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Understanding the spatial distribution of urban forest ecosystem services is essential for urban planners and managers to effectively manage cities and is an essential part of sustainable urban development. Mapping the spatial distribution of urban forest ecosystem services and improving the accuracy of its assessment scale will undoubtedly provide a more accurate reference basis for later management. In this study, we used the i-Tree Eco model and kriging interpolation to quantify and map urban forest ecosystem services and their spatial distribution in Zhengzhou, a city along the lower reaches of the Yellow River in China; analyzed the mapping errors and applicable conditions; and further explored the spatial differences using geographic probes. The i-Tree Eco model estimation results showed that the total carbon storage in the urban forest of Zhengzhou city was 75.7 tons, the annual carbon sequestration was 14.66 tons, the trees and shrubs in the urban area of Zhengzhou city could effectively avoid a total of 307.86 m3 of surface runoff per year, and trees and shrubs removed 411.8 kg/year of air pollution (O3, CO, NO2, PM2.5, PM10, and SO2). The spatial distribution of all urban forest ecosystem services showed significant heterogeneity, but the spatial evaluation precision of different factors varied. GDP and population data showed a negative correlation with ecosystem services, and ecosystem services were abundant in watershed and woodland areas. This study differs from traditional assessments based on regional data due to its improved spatial evaluation accuracy, and the results, discussion, and analysis not only help Zhengzhou’s own urban development, but also provide a basis for the future construction and management of other cities, the Central Plains urban agglomeration, and the surrounding larger regions. This will contribute to the enhancement of ecosystem services and thus improve the ecological conditions of the region. This will also have a positive effect on the health of urban residents.

The transport process of high-temperature air is vital in aerospace fields and has attracted increased attention in recent years. In this paper, an adequate study of factors affecting transport coefficients for high-temperature air is conducted. The results of a different-species model at different pressures and temperatures show that the 9-species air model is applicable to calculate the viscosity and translational thermal conductivity coefficients before significant ionization occurs. Based on the Chapman-Enskog method, simplified mixing rules for calculating viscosity and translational thermal conductivity coefficients of high-temperature air are developed by omitting unimportant matrix elements and assuming the reduced collision integral ratio to a reasonable constant value. The diagonal elements’ magnitude of the transport matrix indicates that collision related to the electrons has a little impact on viscosity but has a great influence on translational thermal conductivity. New simplified mixing rules can accurately calculate the viscosity and translational thermal conductivity coefficients of high-temperature air when dissociation or weak ionization occurs. The improved mixing rules are obviously more accurate than the Wilke mixing rule.

The repair of exercise-induced muscle damage (EIMD) is closely related with inflammation. Branched-chain amino acids (BCAAs), as a nutritional supplement, promote EIMD repair; however, the underlying mechanism remains unclear. In vivo, Sprague–Dawley rats were subjected to Armstrong’s eccentric exercise (a 120-min downhill run with a slope of −16° and a speed of 16 m min−1) to induce EIMD and BCAA supplement was administered by oral gavage. Protein expression of macrophages (CD68 and CD163) and myogenic regulatory factors (MYOD and MYOG) in gastrocnemius was analyzed. Inflammatory cytokines and creatine kinase (CK) levels in serum was also measured. In vitro, peritoneal macrophages from mice were incubated with lipopolysaccharide (LPS) or IL-4 with or without BCAAs in culture medium. For co-culture experiment, C2C12 cells were cultured with the conditioned medium from macrophages prestimulated with LPS or IL-4 in the presence or absence of BCAAs. The current study indicated BCAA supplementation enhanced the M1/M2 polarization of macrophages in skeletal muscle during EIMD repair, and BCAAs promoted M1 polarization through enhancing mTORC1-HIF1α-glycolysis pathway, and promoted M2 polarization independently of mTORC1. In addition, BCAA-promoted M1 macrophages further stimulated the proliferation of muscle satellite cells, whereas BCAA-promoted M2 macrophages stimulated their differentiation. Together, these results show macrophages mediate the BCAAs’ beneficial impacts on EIMD repair via stimulating the proliferation and differentiation of muscle satellite cells, shedding light on the critical role of inflammation in EIMD repair and the potential nutritional strategies to ameliorate muscle damage.

Objective To identify whether median nerve stimulation (MNS) may be a potential candidate for the treatment of consciousness disorders via a systematic review and meta-analysis. Methods PubMed, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information, Wanfang, and SinoMed databases were searched. Risk of bias was assessed using the Cochrane Collaboration’s tool. The Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), electroencephalogram (EEG), days in the Intensive Care Unit (ICU), and cerebral blood flow measures were compared between the median nerve stimulation and control groups. The meta-analysis was conducted using Review Manager software. Results We identified 2244 studies, of which 23 (with data from 1856 patients) qualified for the analysis. MNS improved GCS scores (mean difference [MD] = 2.15), EEG scores (MD = 1.61), cerebral mean blood flow velocity (MD = 4.23), and cerebral systolic blood flow velocity (MD = 10.51). Furthermore, it decreased DRS scores (MD = −1.77) and days in the ICU (MD = −2.02). The effects of MNS on GCS scores increased with longer treatments (1 week, MD = 1.03; 1 month, MD = 2.35) and were better with right MNS (right, MD = 2.36; bilateral, MD = 1.72). Conclusions MNS may promote recovery from consciousness disorders.

Background Current antiretroviral regimens have, for the most part, achieved optimal antiretroviral efficacy and tolerability, transforming HIV infection from a deadly disease into a manageable chronic condition. However, adherence to daily oral drug intake remains an issue, as it is the most important determinant for sustained viral suppression and prevention of the emergence of drug-resistant viral strains. The long-acting injection antiretroviral cabotegravir and rilpivirine combination, a novel drug delivery approach, is about to revolutionise the therapy for people living with HIV. In this protocol, we aim to generate a clinically useful summary of the interventions based on their efficacy.Methods and analysis We searched the literature for eligible studies published from inception up to 16 August 2022 through PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov. Two methodologically trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias in included studies. Statistical heterogeneity will be computed by Cochrane X2 and I2 tests. Sensitivity analysis will be conducted to evaluate the stability of the results. Publication biases will be evaluated by Begg’s and Egger’s tests. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation system. The RevMan V.5.3 and Stata V.14.0 software will be applied for statistical analyses.Ethics and dissemination Ethical approval will not be required for this systematic review because the data used are not linked to the individual patient. The results of this review will be disseminated by being published in a peer-reviewed journal.PROSPERO registration number CRD42022310414

