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Limin Li, Wenli Diao, Ke Zen Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies globally. Each year, more than 500,000 people worldwide are diagnosed with HCC. The onset of HCC is typically unnoticeable, and the prognosis is usually poor. The early diagnosis of HCC and dynamic monitoring of this disease can contribute to more effective therapeutic interventions and improve patient outcomes. To achieve early diagnosis, more sensitive, specific, and easily detectable biomarkers are necessary. Recently, scientists have focused on identifying novel, sensitive, and minimally invasive or noninvasive biomarkers. Micro-ribonucleic acids (miRNAs) are a class of endogenous noncoding single-stranded RNAs that regulate gene expression at the posttranscriptional level. By negatively regulating target-gene expression, miRNAs play a critical role in diverse biological processes, including apoptosis, proliferation, differentiation, and developmental timing. Unique changes in miRNA expression in serum or plasma samples from HCC patients have been reported, suggesting that miRNAs may serve as novel noninvasive biomarkers for diagnosing HCC and evaluating therapeutic responses or as potential therapeutic targets in HCC. This review focuses on recent progress in understanding the role of miRNAs in HCC pathogenesis and progression, and highlights their diagnostic and prognostic value for HCC patients. Keywords: hepatocellular carcinoma, miRNA, biomarker, diagnosis, prognosis

Acidification of the endosomal pathway is important for ligand and receptor sorting, toxin activation, and protein degradation by lysosomal acid hydrolases. Fluorescent probes and imaging methods were developed to measure pH to better than 0.2 U accuracy in individual endocytic vesicles in Swiss 3T3 fibroblasts. Endosomes were pulse labeled with transferrin (Tf), alpha 2-macroglobulin (alpha 2M), or dextran, each conjugated with tetramethylrhodamine and carboxyfluorescein (for pH 5-8) or dichlorocarboxyfluorescein (for pH 4-6); pH in individual labeled vesicles was measured by ratio imaging using a cooled CCD camera and novel image analysis software. Tf-labeled endosomes acidified to pH 6.2 +/- 0.1 with a t1/2 of 4 min at 37 degrees C, and remained small and near the cell periphery. Dextran- and alpha 2M-labeled endosomes acidified to pH 4.7 +/- 0.2, becoming larger and moving toward the nucleus over 30 min; approximately 15% of alpha 2M-labeled endosomes were strongly acidic (pH less than 5.5) at only 1 min after labeling. Replacement of external Cl by NO3 or isethionate strongly and reversibly inhibited acidification. Addition of ouabain (1 mM) at the time of labeling strongly enhanced acidification in the first 5 min; Tf-labeled endosomes acidified to pH 5.3 without a change in morphology. Activation of phospholipase C by vasopressin (50 nM) enhanced acidification of early endosomes; activation of protein kinase C by PMA (100 nM) enhanced acidification strongly, whereas elevation of intracellular Ca by A23187 (1 microM) had no effect on acidification. Activation of protein kinase A by CPT-cAMP (0.5 mM) or forskolin (50 microM) inhibited acidification. Lysosomal pH was not affected by ouabain or the protein kinase activators. These results establish a methodology for quantitative measurement of pH in individual endocytic vesicles, and demonstrate that acidification of endosomes labeled with Tf and alpha 2M (receptor-mediated endocytosis) and dextran (fluid-phase endocytosis) is sensitive to intracellular anion composition, Na/K pump inhibition, and multiple intracellular second messengers.

A study was conducted to examine the production and characterization of monoclonal antibodies to alveolar type II cell lamellar body membranes. Lamellar bodies were obtained from rat lungs which had been cleared of blood while elastase digestion was utilized to isolate alveolar type II cells. Results indicated that the lbm180 protein is a lung lamellar body protein. Findings also showed that secretory granules from various tissues accommodated a number of common features.

There appears to be two surfactant lipid internalization pathways for uptake of liposomes by alveolar type II cells. Intact internalization of liposomes by type II cells seems to be dependent on clathedrin. Cytochalasin D decreases uptake by half, indicating a separate actin-dependent pathway. Liposome uptake appears to occur near intracellular lamellar bodies in a temperature- and energy-dependent manner.

Background: Computed tomography (CT) is currently one of the most useful diagnostic imaging tools for evaluating cardiac disorders in humans and animals. However, studies concerning CT and the feline heart remain scarce. Aim: To create measuring techniques for the feline heart size on CT and to determine the relationships of feline heart size observed on CT with internal parameters including age, bodyweight (BW), and sex. Methods: Four parameters observed on CT including thoracic height/width ratio (THW), relative heart area (RHA), CT vertebral heart score (ctVHS), transverse vertebral heart score (tVHS) in 1.25 mm slice thickness, and both pre- and post-contrast enhanced images were examined. Additionally, radiographic vertebral heart score (rVHS) was also evaluated. Results: THW was significantly influenced by age (p < 0.05). RHA was affected by age and gonadal status of cats (p = 0.001 and p = 0.016, respectively). Age also significantly affected tVHS (p = 0.038). Interestingly, ctVHS was not influenced by age, sex, gonadal status, or BW. tVHS and ctVHS had significant moderately positive correlations with rVHS (r = 0.476; p = 0.048 and r = 0.6112; p = 0.011, respectively). THW and RHA had non-significant correlations with rVHS (r = 0.2642; p = 0.302 and r = 0.1920; p = 0.455, respectively). Conclusion: CT heart size evaluation can be performed in both pre- and post-contrast enhanced images of 1.25 mm slice thickness. tVHS and ctVHS are recommended parameters for evaluating feline heart size in clinical practice. [Open Vet J 2023; 13(3.000): 337-347]

