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Background: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. Methods: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. Results: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. Conclusions: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury. [ABSTRACT FROM AUTHOR]

Background and Purpose: Activation of the renin‐angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen‐like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)‐induced hypertension and tubulointerstitial fibrosis was investigated. Experimental Approach: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) renal tubular‐specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II‐induced renal interstitial fibrosis. In vitro, HIF‐1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. Key Results: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II‐induced hypertension model. Tubular‐specific knockdown of LIMS1 ameliorated Ang II‐induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF‐1α in tubular cells and that tubular HIF‐1α knockout ameliorates LIMS1‐mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II‐induced tubulointerstitial fibrosis by interacting with vimentin. Conclusion and Implications: We conclude that HIF‐1α transcriptionally regulated LIMS1 plays a central role in Ang II‐induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II‐induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD. [ABSTRACT FROM AUTHOR]

A photocatalyst-free hydrothiolation reaction of aromatic gem-difluoroalkenes was developed under the irradiation of blue light in dimethyl carbonate as a green solvent, leading to α,α-difluoroalkylthioethers in good yields. [ABSTRACT FROM AUTHOR]

Aim: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. Methods: ESI‐QTRAP‐MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. Results: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition‐mediated tubule injury recovery. Reactive oxygen species/NF‐κB signaling activation played a vital role in fumarate‐mediated tubule injury. Conclusion: Our studies demonstrated that the mitochondrial‐derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate‐mediated ROS/NF‐κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury. [ABSTRACT FROM AUTHOR]

The teacher–student framework is widely employed for cross-domain object detection. However, it suffers from two problems. One is that large distribution discrepancies will cause critical performance drops. The other is that the samples that deviate from the overall distributions of both domains will greatly mislead the model. To solve these problems, we propose a style-guided adversarial teacher (SGAT) method for domain adaptation. Specifically, on the domain level, we generate target-like images based on source images to effectively narrow the gaps between domains. On the sample level, we denoise samples by estimating the probability density ratio of the 'target-style' and target distributions, which could filter out the unrelated samples and highlight the related ones. In this way, we could guarantee reliable samples. With these reliable samples, we learn the domain-invariant features through teacher–student mutual learning and adversarial learning. Extensive experiments verify the effectiveness of our method. In particular, we achieve 52.9% mAP on Clipart1k and 42.7% on Comic2k, which are 6.4% and 5.0% higher than the compared baselines. [ABSTRACT FROM AUTHOR]

Background: Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. Methods: Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. Results: We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. Conclusions: Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice. [ABSTRACT FROM AUTHOR]

Sustained cardiac hypertrophy damages the heart and weakens cardiac function, often leading to heart failure and even death. Pathological cardiac hypertrophy has become a central therapeutic target for many heart diseases including heart failure. However, the underlying mechanisms of cardiac hypertrophy, especially the involvement of autophagy program, are still ill‐understood. Synaptotagmin‐7 (Syt7), a multifunctional and high‐affinity calcium sensor, plays a pivotal role in asynchronous neurotransmitter release, synaptic facilitation, and vesicle pool regulation during synaptic transmission. However, little is known about whether Syt7 is expressed in the myocardium and involved in the pathogenesis of heart diseases. Here we showed that Syt7 was significantly upregulated in Ang II‐treated hearts and cardiomyocytes. Homozygous syt7 knockout (syt7−/−) mice exhibited significantly attenuated cardiac hypertrophy and fibrosis and improved cardiac function. We further found that Syt7 exerted a pro‐hypertrophic effect by suppressing the autophagy process. In exploring the upstream mechanisms, microRNA (miR)‐93 was identified to participate in the regulation of Syt7 expression. miR‐93 protected hearts against Ang II‐induced hypertrophy through targeting Syt7‐autophagy pathway. In summary, our data reveal a new cardiac hypertrophy regulator and a novel hypertrophy regulating model composed of miR‐93, Syt7 and autophagy program. These molecules may serve as potential therapeutic targets in the treatment of cardiac hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

