Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.

Persister cells (PS) selected for anticancer therapy have been recognized as a significant contributor to the development of treatment-resistant malignancies. It is found that imposing glutamine restriction induces the generation of PS, which paradoxically bestows heightened resistance to glutamine restriction treatment by activating the integrated stress response and initiating the general control nonderepressible 2-activating transcription factor 4-alanine, serine, cysteine-preferring transporter 2 (GCN2-ATF4-ASCT2) axis. Central to this phenomenon is the stress-induced ATF4 translational reprogramming. Unfortunately, directly targeting ATF4 protein has proven to be a formidable challenge because of its flat surface. Nonetheless, a G-quadruplex structure located within the promoter region of ATF4 (ATF4-G4) is uncovered and resolved, which functions as a transcriptional regulator and can be targeted by small molecules. The investigation identifies the natural compound coptisine (COP) as a potent binder that interacts with and stabilizes ATF4-G4. For the first time, the high-resolution structure of the COP-ATF4-G4 complex is determined. The formation of this stable complex disrupts the interaction between transcription factor AP-2 alpha (TFAP2A) and ATF4-G4, resulting in a substantial reduction in intracellular ATF4 levels and the eventual death of cancer cells. These seminal findings underscore the potential of targeting the ATF4-G4 structure to yield significant therapeutic advantages within the realm of persister cancer cells induced by glutamine-restricted therapy.

BinVPR: Binary Neural Networks towards Real-Valued for Visual Place Recognition.

Visual Place Recognition (VPR) aims to determine whether a robot or visual navigation system locates in a previously visited place using visual information. It is an essential technology and challenging problem in computer vision and robotic communities. Recently, numerous works have demonstrated that the performance of Convolutional Neural Network (CNN)-based VPR is superior to that of traditional methods. However, with a huge number of parameters, large memory storage is necessary for these CNN models. It is a great challenge for mobile robot platforms equipped with limited resources. Fortunately, Binary Neural Networks (BNNs) can reduce memory consumption by converting weights and activation values from 32-bit into 1-bit. But current BNNs always suffer from gradients vanishing and a marked drop in accuracy. Therefore, this work proposed a BinVPR model to handle this issue. The solution is twofold. Firstly, a feature restoration strategy was explored to add features into the latter convolutional layers to further solve the gradient-vanishing problem during the training process. Moreover, we identified two principles to address gradient vanishing: restoring basic features and restoring basic features from higher to lower layers. Secondly, considering the marked drop in accuracy results from gradient mismatch during backpropagation, this work optimized the combination of binarized activation and binarized weight functions in the Larq framework, and the best combination was obtained. The performance of BinVPR was validated on public datasets. The experimental results show that it outperforms state-of-the-art BNN-based approaches and full-precision networks of AlexNet and ResNet in terms of both recognition accuracy and model size. It is worth mentioning that BinVPR achieves the same accuracy with only 1% and 4.6% model sizes of AlexNet and ResNet.

High-Precision Fiber Noise Detection and Comparison over a 260 km Field Fiber Link.

In this paper, we present a high-precision optical frequency noise detection and comparison technique using a two-way transfer method over a 260 km field fiber link. This method allows for the comparison of optical frequencies between remote optical references without the need for data transfer through communication. We extend a previously established two-way comparison technique to obtain all data at the local site. Two optical carrier signals are injected into the bidirectional fiber from both ends, and one carrier is reflected back from the remote end. This enables the phase comparison of the two carrier signals at a single site without the need to transmit experimental data. The common-mode frequency noise induced by the bidirectional fiber link is detected and effectively suppressed without the need for sophisticated active fiber noise control. Our demonstration system, which uses a 260 km field fiber link and a common laser source, achieves a fractional instability of 2.5×10-17 at 1 s averaging time and scales down to 3.5×10-21 at 8000 s. This scheme offers the distinct advantage of completing the comparison at a single site, eliminating the need for remote data transfer via communication. This method is expected to enhance reliability for high-precision frequency comparisons between remote optical clocks and advanced atomic clocks.

