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We attempted to analyze the clinical value of microRNA (miR)-590-3p in diabetic nephropathy (DN) patients and its role in high glucose (HG)-induced renal tubular epithelial cell (HK-2) injury. Serum levels of miR-590-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Spearman correlation coefficient analysis of the correlation between miR-590-3p and clinical indicators. The diagnostic value of miR-590-3p was analyzed by the receiver operating characteristic (ROC) curve. Then, the DN cell model induced by HG in HK-2 cells was established. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and CCK-8 assay were employed to assess cell inflammation, oxidative stress, apoptosis, and proliferation. Dual-luciferase reporter assay confirmed the target of miR-590-3p. Serum miR-590-3p was reduced in patients of DN, which was positively correlated with eGFR and negatively associated with albuminuria. Furthermore, miR-590-3p also can diagnose patients of DN from healthy subjects or patients of T2DM. Furthermore, miR-590-3p was decreased in a concentration- and time-dependent manner during HG-induction. miR-590-3p overexpression bated HG-induced inhibition effect on cell proliferation and promotion effects on apoptosis, oxidative stress, and inflammation. C-X3-C motif chemokine ligand1 (CX3CL1) is the target of miR-590-3p, whose levels were enhanced in DN patients and are negatively regulated by miR-590-3p. Our discoveries offered new insights that reduced miR-590-3p as a potential biomarker for the diagnosis of DN, and elevated miR-590-3p can alleviate renal tubular injury by HG-induced through targeting CX3XL1, which may be a novel target for improving the development of DN.

Invasive fungal infections including Candidiasis and Aspergillosis are associated with considerable morbidity and mortality in immunocompromised individuals, such as cancer patients. Aurora B is a key mitotic kinase required for the cell division of eukaryotes from fungus to man. Here, we identified a novel Aurora B inhibitor GSK650394 that can inhibit the recombinant Aurora B from human and Aspergillus fumigatus, with IC50 values of 5.68 and 1.29 ��M, respectively. In HeLa and HepG2 cells, GSK650394 diminishes the endogenous Aurora B activity and causes cell cycle arrest in G2/M phase. Further cell-based assays demonstrate that GSK650394 efficiently suppresses the proliferation of both cancer cells and Aspergillus fumigatus. Finally, the molecular docking calculation and site-directed mutagenesis analyses reveal the molecular mechanism of Aurora B inhibition by GSK650394. Our work is expected to provide new insight into the combinational therapy of cancer and Aspergillus fumigatus infection.

Background. Atherosclerosis is a chronic process that takes place in the vascular wall and causes various cardiovascular diseases (CVDs). Micro-RNA-149 (miR-149) mediates many physiological and pathological processes, including atherosclerosis. However, it is unclear about the roles of miR-149 in endothelial injury. Here, we explored the protective effect and related mechanism of miR-149 in endothelial cells induced with oxidized low-density lipoprotein (ox-LDL). Methods. Human endothelial cell lines (HUVECs) were exposed to ox-LDL to induce endothelial injury. Cell viability was determined by the CCK-8 assay. Autophagy was detected by immunofluorescence. RT-qPCR and western blot were carried out to determine the mRNA and protein expressions of Akt and mTOR. Results. The miR-149 level in HUVECs was reduced by ox-LDL (100 μg/mL) incubation in a time-dependent manner. miR-149-mimic transfection markedly protected HUVECs from ox-LDL-induced injury, with increased cell viability and reduced caspase-3 activity. miR-149 mimics enhanced HUVEC autophagy, which was induced initially by ox-LDL. miR-149 mimics also markedly downregulated the expression of Akt, p-Akt, mTOR, and p-mTOR in ox-LDL-treated HUVECs. The miR-149-induced protection against HUVECs injury could be reversed by cotreatment with 3-methyladenine (3-MA, an autophagy inhibitor) or insulin (an activator of Akt/mTOR pathway). Conclusions. miR-149 prevents ox-LDL-induced endothelial cell injury by enhancing autophagy via increasing Akt and mTOR expressions.

Background Phosphorus (P) is essential for plant growth and development, and low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Long noncoding RNAs (lncRNAs) have recently been reported to be key regulators in the responses of plants to stress conditions, but the mechanism through which LP stress mediates the biogenesis of lncRNAs in soybean remains unclear. Results In this study, to explore the response mechanisms of lncRNAs to LP stress, we used the roots of two representative soybean genotypes that present opposite responses to P deficiency, namely, a P-sensitive genotype (Bogao) and a P-tolerant genotype (NN94156), for the construction of RNA sequencing (RNA-seq) libraries. In total, 4,166 novel lncRNAs, including 525 differentially expressed (DE) lncRNAs, were identified from the two genotypes at different P levels. GO and KEGG analyses indicated that numerous DE lncRNAs might be involved in diverse biological processes related to phosphate, such as lipid metabolic processes, catalytic activity, cell membrane formation, signal transduction, and nitrogen fixation. Moreover, lncRNA-mRNA-miRNA and lncRNA-mRNA networks were constructed, and the results identified several promising lncRNAs that might be highly valuable for further analysis of the mechanism underlying the response of soybean to LP stress. Conclusions These results revealed that LP stress can significantly alter the genome-wide profiles of lncRNAs, particularly those of the P-sensitive genotype Bogao. Our findings increase the understanding of and provide new insights into the function of lncRNAs in the responses of soybean to P stress.

We investigated the role of telomerase and telomere repeat-binding factor 2 (TRF2 or TERF2) in T-cell dysfunction in chronic viral infection. We found that the expression and activity of telomerase in CD4+ T (CD4T) cells from patients with hepatitis C virus (HCV) infections or people living with HIV (PLWH) were intact, but TRF2 expression was significantly inhibited at the post-transcriptional level, suggesting that TRF2 inhibition is responsible for the CD4T cell dysfunction observed during chronic viral infection. Silencing TRF2 expression in CD4T cells derived from healthy subjects induced telomeric DNA damage and CD4T cell dysfunction without affecting telomerase activity or translocation – similar to what we observed in CD4T cells from HCV patients and PLWH. These findings indicate that premature T-cell aging and dysfunction during chronic HCV or HIV infection are primarily caused by chronic immune stimulation and T-cell overactivation and/or proliferation that induce telomeric DNA damage due to TRF2 inhibition, rather than telomerase disruption. This study suggests that restoring TRF2 presents a novel approach to prevent telomeric DNA damage and premature T-cell aging, thus rejuvenating T-cell functions during chronic viral infection.

In higher plants, light capture of chlorophyll a/b binding protein (Lhc) plays a crucial role in the plant's response to adverse environment. So far, the family has not been systematically identified in grapes. In this study, 20 VvLhcs were identified in the grape genome, which were distributed in 13 of 19 grape chromosomes and divided into 7 developing branches. The results of gene duplication analysis showed that 6 VvLhcs formed fragment duplication events, while there was no tandem duplication in VvLhcs. Exon–intron structure analysis showed that they had a wide number of exons. Protein conserved motif analysis showed that VvLhcs contained more similar motif structures in the same phylogenetic branch. The cis-acting elements in the VvLhcs promoter region mainly respond to light, plant hormones and abiotic stresses. In addition, qRT-PCR results showed that different proportions of salt stress and red-blue light affected the expression of VvLhcs and the expression patterns of genes in different grape varieties were different. The results for further study on different grape varieties in different combinations of red and blue light of the Lhc provide a theoretical basis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-022-01204-5.