Tubulointerstitial fibrosis (TIF) plays a crucial role in the progression of diabetic kidney disease (DKD). However, the underlying molecular mechanisms remain obscure. The present study aimed to examine whether transmembrane member 16A (TMEM16A), a Ca2+-activated chloride channel, contributes to the development of TIF in DKD. Interestingly, we found that TMEM16A expression was significantly up-regulated in tubule of murine model of DKD, which was associated with development of TIF. In vivo inhibition of TMEM16A channel activity with specific inhibitors Ani9 effectively protects against TIF. Then, we found that TMEM16A activation induces tubular mitochondrial dysfunction in in vivo and in vitro models, with the evidence of the TMEM16A inhibition with specific inhibitor. Mechanically, TMEM16A mediated tubular mitochondrial dysfunction through inhibiting PGC-1α, whereas overexpression of PGC-1α could rescue the changes. In addition, TMEM16A-induced fibrogenesis was dependent on increased intracellular Cl−, and reducing intracellular Cl− significantly blunted high glucose-induced PGC-1α and profibrotic factors expression. Taken together, our studies demonstrated that tubular TMEM16A promotes TIF by suppressing PGC-1α-mediated mitochondrial homeostasis in DKD. Blockade of TMEM16A may serve as a novel therapeutic approach to ameliorate TIF. [ABSTRACT FROM AUTHOR]

TESCAN Integrated Mineral Analyzer (TIMA) is an analysis system based on a scanning electron microscope that incorporates multiple X-ray spectrometers and other detectors. It could automatically identify minerals and produce images. TIMA has been widely applied in earth sciences, including petrology, mineralogy, geochemistry, petroleum, and paleontology, particularly in the rapid analysis of some geological samples with complex mineral composition and structure and small grain size, and a large number of repetitive samples to obtain statistical data for research purposes. In order to achieve the goals of analysis and save costs, it is crucial to select the optimal analytical conditions, but this aspect is often overlooked. This article takes sample of gold-bearing pyrite-sericite- quartz altered rock from the Huachanggou gold deposit in Lueyang County, Shaanxi Province, as an example. Using TIMA, the samples were analyzed under different scanning modes, analysis types, and various experimental parameter settings. The study compared the mineral phase composition data, image quality of mineral phase maps and elemental distribution maps in a small field, as well as statistical data such as mineral grain size. The results indicate that the main factors influencing the quality of TIMA analysis Eire the backscattered electron (BSE) pixel spacing, energy-dispersive X-ray spectroscopy (EDS) test dot spacing, and X-ray acquisition counts. The selection of analytical conditions primarily depends on the mineral composition, mineral grain size, and the purpose of the analysis. [ABSTRACT FROM AUTHOR]

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potential cancer biomarkers. Little is known about the role of HNRNPR, an essential member of the hnRNP family, in human tumours. This study aims to explore the potential value of HNRNPR across cancers, based on The Cancer Genome Atlas (TCGA). The expression level, mutation, DNA methylation, phosphorylation status, survival status, pathological stage, tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration, and immune signature related to HNRNPR were analyzed. HNRNPR expression level was increased in several types of cancer and was associated with poor prognosis, especially in liver hepatocellular carcinoma (LIHC). HNRNPR was also correlated with antitumour immunity, and associated with TMB, MSI, and immune cell activation status across cancers. Furthermore, nomograms were established to predict the prognosis of LIHC, based on HNRNPR and other clinical characteristics. Functional enrichment analysis showed the mechanisms of HNRNPR‐mediated LIHC progression. Loss‐of‐function experiments demonstrated that inhibition of HNRNPR could remarkably suppress hepatocellular carcinoma (HCC) cell proliferation, migration, invasion, and Epithelial‐Mesenchymal Transition abilities. Our study offers a comprehensive understanding of the oncogenic roles of HNRNPR across different tumours, and demonstrates that HNRNPR might foster the proliferation, migration, and invasion abilities of HCC cells. [ABSTRACT FROM AUTHOR]

Purpose: Most Hepatocellular carcinoma (HCC) patients are in advanced or metastatic stage at the time of diagnosis. Prognosis for advanced HCC patients is dismal. This study was based on our previous microarray results, and aimed to explore the promising diagnostic and prognostic markers for advanced HCC by focusing on the important function of KLF2. Methods: The Cancer Genome Atlas (TCGA), Cancer Genome Consortium database (ICGC), and the Gene Expression Comprehensive Database (GEO) provided the raw data of this study research. The cBioPortal platform, CeDR Atlas platform, and the Human Protein Atlas (HPA) website were applied to analyze the mutational landscape and single-cell sequencing data of KLF2. Basing on the results of single-cell sequencing analyses, we further explored the molecular mechanism of KLF2 regulation in the fibrosis and immune infiltration of HCC. Results: Decreased KLF2 expression was discovered to be mainly regulated by hypermethylation, and indicated a poor prognosis of HCC. Single-cell level expression analyses revealed KLF2 was highly expressed in immune cells and fibroblasts. The function enrichment analysis of KLF2 targets indicated the crucial association between KLF2 and tumor matrix. 33-genes related with cancer associated fibroblasts (CAFs) were collected to identify the significant association of KLF2 with fibrosis. And SPP1 was validated as a promising prognostic and diagnostic marker for advanced HCC patients. CXCR6 CD8+ T cells were noted as a predominant proportion in the immune microenvironment, and T cell receptor CD3D was discovered to be a potential therapeutic biomarker for HCC immunotherapy. Conclusion: This study identified that KLF2 is an important factor promoting HCC progression by affecting the fibrosis and immune infiltration, highlighting its great potential as a novel prognostic biomarker for advanced HCC. [ABSTRACT FROM AUTHOR]