Understanding the nutritional benefits through plant proteins-probiotics interactions: mechanisms, challenges, and perspectives.

The nutritional benefits of combining probiotics with plant proteins have sparked increasing research interest and drawn significant attention. The interactions between plant proteins and probiotics demonstrate substantial potential for enhancing the functionality of plant proteins. Fermented plant protein foods offer a unique blend of bioactive components and beneficial microorganisms that can enhance gut health and combat chronic diseases. Utilizing various probiotic strains and plant protein sources opens doors to develop innovative probiotic products with enhanced functionalities. Nonetheless, the mechanisms and synergistic effects of these interactions remain not fully understood. This review aims to delve into the roles of promoting health through the intricate interplay of plant proteins and probiotics. The regulatory mechanisms have been elucidated to showcase the synergistic effects, accompanied by a discussion on the challenges and future research prospects. It is essential to recognize that the interactions between plant proteins and probiotics encompass multiple mechanisms, highlighting the need for further research to address challenges in achieving a comprehensive understanding of these mechanisms and their associated health benefits.

Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single-stranded DNA-binding protein 1 (SSBP1) promoter region.

BACKGROUND AND PURPOSE: Osteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration. Nevertheless, the intricate molecular mechanisms underpinning SNG's actions in osteosarcoma remain elusive, necessitating further elucidation. EXPERIMENTAL APPROACH: Single-stranded DNA-binding protein 1 (SSBP1) was screened out by differential proteomic analysis. Apoptosis, cell cycle, reactive oxygen species (ROS) and mitochondrial changes were assessed via flow cytometry. Western blotting and quantitative real-time reverse transcription PCR (qRT-PCR) were used to determine protein and gene levels. The antitumour mechanism of SNG was explored at a molecular level using chromatin immunoprecipitation (ChIP) and dual luciferase reporter plasmids. KEY RESULTS: Our investigation revealed that SNG exerted an up-regulated effect on SSBP1, disrupting mitochondrial function and inducing apoptosis. In-depth analysis uncovered a mechanism whereby SNG hindered the JAK/signal transducer and activator of transcription 3 (STAT3) signalling pathway, relieved the inhibitory effect of STAT3 on SSBP1 transcription, and inhibited the downstream PI3K/Akt/mTOR signalling axis, ultimately activating apoptosis. CONCLUSIONS AND IMPLICATIONS: The study delved further into elucidating the anticancer mechanism of SNG in osteosarcoma. Notably, we unravelled the previously undisclosed apoptotic potential of SSBP1 in osteosarcoma cells. This finding holds substantial promise in advancing the development of novel anticancer drugs and identification of therapeutic targets.

Discovery of a potent inhibitor of chaperone-mediated autophagy that targets the HSC70-LAMP2A interaction in non-small cell lung cancer cells.

BACKGROUND AND PURPOSE: Chaperone-mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered. EXPERIMENTAL APPROACH: Levels of CMA in non-small cell lung cancer (NSCLC) tissue samples were confirmed by tyramide signal amplification dual immunofluorescence assay. High-content screening was performed based on CMA activity, to identify potential inhibitors of CMA. Inhibitor targets were determined by drug affinity responsive target stability-mass spectrum and confirmed by protein mass spectrometry. CMA was inhibited and activated to elucidate the molecular mechanism of the CMA inhibitor. KEY RESULTS: Suppression of interactions between HSC70 and LAMP2A blocked CMA in NSCLC, restraining tumour growth. Polyphyllin D (PPD) was identified as a targeted CMA small-molecule inhibitor through disrupting HSC70-LAMP2A interactions. The binding sites for PPD were E129 and T278 at the nucleotide-binding domain of HSC70 and C-terminal of LAMP2A, respectively. PPD accelerated unfolded protein generation to induce reactive oxygen species (ROS) accumulation by inhibiting HSC70-LAMP2A-eIF2α signalling axis. Also, PPD prevented regulatory compensation of macroautophagy induced by CMA inhibition via blocking the STX17-SNAP29-VAMP8 signalling axis. CONCLUSIONS AND IMPLICATIONS: PPD is a targeted CMA inhibitor that blocked both HSC70-LAMP2A interactions and LAMP2A homo-multimerization. CMA suppression without increasing the regulatory compensation from macroautophagy is a good strategy for NSCLC therapy.

