Search

Abstract Fusarium oxysporum (Schl.) f.sp. melonis, which causes muskmelon wilt disease, is a destructive filamentous fungal pathogen, attracting more attention to the search for effective fungicides against this pathogen. In particular, Silver nanoparticles (AgNPs) have strong antimicrobial properties and they are not easy to develop drug resistance, which provides new ideas for the prevention and control of muskmelon Fusarium wilt (MFW). This paper studied the effects of AgNPs on the growth and development of muskmelon, the control efficacy on Fusarium wilt of muskmelon and the antifungal mechanism of AgNPs to F. oxysporum. The results showed that AgNPs could inhibit the growth of F. oxysporum on the PDA and in the PDB medium at 100–200 mg/L and the low concentration of 25 mg/L AgNPs could promote the seed germination and growth of muskmelon seedlings and reduce the incidence of muskmelon Fusarium wilt. Further studies on the antifungal mechanism showed that AgNPs could impair the development, damage cell structure, and interrupt cellular metabolism pathways of this fungus. TEM observation revealed that AgNPs treatment led to damage to the cell wall and membrane and accumulation of vacuoles and vessels, causing the leakage of intracellular contents. AgNPs treatment significantly hampered the growth of mycelia in the PDB medium, even causing a decrease in biomass. Biochemical properties showed that AgNPs treatment stimulated the generation of reactive oxygen species (ROS) in 6 h, subsequently producing malondialdehyde (MDA) and increasing protective enzyme activity. After 6 h, the protective enzyme activity decreased. These results indicated that AgNPs destroy the cell structure and affect the metabolisms, eventually leading to the death of fungus.

Abstract Mitochondrial dysfunction, characterized by elevated oxidative stress, impaired energy balance, and dysregulated mitochondrial dynamics, is a hallmark of metabolic syndrome (MetS) and its comorbidities. Ferulic acid (FA), a principal phenolic compound found in whole grains, has demonstrated potential in ameliorating oxidative stress and preserving energy homeostasis. However, the influence of FA on mitochondrial health within the context of MetS remains unexplored. Moreover, the impact of FA on autophagy, which is essential for maintaining energy homeostasis and mitochondrial integrity, is not fully understood. Here, we aimed to study the mechanisms of action of FA in regulating mitochondrial health and autophagy using palmitate-treated HepG2 hepatocytes as a MetS cell model. We found that FA improved mitochondrial health by restoring redox balance and optimizing mitochondrial dynamics, including biogenesis and the fusion/fission ratio. Additionally, FA was shown to recover autophagy and activate AMPK-related cell signaling. Our results provide new insights into the therapeutic potential of FA as a mitochondria-targeting agent for the prevention and treatment of MetS.

Abstract Corynespora cassiicola is a highly diverse fungal pathogen that commonly occurs in tropical, subtropical, and greenhouse environments worldwide. In this study, the isolates were identified as C. cassiicola, and the optimum growth and sporulation were studied. The phenotypic characteristics of C. cassiicola, concerning 950 different growth conditions, were tested using Biolog PM plates 1–10. In addition, the strain of C. cassiicola DWZ from tobacco hosts was sequenced for the using Illumina PE150 and Pacbio technologies. The host resistance of tobacco Yunyan 87 with different maturity levels was investigated. In addition, the resistance evaluation of 10 common tobacco varieties was investigated. The results showed that C. cassiicola metabolized 89.47% of the tested carbon source, 100% of the nitrogen source, 100% of the phosphorus source, and 97.14% of the sulfur source. It can adapt to a variety of different osmotic pressure and pH environments, and has good decarboxylase and deaminase activities. The optimum conditions for pathogen growth and sporulation were 25–30 °C, and the growth was better on AEA and OA medium. The total length of the genome was 45.9 Mbp, the GC content was 51.23%, and a total of 13,061 protein-coding genes, 202 non-coding RNAs and 2801 and repeat sequences were predicted. Mature leaves were more susceptible than proper mature and immature leaves, and the average diameter of diseased spots reached 17.74 mm at 12 days. None of the tested ten cultivars exhibited obvious resistance to Corynespora leaf spot of tobacco, whereby all disease spot diameters reached > 10 mm and > 30 mm when at 5 and 10 days after inoculation, respectively. The phenotypic characteristics, genomic analysis of C. cassiicola and the cultivar resistance assessment of this pathogen have increased our understanding of Corynespora leaf spot of tobacco.

Abstract Background The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. Methods OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. Results Pla-Exos derived from active TAO patients (Pla-ExosTAO−A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO−A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO−A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. Conclusion Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.

Abstract The neural network method is a type of machine learning that has made significant advances over the past few years in a variety of fields, particularly text, speech, images, videos, etc. In areas where data is unstructured, traditional machine learning has not been able to surpass the ’glass ceiling’; therefore, researchers have turned to neural networks as auxiliary tools to achieve significant breakthroughs or develop new research methods. An array of computational chemistry challenges can be addressed using neural networks, including virtual screening, quantitative structure-activity relationships, protein structure prediction, materials design, quantum chemistry, and property prediction, among others. This paper proposes a strategy for predicting the chemical properties of fruits by using graph neural networks, and it aims to provide some guidance to researchers and streamline the identification process.

Daylily (Hemerocallis citrina) is a perennial herb of the genus Hemerocallis of Liliaceae. It is also an economically important crop and is widely cultivated. Daylily has nutritional, medicinal and ornamental values. The research literature shows that daylily is a high-quality food raw material rich in soluble sugars, ascorbic acid, flavonoids, dietary fiber, carotenoids, mineral elements, polyphenols and other nutrients, which are effective in clearing heat and diuresis, resolving bruises and stopping bleeding, strengthening the stomach and brain, and reducing serum cholesterol levels. This article reviews the main nutrients of daylily and summarizes the drying process of daylily. In addition, due to the existence of active ingredients, daylily also has a variety of biological activities that are beneficial to human health. This article also highlights the nutritional quality of daylily, the research progress of dried vegetable rehydration technology and dried daylily. In the end, the undeveloped molecular mechanism and functional research status of daylily worldwide are introduced in order to provide reference for the nutritional quality research and dried processing industry of daylily.

