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Background: Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown. Methods: Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using postn -promoter FMO2, miR1a/miR133a-FMO2 lentivirus, and enzymatic activity mutant FMO2 lentivirus after MI. Results: A significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 (small mothers against decapentaplegic 2/3) phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling. Conclusions: Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

Background Unfolded protein response (UPR), an orchestrating adaptive mechanism activated by endoplasmic reticulum (ER) stress, plays an instrumental protumoral roles in several kinds of cancers, and high unfolded protein response is correlated to poorer prognosis and malignant hallmark. Considerable evidence indicates that UPR induced by oncogenic conditions is a distinguishing feature of cancer. Methods Bioinformatics mining was carried out by using the public pancer data of TCGA and other public databases to analyze the differential gene expression profiles of the patients and Cox regression analysis to find out the differentially expressed endoplasmic reticulum stress related genes with prognostic value. ER-stress Potential Index (EPI) was defined to computationally dissect the UPR trends via gene set enrichment analysis using R package ‘GSVA’. Combined with TCGA and GEO databases, the clinical characteristics of EPI were comprehensively analyzed in LIHC. Virtual screening was performed to find out potential compounds targeting STC2, which was a good diagnostic marker and pharmacological target towards endoplasmic reticulum stress in LIHC. Results Pan-cancer analysis results showed that unfolded protein response pathway was generally positive associated with poor prognosis of patients across different cancer types. It would be an important and ubiquitous mechanism in different tumors. High EPI was positive associated with tumor malignant phenotype, including higher death rate, recurrence rate, metastatic risk, larger tumor size and other undesirable aggressive clinical traits. In addition, EPI was also responsible for immune evasion via upregulating the expression of immunosuppressive gene and facilitating the production of pro-inflammatory and immunomodulatory cytokines. Besides, EPI played pivotal role in liver cancers’ resistance of chemotherapy and therapeutic targeting UPR would be enhance the anti-tumor effectiveness. STC2 would be a good diagnostic marker and pharmacological target in LIHC. Through virtual screening, we found that flavonoids compounds could be a good compound targeting STC2. Flavonoids could become a good pharmaceutical therapeutic candidate in unique or adjuvant therapeutic approaches toward LIHC. Conclusion EPI was associated with subtypes and clinical features and providing new insight into tumor biology and can guide efficient pharmalogical intervention of unfolded protein response to help patients.

Background Impaired respiratory function caused by respiratory muscle dysfunction is one of the common consequences of chronic obstructive pulmonary disease (COPD). In this study, two-dimensional shear wave elastography (2D-SWE) was used to measure diaphragm stiffness (DS) and intercostal muscle stiffness (IMS) in patients with COPD; in addition, the value of 2D-SWE in evaluating respiratory function was determined. Methods In total, 219 consecutive patients with COPD and 20 healthy adults were included. 2D-SWE was used to measure the DS and IMS, and lung function was also measured. The correlation between respiratory muscle stiffness and lung function and the differences in respiratory muscle stiffness in COPD patients with different severities were analysed. Results 2D-SWE measurements of the DS and IMS presented with high repeatability and consistency, with ICCs of 0.756 and 0.876, respectively, and average differences between physicians of 0.10 ± 1.61 and 0.07 ± 1.65, respectively. In patients with COPD, the DS and IMS increased with disease severity (F1 = 224.50, F2 = 84.63, P 1)/forced vital capacity (FVC), predicted FEV1% value, residual volume (RV), total lung capacity (TLC), RV/TLC, functional residual capacity (FRC) and inspiratory capacity (IC) of DS (r1=-0.81, r2=-0.63, r3 = 0.65, r4 = 0.54, r5 = 0.60, r6 = 0.72 and r7=-0.41, respectively; P 1=-0.76, r2=-0.57, r3 = 0.57, r4 = 0.47, r5 = 0.48, r6 = 0.60 and r7=-0.33, respectively; P Conclusion 2D-SWE has potential for use in evaluating DS and IMS. A specific correlation was observed between respiratory muscle stiffness and lung function. With the worsening of the severity of COPD and the progression of lung function impairment, the DS and IMS gradually increased.

