithm). It is revealed that the tem-algorithm (around 118.75 GHz) has a superior performance for CDL along with the optimal values of most evaluation metrics. Although the all-algorithm uses all available frequencies, it shows inferior ability for CDL. Followed are the win-algorithm and hum-algorithm, and the win-algorithm performs better. The analysis also indicates that the latitude, zenith angle, and the azimuth are the top-ranking features for all four algorithms. The presented algorithm CDL can be applied in the quality control processes of assimilating microwave radiances or in the retrieval of atmospheric and surface parameters for cloud filtering.

Friedelin, the most rearranged pentacyclic triterpene, also exhibits remarkable pharmacological and anti-insect activities. In particular, celastrol with friedelin as the skeleton, which is derived from the medicinal plant Tripterygium wilfordii, is a promising drug due to its anticancer and antiobesity activities. Although a previous study achieved friedelin production using engineered Saccharomyces cerevisiae, strains capable of producing high-level friedelin have not been stably engineered. In this study, a combined strategy was employed with integration of endogenous pathway genes into the genome and knockout of inhibiting genes by CRISPR/Cas9 technology, which successfully engineered multiple strains. After introducing an efficient TwOSC1T502E, all strains with genetic integration (tHMG1, ERG1, ERG20, ERG9, POS5, or UPC2.1) showed a 3.0∼6.8-fold increase in friedelin production compared with strain BY4741. Through further double knockout of inhibiting genes, only strains GD1 and GD3 produced higher yields. Moreover, strains GQ1 and GQ3 with quadruple mutants (bts1; rox1; ypl062w; yjl064w) displayed similar increases. Finally, the dominant strain GQ1 with TwOSC1T502E was cultured in an optimized medium in shake flasks, and the final yield of friedelin reached 63.91 ± 2.45 mg/L, which was approximately 65-fold higher than that of the wild-type strain BY4741 and 229% higher than that in ordinary SD-His-Ura medium. It was the highest titer for friedelin production to date. Our work provides a good example for triterpenoid production in microbial cell factories and lays a solid foundation for the mining, pathway analysis, and efficient production of valuable triterpenoids with friedelin as the skeleton.

BackgroundAgeism is a global challenge, which leads to a range of adverse outcomes for elderly people worldwide, which maybe more severe among urban older adults in a competitive society. However, how self-perceived ageism influences the quality of life in a sample of urban older adults remains inconclusive.ObjectivesThe current study aims to assess the status of self-perceived stigma among urban Chinese older adults, identify its relationship with quality of life, and further explore whether both attitude toward own aging and traditionality moderate this relationship.Materials and MethodsPrimary data were collected through cross-sectional surveys among urban older adults in three provinces of China from October 2019 to December 2020. A total of 764 urban older adults were valid participants (effective response rate = 81.28%) and completed questionnaires via anonymous face-to-face interviews. Socio-demographic factors, self-perceived stigma, attitude toward own aging, traditionality, and quality of life were assessed using questionnaires that included the Self-perceived Stigma, Attitude Toward Own Aging, Traditionality, and SF-8 Scales.ResultsFor urban Chinese older adults, the average score of self-perceived stigma was 2.041 ± 0.726. Self-perceived stigma (β = −0.391, p < 0.05) and attitude toward own aging (β = −0.211, p < 0.05) both influenced quality of life. Additionally, attitude toward own aging (β = −0.530, p < 0.05) and traditionality (β = −0.525, p < 0.05) moderated the association between self-perceived stigma and quality of life. Simple slope analysis revealed that when the level of negative attitude toward own aging and traditionality was higher, the strength of the influence of self-perceived stigma on quality of life was stronger.ConclusionUrban Chinese older adults were aware of the self-perceived stigma, which contributes to decreased quality of life. Attitude toward own aging and traditionality could moderate the association between self-perceived stigma and quality of life. When negative attitudes toward own aging and traditionality are higher, self-perceived stigma has a greater effect on the quality of life. More interventions related to relieving self-perceived stigma, traditionality, and negative attitude toward own aging should be considered to build a new modern society that emphasizes health, friendliness, well-being, and dignity for all ages.

