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Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide, and novel therapeutic targets still need to be investigated to alleviate myocardial injury and the ensuing maladaptive cardiac remodelling. Accumulating studies have indicated that lncRNA H19 might exert a crucial regulatory effect on cardiovascular disease. In this study, we aimed to explore the biological function and molecular mechanism of H19 in MI. To investigate the biological functions of H19, miRNA‐22‐3p and KDM3A, gain‐ and loss‐of‐function experiments were performed. In addition, bioinformatics analysis, dual‐luciferase reporter assays, RNA immunoprecipitation (RIP) assays, RNA pull‐down assays, quantitative RT‐PCR and Western blot analyses as well as rescue experiments were conducted to reveal an underlying competitive endogenous RNA (ceRNA) mechanism. We found that H19 was significantly down‐regulated after MI. Functionally, enforced H19 expression dramatically reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating myocardial apoptosis and decreasing inflammation. However, H19 knockdown resulted in the opposite effects. Bioinformatics analysis and dual‐luciferase assays revealed that, mechanistically, miR‐22‐3p was a direct target of H19, which was also confirmed by RIP and RNA pull‐down assays in primary cardiomyocytes. In addition, bioinformatics analysis and dual‐luciferase reporter assays also demonstrated that miRNA‐22‐3p directly targeted the KDM3A gene. Moreover, subsequent rescue experiments further verified that H19 regulated the expression of KDM3A to ameliorate MI‐induced myocardial injury in a miR‐22‐3p‐dependent manner. The present study revealed the critical role of the lncRNAH19/miR‐22‐3p/KDM3A pathway in MI. These findings suggest that H19 may act as a potential biomarker and therapeutic target for MI.

Cavity design is crucial for single-mode semiconductor lasers such as the ubiquitous distributed feedback and vertical-cavity surface-emitting lasers. By recognizing that both of these optical resonators feature a single mid-gap mode localized at a topological defect in the one-dimensional lattice, we upgrade this topological cavity design concept into two dimensions using a honeycomb photonic crystal with a vortex Dirac gap by applying the generalized Kekulé modulations. We theoretically predict and experimentally show on a silicon-on-insulator platform that the Dirac-vortex cavities have scalable mode areas, arbitrary mode degeneracies, vector-beam vertical emission and compatibility with high-index substrates. Moreover, we demonstrate the unprecedentedly large free spectral range, which defies the universal inverse relation between resonance spacing and resonator size. We believe that our topological micro-resonator will be especially useful in applications where single-mode behaviour is required over a large area, such as the photonic-crystal surface-emitting laser.Surface emission from a topological mid-gap cavity shows large free spectral range and arbitrary mode degeneracy.

Lithium niobate (LN) thin film has received much attention as an integrated photonic platform, due to its rich and great photoelectric characteristics, based on which various functional photonic devices, such as electro-optic modulators and nonlinear wavelength converters, have been demonstrated with impressive performance. As an important part of the integrated photonic system, the long-awaited laser and amplifier on the LN thin-film platform have made a series of breakthroughs and important progress recently. In this review paper, the research progress of lasers and amplifiers realized on lithium niobate thin film platforms is reviewed comprehensively. Specifically, the research progress on optically pumped lasers and amplifiers based on rare-earth ions doping of LN thin films is introduced. Some important parameters and existing limitations of the current development are discussed. In addition, the implementation scheme and research progress of electrically pumped lasers and amplifiers on LN thin-film platforms are summarized. The advantages and disadvantages of optically and electrically pumped LN thin film light sources are analyzed. Finally, the applications of LN thin film lasers and amplifiers and other on-chip functional devices are envisaged.

Microresonators of ultrahigh quality (Q) factors represent a crucial type of photonic devices aiming at ultra-high spectral resolution, ultra-high sensitivity to the environmental perturbations, and efficient nonlinear wavelength conversions at low threshold pump powers. Lithium niobate on insulator (LNOI) microdisks of high Q factors are particularly attractive due to its large second-order nonlinear coefficient and strong electro-optic property. In this letter, we break through the long standing bottleneck in achieving the Q factors of LNOI microresonators beyond 108, which approaches the intrinsic material absorption limit of lithium niobate (LN). The ultra-high Q factors give rise to a rich family of nonlinear optical phenomena from optical parametric oscillation (OPO) to harmonics generation with unprecedented characteristics including ultra-low pump threshold, high wavelength conversion efficiency, and ultra-broad operation bandwidth. Specifically, the threshold of OPO is measured to be only 19.6 μW, and the absolute conversion efficiency observed in the second harmonic generation reaches 23%. The record-breaking performances of the on-chip ultra-high Q LNOI microresonators will have profound implication for both photonic research and industry.