Widely flexible and finely adjustable nonlocal dispersion cancellation with wavelength tuning.

In fiber-based quantum information processing with energy-time entangled photon pairs, optimized dispersion compensation is vital to preserve the strong temporal correlation of the photon pairs. We propose and experimentally verify that, by simply tuning the wavelength of the entangled photon pairs, nonlocal dispersion cancellation (NDC) can provide a widely flexible and finely adjustable solution for optimizing the dispersion compensation, which cannot be reached with the traditional local dispersion cancellation (LDC) instead. By way of example, when a 50 km-long single-mode fiber (SMF) is dispersion compensated by a 6.2-km-long commercial dispersion compensating fiber (DCF) based on the LDC configuration, it will lead to an almost invariant over-compensation in the wavelength range of 1500-1600 nm which restricts the observed temporal coincidence width of the self-developed energy-time entangled photon-pairs source to a minimum of ∼110 ps. While in the NDC configuration, the dispersion compensation can be readily optimized by tuning the signal wavelength to 1565.7 nm and a minimum coincidence width of 86.1 ± 0.7 ps is observed, which is mainly limited by the jitter of the single-photon detection system. Furthermore, such optimized dispersion compensation can also be achieved as the fiber length varies from 48 km to 60 km demonstrating the wide flexibility of NDC. Thanks to these capabilities, elaborate dispersion compensation modules are no longer required, which makes NDC a more versatile tool in fiber-based quantum information and metrology applications.

Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient.

Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8+ exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future.

Single-photon microwave photonics.

With the rapid development of microwave photonics technology, high-speed processing and ultra-weak signal detection capability have become the main bottlenecks in many applications. Thanks to the ultra-weak signal detection capability and the extremely low timing jitter properties of single-photon detectors, the combination of single-photon detection and classical microwave photonics technology may provide a solution to break the above bottlenecks. In this paper, we first report a novel concept of single-photon microwave photonics (SP-MWP), a SP-MWP signal processing system with phase shifting and frequency filtering functionalities is demonstrated based on a superconducting nanowire single photon detector (SNSPD) and a successive time-correlated single photon counting (TCSPC) module. Experimental results show that an ultrahigh optical sensitivity down to -100 dBm has been achieved, and the signal processing bandwidth is only limited by the timing jitter of single-photon detectors. In the meantime, the proposed system demonstrates an ultrahigh anti-interference capability, only the signal which is phase locked by the trigger signal in TCSPC can be extracted from the detected signals combining with noise and strong interference. The proposed SP-MWP concept paves a way to a novel interdisciplinary field of microwave photonics and quantum mechanism, named by quantum microwave photonics.

Effects of selenate and selenite on selenium accumulation and speciation in lettuce.

Lettuce is a common vegetable in hydroponic production. In this paper, a selenium (Se)-biofortification method was provided. The Se content, speciation, and the effects of different concentrations of selenate and selenite on lettuce growth and amino acids were investigated. The results showed that lettuce had strong ability to accumulate exogenous selenium, and inorganic Se could be effectively converted into organic Se. The proportion of organic Se in the shoots under treatment with 4 µmol L-1 selenite was 100%. Selenomethionine was the main organic Se, accounting for 51% (selenate) and 90% (selenite) of the total Se. Adding Se improves photosynthesis of lettuce and promotes growth. The growth with 2 µmol L-1 selenate and 4 µmol L-1 selenite was better than CK, and the shoot fresh weight was increased by 143.22% and 166.98%, respectively. Furthermore, the optimum Se application is 2 µmol L-1, and some areas can apply 4 µmol L-1 selenite. But Se-excessive areas are not recommended to grow selenium-rich foods. Therefore, lettuce has strong biofortification potential.