Background: Tubulointerstitial inflammation (TII) is a critical pathological feature of kidney disease leading to renal fibrosis, and its treatment remains a major clinical challenge. We sought to explore the role of quercetin, a potential exosomes inhibitor, in exosomes release and TII. Methods: The effects of quercetin on exosomes release and TII were examined by two TII mouse models: the unilateral ureteral obstruction (UUO) models and the LPS-induced mouse models. In vitro, exosomes-mediated crosstalk between tubular epithelial cells (TECs) and macrophages was performed to investigate the mechanisms by which quercetin inhibited exosomes and TII. Results: In this study, we found that exosomes-mediated crosstalk between TECs and macrophages contributed to the development of TII. In vitro, exosomes released from LPS-stimulated TECs induced increased expression of inflammatory cytokines and fibrotic markers in Raw264·7 cells and vice versa. Interestingly, heat shock protein 70 (Hsp70) or Hsp90 proteins could control exosomes release from TECs and macrophages both in vivo and in vitro. Importantly, quercetin, a previously recognized heat shock protein inhibitor, could significantly reduce exosomes release in TII models by down-regulating Hsp70 or Hsp90. Quercetin abrogated exosomes-mediated intercellular communication, which attenuated TII and renal fibrosis accordingly. Conclusion: Quercetin could serve as a novel strategy for treatment of tubulointerstitial inflammation by inhibiting the exosomes-mediated crosstalk between tubules and macrophages. [ABSTRACT FROM AUTHOR]

Background: Sustained cardiac hypertrophy often develops maladaptive myocardial remodeling, and eventually progresses to heart failure and sudden death. Therefore, maladaptive hypertrophy is considered as a critical therapeutic target for many heart diseases. Mitophagy, a crucial mechanism in mitochondria quality control and cellular homeostasis, has been implicated in diverse cardiac disorders such as myocardial infarction, diabetic cardiomyopathy, cardiac hypertrophy and heart failure. However, what role mitophagy plays in heart diseases remains an enigma. PARKIN functions as an E3 ubiquitin protein ligase and mediates mitophagy cascades. It is still unclear whether PARKIN participates in the regulation of cardiac hypertrophy. Results: PARKIN was downregulated in cardiomyocytes and hearts under hypertrophic stress. Enforced expression of PARKIN inhibited Ang II-induced cardiomyocyte hypertrophy. Compared to wide-type mice with Ang II-induced cardiac hypertrophy, Parkin transgenic mice subjected to Ang II administration showed attenuated cardiac hypertrophy and improved cardiac function. In addition, mitophagy machinery was impaired in response to Ang II, which was rescued by overexpression of PARKIN. PARKIN exerted the anti-hypertrophy effect through restoring mitophagy. In further exploring the underlying mechanisms, we found that PARKIN was transcriptionally activated by FOXO3a. FOXO3a promoted mitophagy and suppressed cardiac hypertrophy by targeting Parkin. Conclusions: The present study reveals a novel cardiac hypertrophy regulating model composed of FOXO3a, PARKIN and mitophagy program. Modulation of their levels may provide a new approach for preventing cardiac hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

Peritubular capillaries (PTCs) are closely related to renal tubules in structure and function, and both are pivotal regulators in the development and progression of acute kidney injury (AKI). However, the mechanisms that underlie the interaction between PTCs and tubules during AKI remain unclear. Here we explored a new mode of tubulovascular crosstalk mediated by small extracellular vesicles (sEV) after AKI. In response to renal ischemia/reperfusion (I/R) injury, endothelial proliferation of PTCs and tubular expression of vascular endothelial growth factor-A (VEGF-A) were increased, accompanied by a remarkable redistribution of cytoplasmic VEGF-A to the basolateral side of tubular cells. Meanwhile, the secretion mode of VEGF-A was converted in the injured tubular cells, which showed a much greater tendency to secrete VEGF-A via sEV other than the free form. Interestingly, tubular cell-derived VEGF-A-enriched sEV (sEV-VEGF-A) turned out to promote endothelial proliferation which was regulated by VEGF receptors 1 and 2. Furthermore, inhibition of renal sEV secretion by Rab27a knockdown resulted in a significant decrease in the proliferation of peritubular endothelial cells in vivo. Importantly, taking advantage of the newly recognized endogenous repair response of PTCs, exogenous supplementation of VEGF-A + sEV efficiently recused PTC rarefaction, improved renal perfusion, and halted the AKI to CKD transition. Taken together, our study uncovered a novel intrinsic repair response after AKI through renal tubule-PTC crosstalk via sEV-VEGF-A, which could be exploited as a promising therapeutic angiogenesis strategy in diseases with ischemia. [ABSTRACT FROM AUTHOR]