Computer-assisted Surgery system (CAS) is an effective medical imaging simulation tool, which is widely used in preoperative planning of surgery. The objective of this study is to investigate the clinical application of CAS in pediatric mediastinal tumor resection.This retrospective study investigated 74 children who underwent mediastinal tumor resection between June 2008 and June 2022 at the pediatric surgical center of the Affiliated Hospital of Qingdao University and Qingdao Women and Children's Hospital. Preoperative chest computed tomography imaging was performed on all children. A total of 44 children (the CAS-assisted group) underwent clinical image 3D reconstruction and preoperative simulation using Hisense CAS. The control group consisted of 30 children who underwent a conventional procedure without CAS. The demographic, preoperative, and complication data were analyzed and compared between the two groups. t-test, Mann-Whitney U test, XThe median operative duration was 119.00 min in the CAS-assisted group and 140.50 min in the control group. The median intraoperative blood loss of the CAS-assisted group and the control group was 14.00 and 31.00 ml respectively. Relative to the control groups, the CAS-assisted group experienced shorter operative duration time (p = 0.041), and less intraoperative blood loss (p 0.001). The difference in postoperative drain indwelling between the CAS-assisted group (median:4.00 days) and the control group (median:7.00 days) reached a statistical significance (p = 0.001). And the duration of hospitalization after the operation for the CAS-assisted group (median:7.00 days) was shorter than that for the control group (median:9.00 days) (p = 0.001). No significant difference could be found in the rate of blood transfusion (p = 0.258) and the incidence of postoperative complications (p = 0.719) between the two groups.Hisense CAS could effectively assist surgeons to clearly determine the anatomical site of tumors and provide accurate preoperative simulation for surgeons, so as to assist surgeons to specify effective surgical plans for patients.

Ubiquitin-specific peptidases7 (USP7) participates in the regulation of various metabolic and immune disorders. However, the role of USP7 in lupus nephritis (LN) remains unknown. The current study set out to elucidate the regulatory role of USP7 in LN together with JMJD3 and NF-κB. SLE MRL/LPR mice and mouse glomerular mesangial cells SV40 MES 13 cells were employed for in vivo or vitro experiments. USP7, JMJD3 and NF-κB expression in MRL/LPR mice were detected, followed by investigation of their functions in the proliferation of mesangial cells and mesangial matrix. Subsequently, the interaction among USP7, JMJD3 and NF-κB was determined by means of ChIP and co-immunoprecipitation assay. The results indicated that USP7, JMJD3, p-NF-κB p65 were all highly-expressed in MRL/LPR mice. USP7 promoted the proliferation of mesangial cells and mesangial matrix, and stabilized the JMJD3 protein via deubiquitination in SV40 MES 13 cells. Meanwhile, silencing of JMJD3 inhibited the promotive effect of USP7 on the proliferation of mesangial cells and mesangial matrix. Furthermore, JMJD3 increased the expression of NF-κB p65 through demethylation, whereas silencing JMJD3 alleviated the proliferation of mesangial cells and mesangial matrix. Lastly, NF-κB p65 was proved to aggravate LN pathogenesis. Altogether, our findings highlighted that USP7 promoted the occurrence of LN by regulating the NF-κB p65 signaling pathway via stabilization of JMJD3.

BackgroundDiabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes and the strongest initiating risk factor for diabetic foot ulceration. Early diagnosis of DPN through screening measures is, therefore, of great importance for diabetic patients. Recently, shear wave elastography (SWE) has been used as a method that is complementary to neuroelectrophysiological examination in the diagnosis of DPN. We aimed to conduct a meta-analysis based on currently available data to evaluate the performance of tibial nerve stiffness on SWE for diagnosing DPN.MethodsBoth PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for studies that investigated the diagnostic performance of SWE for DPN up to March 1th, 2022. Three measures of diagnostic test performance, including the summary area under receiver operating characteristics curve (AUROC), the summary sensitivity and specificity, and the summary diagnostic odds ratios were used to assess the diagnostic accuracy of SWE. All included studies were published between 2017 and 2021.ResultsSix eligible studies (with 170 DPN patients, 28 clinically defined DPN patients, 168 non-DPN patients, and 154 control participants) that evaluated tibial nerve stiffness were included for meta-analysis. The summary sensitivity and specificity of SWE for tibial nerve stiffness were 75% (95% confidence interval [CI]: 68–80%) and 86% (95% CI: 80–90%), respectively, and the summary AUROC was 0.84 (95% CI: 0.81–0.87), for diagnosing DPN. A subgroup analysis of five two-dimensional SWE studies revealed similar diagnostic performance, showing the summary sensitivity and specificity of 77% (95% CI: 69–83%) and 86% (95% CI: 79–91%), respectively, and a summary AUROC value of 0.86 (95% CI: 0.83–0.89).ConclusionsSWE is found to have good diagnostic accuracy for detecting DPN and has considerable potential as an important and noninvasive adjunctive tool in the management of patients with DPN.

Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown.Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted usingA significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling.Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

The adsorption/desorption process of flavonoids obtained from bamboo shoots residues of

Background: In recent years, the prevalence and mortality of autism spectrum disorder (ASD) have been increasing. The clinical features are different with different cases, so the treatment ways are different for each one. Objective: Baohewan Heshiwei Wen Dan Tang (BHWDT) has been recommended for treating autistic spectrum disorder. To investigate the mechanism of action and how the compounds interact with ASD targets, network pharmacology and molecular docking methods were used in this study. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the active components according to index of oral bio-activity and drug-likeness. Then, TCMSP and Swiss Target Prediction databases were used to screen potential target genes of active components. The related target genes of ASD were obtained from the Gene Cards database. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. Composition- target-pathway (C-T-P) and a protein-protein interaction (PPI) networks were built with Cytoscape 3.8.2 software. Results: The interaction of the main active components of BHWDT was verified by molecular docking. The key targets of MAPK1, IL6, CXCL8 and TP53 of BHWDT were obtained. The key active components Quercetin, Kaempferol and Iuteolin of BHWDT could bind with MAPK1, IL6, CXCL8 and TP53 of BHWDT, respectively. Conclusion: BHWDT can be highly effective for treating ASD and this study can help us to understand multiple targets and multiple pathways mechanism.

CD36 plays a critical role in lipid metabolism, which is closely associated with human immunity. However, the role of CD36 in cancer remains unclear. We performed a pan-cancer analysis to elucidate the potential role of CD36 in cancer by investigating its prognostic value and current predictors for the efficacy of immune checkpoint inhibitors (ICIs) in multiple cancer types. CD36 expression in cancer cell lines, tumor tissue, and their adjacent normal tissues displayed heterogeneity among different cancers. Immunohistochemistry was used to detect CD36 expression and confirmed the results. CD36 expression significantly affects prognosis in the six cancer types. High CD36 expression was marginally associated with poorer prognosis in four of them and improved prognosis in the remaining two types. CD36 expression was significantly correlated with the 6 immune infiltrates in most cancer types. In addition, CD36 gene expression was positively correlated with Stromal score, Immune score, and ESTIMATE score. A total of 47 immune checkpoint genes were collected and their relationship with CD36 expression was analyzed. CD36 expression was significantly associated with multiple stimulatory and inhibitory checkpoint molecules with a disease-specific pattern. As to the genes reported to positively relate to the efficacy of ICIs, CD36 expression was positively correlated with most of them but negatively associated with a small proportion of cancer type-specific patterns. Concerning the genes negatively related to the efficacy of ICIs, CD36 expression was positively correlated with NRP1 and TNFSF15 in multiple cancers. CD36 expression was negatively correlated with tumor neoantigen burden in most cancer types. However, CD36 expression was negatively correlated with tumor mutation burden in most cancer types. The correlation between CD36 expression and the four methyltransferases was also significant in multiple cancers, but also with a cancer type-specific pattern. In summary, the current study found CD36 expression and its prognostic value in multiple cancer types. In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs. The practical application value of CD36 is disease specific.

The utilization of bamboo industry exhibits varied but still needs to be improved. Bamboo leaf flavonoid (BLF) is an important resource of bamboo which has become a research focus. However, the isolation and purification techniques of four flavonoid carbon glycosides (orientin, isoorientin, vitexin, and isovitexin) from BLF were still confronted with difficulties due to their complex and similar structures, which obstructed the development of bamboo utilization. In this article, a purification technology of four flavonoid carbon glycosides from BLF by Sephadex LH-20 was improved. The results were evaluated by HPLC and pharmacological activity. Specifically, the eluent, flow rate, and loading amount were investigated, respectively. According to the results, the eluent would dominate the isolation effect among three factors. High concentration of isoorientin and four flavonoid carbon glycosides would be obtained under the optimized condition (The eluent was 70 % methanol, the loading amount was 1.5 g, and the flow rate was 0.5 mL/min). Meanwhile, the link between flavonoid carbon glycosides content and their antioxidant activity in vitro was also revealed. Overall, the results suggested that BLF may serve as potential functional food additives and medicine.