IntroductionSarcoidosis is a chronic granulomatous disease of unknown etiology. A variety of studies have pointed out that almost every part of the body can be affected, but it most often affected the lungs and intrathoracic lymph nodes. However, cases of sarcoidosis involving multiple organs in one patient are rarely reported. We describe a unique case of sarcoidosis, which was characterized by multiorgan involvement, including leg ulcers, splenomegaly, pancytopenia, and polyserositis. Glucocorticoids were effective during the treatment of the above lesions. This case highlights the diversity of clinical manifestations of sarcoidosis and emphasizes the importance of its differential diagnosis and the periodical follow-up. These are crucial to physicians in the diagnosis and treatment of sarcoidosis.Main Symptoms and Important Clinical FindingsA 30-year-old male complained about intermittent fever 3 years ago. A computed tomographic scan of the chest showed lymphadenopathy in the mediastinum and hilar regions. Routine blood tests showed leukopenia and mild anemia. The pathologic result of mediastinal lymph node biopsy was granulomatous lesions; thus, the patient was diagnosed with type II sarcoidosis without glucocorticoid therapy. In the following 2 years, the patient suffered from intermittent fever accompanied by dyspnea, fatigue, occasional cough, less sputum, and apparent weight loss. Abnormal physical examinations included leg ulcers and splenomegaly. Laboratory and physical tests revealed pancytopenia, polyserositis, and enlargement of lymph nodes. The pathological findings of leg ulceration, pleura, and left supraclavicular lymph node all suggested granulomas.Diagnosis, Interventions, and OutcomesIt strongly suggested sarcoidosis since tuberculosis, lymphoma, and connective tissue disease were all excluded. Due to severe conditions and multiorgan involvement, we tried to provide methylprednisolone for this patient. After 9 months of oral glucocorticoids therapy, his subjective symptoms as well as hematological and radiological findings were all improved. His leg skin ulceration and scab were also completely disappeared.ConclusionSarcoidosis has diverse clinical presentations, and many patients present with atypical symptoms. It needs to be timely identified by the clinician and carefully differentiated from other diseases with similar findings so as to make an accurate diagnosis. In this case, the patient had a poor clinical response to glucocorticoids in the early stage of treatment due to the severe condition and multi-organ involvement. It is worth noting that the patient had improved significantly after 9 months of treatment of corticosteroids, which suggested that follow-up is critical.

Background The FAT atypical cadherin 1/2/3/4 (FAT1/2/3/4) has been linked to the occurrence and development of various cancers. However, the prognostic and immunological role of FAT1/2/3/4 in non-small cell lung cancer (NSCLC) has not been clarified. Methods The association of FAT1/2/3/4 mutations with tumor mutation burden (TMB), tumor immunity in the microenvironment, and response to ICIs in NSCLC was investigated. Whole-exome sequencing data of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) samples from the Cancer Genome Atlas (TCGA), and an immunotherapy data set comprising mutation and survival data of 75 NSCLC patients were analyzed. Two independent pan-cancer cohorts with large samples were used to validate the prognostic value of FAT1/2/3/4 mutations in immunotherapy. Results A high mutation rate of FAT1/2/3/4 (57.3%, 603/1052) was observed in NSCLC patients. TMB was significantly higher in samples with mutated FAT1/2/3/4 compared to samples with wildtype FAT1/2/3/4 ( P < .05). FAT2 mutation was found to be an independent prognostic biomarker in LUAD. FAT1/2/3/4 were aberrantly expressed in LUAD and LUSC, and high FAT2 expression strongly correlated with high PD-L1 levels in LUAD. Moreover, LUAD patients with FAT1 mutations showed significantly high activated dendritic cells infiltration, whereas those with FAT2/3/4 mutations had high infiltration of CD8 + T-cells, M1 macrophages, activated memory CD4 + T-cells, and helper follicular T-cells. It was also observed that FAT1/2/4 mutations were significantly associated with better enhanced objective response and durable clinical benefit, whereas FAT1/2/3 mutations correlated with longer progression-free survival in ICI-treated NSCLC cohort. FAT1/4 mutations were related to better overall survival in pan-cancer patients treated with ICIs. Conclusions FAT family genes are potential prognostic and immunological biomarkers and correlate with response to ICIs in NSCLC.