Background This study endeavored to develop a nicotinamide adenine dinucleotide (NAD+) metabolism-related biomarkers in gastric cancer (GC), which could provide a theoretical foundation for prognosis and therapy of GC patients. Methods In this study, differentially expressed genes (DEGs1) between GC and paraneoplastic tissues were overlapped with NAD+ metabolism-related genes (NMRGs) to identify differentially expressed NMRGs (DE-NMRGs). Then, GC patients were divided into high and low score groups by gene set variation analysis (GSVA) algorithm for differential expression analysis to obtain DEGs2, which was overlapped with DEGs1 for identification of intersection genes. These genes were further analyzed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain prognostic genes for constructing a risk model. Enrichment and immune infiltration analyses further investigated investigate the different risk groups, and qRT-PCR validated the prognostic genes. Results Initially, we identified DE-NMRGs involved in NAD biosynthesis, with seven (DNAJB13, CST2, THPO, CIDEA, ONECUT1, UPK1B and SNCG) showing prognostic significance in GC. Subsequent, a prognostic model was constructed in which the risk score, derived from the expression profiles of these genes, along with gender, emerged as robust independent predictors of patient outcomes in GC. Enrichment analysis linked high-risk patients to synaptic membrane pathways and low-risk to the CMG complex pathway. Tumor immune infiltration analysis revealed correlations between risk scores and immune cell abundance, suggesting a relationship between NAD+ metabolism and immune response in GC. The prognostic significance of our identified genes was validated by qRT-PCR, which confirmed their upregulated expression in GC tissue samples. Conclusion In this study, seven NAD+ metabolism-related markers were established, which is of great significance for the development of prognostic molecular biomarkers and clinical prognosis prediction for gastric cancer patients.

Abstract Despite the successful application of immune checkpoint therapy, no response or recurrence is typical in lung cancer. Cancer stem cells (CSCs) have been identified as a crucial player in immunotherapy-related resistance. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy. Metabolic adaption of CSCs drives tumor resistance, yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive. Here, through metabolomics, transcriptomics, a lung epithelial-specific Cpt1a-knockout mouse model, and clinical analysis, we demonstrate that CPT1A, a key rate-limiting enzyme of fatty acid oxidation, acts with L-carnitine, derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8+ T cells inactivation in lung cancer. Mechanistically, CPT1A restrains ubiquitination and degradation of c-Myc, while c-Myc transcriptionally activates CPT1A expression. The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating, thereby suppressing ferroptosis in CSCs. Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. The results illustrate the potential of a mechanism-guided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CSCs to improve the efficacy of lung cancer immunotherapy.

Objective To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. Methods High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. Results The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. Conclusion ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Objective To investigate asymptomatic infection of hepatitis B virus(HBV) among hepatitis B vaccinated donors in Shenzhen, and analyze its serological and molecular characteristics. Methods The HBsAg ELISA positive blood samples of blood donors born after 1992 were collected. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were further detected by Roche electrochemiluminescence immunoassay (ECL). BCP/PC and S regions were amplified by Nested-PCRs, HBV DNA quantification were adopted by qPCR simultaneously, and the sequences were also analyzed. Results A total of 46 632 blood samples of donors(31 612 males and 15 020 females) from December 2020 to January 2022 collected, and 99 samples with HBsAg ELISA positive were screened out. After tested by ECL, Nested-PCRs, and real-time fluorescence PCR, 61 were confirmed HBsAg positive, with the positive rate at 0.13% (61/46 632), including 49 males (0.16%, 49/31 612) and 12 females (0.08%, 12/15 020). The HBsAg positive rate of males was higher than that of females (P

Abstract The COVID-19 outbreak has dramatically impacted the economy, particularly consumption behaviors. Studies on how consumption responses to COVID-19 can be a powerful aid for urban consumption recovery. In this paper, based on a high-frequency consumption dataset from January 6, 2020, to April 28, 2020 covering 18 sectors and dataset from the corresponding lunar period in 2021, we look at how COVID-19 changed how people spent their money by looking at patterns of recession and recovery during the pandemic. Specifically, we first explore the recession-recovery pattern of national consumption and the effects of various policies and quantify it using regression methods. Then, recession-recovery patterns across cities are widely studied. We also reveal how consumption structures change during a pandemic and the relationship between patterns of change in citizens’ consumption and the socioeconomic characteristics of cities. And the specific empirical analysis is provided through panel regression models. In general, national consumption represented a Vshaped pattern during the pandemic, experiencing a dramatic decline and a rapid rebound. Consumption is significantly inhibited by lockdown, while it is stimulated positively but gradually by easing policies. Consumption patterns at the city level are associated with socioeconomic characteristics. Cities with high-income groups experience a more significant decline, and cities with a high share of the secondary sector have a higher recovery rate in consumption. The consumption structure redistributes but does not fundamentally change. During the recession and early recovery phase, consumption related to basic living saw a significant rise, whereas leisure-related consumption dropped dramatically and recovered slowly. Our study can assist policymakers in implementing diversified market provisions and targeted lockdown policy adjustments for consumption recovery in cities with different socioeconomic backgrounds.

Despite extensive research highlighting the pivotal role of MYB transcription factors in regulating anthocyanin biosynthesis, the interactive regulatory network involving these MYB factors in pear fruits remains inadequately characterized. In this study, the anthocyanin-regulatory gene PbrMYB114 was successfully cloned from ‘Yuluxiang’ pear (Pyrus bretschneideri) fruits, and its influence on anthocyanin accumulation was confirmed through transient expression assays. Specifically, the co-transformation of PbrMYB114 with its partner PbrbHLH3 in pears served to validate the functional role of PbrMYB114. Subsequently, PbrMYB114 was employed as bait in a yeast two-hybrid screening assay, using a ‘Yuluxiang’ pear protein library, which led to the identification of 25 interacting proteins. Further validation of the interactions between PbrMYB114 and PbrMT2/PbrMT3 was conducted. Investigations into the role of PbrMT2 and PbrMT3 in ‘Duli’ seedlings (Pyrus betulaefolia) revealed their potential to enhance anthocyanin accumulation. The outcomes of these studies provide novel insights into the protein network that regulates pear anthocyanin biosynthesis, particularly the functional interactions among PbrMYB114 and associated proteins.

Objective To analyze the results of different methods for reactive samples screened by the enzyme linked immunosorbent assay (ELISA) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood donors. Methods From March to April 2020, a total of 8 632 blood samples in Shenzhen were screened for SARS-CoV-2 total antibodies (TAb, including IgG, IgM, IgA) in plasma using ELISA(PC group), the antibody reactivity samples and their follow up plasma samples (FC group), and samples of disease control group(DC group) from January to April 2020 were detected using the following methods: 1) ELISA method for detecting IgG, IgM, and (or without detection) TAb; 2) pseudovirus neutralizing antibody test(pVNT); 3) western blot (WB) of SARS-CoV-2 antibody. The negative control group(NC group) from February to April 2020 performed ELISA and WB testing. Results Among the 34 total antibody positive samples, 2 were positive for pVNT test, and the total antibody, IgG and WB in the initial screening and tracking testing were positive. Thereafter, it was determined to be confirmed positive. The other 2 cases were positive for pVNT test, while the samples with positive WB results were in the follow-up stage. The TAb, IgG, and pVNT results did not conform to the dynamic evolution of antibodies, and cannot be determined as confirmed positive. Conclusion The infection status of antibody reactivity samples screened by SARS-CoV-2 ELISA can be judged by the logic of pVNT, WB and the dynamic change of antibody.

