Dysregulated inter-mitochondrial crosstalk in glioblastoma cells revealed by in situ cryo-electron tomography.

Glioblastomas (GBMs) are the most lethal primary brain tumors with limited survival, even under aggressive treatments. The current therapeutics for GBMs are flawed due to the failure to accurately discriminate between normal proliferating cells and distinctive tumor cells. Mitochondria are essential to GBMs and serve as potential therapeutical targets. Here, we utilize cryo-electron tomography to quantitatively investigate nanoscale details of randomly sampled mitochondria in their native cellular context of GBM cells. Our results show that compared with cancer-free brain cells, GBM cells own more inter-mitochondrial junctions of several types for communications. Furthermore, our tomograms unveil microtubule-dependent mitochondrial nanotunnel-like bridges in the GBM cells as another inter-mitochondrial structure. These quantified inter-mitochondrial features, together with other mitochondria-organelle and intra-mitochondrial ones, are sufficient to distinguish GBM cells from cancer-free brain cells under scrutiny with predictive modeling. Our findings decipher high-resolution inter-mitochondrial structural signatures and provide clues for diagnosis and therapeutic interventions for GBM and other mitochondria-related diseases.

Procoagulant Properties of Mesenchymal Stem Cells and Extracellular Vesicles: A Novel Aspect of Thrombosis Pathogenesis.

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and secrete extracellular vesicles (EVs) that transport bioactive molecules and mediate intercellular communication. MSCs and MSC-derived EVs (MSC-EVs) have shown promising therapeutic effects in several diseases. However, their procoagulant activity and thrombogenic risk may limit their clinical safety. In this review, we summarize current knowledge on procoagulant molecules expressed on the surface of MSCs and MSC-EVs, such as tissue factor and phosphatidylserine. Moreover, we discuss how these molecules interact with the coagulation system and contribute to thrombus formation through different mechanisms. Additionally, various confounding factors, such as cell dose, tissue source, passage number, and culture conditions of MSCs and subpopulations of MSC-EVs, affect the expression of procoagulant molecules and procoagulant activity of MSCs and MSC-EVs. Therefore, herein, we summarize several strategies to reduce the surface procoagulant activity of MSCs and MSC-EVs, thereby aiming to improve their safety profile for clinical use.

Vacancy Suppression and Resonant Level Rendering Extraordinary Power Factor in Sn0.99In0.01Te/Tourmaline Composite.

SnTe, as a potential medium-temperature thermoelectric material, reaches a maximum power factor (PF) usually above 750 K, which is not conducive to continuous high-power output in practical applications. In this study, PF is maintained at high values between 18.5 and 25 µW cm-1 K-2 for Sn0.99In0.01Te-x wt% tourmaline samples within the temperature range of 323 to 873 K, driving the highest PFeng of 1.2 W m-1 K-1 and PFave of 22.5 µW cm-1 K-2, over 2.5 times that of pristine SnTe. Such an extraordinary PF is attributed to the synergy of resonant levels and Sn vacancy suppression. Specifically, the Seebeck coefficient increases dramatically, reaching 88 µV K-1 at room temperature. Meanwhile, by Sn vacancy suppression, carrier concentration, and mobility are optimized to ≈1019 cm-3 and 740 cm2 V-1 s-1, respectively. With the tourmaline compositing, Sn vacancies are further suppressed and the thermal conductivity simultaneously decreases, with the minimum lattice thermal conductivity of 0.9 W m-1 K-1. Finally, the zT value ≈0.8 is obtained in the Sn0.99In0.01Te sample. The peak of the power output density reaches 0.89 W cm-2 at a temperature difference of 600 K. Such SnTe alloys with high and "temperature-independent" PF will offer an option for realizing high output power in thermoelectric devices.

Secure key generation and distribution scheme based on historical fiber channel state information with LSTM.