The aim of this study was to test the effectiveness, safety and stability of the 5G communication technology in clinical laparoscopic telesurgery.An ultra-remote radical cystectomy (network communication distance of nearly 3000 km) was performed on patient diagnosed with T2N0M0 stage bladder cancer using a domestically produced "MicroHand" surgical robot.The network delay, operative time, blood loss, intraoperative complications, postoperative recovery, and hospitalisation time were recorded. The 5G network was used throughout the operation, with an average total delay of 254 ms. The operation went well and the patient recovered smoothly.Ultra-remote clinical laparoscopic surgery can be performed safely and smoothly. More importantly, our model can provide insights for promoting the future development of telesurgery in China.

Background The measurement of liver stiffness (LS) and spleen stiffness (SS) based on ultrasound elastography can be used for non-invasive assessment of portal hypertension (PH). However, there are few studies on the corresponding mechanism of increased spleen stiffness. Our aim was to use two-dimensional shear wave elastrography (2D-SWE) to evaluate the relationship between LS and SS and the severity of PH in rats. And explore the mechanism of the increase of LS and SS in PH. Methods Sixty male Sprague–Dawley rats were randomly divided into portal hypertension (PH group, n = 45) and normal control (NC group, n = 15). At 12 weeks, LS and SS was detected by 2D-SWE in vivo. Related hemodynamic parameters and portal vein pressure (PVP) was measured. Spleen and liver 2D-SWE detection was performed again after sacrifice. Pathological changes were observed. Results The SS and LS were increased in PH group (P P r = 0.624, P r = 0.633, P r = 0.905, P Conclusions Spleen and liver measurement by 2D-SWE may be helpful in evaluating PVP. The correlation between SS and PVP is stronger than LS in rats measured by 2D-SWE. Hemodynamic circulation are important in the elevation of SS with portal hypertension. Pathological changes also have a degree of influence, but have more significance for the elevation of LS. SS may be a more effective noninvasive predictor of PH than LS.

In arid ecosystems, where the soil is directly exposed to the action of the wind due to sparse vegetation, dust aerosolization is a consequence of soil degradation and concomitantly, a major vector of microbial dispersal. Disturbances such as livestock grazing or fire can exacerbate wind erosion and dust production. Here, we sampled surface soils in 29 locations across an arid landscape in southwestern USA and characterized their prokaryotic and fungal communities. At four of these locations, we also sampled potential fugitive dust. By comparing the composition of soil and dust samples, we determined the role of dust dispersal in structuring the biogeography of soil microorganisms across the landscape. For Bacteria/Archaea, we found dust associated taxa to have on average, higher regional occupancies compared to soil associated taxa. Complementarily, we found dust samples to harbour a higher amount of widely distributed taxa compared to soil samples. Overall, our study shows how dust dispersal plays a role in the spatial distribution of soil Bacteria/Archaea, but not soil Fungi, and might inform indicators of soil health and stability in arid ecosystems.

BackgroundMeasurement of hepatic venous pressure gradients is the gold standard for assessing portal hypertension (PH) but is invasive with potential complications. We aimed to assess the performance in liver and spleen stiffness measurement (LSM and SSM, respectively) by two-dimensional shear wave elastography (2D-SWE) and composite scores including liver stiffness-spleen diameter to platelet ratio score (LSPS), platelet (PLT) count/spleen diameter ratio (PSR), aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), and AST-to-PLT ratio index (APRI) for diagnosing PH in nonalcoholic fatty liver disease (NAFLD) rat models.MethodsAnimal models with PH in NAFLD were established in 65 rats, which then underwent 2D-SWE measurements. Morphological and biological parameters were collected for calculation of four composite scores. Correlations of noninvasive methods with portal venous pressure were evaluated by Spearman correlation analysis. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of noninvasive methods in predicting PH.ResultsLSM and SSM were significantly associated with portal venous pressure (r = 0.636 and 0.602, respectively; all P < 0.001). The AUCs of LSM and SSM in the diagnosis of PH were 0.906 (95% confidence interval [CI]:0.841–0.97) and 0.87 (95% CI:0.776–0.964), respectively, and were significantly higher than those in composite scores. The AUCs for LSPS, PSR, AAR, and APRI were 0.793, 0.52, 0.668, and 0.533, respectively, for diagnosing PH. The AUCs of the combined models of LSM and SSM, LSM and PLT, SSM and PLT, and LSM, SSM and PLT were 0.923, 0.913, 0.872, and 0.923, respectively. The four combined models showed no statistical differences compared to LSM and SSM in evaluating PH (all P > 0.05).ConclusionsLSM and SSM by 2D-SWE can be used as promising noninvasive parameters for diagnosing PH in NAFLD and have higher accuracy than composite scores. The combined models, compared to LSM and SSM, did not significantly improve the performance in diagnosing PH.