Objective To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). Methods Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4+ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. Results CD4+ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4+ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/106 CD4+ T cell′s respectively. Conclusion The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

Objective To analyze the SARS-CoV-2 detection results among blood donors in different periods of COVID-19 pandemic control in Shenzhen and assess the antibody levels and infection status of blood donors in different periods, so as to provide reference for subsequent blood testing strategies. Methods A total of 4 768 plasma samples of blood donors were subjected to pooled testing by nucleic acid testing(NAT) with 8 samples per pool. Additionally, these samples were subjected to a 1000-fold dilution, and the detection of SARS-CoV-2 total antibody was performed by enzyme-linked immunosorbent assay (ELISA). The 4 768 plasma samples were collected from blood donors at different time points in Shenzhen, with inquiries made to determine whether donors during the COVID-19 pandemic were in the convalescence. The antibody positive rates in blood screening samples during different periods of the pandemic and samples from individuals in the convalescence of COVID-19 infection were analyzed. Furthermore, the antibody levels were examined for differences based on gender, age, and blood type. Results All 4 768 plasma samples from blood donors were negative by NAT, while 2 342 samples were detected positive by the SARS-CoV-2 total antibody detection, with a positive rate of 49.1%. These samples from four periods (September 30 to October 3, 2022; November 3 to 6, 2022; December 27 to 31, 2022; January 6 to 18, 2023) were subjected to a 1 000-fold dilution for COVID-19 antibody detection, and the positive rates were 21.3%, 15.8%, 65.9%, and 93.9%, respectively. Conclusion The prevalence of COVID-19 antibodies among blood donors in Shenzhen during different periods of the pandemic varied significantly. There was no difference in antibody prevalence among different genders and blood types, while younger individuals exhibited a higher prevalence of antibodies. The risk of COVID-19 transmission through blood transfusion was found to be extremely low.

Abstract Background Epigenetic modifications of RNA significantly contribute to the regulatory processes in tumors and have, thus, received considerable attention. The m6A modification, known as N6-methyladenosine, is the predominant epigenetic alteration found in both eukaryotic mRNAs and ncRNAs. Main body m6A methylation modifications are dynamically reversible and are catalyzed, removed, and recognized by the complex of m6A methyltransferase (MTases), m6A demethylase, and m6A methyl recognition proteins (MRPs). Published evidence suggests that dysregulated m6A modification results in abnormal biological behavior of mature mRNA, leading to a variety of abnormal physiological processes, with profound implications for tumor development in particular. Conclusion Abnormal RNA processing due to dysregulation of m6A modification plays an important role in tumor pathogenesis and potential mechanisms of action. In this review, we comprehensively explored the mechanisms by which m6A modification regulates mRNA and ncRNA processing, focusing on their roles in tumors, and aiming to understand the important regulatory function of m6A modification, a key RNA epigenetic modification, in tumor cells, with a view to providing theoretical support for tumor diagnosis and treatment. Video Abstract

Abstract In this study, we examined the impact of demyelinating and neuroinflammation on trigeminal neuralgia (TN) by utilizing models of chronic constriction injury to the infraorbital nerve (CCI). The CCI rats were treated with either VX-765 (an inhibitor of caspase-1) or a control solution of PBS/DMSO to observe the effects on neurobehavioral and neuropathological outcomes. The histochemical changes, pyroptosis-related proteins were assessed using immunohistochemistry, Elisa, and western blotting. RSC96 cells were pretreated with belnacasan (VX-765, an inhibitor of caspase-1), Gasdermin D(GSDMD)-targeting siRNAs, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (Znpp) before being exposed to H2O2. Following these treatments, the Reactive oxygen species (ROS) level, cell viability, percentage of pyroptosis, pyroptosis-related proteins, nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 level was measured. The scanning electron microscopy revealed increased ball-like bulge and membrane pore formation in the CCI group. In the CCI and CCI+ Vehicle groups, we found ROS level and expression of pyroptosis-related proteins increased. While, treatment with VX-765resulted in a decreased expression of GSDMD, IL-1, IL-18, and caspase-1 decreased. In the in-vitro study, RSC96 cells showed mild pyroptosis and overall mild edema after being exposed to H2O2. The ROS level, percentage of pyroptosis, pyroptosis-related proteins, Nrf2 and HO-1 level increased significantly in the H2O2 group. While, the percentage of pyroptosis and pyroptosis-related proteins decreased significantly in the H2O2 + VX-765 group, H2O2 + siRNA group, and H2O2 + VX-765 + siRNA group. After treatment with HO-1-inhibitor Znpp and HO-1-activator Copp, the percentage of pyroptosis and pyroptosis-related proteins increased and decreased significantly respectively. In conclusions, the pyroptosis of Schwann cell in the CCI model generated the demyelination of TN nerve. The ROS is an upstream event of NLRP3 inflammasome activation which induced eventual pyroptosis. The Nrf2/HO-1 signaling pathway could protect the H2O2-induced pyroptosis in RSC96 cells.

The bulkhead additional thrust during shield tunneling, the force of friction between shield and soil, and the additional grouting pressure can cause additional stress in the surrounding soil, thereby disturbing existing buildings and structures. However, few studies focused on the disturbance situation when the shield tunneling machine approaches the receiving well. If the additional stress and deformation of the receiving well are too excessive, it could result in the collapse of the receiving well. Based on the two-stage method, this study derived the calculation formula of the additional stress and deformation of the receiving well enclosure structure caused by shield tunneling. Taking a shield machine receiving engineering as the context, this study established a numerical simulation model and compared theoretical calculation, the results of numerical simulation model and on-site monitoring data. Finally, the additional stress of the receiving well is analyzed. The research findings demonstrate that the theoretical prediction results, numerical simulation calculation results, and on-site monitoring data exhibit relatively small calculation errors, which validated the applicability of the theoretical prediction formula and numerical simulation model. As the distance between the shield machine and the receiving well decreases, the disturbance to the receiving well increases sharply. When the distance between the cutter head and the receiving well is less than three times the shield length, it is crucial to enhance the deformation monitoring of the receiving well. The primary factors affecting the additional load and deformation of the receiving well enclosure structure are the force of friction between shield and soil and the additional thrust of the cutterhead. The disturbance caused by the additional grouting pressure on the enclosure structure can be ignored.

