Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Prohibitin 1 ...(PHB1) is known for its significant anti-proliferative activity. However, the role of PHB1 in PASMCs and PAH have not been elucidated.
Monocrotaline (MCT 60 mg/kg) was used to build a PAH model in SD rats. Right ventricular systolic pressure (RVSP) and right ventricle (RV) hypertrophy were measured. Morphology of pulmonary vessels was observed by Hematoxylin-Eosin (HE) staining. Expression of PHB1 in pulmonary arteries and PASMCs was determinated by immunoblot and immunofluorescence. Cell proliferation was detected by CCK8 and EDU when PASMCs were stimulated by PDGF-BB (20 ng/mL). Furthermore, siRNA for PHB1 and Akt inhibitor were conducted to investigate the mechanism behind the role of PHB1 and AKT signaling pathway in PASMCs proliferation and apoptosis.
The protein expression of PHB1 in PAH rats lung tissue was significantly up-regulated accompanied by elevated RVSP and enhanced RV hypertrophy. Immunohistochemistry showed that PHB1 was mainly localized in the pulmonary vascular smooth muscle layer. PDGF-BB significantly up-regulated the expression of PHB1 in rat primary PASMCs in a time- and dose-dependent manner. After PHB1 knock down, PASMCs proliferation was significantly suppressed while apoptosis was significantly recovered. Meanwhile the level of proliferating cell nuclear antigen (PCNA) and P-Akt were significantly down-regulated. Perifosine (Akt inhibitor) also significantly inhibit proliferation of PASMCs.
PHB1 contributes to pulmonary vascular remodeling by accelerating proliferation of PASMCs which involves AKT phosphorylation.
In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with FIGO stage, histological grade, lymph node ...metastasis and poor survival of EOC patients. Multivariate Cox regression analysis showed that CCAT1 was an independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1 upregulation promoted EOC cell EMT, migration and invasion. We further identified and confirmed that miR-152 and miR-130b were the targets of CCAT1, and CCAT1 functioned by targeting miR-152 and miR-130b. Subsequently, ADAM17 and WNT1, and STAT3 and ZEB1 were confirmed to be the targets of miR-152 and miR-130b, respectively, and could be regulated by CCAT1 in EOC cells. Knockdown of anyone of these four proteins inhibited EOC cell EMT, migration and invasion. Taken together, our study first revealed a critical role of CCAT1-miR-152/miR-130b-ADAM17/WNT1/STAT3/ZEB1 regulatory network in EOC cell metastasis. These findings provide great insights into EOC initiation and progression, and novel potential therapeutic targets and biomarkers for diagnosis and prognosis for EOC.
•CCAT1 is upregulated in EOC and associated with the prognosis of EOC patients.•CCAT1 promotes EOC cell EMT, migration and invasion.•miR-152 and miR-130b are the targets of CCAT1.•ADAM17 and WNT1, and STAT3 and ZEB1 are separately targets of miR-152 and miR-130.•CCAT1 functions via regulation of ADAM17, WNT1, STAT3 and ZEB1 expression.
Temporomandibular disorders (TMD) affect the temporomandibular joint and associated structures. Despite its prevalence and impact on quality of life, the underlying mechanisms of TMD remain unclear. ...Magnetic resonance imaging studies suggest brain abnormalities in patients with TMD. However, these lines of evidence are essentially observational and cannot infer a causal relationship. This study employs Mendelian randomisation (MR) to probe causal relationships between TMD and brain changes.
Genome-wide association study (GWAS) summary statistics for TMD were collected, along with brain imaging-derived phenotypes (IDPs). Instrumental variables were selected from the GWAS summary statistics and used in bidirectional 2-sample MR analyses. The inverse-variance weighted analysis was chosen as the primary method. In addition, false discovery rate (FDR) correction of P value was used.