Polyfluoroaryl compounds belong to privileged moieties and engender distinct properties in many pharmaceuticals, agrochemicals, and materials. Over the past decade, considerable seminal reports and reviews have merely paid close attention to fluoroalkylation chemistry, such as trifluoromethylation, difluoroalkylation, perfluoroalkylation, trifluoromethylthiolation or trifluoromethoxylation. Polyfluoroarylation has inevitably lagged somewhat behind its fluoroalkylation counterparts, emanating from a lack of awareness and understanding of the synthetic significance. Together with the renaissance of photochemistry, the photocatalytic polyfluoroarylation using polyfluoroarenes as an inexpensive and easy-available radical precursor has emerged as a topical interest and vibrant area of chemical research. In this review, we have endeavored to present the state-of-the-art in photocatalytic polyfluoroarylation since 2014, and the discussions cover the basic concept, reaction design, mechanistic insight, and research prospects, which are organized by the reaction types. We hope this review will provide a comprehensive overview of this topic and stimulate significant research interest. [ABSTRACT FROM AUTHOR]

A series of hyper-crosslinked porous organic polymers (POPs) were constructed by a facile Friedel–Crafts alkylation reaction of the photoactive unit 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) with formaldehyde dimethyl acetal (FDA), which contains a certain quantity of hydrophilic ether group residues at the terminal of the polymetric networks to improve the dispersibility of POPs. Among them, POP-3 was demonstrated to be a robust heterogeneous photocatalyst for visible-light-promoted aqueous organic transformations, including the C(sp3)–P bond construction and selective oxidation of sulfides in water under mild conditions. Synthetic application of this protocol can be expediently extended to the phosphorylation of commercial drug molecules and the detoxification of the mustard gas simulant CEES. Moreover, the finely designed POP catalysts showed excellent stability, a high surface area and pore volume, and outstanding photoelectric response capability, along with good catalytic performance and reusability properties, which make these materials economical, sustainable, and eco-friendly photocatalysts. [ABSTRACT FROM AUTHOR]

Background: The survival advantage of postoperative chemotherapy for high-risk stage II colon cancer (CC) patients remains unclear. Objectives: The purpose was to evaluate the survival of high-risk stage II CC cases treated with chemotherapy and to construct survival prediction models to predict the survival benefit from chemotherapy. Design: The study is a retrospective observational cohort study. Methods: Data on patients with stage II CC diagnosed from 2005 to 2019 who underwent radical surgery were obtained from the Surveillance, Epidemiology and End Results (SEER) database. A 1:1 propensity score matching (PSM) was applied to obtain two cohorts, chemotherapy versus no chemotherapy. A chi-square analysis was used to assess the differences before and after PSM in the above two groups. Kaplan–Meier survival analysis and Cox proportional hazards regression were applied to investigate the 5- and 10-year overall survival (OS) and cancer cause-specific survival (CSS). The predictive power of the constructed models was assessed by the concordance index (C-index) and calibration curves. Results: Of the 37,050 cases, 14,744 (39.8%) stage II CC were at high-risk and 29.2% of them received chemotherapy. Age, T stage, marital status, histologic grade, gender, and site independently influenced the reception of chemotherapy. The survival advantage of chemotherapy in the high-risk patients remained positive before and after PSM. The estimated 3, 5, and 10 years OS rates of chemotherapy group were 9.3, 10.7, and 15.6% higher than the nonchemotherapy group, respectively. Four nomograms predicting OS and CSS were established, with great discrimination (C-index between 0.627 and 0.691) and excellent calibration. Conclusion: Postoperative chemotherapy is beneficial for high-risk stage II CC patients, including the elderly patients (over 65 years of age). Our study developed nomograms to quantify the survival benefit of chemotherapy among high-risk stage II CC patients to develop personalized treatment recommendations and guide management decisions. [ABSTRACT FROM AUTHOR]