Objective. The current study aimed to compare the characteristics of chromosome abnormalities detected by conventional G-banding karyotyping, chromosome microarray analysis (CMA), or fluorescence in situ hybridization (FISH)/CNVplex analysis and further explore the application value of combined karyotype analysis and CMA in prenatal diagnosis with a larger sample size. Methods. From March 2019 to March 2021, 3710 amniocentesis samples were retrospectively collected from women who accepted prenatal diagnosis at 16 to 22 + 6 weeks of pregnancy. The pregnant women underwent karyotype analysis and CMA. In the case of fetal chromosomal mosaicism, FISH or CNVplex analysis was utilized for validation. Results. In total, 3710 G-banding karyotype results and CMA results from invasive prenatal diagnosis were collected. Of these, 201 (5.41%) fetuses with an abnormal karyotype were observed. The CMA analysis showed that the abnormality rate was 9.14% (340/3710). The detection rate of CMA combined with karyotype analysis was 0.35% higher than that of CMA alone and 4.08% higher than that of karyotyping alone. Additionally, 12 cases had abnormal karyotype analysis, despite normal CMA results. To further detect the chromosome mosaicism, we used FISH analysis to correct the karyotype results of case 1. Correspondingly, a total of 157 cases showed abnormal CMA results but normal karyotype analysis. We also found chromosomal mosaicism in 4 cases using CMA. Moreover, CNVplex and CMA demonstrated that representative case 15 was mosaicism for trisomy 2. Conclusions. Conventional G-banding karyotyping and CMA have their own advantages and limitations. A combination of karyotype analysis and CMA can increase the detection rate of chromosome abnormalities and make up for the limitation of signal detection.

Purpose: Skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. Abnormal muscle quantity of the lower limbs is a manifestation of skeletal muscle dysfunction in patients with COPD. Shear wave ultrasound elastography (SWE) is a novel and possible tool to evaluate qualitative muscle parameters. This study explores the feasibility of SWE to measure the stiffness of the rectus femoris and evaluates its value in predicting sarcopenia in patients with COPD.Methods: Ultrasound examination of the rectus femoris was performed to determine the mean elasticity index (SWEmean), cross-sectional area (RFcsa), and thickness (RFthick) using grayscale ultrasonography (US) and SWE in 53 patients with COPD and 23 age-matched non-COPD healthy controls. The serum levels of circulating biomarkers (GDF15, resistin, and TNF-α) were measured using ELISA. The definition of sarcopenia followed the guidelines from the Asian Working Group for Sarcopenia. Receiver operating characteristic (ROC) curve analysis of the SWEmean, RFthick, and RFcsa was used to evaluate their predictive ability for sarcopenia.Results: The intraobserver and interobserver repeatability of SWE performance was excellent (all correlation coefficients > 0.95; p

Background The pericoronary fat attenuation index (FAI) is assessed using standard coronary computed tomography angiography, and it has emerged as a novel imaging biomarker of coronary inflammation. The present study assessed whether increased pericoronary FAI values on coronary computed tomography angiography were associated with vulnerable plaque components and their intracellular cytokine levels in patients with non‐ST elevation acute coronary syndrome. Methods and Results A total of 195 lesions in 130 patients with non‐ST elevation acute coronary syndrome were prospectively included. Lesion‐specific pericoronary FAI, plaque components and other plaque features were evaluated by coronary computed tomography angiography. Local T cell subsets and their intracellular cytokine levels were detected by flow cytometry. Lesions with pericoronary FAI values >−70.1 Hounsfield units exhibited spotty calcification (43.1% versus 25.0%, P=0.015) and low‐attenuation plaques (17.6% versus 4.2%, P=0.016) more frequently than lesions with lower pericoronary FAI values. Further quantitative plaque compositional analysis showed that increased necrotic core volume (Pearson’s r=0.324, P

Summary: Implantable devices and systems have been emerging as powerful tools for neuroscience research and medical applications. Here we report a wireless, dual-channel optoelectronic system for functional optogenetic interrogation of superior colliculus (SC), a layered structure pertinent to defensive behaviors, in rodents. Specifically, a flexible and injectable probe comprises two thin-film microscale light-emitting diodes (micro-LEDs) at different depths, providing spatially resolved optical illuminations within the tissue. Under remote control, these micro-LEDs interrogate the intermediate layer and the deep layer of the SC (ILSC and DLSC) of the same mice, and deterministically evoke distinct freezing and flight behaviors, respectively. Furthermore, the system allows synchronized optical stimulations in both regions, and we discover that the flight response dominates animals' behaviors in our experiments. In addition, c-Fos immunostaining results further elucidate the functional hierarchy of the SC. These demonstrations provide a viable route to unraveling complex brain structures and functions.