Background Selection of high-risk subjects for endoscopic screening of esophageal squamous cell carcinoma (ESCC) lacks individual predictive tools based on environmental risk factors. Methods We performed a large population-based case-control study of 1418 ESCC cases and 1992 controls in a high-risk area of China. Information on potential risk factors was collected via face-to-face interview using an electronic structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, and predictive nomograms were established accordingly. A weighted analysis was further conducted to introduce age into predictive nomograms due to frequency matching study design. Results Most cases were usually exposed to 4 to 6 risk factors, but most controls were usually exposed to 3 to 5 risk factors. The AUCs of male and female predictive nomograms were 0.75 (95%CI: 0.72, 0.77) and 0.76 (95%CI: 0.73, 0.79), respectively. The weighted analysis adding age in the predictive model improved the AUC in both men and women (0.81 (95%CI: 0.79, 0.84) and 0.88 (95%CI: 0.85, 0.90), respectively). Conclusions An easy-to-use preclinical predictive tool is provided to select candidate population with high ESCC risk for endoscopic screening. Its usefulness needs to be further evaluated in future screening practice.

Background There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. Methods We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. Results Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P P P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. Conclusions The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

Coronavirus disease 2019 (COVID‐19) have become a pandemic in the world. This study is aim to explore risk factors for COVID‐19 severity in the early stage and the correlation between the viral shedding and COVID‐19 severity. We included inpatient with laboratory confirmed COVID‐19 who had been discharged by 9 March 2020. The medical record data and dynamic change of biochemical indicators in‐hospital were compared between common and severe patients. Eighty patients were included in this study. Multivariable regression demonstrated increasing odds of severity associated with the duration of fever (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.10‐1.82, per day increase; P = .007), C‐reactive protein (CRP) (OR, 1.26; 95% CI, 1.04‐1.52; P = .02), and PO2, Highlights In this study, we found that the duration of fever, elevated CRP and PO2 < 80 mmHg on admission were associated with the COVID‐19 severity in the early stage and there is no correlation between the viral shedding and COVID‐19 severity.

Background Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment. Methods Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran’s Q test and I2 statistics. Results A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up. Conclusion Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.

Clostridioides difficile, which causes life-threatening diarrheal disease, presents an urgent threat to health care systems. In this study, we present a retrospective genomic and epidemiological analysis of C. difficile in a large teaching hospital. First, we collected 894 nonduplicate fecal samples from patients during a whole year to elucidate the C. difficile molecular epidemiology. We then presented a detailed description of the population structure of C. difficile based on 270 isolates separated between 2015 and 2020 and clarified the genetic and phenotypic features by MIC and whole-genome sequencing. We observed a high carriage rate (19.4%, 173/894) of C. difficile among patients in this hospital. The population structure of C. difficile was diverse with a total of 36 distinct STs assigned. In total, 64.8% (175/270) of the isolates were toxigenic, including four CDT-positive (C. difficile transferase) isolates, and 50.4% (135/268) of the isolates were multidrug-resistant. Statistically, the rates of resistance to erythromycin, moxifloxacin, and rifaximin were higher for nontoxigenic isolates. Although no vancomycin-resistant isolates were detected, the MIC for vancomycin was higher for toxigenic isolates (P < 0.01). The in-hospital transmission was observed, with 43.8% (110/251) of isolates being genetically linked to a prior case. However, no strong correlation was detected between the genetic linkage and epidemiological linkage. Asymptomatic colonized patients play the same role in nosocomial transmission as infected patients, raising the issue of routine screening of C. difficile on admission. This work provides an in-depth description of C. difficile in a hospital setting and paves the way for better surveillance and effective prevention of related diseases in China. IMPORTANCE Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries. However, research on CDI remains limited in China. Here, we characterized the comprehensive spectrum of C. difficile by whole-genome sequencing (WGS) in a Chinese hospital, showing a high detection rate among patients, diverse genome characteristics, a high level of antibiotic resistance, and an unknown nosocomial transmission risk of C. difficile. During the study period, two C. difficile transferase (CDT)-positive isolates belonging to a new multilocus sequence type (ST820) were detected, which have caused serious clinical symptoms. This work describes C. difficile integrally and provides new insight into C. difficile surveillance based on WGS in China.

Sulforaphane (SF) is one of the most effective natural products in preventing and fighting cancer, found in cruciferous plants. In this study, broccoli hairy roots grown for 20 d were used as the experimental material, and it was treated with 500 μmol/L melatonin (MT) for 0, 12 and 32 h to explore the effect of MT on the conversion of glucoraphanin (GRA) to SF. Results showed that the yields of GRA and SF were the largest under MT treatment for 12 h, which were 1.53 and 1.93-fold, respectively, compared to 0 h. However, Myrosinases activity was the highest under MT treatment for 32 h, which was 1.42-fold compared to that of the 0 h. The differential expression of key genes involved in GRA conversion to SF in broccoli hairy roots was identified transcriptome sequencing, and the path of the transformation from GRA to SF was simulated, which provided a theoretical basis for establishing an efficient transformation system from GRA to SF.

Background. Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce. Objective. To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients. Methods. Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group ( n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 μs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl–Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle. Results. Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment ( p < 0.01 ). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group ( p < 0.05 ). Conclusion. CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.

Background A number of studies have shown that genetic factor plays an important role in etiology of panic disorder (PD). The aim of the present study was to examine the association of serotonin-related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug. Methods Two hundred thirty-three patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), 5-HTR1A rs6295, 5-HTR2A rs6313 and COMT rs4680 gene polymorphisms were genotyped and assessed for the potential association. Results The allelic model showed that the SLC6A4 rs140701 polymorphism variant was significantly associated with increased risk of PD (OR = 0.624, 95% CI 0.450–0.864, p p p Conclusions The present study suggests that the SLC6A4 rs140701 polymorphism variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertraline in the treatment of PD.

The inflammatory proliferation of fibroblast-like synoviocytes (FLSs) and functional imbalances in T lymphocytes play critical roles in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of Huayu Tongbi Fang (HYTB, a traditional herbal formula) in RA treatment has been validated. In this study, we aimed to explore the regulatory mechanisms of HYTB on the proliferation and differentiation of T lymphocytes, and the inhibitory effect of HYTB on inflammatory proliferation of FLSs. The RCS-364 (Rat FLSs) cells were cocultured with rat splenic lymphocytes that were induced by interleukin-1β in Transwell chambers. After freeze-dried HYTB powder treatment, the percentage of T-cell subset and apoptosis rates of FLSs were measured using flow cytometry. Furthermore, protein expression of key molecules of NF-κB and JAK/STAT signaling pathways was quantified using Western blot. The granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured using enzyme-linked immunosorbent assay. The results showed that HYTB could inhibit the inflammatory proliferation of FLSs through inducing cell apoptosis. Additionally, HYTB treatment could intervene in the proliferation and differentiation of T lymphocytes and regulate protein expression of key molecules in NF-κB and JAK/STAT cell signaling pathways. Moreover, it could inhibit FLS activation by suppressing GM-CSF production by T cells and FLSs. Therefore, the HYTB formula should be used as a traditional medicine against RA in modern complementary and alternative therapies.