In environmentally sensitive areas, especially the arid and semi-arid regions, the greening stability process and its influencing factors can directly affect the sustainable development of the ecological environment. In this study, multi-source remote sensing data such as land use/cover data, MODIS NDVI, and soil moisture, methods such as stability index, vegetation quantitative remote sensing, and Geodetector were employed to analyze the sustainability of the greening process in the Mu Us Sandy in 2000-2020, which were viewed from three aspects: changes in stability of land use types and function, soil moisture change and influencing factors on greening stability. The results showed that, (1) From the stability of land use types, continuous stable ecological land accounted for more than 50%, showing that decreased from northwest toward southeast. (2) From the functional stability, NDVI showed a fluctuated growth (0.035/a), with an increasing distribution pattern from northwest to southeast. Additionally, Vegetation changes were unstable and concentrated in the western part of the study area (OtogBanner and Otog Front Banner), while the eastern part was stable, in which vegetation improvement took the main position. Moreover, mobile dunes almost disappeared, and semi-fixed dunes decreased and gradually shrank to the west of the sandy area, while fixed dunes soared and were concentrated in the middle of the sandy land. (3) From the soil moisture change, soil moisture at different underground depths showed an overall increasing trend, but the deep soil moisture was higher than the shallow, and spatial distribution varied greatly. (4) From the influencing factors, natural factors significantly influence greening stability, among which precipitation had a particularly profound impact, and interactions with other natural and social factors were higher explanatory. The paper aims to explore whether the ecological environment is developing in a good and orderly direction in the Mu Us Sandy Land, and the potential factors that cause its changes, to provide a theoretical basis for scientific governance in the Mu Us Sandy Land and other arid and semi-arid areas in the future.

Abstract Background Cell pyroptosis has a strong proinflammatory effect, but it is unclear whether pyroptosis of liver macrophages exacerbates liver tissue damage during liver ischemia‒reperfusion (I/R) injury. Maresin1 (MaR1) has a strong anti-inflammatory effect, and whether it can suppress liver macrophage pyroptosis needs further study. Methods This study aimed to investigate whether MaR1 can alleviate liver I/R injury by inhibiting macrophage pyroptosis. The effects of MaR1 on cell pyroptosis and mitochondrial damage were studied by dividing cells into control, hypoxia/reoxygenation, and hypoxia/reoxygenation + MaR1 groups. Knocking out RORa was used to study the mechanism by which MaR1 exert its protective effects. Transcriptome analysis, qRT‒PCR and Western blotting were used to analyze gene expression. Untargeted metabolomics techniques were used to analyze metabolite profiles in mice. Flow cytometry was used to assess cell death and mitochondrial damage. Results We first found that MaR1 significantly reduced liver I/R injury. We observed that MaR1 decreased liver I/R injury by inhibiting liver macrophage pyroptosis. Then, we discovered that MaR1 promotes mitochondrial oxidative phosphorylation, increases the synthesis of ATP, reduces the generation of ROS, decreases the impairment of mitochondrial membrane potential and inhibits the opening of mitochondrial membrane permeability transition pores. MaR1 inhibits liver macrophage pyroptosis by protecting mitochondria. Finally, we found that MaR1 exerts mitochondrial protective effects through activation of its nuclear receptor RORa and the PI3K/AKT signaling pathway. Conclusions During liver I/R injury, MaR1 can reduce liver macrophage pyroptosis by reducing mitochondrial damage, thereby reducing liver damage.

Abstract. Background:. Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples. Methods:. From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR. Results:. We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). Conclusion:. MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.

Abstract Recent studies have shown a correlation between high-density lipoprotein cholesterol (HDL-C) and bone mineral density (BMD) in adults, but their relationship is unclear in adolescents. This study aimed to explore whether a correlation existed between them among adolescents aged 12–19. Data analyzed in our study was fetched from the National Health and Nutrition Examination Survey (NHANES) database 2011–2018. The relationship between HDL-C level and total BMD value was analyzed by multivariate logistic regression models, fitted smoothing curves, and generalized additive models. 3770 participants participated in this analysis. After adjusting for all relevant covariates involved in this study, we found a negative correlation between HDL-C levels and total bone density in male adolescents.Furthermore, the stratified analysis showed that all covariables-adjusted models retained the negative correlation excepting female, black, or Mexican American subgroups. An inverted U-shaped curve represented the correlation of HDL-C and total BMD among adolescents aged 16 to 19, and the turning point was 1.06 mmol/L. After adjusting for all relevant covariates involved in this study, the study found a negative correlation between HDL-C levels and total BMD in male adolescents aged 12 to 19, particularly among those of races other than Black and Mexican. There was a saturation effect between HDL-C level and total BMD in 16–19-year-old adolescents. The turning point was 1.06 mmol/L. Therefore, HDL-C might be a biomarker to detect bone health and further perform a more detailed examination.

Background Coronary artery disease (CAD) and cognitive impairment (CI) have become significant global disease and medical burdens. There have been several reports documenting the alterations in regional brain function and their correlation with CI in CAD patients. However, there is limited research on the changes in brain network connectivity in CAD patients. To investigate the resting-state connectivity and further understand the effective connectivity strength and directionality in patients with CAD, we utilized degree centrality (DC) and spectral dynamic causal modeling (spDCM) to detect functional hubs in the whole brain network, followed by an analysis of directional connections. Using the aforementioned approaches, it is possible to investigate the hub regions and aberrant connections underlying the altered brain function in CAD patients, providing neuroimaging evidence for the cognitive decline in patients with coronary artery disease. Materials and Methods This study was prospectively conducted involving 24 patients diagnosed with CAD and 24 healthy controls (HC) who were matched in terms of age, gender, and education. Functional MRI (fMRI) scans were utilized to investigate brain activity in these individuals. Neuropsychological examinations were performed on all participants. DC analysis and spDCM were employed to investigate abnormal brain networks in patients with CAD. Additionally, the association between effective connectivity strength and cognitive function in patients with CAD was examined based on the aforementioned results. Results By assessing cognitive functions, we discovered that patients with CAD exhibited notably lower cognitive function compared to the HC group. By utilizing DC analysis and spDCM, we observed significant reductions in DC values within the left parahippocampal cortex (PHC) and the left medial temporal gyrus (MTG) in CAD patients when compared to the control group. In terms of effective connectivity, we observed the absence of positive connectivity between the right superior frontal gyrus (SFG) and PHC in CAD patients. Moreover, there was an increase in negative connectivity from PHC and MTG to SFG, along with a decrease in the strength of positive connectivity between PHC and MTG. Furthermore, we identified a noteworthy positive correlation (r = 0.491, p = 0.015) between the strength of connectivity between the PHC and the MTG and cognitive function in CAD patients. Conclusions These research findings suggest that alterations in the connectivity of the brain networks involving SFG, PHC, and MTG in CAD patients may mediate changes in cognitive function.

