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Defect detection tasks of solid propellants (SPs), involving size, shape, and surface defects, are essential for ensuring the quality of many industrial products. Developing separate models for three tasks, however, is complicated and inefficient due to the redundant deployment. Multitask learning (MTL), with its potential for knowledge sharing, may greatly reduce the space and power consumption, but still faces the challenges of destructive interference and empirical tradeoffs between tasks. To this end, a novel end-to-end network for multidefect detection of SPs is put forth: 1) a new setting for MTL without any empirical tradeoffs is introduced, in which the knowledge is shared while the models are not visible to each other among diverse tasks; 2) in this setting, a bilateral feature extractor is constructed to extract both low- and high-level features, and a feature fusion module is further exploited to encourage each task to adaptively learn the task-specific knowledge; 3) an end-to-end training manner with a dynamic balance strategy and a gradient stop-flow strategy is designed to ensure that different tasks can benefit from, but do not interfere with, each other; 4) the introduction of semantic knowledge from the size detection branch enables the surface detection branch to learn semantic features beyond only pixel-to-pixel mapping. A smoothness construction loss is further designed to boost the performance of the surface detection task. Experimental results on an image dataset from a real-world manufacturing line show that the setting for MTL has the superiority in terms of the model size, inference speed, and detection accuracy.

Integrated circuit (IC) marking inspection is a crucial task to ensure product quality in electronics manufacturing. Due to the diversity of marking appearance, high environmental complexity, and massive annotation costs, it is, however, still a great challenge to accurately recognize IC markings in a real-time fashion at some production stages, such as surface mount technology (SMT). In this article, an end-to-end deep learning model with three branches is put forth for IC marking inspection. The saliency activation branch provides powerful shared feature representation, and by incorporating with the weakly supervised mechanism, it can generate precise character localization information with coarse-grained annotation. The direction recognition and character recognition branches utilize shared saliency maps to sample word-level and character-level features, respectively, such that the network can properly recognize markings in different orientations, and especially perform well on the chips with multidirectional markings. The proposed character box refinement method allows the network to adapt to tiny size and tight-layout IC markings, and a new loss function called ED-Loss is designed for error estimation between the unaligned sequences. Experiments on a real SMT chip dataset with highly diverse IC images show that the model reaches a recall rate of 96.34%, with an inspection speed close to 30 fps. The comparative experiments with the state-of-the-art models demonstrate that our model has superior performances in terms of accuracy, efficiency, and adaptability.

Tubular epithelial cells (TECs) exposed to hypoxia incite tubulointerstitial inflammation (TII), while the exact mechanism is unclear. In this study, we identified that hypoxia evoked tubule injury as evidenced by tubular hypoxia-inducible factor-1α and kidney injury molecule-1 (KIM-1) expression and that renal small extracellular vesicle (sEV) production was increased with the development of TII after ischemia-reperfusion injury (IRI). Intriguingly, KIM-1-positive tubules were surrounded by macrophages and co-localized with sEVs. In vitro, KIM-1 expression and sEV release were increased in hypoxic TECs and the hypoxia-induced inflammatory response was ameliorated when KIM-1or Rab27a, a master regulator of sEV secretion, was silenced. Furthermore, KIM-1 was identified to mediate hypoxic TEC-derived sEV (Hypo-sEV) uptake by TECs. Phosphatidylserine (PS), a ligand of KIM-1, was present in Hypo-sEVs as detected by nanoflow cytometry. Correspondingly, the inflammatory response induced by exogenous Hypo-sEVs was attenuated when KIM-1was knocked down. In vivo, exogenous-applied Hypo-sEVs localized to KIM-1-positive tubules and exacerbated TII in IRI mice. Our study demonstrated that KIM-1 expressed by injured tubules mediated sEV uptake via recognizing PS, which participated in the amplification of tubule inflammation induced by hypoxia, leading to the development of TII in ischemic acute kidney injury.

A highly site-selective trifluoromethylaminoxylation of activated and unactivated olefins was reported under metal-free conditions. The method provides direct access to diverse β-trifluoromethyl trisubstituted hydroxylamines, tertiary alcohols, isoxazolines, isoxazolidines, and amino alcohols. The SET process between hydroxylamine and the hypervalent iodine–CF3reagent is proposed to produce two free radicals for the regio- and diastereoselective addition to alkenes. The synthetic potential of the protocol was established via the late-stage functionalization of the products and a series of postreaction modifications.

Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells–derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/dbmice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 μg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/dbmice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN.