Aim. To analyze the pooled incidence rate in repositioning surgery by considering different materials and designs. Methods. All published studies investigating the repositioning surgery of toric intraocular lenses (IOLs) before September 1, 2020, were searched and evaluated. The R3.5.2 software was used to extract the data, and a single arm meta-analysis was performed. Results. 19 cases from 18 published studies articles were included in the meta-analysis. The pooled incidence rate in repositioning surgery was 2% (I2 = 53%, Pheterogeneity

The key module for autonomous mobile robots is path planning and obstacle avoidance. Global path planning based on known maps has been effectively achieved. Local path planning in unknown dynamic environments is still very challenging due to the lack of detailed environmental information and unpredictability. This paper proposes an end-to-end local path planner n-step dueling double DQN with reward-based ϵ-greedy (RND3QN) based on a deep reinforcement learning framework, which acquires environmental data from LiDAR as input and uses a neural network to fit Q-values to output the corresponding discrete actions. The bias is reduced using n-step bootstrapping based on deep Q-network (DQN). The ϵ-greedy exploration-exploitation strategy is improved with the reward value as a measure of exploration, and an auxiliary reward function is introduced to increase the reward distribution of the sparse reward environment. Simulation experiments are conducted on the gazebo to test the algorithm’s effectiveness. The experimental data demonstrate that the average total reward value of RND3QN is higher than that of algorithms such as dueling double DQN (D3QN), and the success rates are increased by 174%, 65%, and 61% over D3QN on three stages, respectively. We experimented on the turtlebot3 waffle pi robot, and the strategies learned from the simulation can be effectively transferred to the real robot.

Photosynthetic capacity is usually affected by light intensity in the field. In this study, photosynthetic characteristics of four different Triticeae crops (wheat, triticale, barley, and highland barley) were investigated based on chlorophyll fluorescence and the level of photosynthetic proteins under high light. Compared with wheat, three cereals (triticale, barley, and highland barley) presented higher photochemical efficiency and heat dissipation under normal light and high light for 3 h, especially highland barley. In contrast, lower photoinhibition was observed in barley and highland barley relative to wheat and triticale. In addition, barley and highland barley showed a lower decline in D1 and higher increase in Lhcb6 than wheat and triticale under high light. Furthermore, compared with the control, the results obtained from PSII protein phosphorylation showed that the phosphorylation level of PSII reaction center proteins (D1 and D2) was higher in barley and highland barley than that of wheat and triticale. Therefore, we speculated that highland barley can effectively alleviate photodamages to photosynthetic apparatus by high photoprotective dissipation, strong phosphorylation of PSII reaction center proteins, and rapid PSII repair cycle under high light.

The COVID-19 pandemic is an unprecedented crisis that has taken the world by storm, and it has taken an especially immense toll on the healthcare sector. Although much effort has been made to make changes in key areas such as clinical practice, national policy and research, we believe that it is just as important to evaluate the impact of the crisis on postgraduate medical training. To this end, we would like to share our experience within an anaesthesiology residency programme in Singapore, the SingHealth Anaesthesiology Residency Programme, which we hope will benefit other training programmes and anyone involved in postgraduate medical education as a whole. Key challenges identified include restrictions on teaching events, difficulties in completing core posting requirements, changes in clinical workload, postponement of examinations, exposure risk (particularly in relation to aerosol-generating procedures) and psychological burden. Strategies that have been implemented to tackle these challenges are also described, including the use of online platforms, modifications to posting and promotion requirements, manpower adjustments, provision of protective equipment and training in infectious disease protocols. Ultimately, we believe that a supportive work environment is essential to ensure the wellbeing of residents in times of crisis.

Unmanned driving technology has always been one focus of mine smart transportation, which is a crucial component of smart mines. However, the descriptions of both the intelligent transportation system and its industrial application are not comprehensive. In order to have an all-encompassing and comprehensive understanding of both the intelligent coal mine transportation system and its industrial application with the intelligent system, this paper summarizes and analyzes the current research status of unmanned driving technology in mines and the industrial application of current mining transportation vehicles. It begins by outlining the current research state of unmanned driving technology in mines and then assesses the advancement of unmanned driving technology. The unmanned transportation system in mines is also introduced, together with its components for perception, location, path planning, vehicle control, and multi-vehicle scheduling. In addition, each component is described in combination with the current artificial intelligent unmanned technology individually. Then, some typical categories of intelligent industrial vehicles are introduced for learning about the conditions of their actual application. There are almost four hundred coal mines that have researched unmanned driving technology, and some companies have applied the unmanned technology to realize transportation with an efficiency enhancement of 70~80%. Finally, currently existing challenges and future research are analyzed and proposed. This review may provide more comprehensive knowledge of the intelligent coal mine, accelerating the development of intelligent technology and helping to build a new management and control model.

Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) is a rare compound in licorice and its short supply limits the wide applications in the pharmaceutical, cosmetic, and food industries. In this study, de novo biosynthesis of GAMG was achieved in engineered Saccharomyces cerevisiae strains based on the CRISPR/Cas9 genome editing technology. The introduction of GAMG biosynthetic pathway resulted in the construction of a GAMG-producing yeast strain for the first time. Through optimizing the biosynthetic pathway, improving the folding and catalysis microenvironment for cytochrome P450 enzymes (CYPs), enhancing the supply of UDP-glucuronic acid (UDP-GlcA), preventing product degradation, and optimizing the fermentation conditions, the production of GAMG was increased from 0.02 μg/L to 92.00 μg/L in shake flasks (4,200-fold), and the conversion rate of glycyrrhetic acid (GA) to GAMG was higher than 56%. The engineered yeast strains provide an alternative approach for the production of glycosylated triterpenoids.

Retinoic acid (RA) signaling has long been speculated to regulate embryo implantation, because many enzymes and proteins responsible for maintaining RA homeostasis and transducing RA signals are tightly regulated in the endometrium during this critical period. However, due to a lack of genetic data, it was unclear whether RA signaling is truly required for implantation and which specific RA signaling cascades are at play. Herein we utilize a genetic murine model that expresses a dominant-negative form of RA receptor (RAR) specifically in female reproductive organs to show that functional RA signaling is fundamental to female fertility, particularly implantation and decidualization. Reduction in RA signaling activity severely affects the ability of the uterus to achieve receptive status and decidualize, partially through dampening follistatin expression and downstream activin B/bone morphogenetic protein 2 signaling. To confirm translational relevance of these findings to humans, human endometrial stromal cells (hESCs) were treated with a pan-RAR antagonist to show that in vitro decidualization is impaired. RNA interference perturbation of individual RAR transcripts in hESCs revealed that RARα in particular was essential for proper decidualization. These data provide direct functional evidence that uterine RAR-mediated RA signaling was crucial for mammalian embryo implantation, and its disruption led to failure of uterine receptivity and decidualization, resulting in severely compromised fertility.

Background: Although an increasing number of studies have reported that telemonitoring (TM) in patients with chronic obstructive pulmonary disease (COPD) can be useful and efficacious for hospitalizations and quality of life, its actual utility in detecting and managing acute exacerbation of COPD (AECOPD) is less established. This meta-analysis aimed to identify the best available evidence on the effectiveness of TM targeting the early and optimized management of AECOPD in patients with a history of past AECOPD compared with a control group without TM intervention.Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from 1990 to May 2020. Primary endpoints included emergency room visits and exacerbation-related readmissions. P-values, risk ratios, odds ratios, and mean differences with 95% confidence intervals were calculated.Results: Of 505 identified citations, 17 original articles with both TM intervention and a control group were selected for the final analysis (N = 3,001 participants). TM was found to reduce emergency room visits [mean difference (MD) −0.70, 95% confidence interval (CI) −1.36 to −0.03], exacerbation-related readmissions (risk ratio 0.74, 95% CI 0.60–0.92), exacerbation-related hospital days (MD −0.60, 95% CI −1.06 to −0.13), mortality (odds ratio 0.71, 95% CI 0.54–0.93), and the St. George's Respiratory Questionnaire (SGRQ) score (MD −3.72, 95% CI −7.18 to −0.26) but did not make a difference with respect to all-cause readmissions, the rate of exacerbation-related readmissions, all-cause hospital days, time to first hospital readmission, anxiety and depression, and exercise capacity. Furthermore, the subgroup analysis by observation period showed that longer TM (≥12 months) was more effective in reducing readmissions.Conclusions: TM can reduce emergency room visits and exacerbation-related readmissions, as well as acute exacerbation (AE)-related hospital days, mortality, and the SGRQ score. The implementation of TM intervention is thus a potential protective therapeutic strategy that could facilitate the long-term management of AECOPD.Systematic Review Registration: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews (number: CRD42020181459).

