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Abstract Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the β-CASP and the β-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.

A remarkable improvement in the conductivity of grown nitrogen-doped p-type β-Ga2O3 films was successfully achieved via the thermal oxidation of GaN in N2O ambient at 1100 °C. In the vacuum test environment, its room temperature Hall hole concentration is 1.64 × 1017 cm−3, the Hall resistivity is 7.66 Ω cm, the Hall hole mobility is 4.98 cm2 V−1 s−1, and the acceptor ionization energy is 0.087 eV. In addition, the compositions and properties were also extensively investigated. When the oxidation temperature was raised from 900 to 1100 °C, the FWHM of the {2¯ 01}-oriented β-Ga2O3 diffraction peak from the X-ray diffraction (XRD) pattern decreased to 0.237°, confirming an improvement in the crystalline quality of the β-Ga2O3 nanocrystal structure. From both the cross-sectional view of the field emission scanning electron microscopy (FESEM) image and the cross-sectional lamellae prepared by focused ion beam (FIB) milling, it was observed that the generated β-Ga2O3 film transformed into a two-layer morphology when oxidized at 1100 °C. The top layer is a rather loose film composed of nanorods, and the selected area electron diffraction (SAED) pattern of a nanorod confirmed it as high-quality (6¯ 03)-dominated monocrystal β-Ga2O3. The second layer is a comparatively compact β-Ga2O3 film. This approach to the efficient growth of p-type β-Ga2O3 can broaden the applicability of these two-layered structures. The randomly distributed monocrystal nanorods on the top layer are an appropriate candidate for the photocatalyst, while the relatively more compact second layer with high p-type conductivity can be employed in high-performance solar-blind UV photodetectors or high-power electronic devices.

Abstract Doxorubicin (DOX) is an efficacious and widely used drug for human malignancy treatment, but its clinical application is limited due to side effects, especially cardiotoxicity. Our present study revealed that DOX could induce apoptosis in cardiomyocytes. Herein, we screened the dysregulated long noncoding RNAs (lncRNAs) in DOX-treated cardiomyocytes. Notably, overexpression of lncRNA NONMMUT015745 (lnc5745) could alleviate DOX-induced cardiomyocyte apoptosis both in vitro and in vivo. Conversely, silencing lnc5745 promotes cardiomyocyte apoptosis. Moreover, Rab2A, a direct target of lnc5745, possesses a protective effect in DOX-induced cardiotoxicity once knocked down. Importantly, we verified that the p53-related apoptotic signalling pathway was responsible for the lnc5745-mediated protective role against DOX-induced cardiomyocyte apoptosis. Mechanistically, Rab2A interacts with p53 and phosphorylated p53 on Ser 33 (p53 (Phospho-Ser 33)), promotes p53 phosphorylation, thereby activating the apoptotic pathway. Taken together, our results suggested that lnc5745 protects against DOX-induced cardiomyocyte apoptosis through suppressing Rab2A expression, modifying p53 phosphorylation, thereby regulating p53-related apoptotic signalling pathway. Our findings establish the functional mode of the lnc5745-Rab2A-p53 axis in DOX-induced cardiotoxicity. The development of new strategies targeting the lnc5745-Rab2A-p53 axis could attenuate DOX-induced cardiotoxicity, which is beneficial to its clinical anti-tumour application.

Lung cancer (LC) is a commonly diagnosed cancer with an unsatisfactory prognosis. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that mediate cell-cell communication by transporting various biomacromolecules, such as nucleic acids, proteins, and lipids. Noncoding RNAs (ncRNAs), including microRNAs, circular RNAs, and long noncoding RNAs, are important noncoding transcripts that play critical roles in a variety of physiological and pathological processes, especially in cancer. ncRNAs have been verified to be packaged into EVs and transported between LC cells and stromal cells, regulating multiple LC malignant phenotypes, such as proliferation, migration, invasion, epithelial-mesenchymal transition, metastasis, and treatment resistance. Additionally, EVs can be detected in various body fluids and are associated with the stage, grade, and metastasis of LC. Herein, we summarize the biological characteristics and functions of EV ncRNAs in the biological processes of LC, focusing on their potential to serve as diagnostic and prognostic biomarkers of LC as well as their probable role in the clinical treatment of LC. EV ncRNAs provide a new perspective for understanding the mechanism underlying LC pathogenesis and development, which might benefit numerous LC patients in the future.