BackgroundAt present, there is increasing evidence that both competitive endogenous RNAs (ceRNAs) and immune status in the tumor microenvironment (TME) can affect the progression of gastric cancer (GC), and are closely related to the prognosis of patients. However, few studies have linked the two to jointly determine the prognosis of patients with GC. This study aimed to develop a combined prognostic model based on ceRNAs and immune biomarkers.MethodsFirst, the gene expression profiles and clinical information were downloaded from TCGA and GEO databases. Then two ceRNA networks were constructed on the basis of circRNA. Afterwards, the key genes were screened by univariate Cox regression analysis and Lasso regression analysis, and the ceRNA-related prognostic model was constructed by multivariate Cox regression analysis. Next, CIBERSORT and ESTIMATE algorithms were utilized to obtain the immune cell infiltration abundance and stromal/immune score in TME. Furthermore, the correlation between ceRNAs and immunity was found out through co-expression analysis, and another immune-related prognosis model was established. Finally, combining these two models, a comprehensive prognostic model was built and visualized with a nomogram.ResultsThe (circRNA, lncRNA)-miRNA-mRNA regulatory network of GC was constructed. The predictive power of ceRNA-related and immune-related prognosis models was moderate. Co-expression analysis showed that the ceRNA network was correlated with immunity. The integrated model of combined ceRNAs and immunity in the TCGA training set, the AUC values of 1, 3, and 5-year survival rates were 0.78, 0.76, and 0.78, respectively; in the independent external validation set GSE62254, they were 0.81, 0.79, and 0.78 respectively; in GSE15459, they were 0.84, 0.88 and 0.89 respectively. Besides, the prognostic score of the comprehensive model can predict chemotherapeutic drug resistance. Moreover, we found that plasma variant translocation 1 (PVT1) and infiltrating immune cells (mast cells) are worthy of further investigation as independent prognostic factors.ConclusionsTwo ceRNA regulatory networks were constructed based on circRNA. At the same time, a comprehensive prognosis model was established, which has a high clinical significance for prognosis prediction and chemotherapy drug selection of GC patients.

Drug resistance is a major challenge in the treatment of epilepsy. Drug-resistant epilepsy (DRE) accounts for 30% of all cases of epilepsy and is a matter of great concern because of its uncontrollability and the high burden, mortality rate, and degree of damage. At present, considerable research has focused on the development of predictors to aid in the early identification of DRE in an effort to promote prompt initiation of individualized treatment. While multiple predictors and risk factors have been identified, there are currently no standard predictors that can be used to guide the clinical management of DRE. In this review, we discuss several potential predictors of DRE and related factors that may become predictors in the future and perform evidence rating analysis to identify reliable potential predictors.

ObjectiveThe purpose of this study was to assess the short-term and long-term outcomes of ventriculoperitoneal shunt (VPS) placement in patients with cryptococcal meningitis (CM).MethodsWe performed a retrospective analysis of all patients with CM admitted to the Peking Union Medical College Hospital from September 1990 to January 2021. We collected related clinical features to analyze the short- and long-term outcomes of VPS at 1 month and 1 year at least the following therapy, respectively. Overall survival (OS) was compared with all patients and a subgroup of critically ill cases by the Kaplan–Meier method with the log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors.ResultsWe enrolled 98 patients, fifteen of whom underwent VPS. Those who received VPS had a lower cerebrospinal fluid (CSF) Cryptococcus burden (1:1 vs. 1:16; p = 0.046), lower opening pressures (173.3 mmH2 O vs. 224 mmH2O; p = 0.009) at lumbar punctures, and a lower incidence of critical cases (6.7 vs. 31.3%; p = 0.049). According to our long-term follow-up, no significant difference was shown in the Barthel Index (BI) between the two groups. Two patients in the VPS group suffered postoperative complications and had to go through another revision surgery. According to survival analysis, overall survival (OS) between the VPS and non-VPS groups was not significantly different. However, the Kaplan–Meier plots showed that critical patients with VPS had better survival in OS (p < 0.009). Multivariable analyses for critical patients showed VPS was an independent prognostic factor.ConclusionA VPS could reduce the intracranial pressure (ICP), decrease the counts of Cryptococcus neoformans by a faster rate and reduce the number of critical cases. The VPS used in critical patients with CM has a significant impact on survival, but it showed no improvement in the long-term Barthel Index (BI) vs. the conservative treatment and could lead to postoperative complications.

Candida haemulonii var. vulnera is a rare variant of C. haemulonii, which has been previously reported to cause human infections. Owing to the close kinship between C. haemulonii sensu stricto and C. haemulonii var. vulnera, accurate identification of C. haemulonii var. vulnera relied on DNA sequencing assay targeting, for example, rDNA internal transcribed spacer (ITS) region. In this work, two strains of C. haemulonii var. vulnera were collected from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET). The identification capacity of three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 YST ID biochemical methods were evaluated against ITS sequencing. In addition, antifungal susceptibility testing was performed using Sensititre YeastOne. Moreover, we comprehensively screened drug-resistant related genes by whole-genome sequencing. The two strains were not correctly identified to species variant level using MALDI-TOF MS and YST ID cards. Both strains were resistant to amphotericin B (minimum inhibitory concentration [MIC] > 2 μg/ml). Moreover, strain F4564 and F4584 exhibited high MIC to fluconazole (>256 μg/ml) and 5-flucytosine (>64 μg/ml), respectively, which were supposed to result from key amino acid substitutions Y132F and G307A in Erg11p and V58fs and G60K substitutions in Fur1p. The rare species C. haemulonii var. vulnera has emerged in China, and such drug-resistant fungal species that can cause invasive diseases require further close attention.

A novel super-junction (SJ) double-trench metal oxide semiconductor field effect transistor (DT-MOS) is proposed and studied using Synopsys Sentaurus TCAD in this article. The simulation results show that the proposed MOSFET has good static performance and a longer short-circuit withstand time (tsc). The super-junction structure enables the device to possess an excellent compromise of breakdown voltage (BV) and specific on-resistance (Ron,sp). Under short-circuit conditions, the depletion of p-pillar, p-shield, and floating p regions can effectively reduce saturation current and improve short-circuit capability. The proposed device has minimum gate-drain charge (Qgd) and gate-drain capacitance (Cgd) compared with other devices. Moreover, the formation of floating p regions will not lead to an increase in process complexity. Therefore, the proposed MOSFET can maintain good dynamic and static performance and short-circuit ability together without increasing the difficulty of the process.