Machine learning methods for state of charge (SOC) estimation of lithium-ion batteries (LiBs) face the problem of domain shift. Varying conditions, such as different ambient temperatures, can cause performance degradation of the estimators due to data distribution discrepancy. Some transfer learning methods have been utilized to tackle the problem. At real-time transfer, the source model is supposed to keep updating itself online. In the process, source domain data are usually absent because the storage and acquisition of all historical running data can involve violating the privacy of users. However, existing methods require coexistence of source and target samples. In this article, we discuss a more difficult yet more practical source-free setting where there are only the models pretrained in source domain and limited target data can be available. To address the challenges of the absence of source data and distribution discrepancy in cross-domain SOC estimation, we propose a novel source-free temperature transfer network (SFTTN), which can mitigate domain shift adaptively. In this article, cross-domain SOC estimation under source-free transfer setting is discussed for the first time. To this end, we define an effective approach named minimum estimation discrepancy (MED), which attempts to align domain distributions by minimizing the estimation discrepancy of target samples. Extensive transfer experiments and online testing at fixed and changing ambient temperatures are performed to verify the effectiveness of SFTTN. The experiment results indicate that SFTTN can achieve robust and accurate SOC estimation at different ambient temperatures under source-free scenario.

ABSTRACTNon-small cell lung cancer (NSCLC) is the most common lung cancer with a highest mortality rate. MiR-497-5p has been reported as tumor suppressor in many cancers, but the role and mechanism of miR-497-5p in regulating NSCLC progression are still largely unknown in vitro and in vivo. Here, miR-497-5p was significantly downregulated in human NSCLC tissues and cell lines, compared with matched adjacent tissues and normal lung epithelial cell line. Then, miR-497-5p mimic and inhibitor were, respectively, transfected into human NSCLC cells A549 and H460, CCK-8 assay, transwell assay, and flow cytometry were used to detect the capacities of cell proliferation, invasion and apoptosis. MiR-497-5p negatively regulated proliferation and invasion of NSCLC cancer cells. MiR-497-5p was demonstrated to directly bound to 3’-UTR of CX3CL1 mRNA and post-transcriptionally suppressed its expression thus inactivating its downstream oncogenic pathway ERK/AKT. Moreover, transfection with short hairpin RNA (shRNA) against CX3CL1 decreased capacity of cell proliferation and invasion and promoted cell apoptosis in NSCLC cells. In addition, ERK inhibitor U0126 attenuated the promotion effect of miR-497-5p inhibitor on activation of ERK/AKT and cell proliferation and migration. Finally, overexpression of miR-497-5p substantially suppressed activation of the ERK/AKT pathway and tumor growth in tumor-bearing mice in vivo. Taken together, our findings showed that miR-497-5p is downregulated in human NSCLC tissues and cell lines, and it inhibited tumor growth and cell invasion by targeting CX3CL1 gene to inactivate the ERK/AKT pathway in NSCLC cells.

Introduction:Acute kidney injury (AKI) is a major public health problem worldwide. However, there is no definitive therapies to treat established AKI. In this study, we used FG-4592 to induce hypoxia inducible factor (HIF) expression in cells and then explored whether the extracellular vesicles (EVs) secreted by HIF-upregulated cells could alleviate ischemia/reperfusion injury (IRI)-induced AKI. Methods:FG-4592/HK2-EVs and FG-4592/HEK293-EVs were prepared by treating HK2 or HEK293 cells with FG-4592 for 24 h, respectively. HK2 cells under hypoxia were treated with FG-4592/HK2-EVs or FG-4592/HEK293-EVs to observe the therapeutic effect of EVs on H/R-induced apoptosis and inflammation. Mice were treated with FG-4592/HEK293-EVs after IRI to observe whether FG-4592/HEK293-EVs treatment could alleviate ischemic AKI. Results:The expression of HIF was induced by FG-4592 in a dose-dependent manner in HK2 and HEK293 cells under normoxia. In vitro, FG-4592/HK2-EVs and FG-4592/HEK293-EVs inhibited apoptosis and inflammation induced by H/R. In vivo, treatment with FG-4592/HEK293-EVs significantly ameliorated renal tubular injury and inflammation caused by IRI. In addition, the expression of HIF-1α in cells and kidneys was significantly downregulated by FG-4592/HK2-EVs and FG-4592/HEK293-EVs treatment. Conclusion:This study demonstrated that EVs derived from HK2 or HEK293 cells after FG-4592 treatment could alleviate renal tubular injury and inflammation, suggesting a novel therapeutic role of FG-4592/EVs in the treatment of AKI.

Development of an efficient, stereoselective, sustainable synthesis of chiral aryl β‐hydroxy α‐amino acids and their derivatives is of paramount importance, owing to the broad utility of these molecules in pharmaceutical application and asymmetric synthesis. We report a systematic study on ketoreductase (KRED)‐catalyzed dynamic reductive kinetic resolution (DYRKR) of aryl α‐amino β‐keto esters 6, furnishing 20 structurally diverse chiral syn‐aryl β‐hydroxy α‐amino esters (syn‐(2S,3R)‐7) in moderate‐to‐excellent isolated yield (up to 93%), along with moderate‐to‐excellent diastereoselectivity (up to >99 : 1 dr) and excellent enantioselectivity (mostly >99% ee). The practical synthesis potential of our developed method was showcased by the asymmetric, chemo‐enzymatic total synthesis of thiamphenicol (1). A generic, efficient, and highly stereoselective synthesis of valuable chiral syn‐aryl β‐hydroxy α‐amino esters (syn‐(2S,3R)‐7) was developed through ketoreductase‐catalyzed dynamic reductive kinetic resolution of aryl α‐amino β‐keto esters 6. The practical synthesis potential of this developed method was showcased by the asymmetric, chemo‐enzymatic total synthesis of thiamphenicol (1).