In this paper, a scheme to realize unclonable physical-layer security key generation and distribution (PL-SKGD) based on historical fiber channel state information (HFCSI) is proposed. PL-SKGD schemes based on channel characteristics for enhancing the physical-layer security of optical networks have been proposed in recent years. However, there are potential disadvantages in these schemes, such as 1) low key generation rate (KGR): the slow frequency of the analog waveform change of the channel characteristic leading to low KGR; 2) incompatibility with existing infrastructure: active scrambling to increase the frequency of channel characteristic changes, or tracking changes of channel characteristics requires additional devices; 3) easy to be cloned: all of the optical channel state information is reflected in the signal transmitted inside the fiber, which makes it easy to reproduce by illegal eavesdropper through features analysis and other methods. In order to solve the above problems, a PL-SKGD scheme is designed which uses the chain structure composed of long short-term memory neural network (LSTM-NN) units to learn and store the unique mapping relationship between historical channel time series and provides unclonability based on the fundamental fact that the eavesdropper Eve can never obtain the full HFCSI. The simulation conducted in a quadrature phase shift keying point-to-point optical link system verified successfully that KGR = 0.82 Gbit/s error-free SKGD. The loss function of LSTM-NN drops sharply in the early stages of training and remains a small value. The security of the SKGD system is analyzed, which effectively improves the unclonability of the system. Finally, it is verified that the optimal fiber channel length for error-free SKGD of the proposed scheme is 150 km considering the error correction capability of information reconciliation and weighing key sequence error rate and valid bit generation rate.

Impact of preoperative transcatheter arterial chemoembolization (TACE) on postoperative long-term survival in patients with nonsmall hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: The purpose of this propensity score matching (PSM) analysis was to compare the effects of preoperative transcatheter arterial chemoembolization (TACE) and non-TACE on the long-term survival of patients who undergo radical hepatectomy. METHODS: PSM analysis was performed for 387 patients with hepatocellular carcinoma (HCC) (single > 3 cm or multiple) who underwent radical resection of HCC at our centre from January 2011 to June 2018. The patients were allocated to a preoperative TACE group (n = 77) and a non-TACE group (n = 310). The main outcome measures were progression-free survival (PFS) and overall survival (OS) since the treatment date. RESULTS: After PSM, 67 patients were included in each of the TACE and non-TACE groups. The median PFS times in the preoperative TACE and non-TACE groups were 24.0 and 11.3 months, respectively (p = 0.0117). The median OS times in the preoperative TACE and non-TACE groups were 41.5 and 29.0 months, respectively (p = 0.0114). Multivariate Cox proportional hazard regression analysis revealed that preoperative TACE (hazard ratio, 1.733; 95% CI, 1.168-2.570) and tumour thrombosis (hazard ratio, 0.323; 95% CI, 0.141-0.742) were independent risk factors significantly associated with OS. CONCLUSIONS: Preoperative TACE is related to improving PFS and OS after resection of HCC. Preoperative TACE and tumour thrombus volume were also found to be independent risk factors associated with OS.

Modular preparation of biphenyl triazoles via click chemistry as non-competitive hyaluronidase inhibitors.

Hyaluronidase is a promising target in drug discovery, given its overexpression in a range of physiological and pathological processes, including tumor migration, skin aging, sagging, and wrinkling, as well as inflammation and bacterial infections. In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6, as well as quinoline-containing triazoles 15 and 16, as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulated macrophages. Remarkably, compound 6 significantly reduced NO release by 74 % at a concentration of 20 µM.

Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

Extended lymphadenectomy based on the TRIANGLE for pancreatic head cancer: a single-center experience.