Abstract Immune checkpoint blockades are the most promising therapy in lung adenocarcinoma (LUAD). However, the response rate remains limited, underscoring the urgent need for effective sensitizers. Interleukin 4 induced 1 (IL4I1) is reported to have immunoinhibitory and tumor‐promoting effects in several cancers. However, the targetable value of IL4I1 in sensitizing the immunotherapy is not clear, and there is a lack of effective small molecules that specifically target IL4I1. Here, we show that silencing IL4I1 significantly remodels the immune microenvironment via inhibiting aryl hydrocarbon receptor (AHR) signaling, thereby enhancing the efficacy of anti‐PD‐1 antibody in LUAD, which suggests that IL4I1 is a potential drug target for the combination immunotherapy. We then identify thymol as the first small molecule targeting IL4I1 transcription through a drug screening. Thymol inhibits the IL4I1 expression and blocks AHR signaling in LUAD cells. Thymol treatment restores the antitumor immune response and suppresses the progression of LUAD in an orthotopic mouse model. Strikingly, the combination treatment of thymol with anti‐PD‐1 antibody shows significant tumor regression in LUAD mice. Thus, we demonstrate that thymol is an effective small molecule to sensitize the PD‐1 blockade in LUAD via targeting IL4I1, which provides a novel strategy for the immunotherapy of LUAD.

Background Myopia is the most common refractive error because excessive increase in the axial length of a myopic eye leads to the thinning of the posterior scleral pole and can cause serious complications resulting in blindness. Thus, myopia has become a great concern worldwide. Dopamine (DA) plays a role in the development of myopia. Moreover, in Parkinson’s disease, it has been proved that vascular endothelial growth factor 165 (VEGF165) can promote the survival and recovery of DA neurons, resulting in increased DA secretion in the striatum, thereby treating neuropathy. Therefore, we speculate that VEGF165 can also promote the release of DA in the retina to inhibit the occurrence and development of myopia. We aimed to investigate the effect of VEGF165 on DA levels in the retinas of guinea pigs with form-deprivation myopia (FDM) and the effects of DA on myopia prevention and control. Methods Healthy 3-week-old pigmented guinea pigs were randomly divided into blank, FDM, phosphate buffer saline (PBS), 1, 5, and 10 ng groups. The FDM model was established by covering the right eye continuously with a translucent latex balloon pullover for 14 days. The pigs in the PBS, 1, 5, and 10 ng groups were injected with PBS buffer and 1, 5, and 10 ng of VEGF165 recombinant human protein, respectively, in the vitreous of the right eye before masking. The refractive error and axial length were measured before and after modeling. All retinas were used for biomolecular analyses after 14 days. Results We found that the intravitreal injection of VEGF165 elevated DA levels in the retina and was effective in slowing the progression of myopia, and 1 ng of VEGF165 was the most effective. Moreover, the number of vascular endothelial cell nuclei in the 1 ng group was lower than that in the other VEGF165 groups. Conclusions Our data suggest that VEGF165 has a promoting effect on DA in the retinas of guinea pigs with FDM, potentially controlling the development of myopia.

Objective In an effort to prevent transfusion-transmitted hepatitis B infection, universal HBsAg screening, HBsAg+ MP nucleic acid test(NAT) for HBV and HBsAg + individual(ID) NAT were analyzed for cost-effectiveness. Methods On the basis of screening data and the documented parameter, the number of window period infections, chronic infections and occult infections was constructed, and cost-benefit analysis was conducted. Results Of 132 208 donations, the yield rate of ID NAT for HBsAg-/DNA+ (0.11%) was significantly higher than HBsAg+ MP NAT(0.058%). Furthermore, the predicted preventing transfusion transmitted HBV cases by ID NAT is 1.25 times as that by MP-6 NAT, so did the benefits. The cost-benefit of the three screening models were 1∶63.6、1∶28.6 and 1∶53.4. Conclusion Universal HBsAg in combination with ID HBV NAT screening was the most effective among all screening strategy. It is necessary to applied HBsAg and ID HBV NAT screening for the safety of blood transfusion.

Abstract The MYC oncogenic family is dysregulated in diverse tumors which is generally linked to the poor prognosis of tumors. The members in MYC family are transcription factors which are responsible for the regulation of various genes expression. Among them, c-MYC is closely related to the progression of tumors. Furthermore, c-MYC aberrations is tightly associated with the prevalence of breast cancer. Tumor microenvironment (TME) is composed of many different types of cellular and non-cellular factors, mainly including cancer-associated fibroblasts, tumor-associated macrophages, vascular endothelial cells, myeloid-derived suppressor cells and immune cells, all of which can affect the diagnosis, prognosis, and therapeutic efficacy of breast cancer. Importantly, the biological processes occurred in TME, such as angiogenesis, immune evasion, invasion, migration, and the recruition of stromal and tumor-infiltrating cells are under the modulation of c-MYC. These findings indicated that c-MYC serves as a critical regulator of TME. Here, we aimed to summarize and review the relevant research, thus to clarify c-MYC is a key mediator between breast cancer cells and TME. Video Abstract

Abstract Background Isolated sulfite oxidase deficiency (ISOD) caused by sulfite oxidase gene (SUOX) mutations is a rare neurometabolic disease associated with ectopia lentis (EL). However, few genotype–phenotype correlations have been established yet. Methods Potentially pathogenic SUOX mutations were screened from a Chinese cohort of congenital EL using panel-based next-generation sequencing and analyzed with multiple bioinformatics tools. The genotype–phenotype correlations were evaluated via a systematic review of SUOX mutations within our data and from the literature. Results A novel paternal missense mutation, c.205G > C (p.A69P), and a recurrent maternal nonsense mutation, c.1200 C > G (p.Y400*), of SUOX were identified in a 4-year-old boy from 312 probands. The biochemical assays manifested elevated urine sulfite and S-sulfocysteine accompanied by decreased homocysteine in the blood. The patient had bilateral EL and normal fundus, yet minimal neurological involvement and normal brain structure. Molecular modeling simulation revealed the p.A69P mutant had an unstable structure but an unchanged affinity for sulfite, while the truncated p.Y400* mutant showed decreased binding capacity. Genotype–phenotype analysis demonstrated patients with biallelic missense mutations had milder symptoms (P = 0.023), later age of onset (P

Objective To analyze the cost-effectiveness of ELISA grey area strategy through establishing the health economics model. Methods The serological grey area strategy evaluation model was composed of screening strategy subdecision tree, pathogen infection subdecision tree and pathogen detection subdecision tree. The key parameters in the model were obtained from literatures and research data. The cost-effectiveness of setting ELISA grey area strategy was compared by software, and multifactor sensitivity analysis was conducted. Results After setting the ELISA grey area, extra samples(5.86 cases/100 000) with serological false negativity could be detected, including HBV samples at 4.93/100 000, HCV samples at 0.27/100 000, HIV samples at 0/100 000, syphilis samples at 0.66/100 000. To yield an additional seropositive sample out of every 100 000 blood donors, blood center will afford extra 1 million yuan about. Conclusion Through this study, a cost-effectiveness evaluation model of serological detection strategy was established. Although the ELISA grey area setting can yield a small number of seropositive samples, the cost is much higher than the current affordability.