Background Cold stress is one of the primary environmental factors that affect plant growth and productivity, especially for crops like Brassica napus that live through cold seasons. Till recently, although a number of genes and pathways involved in B. napus cold response have been revealed by independent studies, a genome-wide identification of the key regulators and the regulatory networks is still lack. In this study, we investigated the transcriptomes of cold stressed semi-winter and winter type rapeseeds in short day condition, mainly with the purpose to systematically identify the functional conserved transcription factors (TFs) in cold response of B. napus. Results Global modulation of gene expression was observed in both the semi-winter type line (158A) and the winter type line (SGDH284) rapeseeds, in response to a seven-day chilling stress in short-day condition. Function analysis of differentially expressed genes (DEGs) revealed enhanced stresses response mechanisms and inhibited photosynthesis in both lines, as well as a more extensive inhibition of some primary biological processes in the semi-winter type line. Over 400 TFs were differentially expressed in response to cold stress, including 56 of them showed high similarity to the known cold response TFs and were consistently regulated in 158A and SGDH284, as well as 25 TFs which targets were over-represented in the total DEGs. A further investigation based on their interactions indicated the critical roles of several TFs in cold response of B. napus. Conclusion In summary, our results revealed the alteration of gene expression in cold stressed semi-winter and winter ecotype B. napus lines and provided a valuable collection of candidate key regulators involved in B. napus response to cold stress, which could expand our understanding of plant stress response and benefit the future improvement of the breed of rapeseeds.

Summary Coriander (Coriandrum sativum L. 2n = 2x = 22), a plant from the Apiaceae family, also called cilantro or Chinese parsley, is a globally important crop used as vegetable, spice, fragrance and traditional medicine. Here, we report a high‐quality assembly and analysis of its genome sequence, anchored to 11 chromosomes, with total length of 2118.68 Mb and N50 scaffold length of 160.99 Mb. We found that two whole‐genome duplication events, respectively, dated to ~45–52 and ~54–61 million years ago, were shared by the Apiaceae family after their split from lettuce. Unbalanced gene loss and expression are observed between duplicated copies produced by these two events. Gene retention, expression, metabolomics and comparative genomic analyses of terpene synthase (TPS) gene family, involved in terpenoid biosynthesis pathway contributing to coriander’s special flavour, revealed that tandem duplication contributed to coriander TPS gene family expansion, especially compared to their carrot counterparts. Notably, a TPS gene highly expressed in all 4 tissues and 3 development stages studied is likely a major‐effect gene encoding linalool synthase and myrcene synthase. The present genome sequencing, transcriptome, metabolome and comparative genomic efforts provide valuable insights into the genome evolution and spice trait biology of Apiaceae and other related plants, and facilitated further research into important gene functions and crop improvement.

Purpose. To observe the effect of a brain-computer interface-operated lower limb rehabilitation robot (BCI-LLRR) on functional recovery from stroke and to explore mechanisms. Methods. Subacute-phase stroke patients were randomly divided into two groups. In addition to the routine intervention, patients in the treatment group trained on the BCI-LLRR and underwent the lower limb pedal training in the control group, both for the same time (30 min/day). All patients underwent assessment by instruments such as the National Institutes of Health Stroke Scale (NIHSS) and the Fugl–Meyer upper and lower limb motor function and balance tests, at 2 and 4 weeks of treatment and at 3 months after the end of treatment. Patients were also tested before treatment and after 4 weeks by leg motor evoked potential (MEP) and diffusion tensor imaging/tractography (DTI/DTT) of the head. Results. After 4 weeks, the Fugl–Meyer leg function and NIHSS scores were significantly improved in the treatment group vs. controls ( P < 0.01 ). At 3 months, further significant improvement was observed. The MEP amplitude and latency of the treatment group were significantly improved vs. controls. The effect of treatment on fractional anisotropy values was not significant. Conclusions. The BCI-LLRR promoted leg functional recovery after stroke and improved activities of daily living, possibly by improving cerebral-cortex excitability and white matter connectivity.

Numerous reports have elucidated the important participation of exosomes in the communication between tumor cells and other cancer‐related cells including tumor‐associated macrophages (TAMs) in microenvironment. However, the interchange of exosomes between tumor cells and TAMs in the progression of lung adenocarcinoma (LUAD) remains largely enigmatic. Herein, we discovered that LUAD cells induced the M2 polarization of TAMs and the M2‐polarized macrophages facilitated LUAD cell invasion and migration and tumor metastasis in vivo. In detail, LUAD cells secreted exosomes to transport miR‐19b‐3p into TAMs so that miR‐19b‐3p targeted PTPRD and inhibited the PTPRD‐mediated dephosphorylation of STAT3 in TAMs, leading to STAT3 activation and M2 polarization. Also, the activated STAT3 transcriptionally induced LINC00273 in M2 macrophages and exosomal LINC00273 was transferred into LUAD cells. In LUAD cells, LINC00273 recruited NEDD4 to facilitate LATS2 ubiquitination and degradation, so that the Hippo pathway was inactivated and YAP induced the transcription of RBMX. RBMX bound to miR‐19b‐3p to facilitate the packaging of miR‐19b‐3p into LUAD cell‐derived exosomes. Collectively, our results revealed the mechanism underlying the interactive communication between LUAD cells and TAMs through elucidating the exchange of exosomal miR‐19b‐3p and LINC00273 and proved the prometastatic effect of the interchange between two cells. These discoveries opened a new vision for developing LUAD treatment., LUAD cell‐derived exosomal miR‐19b‐3p induce M2 polarization in THP‐1 cells by targeting PTPRD/STAT3 and STAT3 activated LINC00273 was transmitted by M2 macrophage‐derived exosomes to LUAD cells, activating YAP to induce RBMX‐mediated packaging of miR‐19b‐3p into LUAD cell‐derived exosomes.

Eye-tracking can help decode the intricate control mechanism in human performance. In healthcare, physicians-in-training require extensive practice to improve their healthcare skills. When a trainee encounters any difficulty in the practice, they will need feedback from experts to improve their performance. Personal feedback is time-consuming and subjected to bias. In this study, we tracked the eye movements of trainees during their colonoscopic performance in simulation. We examined changes in eye movement behavior during the moments of navigation loss (MNL), a signature sign for task difficulty during colonoscopy, and tested whether deep learning algorithms can detect the MNL by feeding data from eye-tracking. Human eye gaze and pupil characteristics were learned and verified by the deep convolutional generative adversarial networks (DCGANs); the generated data were fed to the Long Short-Term Memory (LSTM) networks with three different data feeding strategies to classify MNLs from the entire colonoscopic procedure. Outputs from deep learning were compared to the expert's judgment on the MNLs based on colonoscopic videos. The best classification outcome was achieved when we fed human eye data with 1000 synthesized eye data, where accuracy (91.80%), sensitivity (90.91%), and specificity (94.12%) were optimized. This study built an important foundation for our work of developing an education system for training healthcare skills using simulation.