Diabetic retinopathy (DR) was identified as a leading cause of blindness and vision impairment in 2020. In addition to vasculopathy, DR has been found to involve retinal neurons, including amacrine cells and retinal ganglion cells. Despite possessing features that are susceptible to diabetic conditions, photoreceptor cells have received relatively little attention with respect to the development of DR. Until recently, studies have suggested that photoreceptors secret proinflammatory molecules and produce reactive oxygen species that contribute to the development of DR. However, the effect of hyperglycemia on photoreceptors and its underlying mechanism remains elusive. In this study, the direct effect of high glucose on photoreceptor cells was investigated using a 661w photoreceptor-like cell line. A data-independent sequential window acquisition of all theoretical mass spectra (SWATH)-based proteomic approach was employed to study changes induced by high glucose in the proteomic profile of the cells. The results indicated that high glucose induced a significant increase in apoptosis and ROS levels in the 661w cells, with mitochondrial dysfunction among the major affected canonical pathways. The involvement of mitochondrial dysfunction was further supported by increased mitochondrial fission and reduced mitochondrial bioenergetics. Collectively, these findings provide a biological basis for a possible role of photoreceptors in the pathogenesis of DR.

(1) Background: Chinese physicians have encountered serious physical and verbal attacks in recent decades due to poor patient–physician relationships, leading to a broad spectrum of negative consequences. This study aims to assess the status of intergroup threats perceived by physicians and explore its association with organizational psychology, behavior, and well-being during the COVID-19 pandemic. (2) Methods: We conducted a cross-sectional online survey with physicians from November to December 2020 in three provinces: Heilongjiang Province, Henan Province, and Zhejiang Province, in China. A total of 604 physicians were recruited to complete an anonymous questionnaire. There were 423 valid questionnaires. (3) Results: We developed a 25-item intergroup threat scale with four dimensions: interest damage, performance impairment, value derogation, and unjust sentiment. Internal consistency reliability analyses showed that the four dimensions and overall scale exhibited high internal consistency (0.756–0.947). Additionally, the average scores for physicians’ perceived overall intergroup threat, interest damage, performance impairment, value derogation, and unjust sentiment were 4.35 ± 0.51, 4.24 ± 0.73, 4.33 ± 0.58, 4.22 ± 0.65, and 4.53 ± 0.55, respectively. Moreover, this study shows that the intergroup threats perceived positively by physicians were associated with psychological stress (β = 0.270, p < 0.01), emotional exhaustion (β = 0.351, p < 0.01), turnover intention (β = 0.268, p < 0.01), and defensive medical behavior (β = 0.224, p < 0.01), and were negatively associated with job satisfaction (β = −0.194, p < 0.01) and subjective well-being (β = −0.245, p < 0.01). (4) Conclusions: The newly developed scale in this study is a reliable tool for measuring intergroup threats perceived by Chinese physicians. Physicians in China were suffering high-level intergroup threats during the anti-COVID-19 pandemic, which has a significant impact on damage to organizational psychology, behavior, and well-being. Intergroup threats perceived by physicians not only enlarged the risk of emotional exhaustion and psychological stress but also threatened organizational well-being. Moreover, greater intergroup threats were associated with a lower job satisfaction, more frequent defensive medical behavior, and a higher turnover intention for physicians. The results of this study suggest that essential intervention and governance measures should be considered to protect physicians’ well-being and benefits in China, which are urgently needed.

The concentration of ice nucleating particles (INPs) in the cloud layer affects cloud processes more importantly than at the ground level. To make up for deficiencies in the observation of the vertical distribution of INPs over different background regions of China, airborne sampling of INPs was carried out at the altitudes of 2000–5500 m over Turpan, Xinjiang, northwest China on 29 December 2019, and the samples were analyzed in a static vacuum water vapor diffusion chamber. The sources and relationships of the INPs with meteorological conditions and the variation of the concentrations of aerosol particles of different sizes were explored. The results indicate that the concentration of INPs varies from 0.25 to 15.7 L−1 when the nucleation temperature changes from −17 to −26 °C and the relative humidity with respect to water (RHw) varies from 95 to 105%. The existence of an inversion layer near the planetary boundary layer (PBL) inhibits the vertical transport of aerosols, thus affecting the vertical distribution of INP concentration. INPs in the free atmosphere mainly originate from fine-mode aerosol particles transported from long distances by westerly winds and do not change significantly with height. The air mass in the PBL is short-range transported, and the INP concentration reaches 15.7 L−1 at T =−26 °C and RHw = 105%, which is obviously higher than that above the PBL. The analyses provide evidence that the meteorological conditions played an important part in regulating the vertical distribution of INPs.