Introduction. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes to a poor prognosis. Reliable biomarkers to predict adverse outcomes during hospitalization are important. Aim. To investigate the relationship between the serum cholinesterase (ChE) level and adverse clinical outcomes, including hypoxemia severity, hypercapnia, duration of hospital stay (DoHS), and noninvasive ventilation (NIV) requirement, in patients with AECOPD. Methods. Patients hospitalized with AECOPD in the Wuhu Hospital of Traditional Chinese Medicine between January 2017 and December 2021 were included. Results. A total of 429 patients were enrolled. The serum ChE level was significantly lower in patients with hypercapnia, who required NIV during hospitalization and who had a DoHS of >10 days, with an oxygenation index < 300. The ChE level was correlated negatively with the C-reactive protein level and neutrophil-to-lymphocyte ratio and correlated positively with the serum albumin level. Multivariate logistic regression analysis indicated that a serum ChE level of ≤4116 U/L (OR = 2.857, 95% CI = 1.46–5.58, p=0.002) was associated significantly with NIV requirement. Conclusions. The serum ChE level was correlated significantly with complicating severe hypoxemia, hypercapnia, prolonged DoHS, and the need for NIV in patients hospitalized with AECOPD. The serum ChE level is a clinically important risk-stratification biomarker in patients hospitalized with AECOPD.

Purpose: A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa). Patients and methods: Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated. Results: In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P= 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P&lt; 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P= 0.660, P= 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P= 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage. Conclusion: The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.

Incomplete recovery from episodes of acute kidney injury (AKI) can predispose patients to develop chronic kidney disease (CKD). Although hypoxia-inducible factor-1α (HIF-1α) is a master regulator of the response to hypoxia/ischemia, the role of HIF-1α in CKD progression following incomplete recovery from AKI is poorly understood. Here, we investigated this issue using moderate and severe ischemia/reperfusion injury (I/RI) mouse models. We found that the outcomes of AKI were highly associated with the time course of tubular HIF-1α expression. Sustained activation of HIF-1α, accompanied by the development of renal fibrotic lesions, was found in kidneys with severe AKI. The AKI to CKD progression was markedly ameliorated when PX-478 (a specific HIF-1α inhibitor, 5 mg· kg−1·d−1, i.p.) was administered starting on day 5 after severe I/RI for 10 consecutive days. Furthermore, we demonstrated that HIF-1α C-terminal transcriptional activation domain (C-TAD) transcriptionally stimulated KLF5, which promoted progression of CKD following severe AKI. The effect of HIF-1α C-TAD activation on promoting AKI to CKD progression was also confirmed in in vivo and in vitro studies. Moreover, we revealed that activation of HIF-1α C-TAD resulted in the loss of FIH-1, which was the key factor governing HIF-1α-driven AKI to CKD progression. Overexpression of FIH-1 inhibited HIF-1α C-TAD and prevented AKI to CKD progression. Thus, FIH-1-modulated HIF-1α C-TAD activation was the key mechanism of AKI to CKD progression by transcriptionally regulating KLF5 pathway. Our results provide new insights into the role of HIF-1α in AKI to CKD progression and also the potential therapeutic strategy for the prevention of renal diseases progression.

The task of image–text matching refers to measuring the visual-semantic similarity between an image and a sentence. Recently, the fine-grained matching methods that explore the local alignment between the image regions and the sentence words have shown advance in inferring the image–text correspondence by aggregating pairwise region-word similarity. However, the local alignment is hard to achieve as some important image regions may be inaccurately detected or even missing. Meanwhile, some words with high-level semantics cannot be strictly corresponding to a single-image region. To tackle these problems, we address the importance of exploiting the global semantic consistence between image regions and sentence words as complementary for the local alignment. In this article, we propose a novel hybrid matching approach named Cross-modal Attention with Semantic Consistency (CASC) for image–text matching. The proposed CASC is a joint framework that performs cross-modal attention for local alignment and multilabel prediction for global semantic consistence. It directly extracts semantic labels from available sentence corpus without additional labor cost, which further provides a global similarity constraint for the aggregated region-word similarity obtained by the local alignment. Extensive experiments on Flickr30k and Microsoft COCO (MSCOCO) data sets demonstrate the effectiveness of the proposed CASC on preserving global semantic consistence along with the local alignment and further show its superior image–text matching performance compared with more than 15 state-of-the-art methods.