Polyrhachis vicina Roger Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Through the EGR1/BACE1/APP Axis.

Memory deficits and loss are the earliest and most prominent features of Alzheimer's disease (AD). This study was aimed to clarify the mechanistic basis of an active fraction of Polyrhachis vicina Roger (AFPR) on the memory abilities of AD rat models, which involves early growth response 1 (EGR1) expression and ß-secretase 1 (BACE1)-mediated deposition of amyloid ß peptide (Aß). An AD rat model was developed by Aß25-35, which was further treated with AFPR alone or in combination with lentiviral EGR1. The Morris water maze test and HE and Fluoro-Jade C staining were adopted to observe the memory behaviors, hippocampus neuron morphology, and Aß deposition. Aß25-35-induced SK-N-SH and HT22 neurons were subjected to AFPR for in vitro experiments on neuronal viability and apoptosis. AFPR improved the impaired memory function, preserved the neuron structure, and suppressed Aß deposition in AD rat models. Further, the expression of APP pathway-related proteins was downregulated by AFPR in both rat and cellular models. Moreover, AFPR inhibited the Aß25-35-induced neuronal apoptosis. AFPR suppressed the expression of EGR1, downregulated the BACE1 expression via impeding the binding of EGR1 to the BACE1 promoter, and thus blocked the activation of the APP signaling, ultimately protecting neurons. Notably, the aforementioned effects of AFPR were in a concentration-dependent manner; among three doses, 3.65, 15.6, and 30 mg/(kg·d), high-dose AFPR exhibited the most appreciable effects. In conclusion, AFPR inhibited the BACE1 expression by repressing the binding of EGR1 to the promoter of BACE1, thereby suppressing the Aß deposition and improving the memory function of AD rats.

Implementation of field two-way quantum synchronization of distant clocks across a 7†km deployed fiber link.

The two-way quantum clock synchronization has been shown to provide femtosecond-level synchronization capability and security against symmetric delay attacks, thus becoming a prospective method to compare and synchronize distant clocks with enhanced precision and safety. In this letter, a field test of two-way quantum synchronization between a H-maser and a Rb clock linked by a 7 km-long deployed fiber is implemented by using time-energy entangled photon-pair sources. Limited by the intrinsic frequency stability of the Rb clock, the achieved time stability at 30 s is measured as 32 ps. By applying a fiber-optic microwave frequency transfer technology to build frequency syntonization between the separated clocks, the limit set by the intrinsic frequency stability of the Rb clock is overcome. A significantly improved time stability of 1.9 ps at 30 s is achieved, which is mainly restrained by the low number of acquired photon pairs due to the low sampling rate of the utilized coincidence measurement system. Such implementation demonstrates the high practicability of the two-way quantum clock synchronization method for promoting field applications.

The Application of Low-Frequency Transition in the Assessment of the Second-Order Zeeman Frequency Shift.

Second-order Zeeman frequency shift is one of the major systematic factors affecting the frequency uncertainty performance of cesium atomic fountain clock. Second-order Zeeman frequency shift is calculated by experimentally measuring the central frequency of the (1,1) or (-1,-1) magnetically sensitive Ramsey transition. The low-frequency transition method can be used to measure the magnetic field strength and to predict the central fringe of (1,1) or (-1,-1) magnetically sensitive Ramsey transition. In this paper, we deduce the formula for magnetic field measurement using the low-frequency transition method and measured the magnetic field distribution of 4 cm inside the Ramsey cavity and 32 cm along the flight region experimentally. The result shows that the magnetic field fluctuation is less than 1 nT. The influence of low-frequency pulse signal duration on the accuracy of magnetic field measurement is studied and the optimal low-frequency pulse signal duration is determined. The central fringe of (-1,-1) magnetically sensitive Ramsey transition can be predicted by using a numerical integrating of the magnetic field "map". Comparing the predicted central fringe with that identified by Ramsey method, the frequency difference between these two is, at most, a fringe width of 0.3. We apply the experimentally measured central frequency of the (-1,-1) Ramsey transition to the Breit-Rabi formula, and the second-order Zeeman frequency shift is calculated as 131.03 × 10-15, with the uncertainty of 0.10 × 10-15.