Background: Music therapy has been widely used clinically to relieve insomnia disorder patients. However, the efficacy of music therapy in the treatment of insomnia disorder patients is uncertain. The purpose of this study is to determine the effectiveness and safety of music therapy in the treatment of insomnia disorder patients. Methods: Search PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, China Biomedical Literature Database, and search-related randomized controlled trials. Two reviewers will independently select studies, collect data, and evaluate methodological quality through the Cochrane Deviation Risk Tool. Revman V.5.3 will be used for meta-analysis. Results: This study will evaluate the current status of music therapy treatment for insomnia disorder patients, aiming to illustrate the effectiveness and safety of music therapy treatment. Conclusion: This study will provide a basis for judging whether music therapy is effective in treating insomnia disorder patients. INPLASY registration number: INPLASY202150087.

Embedded data are used to retrieve phases quicker with high accuracy in phase-modulated holographic data storage (HDS). We propose a method to design an embedded data distribution using iterations to enhance the intensity of the high-frequency signal in the Fourier spectrum. The proposed method increases the antinoise performance and signal-to-noise ratio (SNR) of the Fourier spectrum distribution, realizing a more efficient phase retrieval. Experiments indicate that the bit error rate (BER) of this method can be reduced by a factor of one after 10 iterations. [Image: see text]

Pulse lavage (PL) debridement and ultrasound are both known to be the treatment of biofilm-related periprosthetic joint infection (PJI). However, the efficacy of these in combination is unknown in eradicating biofilm from the orthopaedic metal implant surface. This study was conducted to understand the efficacy of PL and ultrasound in combination in eradicating bacterial biofilms on titanium alloy in vitro. Biofilms of Staphylococcus aureus strains were grown on titanium alloy coupons for 24 h. Then, the coupons were taken to each treatment group: (i) debrided with PL, (ii) exposed to ultrasound, or (iii) exposed to both. An untreated biofilm was set as a control group. Viable plate count and confocal microscopy using live/dead staining was used to measure the amount of biofilm. Viable plate count showed an approximate two-log reduction in CFU/cm2 in PL alone, from an initial cell count on the mental surface of approximately 109 CFU/cm2. The ultrasound caused an approximate seven-log reduction, and the combination group eradicated viable biofilm bacteria completely. Confocal imaging corroborated the CFU data. Our results indicate that PL and ultrasound both are remarkably in eradicating biofilm, and the combination of PL and ultrasound is more effective than alone in reducing biofilm.

Background Although total knee arthroplasty (TKA) is an efficacious treatment for end-stage osteoarthritis, ~20% of patients are dissatisfied with the results. We determined which factors contribute to patient satisfaction and compared the various scoring systems before and after surgery. Methods In this retrospective cohort study, 545 patients were enrolled and evaluated preoperatively and 1 year postoperatively. Patient demographics, as well as scores for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form (SF)-12, and 1989 Knee Society Clinical Rating System (1989 KSS), were recorded preoperatively and postoperatively. The possible predictors were introduced into a prediction model. Scores for overall satisfaction and the 2011 Knee Society Score (2011 KSS) were also assessed after TKA to identify the accuracy and agreement of the systems. Results There were 134 male patients and 411 female patients, with an overall prevalence of satisfaction of 83.7% 1 year after surgery. A history of surgery (p < 0.001) and the 1989 KSS and SF-12 were of the utmost importance in the prediction model, whereas the WOMAC score had a vital role postoperatively (change in WOMAC pain score, p < 0.001; change in WOMAC physical function score, p < 0.001; postoperative WOMAC pain score, p = 0.004). C-index of model was 0.898 > 0.70 (95% confidence interval (CI): 0.86-0.94). The Hosmer-Lemeshow test showed a p value of 0.586, and the AUC of external cohort was 0.953 (sensitivity=0.87, specificity=0.97). The agreement between the assessment of overall satisfaction and the 2011 KSS satisfaction assessment was general (Kappa=0.437 > 0.4, p < 0.001). Conclusion A history of surgery, the preoperative 1989 KSS, and the preoperative SF-12 influenced patient satisfaction after primary TKA. We recommend the WOMAC (particularly the pain subscale score) to reflect overall patient satisfaction postoperatively.

Background Growth performance is significant in broiler production. In the growth process of broilers, gene expression varies at different growth stages. However, limited research has been conducted on the molecular mechanisms of muscle growth and development in yellow-feathered male chickens. Results In the study, we used RNA-seq to study the transcriptome of the breast muscle of male Jinghai yellow chickens at 4 (M4F), 8 (M8F) and 12 weeks (M12F) of age. The results showed that 4608 differentially expressed genes (DEGs) were obtained by comparison in pairs of the three groups with Fold Change (FC) ≥ 2 and False Discovery Rate (FDR) ≤ 0.05, and 83, 3445 and 3903 DEGs were obtained separately from M4FvsM8F, M4FvsM12F and M8FvsM12F. Six genes were found as co-differentially expressed in the three age groups, namely SNCG, MYH1A, ARHGDIB, ENSGALG00000031598, ENSGALG00000035660 and ENSGALG00000030559. The GO analysis showed that 0, 304 and 408 biological process (BP) were significantly enriched in M4FvsM8F, M4FvsM12F and M8FvsM12F groups, respectively. KEGG pathway enrichment showed that 1, 2, 4 and 4 pathways were significantly enriched in M4FvsM8F, M4FvsM12F, M8FvsM12F and all DEGs, respectively. They were steroid biosynthesis, carbon metabolism, focal adhesion, cytokine-cytokine receptor interaction, biosynthesis of amino acids and salmonella infection. We constructed short hairpin RNA (shRNA) to interfere the differentially expressed gene RAC2 in DF-1 cells and detected mRNA and protein expression of the downstream genes PAK1 and MAPK8. Results of qPCR showed that RAC2, PAK1 and MAPK8 mRNA expression significantly decreased in the shRAC2–2 group compared with the negative control (NC) group. Western Blot (WB) results showed that the proteins of RAC2, PAK1 and MAPK8 also decreased in the shRAC2–2 group. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) assay both showed that the proliferation of DF-1 cells was significantly inhibited after transfection of shRAC2–2. Conclusions The results of RNA-seq revealed genes, BP terms and KEGG pathways related to growth and development of male Jinghai yellow chickens, and they would have important guiding significance to our production practice. Further research suggested that RAC2 might regulate cell proliferation by regulating PAKs/MAPK8 pathway and affect growth of chickens.