Renal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), characterized by tubulointerstitial inflammation. Currently, progress in developing effective therapies to prevent or ameliorate AKI by anti-inflammation remains slow. Emerging studies have suggested that NLRP3 (the NOD-, LRR- and pyrin domain-containing 3) inflammasome plays a key role in a wide spectrum of kidney disease models including I/R injury. In this study, we investigated the renal protective effects of A68930, a specific agonist for the D-1 dopamine receptor (DRD1), which was recently recognized to downregulate NLRP3 inflammasome via DRD1 signaling. AKI was induced by renal I/R injury and A68930 was intraperitoneally injected 3 times after renal reperfusion. We showed that A68930 significantly ameliorated renal dysfunction. Meanwhile, A68930 markedly reduced macrophages and T cells infiltration, renal pro-inflammatory cytokines production (TNF-α, IL-6, IL-1β), serum pro-inflammatory cytokine (TNF-α and IL-6) and NLRP3 inflammasome activation. Additionally, A68930 attenuated I/R-induced mitochondria injury, which was observed by transmission electron microscopy. In summary, our results demonstrated that activation of DRD1 by A68930 inhibited renal and systematic inflammation, and improved kidney function in I/R induced AKI model, which was probably related to the inhibition of the NLRP3 inflammasome activation.

Background:Although renal anemia has attracted widespread attention, a large proportion of chronic kidney disease (CKD) patients with anemia still do not meet the hemoglobin (Hb) targets. The discovery of prolyl hydroxylase domain (PHD) enzymes as regulators of hypoxia-inducible factor (HIF)-dependent erythropoiesis has led to the development of novel therapeutic agents for renal anemia. Roxadustat, the first small-molecule HIF-PHD inhibitor, has completed the phase 3 trials. There are currently more than 15 phase 3 clinical trials worldwide assessing the efficacy and safety of roxadustat in CKD patients with anemia. This review will summarize recent findings of roxadustat in the treatment of renal anemia. Summary:Although the administration of erythropoiesis-stimulating agents (ESAs) and iron supplementation are a well-established and highly effective therapeutic approach for renal anemia, there are several safety concerns. Current findings from phase 2 and 3 trials suggest that roxadustat is clinically effective and well tolerated. On the one hand, roxadustat could increase endogenous erythropoietin (EPO) levels within or near physiological range in a titratable manner by inducing HIF pathway activation transiently. On the other hand, roxadustat also improves iron metabolism by decreasing serum hepcidin and increasing intestinal iron absorption, which is beneficial to functional iron deficiency and absolute iron deficiency. More importantly, the erythropoietic response of roxadustat is independent of baseline inflammatory state of CKD patients. Thus, the discovery of roxadustat will revolutionize the treatment strategy for renal anemia. Key Messages:Roxadustat is an emerging and promising therapeutic approach against anemia in CKD patients, which differs from those of conventional ESAs. Roxadustat corrects anemia of CKD patients through multiple pathways, beyond elevating EPO levels within physiological range, and also by handling iron metabolism (particularly decreasing the hepcidin levels). Furthermore, the Hb response of roxadustat is independent of the inflammatory microenvironment.

A new protocol for SO bond formation was developed by electrochemical oxidative cross‐coupling between alcohols and thiophenols. With this strategy, a series of valuable sulfinic ester derivatives were synthesized up to 96% yield from basic starting materials. A preliminary mechanistic investigation reveals that this reaction involves oxygen reduction reaction (ORR). A new protocol for SO bond formation was developed by electrochemical oxidative cross‐coupling between alcohols and thiophenols.

Tubulointerstitial inflammation is a common characteristic of acute and chronic kidney injury. However, the mechanism by which the initial injury of tubular epithelial cells (TECs) drives interstitial inflammation remains unclear. This paper aims to explore the role of exosomal miRNAs derived from TECs in the development of tubulointerstitial inflammation. Global microRNA(miRNA) expression profiling of renal exosomes was examined in a LPS induced acute kidney injury (AKI) mouse model and miR-19b-3p was identified as the miRNA that was most notably increased in TEC-derived exosomes compared to controls. Similar results were also found in an adriamycin (ADR) induced chronic proteinuric kidney disease model in which exosomal miR-19b-3p was markedly released. Interestingly, once released, TEC-derived exosomal miR-19b-3p was internalized by macrophages, leading to M1 phenotype polarization through targeting NF-κB/SOCS-1. A dual-luciferase reporter assay confirmed that SOCS-1 was the direct target of miR-19b-3p. Importantly, the pathogenic role of exosomal miR-19b-3p in initiating renal inflammation was revealed by the ability of adoptively transferred of purified TEC-derived exosomes to cause tubulointerstitial inflammation in mice, which was reversed by inhibition of miR-19b-3p. Clinically, high levels of miR-19b-3p were found in urinary exosomes and were correlated with the severity of tubulointerstitial inflammation in patients with diabetic nephropathy. Thus, our studies demonstrated that exosomal miR-19b-3p mediated the communication between injured TECs and macrophages, leading to M1 macrophage activation. The exosome/miR-19b-3p/SOCS1 axis played a critical pathologic role in tubulointerstitial inflammation, representing a new therapeutic target for kidney disease.

Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Therefore, proangiogenesis therapy is considered a potentially effective strategy for limiting CKD-associated myopathy. Hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia; however, little evidence was available from CKD models. Here, we assessed whether pharmacological activation of HIF by MK-8617 (MK), a novel orally active HIF-PHI, improves CKD-associated myopathy. Mice were divided into sham or CKD groups, and CKD mice were subdivided into CKD + vehicle or MK treatment groups (1.5, 5, or 12.5 mg/kg for 12 wk). In CKD mice, skeletal muscle mass, mitochondrial amount, and exercise capacity decreased compared with sham mice. Compared with the CKD + vehicle group, low (1.5 mg/kg) and medium (5 mg/kg) doses of MK, but not the high dose (12.5 mg/kg), significantly restored these changes and was accompanied by incremental increases in HIF-1α. Furthermore, increased capillary density and area were observed in a MK dose-dependent manner, which is likely related to an improved VEGF response in the skeletal muscle of CKD mice. In addition, macrophage and proinflammatory cytokines, including monocyte chemoattractant protein 1, TNF-α, and IL-6, significantly increased in the high-dose MK group. These results indicate that HIF-PHI provides a potential therapeutic strategy to improve CKD-associated myopathy.

Although the distribution of progestagens in aquatic environments has been widely reported, details on their uptake, elimination, and biotransformation in fish have received little attention. This study investigated the uptake, elimination, and biotransformation potential of a progestagen, cyproterone acetate (CPTA), in Nile tilapia (Oreochromis niloticus) exposed to an environmentally relevant concentration under semistatic regimes. CPTA in tilapia tissues followed a similar pattern, reaching a concentration plateau within 4 days of exposure, and dropping to below limits of quantitation within 4 days of elimination. The calculated steady-state bioconcentration factors suggest a low bioconcentration potential of CPTA in juvenile tilapia. Results of enzymatic hydrolysis treatments revealed that no conjugates of CPTA were present in tissues, but conjugated biotransformation products of CPTA were found in bile, liver, and muscle. Most CPTA entered tissues and then was biotransformed into seven different products by phase I and phase II metabolism. The concentrations of endogenous cortisol were significantly influenced by CPTA in plasma and liver during the uptake period. These findings suggest that biotransformation products of CPTA should be considered for the assessment of the bioconcentration potential and ecological effects of progestagens.

The fault tree analysis has been extensively implemented in failure analysis of engineered systems. In most cases, the probabilities of basic events, e.g. components’ failures, are represented by crisp values in the fault tree analyses. However, due to lack of knowledge, scarcity of failure data, or vague judgments from experts, it may produce parameter uncertainty associated with degradation models of components/systems, and such model parameter uncertainty can be quantified by the epistemic uncertainty. In addition, the common cause failure, related to the simultaneous failures of two or more components caused by physical interactions or shared environments, often exists in advanced engineered systems and computing systems. In this paper, by considering both the common cause failure and the epistemic uncertainty associated with model parameters, an evidential network model embedded with common cause failure is proposed to facilitate system failure analysis. The detailed transformations from some logic gates of a fault tree to an evidential network model are given. Moreover, the conditional belief mass tables are constructed to quantify the dependency between the states of components and the entire system. An engineering case of an aero-engine oil system, together with comparative results, is presented to demonstrate the effectiveness of the proposed evidential network model.

Hypoxia promotes tubulointerstitial inflammation in the kidney. Although hypoxia inducible factor-1α (HIF-1α) is a master regulator of the response to hypoxia, the exact mechanisms through which HIF-1α modulates the induction of tubulointerstitial inflammation are still largely unclear. We demonstrated tubulointerstitial inflammation and increased tubular HIF-1α expression in murine models of ischemia/reperfusion injury and unilateral ureteral obstruction. Increased expression of HIF-1α in tubular epithelial cells was associated with selective shedding of microRNA-23a (miRNA-23a)-enriched exosomes in vivoand systemic inhibition of miRNA-23a prior to ischemia/reperfusion injury attenuated tubulointerstitial inflammation. In vitro, uptake of miRNA-23a-enriched exosomes by macrophages triggered their reprogramming into a pro-inflammatory state via suppression of the ubiquitin editor A20. To confirm the effect of miRNA-23a-containing exosomes on tubulointerstitial inflammation, we exposed tubular epithelial cells to hypoxic conditions to promote the release of miRNA-23a-containing exosomes. Injection of these miRNA-23a-enriched exosomes into uninjured renal parenchyma resulted in increased inflammatory infiltration in vivo. Taken together, our studies demonstrate that the HIF-1α-dependent release of miRNA-23a-enriched exosomes from hypoxic tubular epithelial cells activates macrophages to promote tubulointerstitial inflammation. Blockade of exosome-mediated miRNA-23a transfer between tubular epithelial cells and macrophages may serve as a novel therapeutic approach to ameliorate tubulointerstitial inflammation.

IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glomerulopathy controls. Transmission electron microscopy and nanoparticle tracking analysis confirmed the size and morphology characteristic of urinary exosomes. Exosome markers (Alix and CD63) as well as renal cell markers [aquaporin 2 (AQP2) and nephrin] were detected, which indicate the renal origin of urinary exosomes. Exosome excretion was increased markedly in IgAN patients compared with controls and correlated with levels of proteinuria and tubular injury. More important, urinary exosome excretion correlated with greater histologic activity (mesangial hypercellularity, crescents, and endocapillary hypercellularity). Profiling of the inflammation-related mRNA revealed that exosomal chemokine (C-C motif) ligand 2 (CCL2) was up-regulated in IgAN patients. In a validation study, CCL2was exclusively highly expressed in IgAN patients compared with healthy controls as well as minimal change disease and membrane nephropathy patients. Also, a correlation between exosomal CCL2and estimated glomerular filtration rate levels was found in IgAN. Exosomal CCL2was correlated with tubulointerstitial inflammation and C3 deposition. High CCL2levels at the time of renal biopsy were associated with subsequent deterioration in renal function. Thus, urinary exosomes and exosomal CCL2mRNA are promising biomarkers reflecting active renal histologic injury and renal function deterioration in IgAN.

The novel AgCl/Ag2SO3hybrids as an efficient photocatalyst had been fabricated by an in situsynthetic method. The correlations between the structure and the photocatalytic properties of the as‐fabricated hybrids were analyzed. Experimental results exhibited that with increasing the amount of Ag2SO3, the degradation rate of the as‐obtained samples was firstly increased and then decreased under the visible light irradiation. When the mass ratio of AgCl to Ag2SO3was 1:2, in 30 min, it displayed the highest degradation rate of 99.2% for rhodamine‐B, which was obviously higher than 46.1, 60.5, and 14.6% of pure AgCl, Ag2SO3, and TiO2(P25), respectively. Similar results could be found in degradation of methyl orange. It had the maximum of 97.4% in 90 min, which was higher than 55.2, 48.7, and 12.7% of pure AgCl, Ag2SO3, and P25, respectively. Moreover, the as‐prepared hybrids possessed the enhanced separation and transfer of photo‐generated electron–hole pairs compared to the pure samples. In addition, the holes and superoxide radicals played the dominant role and the hydroxyl radicals played the secondary role during the process of photocatalytic degradation.

Plant-based diagnosis is important for determining the status of crop nitrogen (N) nutrition. We aimed to localize a critical N dilution curve and validate the applicability for maize hybrids in the North China Plain (NCP), and to explore the feasibility of using leaf chlorophyll (Chl) to estimate N nutrition index (NNI). Here, the use of a gradient of N fertilizer treatments with maize hybrids was conducted for 2 years, and Chl content from the youngest collared leaf in addition to NNI values were determined for the first season. The parameters of the fitted critical N curve were essentially identical across hybrids and years. The localized curve (Nc= 33.395 W−0.396) and NNI could strongly distinguish plant N status. Chl and relative Chl (R-Chl) increased with increasing N rates, and both were significantly positively related to NNI. Genotype influence was not significant when Chl was normalized to R-Chl, and the response curves of NNI as a function of R-Chl were more stable between the two hybrids. The relationships between relative yield and NNI and R-Chl were expressed as quadratic functions, but the slopes/intercepts varied across hybrids and stages. Therefore, the localization and validation of the critical N dilution curve for summer maize in NCP was confirmed, there were no differences among hybrids and climates, and the R-Chl index was suggested as a candidate for estimating NNI under this conditions. However, further investigations are needed before these results are applied to practical production.

ABSTRACTThis study aimed to investigate the expression and function of BKCachannels in the Sphincter of Oddi (SO) in a rabbit model of hypercholesterolemia (HC). New Zealand white rabbits were randomly divided into 2 groups: the control group was fed standard chow (n= 18) whereas the high-cholesterol group was fed cholesterol-enriched chow containing 1.5% cholesterol (n= 18). The serum cholesterol level was significantly greater in the HC groups than in the control group, but there was no significant difference in body weight between the control and HC groups. Although the total protein expression of BKCaα- and β1-subunit was not significantly different between the control and HC groups, the Tyr-phosphorylation of BKCaα-subunit was significantly decreased in the HC group than in the control group. In addition, hypercholesterolemia significantly increased Acetylcholine (ACh)-induced contraction of the SO rings. Pretreatment with 30 μM NS1619, a BKCachannel agonist, significantly reduced ACh-induced contraction of the SO rings in HC rabbits. Moreover, pretreatment with 100 μM Na3OV4, a protein tyrosine phosphatase inhibitor, significantly reduced ACh-induced contraction of the SO rings in HC rabbits, whereas it significantly increased upon pretreating with 10 μM Genistein, a tyrosine kinase inhibitor. Whole-cell patch clamp recordings showed that BKCacurrent density was significantly lower in SOSMCs from HC group than that from control group. Our findings suggest that hypercholesterolemia-induced downregulation of BKCachannel, and Tyr-phosphorylation of BKCaα-subunit may contribute to the hyperresponsiveness of the SO ring in HC rabbits.