Since the 1970s, certain areas within the Three-Rivers Headwater Region (TRHR) of China have faced severe land degradation due to the combined effects of climate change and human activities, leading to restricted ecological service functions and hindering the achievement of sustainable development goals (SDGs). Land degradation in the TRHR has received widespread attention. However, the current research mainly focuses on single-dimensional degradation and lacks a comprehensive evaluation of patterns and structures, as well as above-ground and underground assessments. To address this gap, this study employed the SDG indicator 15.3.1 framework, comprehensively considering fragmentation and habitat quality index based on land cover changes, grassland degradation index, and soil water erosion index. These indexes represent the three land degradation pathways of landscape degradation, vegetation degradation, and soil erosion. This study assessed land degradation patterns in the TRHR from 2000 to 2020. Results show that approximately 44.67% of the TRHR experienced land degradation during this period, mainly in meadow-dominated regions. Additionally, 5.64% of the regions experienced the superimposition of two or more land degradation pathways, with the frequent coexistence of soil erosion and grassland degradation, accounting for 4.1% of the affected areas. Landscape degradation affected approximately 2.39% of the regions, characterized by increased grassland fragmentation or habitat quality degradation. In terms of grassland degradation, 22.26% of the regions showed medium degradation, while 7.21% and 5.63% experienced moderate and severe degradation, respectively. Moreover, approximately 13.36% of the region faced a worsening situation of soil erosion. Approximately 55.34% of the study area underwent land improvement, with significant enhancements mainly concentrated in the western and eastern regions. The regrowth of grassland in the western region and the enhancement and homogenization of grassland productivity in the eastern region played pivotal roles in promoting land improvement. This study provides critical insights into the land degradation pattern in the TRHR over the past 20 years, offering valuable references for formulating and implementing measures to protect and construct the ecological security barrier of the plateau.

Seasonal freezing depth change is important in many environmental science and engineering applications. However, such changes are rare at region scales, especially over China, in the long time series. In this study, we evaluated the annual changes in seasonal maximum freezing depth (MFD) over China from 1971 to 2020 using an ensemble-modeling method based on support vector machine regression (SVMR) with 600 repetitions. Remote sensing data and climate data were input variables used as predictors. The models were trained using a large amount of annual measurement data from 600 meteorological stations. The main reason for using SVMR here was because it has been shown to perform better than random forests (RF), k-nearest neighbors (KNN), and generalized linear regression (GLR) in these cases. The prediction results were generally consistent with the observed MFD values. Cross validation showed that the model performed well on training data and had a better spatial generalization ability. The results show that the freezing depth of seasonally frozen ground in China decreased year by year. The average MFD was reduced by 3.64 cm, 7.59 cm, 5.54 cm, and 5.58 cm, in the 1980s, 1990s, 2000s, and 2010s, respectively, compared with the decade before. In the last 50 years, the area occupied by the freezing depth ranges of 0–40 cm, 40–60 cm, 60–80 cm, 80–100 cm, and 120–140 cm increased by 99,300 square kilometers, 146,200 square kilometers, 130,300 square kilometers, 115,600 square kilometers, and 83,800 square kilometers, respectively. In addition to the slight decrease in freezing depth range of 100–120 cm, the reduced area was 29,500 square kilometers. Freezing depth ranges greater than 140 cm showed a decreasing trend. The freezing depth range of 140–160 cm, which was the lowest range, decreased by 89,700 square kilometers. The 160–180 cm range decreased by 120,500 square kilometers, and the 180–200 cm range decreased by 161,500 square kilometers. The freezing depth range greater than 200 cm, which was the highest reduction range, decreased by 174,000 square kilometers. Considering the lack of data on the change in MFD of seasonally frozen ground in China in recent decades, machine learning provides an effective method for studying meteorological data and reanalysis data in order to predict the changes in MFD.

L-ascorbic acid (vitamin C, VC), an essential nutrient obtained from the diet to maintain various vital signs for the human body, is a crucial indicator of food quality and nutritional value. Herein, high-performance liquid chromatography with electrochemical detection (HPLC-ECD) was developed and validated with the advantages of higher sensitivity, simpler operation processes, and more rapid detection in measuring VC levels in honey samples when compared with the common methods (titration, spectrophotometric, and HPLC-DAD methods). The results of the HPLC-ECD methodological validation showed that the limit of detection (LOD) was 0.0043 µg mL−1; the relative standard deviations (RSDs) of the intra- and inter-day values were between 2.51% and 5.15%, and the regression coefficient was >0.999 in the linear range of 0.1 to 20 µg mL−1. The validated HPLC-ECD method was also successfully utilized to evaluate the VC levels in different varieties of honey samples with various storage durations as well as in fruit and biological samples. This study provided a perspective for the further accurate determination of VC content in food and biological samples.

Abstract China accounts for 25% of the global greening. There are temporal and spatial differences of China’s greening and intrinsic driving forces. Thus, it is crucial to determinize the contributions of human activities and climate change on greening at region scale. The Beijing–Tianjin–Hebei Region (BTHR) is one of the most active areas with human activities in China. It is necessary to explore negative or positive impacts of human activities on the regional greening or browning under climate change. A time series of annual vegetation coverage from satellite data was selected to quantify regional greening in the BTHR from 2000 to 2019 and their responses to climate change and human activities. Results showed generally widespread greening over the last 20 years at an average increased rate of 0.036 decade−1 in vegetation coverage (P

Abstract Transient receptor potential canonical (TRPC) channels are the most prominent nonselective cation channels involved in various diseases. However, the function, clinical significance, and molecular mechanism of TRPCs in colorectal cancer (CRC) progression remain unclear. In this study, we identified that TRPC1 was the major variant gene of the TRPC family in CRC patients. TRPC1 was upregulated in CRC tissues compared with adjacent normal tissues and high expression of TRPC1 was associated with more aggressive tumor progression and poor overall survival. TRPC1 knockdown inhibited cell proliferation, cell-cycle progression, invasion, and migration in vitro, as well as tumor growth in vivo; whereas TRPC1 overexpression promoted colorectal tumor growth and metastasis in vitro and in vivo. In addition, colorectal tumorigenesis was significantly attenuated in Trpc1 -/- mice. Mechanistically, TRPC1 could enhance the interaction between calmodulin (CaM) and the PI3K p85 subunit by directly binding to CaM, which further activated the PI3K/AKT and its downstream signaling molecules implicated in cell cycle progression and epithelial-mesenchymal transition. Silencing of CaM attenuated the oncogenic effects of TRPC1. Taken together, these results provide evidence that TRPC1 plays a pivotal oncogenic role in colorectal tumorigenesis and tumor progression by activating CaM-mediated PI3K/AKT signaling axis. Targeting TRPC1 represents a novel and specific approach for CRC treatment.