Background: We analysed the survival of colorectal cancer (CRC) patients with lung metastasis and lung-only metastasis and determined the risk factors for lung metastasis in CRC patients.Methods: Data from colorectal cancer patients with lung metastasis diagnosed from 2010 to 2015 were obtained from the SEER database. Survival was analysed using the Kaplan-Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. The predictive ability of the nomgram was assessed by the concordance index (C-index) and calibration curves. The data from the SEER database for the period 2016-2019 was used as an external validation set. The characteristics of 70 CRC patients treated at Shanghai East Hospital between 2016 and 2019 were retrospectively analysed and data from China was chosen as an external validation set.Results: The median survival time for colorectal cancer patients with lung metastasis was 12 months, while this value was 24 months in patients with lung-only metastasis. Among all CRC patients with lung metastasis, age, grade, T stage, N stage, presence of liver, brain or bone metastasis, anatomic site and surgery were related to overall survival (OS). In CRC patients with lung-only metastasis, age, T stage, marital status, chemotherapy and surgery were independent prognostic factors affecting OS. Two nomograms predicting OS were established, with great discrimination (C-index between 0.67 and 0.81) and excellent calibration. Factors including age, race, sex, tumour grade, T stage, N stage, presence of liver, brain or bone metastasis, marital status, insurance status and anatomic location were related to the occurrence of lung metastasis in CRC patients.Conclusion: We developed two reliable clinical prediction models among CRC patients to predict the OS rates in patients with lung metastasis and lung metastasis only. [ABSTRACT FROM AUTHOR]

Clothing is considered to be an important element of human social activities. With the increasing maturity of 3D printing technology, functional 3D printing technology can realize the perfect combination of clothing and electronic devices while helping smart clothing to achieve specific functions. Furthermore, the application of functional 3D printing technology in clothing not only provides people with the most comfortable and convenient wearing experience, but also completely subverts consumers' perception of traditional clothing. This paper introduced the progress of the application of 3D printing from the aspect of traditional clothing and smart clothing through two mature 3D printing technologies normally used in the field of clothing, and summarized the challenges and prospects of 3D printing technology in the field of smart clothing. Finally, according to the analysis of the gap between 3D-printed clothing and traditionally made clothing due to the material limitations, this paper predicted that the rise in intelligent materials will provide a new prospect for the development of 3D-printed clothing. This paper will provide some references for the application research of 3D printing in the field of smart clothing. [ABSTRACT FROM AUTHOR]

In recent years, individual learning path planning has become prevalent in online learning systems, while few studies have focused on teaching path planning for traditional classroom teaching. This paper proposes a target-oriented teaching path optimization scheme for cloud computing-assisted instructions, in which a sequence of learning contents is arranged to ensure the maximum benefit for a given group of students. First, to evaluate the teaching performance, we investigate various student models and define some teaching objectives, including the pass rate, the excellence rate, the average score, and related constraints. Second, a new Deep Reinforcement Learning (DRL)-based teaching path planning method is proposed to tackle the learning path by maximizing a multi-objective target while satisfying all teaching constraints. It adopts a Proximal Policy Optimization (PPO) framework to find a model-free solution for achieving fast convergence and better optimality. Finally, extensive simulations with a variety of commonly used teaching methods show that our scheme provides nice performance and versatility over commonly used student models. [ABSTRACT FROM AUTHOR]