Medical image registration is a fundamental and important technique in the field of medical image analysis. This study proposes a novel unsupervised end‐to‐end registration network, aiming to enable the model to actively acquire image features in the field of medical imaging with limited samples, which efficiently integrates multi‐scale features to achieve higher accuracy in registration. By utilizing region‐to‐region routing, this model actively preserves the most relevant features of the images, thereby improving training and learning efficiency. The model is evaluated by several publicly available datasets. The new network proposed in this study achieved the best registration accuracy among various advanced traditional and learning‐based methods. A novel unsupervised end‐to‐end neural network registration model, AHN, is proposed for the registration evaluation of 3D brain MRI scans on publicly available datasets. Experimental results demonstrate that this method exhibits highly advanced registration performance. Medical image registration is a classical application of computer technology in the field of medicine, serving as a fundamental yet challenging area that still requires significant breakthroughs.

In order to obtain the best CO2 blasting drilling efficiency and improve the gas permeability coefficient of the coal seam in the mining area, a research method of liquid CO2 phase change blasting in the coal seam based on electrochemical numerical simulation is proposed. In this paper, the electrochemical numerical simulation of coalbed methane caused by liquid CO2 phase change blasting is studied through theoretical analysis, the antireflection mechanism of liquid carbon dioxide gas explosion on broken coal seam is obtained, and the initial fracture length of coal body caused by gas explosion stress wave is deduced by the mathematical model. A method for improving CBM desorption with nonmechanical coal was proposed, namely, a method for electrochemically strengthening CBM desorption. A comprehensive theory and application system of liquid carbon dioxide phase change gas explosion and anti-reflection technology are established by combining theoretical analysis, experimental research, and numerical simulation with field industrial comparative experiment. According to the gas tracing method, the precise measurement of the working face shows that the impact radius of the collision caused by the explosion of the liquid carbon dioxide phase change gas is 2 m. Gas emissions increased the emissions of coal seam drilling in the affected areas by 4 to 8 times, and the gas emission attenuation coefficient decreased from 0.76 times to 0.93 times. The carbon dioxide phase change gas cracking theory and antireflection theory and their application technology system are systematically studied. The research shows that the liquid carbon dioxide phase transfer gas blasting and infiltration technology is not limited by the geological conditions of the coal seam and has the characteristics of high efficiency and inherent climate. In view of the wide area of coal mines and the harsh geological conditions of coal seams, carbon dioxide phase change gas-induced cracking antireflection technology has application prospects and expandability.

Background Studies have reported age as a risk factor for cardiovascular disease (CVD)‐related mortality; however, only a few studies have focused on the relationship between age and CVD‐related mortality, especially among major gastrointestinal cancers. Method The present retrospective cohort enrolled patients with colorectal, pancreatic, hepatocellular, gastric, and esophageal cancer between 2000 to 2015 from the Surveillance, Epidemiology and End Results Registry (SEER). Standardized mortality ratio (SMR), competing risk regression, and restricted cubic spline (RCS) analyses were used in our study. Results We analyzed 576,713 patients with major gastrointestinal cancers (327,800 patients with colorectal cancer, 93,310 with pancreatic cancer, 69,757 with hepatocellular cancer, 52,024 with gastric cancer, and 33,822 with esophageal cancer). Overall, CVD‐related mortality gradually decreased every year, and the majority were older patients. All cancer patients had a higher CVD‐related mortality rate than the general U.S. population. The adjusted sub‐hazard ratios for middle‐aged with colorectal cancer, pancreatic cancer, hepatocellular cancer, gastric cancer, and esophageal cancer were 2.55 (95% CI: 2.15–3.03), 1.77 (95% CI: 1.06–2.97), 2.64 (95% CI: 1.60–4.36), 2.15 (95% CI: 1.32–3.51), and 2.28 (95% CI: 1.17–4.44), respectively. The adjusted sub‐hazard ratios for older patients with colorectal cancer, pancreatic cancer, hepatocellular cancer, gastric cancer, and esophageal cancer were 11.23 (95% CI: 9.50–13.27), 4.05 (95% CI: 2.46–6.66), 4.47 (95% CI: 2.72–7.35), 7.16 (95% CI: 4.49–11.41), and 4.40 (95% CI: 2.28–8.48), respectively. A non‐linear relationship between age at diagnosis and CVD‐related mortality was found in colorectal cancer, pancreatic cancer, and esophageal cancer; their reference ages were 67, 69, and 66 years old, respectively. Conclusion This study demonstrated that age was a risk factor for CVD‐related mortality among major gastrointestinal cancers.