A new structure for PNPN tunnel field-effect transistors (TFETs) has been designed and simulated in this work. The proposed structure incorporates the polarity bias concept and the gate work function engineering to improve the DC and analog/RF figures of merit. The proposed device consists of a control gate (CG) and a polarity gate (PG), where the PG uses a dual-material gate (DMG) structure and is biased at −0.7 V to induce a P+ region in the source. The PNPN structure introduces a local minimum on the conduction band edge curve at the tunneling junction, which dramatically reduces the tunneling width. Furthermore, we show that incorporating the DMG architecture further enhances the drive current and improves the subthreshold slope (SS) characteristics by introducing an additional electric field peak. The numerical simulation reveals that the electrically doped PNPN TFET using DMG improves the DC and analog/RF performances in comparison to a conventional single-material gate (SMG) device.

Circular RNAs (circRNAs) are a large class of noncoding RNAs that are emerging as critical regulators of various cellular processes that are involved in the physiopathological mechanism of many human diseases, such as cardiovascular disease, atherosclerosis, diabetes mellitus, and carcinogenesis. Autophagy is a conserved and catabolic cellular process that degrades unfolded, misfolded, or damaged protein aggregates or organelles to maintain cellular homeostasis under physiological and pathological conditions. Increasing evidence has shown a link between circRNAs and autophagy that is closely related to the occurrence and development of human diseases, including cancer. In this review, we highlight recent advances in understanding the functions and mechanisms of circRNAs in the regulation of autophagy in cancer. These autophagy-related circRNAs contribute to cancer development and progression in various types of human cancer by activating or inhibiting autophagy. Cumulative research on the relationship between circRNAs and autophagy regulation provides critical insight into the essential role that circRNAs play in carcinogenesis and suggests new targets for tumor therapy.

Cardiovascular diseases (CVDs) remain the world’s leading cause of death. Cardiomyocyte autophagy helps maintain normal metabolism and functioning of the heart. Importantly, mounting evidence has revealed that autophagy plays a dual role in CVD pathology. Under physiological conditions, moderate autophagy maintains cell metabolic balance by degrading and recycling damaged organelles and proteins, and it promotes myocardial survival, but excessive or insufficient autophagy is equally deleterious and contributes to disease progression. Noncoding RNAs (ncRNAs) are a class of RNAs transcribed from the genome, but most ncRNAs do not code for functional proteins. In recent years, increasingly, various ncRNAs have been identified, and they play important regulatory roles in the physiological and pathological processes of organisms, as well as in autophagy. Thus, determining whether ncRNA-regulated autophagy plays a protective role in CVDs or promotes their progression can help us to develop ncRNAs as therapeutic targets in autophagy-related CVDs. In this review, we briefly summarize the regulatory roles of several important ncRNAs, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the autophagy of various CVDs to provide a theoretical basis for the etiology and pathogenesis of CVDs and develop novel therapies to treat CVDs.

Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.

In this paper, we propose and investigate an electrically doped (ED) PNPN tunnel field effect transistor (FET), in which the drain side tunneling barrier width is effectively controlled to obtain a suppressed ambipolar current. We present that the proposed PNPN tunnel FETs can be realized without chemically doped junctions by applying the polarity bias concept to a doped N+/P− starting structure. Using numerical device simulations, we demonstrate how the tunneling barrier width on the drain side can be influenced by several design parameters, such as the gap length between the channel and the drain (Lgap), the working function of the polarity gate, and the dielectric material of the spacer. The simulation results show that an ED PNPN tunneling FET with an ED drain, which has been explored for the first time, exhibits a low ambipolar current of 5.87 × 10−16 A/µm at a gap length of 20 nm. The ambipolar current is reduced by six orders of magnitude compared to that which occurs with a conventional ED PNPN tunnel FET with a uniformly doped drain, while the average subthreshold slope and the ON state and OFF state currents remained nearly identical.