Abstract The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss‐of‐function and gain‐of‐function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

Abstract Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H2O2). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H2O2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

ABSTRACT: Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown. We sought to determine the relationship between a family history of cancer and lung cancer risk among Chinese non-smoking females based on a multi-center prospective population-based cohort study involving 547,218 individuals between 2013 and 2019. A total of 1620 lung cancer cases occurred during a median follow-up of 3.9 years. Multivariable Cox regression showed that a family history of lung cancer in first-degree relatives significantly increased the risk of lung cancer (HR: 1.50, 95%CI: 1.29, 1.75, P

Abstract Background Brain tumor segmentation is a challenging problem in medical image processing and analysis. It is a very time-consuming and error-prone task. In order to reduce the burden on physicians and improve the segmentation accuracy, the computer-aided detection (CAD) systems need to be developed. Due to the powerful feature learning ability of the deep learning technology, many deep learning-based methods have been applied to the brain tumor segmentation CAD systems and achieved satisfactory accuracy. However, deep learning neural networks have high computational complexity, and the brain tumor segmentation process consumes significant time. Therefore, in order to achieve the high segmentation accuracy of brain tumors and obtain the segmentation results efficiently, it is very demanding to speed up the segmentation process of brain tumors. Results Compared with traditional computing platforms, the proposed FPGA accelerator has greatly improved the speed and the power consumption. Based on the BraTS19 and BraTS20 dataset, our FPGA-based brain tumor segmentation accelerator is 5.21 and 44.47 times faster than the TITAN V GPU and the Xeon CPU. In addition, by comparing energy efficiency, our design can achieve 11.22 and 82.33 times energy efficiency than GPU and CPU, respectively. Conclusion We quantize and retrain the neural network for brain tumor segmentation and merge batch normalization layers to reduce the parameter size and computational complexity. The FPGA-based brain tumor segmentation accelerator is designed to map the quantized neural network model. The accelerator can increase the segmentation speed and reduce the power consumption on the basis of ensuring high accuracy which provides a new direction for the automatic segmentation and remote diagnosis of brain tumors.

Abstract Background Long non-coding RNA (LncRNA) controls cell proliferation and plays a significant role in the initiation and progression of esophageal squamous cell carcinoma (ESCC). N6-methyladenosine (m6A) modification now is recognized as a master driver of RNA function to maintain homeostasis in cancer cells. However, how m6A regulates LncRNA function and its role in tumorigenesis of ESCC remain unclear. Methods Multiple ESCC datasets were used to analyze gene expression in tumor tissues and normal tissues. Kaplan-Meier method and the ROC curve were conducted to evaluate the prognostic value and diagnostic value of LINC00022 in ESCC, respectively. Both gain-of-function and loss-of-function experiments were employed to investigate the effects of LINC00022 on ESCC growth in vitro and in vivo. Bioinformatics analysis, colorimetric m6A assay, RIP, MeRIP and co-IP was performed to explore the epigenetic mechanism of LINC00022 up-regulation in ESCC. Results Here we report that m6A demethylation of LncRNA LINC00022 by fat mass and obesity-associated protein (FTO) promotes tumor growth of ESCC in vivo. Clinically, we revealed that LINC00022 was up-regulated in primary ESCC samples and was predictive of poor clinical outcome for ESCC patients. Mechanistically, LINC00022 directly binds to p21 protein and promotes its ubiquitination-mediated degradation, thereby facilitating cell-cycle progression and proliferation. Further, the elevated FTO in ESCC decreased m6A methylation of LINC00022 transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2. Over-expression of FTO was shown to drive LINC00022-dependent cell proliferation and tumor growth of ESCC. Conclusions Thus, this study demonstrated m6A-mediated epigenetic modification of LncRNA contributes to the tumorigenesis in ESCC and LINC00022, specific target of m6A, serves as a potential biomarker for this malignancy.

Abstract Objective Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. Materials and methods Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I–II) and advanced-stage (clinical stage III–IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan–Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. Results In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. Conclusion In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.

Hirsutella are globally distributed entomopathogenic fungi that offer important economic applications in biological control and biomedicine. Hirsutella was suppressed in favour of Ophiocordyceps affected by the ending of dual nomenclature for pleomorphic fungi in 2011. Currently, Hirsutella has been resurrected as a genus under Ophiocordycipitaceae. In this study, we introduce two new species of Hirsutella, based on morphological and phylogenetic analyses. Hirsutella flava and H. kuankuoshuiensis are pathogenic on different species of larval Lepidoptera in China. Hirsutella flava primarily differs from related species by its awl-shaped base; long and narrow neck, 24–40.8 × 2.2–2.5 μm; long and narrow cymbiform or fusoid conidia, 6.5–10 × 2.1–4.3 μm. Hirsutella kuankuoshuiensis has two types of phialides and distinctive 9.9–12.6 × 2.7–4.5 μm, clavate or botuliform conidia. The distinctions amongst the new species and phylogenetic relationships with other Hirsutella species are discussed.

Abstract A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host’s innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching.Trial registration number[http://www.chictr.org.cn], identifier [ChiCTR1900022994].

Structures containing galactose and GalNAc residues are specifically recognized by asialoglycoprotein receptors, allowing them to selectively internalize by hepatocytes for drug-targeting delivery. However, methods for direct synthesis of GalNAc glycosides are still challenging due to the poor participating group of 2-acetamido. Here, we develop a facile strategy to synthesize various GalNAc glycosides by employing a series of rare earth metal triflates, and the results demonstrate that both α-glycosides and β-glycosides of GalNAc can be obtained by conducting with Hf(OTf)4 and Sc(OTf)3, respectively. These applicable results indicate that any interested GalNAc-containing substrates could be prepared by this simple strategy.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy. Recommendations for RA, specifically on pharmacotherapy, are essential in clinical practice. However, the direction and strength of recommendations are controversial across current clinical practice guidelines (CPGs) of RA.Objective: To systematically analyze the consistency of recommendations regarding pharmacotherapy of RA across CPGs.Methods: 11 electronic databases and websites were comprehensively searched from inception to 14 March 2022, to identify CPGs for diagnosis, therapy, and management of RA. Unambiguous and discrete specifications of the population-intervention-comparison (PIC) framework were used to classify the recommendations. Based on the PIC framework, consistency analyses across CPGs on pharmacotherapy of RA were performed. Two researchers reached a consensus on coding the direction and strength of each recommendation.Results: Finally, 26 CPGs were included in this study, and 14 of them, which included pharmacotherapy, were performed consistency analysis. 1) 64 recommendations from 14 CPGs were classified into 18 PICs. 2) Seven PICs (38%) were consistent in direction and strength, 10 PICs (56%) were consistent in direction but inconsistent in strength, and one PIC (6%) was inconsistent in direction (hydroxychloroquine, HCQ). 3) Sensitivity analysis tested the robustness, and the inconsistency remained high.Conclusion: The direction was highly consistent among the recommendations of pharmacotherapy for RA, but the strength was highly inconsistent. Reasons for the inconsistency need to be further investigated, and consistent recommendations could guide the pharmacotherapy of RA in clinical practice.