BACKGROUND: This study was to compare the safety and efficacy of different lymphadenectomy methods in patients with pancreatic head cancer undergoing pancreaticoduodenectomy (PD). MATERIAL AND METHODS: A total of 150 patients were included in this study. Patients were divided into Group A (n = 79), Group B (n = 44), and Group C (n = 27) according to the different lymphadenectomy methods. The clinical endpoint was time to progression (TTP) and overall survival (OS). Postoperative complications of different lymphadenectomy methods were compared respectively. TTP and OS of the three groups were compared by Kaplan-Meier curves. RESULTS: There were no significant differences between the three groups in operative time (P = 0.300), death in the hospital (P = 0.253), postoperative hemorrhage (P = 0.863), postoperative pancreatic fistula (POPF) B/C (P = 0.306), bile leakage (P = 0.215), intestinal fistula (P = 0.177), lymphatic leakage (P = 0.267), delayed gastric emptying [(DGE) (P = 0.283)], ICU stay (P = 0.506), and postoperative hospital stay [(PHS) (P = 0.810)]. Median TTP in Groups B and C was significantly longer than in Group A (log-rank test, A vs B: P = 0.0005, A vs C: P = 0.0001). Median OS between the three groups has no statistical difference (P = 0.1546). CONCLUSIONS: Extended lymphadenectomy methods based on the TRIANGLE do not increase perioperative complications significantly and can effectively delay tumor progression in patients with pancreatic head cancer.

Zinc Finger Protein BCL11A Contributes to the Abortive Infection of Hirame novirhabdovirus (HIRRV) in B Lymphocytes of Flounder (Paralichthys olivaceus).

Hirame novirhabdovirus (HIRRV) infection is characterized by a pronounced viremia, and the high viral load is typically detected in immune-related organs and the circulatory system. In the present study, we demonstrated that HIRRV has the capacity to invade part of flounder membrane-bound IgM (mIgM+) B lymphocyte. Eight quantitative real-time PCR (qRT-PCR) standard curves involving HIRRV genomic RNA (gRNA), cRNA, and six mRNAs were established based on the strand-specific reverse transcription performed with tagged primers. It was revealed that viral RNA synthesis, especially the replication of gRNA, was inhibited in B cells, and the intracellular HIRRV even failed to produce infectious viral particles. Moreover, a range of genes with nucleic acid binding activity or related to viral infection were screened out based on the transcriptome analysis of HIRRV-infected B cells, and five molecules were further selected because of their different expression patterns in HIRRV-infected B cells and hirame natural embryo (HINAE) cells. The overexpression of these genes followed by HIRRV infection and RNA binding protein immunoprecipitation (RIP) assay revealed that the flounder B cell lymphoma/leukemia 11A (BCL11A), a highly conserved zinc finger transcription factor, is able to inhibit the proliferation of HIRRV by binding with full-length viral RNA mainly via its zinc finger domains at the C terminus. In conclusion, these data indicated that the high transcriptional activity of BCL11A in flounder mIgM+ B lymphocytes is a crucial factor for the abortive infection of HIRRV, and our findings provide new insights into the interaction between HIRRV and teleost B cells. IMPORTANCE HIRRV is a fish rhabdovirus that is considered as an important pathogen threatening the fish farming industry represented by flounder because of its high infectivity and fatality rate. To date, research toward understanding the complex pathogenic mechanism of HIRRV is still in its infancy and faces many challenges. Exploration of the relationship between HIRRV and its target cells is interesting and necessary. Here, we revealed that flounder mIgM+ B cells are capable of suppressing viral RNA synthesis and result in an unproductive infection of HIRRV. In addition, our results demonstrated that zinc finger protein BCL11A, a transcription factor in B cells, is able to suppress the replication of HIRRV. These findings increased our understanding of the underlying characteristics of HIRRV infection and revealed a novel antiviral mechanism against HIRRV based on the host restriction factor in teleost B cells, which sheds new light on the research into HIRRV control.

Fingerprint construction of optical transmitters based on the characteristic of electro-optic chaos for secure authentication.

In this paper, an optical transmitter authentication method using hardware fingerprints based on the characteristic of electro-optic chaos is proposed. By means of phase space reconstruction of chaotic time series generated by an electro-optic feedback loop, the largest Lyapunov exponent spectrum (LLES) is defined and used as the hardware fingerprint for secure authentication. The time division multiplexing (TDM) module and the optical temporal encryption (OTE) module are introduced to combine chaotic signal and the message to ensure the security of the fingerprint. Support vector machine (SVM) models are trained to recognize legal and illegal optical transmitters at the receiver. Simulation results show that LLES of chaos has the fingerprint characteristic and is highly sensitive to the time delay of the electro-optic feedback loop. The trained SVM models can distinguish electro-optic chaos generated by different feedback loops with a time delay difference of only 0.03ns and have a good anti-noise ability. Experimental results show that the recognition accuracy of the authentication module based on LLES can reach 98.20% for both legal and illegal transmitters. Our strategy can improve the defense ability of optical networks against active injection attacks and has high flexibility.