Abstract Gastric cancer (GC) is one of the most common malignant tumours in the world and has high morbidity and mortality. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently linked circular structures. In recent years, plentiful circRNAs have been discovered that participate in many biological processes, including the initiation and development of tumours. Increasing evidences suggest important biological functions of circRNAs, implying that circRNAs may serve as vital new biomarkers and targets for disease diagnosis and prognosis. Among these, circRNAs are tend to aberrantly expressed and are regarded as potential biomarkers in the carcinogenesis and progression of GC. This review systematically summarised the biogenesis, biological properties and functions of circRNAs, with a focus on their relationship with GC, as well as their probable clinical implications on GC. As our cognition of the relation between circRNAs and GC deepens, more molecular mechanisms of GC progression will be discovered, and new therapeutic strategies will be used for the prevention and treatment of GC.

Abstract Background X‐linked hypophosphatemic rickets (XLH) is a heterogeneous genetic phosphate wasting disorder that occupies the majority of inheritable hypophosphatemic rickets (HR). XLH is caused by loss‐of‐function mutations in the phosphate‐regulating endopeptidase gene (PHEX) located on the X chromosome. Method In this study, we performed whole‐exome sequencing (WES) on the proband to identify the causative gene. The mutations were analyzed by predictive online software, such as PolyPhen‐2. Plasmids containing the wild‐type (WT) and mutant cDNA of the candidate gene were transfected into HEK293, then, the expression, cellular localization, and glycosylation state of the candidate proteins were detected by western blot, immunostaining, and endoglycosidase H digestion. The expression and concentration of related factor were measured by RT‐PCR and ELISA. Results We identified a novel missense mutation c.2179T>C in the PHEX that results in the substitution of p.Phe727Leu (F727L). This mutation was predicted to be disease‐causing by all four predictive online software. In vitro studies demonstrated that the F727L substitution hindered the intracellular trafficking of the mutant PHEX, with ~59% of mutant PHEX protein retained in the endoplasmic reticulum (ER) and only ~16% of the mutant protein localized on the cell surface. Endoglycosidase H digestion assay showed that the mutant F727L PHEX protein was not fully glycosylated. The concentration of intact FGF23 in hFOB1.19 cell culture medium collected from the mutant PHEX group was the highest (62.9 pg/ml) compared to the WT group (32.1 pg/ml) and control group (23.5 pg/ml). Conclusion Our results confirmed that the mutant PHEX protein was lowly glycosylated and retarded within the ER, the intact FGF23 level in cell culture media caused by the mutant PHEX protein was significantly elevated compared to that of the WT group, which may explain why the single base mutation in the PHEX led to XLH syndrome in this family.

Little is known about the role of long lncRNAs in autophagy. The authors identify lncCAIF, and show that it suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53 -mediated transcription of myocardin.

In this paper, we present an in-built N+ pocket electrically doped tunnel FET (ED-TFET) based on the polarity bias concept that enhances the DC and analog/RF performance. The proposed device begins with a MOSFET like structure (n-p-n) with a control gate (CG) and a polarity gate (PG). The PG is biased at −0.7 V to induce a P+ region at the source side, leaving an N+ pocket between the source and the channel. This technique yields an N+ pocket that is realized in the in-built architecture and removes the need for additional chemical doping. Calibrated 2-D simulations have demonstrated that the introduction of the N+ pocket yields a higher ION and a steeper average subthreshold swing when compared to conventional ED-TFET. Further, a local minimum on the conduction band edge (EC) curve at the tunneling junction is observed, leading to a dramatic reduction in the tunneling width. As a result, the in-built N+ pocket ED-TFET significantly improves the DC and analog/RF figure-of-merits and, hence, can serve as a better candidate for low-power applications.