Abstract Subthalamic nucleus (STN) deep brain stimulation (DBS) has been proven to be an alternative target choice for refractory isolated cervical dystonia (CD). However, assessments of its short and long-term safety, efficacy, and sustained effectiveness have been limited to few reports. Here, we evaluated nine consecutive refractory isolated CD patients who underwent bilateral STN DBS and accepted to short and long-term follow-up in this retrospective study. Seven time points were used to see the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores (pre-operation [baseline], 1, 3, 6, 12, 24 months post-operation and last follow-up) to assess improvement of dystonic symptoms. The 36-item Short-Form General Health Survey (SF-36) scores obtained at pre-operation and last follow-up to assess the changes in quality of life. All patients tolerated surgery well and acquired observable clinical benefits from STN DBS therapy. All patients achieved a considerable improvement in quality of life at the last follow-up. The hardware-related adverse events can be tolerated and the stimulation-related adverse events can be ameliorated by programming. Our data support the idea that bilateral STN DBS is a safety and effective method for the treatment of refractory isolated CD, with persistent and remarkable improvement in both movement and quality of life.

Abstract Background Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). Methods Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. Results High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. Conclusion Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.

OBJECTIVES This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p

IntroductionThe importance of global competence has been acknowledged in medical care as well as medical education. This study aims to develop a scale assessing the global competence of medical students, determine the factor structure and internal consistency of the scale and explore the underlying factors influencing the global competence of Chinese medical students in 8-year programs.MethodsA questionnaire (Global Competence Assessment Scale for Medical Students, MS-GCAS) was developed, and a cross-sectional multicenter survey was conducted in 1062 medical students from 10 medical schools in China. Questionnaire data were analyzed using exploratory factor analysis and multiple linear regression.ResultsThe exploratory factor analysis revealed a three-factor scale. The MS-GCAS has good internal consistency (Cronbach's alpha = 0.79 to 0.87). In the multivariate regression analyses, medical education stage (pDiscussionThe MS-GCAS has the potential to serve as a tool to measure the global competence of medical students. This three-factor scale can be used by medical education researches to improve future versions. Medical schools should conduct further educational reforms to promote students' global competence.

Objective To establish a routine screening method for unexpected antibodies of blood donors, analyze the results of centralized screening for unexpected antibody of blood donors in the blood center, and compare the cost of centralized and decentralized screening modes. Methods A total of 35 591 blood donors were screened for unexpected antibodies from March 31, 2021 to July 31, 2021, using microcolumn gel method. Unexpected antibody screening reactive samples were further confirmed by the Transfusion Research Institute of Shenzhen Blood Center, and the demographic characteristics were further determined through the analysis of unexpected antibody positive population. The direct cost and indirect cost of centralized and decentralized unexpected antibody screening mode were compared. Results Forty unexpected antibody positive samples were confirmed in Shenzhen, with the positive rate at 0.11%(40/35 591), among which MNS, Rh and Lewis system accounted for 35% (14/40), 32.5% (13/40) and 17.5% (7/40), respectively. Males and females accounted for 45% (18/40) and 55% (22/40), respectively (P0.05). Unexpected antibody screening in a centralized way saved about 1.16 million yuan per year. Conclusion It is necessary to carry out unexpected antibody screening for all blood donors, and centralized screening is more economical than decentralized screening.

Objective To assess three severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2) enzyme linked immunosorbent assays (ELISA) and one pseudotype lentivirus-based neutralization test (ppNAT) in detecting the convalescent plasma antibody levles from COVID-19. Methods 30 COVID-19 convalescent plasma samples were screened for antibodies against SARS-CoV-2 using three kinds of SARS-CoV-2 ELISA reagents and one ppNAT test in Shenzhen. The controls consisted of plasma samples from 32 healthy blood donors in February 2019. The diagnostic efficacy analysis of various SARS-CoV-2 ELISA reagents was performed using real-time fluorescent Polymerase Chain Reaction (RT-PCR). We also analyzed correlation between different immunological reagents and the age, gender, hospitalization, and severity of illness. Results The positive yielding rate of ppNAT and three kinds of IgG ELISA was higher than that of IgM ELISA. The positive yielding rates of three kinds of IgG ELISA were 100%(30/30), 93.33%(28/30), and 96.67%(29/30) respectively, while the yielding rates in control group were all 0. The positive yielding rate of three IgM ELISAs were 93.33%(28/30), 70%(21/30)and 46.67% (14/30). All the cases from negative control group were negative for IgG and IgM. Pearson correlation coefficient was calculated; there was a strong correlation between ELISA reagent 2 IgG and ELISA reagent 3 IgG (r=0.765, P0.05). Conclusion In the convalescent plasma with nucleic acid confirmed covid-19, the yielding rates of different IgM antibodies varied greatly. Antibody levels were influenced by age to some extent.

Objective To evaluate the performance and clinical application of a high-throughput nucleic acid blood screening detection system for SARS-CoV-2, so as to provide basis and technical means for its application in detection of plasma from recovered COVID-19 patients. Methods The SARS-CoV-2 nucleic acid was detected by real-time fluorescence quantitative PCR, and the sensitivity, precision, anti-interference and other parameters were evaluated. Blood donor samples collected during COVID-19 epidemic period were screened using the detection system to evaluate its applicability. Results The detection limits of gene N and ORF 1ab were 3.98 copies/mL and 9.38 copies/mL, respectively. The CV of high and low concentration samples were both less than 5%. Hemoglobin at 500 mg/dL and triglyceride at 3g/dL had little effect on the results. The detection system can effectively prevent carryover, thus avoiding false positive results. The SARS-CoV-2 nucleic acid blood screening was carried out in a total of 39 306 blood samples, and all samples were negative. Conclusion The established method can meet the needs of SARS-CoV-2 nucleic acid screening therefore ensure the safe application of plasma from recovered COVID-19 patients.

