Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are the first known unique molecular signatures of ASC.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with high morbidity and mortality. Circulating histones (CHs), a group of damage-associated molecular pattern molecules mainly derived from neutrophil extracellular traps, play a crucial role in sepsis by mediating inflammation response, organ injury and death through Toll-like receptors or inflammasome pathways. Herein, we first elucidate the molecular mechanisms of histone-induced inflammation amplification, endothelium injury and cascade coagulation activation, and discuss the close correlation between elevated level of CHs and disease severity as well as mortality in patients with sepsis. Furthermore, current state-of-the-art on anti-histone therapy with antibodies, histone-binding proteins (namely recombinant thrombomodulin and activated protein C), and heparin is summarized to propose promising approaches for sepsis treatment.

The management of PCa in China differs from that in Western countries. To date surgical castration represents standard treatment. Screening detection of PCa could help detect earlier stage tumors and improve the outcome in patients.

Cardiovascular diseases have high morbidity and mortality rates worldwide, and their treatment and prevention are challenging. MicroRNAs are a series of noncoding RNAs with highly conserved sequences and regulate gene expression by inhibiting mRNA transcription or degrading targeting proteins. MicroRNA-210 is significantly upregulated during hypoxia and plays a protective role by inhibiting apoptosis and regulating cell proliferation, differentiation, migration, mitochondrial metabolism, and angiogenesis in hypoxic cells. MicroRNA-210 expression is altered in cardiovascular diseases such as atherosclerosis, acute myocardial infarction, preeclampsia, aortic stenosis, and heart failure, and overexpression of microRNA-210 in some of these diseases exerts protective effects on target organs. Furthermore, chronically upregulated miR-210 potentially plays a marked pathogenic role in specific situations. This review primarily focuses on the upstream pathways, downstream targets, clinical progress in cardiovascular disease, and potential applications of microRNA-210.

Rhenium disulfide (ReS 2 ), a member of group VII transition metal dichalcogenides (TMDs), has attracted increasing attention because of its unique distorted 1T structure and electronic and optical properties, which are much different from those of group VI TMDs (MoS 2 , WS 2 , MoSe 2 , WSe 2 , etc.). It has been proved that bulk ReS 2 behaves as a stack of electronically and vibrationally decoupled monolayers, which offers remarkable possibilities to prepare a monolayer ReS 2 facilely and offers a novel platform to study photonic properties of TMDs. However, due to the large and layer-independent bandgap, the nonlinear optical properties of ReS 2 from the visible to midinfrared spectral range have not yet been investigated. Here, the band structure of ReS 2 with the introduction of defects is simulated by the ab initio method, and the results indicate that the bandgap can be reduced from 1.38 to 0.54 eV with the introduction of defects in a suitable range. In the experiment, using a bulk ReS 2 with suitable defects as the raw material, a few-layered broadband ReS 2 saturable absorber (SA) is prepared by the liquid phase exfoliation method. Using the as-prepared ReS 2 SA, passively Q-switched solid-state lasers at wavelengths of 0.64, 1.064, and 1.991 μm are investigated systematically. Moreover, with cavity design, a femtosecond passively modelocked laser at 1.06 μm is successfully realized based on the as-prepared ReS 2 SA for the first time. The results present a promising alternative for a rare broadband optical modulator and indicate the potential of ReS 2 in generating Q-switched and mode-locked pulsed lasers. It is further anticipated that this work may be helpful for the design of 2D optoelectronic devices with variable bandgaps.

Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

Background/Aims: The myocardial energy metabolism shift is one of the most important pathological features of ischemic heart disease (IHD). Although several microRNAs (miRs) are involved in the regulation of myocardial energy metabolism, their exact effects and underlying mechanisms remain unclear. The aim of this study was to investigate whether microRNA(miR-210) regulates the energy metabolism shift during oxidative stress in H9c2 cardiomyocytes. Methods: Cell survival was analyzed via CCK assay. The energy metabolism shift was detected by lactate assay, ATP assay and RT² profiler glucose metabolism PCR array. Protein and mRNA expression levels were determined by western blot and qPCR. We also used kits to detect the activity of Complex I, Sirt3 and the NAD⁺/NADH ratio. Results: We determined that miR-210 promoted the energy metabolism shift. The iron-sulfur cluster assembly protein (ISCU) was a target of miR-210. Additionally, we detected the activity of complex I and found that miR-210 inhibits mitochondrial respiration. Interestingly, miR-210 may also indirectly regulate SIRT3 by regulating ISCU. Conclusion: Our results confirm that miR-210 is essential and sufficient for modulating the cellular energy metabolism shift during H₂O₂-induced oxidative stress in H9c2 cardiomyocytes by targeting ISCU.

A novel two-dimensional (2D) material member in the transition metal dichalcogenides family, few-layered rhenium disulfide (ReS) was prepared by liquid phase method successfully. By using the open-aperture Z-scan method, the saturable absorption properties at 2.8 μm were characterized with a saturable fluence of 22.6  μJ/cm and a modulation depth of 9.7%. A passively Q-switched solid-state laser at 2.8 μm was demonstrated by using the as-prepared ReS saturable absorber successfully. Under an absorbed pump power of 920 mW, a maximum output power of 104 mW was obtained with a pulse width of 324 ns and a repetition rate of 126 kHz. To the best of our knowledge, this is the first demonstration of applying ReS in an all-solid-state laser. Moreover, this represents the shortest pulses in Q-switched MIR lasers based on a 2D material as the saturable absorber, which demonstrated the superiority of ReS acting as an optical modulator for generating short-pulsed lasers. The results well prove that 2D ReS is a reliable optical modulator for MIR solid-state lasers.