Microbes, similar to plants and animals, exhibit biogeographic patterns. However, in contrast with the considerable knowledge on the island biogeography of higher organisms, we know little about the distribution of microorganisms within and among islands. Here, we explored insular soil bacterial and fungal biogeography and underlying mechanisms, using soil microbiota from a group of land-bridge islands as a model system. Similar to island species-area relationships observed for many macroorganisms, both island-scale bacterial and fungal diversity increased with island area; neither diversity, however, was affected by island isolation. By contrast, bacterial and fungal communities exhibited strikingly different assembly patterns within islands. The loss of bacterial diversity on smaller islands was driven primarily by the systematic decline of diversity within samples, whereas the loss of fungal diversity on smaller islands was driven primarily by the homogenization of community composition among samples. Lower soil moisture limited within-sample bacterial diversity, whereas smaller spatial distances among samples restricted among-sample fungal diversity, on smaller islands. These results indicate that among-island differences in habitat quality generate the bacterial island species-area relationship, whereas within-island dispersal limitation generates the fungal island species-area relationship. Together, our study suggests that different mechanisms underlie similar island biogeography patterns of soil bacteria and fungi.

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by abnormal T and B cells. B-cell activating factor (BAFF) has been suggested to play a crucial role in lupus by promoting the proliferation, differentiation, and survival of B cells. Increased serum levels of BAFF have been found in patients with lupus. However, the expression of BAFF and its receptors on immune cells and in skin has not been systematically reported before. Here, we report that SLE patients showed increased levels of BAFF on circulating CD3+ T cells and B-cell maturation antigen (BCMA) on CD14+ monocytes and dramatically increased expression of BAFF in lupus skin lesions compared with those of healthy controls. TACI was undetectable on circulating immune cells. An increased serum level of BAFF was also confirmed in lupus patients in this study. Our findings may provide a better understanding of the pathogenesis and predictors of BAFF antibody treatment response, as well as potential targets for skin therapies.

The aim of the work described here was to investigate the value of point-of-care ultrasound (POCUS) in the early assessment of the severity of pulmonary edema in rabbits. A rabbit oleic acid (OA)-induced pulmonary edema model was used. Thirty-two New Zealand rabbits were randomly divided into four groups: a control group and three pulmonary edema groups (mild, moderate and severe). Features of transthoracic B-line artifacts (BLA), blood pH, PaO2 and PaCO2, serum inflammatory factors, lung coefficient (LC), lung wet-to-dry weight ratio (W/D) and lung histopathology were assessed. BLA features and severity of pulmonary edema were semiquantitatively scored. Correlations between the number of BLA and PaO2, PaCO2, serum inflammatory factors, LC and W/D were analyzed. An additional 8 rabbits with severe pulmonary edema were used as the verified group, in which the lung was divided into ex vivo BLA (BLA-ev)-free (BLA-ev-free) and BLA-ev-clustered subregions depending on the features of BLA-ev recorded by ex vivo lung ultrasound. Lung specimens from each subregion were collected for histopathological examination. Relationships between features of BLA-ev and lung histopathological abnormalities were analyzed. With increasing doses of OA, number of BLA, W/D and levels of serum inflammatory factors decreased. Meanwhile, lung pathologic abnormalities were aggravated. In addition, time of appearance of BLA, blood pH and PaO2, and PaCO2 decreased dose dependently on OA (p