Optical transmitter fingerprint construction and identification based on chaotic phase space reconfiguration.

An optical transmitter identification scheme based on optical chaotic phase space reconfiguration for secure communication is proposed to target injection attacks in the physical layer of optical networks. First, a feature fingerprint construction method based on reconfigured phase space of optical chaos is proposed. Then the fingerprint is controlled by the feedback intensity and filtering bandwidth of chaos. The in-phase and quadrature-phase encryption (IQE)/decryption (IQD) ensures the loading of fingerprints and realizes the confidential communication. In the experiment, the recognition rate of three transmitters is up to 99.3%. In the simulation, the recognition rate of five optical transmitters reaches 100% after 600 km transmission. The bit error rate of 25 GBaud QPSK signal after 300 km transmission at 25 dB OSNR is 1.6 × 10-3. Compared with the traditional optical transmitter identification methods, the fingerprint of this scheme is controllable. The IQE and IQD not only realize the chaotic fingerprint loading but also ensure the secure transmission of the signal avoiding the synchronization and time delay exposure problems in traditional chaotic communication systems. It is robust to device parameters, with low implementation difficulty and low cost. Therefore, this scheme has research and application value for secure communication in the physical layer of optical networks.

Physical-layer encryption and authentication scheme based on SKGD and 4D hyper-chaos.

In this paper, a scheme to realize encryption and digital identity authentication at the same time is proposed for enhancing the physical-layer security of point-to-point optical links (PPOL). Exploiting identity code encrypted by the key as authentication information effectively resists passive eavesdropping attacks in fingerprint authentication. The proposed scheme theoretically realizes secure key generation and distribution (SKGD) by phase noise estimation of the optical channel and the generation of identity codes with good randomness and unpredictability by the four-dimensional (4D) hyper-chaotic system. The local laser, erbium doped fiber amplifier (EDFA), and public channel provide the entropy source of uniqueness and randomness to extract symmetric key sequences for legitimate partners. The simulation conducted in a quadrature phase shift keying (QPSK) PPOL system over 100km standard single mode fiber verify successfully that 0.95Gbit/s error-free SKGD. The unpredictability and high sensitivity to the initial value and control parameters of the 4D hyper-chaotic system provide a huge space of ~10125 for identity codes, which is sufficient to resist exhaustive attack. With the proposed scheme, the security level of key and identity can be increased markedly.

Hadh deficiency induced oligoasthenoteratozoospermia through the TNF-α/Bcl-2 pathway in male mice.

The process of spermatogenesis is a complex and delicate process that is still not fully understood. In this study, we examined the role of fatty acid oxidase 3-hydroxy acyl CoA dehydrogenase (HADH) in maintaining normal spermatogenesis in mice. In male mice, ablation of the Hadh gene using CRISPR/Cas9 technology arrested spermatocyte meiosis, increased multinucleated giant germ cells and vacuoles in seminiferous tubules, and accompanied with acrosomal dysplasia. Hadh-/- male mice showed the typical features of oligoasthenoteratozoospermia (OAT), including decreased sperm concentration and motility and increased sperm abnormalities. Next, we explored the molecular events in the testes of the mutant mice. We found fatty acids accumulated in the testis of Hadh-/- mice. And also, inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased, apoptosis-related protein Bcl-2 was decreased, and Bax and cleaved-Caspase3 were increased in Hadh-/- male mice testis. After using etanercept, a specific inhibitor of TNF-α, testis injury caused by Hadh knockout was significantly alleviated, the sperm quality and motility were improved, and germ cell apoptosis was reduced. So our study demonstrated that Hadh deletion caused an increase in fatty acids. The accumulated fatty acids further induced testicular inflammation and germ cell apoptosis through the TNF-α/Bcl-2 signaling pathway, finally resulting in OAT in the Hadh-/- mice. Inhibiting TNF-α may be used as a new treatment approach for testicular inflammation and OAT.