Eleven IDPs related to brain imaging alterations showed significant causal associations with TMD (P-FDR < .05), validated through sensitivity analysis. In forward MR, the mean thickness of left caudal middle frontal gyrus (OR, 0.76; 95% CI, 0.67–0.87; P-FDR = 1.15 × 10−2) and the volume of right superior frontal gyrus (OR, 1.24; 95% CI, 1.10–1.39; P-FDR = 2.26 × 10−2) exerted significant causal effects on TMD. In the reverse MR analysis, TMD exerted a significant causal effect on 9 IDPs, including the mean thickness of the left medial orbitofrontal cortex (β = −0.10; 95% CI, −0.13 to −0.08; P-FDR = 2.06 × 10−11), the volume of the left magnocellular nucleus (β = −0.15; 95% CI, −0.22 to −0.09; P-FDR = 3.26 × 10−4), the mean intensity of the right inferior-lateral ventricle (β = −0.09; 95% CI, −0.14 to −0.04; P-FDR = 2.23 × 10−2), the volume of grey matter in the anterior division of the left superior temporal gyrus (β = 0.09; 95% CI, 0.04–0.14; P-FDR = 1.69 × 10−2), and so forth.
This study provides genetic evidence supporting the bidirectional causal associations between TMD and brain IDPs, shedding light on potential neurobiological mechanisms underlying TMD development and its relationship with brain structure.
A BitTorrent-like peer-to-peer file-sharing system can be reduced into a system of addition-min fuzzy relation inequalities. Addition-min is a new composition, and the solution set of addition-min ...fuzzy relation inequalities differs much from that of general max-t-norm fuzzy relation inequalities or equations. In order to avoid network congestion and improve the stability of data transmission, a min-max programming problem is proposed subject to addition-min fuzzy relation inequalities in this paper. Based on some relevant theorems on resolution, a novel algorithm is developed step by step to find an optimal solution of the proposed problem. Moreover, an application example is given to illustrate the feasibility and efficiency of the algorithm. Finally, some further discussions are made concerning the optimal solution of the proposed problem.
Flexible hydroelectric generators (HEGs) are promising self‐powered devices that spontaneously derive electrical power from moisture. However, achieving the desired compatibility between a continuous ...operating voltage and superior current density remains a significant challenge. Herein, a textile‐based van der Waals heterostructure is rationally designed between conductive 1T phase tungsten disulfide@carbonized silk (1T‐WS2@CSilk) and carbon black@cotton (CB@Cotton) fabrics with an asymmetric distribution of oxygen‐containing functional groups, which enhances the proton concentration gradients toward high‐performance wearable HEGs. The vertically staggered 1T‐WS2 nanosheet arrays on the CSilk fabric provide abundant hydrophilic nanochannels for rapid carrier transport. Furthermore, the moisture‐induced primary battery formed between the active aluminum (Al) electrode and the conductive textiles introduces the desired electric field to facilitate charge separation and compensate for the decreased streaming potential. These devices exhibit a power density of 21.6 µW cm−2, an open‐circuit voltage (Voc) of 0.65 V sustained for over 10 000 s, and a current density of 0.17 mA cm−2. This performance makes them capable of supplying power to commercial electronics and human respiratory monitoring. This study presents a promising strategy for the refined design of wearable electronics.
Through constructing 2D nanosheet arrays and moisture‐induced primary battery system, a high‐performance and flexible hydroelectric generator is developed with a sustained open‐circuit voltage of 0.65 V, and an excellent short‐circuitcurrent of 0.51 mA. Moreover, these prepared flexible hydroelectric generators can be used in the wearable self‐powered field.
Low-rate Distributed Denial-of-Service (low-rate DDoS) attacks are a new challenge to cyberspace, as the attackers send a large amount of attack packets similar to normal traffic, to throttle ...legitimate flows. In this paper, we propose a measurement—expectation of packet size—that is based on the distribution difference of the packet size to distinguish two typical low-rate DDoS attacks, the constant attack and the pulsing attack, from legitimate traffic. The experimental results, obtained using a series of real datasets with different times and different tolerance factors, are presented to demonstrate the effectiveness of the proposed measurement. In addition, extensive experiments are performed to show that the proposed measurement can detect the low-rate DDoS attacks not only in the short and long terms but also for low packet rates and high packet rates. Furthermore, the false-negative rates and the adjudication distance can be adjusted based on the detection sensitivity requirements.