IgE multiple myeloma (MM) is a rare subtype of MM that is easily misdiagnosed. We report a rare case of IgE-MM and investigate the application of the SLiM-CRAB criteria to screen for high-risk smoldering MM (SMM) patients, so as to summarize the causes and methods used to prevent missed diagnosis or misdiagnosis in IgE-MM.The serum monoclonal protein (M-protein) classification and IgE quantification was performed and sent to several individual institutions. The results were collected and the causes of IgE detection defects were analyzed.Upon admission to our hospital, the patient's serum free kappa light chain was 1069.9 mg/L, free lambda light chain was 9.2 mg/L, and free kappa/lambda ratio was 115.9, which met the SLiM criteria, but without CRAB features. Immunofixation electrophoresis (IF) showed "M-like protein aggregation bands" in all lanes. After pretreatment with 1% β-mercaptoethanol to depolymerize the aggregation of monoclonal protein, the "M-like protein aggregation bands disappeared. The other five institutions did not provide the correct typing results. The quantification of serum IgE was as high as 2.06 × 10High-risk biomarkers in SLiM criteria can achieve good therapeutic effects in rare IgE-MM patients. Serum immunofixation performed without antisera against IgE, insufficient identification of the lytic bands produced by high macromolecule aggregation in IF, and the absence of a prozone effect avoidance procedure during IgE quantitative detection are the primary causes of missed diagnosis or misdiagnosis in patients with IgE-MM.

Low molybdenum (Mo) bioavailability in acidic soil obstructs vegetable nitrogen assimilation and thus increases the health risk of vegetable ingestion due to nitrate accumulation. Constantly providing available Mo in acidic soil is a challenge for decreasing nitrate accumulation in vegetables. In this study, three Mo application methods, including biochar-based Mo slow-release fertilizer (Mo-biochar), seed dressing, and basal application, were investigated to enhance Mo bioavailability in acidic soil and nitrogen assimilation in Chinese flowering cabbage (Brassica parachinensis). The results showed that Mo-biochar constantly and sufficiently supplied Mo nutrients throughout the growing period of Brassica parachinensis, as evidenced by the soil available Mo, plant Mo uptake, and Mo values. The improved Mo supply was attributed to the alleviation of acidic soil (pH from 5.10 to 6.99) and the slow release of Mo adsorbed on biochar. Mo-biochar increased the nitrate reductase (NR) activity by 238.6% and glutamate dehydrogenase activity by 27.5%, indicating an enhancement of the rate-limiting steps of nitrogen assimilation, especially for nitrate reduction and amino acid synthesis. The increase in Mo-containing NR could be directly ascribed to the high level of Mo in Brassica parachinensis. Compared with the control, the nitrate content of Brassica parachinensis decreased by 42.9% due to the nitrate reduction induced by increased NR. Additionally, Mo-biochar was beneficial to vegetable growth and quality. In contrast, the transformation from NO

Directed by the strategy of C–H activation, an efficient construction of the isatin skeleton was developed through aerobic oxidation of glycine esters. The reactions were performed under CF3COOH/O2 conditions in the absence of metal catalysts. The reaction mechanisms were investigated with control experiments.

Summary Among all the solutions to improve long-term stability of perovskite solar cells, p-i-n heterojunction with all-metal-oxide charge transporting layers show their attractive features. However, these devices require an efficient electron-transporting layer (ETL) fabricated on top of the perovskites in which the commonly used oxide nanocrystals are limited by their imperfect surface. Here, a novel surface-passivation strategy was adopted by anchoring ZnO nanoparticles with fullerene nano-shells (Fa-ZnO) to mitigate trap states and passivate surface hydroxyl groups. We evidence the Fa-ZnO can be easily processed on top of perovskite as a high-quality ETL that improves electron extraction efficiency and suppresses ion diffusion/moisture penetration. In addition, the presence of fullerene shells allows Fa-ZnO nanoparticles to penetrate into perovskite precursors before crystallization, resulting in n-type sensitized configuration. With mesoscopic NiOx as hole-collecting contact, the p-n dual sensitization configuration has enabled all-metal-oxide devices to achieve state-of-the-art efficiencies of 21.1% with greatly improved performance longevity.