Pulsed vapor cell atomic clock with a differential Faraday rotation angle detection.

Laser intensity noise is one of the main limiting factors in pulsed vapor cell clocks. To reduce the contribution of the laser intensity noise to detection signal in the pulsed optically pumped atomic clock, a scheme based on the differential Faraday rotation angle is proposed. Theoretically, the Ramsey fringes, the sensitivity of clock frequency to laser intensity fluctuation and the signal to noise ratio for absorption, differential, and Faraday rotation angle methods are calculated and compared. Using a Wollaston prism rotated 45°relative to the incident polarization, and two photodetectors, Ramsey fringes of three detection methods are obtained simultaneously. In the proposed scheme, the long-term Faraday rotation angle fluctuation is 0.66% at 30000s, which is much smaller than fluctuation of traditional absorption signal 3.9% at 30000s. And the contribution of laser intensity noise to clock instability is also reduced. Using optimized photodetector with high common mode rejection ratio, a better performance should be expected. This proposed scheme is attractive for the development of high performance vapor clock based on pulsed optically pumped.

The effect of rosuvastatin on cardiogenic cerebral infarction.

OBJECTIVE: To investigate the effect of rosuvastatin on cardiogenic cerebral infarction and its related effects on patients' neurological function, lipid levels, inflammatory factor levels, and oxidative stress status. METHODS: 300 patients with cardiogenic cerebral infarction were recruited as the study cohort and randomly divided into an observation group and a control group. Routine treatment, including urinary kallikrein injections and bayaspirin tablets were given to the patients in the control group for one month. Rosuvastatin was given once a day in addition to the treatment the control group received to the patients in the observation group, also for one month. The two groups' treatment efficacies were compared. Also, the two groups' NIHSS and mRS scores, lipid and inflammatory factor levels, and their oxidative stress statuses were also compared. RESULTS: The total effective rate in the observation group was significantly higher than it was in the control group (74.0% vs 84.7%, P=0.023). The NIHSS and mRS scores in the observation group were significantly lower than they were in the control group (all P<0.001). Compared with their levels after the treatment in the control group, the cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in the observation group were significantly decreased and the high-density lipoprotein cholesterol (HDL-C) was significantly increased (all P<0.001). Moreover, after the treatment, the inflammatory factors, such as the tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) levels, and the oxidative stress status, such as the oxidatively modified low density lipoprotein (ox-LDL) levels, were significantly lower than they were in the control group, but the superoxide dimutase (SOD) levels were significantly higher. CONCLUSIONS: Rosuvastatin remarkably improves the treatment efficacy and neurological function in cardiogenic cerebral infarction patients, and is associated with the improvement of the lipid levels, the inflammatory response, and the oxidative stress status.

Polyphyllin I promotes cell death via suppressing UPR-mediated CHOP ubiquitination and degradation in non-small cell lung cancer.

Polyphyllin I (PPI) purified from Polyphyllarhizomes displays puissant cytotoxicity in many kinds of cancers. Several researches investigated its anti-cancer activity. But novel mechanisms are still worth investigation. This study aimed to explore PPI-induced endoplasmic reticulum (ER) stress as well as the underlying mechanism in non-small cell lung cancer (NSCLC). Cell viability or colony-forming was detected by MTT or crystal violet respectively. Cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were assessed by flow cytometry. Gene and protein levels were evaluated by qRT-PCR and immunoblotting respectively. Protein interaction was determined by immunoprecipitation or immunofluorescence assay. Gene overexpression or silencing was carried out by transient transfection with plasmids or small interfering RNAs. The Cancer Genome Atlas (TCGA) database was used for Gene Set Enrichment Analysis (GSEA), survival analysis, gene expression statistics or pathway enrichment assay. PPI inhibited the propagation of NSCLC cells, increased non-viable apoptotic cells, arrested cell cycle at G2/M phase, induced ROS levels but failed to decrease mitochondrial membrane potential. High levels of GRP78 indicates poor prognosis in NSCLC patients. PPI selectively suppressed unfolded protein response (UPR)-induced GRP78 expression, subsequently protected CHOP from GRP78-mediated ubiquitination and degradation. We demonstrated that the natural product PPI, obtained from traditional herbal medicine, deserves for further study as a valuable candidate for lead compound in the chemotherapy of NSCLC.