Summary: Background: Optimal uptake rates of low-dose computed tomography (LDCT) scans are essential for lung cancer screening (LCS) to confer mortality benefits. We aimed to outline the process model of the LCS programme in China, identify the high-risk individuals with low uptake based on a prospective multi-centre population-based cohort, and further explore associated structural characteristics. Methods: A total of 221,955 individuals at high-risk for lung cancer from the National Lung Cancer Screening cohort were included. The logistic regression model was performed to identify the individual characteristics associated with the uptake of LCS, defined as whether the high-risk individual undertook LDCT scans in designated hospitals within six months following the initial risk assessment. The linear regression model was adopted to explore the structural characteristics associated with the uptake rates in 186 communities. Findings: The overall uptake rate was 33·0%. The uptake rate was negatively correlated with the incidence of advanced-stage lung cancer (Pearson's coefficient −0·88, p-value 0·0007). Multivariable regression models found that lower uptake rates were associated with males (OR 0·88, 95%CI 0·85–0·91), current smokers (OR 0·93, 95%CI 0·90–0·96), individuals with depressive symptoms (OR 0·92, 95%CI 0·90–0·94), and the structural characteristics, including longer structural delays in initiating LDCT scans (30–90 days vs. ≤14 days: β −7·17, 95%CI −12·76∼ −1·57; >90 days vs. ≤14 days: β −13·69, 95%CI −24·61∼ −2·76), no media-assisted publicity (β −6·43, 95%CI −11·26∼ −1·60), and no navigation assistance (β −5·48, 95%CI −10·52∼ −0·44). Interpretation: Multifaceted interventions are recommended, which focus on poor-uptake individuals and integrate the ‘assessment-to-timely-screening’ approach to minimise structural delays, media publicity, and a navigation assistance along the centralised screening pathway. Funding: Ministry of Finance and National Health Commission of the People's Republic of China.

Image processing and analysis based on deep learning are becoming mainstream and increasingly accessible for solving various scientific problems in diverse fields. However, it requires advanced computer programming skills and a basic familiarity with character user interfaces (CUIs). Consequently, programming beginners face a considerable technical hurdle. Because potential users of image analysis are experimentalists, who often use graphical user interfaces (GUIs) in their daily work, there is a need to develop GUI-based easy-to-use deep learning software to support their work. Here, we introduce JustDeepIt, a software written in Python, to simplify object detection and instance segmentation using deep learning. JustDeepIt provides both a GUI and a CUI. It contains various functional modules for model building and inference, and it is built upon the popular PyTorch, MMDetection, and Detectron2 libraries. The GUI is implemented using the Python library FastAPI, simplifying model building for various deep learning approaches for beginners. As practical examples of JustDeepIt, we prepared four case studies that cover critical issues in plant science: (1) wheat head detection with Faster R-CNN, YOLOv3, SSD, and RetinaNet; (2) sugar beet and weed segmentation with Mask R-CNN; (3) plant segmentation with U2-Net; and (4) leaf segmentation with U2-Net. The results support the wide applicability of JustDeepIt in plant science applications. In addition, we believe that JustDeepIt has the potential to be applied to deep learning-based image analysis in various fields beyond plant science.

Bioactive coatings are promising for improving osseointegration and the long-term success of titanium dental or orthopaedic implants. Biomimetic octacalcium phosphate (OCP) coating can be used as a carrier for osteoinductive agents. κ-Carrageenan, a highly hydrophilic and biocompatible seaweed-derived sulfated-polysaccharide, promotes pre-osteoblast activity required for bone regeneration. Whether κ-carrageenan can functionalize OCP-coating to enhance osseointegration of titanium implants is unclear. This study aimed to analyze carrageenan-functionalized biomimetic OCP-coated titanium structure, and effects of carrageenan functionalization on pre-osteoblast behavior and osteogenic differentiation. Titanium discs were coated with OCP/κ-carrageenan at 0.125–2 mg/ml OCP solution, and physicochemical and biological properties were investigated. κ-Carrageenan (2 mg/ml) in the OCP coating of titanium discs decreased the pore size in the sheet-like OCP crystal by 41.32%. None of the κ-carrageenan concentrations tested in the OCP-coating did affect hydrophilicity. However, κ-carrageenan (2 mg/ml) increased (1.26-fold) MC3T3-E1 pre-osteoblast spreading at 1 h i.e., κ-Carrageenan in the OCP-coating increased pre-osteoblast proliferation (max. 1.92-fold at 2 mg/ml, day 1), metabolic activity (max. 1.50-fold at 2 mg/ml, day 3), and alkaline phosphatase protein (max. 4.21-fold at 2 mg/ml, day 3), as well as matrix mineralization (max. 5.45-fold at 2 mg/ml, day 21). κ-Carrageenan (2 mg/ml) in the OCP-coating increased gene expression of Mepe (4.93-fold) at day 14, and Runx2 (2.94-fold), Opn (3.59-fold), Fgf2 (3.47-fold), Ocn (3.88-fold), and Dmp1 (4.59-fold) at day 21 in pre-osteoblasts. In conclusion, κ-carrageenan modified the morphology and microstructure of OCP-coating on titanium discs, and enhanced pre-osteoblast metabolic activity, proliferation, and osteogenic differentiation. This suggests that κ-carrageenan-functionalized OCP coating may be promising for in vivo improvement of titanium implant osseointegration.

RNA sequencing (RNA-seq) technology has now become one of the standard tools for studying biological mechanisms at the transcriptome level. Advances in RNA-seq technology have led to the emergence of a large number of publicly available tools for RNA-seq data analysis. Most of them target linear genome sequences although it is necessary to study organisms with circular genome sequences. For example, by studying the infection mechanisms of viroids which comprise 246–401 nucleotides circular RNAs and target plants, tremendous economic and agricultural damage may be prevented. Unfortunately, using the available tools to construct workflows for the analysis of circular genome sequences is difficult, especially for non-bioinformaticians. To overcome this limitation, we present CircSeqAlignTk, an easy-to-use and richly documented R package. CircSeqAlignTk performs end-to-end RNA-seq data analysis, from alignment to the visualization of circular genome sequences, through a series of functions. Additionally, it implements a function to generate synthetic sequencing data that mimics real RNA-seq data obtained from biological experiments. CircSeqAlignTk not only provides an easy-to-use analysis interface for novice users but also allows developers to evaluate the performance of alignment tools and new workflows.