The Chenab basin is located in northwest India and eastern Pakistan. Glaciers in Chenab basin, as local freshwater resources, are very important to the regional ecological environment and development. At the same time, SBAS InSAR can monitor the deformation of the ground for a long time, the monitoring accuracy can reach mm level, and can obtain the time series change of deformation, whcih provides a new idea and method for glacier detection. In this study, the deformation from SBAS InSAR was combined with glacial area data to study the glacial changes in Chenab Basin. Sentinel-1 and Landsat series images were used to obtain the deformation and change in the area of glaciers by SBAS InSAR and the semi-automated method. The results showed that glaciers in the Chenab basin retreated rapidly, especially in the past ten years. The glacier area decreased by 88.05 km2 in 1990∼2000 and 118.86 km2 in 2000∼2010, and the glacier area decreased by 236.01 km2 in 2010∼2020, which was the largest rate of change of 9.49%. Moreover, glacial deformation decreased in 2020, and the deformation rate ranged from -146.3 mm/a to 119.52 mm/a. Most glaciers had deformation rates between -50 mm/a and 50 mm/a. Influenced by precipitation and temperature, glacial deformation in the Chenab basin started to change in August, the maximum accumulation was 6,828.43 mm, and the minimum ablation was -20,656.41 mm. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of triggering receptor expressed on myeloid cells 2 (TREM‐2) in the healthy and diseased tissue, including gingivitis or periodontitis, and then to assess whether it has an impact on the development of periodontitis. Methods and materials: The gingival tissues from healthy controls, gingivitis, and periodontitis underwent hematoxylin–eosin and immunohistochemical staining, and the association of TREM‐2 expression or TREM‐2+ cell counts with clinical parameters was assessed. An anti‐TREM‐2 antibody was used to block the osteoclastogenesis in vitro and during the experimental periodontitis by injection into the gingiva. The relative gene expression of TREM‐2 in different gingival tissues was analyzed by quantitative PCR. Results: In the gingival tissues of periodontitis, TREM‐2 expression and TREM‐2+ cell counts were significantly higher than those of gingivitis and healthy controls (p<0.05). In the group of periodontitis showing moderate signs, the gingival tissues displayed significantly lower TREM‐2 expression, in contrast with the group with advanced periodontal symptoms (p < 0.05). Consistently, blocking TREM‐2 significantly decreased osteoclast formation both in vitro and in vivo (p < 0.05). Conclusion: Increased TREM‐2 expression and TREM‐2+ cells were positively associated with the development of periodontitis. Osteoclast differentiation and stimulating alveolar bone loss were partly relied on TREM‐2, which could be a target to be blocked for attenuating osteoclastogenesis in periodontitits. [ABSTRACT FROM AUTHOR]

Non-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. [ABSTRACT FROM AUTHOR]

Minerals such as calcium carbonates and calcium phosphates are often used as drug protein carriers, which are urgently required for drug protein‐based therapy, due to their high biocompatibility. However, their performance is constrained by some obstacles, such as the low loading capacity and short circulation half‐life. Inspired by the in vivo growth of biominerals via the soluble protein‐stabilized amorphous precursors, herein drug proteins are directly used to stabilize amorphous carbonated calcium phosphate (ACCP) in a controlled mineralization environment. The bioactivity of the drugs in the ACCP carrier is preserved due to the mild synthesis condition. The intrinsically high absorption capability of the ACCP nanoparticles (NPs) leads to an ultra‐high protein loading capacity. In addition, the amorphous nature of the carrier ensures the homogeneous distribution of the protein molecules in the carrier, by which the drugs exhibit long‐term release in vitro. The effectiveness of this strategy by the high osteogenic ability of insulin‐like growth factor‐1 loaded ACCP NPs is demonstrated. Therefore, this biomimetic strategy provides a promising nanoplatform for drug protein‐based applications. [ABSTRACT FROM AUTHOR]

In recent decades, the continuously changed glaciers in the Himalayas not only affected process of atmospheric flow and water cycle in the plateau but also increased the frequency of secondary disasters, such as ice collapse and outburst floods. Therefore, the monitoring of Himalayas glacial change is of great significance in the aspects of climate change and disaster prevention and reduction. The Himalayas glacier outlines in China were extracted by ratio threshold and visual interpretation based on the Landsat TM/ETM+/OLI data and glacier catalogue data. Based on the ASTER GDEM data, the distribution and change characteristics at different altitudes were studied, and the surface moraine was identified to study the influence of glacial area variations. In addition, Glaciers were divided into marine and continental glaciers in this study, and the distribution and changes of the two types of glaciers were analyzed. Also, a comprehensive analysis of a long time series was performed. The results showed that: (1) From 1990 to 2015, the glaciers in the study area showed an overall trend of melting; the annual melting speed gradually accelerated from 0.48%/a to 0.75%/a. The total melting glacial area was 828.16 km2, and the melting rate of the glaciers in the western section was the highest, at 0.63%. (2) The total area of continental glaciers was larger than that of marine glaciers, and its reduction was relatively larger, too. (3) The average size of debris-covered glaciers was 10 times that of debris-free glaciers, but their rate of change (8.1%) was 1/2 of that of debris-free glaciers (17.8%). (4) The number of glaciers gradually decreased as the size of glaciers increased. The glaciers with grades of >50 km2, 0.5∼1 km2, and 1∼2 km2 had large change rates, which were 20.1%, 19.1%, and 18.5%, respectively. In summary, the Himalayas glaciers in China were melting at an accelerated rate and their numbers were gradually decreasing from 1990 to 2015. The location, type, elevation, size and debris cover of a glacier are all important factors influencing glacier change. It has been found that the lower the elevation or the smaller the size of the glacier, the greater the likelihood of glacier ablation, and the debris can inhibit the melting of glaciers to a certain extent. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Comprehensive analysis of KLF2 as a prognostic biomarker associated with fibrosis and immune infiltration in advanced hepatocellular carcinoma" published in BMC Bioinformatics. The correction addresses an error in the funding statement of the original article. The correct funding sources are provided in the correction notice. The correction has been made to the original article. The publisher, Springer Nature, maintains a neutral stance on jurisdictional claims and institutional affiliations. [Extracted from the article]