Nowadays, as a consequence of the mushrooming growth of photoinduced electron transfer (PET), the water-involved photooxygenation reactions based on unsaturated bonds are becoming manifold and predominant. In this mini-review, we have summarized the recent advances in photochemical transformations using water as an oxygen source since 2020, and highlighted the sustainable feature brought by harnessing the green properties of water in photoreactions. Relevant reports are comprehensively organized by the type of O-containing product targets, including silanols, alcohols, carbonyls, phenols, diaryl ethers, and oxazolines. We hope this review would provide a prospective overview of this topic and stimulate significant research interest.

Background: We aimed to assess the clinical value of 18F-PSMA-1007 and 68Ga-PSMA-11 PET/MRI in the gross tumor volume (GTV) delineation of radiotherapy for prostate cancer (PCa). Methods: Sixty-nine patients were retrospectively enrolled (57 in the 18F subgroup and 12 in the 68Ga subgroup). Three physicians delineated the GTV and tumor length by the visual method and threshold method with thresholds of 30%, 40%, 50%, and 60% SUVmax. The volume correlation and differences in GTVs were assessed. The dice similarity coefficient (DSC) was applied to estimate the spatial overlap between GTVs. For 51 patients undergoing radical prostatectomy, the tumor length (Lpath) of the maximum area was measured, and compared with the longest tumor length obtained based on the images (LMRI, LPET/MRI, LPET, LPET30%, LPET40%, LPET50%, LPET60%) to determine the best delineation method. Results: In the 18F subgroup, (1) GTV-PET/MRI (p&lt; 0.001) was significantly different from the reference GTV-MRI. DSC between them was > 0.7. (2) GTV-MRI (R2= 0.462, p&lt; 0.05) was the influencing factor of DSC. In the 68Ga subgroup, (1) GTV-PET/MRI (p&lt; 0.05) was significantly different from the reference GTV-MRI. DSC between them was > 0.7. (2) There was a significant correlation between GTV-MRI (r= 0.580, p&lt; 0.05) and DSC. The longest tumor length measured by PET/MRI was in good agreement with that measured by histopathological analysis in both subgroups. Conclusion: It is feasible to visually delineate GTV on PSMA PET/MRI in PCa radiotherapy, and we emphasize the utility of PET/MRI fusion images in GTV delineation. In addition, the overlap degree was the highest between GTV-MRI and GTV-PET/MRI, and it increased with increasing volume.

Calcium phosphate (CaP) is frequently used as coating for bone implants to promote osseointegration. However, commercial CaP coatings via plasma spraying display similar microstructures, and thus fail to provide specific implants according to different surgical conditions or skeletal bone sites. Herein, inspired by the formation of natural biominerals with various morphologies mediated by amorphous precursors, CaP coatings with tunable microstructures mediated by an amorphous metastable phase are fabricated. The microstructures of the coatings are precisely controlled by both polyaspartic acid and Mg2+. The cell biological behaviors, including alkaline phosphatase activity, mineralization, and osteogenesis‐related genes expression, on the CaP coatings with different microstructures, exhibit significant differences. Furthermore, in vivo experiments demonstrate the osseointegration in different types of rats and bones indeed favors different CaP coatings. This biomimetic strategy can be used to fabricate customized bone implants that can meet the specific requirements of various surgery conditions. CaP coatings with tunable microstructures are produced from amorphous precursors. These coatings exhibit distinct degradation rate and osteogenesis‐related cell behavior, and thus can meet the specific requirements of bone healing in different animal models and different skeletal bone sites.

A series of porphyrin sensitizers with different central metal ions (PMn, PFe, PCo, PNi, PCu, and PZn) have been studied based on density functional theory (DFT). The geometric structure of the dyes was optimized and the frontier molecular orbital were calculated. The result shows that the LUMO levels of PFe, PNi and PZn were much lower than that of PMn, PCo and PCu, which suggest a lower energy barrier for electron transfer from the donor to the acceptor tunneling. Furthermore, the energy gap of HOMO and LUMO for PFe was only 0.81 eV, it indicates a significant red shift of the absorption spectrum. The LUMO of PMn, PNi, PCu and PZn were mainly decocalized on the porphyrin core and the bridge moiety, which was beneficial to electronic transport.

The paper uses modern control theory and mechanical and structural vibration theory to study a mass-spring system of three degrees. Using Newton's first law analyzing the force of the object, drawn the simulation diagram from the control perspective. Reflecting all changes of the independent variables and their relationships. And revealing the characteristics of the system. We also analyzed the system can not only be controlled but also can be observed, understanding the inherent nature of the system further. About the dynamic characteristics of the system, we use the main formation method to calculate the natural frequency, the main formation and displacement response of the system[1].