Background The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors showing significant outcomes in treating germline BRCA1/2 (g BRCA1/2 ) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (s BRCA1/2 ) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1 , BRCA2 , and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing. Methods A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1 , BRCA2 , and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing. Results Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2 , BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1 -mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2 , p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2 , p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants ( BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant ( PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB. Conclusion Our study depicted the mutational patterns of BRCA1 , BRCA2 , and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.

Hepatitis E is recognized as a significant zoonotic disease burden in China, with the hepatitis E virus (HEV) identified as the etiological agent responsible for this disease. HEV exhibits no specific host tropism, which facilitates its transmission among various mammalian species, including humans, pigs, cattle, goats, and others. Currently, the availability of effective therapeutic agents and vaccines for HEV infection is limited. Therefore, a comprehensive understanding of the epidemiological characteristics of HEV, and the existing detection methods, is crucial for disease prevention and control. In this review, we provide an overview of the current knowledge on HEV in China, mainly focusing on detection strategies, molecular characteristics, and the prevalence of this pathogen in the human population and other susceptible species. This review will be useful to enhance public awareness of HEV and to accelerate disease control efforts in the future.

Background Cannabinoid-2 receptor (CB2R) plays an important role in the cascading inflammation following ischemic injury. The toll-like receptors 4 (TLR4)/matrix metalloproteinase 9 (MMP9) signal pathway is involved in blood-brain barrier dysfunction induced by ischemia stroke. The aim of this study is to investigate the roles of exogenous activation of CB2R on attenuating neurological deficit and blood-spinal cord barrier (BSCB) disruption during rat spinal cord ischemia reperfusion (I/R) injury, through modulation of the TLR4/MMP9 axis. Methods Animals were intraperitoneally pretreated with TLR4 inhibitor TAK-242, CB2R agonist JWH-133 with or without CB2R antagonist AM630, or equivalent volume of vehicle 1 h before undergoing 14-min occlusion of descending aorta or sham operation. One, two, three, and 7 days after reperfusion, hindlimb locomotor function was evaluated with Basso, Beattie, and Bresnahan (BBB) Locomotor Scale, BSCB integrity was detected by measurement of Evans blue (EB) extravasation and spinal cord edema. The protein expression levels of CB2R, tight junction protein Zonula occluden-1 (ZO-1), TLR4, MMP9, MyD88, NF-κB p65, and NF-κB p-p65 were determined by western blot. The MMP9 activity was analyzed by gelatin zymography. Double immunofluorescence staining was used to identify the perivascular localization of CB2R, TLR4, MMP9, and reactive astrocytes, as well as the colocalization of CB2R, TLR4, and MMP9 with reactive astrocytes. Results JWH-133 pretreatment attenuated hindlimb motor functional deficit and BSCB leakage, along with preventing downregulation of ZO-1 and upregulation of TLR4/MMP9, similar to the effects of TAK-242 preconditioning. JWH-133 or TAK-242 pretreatment reduced the perivascular expression of TLR4/MMP9 and reactive astrocytes following injury. JWH-133 pretreatment also downregulated MyD88/NF-κB level, MMP9 activity, and the astrocytic TLR4/MMP9 after I/R injury. Conclusions Exogenous activation of CB2R by JWH-133 attenuated neurological deficit and BSCB disruption after spinal cord I/R injury via inhibition of TLR4/MMP9 expression.