The highest incidence of esophageal squamous cell carcinoma (ESCC) occurs in China. Cancer stem cells play key roles for tumor progression. Gene amplified in squamous cell carcinoma 1 (GASC1) is essential to maintain self-renewal and differentiation potential of embryonic stem cells. This study aimed to reveal the effect and mechanism of GASC1 on ESCC stemness. The biological function of GASC1 in ESCC was evaluated both in vitro and in vivo. ChIP assay was performed to determine the molecular mechanism of GASC1 in epigenetic regulation of NOTCH1. We found that GASC1 expression was increased in poor differentiated ESCC cells and tissues. ESCC patients with a high level of GASC1 presented a significantly worse survival rate. GASC1 expression in purified ALDH+ ESCC cells was significantly higher than that in ALDH- cells. The stemness of ESCC was dramatically decreased after GASC1 blockade. Furthermore, blockade of GASC1 decreased NOTCH1 expression via increase of NOTCH1 promoter H3K9me2 and H3K9me3. Moreover, the impaired stemness after blockade of GASC1 could be reversed after transfection of NOTCH1 overexpression lentiviral vector. GASC1 promoted stemness in ESCC cells via NOTCH1 promoter demethylation. Therefore, GASC1/NOTCH1 signaling might be a potential therapeutic target for the treatment of ESCC patients.

Background The UL31 protein of herpes simplex virus 1 (HSV-1) plays an important role in the HSV-1 replication, however, its pinpoint functions in the life cycle of the virus have yet to be adequately elucidated. Objectives An antiserum specific for detecting HSV-1 UL31 was prepared as the foundation for future research on the role of UL31 in the course of HSV-1 infection. Materials and methods Recombinant protein of UL31 was expressed in Escherichia coli, which was then purified and employed to raise the level of antiserum in mice. Subsequently, western blot and immunofluorescence assay (IFA) were utilized to detect the specific antiserum. Results The recombinant UL31 protein consisting of N-terminal 27 aa of UL31 was fused to EYFP and His-tag. It was expressed, purified, and applied to the preparation of the antiserum. Western blot analysis and IFA demonstrated that this antiserum could detect both the recombinant UL31 and the native UL31. Conclusions Our results manifest that this antiserum could be conducive to further investigations concerning the roles of UL31 in the HSV-1 infection.

Background: Acupuncture has been widely used clinically to relieve chronic severe constipation. However, the efficacy of acupuncture in the treatment of chronic severe constipation is uncertain. The purpose of this study is to determine the effectiveness and safety of acupuncture in the treatment of chronic severe constipation. Methods: Search PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, China Science, and Technology Journal Database, China Biomedical Literature Database, and search related randomized controlled trials. Two reviewers will independently select studies, collect data, and evaluate methodological quality through the Cochrane Deviation Risk Tool. Revman V.5.3 will be used for meta-analysis. Results: This study will evaluate the current status of acupuncture treatment for chronic severe constipation, aiming to illustrate the effectiveness and safety of acupuncture treatment. Conclusion: This study will provide a basis for judging whether acupotomy is effective in treating chronic severe constipation. INPLASY registration number: INPLASY202070002

Background Axial spondyloarthritis (axial SpA) is a chronic inflammatory disorder could lead to disability due to the failure of timely treatment. The role of lymphocyte-to-monocyte ratio (LMR) in axial SpA remains unclear. The aim of this study was to investigate the role of LMR in axial SpA diagnosis, disease activity classification and sacroiliitis staging. Methods Seventy-eight axial SpA patients [51males and 27 females; mean age 41.0 (29–52) years] and 78 healthy controls (HCs) [55males and 23 females; mean age 40 (30–53) years] were enrolled in this study. The diagnosis of axial SpA was performed according to the New York criteria or the Assessment of Spondyloarthritis international Society (ASAS) classification criteria, whereas the staging of sacroiliitis in axial SpA patients was determined by X-ray examination. Comparisons of LMR levels between groups were performed using t test. Pearson or Spearman correlation analysis were used to assess correlations between LMR and other indicators. Receiver operating characteristic (ROC) curves were used to determine the role of LMR in the diagnosis of axial SpA. Results Higher neutrophil-to-lymphocyte ratio(NLR), red blood cell distribution width(RDW), platelet-to-lymphocyte ratio(PLR), mean platelet volume(MPV), erythrocyte sedimentation rate (ESR), and C-reactive protein(CRP) levels and lower red blood cell (RBC), hemoglobin (Hb), Hematocrit (Hct), LMR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin/globulin (A/G) levels were noted in axial SpA patients compared to HCs. Positive correlations were observed between LMR and RBC, Hb, Hct and A/G, whereas negative correlations were found between LMR and NLR, PLR, AST, and TBIL (P ). ROC curves showed that the area under the curve (AUC) for LMR in the diagnosis of ankylosing spondylitis was 0.803 (95% CI = 0.734–0.872) with a sensitivity and specificity of 62.8 and 87.2%, respectively, and the AUC (95% CI) for the combination of ESR, CRP and LMR was 0.975 (0.948–1.000) with a sensitivity and specificity of 94.9 and 97.4%, respectively. LMR levels were lower (P ) and significant differences in LMR values were observed among different stages (P Conclusions Our study suggested that LMR might be an important inflammatory marker to identify axial SpA and assess disease activity and X-ray stage of sacroiliitis.

Ginkgolide B (GB) is an active ingredient extracted from Ginkgo biloba leaves. However, the effects of GB on cardiac hypertrophy remain unclear. The study is aimed at determining whether GB could alleviate cardiac hypertrophy and exploring its underlying molecular mechanism. Rat cardiomyocyte cell line H9c2 cells were pretreated with GB and incubated with angiotensin II (Ang II) to simulate an in vitro cardiac hypertrophy model. Cell viability, cell size, hypertrophy markers, and autophagy were determined in H9c2 cells after Ang II treatment. Proteins involved in autophagy and the SIRT1 pathway were determined by western blot. Our data demonstrated that GB attenuated Ang II-induced cardiac hypertrophy and reduced the mRNA expressions of hypertrophy marker, atrial natriuretic peptide (ANP), and β-myosin heavy chain (β-MHC). GB further increased Ang II-induced autophagy in H9c2 cells and modulated expressions of autophagy-related proteins Beclin1 and P62. Modulation of autophagy using autophagy inhibitor 3-methyladenine (3-MA) could abrogate GB-downregulated transcription of NPPA. We then showed that GB attenuated Ang II-induced oxidative stress and reduction in SIRT1 and FoxO1 protein expression. Finally, the effect of GB on autophagy and cardiac hypertrophy could be reversed by SIRT1 inhibitor EX-527. GB inhibits Ang II-induced cardiac hypertrophy by enhancing autophagy via the SIRT1-FoxO1 signaling pathway and might be a potential agent in treating pathological cardiac hypertrophy.