Abstract The information captured by the gist signal, which refers to radiologists’ first impression arising from an initial global image processing, is poorly understood. We examined whether the gist signal can provide complementary information to data captured by radiologists (experiment 1), or computer algorithms (experiment 2) based on detailed mammogram inspection. In the first experiment, 19 radiologists assessed a case set twice, once based on a half-second image presentation (i.e., gist signal) and once in the usual viewing condition. Their performances in two viewing conditions were compared using repeated measure correlation (rm-corr). The cancer cases (19 cases × 19 readers) exhibited non-significant trend with rm-corr = 0.012 (p = 0.82, CI: −0.09, 0.12). For normal cases (41 cases × 19 readers), a weak correlation of rm-corr = 0.238 (p

Several studies have reported the deleterious effects of excessive salt stress on Triticum aestivum L. seedlings. Seed pretreatment with exogenous salicylic acid (SA) enhances plants to tolerate salt stress. Herein, the present study aims to investigate the potential of plant-growth-promoting fungus Trichoderma longibrachiatum (TG1) to increase the plant growth and enhance the salicylic acid (SA) contents and antioxidants activity in wheat seedlings under different concentrations of salt stress. Wheat seeds were pretreated in TG1 spore suspension before exposure to different salt stresses. Compared with 0, 50, 100, 150 salt stresses, the TG1 and NaCl increased the wheat seeds germination rate, germination potential and germination index significantly; the shoot height and root length were increased by an average of 39.45% and 29.73%, respectively. Compared to NaCl stress across the four concentrations (0, 50, 100, and 150 mM), the TG1 treated wheat seedlings increased SA concentration and phenylalanine ammonia-lyase activity (PAL) by an average of 55.87% and 24.10% respectively. In addition, the TG1+NaCl-treated seedlings increased superoxide dismutase (SOD), peroxidases (POD), and catalase (CAT) activities in the shoot by an average of 47.68%, 23.68%, and 38.65% respectively compared to NaCl-stressed seedlings. Significantly, the genes, SOD, CAT, and POD were relatively up-regulated in the salt-tolerant TG1-treated seedlings at all NaCl concentrations in comparison to the control. Wheat seedlings treated with TG1+NaCl increased the transcript levels of SOD, POD and CAT by 1.35, 1.85 and 1.04-fold at 50 mM NaCl concentration, respectively, compared with 0 mM NaCl concentration. Our results indicated that seeds pretreatment with TG1 could increase endogenous SA of plants and promote seedling growth under salt stress by improving enzymatic antioxidant activities and gene expression.

Abstract Background Sorafenib is a kinase inhibitor that is used as a first-line therapy in advanced hepatocellular carcinoma (HCC) patients. However, the existence of sorafenib resistance has limited its therapeutic effect. Through RNA sequencing, we demonstrated that miR-138-1-3p was downregulated in sorafenib resistant HCC cell lines. This study aimed to investigate the role of miR-138-1-3p in sorafenib resistance of HCC. Methods In this study, quantitative real-time PCR (qPCR) and Western Blot were utilized to detect the levels of PAK5 in sorafenib-resistant HCC cells and parental cells. The biological functions of miR-138-1-3p and PAK5 in sorafenib-resistant cells and their parental cells were explored by cell viability assays and flow cytometric analyses. The mechanisms for the involvement of PAK5 were examined via co-immunoprecipitation (co-IP), immunofluorescence, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). The effects of miR-138-1-3p and PAK5 on HCC sorafenib resistant characteristics were investigated by a xenotransplantation model. Results We detected significant down-regulation of miR-138-1-3p and up-regulation of PAK5 in sorafenib-resistance HCC cell lines. Mechanistic studies revealed that miR-138-1-3p reduced the protein expression of PAK5 by directly targeting the 3′-UTR of PAK5 mRNA. In addition, we verified that PAK5 enhanced the phosphorylation and nuclear translocation of β-catenin that increased the transcriptional activity of a multidrug resistance protein ABCB1. Conclusions PAK5 contributed to the sorafenib resistant characteristics of HCC via β-catenin/ABCB1 signaling pathway. Our findings identified the correlation between miR-138-1-3p and PAK5 and the molecular mechanisms of PAK5-mediated sorafenib resistance in HCC, which provided a potential therapeutic target in advanced HCC patients.

Introduction Family caregivers play a key role in providing ongoing long-term care and assistance to their loved ones during cancer treatment. However, family caregivers of patients with lung cancer are frequently unprepared for their roles and they may undergo psychological distress, thus reducing their own quality of life while affecting patients’ health outcomes. Interventions that specifically target this population are lacking. This study aims to evaluate the effectiveness of a perioperative support programme on family caregivers of patients with early-stage lung cancer.Methods and analysis This study is guided by the Stress-Coping Model. Family caregivers of patients diagnosed with early-stage lung cancer and those who are scheduled for lung resection treatment will be invited to participate. Participants will be randomised to groups that either receive the perioperative support programme or usual care. The intervention consists of four face-to-face intervention sessions during the hospital stay and two weekly telephone follow-up sessions after discharge. Primary and secondary outcomes will be assessed at baseline and at 4 and 12 weeks after the intervention. Primary outcomes will include psychological distress and secondary outcomes will include caregiving burden, quality of life, coping style and social support. Generalised estimation equation model will be used to analyse the intervention effects.Ethics and dissemination The study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University (LYG2022003). The authors will disseminate the study’s findings by publishing them in international scientific journals.Trial registration number ChiCTR2200058280.

Mammography interpretation is challenging with high error rates. This study aims to reduce the errors in mammography reading by mapping diagnostic errors against global mammographic characteristics using a radiomics-based machine learning approach. A total of 36 radiologists from cohort A (n = 20) and cohort B (n = 16) read 60 high-density mammographic cases. Radiomic features were extracted from three regions of interest (ROIs), and random forest models were trained to predict diagnostic errors for each cohort. Performance was evaluated using sensitivity, specificity, accuracy, and AUC. The impact of ROI placement and normalization on prediction was investigated. Our approach successfully predicted both the false positive and false negative errors of both cohorts but did not consistently predict location errors. The errors produced by radiologists from cohort B were less predictable compared to those in cohort A. The performance of the models did not show significant improvement after feature normalization, despite the mammograms being produced by different vendors. Our novel radiomics-based machine learning pipeline focusing on global radiomic features could predict false positive and false negative errors. The proposed method can be used to develop group-tailored mammographic educational strategies to help improve future mammography reader performance.