In this letter, a novel true random number generator (TRNG) with high energy‐efficient and throughput is proposed for cryptographic systems. The current starve based ring oscillator (CSRO) is biased ...in the subthrehold region as an entropy source. An individual ring oscillator (RO) is sampled using multiple sampling points of the CSRO working in the sub‐threshold region to obtain a multi‐channel sequence output, thereby fully exploiting the randomness of the entropy source. The proposed TRNG is implemented using a standard 40nm CMOS technology and the simulation results show that it provides high‐quality and 20.66 Mbps random sequences while only consuming 11.46 μW at 1.1 V, 25°C. In addition, the proposed TRNG passes the NIST SP 800‐22 and the NIST SP 800‐90B tests without post‐processing and outperforms the state‐of‐the‐art in terms of energy consumption per bit of the output bitstream, reaching 0.555pJ/bit.
In this letter, we proposed a novel true random number generator (TRNG) based on multi‐stage sampling of the current starve‐based ring oscillator (CSRO) to reduce the power consumption per bit of the output binary sequence. The simulation results show that it provides high‐quality and 20.66 Mbps random sequences while only consuming 11.46 μW at 1.1 V, 25°C which means its energy consumption per bit reaches 0.555pJ/bit, much lower than existing conventional design. The proposed TRNG also passes the NIST 800‐22 and NIST SP 800‐90B tests.
In recent years, recycling of numerous spent lithium-ion battery cathode materials has received increasing attention in order to protect the environment as well as to conserve resources, and the ...recovery of spent LiFePO4 (LFP) by direct regeneration has been widely studied. A considerable body of literature has delved into the failure mechanism of LFP. The mechanism is characterized by an irreversible phase change, which is primarily attributed to the sluggish diffusion of lithium ions (Li+) during cycling. Additionally, the migration of iron (Fe) ions to occupy Li+ sites further impedes Li+ diffusion. Consequently, the electrochemical performance of directly regenerated LFP is diminished by the phenomenon of Li defects. Here, a method of direct regeneration of LFP based on a doping strategy using environmentally friendly and economically efficient natural biomass amino acids has been developed, which inhibits Fe ion migration and improves the diffusion kinetics of Li+ and electrons by constructing a nitrogen-doped carbon coating. The regenerated LFP cathode exhibits excellent cycling stability and rate performance (98.7% capacity retention over 100 cycles at 1C current density and a high capacity retention of 87.9% after 500 cycles at 1C).
Mesenchymal stem cells-derived exosomes (MSC-exos) have attracted great interest as a cell-free therapy for acute kidney injury (AKI). However, the
biodistribution of MSC-exos in ischemic AKI has not ...been established. The potential of MSC-exos in promoting tubular repair and the underlying mechanisms remain largely unknown.
Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to characterize the properties of human umbilical cord mesenchymal stem cells (hucMSCs) derived exosomes. The biodistribution of MSC-exos in murine ischemia/reperfusion (I/R) induced AKI was imaged by the IVIS spectrum imaging system. The therapeutic efficacy of MSC-exos was investigated in renal I/R injury. The cell cycle arrest, proliferation and apoptosis of tubular epithelial cells (TECs) were evaluated
and in HK-2 cells. The exosomal miRNAs of MSC-exos were profiled by high-throughput miRNA sequencing. One of the most enriched miRNA in MSC-exos was knockdown by transfecting miRNA inhibitor to hucMSCs. Then we investigated whether this candidate miRNA was involved in MSC-exos-mediated tubular repair.
imaging showed that MSC-exos was efficiently homing to the ischemic kidney and predominantly accumulated in proximal tubules by virtue of the VLA-4 and LFA-1 on MSC-exos surface. MSC-exos alleviated murine ischemic AKI and decreased the renal tubules injury in a dose-dependent manner. Furthermore, MSC-exos significantly attenuated the cell cycle arrest and apoptosis of TECs both
and
. Mechanistically, miR-125b-5p, which was highly enriched in MSC-exos, repressed the protein expression of p53 in TECs, leading to not only the up-regulation of CDK1 and Cyclin B1 to rescue G2/M arrest, but also the modulation of Bcl-2 and Bax to inhibit TEC apoptosis. Finally, inhibiting miR-125b-5p could mitigate the protective effects of MSC-exos in I/R mice.
MSC-exos exhibit preferential tropism to injured kidney and localize to proximal tubules in ischemic AKI. We demonstrate that MSC-exos ameliorate ischemic AKI and promote tubular repair by targeting the cell cycle arrest and apoptosis of TECs through miR-125b-5p/p53 pathway. This study provides a novel insight into the role of MSC-exos in renal tubule repair and highlights the potential of MSC-exos as a promising therapeutic strategy for AKI.
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