African swine fever (ASF) is a serious contagious disease that causes fatal haemorrhagic fever in domestic and wild pigs, with high morbidity. It has caused devastating damage to the swine industry worldwide, necessitating the focus of attention on detection of the ASF pathogen, the African swine fever virus (ASFV). In order to overcome the disadvantages of conventional diagnostic methods (e.g. time-consuming, demanding and unintuitive), quick detection tools with higher sensitivity need to be explored. In this study, based on the conserved p72 gene sequence of ASFV, we combined the Cas12a-based assay with recombinase polymerase amplification (RPA) and a fluorophore-quencher (FQ)-labeled reporter assay for rapid and visible detection. Five crRNAs designed for Cas12a-based assay showed specificity with remarkable fluorescence intensity under visual inspection. Within 20 minutes, with an initial concentration of two copies of DNA, the assay can produce significant differences between experimental and negative groups, indicating the high sensitivity and rapidity of the method. Overall, the developed RPA-Cas12a-fluorescence assay provides a fast and visible tool for point-of-care ASFV detection with high sensitivity and specificity, which can be rapidly performed on-site under isothermal conditions, promising better control and prevention of ASF.

Depression is associated with poorer outcomes in a wide spectrum of surgeries but the specific effects of depression in patients undergoing cervical spine surgery are unknown. This study aimed to evaluate the prevalence and impact of pre-surgical clinical depression on pain and other outcomes after surgery for cervical degenerative disc disease using a national representative database. Data of patients with cervical myelopathy and radiculopathy were extracted from the 2005–2014 US Nationwide Inpatient Sample (NIS) database. Included patients underwent anterior discectomy and fusion (ACDF). Acute or chronic post-surgical pain, postoperative complications, unfavorable discharge, length of stay (LOS) and hospital costs were evaluated. Totally 215,684 patients were included. Pre-surgical depression was found in 29,889 (13.86%) patients, with a prevalence nearly doubled during 2005–2014 in the US. Depression was independently associated with acute or chronic post-surgical pain (aOR: 1.432), unfavorable discharge (aOR: 1.311), prolonged LOS (aOR: 1.152), any complication (aOR: 1.232), respiratory complications/pneumonia (aOR: 1.153), dysphagia (aOR: 1.105), bleeding (aOR: 1.085), infection/sepsis (aOR: 1.529), and higher hospital costs (beta: 1080.640) compared to non-depression. No significant risk of delirium or venous thrombotic events was observed in patients with depression as compared to non-depression. Among patients receiving primary surgery, depression was independently associated with prolonged LOS (aOR: 1.150), any complication (aOR:1.233) and postoperative pain (aOR:1.927). In revision surgery, no significant associations were found for prolonged LOS, any complication or pain. In conclusion, in the US patients undergoing ACDF, pre-surgical clinical depression predicts post-surgical acute or chronic pain, a slightly prolonged LOS and the presence of any complication. Awareness of these associations may help clinicians stratify risk preoperatively and optimize patient care.

Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-γ in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4+ cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-γ, and percentage of Th-17 cells in CD4+ cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.

Crop traits such as aboveground biomass (AGB), total leaf area (TLA), leaf chlorophyll content (LCC), and thousand kernel weight (TWK) are important indices in maize breeding. How to extract multiple crop traits at the same time is helpful to improve the efficiency of breeding. Compared with digital and multispectral images, the advantages of high spatial and spectral resolution of hyperspectral images derived from unmanned aerial vehicle (UAV) are expected to accurately estimate the similar traits among breeding materials. This study is aimed at exploring the feasibility of estimating AGB, TLA, SPAD value, and TWK using UAV hyperspectral images and at determining the optimal models for facilitating the process of selecting advanced varieties. The successive projection algorithm (SPA) and competitive adaptive reweighted sampling (CARS) were used to screen sensitive bands for the maize traits. Partial least squares (PLS) and random forest (RF) algorithms were used to estimate the maize traits. The results can be summarized as follows: The sensitive bands for various traits were mainly concentrated in the near-red and red-edge regions. The sensitive bands screened by CARS were more abundant than those screened by SPA. For AGB, TLA, and SPAD value, the optimal combination was the CARS-PLS method. Regarding the TWK, the optimal combination was the CARS-RF method. Compared with the model built by RF, the model built by PLS was more stable. This study provides guiding significance and practical value for main trait estimation of maize inbred lines by UAV hyperspectral images at the plot level.

Cardiac microvascular endothelial cell (CMEC) dysfunction is considered as a major contributor to the cardiovascular complications in diabetes mellitus, with oxidative stress caused by hyperglycemia playing a critical role in the progression of CMEC dysfunction. Melatonin is a kind of hormone well known for its antioxidant properties, which has potential protective effects against diabetes mellitus and its complications. However, the role of melatonin on CMEC dysfunction caused by hyperglycemia and its molecular mechanisms underlying these effects has not been clarified. Herein, we investigate the protective effects of melatonin on high glucose- (HG-) evoked oxidative stress and apoptosis in CMECs and underlying mechanisms. Our results revealed that melatonin ameliorated the injury caused by HG in primary cultured rat CMECs. Injury can be accompanied by reduced reactive oxygen species (ROS) and malondialdehyde (MDA) production, and enhanced superoxide dismutase (SOD) activity. Meanwhile, melatonin treatment significantly inhibited HG-induced CMEC apoptosis. Moreover, melatonin increased the activity of the AMPK/SIRT1 signaling axis in CMECs under HG condition, whereas administration of the AMPK inhibitor compound C or SIRT1 silencing partially abrogated the beneficial effects of melatonin. In streptozotocin- (STZ-) evoked diabetic mice, melatonin notably ameliorated cardiac dysfunction and activated the AMPK/SIRT1 signaling. In conclusion, our findings revealed that melatonin attenuates HG-induced CMEC oxidant stress, apoptosis injury, and STZ-induced cardiac dysfunction through regulating the AMPK/SIRT1 signaling pathway.

Background Gene transcripts that show invariant abundance during development are ideal as reference genes (RGs) for accurate gene expression analyses, such as RNA blot analysis and reverse transcription–quantitative real time PCR (RT-qPCR) analyses. In a genome-wide analysis, we selected three “Commonly used” housekeeping genes (HKGs), fifteen “Traditional” HKGs, and nine novel genes as candidate RGs based on 80 publicly available transcriptome libraries that include data for receptacle development in eight strawberry cultivars. Results The results of the multifaceted assessment consistently revealed that expression of the novel RGs showed greater stability compared with that of the “Commonly used” and “Traditional” HKGs in transcriptome and RT-qPCR analyses. Notably, the majority of stably expressed genes were associated with the ubiquitin proteasome system. Among these, two 26 s proteasome subunits, RPT6A and RPN5A, showed superior expression stability and abundance, and are recommended as the optimal RGs combination for normalization of gene expression during strawberry receptacle development. Conclusion These findings provide additional useful and reliable RGs as resources for the accurate study of gene expression during receptacle development in strawberry cultivars.