Fast recognition of integrated circuit (IC) markings is an essential but challenging task in electronic device manufacturing lines. This article develops an adaptive deep learning framework to facilitate the fast marking recognition of IC chips. The proposed framework contains four deep learning components, namely, chip segmentation, orientation correction, character extraction, and character recognition. The four components utilize different convolutional neural network structures to guarantee excellent adaptivity to a wide range of IC types and mitigate the influence of the low-quality chip images. In particular, the character extraction model is comprised of two improved label generation strategies and a proposed border correction method, so as to accommodate tiny scale chips and compactly printed markings. Experiments from the chip image dataset of a real laptop manufacturing line reached a recognition Precision of 91.73% and the Recall of 92.93%. The results demonstrate the superiority of the proposed framework to the state-of-the-art models and the effectiveness of handling a great diversity of chips with different scales, shapes, text fonts, marking colors, and layouts. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Risk assessment provides information about patient prognosis, contributing to the risk stratification of patients and the rational allocation of medical resources. We aimed to develop a model for individualized prediction of renal function decline in patients with type 2 DKD (T2DKD). Patients and Methods: In a retrospective observational study, we followed 307 T2DKD patients and evaluated the determinants of 1) risk of doubling in serum creatinine (Scr), 2) risk of eGFR< 15 mL/min/1.73m2 using potential risk factors at baseline. A prediction model represented by a nomogram and a risk table was developed using Cox regression and externally validated in another cohort with 206 T2DKD patients. The discrimination and calibration of the prediction model were evaluated by the concordance index (C-index) and calibration curve, respectively. Results: Four predictors were selected to establish the final model: Scr, urinary albumin/creatinine ratio, plasma albumin, and insulin treatment. The nomogram achieved satisfactory prediction performance, with a C-index of 0.791 [95% confidence interval (CI) 0.762– 0.820] in the derivation cohort and 0.793 (95% CI 0.746– 0.840) in the external validation cohort. Then, all predictors were scored according to their weightings. A risk table with the highest score of 11.5 was developed. The C-index of the risk table was 0.764 (95% CI: 0.731– 0.797), which was similar to the external validation cohort (0.763; 95% CI: 0.714– 0.812). Additionally, the patients were divided into two groups based on the risk table, and significant differences in the probability of outcome events were observed between the high-risk (score > 2) and low-risk (score ≤ 2) groups in the derivation and external validation cohorts (P < 0.001). Conclusion: The nomogram and the risk table using readily available clinical parameters could be new tools for bedside prediction of renal function decline in T2DKD patients. Graphical [ABSTRACT FROM AUTHOR]

