Atmosphere teleconnections from abatement of China aerosol emissions exacerbate Northeast Pacific warm blob events.

During 2010 to 2020, Northeast Pacific (NEP) sea surface temperature (SST) experienced the warmest decade ever recorded, manifested in several extreme marine heatwaves, referred to as "warm blob" events, which severely affect marine ecosystems and extreme weather along the west coast of North America. While year-to-year internal climate variability has been suggested as a cause of individual events, the causes of the continuous dramatic NEP SST warming remain elusive. Here, we show that other than the greenhouse gas (GHG) forcing, rapid aerosol abatement in China over the period likely plays an important role. Anomalous tropospheric warming induced by declining aerosols in China generated atmospheric teleconnections from East Asia to the NEP, featuring an intensified and southward-shifted Aleutian Low. The associated atmospheric circulation anomaly weakens the climatological westerlies in the NEP and warms the SST there by suppressing the evaporative cooling. The aerosol-induced mean warming of the NEP SST, along with internal climate variability and the GHG-induced warming, made the warm blob events more frequent and intense during 2010 to 2020. As anthropogenic aerosol emissions continue to decrease, there is likely to be an increase in NEP warm blob events, disproportionately large beyond the direct radiative effects.

NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression.

Although the patient's survival time in various cancers has significantly increased in recent decades, the overall 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) has remained virtually unchanged due to rapid progression and metastasis. While N-acetyltransferase 10 (NAT10) has been identified as a regulator of mRNA acetylation in many malignancies, its role in PDAC remains unclear. Here, we found that NAT10 mRNA and protein levels were upregulated in PDAC tissues. Increased NAT10 protein expression was significantly correlated with poor prognosis in PDAC patients. Through our experiments, we demonstrated that NAT10 acted as an oncogene to promote PDAC tumorigenesis and metastasis in vitro and in vivo. Mechanistically, NAT10 exerts its oncogenic effects by promoting mRNA stability of receptor tyrosine kinase AXL in an ac4C-dependent manner leading to increased AXL expression and further promoting PDAC cell proliferation and metastasis. Together, our findings highlight the critical of NAT10 in PDAC progression and reveal a novel epigenetic mechanism by which modified mRNA acetylation promotes PDAC metastasis.

A Novel Four-Step Algorithm for Detecting a Single Circle in Complex Images.

Single-circle detection is vital in industrial automation, intelligent navigation, and structural health monitoring. In these fields, the circle is usually present in images with complex textures, multiple contours, and mass noise. However, commonly used circle-detection methods, including random sample consensus, random Hough transform, and the least squares method, lead to low detection accuracy, low efficiency, and poor stability in circle detection. To improve the accuracy, efficiency, and stability of circle detection, this paper proposes a single-circle detection algorithm by combining Canny edge detection, a clustering algorithm, and the improved least squares method. To verify the superiority of the algorithm, the performance of the algorithm is compared using the self-captured image samples and the GH dataset. The proposed algorithm detects the circle with an average error of two pixels and has a higher detection accuracy, efficiency, and stability than random sample consensus and random Hough transform.

The long-term efficacy of transoral incisionless fundoplication with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease.

BACKGROUND: To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD). METHODS: A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital （Shanghai, China）from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects. RESULTS: Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference. CONCLUSION: TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn. TRIAL REGISTRATION: ChiCTR2000034350.

Progress, Challenge, and Perspective of Fabricating Cellulose.

Cellulose as the most abundant biopolymers on Earth, presents appealing performance in mechanical properties, thermal management, and versatile functionalization. Developing fabrication methods to design functional materials and open new application areas. However, cellulose is hard to be dissolved or melt due to its recalcitrant property. Herein, the recent progress of fabricating cellulose is summarized. First, the unique hierarchical structure of cellulose is fully investigated and the resulted processability is analysed in directions of down to nanocellulose, dissolution, and thermoplastic processing. Then, the reported fabrication methods are summarized in three aspects: (1) self-assembly from nano/micro cellulose suspensions, especially the formation of cellulose nanocrystals; (2) dissolution-regeneration-drying, covering spinning and solvent infusion processing; and (3) thermoplastic processing, focusing on the setup and the morphology changes of the prepared products. In each aspect, the flowchart of the fabrication method, the mechanism, fabricated products, and effects of processing parameters are explored. Finally, this review provides a perspective on the further direction of fabricating cellulose, especially the challenges toward mass production.

Calpain Inhibitor Calpeptin Improves Pancreatic Fibrosis in Mice with Chronic Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells.

BACKGROUND: Pancreatic fibrosis is a hallmark feature of chronic pancreatitis (CP), resulting in persistent damage to the pancreas. The sustained activation of pancreatic stellate cells (PSCs) plays a pivotal role in the progression of pancreatic fibrosis and is a major source of extracellular matrix (ECM) deposition during pancreatic injury. METHODS: Calpain is a calcium-independent lysosomal neutral cysteine endopeptidase and was found to be correlated to various fibrotic diseases. Studies have revealed that calpeptin, a calpain inhibitor, can improve the fibrosis process of multiple organs. This study investigated the effect of the calpain inhibitor, calpeptin, on fibrosis in experimental CP and activation of cultured PSCs in mice. CP was induced in mice by repeated injections of cerulein for four weeks in vivo, and the activation process of mouse PSCs was isolated and cultured in vitro. Then, the inhibitory effect of calpeptin on pancreatic fibrosis was confirmed based on the histological damage of CP, the expression of α-smooth muscle actin (α-SMA) and collagen-Iα1(Col1α1), and the decrease in mRNA levels of calpain-1 and calpain-2. RESULTS: In addition, it was revealed that calpeptin can inhibit the activation process of PSCs and induce significant PSCs apoptosis by downregulating the expression of calpain-1, calpain-2 and TGF-ß1, and the expression and phosphorylation of smad3 in vitro. CONCLUSION: These results suggest that the calpain inhibitor, calpeptin, plays a key role in the regulation of PSC activation by inhibiting the TGF-ß1/smad3 signaling pathway, which supports the potential of calpeptin as an inhibitor of pancreatic fibrosis in mice by interfering with calpain.