EGFR mutation mediates resistance to EGFR tyrosine kinase inhibitors in NSCLC: From molecular mechanisms to clinical research.

With the development of precision medicine, molecular targeted therapy has been widely used in the field of cancer, especially in non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a well-recognized and effective target for NSCLC therapies, targeted EGFR therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) has achieved ideal clinical efficacy in recent years. Unfortunately, resistance to EGFR-TKIs inevitably occurs due to various mechanisms after a period of therapy. EGFR mutations, such as T790M and C797S, are the most common mechanism of EGFR-TKI resistance. Here, we discuss the mechanisms of EGFR-TKIs resistance induced by secondary EGFR mutations, highlight the development of targeted drugs to overcome EGFR mutation-mediated resistance, and predict the promising directions for development of novel candidates.

miR-374 improves cerebral ischemia reperfusion injury by targeting Wnt5a.

To date, studies have demonstrated the potential functions of microRNAs in cerebral ischemia reperfusion (IR) injury. Herein, we established a middle cerebral artery occlusion (MCAO) model in rats and then subjected them to reperfusion to explore the role of microRNA-374 (miR-374) in cerebral IR injury. After reperfusion, the endogenous miR-374 level decreased, and the expression of its target gene, Wnt5a, increased in brain tissues. Intracerebral pretreatment of miR-374 agomir attenuated cerebral damage induced by IR, including neurobehavioral deficits, infarction, cerebral edema and blood-brain barrier disruption. Moreover, rats pretreated with miR-374 agomir showed a remarkable decrease in apoptotic neurons, which was further confirmed by reduced BAX expression as well as increased BCL-2 and BCL-XL expression. A dual-luciferase reporter assay substantiated that Wnt5a was the target gene of miR-374. miR-374 might protect against brain injury by downregulating Wnt5a in rats after IR. Thus, our study provided a novel mechanism of cerebral IR injury from the perspective of miRNA regulation.

High-precision nonlocal temporal correlation identification of entangled photon pairs for quantum clock synchronization.

High-precision nonlocal temporal correlation identification in entangled photon pairs is critical to measure the time offset between remote independent time scales for many quantum information applications. The first nonlocal correlation identification was reported in 2009, which extracts the time offset via the algorithm of iterative fast Fourier transformations and their inverse. The best identification resolution is restricted by the peak identification threshold of the algorithm, and thus the time offset calculation precision is limited. In this paper, an improvement for the identification is presented both in resolution and precision via a modified algorithm of direct cross correlation extraction. A flexible resolution down to 1 ps is realized, which is only dependent on the least significant bit resolution of the time-tagging device. The attainable precision is shown to be mainly determined by the inherent timing jitter of single photon detectors, the acquired pair rate, and acquisition time, and a sub-picosecond precision (0.72 ps) has been achieved at an acquisition time of 4.5 s. This high-precision nonlocal measurement realization provides a solid foundation for the field applications of entanglement-based quantum clock synchronization, ranging, and communications.

MicroRNA and long noncoding RNA involvement in gout and prospects for treatment.

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are both types of noncoding RNA. They have been demonstrated to be involved in the regulation of various human inflammatory diseases and can be used as biomarkers for disease diagnosis and prognosis, and even be developed into new drugs. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Recent studies have shown that miRNAs and lncRNAs mediate the progress of gout. Based on the pathogenesis of gout, including hyperuricemia, MSU deposition, acute gouty arthritis and gouty bone erosion, this paper reviewed the role of miRNAs and lncRNAs in the processes and the possible therapeutic targets of miRNAs and lncRNAs in gout.