To optimize a screening method for macroprolactinemia and improve the accuracy of free prolactin (freePRL) detection.Overall efficiency, calculated as the product of the immunoglobulin G (IgG) precipitation rate and the freePRL recovery rate were employed to determine the concentration of the precipitant polyethylene glycol (PEG). Then, an optimized screening method for macroprolactinemia was established. The concentrations of freePRL, obtained by gel filtration chromatography (GFC), from 66 cases were used as the gold standard, and the sensitivity, specificity, accuracy and precision of the optimized and traditional methods for detecting macroprolactinemia were compared.(1) The IgG precipitation rate increased with increasing PEG6000 concentration, and the freePRL recovery rate decreased with increasing PEG6000 concentration; the overall efficiency first increased and then decreased. When the IgG concentrations in the mixture were 10 g/L, 25 g/L and 40 g/L, the concentrations of PEG6000 with the highest overall efficiency were 24%, 20% and 18%, respectively. (2) The effect of high and low IgG on the overall efficiency was 4.7% when using 20% PEG6000, which was lower than the effects when using 18% or 24% PEG6000 (9.2% and 13.2%). (3) In the optimized method established using 20% PEG6000, the macroprolactin (macroPRL) chromatographic peak disappeared, but the freePRL chromatographic peak was retained. The sensitivity of this macroprolactinemia screening method was 96.7%, and the specificity was 100%. (4) The freePRL concentrations obtained by the optimized method for samples from 30 macroprolactinemia cases and 36 true hyperprolactinemia cases were 15.8 (10.2-21.4) ng/mL and 60.2 (51.8-79.9) ng/mL; the concentrations were similar to those obtained using the GFC method (16.3 (11.9-27.2) ng/mL and 68.1 (49.5-92.9) ng/mL, respectively (p0.05)) and higher than those obtained using the traditional method (9.1 (6.1-17.6) ng/mL and 51.4 (43.7-71.9) ng/mL), respectively, p0.05)). (5) The relative deviation between the optimized and GFC methods was -7.0%, which was significantly lower than the relative deviation between the traditional and GFC methods (-21.4%, p0.01). (6) The in-batch coefficients of variation (CVs) for the dual-level quality control materials measured by the optimized method were 1.88% and 1.87%, and the within-laboratory CVs were 2.55% and 2.29%, which were slightly lower than the in-batch CVs (1.93% and 2.81%) and within-laboratory CVs (2.75% and 2.81%) measured by the traditional method.The established optimized method for screening macroprolactinemia using 20% PEG6000 as a precipitant can completely precipitate macroPRL components and effectively retain freePRL components. Compared with traditional methods, the optimized method is simpler, more accurate and more stable for the quantitative detection of freePRL.

Background: The clinical benefit of chemotherapy or endocrine therapy maintenance in patients with metastatic breast cancer (MBC) after first-line chemotherapy, specifically hormone receptor (HR) positive MBC patients remain inconclusive. This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in MBC patients. Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matched analysis of multicentre cohort study in China were evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. The GRADE approach was used to assess quality of evidence in meta-analysis. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Findings: A total of 2,867 patients from 15 RCTs and 760 patients from multicentre cohort were included. The results from meta-analysis showed that chemotherapy maintenance significantly improved PFS (hazard ratio [HR], 0·63; 95% confidence interval (CI) 0·54-0·73; P 0·05). Additionally, treatment effect sizes were greater for OS than for PFS, and a moderate correlation between PFS and OS was identified. Interpretation: This study provided a high evidence for PFS and OS benefits of longer first-line chemotherapy and endocrine therapy maintenance in MBC patients, and there were no difference efficacy between chemotherapy and endocrine therapy maintenance for HR-positive patients. We also suggested that both PFS and OS should be evaluated to determine the effectiveness of maintenance therapy in future clinical trials. Trial Registration: This study is registered with PROSPERO Identifier: CRD42017071858, and ClinicalTrials.gov Identifier: NCT04258163. Funding Statement: This study was supported by grant 2020ZX09201021 from the National Science and Technology Major Project, grant YXRGZN201902 from the Medical Artificial Intelligence Project of Sun Yat-Sen Memorial Hospital, grants 81572596, 81972471, U1601223, 82073408, 81802656, and 82071754 from the National Natural Science Foundation of China, grant 2017A030313828 from the Natural Science Foundation of Guangdong Province, grant 201704020131 from the Guangzhou Science and Technology Major Program, grant 2017B030314026 from the Guangdong Science and Technology Department, grant 2018007 from the Sun Yat-Sen University Clinical Research 5010 Program, grant SYS-C-201801 from the Sun Yat-Sen Clinical Research Cultivating Program, and A2020558 from the Medical Scientific Research Foundation of Guangdong Province. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