Enhanced High-Temperature Wear Performance of H13 Steel through TiC Incorporation by Laser Metal Deposition.

High-temperature wear failure has been a major challenge to die parts. This work provides a comprehensive study on the high-temperature wear performance of a TiC/H13 composite coating prepared by laser metal deposition (LMD). The microstructures of wrought H13 samples, LMD-processed H13 and TiC/H13 samples were systematically investigated. The refined martensite size, the uniform distribution of TiC ceramic particles, as well as their bonding with the matrix endowed the fabricated composite coating with superior hardness. The LMD-prepared TiC/H13 composite coating material demonstrated outstanding wear resistance when compared with other counterparts, mainly due to the high thermal stability and the load-transferring effect triggered by the introduced TiC ceramic particles. The dominated wear mechanism transition from severe ploughing in the wrought H13 material to mild delamination in the TiC/H13 composite coating was confirmed. The present study is expected to shed light on high-temperature wear-resistant coating material design and applications within the highly demanding mould industry.

Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer.

Pancreatic cancer (PC) is one of the most malignant tumors. Rapid progression and distant metastasis are the main causes of patient death. Hypoxia is a hallmark of multiple cancers and is involved in tumor biology. However, little is known about the roles of circRNAs in glycolysis and hypoxia-mediated progression of PC. Here, the expression pattern of hypoxia-related circRNAs was analyzed using RNA sequencing. A unique circRNA termed circRNF13 was found to be upregulated in PC tissues and may be a potential prognostic indicator. HIF-1α and EIF4A3 are involved in regulating the biogenesis of circRNF13. Furthermore, circRNF13 was validated to exert a stimulative effect on cell proliferation, angiogenesis, invasion and glycolysis. Importantly, we found that circRNF13 promoted PDK3 levels by acting as a miR-654-3p sponge, thus promoting the PC malignant process. Collectively, our results reveal that hypoxia-induced circRNF13 mediated by HIF-1α and EIF4A3 promotes tumor progression and glycolysis in PC, indicating the potential of circRNF13 as a prognostic biomarker and therapeutic target for PC.

The pancreatic clock is a key determinant of pancreatic fibrosis progression and exocrine dysfunction.

Chronic pancreatitis (CP) is characterized by progressive fibrosis and exocrine dysregulation, which have long been considered irreversible. As a peripheral oscillator, the pancreas harbors autonomous and self-sustained timekeeping systems in both its endocrine and exocrine compartments, although the role of the latter remains poorly understood. By using different models of CP established in mice with dysfunctional pancreatic clocks, we found that the local clock played an important role in CP pathology, and genetic or external disruption of the pancreatic clock exacerbated fibrogenesis and exocrine insufficiency. Mechanistically, an impaired retinoic acid receptor-related orphan receptor A (Rora)/nuclear receptor subfamily 1, group D, member 1 (Nr1d1)/aryl hydrocarbon receptor nuclear translocator-like (Arntl or Bmal1) loop, called the circadian stabilizing loop, resulted in the deficiency of pancreatic Bmal1, which was responsible for controlling the fibrogenic properties of pancreatic stellate cells (PSCs) and for rewiring the function of acinar cells in a clock-TGF signaling-IL-11/IL-11RA axis-dependent manner. During PSC activation, the antagonistic interaction between Nr1d1 and Rora was unbalanced in response to the loss of cytoplasmic retinoid-containing lipid droplets. Patients with CP also exhibited reduced production of endogenous melatonin. Enhancing the clock through pharmacological restoration of the circadian stabilizing loop using a combination of melatonin and the Rora agonist SR1078 attenuated intrapancreatic pathological changes in mouse models of CP. Collectively, this study identified a protective role of the pancreatic clock against pancreatic fibrosis and exocrine dysfunction. Pancreatic clock-targeted therapy may represent a potential strategy to treat CP.

4D Printing of Magnetoactive Soft Materials for On-Demand Magnetic Actuation Transformation.

Four-dimensional (4D) printed magnetoactive soft material (MASM) with a three-dimensional (3D) patterned magnetization profile possesses programmable shape transformation and controllable locomotion ability, showing promising applications in actuators and soft robotics. However, typical 4D printing strategies for MASM always introduced a printing magnetic field to orient the magneto-sensitive particles in polymers. Such strategies not only increase the cooperative control complexity of a 3D printer but may also induce local agglomeration of magneto-sensitive particles, which disturbs the magnetization of the already-printed structure. Herein, we proposed a novel 4D printing strategy that coupled the traditional 3D injection printing with the origami-based magnetization technique for easy fabrication of MASM objects with a 3D patterned magnetization profile. The 3D injection printing that can rapidly create complex 3D structures and the origami-based magnetization technique that can generate the spatial magnetization profile are combined for fabrication of 3D MASM objects to yield programmable transformation and controllable locomotion. A physics-based finite element model was also developed for the design guidance of origami-based magnetization and magnetic actuation transformation of MASM. We further demonstrated the diverse functions derived from the complex shape deformation of MASM-based robots, including a bionic human hand that played "rock-paper-scissors" game, a bionic butterfly that swung the wings on the flower, and a bionic turtle that crawled on the land and swam in the water.