Aspergillus niger is a major cell factory for citric acid production, and the process of citrate export from mitochondria to cytoplasm is predicted to be one of rate-limiting steps in citric acid accumulation. Currently, the mitochondrial citrate transporters (Ctps) in A. niger are not fully characterized. Here, six putative Ctp encoding genes (ctpA to ctpF) were identified based on their homology with a mitochondrial citrate transporter ScCtp1 from Saccharomyces cerevisiae. Disruption of individual ctpA to ctpF caused varying degrees of decline in citric acid accumulation at different fermentation stages, whereas a mutant strain S1696 with disruption of all six ctps showed complete loss of citiric acid production. S1696 also exhibited delayed growth, reduced conidia formation, and decreased pigmentogenesis. Exogenous addition of citrate partially restored the conidia formation and pigmentogenesis in S1696 mutant. Reintroduction of individual ctps (ctpA to ctpF) into S1696 at the amyA locus showed that ctpA, ctpB, and ctpD restored the citric acid titers to 88.5, 93.8, and 94.6% of the parent strain, respectively. Additionally, the formation of conidia and pigment production was partially restored after reintroduction of ctpA, ctpB, or ctpD. Overexpression of respective ctpA, ctpB, and ctpD in the parent strain resulted in increases in citric acid accumulation by 32.8, 19.3, and 24.2%, respectively. These results demonstrate that CtpA, CtpB, and CtpD play important roles in citric acid transport across the mitochondrial membrane and function in a redundant manner. Enhancement of citric acid transport process can serve as a target for boosting citric acid accumulation in A. niger.

ObjectiveVocal fold nodules (VFNs) are benign lesions, occurring at the junction of the anterior and middle thirds of bilateral vocal cords, for which pediatric prognosis and treatment remains controversial. There is a requirement for a correlation indicator to assess the prognosis by pediatric otolaryngologists.Materials and methodsPatients with VFNs, who were admitted to the department of otolaryngology, were enrolled. The patient’s gender, age, duration of dysphonia, laryngoscopy results and related diseases [allergic rhinitis, sinusitis, laryngopharyngeal reflux (LPR)] were collected and recovery from dysphonia followed up. Correlations between clinical factors and type of laryngoscopic morphology of VFNs were analyzed.ResultsA total of 432 patients with dysphonia were identified, 208 agreed to undergo laryngoscopy and 194 were diagnosed with VFNs as a result. The modal age of patients with dysphonia was between 3 and 7 years with a male: female ratio of 2.1:1 (294:138) and 116 (26.85%; 116/432) had symptoms of allergic rhinitis. The boy to girl ratio among the 194 children with VFNs was about 2.6:1 (140:54) and modal age was consistent with dysphonia. Vocal nodules were the cause of most phonation disorders (93.27%; 194/208) and those with long duration of dysphonia presented more mature (p = 0.026) and discrete types (p = 0.022). Boys were more likely to have mature (p = 0.050) and discrete nodules (p = 0.008). Dysphonia recovery time was closely related to age (p = 0.000), duration of dysphonia (p = 0.000) and morphology of vocal nodules under laryngoscopy (p = 0.000).ConclusionVocal nodules are the most frequent cause of phonation disorders in children. The morphological classification by endoscopy may help with clinical diagnosis and therapy choice. In the case of the older child with longer duration of dysphonia and the appearance of mature, large, discrete nodules by laryngoscopy, active treatment is recommended, such as drug therapy, voice therapy or surgical treatment.

BackgroundAlthough traditional cardiovascular risk factors are closely related to the poor prognosis of acute myocardial infarction (AMI) patients, there are few studies on the relationship of serum phosphorus and calcium with prognosis in AMI patients. The relationship of serum phosphorus and calcium with prognostic biomarkers in AMI remains unclear.Methods and resultsA total of 3,891 AMI patients were enrolled from a prospective cohort study. We investigated the association of serum phosphorus and calcium with prognostic biomarkers. The risk of in-hospital heart failure (HF), post-discharge HF, all-cause mortality and cardiac mortality was estimated across quartiles of serum phosphorus and calcium levels. Serum phosphorus and calcium levels were associated with biomarkers of prognosis. Overall, 969 patients developed in-hospital HF during hospitalization, 549 patients developed post-discharge HF during a median follow-up of 12 months, and 252 patients died, with 170 cardiac deaths since admission. In the fully adjusted model, compared with patients in quartile 2 (Q2), patients with serum phosphorus levels in Q4 were at greater risk of post-discharge HF [sub-distributional hazard ratios (SHR) 1.55; 95% confidence interval (CI), 1.21–1.99], in-hospital HF [odds ratio (OR) 1.84; 95% CI, 1.47–2.31], all-cause mortality (HR 1.59; 95% CI, 1.08–2.32), and cardiac mortality (SHR 1.68; 95% CI, 1.03–2.75). Compared with patients in Q2, patients with corrected calcium levels in Q4 had a higher risk of in-hospital HF (OR 1.62; 95% CI, 1.29–2.04), all-cause mortality (HR 1.99; 95% CI, 1.37–2.88), and cardiac mortality (SHR 1.87; 95% CI, 1.19–2.96; all p-trend < 0.05).ConclusionSerum phosphorus and calcium levels were associated with AMI prognostic biomarkers in AMI. Higher serum phosphorus was independently related to the increased risk of in-hospital HF, postdischarge HF, all-cause mortality and cardiac mortality, and higher serum calcium was independently related to the increased risk of in-hospital HF, all-cause mortality and cardiac mortality after AMI.

With China’s rapid urbanization and socioeconomic development, cultivated land has been experiencing continuous reduction, spatial shift, and ecological degradation in the past few decades, coupled with the decreasing and aging agricultural labor force, thus improving cultivated land utilization efficiency while minimizing associated environmental impacts is one of the major challenges facing China. This study first establishes an index system to access the eco-efficiency of cultivated land use (EECLU) considering both carbon sequestration and carbon emissions, next, employs the Super-SBM model to evaluate the spatial–temporal characteristics of EECLU, then, uses landscape metrics to describe landscape pattern dynamics of cultivated land, and finally conducts panel data analysis to investigate the relationship between landscape pattern changes and the EECLU variations. This framework was applied to Jiangsu Province, a major grain-producing area with a developed economy. The results showed that the average EECLU of the counties in rural Jiangsu from 2000 to 2020 slightly decreased, most counties were in the medium–low efficiency range (0.6–0.8), and Southern Jiangsu generally has the lowest EECLU values while Central Jiangsu has the highest. The total area and the average patch sizes of cultivated land have significantly positive impacts on EECLU, while the shape complexity and patch fragmentation have significantly negative impacts on EECLU. Therefore, comprehensive low-carbon strategies and better management and technology in the agricultural sector are needed to further improve EECLU. On the premise of protecting the total area of cultivated land, larger and more aggregated land patches should be promoted in the land consolidation process, and the cultivated land targeted for occupation or compensation should be able to simplify the overall shape of cultivated land patches.