Background Urinary sediment messenger RNAs (mRNAs) have been shown as novel biomarkers of kidney disease. We aimed to identify targeted urinary mRNAs in diabetic nephropathy (DN) based on bioinformatics analysis and clinical validation. Methods Microarray studies of DN were searched in the GEO database and Nephroseq platform. Gene modules negatively correlated with estimated glomerular filtration rate (eGFR) were identified by informatics methods. Hub genes were screened within the selected modules. In validation cohorts, a quantitative polymerase chain reaction assay was used to compare the expression levels of candidate mRNAs. Patients with renal biopsy–confirmed DN were then followed up for a median time of 21 months. End-stage renal disease (ESRD) was defined as the primary endpoint. Multivariate Cox proportional hazards regression was developed to evaluate the prognostic values of candidate mRNAs. Results Bioinformatics analysis revealed four chemokines (CCL5, CXCL1, CXLC6 and CXCL12) as candidate mRNAs negatively correlated with eGFR, of which CCL5 and CXCL1 mRNA levels were upregulated in the urinary sediment of patients with DN. In addition, urinary sediment mRNA of CXCL1 was negatively correlated with eGFR (r = −0.2275, P = 0.0301) and CCL5 level was negatively correlated with eGFR (r = −0.4388, P < 0.0001) and positively correlated with urinary albumin:creatinine ratio (r = 0.2693, P = 0.0098); also, CCL5 and CXCL1 were upregulated in patients with severe renal interstitial fibrosis. Urinary sediment CCL5 mRNA was an independent predictor of ESRD [hazard ratio 1.350 (95% confidence interval 1.045–1.745)]. Conclusions Urinary sediment CCL5 and CXCL1 mRNAs were upregulated in DN patients and associated with a decline in renal function and degree of renal interstitial fibrosis. Urinary sediment CCL5 mRNA could be used as a potential prognostic biomarker of DN. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the value of morphological feature and signal intensity ratio (SIR) derived from conventional magnetic resonance imaging (MRI) in distinguishing primary central nervous system lymphoma (PCNSL) from atypical glioblastoma (aGBM). Methods: Pathology-confirmed PCNSLs (n = 93) or aGBMs (n = 48) from three institutions were retrospectively enrolled and divided into training cohort (n = 98) and test cohort (n = 43). Morphological features and SIRs were compared between PCNSL and aGBM. Using linear discriminant analysis, multiple models were constructed with SIRs and morphological features alone or jointly, and the diagnostic performances were evaluated via receiver operating characteristic (ROC) analysis. Areas under the curves (AUCs) and accuracies (ACCs) of the models were compared with the radiologists' assessment. Results: Incision sign, T2 pseudonecrosis sign, reef sign and peritumoral leukomalacia sign were associated with PCNSL (training and overall cohorts, P < 0.05). Increased T1 ratio, decreased T2 ratio and T2/T1 ratio were predictive of PCNSL (all P < 0.05). ROC analysis showed that combination of morphological features and SIRs achieved the best diagnostic performance for differentiation of PCNSL and aGBM with AUC/ACC of 0.899/0.929 for the training cohort, AUC/ACC of 0.794/0.837 for the test cohort and AUC/ACC of 0.869/0.901 for the overall cohort, respectively. Based on the overall cohort, two radiologists could distinguish PCNSL from aGBM with AUC/ACC of 0.732/0.724 for radiologist A and AUC/ACC of 0.811/0.829 for radiologist B. Conclusion: MRI morphological features can help differentiate PCNSL from aGBM. When combined with SIRs, the diagnostic performance was better than that of radiologists' assessment. [ABSTRACT FROM AUTHOR]

Fatigue test of a needled C/SiC composite with a notch under tension-tension cyclic loading was completed, and the main fatigue crack propagation curve of the needled composite was obtained by the in situ observation of the fatigue process. By analyzing the influence of the failure number and distribution on the tensile loading subjected by 0° fiber bundles, the relationship between the main fatigue crack propagation and the distribution of 0° fiber bundles in the needled composite was established. By observing the fracture microstructure (especially the distribution of 0° fiber bundles) of the needled composite through scanning electron microscopy, the reasons for the varying fatigue resistance of different notched specimens were also explained. In addition, acoustic emission (AE) was also used to analyze the AE energy characteristics during the fatigue crack propagation process of the needled composite. [ABSTRACT FROM AUTHOR]

Foot process effacement is an important feature of early diabetic nephropathy (DN), which is closely related to the development of albuminuria. Under certain nephrotic conditions, the integrity and function of the glomerular slit diaphragm (SD) structure were impaired and replaced by the tight junction (TJ) structure, resulting in so-called SD-TJ transition, which could partially explain the effacement of foot processes at the molecular level. However, the mechanism underlying the SD-TJ transition has not been described in DN. Here, we demonstrated that impaired autophagic flux blocked p62-mediated degradation of ZO-1 (TJ protein) and promoted podocytes injury via activation of caspase3 and caspase8. Interestingly, the expression of VDR in podocytes was decreased under diabetes conditions, which impaired autophagic flux through downregulating Atg3. Of note, we also found that VDR abundance was negatively associated with impaired autophagic flux and SD-TJ transition in the glomeruli from human renal biopsy samples with DN. Furthermore, VDR activation improved autophagic flux and attenuated SD-TJ transition in the glomeruli of diabetic animal models. In conclusion, our data provided the novel insight that VDR/Atg3 axis deficiency resulted in SD-TJ transition and foot processes effacement via blocking the p62-mediated autophagy pathway in DN. [ABSTRACT FROM AUTHOR]

Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) is a master regulator of adaptive responses to hypoxia. Aside from posttranslational hydroxylation, the mechanism of HIF-1 regulation in AKI remains largely unclear. In this study, the mechanism of HIF-a regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia-reperfusion-, unilateral ureteral obstruction-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB, which plays a central role in the inflammation response, was involved in the increasing expression of HIF-1α in AKI, as evidenced by pharmacological modulation (NF-κB inhibitor BAY11-7082). Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription, which occurred not only under hypoxic conditions but also under normoxic conditions. Moreover, the induced HIF-1α by inflammation protected against tubular injury in AKI. Thus, our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]