The management of acute angle closure combined with an extremely shallow anterior chamber and cataract remains complex. This study evaluated a technique of vitreous needle aspiration combined with phacoemulsification for the treatment of acute angle closure with continuous high intraocular pressure (IOP). We retrospectively reviewed the results of vitreous needle aspiration combined with phacoemulsification in 17 eyes (17 patients) with acute angle closure with continuous high IOP and coexisting visually significant cataracts between September 2018 and April 2020 at the glaucoma unit of the affiliated Changshu Hospital of Xuzhou Medical University. The main outcomes were the best corrected visual acuity (BCVA), IOP, anterior chamber depth (ACD), angle open distance 500 (AOD500), number of antiglaucoma medications, and surgery-associated complications. There were no complications during phacoemulsification and a foldable acrylic intraocular lens was implanted in the capsular bag in all 17 patients. For all patients, vitreous needle aspiration was successful at the first attempt. The BCVA improved from 2.02 ± 0.54 logMAR preoperatively to 0.73 ± 0.57 logMAR postoperatively at the final examination ( p < 0.001 ). The mean IOP was 54.47 ± 5.33 mmHg preoperatively and 15.59 ± 2.35 mmHg at the final examination ( p < 0.001 ) without any medication. The ACD was 1.70 ± 0.16 mm preoperatively and 3.35 ± 1.51 mm at the final examination ( p < 0.001 ). The AOD500 was 0.07 ± 0.02 mm preoperatively and 0.51 ± 0.04 mm at the final examination ( p < 0.001 ). Our vitreous needle aspiration technique can be performed safely in phacoemulsification for the management of acute angle closure with continuous high IOP.

In recent years, chronic liver injury has become a common disease that harms human health. Its clinical manifestations are hepatic steatosis and secondary chronic steatohepatitis, which can quickly transform into liver fibrosis and cirrhosis if not treated in time. Therefore, this study is aimed at searching for new therapeutic targets of chronic liver injury and clarifying the molecular mechanisms of the new targets involved in chronic liver injury. After aquaporin 9 was identified as a target by proteomics, Aqp9-/- mice were constructed using the CRISPR/Cas9 system. Biochemical and morphological tests were used to verify the effect of Aqp9 knockout on early chronic liver injury. Proteomics, molecular biology, and morphology experiments were used to screen and verify the effects of Aqp9 knockout on its downstream pathway. Through the above experiments, we demonstrated that aquaporin 9 could be used as an intervention target for antagonizing the development of early chronic liver injury and its gene knockout affected downstream inflammation, oxidative stress, apoptosis, and pyroptosis by alleviating hepatic lipotoxicity.

Dipterocarpus turbinatus Gaertn. F., naturally distributes in Southern China, which is an elite natural tree with high economic and medicinal value. In study, all chloroplast (cp) genome of Dipterocarpus turbinatus Gaertn. F. was assembled and characterized based on Illumina pair-end sequencing data. The complete chloroplast genome length was 152,279 bp. It contained a large (LSC, 83,862 bp) and a small (SSC, 20,215 bp) single copy region, separated by a pair of inverted repeats of 24,101 bp (IRs). The overall GC content of genome was 37.3%, the corresponding values of LSC, SSC, and IR regions were 35.3, 31.6, and 43.2%, respectively. There were 128 genes in the genome including 84 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Among all genes, 14 genes contain a single intron and 1 gene has two introns. The result showed that Dipterocarpus turbinatus Gaertn. F. was closely related to Vatica mangachapoi.

The complete chloroplast genome sequence of Yunnanopilia longistaminea, an endemic species in southwest China, is presented in this study. The total genome size of Y. longistaminea was 148,503 bp in length, with a typical quadripartite structure including a pair of inverted repeat (IRs, 28,075 bp) regions separated by a large single copy (LSC, 84,547bp) region and a small single copy (SSC, 7805 bp) region. The all GC content was 37.3%. The genome contains 117 genes, including 72 protein-coding genes, 37 tRNA genes, and 8 rRNA genes, 13 genes contain a single intron, and 3 genes have two introns. Further, a maximum-likelihood (ML) phylogenetic tree results that Y. longistaminea was closely related to the genera of Champereia manillana.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018–2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China., Author summary Generally, the clinical diagnosis of acute Q fever, which is caused by Coxiella burnetii, is based on serologic methods that detect the presence antibodies produced by the body to fight the infection. However, the lag time between becoming infected and production of antibodies limits early diagnosis using this method. Here, we confirmed an epidemic of human Q fever in Zhuhai, a contemporary city in China, using clinical metagenomic next-generation sequencing (mNGS) and cell phone location data. Our results indicate that Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai were the likely infection source for the Q fever epidemic. More importantly, we demonstrate that mNGS is a useful tool for rapid and effective public health responses to acute bacterial infections.

Chemical constituents from Zhideke granules were rapidly isolated and identified by ultra-performance liquid chromatography (UPLC) coupled with hybrid quadrupole-orbitrap mass spectrometry (MS) in positive and negative ion modes using both full scan and two-stage threshold-triggered mass modes. The secondary fragment ion information of the target compound was selected and compared with the compound reported in databases and related literatures to further confirm the possible compounds. A total of 47 chemical constituents were identified from the ethyl acetate extract of Zhideke granules, including 21 flavonoids and glycosides, 9 organic acids, 4 volatile components, 3 nitrogen-containing compounds, and 10 other compounds according to the fragmentation patterns, relevant literature, and MS data. The result provides a new method for the analysis of chemical constituents of Zhideke granules which laid the foundation for quality control and the study of pharmacodynamic materials of Zhideke granules.

Gynandropsis gynandra (L.) Briquet is a monoecious herb species in the family Cleomaceae. It is an important commercial crop with medicinal and nutritional values. Here, we sequenced, assembled, and analyzed the complete chloroplast genome of G. gynandra. The circular genome is 158,152 bp in size, consisting of two copies of inverted repeat (IR) regions of 26,181 bp, one large single-copy (LSC) region of 87,242 bp, and one small single-copy (SSC) region of 18,548 bp. The overall GC content was 35.81%. A total of 131 genes were annotated, including 37 tRNA genes, 87 protein-coding genes, and seven rRNA genes. Phylogenetic analysis based on 10 chloroplast genome sequences indicated that G. gynandra was more closely related to Tarenaya hassleriana.

Graphical abstract, Highlights • 743 eccDNAs were detected in Arabidopsis leaf, flower, stem and root tissues. • A large number of tRNAs and transposons were hosted by the eccDNAs. • eccDNAs have inverted repeats at upstream and downstream of the boundaries., Extrachromosomal circular DNA (eccDNA) is independent of the chromosome and exists in many eukaryotes. However, the nature and origin of eccDNA in plants remains unclear. In this study, we sequenced 12 samples from four tissues (leaf, flower, stem and root) with three biological replicates. In total, we found 743 eccDNAs found in at least two samples. Most of eccDNA have inverted repeats ranging from 4 to 12 bp in the boundaries. Interestingly, eccDNA is not only related to transposon activity, but also hosts tRNA genes, suggesting that the eccDNAs may be associated with tRNA abundance which controls protein synthesis under conditions of stress. Our results provide an unprecedented view of eccDNA, which is still naïve in scope.