The reliability assessment of fatigue life of automotive chassis parts is an important part of automobile safety. The fatigue endurance tests of automotive half-axles were carried out. The three-parameter Weibull distribution model was established according to the fatigue life distribution of samples. Using the right approximation method and the genetic algorithm to estimate three parameters of the distribution model and a comparative analysis was made. The results show that the initial life unreliability estimated by the median rank in the right approximation method had a large deviation from the true value, which may cause the iterative algorithm fall into the local optimal solution and affect the estimation accuracy. Therefore, a new parameter estimation method based on dual genetic algorithm was proposed. The newly proposed dual genetic algorithm not only improves the iteration speed, but also improves the accuracy of parameter estimation, which provides new ideas and theoretical basis for reliability assessment of mechanical components.

Objective: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART. Methods: We designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS. Results: Our study included 233 ​PWH (mean age ​= ​36.6 ​± ​11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population. Conclusions: We present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents. The translational potential of this article: The trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.

The Jahn-Teller effect is the spontaneous symmetry breaking of the molecular structure caused by the coupling of electrons and nuclei. Here the authors use ultrafast Coulomb explosion imaging to map the evolution of the fundamental symmetry lowering process in photoionized methane within around 20fs.

Abstract. Prolonged antiretroviral therapy (ART)-free remission post-treatment has been observed and reported in human immunodeficiency virus-1 (HIV-1) infection. The primary factors for such achievement have been linked to the transcriptional inactivation of HIV-1 DNA and immune recovery. Here, we reported a patient with acute HIV-1 infection who immediately received intensified quadruple ART. At month 9 (M9), an old CFDA-approved immuno-suppressive herbal medicine, Tripterygium Wilfordii Hook F (TwHF), was used in addition to ART. The patient was closely monitored. Virological and immunological tests as well as transcriptome analysis were carried out at each visit. The results showed that TwHF reduced serum IP-10 level and inhibited T cell activation. Both ART and TwHF were discontinued in M24, and levels of peripheral blood HIV-1 RNA and DNA remained suppressed for consecutive 12 months. With transcriptome analysis, we found pattern changes linking immuno-activation and amino acid metabolism with viral suppression and rebound. This indicates that the intentional suppression of immuno-activation is a promising approach for a functional cure of HIV-1 infection.

Abstract Background Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions. Methods Two sets of study populations were included: 490 China AIDS Clinical Trial (CACT) participants (Training cohort, followed up for 144 to 288 weeks) and 117 outpatients from Peking Union Medical College Hospital (PUMCH) (Validation cohort, followed up for more than 96 weeks). All patients were chronically HIV-1-infected and achieved successful HIV-1 plasma RNA suppression within week 48. Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, 144 and 288 weeks after combined antiretroviral therapy (cART) initiation were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART. Results The total HIV-1 DNA rapidly decreased from baseline [median = 3.00 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (median = 2.55 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 plasma RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (

Abstract Over the past decades, low‐dose computed tomography (LD‐CT) screening has been widely used for the early detection of lung cancer. Increasing numbers of indeterminate pulmonary nodules are now being discovered. However, it remains challenging to distinguish malignant from benign pulmonary nodules, especially those considered to be small or ground‐glass (GGN) nodules. Liquid biopsies have been successfully applied in the diagnosis of advanced lung cancer, and the potential value for early detection of lung cancer has made great progress. Recent studies have demonstrated the value of various blood‐based tumor biomarkers in determining the nature of pulmonary nodules, including cell‐free DNA (cfDNA), microRNAs (miRNAs), circulating tumor cells (CTCs) and tumor‐associated autoantibodies (AAbs). In this review, we summarize the latest progress of liquid biopsies, and their potential applications and challenges in the diagnosis of malignant pulmonary nodules.

Abstract Background Some long-term non-progressors (LTNPs) have decreasing CD4+ T cell counts and progress to AIDS. Exploring which subsets of CD4+ T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis. Methods Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4+ cell count dropped to

Abstracts: Ionic liquids (ILs)-solid interfacial phenomenon is undoubtedly one of the topic issues in energy related fields, especially bringing great challenges in the development of chemical engineering. Solid-ILs friction under microscale shows outstanding properties such as widely studied electro-controllability by surface potential or electric field, and promising performance of superlubricity. Vast applications, such as boundary lubrication and supercapacitors, have been benefiting from these studies. In this review, we summarized the recent advances of the measurements of solid-ILs friction, and focused on the microscale and fascinating findings. A brief tutorial for this topic, containing both experimental and theoretical methods, was also provided. It was anticipated that this review would help researchers grasp the emerging field and stimulate the advance of new ideas and methods in ILs on solids.

Osmotolerant yeasts are considered one of the major contaminants responsible for spoilage in honey. To address the signature volatile components of jujube honey contaminated by Zygosaccharomyces rouxii, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and chemometrics analyses were used to analyze the variation of volatile substances during early contamination of mature and immature jujube honey. Undecanal, methyl butyrate, methyl 2-nonenoate, methyl hexanoate, and 2-methyl-3-pentanone were identified as signature volatiles of jujube honey contaminated with Z. rouxii. In addition, methyl heptanoate, 2,6,10-trimethyltetradecane, and heptanal were identified as potential volatile signatures for immature jujube honey. The R2 and Q2 of OPLS-DA analyses ranged from 0.736 to 0.955, and 0.991 to 0.997, which indicates that the constructed model was stable and predictive. This study has demonstrated that HS-SPME-GC-MS could be used to distinguish Z. rouxii-contaminated jujube honey from uncontaminated honey based on variation in VOCs, and could provide theoretical support for the use of HS-SPME-GC-MS for the rapid detection of honey decomposition caused by Z. rouxii, which could improve nutritional quality and reduce economic losses.

To address the potential risks to food safety, headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography–ion mobility spectrometry (HS-GC-IMS) were used to analyze the volatile organic compounds (VOCs) generated from chilled chicken contaminated with Staphylococcus aureus during early storage. Together with the KEGG database, we analyzed differential metabolites and their possible biotransformation pathways. Orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to characterize VOCs and identify biomarkers associated with the early stage of chicken meat contamination with S. aureus. The results showed 2,6,10,15-tetramethylheptadecane, ethyl acetate, hexanal, 2-methylbutanal, butan-2-one, 3-hydroxy-2-butanone, 3-methylbutanal, and cyclohexanone as characteristic biomarkers, and 1-octen-3-ol, tetradecane, 2-hexanol, 3-methyl-1-butanol, and ethyl 2-methylpropanoate as potential characteristic biomarkers. This provides a theoretical basis for the study of biomarkers of Staphylococcus aureus in poultry meat.