Abstract It has been shown that there are differences in diagnostic accuracy of cancer detection on mammograms, from below 50% in developing countries to over 80% in developed world. One previous study reported that radiologists from a population in Asia displayed a low mammographic cancer detection of 48% compared with over 80% in developed countries, and more importantly, that most lesions missed by these radiologists were spiculated masses or stellate lesions. The aim of this study was to explore the performance of radiologists after undertaking a training test set which had been designed to improve the capability in detecting a specific type of cancers on mammograms. Twenty-five radiologists read two sets of 60 mammograms in a standardized mammogram reading room. The first test set focused on stellate or spiculated masses. When radiologists completed the first set, the system displayed immediate feedback to the readers comparing their performances in each case with the truth of cancer cases and cancer types so that the readers could identify individual-based errors. Later radiologists were asked to read the second set of mammograms which contained different types of cancers including stellate/spiculated masses, asymmetric density, calcification, discrete mass and architectural distortion. Case sensitivity, lesion sensitivity, specificity, receiver operating characteristics (ROC) and Jackknife alternative free-response receiver operating characteristics (JAFROC) were calculated for each participant and their diagnostic accuracy was compared between two sessions. Results showed significant improvement among radiologists in case sensitivity (+ 11.4%; P

AimsThis systematic review aimed to study the hippocampal and frontal changes of heart failure (HF) patients and HF animal models with cognitive impairment or depression.MethodsA systematic review of the literature was conducted independently by reviewers using PubMed, Web of Science, Embase, and the Cochrane Library databases.Results and conclusions30 studies were included, involving 17 pieces of clinical research on HF patients and 13 studies of HF animal models. In HF patients, the hippocampal injuries were shown in the reduction of volume, CBF, glucose metabolism, and gray matter, which were mainly observed in the right hippocampus. The frontal damages were only in reduced gray matter and have no difference between the right and left sides. The included HF animal model studies were generalized and demonstrated the changes in inflammation and apoptosis, synaptic reduction, and neurotransmitter disorders in the hippocampus and frontal lobes. The results of HF animal model studies complemented the clinical observations by providing potential mechanistic explanations of the changes in the hippocampus and frontal lobes.

ObjectivesThe objective of this research aimed to investigate the correlation involving serum albumin with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).MethodsFrom 2011 to 2020, the National Health and Nutrition Examination Survey (NHANES) surveyed 45462 participants. We used the relevant data to conduct descriptive statistics, linear regression, and Logistic regression analysis.ResultsAfter adjusting for age, sex, and race, as well as all other variables, serum albumin was significantly negatively related to DR (P0.05).ConclusionAlbumin levels in the serum have a quantitatively significant negative correlation with DR. Serum albumin levels in the blood can be used as a reference point for protracted follow-up of people with T2DM.

Phosphorus (P) is an essential element for crop production and a key source of nonpoint pollution in agroecosystems. In this study, we sought to analyze P levels and the factors affecting soil P availability, via P adsorption, in a typical field system that is characterized by the year-round cultivation of vegetables. A total of 190 sites were sampled from vegetable fields in Guangdong Province, South China. Within the research area, average concentrations of 124.49 mg P kg-1 and 1.55 g P kg-1 were recorded for available P (AP) and total P (TP), respectively, which are 8.53- and 1.78-fold higher, respectively, than the corresponding values recorded in 1980. The determined P adsorption maximum (Qm) averaged at 488.38 mg kg-1, which represents a reduction of 16% compared to the values obtained four decades ago. Accumulations of both TP and AP were found to be negatively correlated with the soil’s maximum adsorption buffering capacity (MBC), although no significant correlations with the soil binding energies (k) and Qm, were seen. However, soil pH was found to be significantly correlated with k and Qm. Furthermore, both free Mn oxides (Mnd) and silt concentrations in the soil were found to contribute to explaining the variations in Qm. Collectively, the findings of this study provide evidence to indicate that there has been an excessive accumulation of P in the perennial vegetable fields of Guangdong Province over the past four decades, which may have had negative effects on the P supply potential of the soil by reducing the maximum adsorption buffering capacity.

Evapotranspiration (ET) plays a crucial role in hydrological and energy cycles, as well as in the assessments of water resources and irrigation demands. On a regional scale, particularly in the agro-pastoral ecotone, clarification of the distribution of surface ET and its influencing factors is critical for the rational use of water resources, restoration of the ecological environment, and protection of ecological water sources. The SEBAL model was used to invert the regional ET based on Landsat8 images in the agro-pastoral ecotone of northwest China. The results were indirectly verified by monitoring data from meteorological stations. The correlation between ET and surface parameters was analyzed. Thus, the main factors that affect the surface ET were identified. The results show that the SEBAL model determines an accurate inversion, with a correlation coefficient of 0.81 and an average root mean square error of 0.9 mm/d, which is highly suitable for research on water resources. The correlation coefficients of normalized vegetation index, surface temperature, land surface albedo, net radiation flux with daily ET were 0.5830, 0.8425, 0.3428 and 0.9111, respectively. The normalized vegetation index and the net radiation flux positively correlated with the daily ET, while the surface temperature and land surface albedo negatively correlated with the daily ET. The correlation from strong to weak is the net radiation flux > surface temperature > normalized vegetation index > surface albedo. In terms of spatial distribution, the daily ET of water was the highest, followed by woodland, wetland, cropland, built-up land, shrub land, grassland and bare land. However, the SEBAL model overestimates the inversion of daily ET of built-up land.

The use of adjuvant therapy has provided survival benefits in patients with advanced melanoma. This study aimed to explore the recurrence and prognosis of the PD-1 inhibitor, conventional interferon (IFN), or observation (OBS) on resected stage III acral and cutaneous melanoma patients through a retrospective analysis. Patients with resected stage III melanoma at Fudan University Shanghai Cancer Center from 2017 to 2021 were enrolled with all of their clinicopathologic characteristics collected. They were divided into three groups: PD-1 inhibitor, IFN, and OBS. Survival analyses were performed to indicate the significance of different adjuvant therapies. A total of 199 patients were enrolled (PD-1 n = 126; IFN n = 31; and OBS n = 42), with their median follow-up times being 21 months, 24 months, and 49 months, respectively. The PD-1 inhibitor significantly improved relapse-free survival (p = 0.027) and overall survival (p = 0.033) compared with conventional treatment (IFN+OBS). The superiority of the PD-1 inhibitor was witnessed in stage IIIC/D (p = 0.000) acral (p = 0.05) melanoma patients with ulceration (p = 0.011) or lymph node macrometastasis (p = 0.010). The PD-1 inhibitor significantly reduced local recurrence and systemic metastasis compared with conventional therapy (p = 0.002). In conclusion, adjuvant anti-PD-1 immunotherapy can achieve better survival outcomes in acral and cutaneous melanoma patients compared with conventional treatment, without considering adverse events. More clinical benefits were seen in later-stage acral melanoma patients with ulceration or lymph node macrometastasis.