Abstract Recent investigations of neurological developmental disorders have revealed the Rho-family modulators such as Syde and its interactors as the candidate genes. Although the mammalian Syde proteins are reported to possess GTPase-accelerating activity for RhoA-family proteins, diverse species-specific substrate selectivities and binding partners have been described, presumably based on their evolutionary variance in the molecular organization. A comprehensive in silico analysis of Syde family proteins was performed to elucidate their molecular functions and neurodevelopmental networks. Predicted structural modeling of the RhoGAP domain may account for the molecular constraints to substrate specificity among Rho-family proteins. Deducing conserved binding motifs can extend the Syde interaction network and highlight diverse but Syde isoform-specific signaling pathways in neuronal homeostasis, differentiation, and synaptic plasticity from novel aspects of post-translational modification and proteolysis.

Self-incompatibility responses in Brassica are induced by haplotype-specific interactions between the pistil-expressed SRK receptor and pollen-expressed SP11 ligand. Here, via crystal structures and molecular dynamic simulations, the authors provide a model to explain why binding of cognate partners is favoured and how haplotypes can be distinguished.

Despite the significant progress in the understanding of the phenomenon of lightning and the physics behind it, locating and mapping its occurrence remain a challenge. Such localization and mapping of very high frequency (VHF) lightning radiation sources provide a foundation for the subsequent research on predicting lightning, saving lives, and protecting valuable assets. A major technical challenge in attempting to map the sources of lightning is mapping accuracy. The three common electromagnetic radio frequency-based lightning locating techniques are magnetic direction finder, time of arrival, and interferometer (ITF). Understanding these approaches requires critically reviewing previous attempts. The performance and reliability of each method are evaluated on the basis of the mapping accuracy obtained from lightning data from different sources. In this work, we review various methods for lightning mapping. We study the approaches, describe their techniques, analyze their merits and demerits, classify them, and derive few opportunities for further research. We find that the ITF system is the most effective method and that its performance may be improved further. One approach is to improve how lightning signals are preprocessed and how noise is filtered. Signal processing can also be utilized to improve mapping accuracy by introducing methods such as wavelet transform in place of conventional cross-correlation approaches.

In this paper, we examined the initiation events of ten negative cloud-to-ground (CG) flashes detected close to measurement stations on 12 November (CG-1 to CG-5) and 24 November (CG-6 to CG-10), 2019. All CG flashes were accompanied by microwave and very-high frequency (VHF) radiation pulses. We recorded all the CG flashes from two measurement stations (ST1 and ST2), which are separated by 13.3 km and consist of fast and slow antenna (FA and SA) sensors, a magnetic field (B-field) sensor, a VHF sensor (60 MHz), and a microwave sensor (~1 GHz). The key finding is that all of the microwave radiation pulses detected before the onset of initial electric field changes (IECs) preceded all VHF radiation pulses with an average lead time of 1.53 µs, ranging between 0.3 and 3.0 µs (for all CG flashes within reversal distance). A total of 50%, 17%, and 33% CG flashes were initiated by a single radiation pulse, two radiation pulses, and three radiation pulses, respectively, and were followed by IECs. Some VHF pulses are classified as short VHF radiation pulses (pulse duration less than 0.5 µs). The average duration from the first microwave and VHF pulses to the onset of IECs were 53.4 µs and 32.78 µs, respectively. The VHF radiation pulses detected before the IECs are suggested to be emitted by short-length positive streamers. Because the microwave radiation pulses were detected earlier (average lead time of 1.53 µs) than VHF radiation pulses, it is most likely that the microwave pulses were emitted by an electron avalanche process.

The IEEE802.15.4 beacon-enabled MAC protocol supports a simple coordinator selection mechanism (CSM) in static WSNs as well as mobile WSNs, where CSM normally selects the nearest coordinator. However, CSM is not suitable for constant moving node in mobile WSNs, where node will be switching coordinators too often due to strong mobility and low coverage range. In mobile WSNs, the node needs to select the best coordinator that has potential to provide longest connectivity period. This paper introduces the Intelligent Coordinator Selection Mechanism (ICSM) which supports the node to select the best coordinators. The proposed mechanism is based on link quality indicator (LQI) values of the received beacon frames from the nearby coordinators. The node selects the coordinator for association that has potential to provide the longest connectivity period. Our proposed ICSM reduces the energy consumption, enhance the association period and the throughput, and minimize the number of switching amongst the coordinators. The mobile node connectivity period is improved from 55% to 86% (static) and 94% (mobile), while the number of association attempts are reduced from 13% to 6% (static) and 2% (mobile) coordinators. [ABSTRACT FROM AUTHOR]