Grassland gross primary productivity (GPP) is an important part of global terrestrial carbon flux, and its accurate simulation and future prediction play an important role in understanding the ecosystem carbon cycle. Machine learning has potential in large-scale GPP prediction, but its application accuracy and impact factors still need further research. This paper takes the Mongolian Plateau as the research area. Six machine learning methods (multilayer perception, random forest, Adaboost, gradient boosting decision tree, XGBoost, LightGBM) were trained using remote sensing data (MODIS GPP) and 14 impact factor data and carried out the prediction of grassland GPP. Then, using flux observation data (positions of flux stations) and remote sensing data (positions of non-flux stations) as reference data, detailed accuracy evaluation and comprehensive trade-offs are carried out on the results, and key factors affecting prediction performance are further explored. The results show that: (1) The prediction results of the six methods are highly consistent with the change tendency of the reference data, demonstrating the applicability of machine learning in GPP prediction. (2) LightGBM has the best overall performance, with small absolute error (mean absolute error less than 1.3), low degree of deviation (root mean square error less than 3.2), strong model reliability (relative percentage difference more than 5.9), and a high degree of fit with reference data (regression determination coefficient more than 0.97), and the prediction results are closest to the reference data (mean bias is only −0.034). (3) Enhanced vegetation index, normalized difference vegetation index, precipitation, land use/land cover, maximum air temperature, potential evapotranspiration, and evapotranspiration are significantly higher than other factors as determining factors, and the total contribution ratio to the prediction accuracy exceeds 95%. They are the main factors influencing GPP prediction. This study can provide a reference for the application of machine learning in GPP prediction and also support the research of large-scale GPP prediction.

In complex marine environments, underwater images often suffer from color distortion, blur, and poor visibility. Existing underwater image enhancement methods predominantly rely on the U-net structure, which assigns the same weight to different resolution information. However, this approach lacks the ability to extract sufficient detailed information, resulting in problems such as blurred details and color distortion. We propose a two-branch underwater image enhancement method with an optimized original resolution information strategy to address this limitation. Our method comprises a feature enhancement subnetwork (FEnet) and an original resolution subnetwork (ORSnet). FEnet extracts multi-resolution information and utilizes an adaptive feature selection module to enhance global features in different dimensions. The enhanced features are then fed into ORSnet as complementary features, which extract local enhancement features at the original image scale to achieve semantically consistent and visually superior enhancement effects. Experimental results on the UIEB dataset demonstrate that our method achieves the best performance compared to the state-of-the-art methods. Furthermore, through comprehensive application testing, we have validated the superiority of our proposed method in feature extraction and enhancement compared to other end-to-end underwater image enhancement methods.

A memristor is a kind of nonlinear two-port circuit element with memory characteristics, whose resistance value is subject to being controlled by the voltage or current on both its ends, and thus it has broad application prospects. At present, most of the memristor application research is based on the change of resistance and memory characteristics, which involves how to make the memristor change according to the desired trajectory. Aiming at this problem, a resistance tracking control method of memristors is proposed based on iterative learning controls. This method is based on the general mathematical model of the voltage-controlled memristor, and uses the derivative of the error between the actual resistance and the desired resistance to continuously modify the control voltage, making the current control voltage gradually approach the desired control voltage. Furthermore, the convergence of the proposed algorithm is proved theoretically, and the convergence conditions of the algorithm are given. Theoretical analysis and simulation results show that the proposed algorithm can make the resistance of the memristor completely track the desired resistance in a finite time interval with the increase of iterations. This method can realize the design of the controller when the mathematical model of the memristor is unknown, and the structure of the controller is simple. The proposed method can lay a theoretical foundation for the application research on memristors in the future.

Abstract Background Primary hepatic mucoepidermoid carcinoma (HMEC) is extremely rare and the molecular etiology is still unknown. The CRTC1-MAML2 fusion gene was previously detected in a primary HMEC, which is often associated with MEC of salivary gland in the literature. Methods A 64-year-old male was diagnosed with HMEC based on malignant squamous cells and mucus-secreting cells in immunohistochemical examination. Fluorescence in situ hybridization (FISH) was used to detect the CRTC1-MAML2 fusion gene in HMEC. Whole-exome sequencing and Sanger sequencing were used to reveal the molecular characteristics of HMEC and analysis was performed with public data. Pedigree investigation was performed to identify susceptibility genes. Results Hematoxylin–eosin staining and immunohistochemistry revealed that the tumor cells were composed of malignant epidermoid malignant cells and mucous cells, indicating a diagnosis of HMEC. The CRTC1-MAML2 fusion gene was not detected in the primary HMEC, and somatic mutations in GNAS, KMT2C and ELF3 genes were identified by sequencing. Analyses of public data revealed somatic GNAS alterations in 2.1% hepatobiliary tumors and relation with parasite infection. Heterozygous germline mutations of FANCA, FANCI, FANCJ/BRIP1 and FAN1 genes were also identified. Pedigree investigation verified that mutation of Fanconi’s anemia susceptibility genes were present in the pedigree. Conclusions Here we provide the first evidence of the molecular etiology of a rare HMEC associated with germline Fanconi’s anemia gene mutations and somatic GNAS R201H mutation.

Background: The interaction of gas and liquid can produce many interesting phenomena, such as bubbles rising from the bottom of the liquid. The simulation of two-phase fluids is a challenging topic in computer graphics. To animate the interaction of a gas and liquid, MultiFLIP samples the two types of particles, and a Euler grid is used to track the interface of the liquid and gas. However, MultiFLIP uses the fluid implicit particle (FLIP) method to interpolate the velocities of particles into the Euler grid, which suffer from additional noise and instability. Methods: To solve the problem caused by fluid implicit particles (FLIP), we present a novel velocity transport technique for two individual particles based on the affine particle-in-cell (APIC) method. First, we design a weighed coupling method for interpolating the velocities of liquid and gas particles to the Euler grid such that we can apply the APIC method to the simulation of a two-phase fluid. Second, we introduce a narrowband method to our system because MultiFLIP is a time-consuming approach owing to the large number of particles. Results: Experiments show that our method is well integrated with the APIC method and provides a visually credible two-phase fluid animation. Conclusions: The proposed method can successfully handle the simulation of a twophase fluid.