Soil moisture is a key variable in terrestrial water cycle, playing a key role in the exchange of water and energy in the land-atmosphere interface. The spatiotemporal variations of soil moisture from multiple sources during 1988–2010 are evaluated against in situ observations in the Yellow River basin, China, including the Essential Climate Variable satellite’s passive microwave product (SMECV), ERA-Interim reanalysis (SMERA), the National Centers for Environmental Prediction/Department of Energy’s Reanalysis-2 (SMNCEP), and the Variable Infiltration Capacity model products (SMVIC). The seasonal soil moisture dynamics of SMECV and SMVIC appear to be consistent with SMin situ, with significant soil drying in spring and wetting in summer. SMERA and SMNCEP, however, fail to capture the soil drying before rainy seasons. Remarkably, SMECV shows large agreement with SMin situ in terms of the interannual variations and the long-term drying trends. SMVIC captures the interannual variations but fails to have the long-term trends in SMin situ. As for SMERA and SMNCEP, they fail to capture both the interannual variations and the long-term soil drying trends in SMin situ.

In this paper, for the first time, an n-channel metal-oxide-semiconductor field-effect transistor (NMOSFET) layout with a Z gate and an improved total ionizing dose (TID) tolerance is proposed. The novel layout can be radiation-hardened with a fixed charge density at the shallow trench isolation (STI) of 3.5 × 1012 cm−2. Moreover, it has the advantages of a small footprint, no limitation in W/L design, and a small gate capacitance compared with the enclosed gate layout. Beside the Z gate layout, a non-radiation-hardened single gate layout and a radiation-hardened enclosed gate layout are simulated using the Sentaurus 3D technology computer-aided design (TCAD) software. First, the transfer characteristics curves (Id-Vg) curves of the three layouts are compared to verify the radiation tolerance characteristic of the Z gate layout; then, the threshold voltage and the leakage current of the three layouts are extracted to compare their TID responses. Lastly, the threshold voltage shift and the leakage current increment at different radiation doses for the three layouts are presented and analyzed.

The dispersion properties of the absorption coefficients [α(ν)] of different multi-component silicate oxide glasses have been studied in the frequency region below the boson peak by using THz-time-domain spectroscopy. The value of α(ν)/ν2 has been shown to exhibit a minimum level (R) at low frequency and subsequently a linear increase in the form of r(ν/νBP + E) with increasing frequency, where νBP is the boson peak frequency and R, r, and E are material-specific constants. It has also been found that R ∝ r and E is a constant common to most glasses. This α(ν)/ν2 behavior is ascribed to the dispersion property of the light-vibration coupling coefficient under the reasonable vibrational density of state function. The minimum (constant) and linear terms of the α(ν)/ν2 spectrum are originated from the physical/chemical disorder-induced charge fluctuations in the long-range scale (constant term) and short-range scale (linear term), respectively. The fluctuating charge (σ1) caused by uncorrelated, long-range disorders has primary significance for determining the sub-THz absorption dispersion properties, and its value has been determined for each glass material. [ABSTRACT FROM AUTHOR]

We present a study of the ultrafast dissociation dynamics of the lowest-lying electronic excited states in CO2 by using ultraviolet (UV) and extreme-ultraviolet (XUV) pulses from high-order harmonic generation. We observe two primary dissociation channels: a direct dissociation channel along the Πg1 electronically excited manifold, and a second channel which results from the mixing of electronic states. The direct dissociation channel is found to have a lifetime which is shorter than our experimental resolution, whereas the second channel has a significantly longer lifetime of nearly 200 fs. In this long-lived channel we observe a beating of the vibrational populations with a period of ∼133 fs.