The inflammatory cytokine IL-6 is known to play a causal role in the promotion of cancer, although the underlying mechanisms remain to be completely understood. Interplay between endogenous and environmental cues determines the fate of cancer development. The Eμ-myc transgenic mouse expresses elevated levels of c-Myc in the B cell lineage and develops B cell lymphomas with associated mutations in p53 or other genes linked to apoptosis. We generated Eμ-myc mice that either lacked the IL-6 gene, or lacked the STAT3 gene specifically in B cells to determine the role of the IL-6/JAK/STAT3 pathway in tumor development. Using the Eμ-myc lymphoma mouse model, we demonstrate that IL-6 is a critical tumor promoter during early stages of B cell lymphomagenesis. IL-6 is shown to inhibit the expression of tumor suppressors, notably BIM and PTEN, and this may contribute to advancing MYC-driven B cell tumorigenesis. Several miRNAs known to target BIM and PTEN are upregulated by IL-6 and likely lead to the stable suppression of pro-apoptotic pathways early during the tumorigenic process. STAT3, a classical downstream effector of IL-6, appears dispensable for Eμ-myc driven lymphomagenesis. We conclude that the growth-promoting and anti-apoptotic mechanisms activated by IL-6 are critically involved in Eμ-myc driven tumor initiation and progression, but the B cell intrinsic expression of STAT3 is not required.

BackgroundIndividual protective behaviors play an important role in the control of the spread of infectious diseases. This study aimed to investigate the adoption of protective behaviors by Chinese citizens amid the COVID-19 outbreak and its associated factors.MethodsAn online cross-sectional survey was conducted from 22 January to 14 February 2020 through Wenjuanxing platform, measuring their knowledge, risk perception, negative emotion, response to official communication, and protective behaviors in relation to COVID-19. A total of 3008 people completed the questionnaire, of which 2845 were valid questionnaires.ResultsOn average, 71% of respondents embraced protective behaviors. Those who made no error in the knowledge test (AOR = 1.77,p p p = 0.005), reported good health (AOR = 1.94,p p p ConclusionThe majority of Chinese citizens embraced protective behaviors. Higher levels of protective behaviors are associated with higher knowledge, perceived severity, negative emotion, and attention to and trust in the official governmental media. Official governmental communication is the largest single predictor of protective behaviors.

Objectives: The aim of this study was to explore and compare the customized sound therapy effect between tinnitus sound matching and nonmatching patients in tinnitus customized sound therapy and therapy-related influencing factors. Methods: This prospective study investigated a total of 100 patients with unilateral chronic tinnitus who received customized sound therapy. The participants were dichotomously divided into matching (group A) and nonmatching (group B) groups after 4 stages of tinnitus matching via the tinnitus assistant app (provided by Sound Ocean Company, SuZhou, China). Each group consists of 50 participants. Before and 6 months after the treatment, Hospital Anxiety and Depression Scale (HADS), tinnitus handicap inventory (THI), and tinnitus loudness Visual Analog Scale (VAS) were used to evaluate the customized sound therapy effect and explore other related influencing factors. Results: (1) The HADS-A, HADS-D, THI, and VAS scores of 2 groups were both significantly decreased after treatment. (2) The HADS-A and THI scores improved markedly in group A than that in group B, which could be related to the hearing loss of the tinnitus side ear before treatment; the lighter the degree of hearing loss, the better the improvement. No statistically significant differences were detected in HADS-D and VAS scores between the 2 groups, and also, these were not related to the degree of hearing loss. The differences in age, gender, and tinnitus duration did not show any statistically significant effect on the improvement of the 2 groups. Conclusions: Both tinnitus sound matching and nonmatching of the customized sound therapy brought a significant effect to tinnitus participants. Our study also suggests that THI and HADS-A scores of those with tinnitus matching participants improved markedly as compared to those of nonmatching participants, and the customized sound therapy effect is negatively correlated with the severity of hearing loss.

The frequent interruptions of network operation due to any incident suggest the necessity to study the rules of operational risk propagation in metro networks, especially under fully automatic operations mode. In this study, risk indicator computation models were developed by analyzing risk propagation processes within transfer stations and metro networks. Moreover, indicator variance rules for a transfer station and different structural networks were discussed and verified through simulation. After reviewing the simulation results, it was concluded that under the impacts of both sudden incident and peak passenger flow, the more the passengers coming from platform inlets, the longer the non-incidental line platform total train operation delay and the higher the crowding degree. However, train headway has little influence on non-incidental line platform risk development. With respect to incident risk propagation in a metro network, the propagation speed varies with network structure, wherein an annular-radial network is the fastest, a radial is moderately fast, and a grid-type network is the slowest. The conclusions are supposed to be supports for metro operation safety planning and network design.

Background Salivary interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Porphyromonas gingivalis (Pg) are related to periodontitis. This study aimed to investigate the diagnostic potential of these biomarkers and to build a prediction panel for diagnosing periodontal disease. Methods A total of 80 participants were enrolled in a cross-sectional study and divided into healthy (n = 25), gingivitis (n = 24), and periodontitis (n = 31) groups based on their periodontal exam results. A full mouth periodontal examination was performed and unstimulated saliva was collected. Salivary IL-1β, MMP-8, ICTP, and Pg were assessed using enzyme-linked immunosorbent assay (ELISA) and quantitative real time PCR (qPCR). Their potentials for diagnosing periodontal disease were analyzed and combined prediction panels of periodontal disease were evaluated. Results As a single marker, IL-1β showed the best diagnostic value of the four markers evaluated and exhibited an area under the curve (AUC) value of 0.88 with 90% sensitivity and 76% specificity for discriminating periodontitis subjects from healthy subjects, an AUC value of 0.80 with 83% sensitivity and 76% specificity for discriminating gingivitis subjects from healthy subjects and an AUC value of 0.66 with 68% sensitivity and 64% specificity for differentiating periodontitis subjects from gingivitis subjects. The combination of IL-1β, ICTP, and Pg exhibited the highest efficacy for discriminating periodontitis subjects from healthy subjects (AUC = 0.94) and gingivitis subjects (AUC = 0.77). The combination of IL-1β and MMP-8 exhibited the best ability to discriminate gingivitis from healthy subjects (AUC = 0.84). Conclusions Salivary IL-1β, MMP-8, ICTP, and Pg showed significant effectiveness for diagnosing periodontal disease. The combination of IL-1β, ICTP, and Pg can be used to discriminate periodontitis subjects from healthy subjects and gingivitis subjects, and the combination of IL-1β and MMP-8 can be used to discriminate gingivitis subjects from healthy subjects.

Objective: The aim of this study is to investigate the clinical efficacy of zoledronic acid (ZOL) in the treatment and prevention of osteoporotic vertebral compression fractures (OVCF) after percutaneous kyphoplasty (PKP) for elderly patients. Methods: The PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Embase were investigated through June 2020. All randomized controlled trials (RCT) involving ZOL injections for OVCF were enrolled. Outcome indicators included the bone mineral density (BMD), Visual Analog Scale (VAS), recompression vertebral fracture (RVF), Oswestry Disability Index (ODI), and bone metabolism (Procollagen type I N-terminal propeptide [PINP] and βcross-linked C-telopeptide of type I collagen [β-CTX]), bone cement leakage. Review Manager 5.3 was used to analyze these indicators. Results: In this study, (1) Eight studies had met the eligibility criteria, a total of 578 participants were involved (285 and 293 in the experimental (ZOL) group and control [no ZOL] group, respectively). (2) The BMD scores of patients with OVCF in the experimental group were significantly higher than that in the control group (P