This paper demonstrates that the nature and extent of residual CO2trapping depend on the process by which the CO2phase is introduced into the rock. We compare residual trapping of CO2in Berea Sandstone by imbibing water into a core containing either exsolved CO2or CO2introduced by drainage. X‐ray computed tomography measurements are used to map the spatial distribution of CO2preimbibition and postimbibition. Unlike during drainage where the CO2distribution is strongly influenced by the heterogeneity of the rock, the distribution of exsolved CO2is comparatively uniform. Postimbibition, the CO2distribution retained the essential features for both the exsolved and drainage cases, but twice as much residual trapping is observed for exsolved CO2even with similar preimbibition gas saturations. Residually trapped exsolved gas also disproportionately reduced water relative permeability. Development of process‐dependent parameterization will help better manage subsurface flow processes and unlock benefits from gas exsolution. Process‐dependent trappingEffective gas barrier through degassing processManagement of subsurface flow processes

Vertical greening as an important form of urban green space, it is an effective way to improve the city green coverage rate. This paper discusses the technology and the future trend of urban space stereo virescence, and in Beijing area as example this paper discusses the feasibility and expansibility, in order to help enterprise itself and the development of the industry.

In optical performance monitoring system, the analog to digital converter is needed to detect the peak of nanosecond pulse and get the signal envelope. A scheme based on a designed anti-aliasing filter and analog to digital converter is proposed to broaden the nanosecond pulse and make it easier for the analog to digital converter to catch the peak of the nanosecond pulse. The experimental results demonstrate that, with the proposed scheme, the optical performance system needs less time to get the recovered eye-diagram of high speed optical data signal, and is robust to phase mismatch in the analog to digital converter circuit.

Cyclin-dependent kinase 12 (CDK12) plays a critical role in regulating gene transcription. CDK12 inhibition is a potential anticancer therapeutic strategy. However, several clinical trials have shown that CDK inhibitors might cause renal dysfunction and electrolyte disorders. CDK12 is abundant in renal tubular epithelial cells (RTECs), but the exact role of CDK12 in renal physiology remains unclear. Genetic knockout of CDK12 in mouse RTECs causes polydipsia, polyuria, and hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced Na-K-2Cl cotransporter 2 (NKCC2) levels in the kidney. In addition, CKD12 knockout causes an increase in Slc12a1(which encodes NKCC2) intronic polyadenylation events, which results in Slc12a1truncated transcript production and NKCC2 downregulation. These findings provide novel insight into CDK12 being necessary for maintaining renal homeostasis by regulating NKCC2 transcription, which explains the critical water and electrolyte disturbance that occurs during the application of CDK12 inhibitors for cancer treatment. Therefore, there are safety concerns about the clinical use of these new anticancer drugs.

The objective of this study was to summarize our experience of using local flaps for the reconstruction of neck defects after cervical contractures release, particularly of using the extended deltopectoral flaps whose distal margin was beyond the anterior axillary line even reaching dorsalis for reconstruction of anterior neck scar contractures in a single-stage procedure.

Abstract: A novel design of optical sampling system has been developed by using sum-frequency generation (SFG) in a periodically-poled lithium niobate (PPLN) waveguide and using passive mode-locked fiber laser pulses as optical sampling pulses. The system achieved high temporal resolution and high sensitivity using a 30 mm length PPLN with quasi phase match period of 19.3 μm and 151 fs sampling pulses which were generated by passive modelock fiber laser based on nonlinear polarization rotation (NPR). Clear eye-diagram of 10 Gbit/s non-return-to-zeros (NRZ) pseudorandom binary sequence (PRBS) optical signal were successfully reconstructed by this system.

A technique using artificial neural networks trained with parameters derived from reconstructed eye diagrams for optical performance monitoring in 40-Gbps optical duobinary (ODB) system is demonstrated. Firstly, the optical signal is asynchronously sampled by short pulse in the nonlinear medium such as semiconductor optical amplifier and highly nonlinear fiber, the sampled and collected data is then processed by improved software synchronization algorithm to obtain reconstructed eye diagrams without data clock recovery. Secondly, the features of the reconstructed eye diagrams are extracted to train the three-layer preceptor artificial neural network. Finally, the outputs of trained neural network are used to monitor multiple optical signal impairments. Simulation experiments of optical signal noise ratio (OSNR), chromatic dispersion (CD) and polarization mode dispersion (PMD) monitoring in 40-Gbps ODB system is presented. The proposed monitoring scheme can accurately identify simultaneous impairment with the root-mean-square (RMS) monitoring error less than 3%.

Multiphase La1-xSrxFe1-yCoyO3-δ has been synthesized by sol-gel method and characterized by powder X-diffraction. Structure refinements of multiphase were undertaken to analyze compositions of compounds, and structure parameters were determined by Rietveld method, respectively. It was found that products were easier to be prepared in the condition of a precursor dealed with by high-speed disintegrator, and products synthesized at 1173K were composed of two phases of which La0.75Sr0.25Co0.2Fe0.8O3-δ is an orthorhombic structure with space group Pbnm and La0.46Sr0.54Co0.2Fe0.8O3-δ trigonal structure with space group R-3c. Structure geometry becomes more regular with increasing Sr content.