The explosion-proof diesel engine trackless rubber-tyred vehicle (TRTV) has the disadvantages of high fuel consumption and serious exhaust emissions, while the problems of insufficient power and short endurance limit the development of the explosion-proof battery trackless rubber-tyred vehicle. Hybrid technology can effectively reduce fuel consumption and emissions on the basis of ensuring sufficient power. Exploring the application of hybrid electric trackless rubber-tyred vehicle (HETRTV) has practical significance for coal mine auxiliary transportation. The degree of hybridization (DOH) will directly affect the performance and cost of TRTV, which needs to be focused in the development process. The effects of DOH on dynamic performance, fuel economy, emission performance, and cost were studied based on a simulation by ADVISOR, and the results were verified and analyzed by experiment. Compared with the flameproof diesel engine trackless vehicles, HETRTV with the optimal DOH exhausts has far less gas emissions. The engine fuel consumption and the equivalent fuel consumption of the vehicle are reduced by 33.9% and 12.5%, respectively. The results showed that in spite of a small increase in cost, the HETRTV with the optimal DOH can not only meet the driving requirements of underground working conditions but also greatly improve fuel economy and emission performance.

Abstract Anion exchange membrane fuel cells (AEMFCs) performance have significantly improved in the last decade (>1 W cm−2), and is now comparable with that of proton exchange membrane fuel cells (PEMFCs). At high current densities, issues in the catalyst layer (CL, composed of catalyst and ionomer), like oxygen transfer, water balance, and microstructural evolution, play important roles in the performance. In addition, CLs for AEMFCs have different requirements than for PEMFCs, such as chemical/physical stability, reaction mechanism, and mass transfer, because of different conductive media and pH environment. The anion exchange ionomer (AEI), which is the soluble or dispersed analogue of the anion exchange membrane (AEM), is required for hydroxide transport in the CL and is normally handled separately with the electrocatalyst during the electrode fabrication process. The importance of the AEI–catalyst interface in maximizing the utilization of electrocatalyst and fuel/oxygen transfer process must be carefully investigated. This review briefly covers new concepts in the complex AEMFC catalyst layer, before a detailed discussion on advances in CLs based on the design of AEIs and electrocatalysts. The importance of the structure–function relationship is highlighted with the aim of directing the further development of CLs for high‐performance AEMFC.

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS).Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques.Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups.Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04797819.

Biochar has received much attention as a strategy to enhance soil carbon (C) sequestration and mitigate climate change. Previous studies found that the feedstock and pyrolysis temperature can largely determine biochar properties, which in turn, impact the stability of native soil organic matter (SOM) and soil microorganisms. The Schima superba and Cunninghamia lanceolata are two tree species widely distributed in the subtropical region of southern China, but how the biochars from these two species influence the soil C sequestration and microbial communities of plantation remain poorly understood. In this study, we produced biochars from these two different feedstocks (13C-labeled S. superba and C. lanceolata litters) at three pyrolysis temperatures (350°C, 550°C, 750°C), then added them to the soils from C. lanceolata plantation, and maintained the experiments at 25°C for 112 days. We found both C mineralization and soil microbial community structures were strongly, but inconsistent, affected by biochar feedstock and pyrolysis temperature. The C. lanceolata biochar triggered the negative priming effect faster and greater compared with the S. superba biochar amendment. Biochars produced at 550°C showed the most significant negative priming effect during the whole incubation period, regardless of the different feedstocks. The cumulative amount of CO2 derived from biochars was significantly decreased with pyrolysis temperature (p < 0.05), indicating that biochars prepared at higher temperatures were more stable in the soil. Further, the soil microbial community structure was only affected by biochar pyrolysis temperature rather than biochar feedstock and their interaction. Together, our results reveal that biochar feedstock and pyrolysis temperature may play more important roles in dictating the priming effect than the structure of microbial community for C. lanceolata plantation. Overall, we concluded that the biochars prepared at 550°C could rapidly decrease the turnover of native SOM in a short term and biochar amendment has the potential to be a management practice for soil C sequestration in the C. lanceolata plantation.