In order to improve the seismic performance of long-span double deck steel truss continuous girder bridge, taking Dao Qing Chau Bridge in Fuzhou as an engineering background, the isolation scheme of friction pendulum bearing (FPB) and friction pendulum bearing combined with viscous dampers is applied to study seismic performance. A three-dimensional dynamic model of the bridge is established using SAP2000. Taking three artificial seismic waves as seismic excitation, the seismic response of the seismic structure is calculated by nonlinear time history integration, and is then compared with the seismic response of the seismic reduction and isolation structure. The results show that the friction pendulum bearing (FPB) scheme and combined seismic dissipation and isolation (CSDI) scheme show a good seismic dissipation and isolation effect and ensure the safety of the bridge structure. However, for whole-bridge isolation, friction pendulum bearing (FPB) will produce certain residual deformations and additional stress of the bearing under the conditions of temperature and external load. For the purpose of protecting the bearing, it is recommended to use the combined seismic dissipation and isolation (CSDI) scheme.

In current clinical practice, the standard evaluation for axillary lymph node (ALN) status in breast cancer is based on the invasive procedure and many patients will suffer from operative associated complications. Hence, a novel signature incorporated tumor and lymph node magnetic resonance imaging (MRI) radiomics, clinical and pathological characteristics, and molecular subtypes based on the machine learning approach was established to accurately identify ALN metastasis in early-stage invasive breast cancer patients. Although the misjudgment of ALN status by clinicians according to preoperative MRI are common during clinical practice and even the senior radiologists make mistakes sometimes, this multiomic radiomic signature showed the superiority over clinicians and could precisely discriminate ALN metastasis among different molecular subtype patients. Furthermore, the association between MRI radiomic features and tumor-microenvironment features including immune cells, long non-coding RNAs, and types of methylated sites were found, which revealed the potential biological underpinning of MRI radiomics.

There are no satisfying approaches to identify high- and low-risk recurrence patients with early-stage breast cancer in current clinical practice. Patients might be overtreated or undertreated due to the inaccurate prediction of recurrence risk. Herein, machine learning magnetic resonance imaging radiomic-based signature that integrates the intratumoral and peritumoral radiomic signatures, and clinicopathological characteristics was developed to classify high- and low-risk recurrence patients and predict recurrence within multicentre cohorts. The radiomic-clinical signature could also discriminate high- from low-risk recurrence patients among different breast cancer molecular subtype, and HR+/Her2-, T1N0M0 stage patients. Furthermore, it was observed that the neoadjuvant chemotherapy improved survival in high-risk Luminal subtype patients compared with the adjuvant chemotherapy. The survival-associated radiomic features also showed the correlation with the immune microenvironment. The radiomic-clinical signature presented the feasibility of predicting recurrence risk and assisting clinical decision-making in early-stage invasive breast cancer patients.

In order to reduce the pollution of electric vehicle charging modules to power grid and improve the disadvantages of low efficiency, low power and low system reliability, a multi-charging module design scheme based on average current method was proposed. The proposed module consists of three-phase VIENNA rectifying circuit with a high power factor and LLC resonant converter. The one cycle control strategy is adopted to realize the power factor correction of the front stage and reduce the pollution caused by harmonics. The control strategy of average current method is adopted between modules to ensure the same output current of each charging module. In this paper, the working principle and control strategy of each module are analyzed. At last, two 4KW experimental prototypes are developed, and the feasibility of the multi-charge module scheme designed in this paper is verified through experiments.

The overwhelming taxonomic diversity and metabolic complexity of microorganisms can be simplified by a life-history classification; copiotrophs grow faster and rely on resource availability, whereas oligotrophs efficiently exploit resource at the expense of growth rate. Here, we hypothesize that community-level traits inferred from metagenomic data can distinguish copiotrophic and oligotrophic microbial communities. Moreover, we hypothesize that oligotrophic microbial communities harbor more unannotated genes. To test these hypotheses, we conducted metagenomic analyses of soil samples collected from copiotrophic vegetated areas and from oligotrophic bare ground devoid of vegetation in an arid-hyperarid region of the Sonoran Desert, Arizona, USA. Results supported our hypotheses, as we found that multiple ecologically informed life-history traits including average 16S ribosomal RNA gene copy number, codon usage bias in ribosomal genes and predicted maximum growth rate were higher for microbial communities in vegetated than bare soils, and that oligotrophic microbial communities in bare soils harbored a higher proportion of genes that are unavailable in public reference databases. Collectively, our work demonstrates that life-history traits can distill complex microbial communities into ecologically coherent units and highlights that oligotrophic microbial communities serve as a rich source of novel functions.