Mechanism Research on Excited-State Photoinduced Electron Transfer in a Pyrazine Derivative under an External Electric Field.

In this study, a charge-transfer complex was formed between 3-(4-(di([1,1'-biphenyl]-4-yl)amino)phenyl) (dpTPA) and acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile (APDC) (dpTPAAP) that exhibited a wide range of charge-transfer absorption that extended to the near-infrared region. The rate of charge transfer as regulated by an external electric field (Fext) was quantitatively depicted using first-principles quantum mechanics. The results show that the rates of charge separation and charge recombination were affected by Fext and were distinctly susceptible to it in the forward direction. According to the Marcus rate analysis of the dpTPAAP system with different values of Fext, its influence needs to be considered when simulating electron transfer on the bulk and the interfaces in organic semiconductors. This work advances our knowledge of the impact of Fext on solar-cell-based photoactive materials and provides a means to design novelty devices.

Driving forces of hydrological health and multifractal response of fish habitat in regulated rivers.

Climate change and anthropogenic activities are major influences on the hydrological cycle, further altering river hydrological health. However, the characteristics of the forces in driving the variations of hydrological health at long-short time scales (annual, seasonal, monthly), as well as the potential impacts of these variations on aquatic habitats, remain unclear. In this study, the flow threshold method was introduced to identify the inherent characteristics of river hydrological health degree (RHD) evolution in the upper reaches of the Yangtze River (URYR) through the extreme-point symmetric modal decomposition (ESMD) method and range of variation approach (RVA). The RHD under unregulated conditions was reconstructed to quantify the impacts of anthropogenic activities and climate change. Subsequently, a multifractal model was proposed to establish the relationship between RHD and habitat-weighted usage area (WUA) during the spawning period of the Four Famous Major Carps, aiming to analyze the response mechanisms of habitat conditions to RHD fluctuations. The results showed that the RHD in the URYR exhibited degradation characteristics, experiencing a moderate change with a value of 0.44. Climate change was identified as the dominant factor causing the annual-scale decline in RHD, with an average impact weight of 62.9%. At the annual scale, Anthropogenic activities exacerbate (-3.4), counteract (20.1), and counteract (20.5) the adverse climatic impacts at Yichang, Cuntan, and Zhutuo stations, respectively. Additionally, the effect of human activities during the flood season is slight, with the most favorable and unfavorable impacts occurring in December (50.7) at the Zhutuo station and in October (-27.2) at the Yichang station. Under the influence of driving forces, the multifractal correlation of the RHD-WUA system tended to homogenized as the time window increased, indicating the presence of potential nonlinear dependence, asymmetric fractal characteristics, and positive-to-negative persistence transitions. Therefore, modeling river health considering fish habitat cannot be limited to linear paradigms. The findings provide valuable insights for the management and restoration of aquatic ecosystems.

Effect of elevated fasting blood glucose level on the 1-year mortality and sequelae in hospitalized COVID-19 patients: A bidirectional cohort study.

To observe the predictive effect of fasting blood glucose (FBG) level on the prognosis, clinical sequelae, and pulmonary absorption in hospitalized coronavirus disease 2019 (COVID-19) patients with and without a history of diabetes, respectively, and to evaluate the correlation between the dynamic changes of FBG and poor prognosis. In this bidirectional cohort study, we enrolled 2545 hospitalized COVID-19 patients (439 diabetics and 2106 without a diabetic history) and followed up for 1 year. The patients were divided according to the level of admission FBG. The dynamic changes of FBG were compared between the survival and the death cases. The prediction effect of FBG on 1-year mortality and sequelae was analyzed. The 1-year all cause mortality rate and in-hospital mortality rate of COVID-19 patients were J-curve correlated with FBG (p < 0.001 for both in the nondiabetic history group, p = 0.004 and p = 0.01 in the diabetic history group). FBG ≥ 7.0 mmol/L had a higher risk of developing sequelae (p = 0.025) and have slower recovery of abnormal lung scans (p < 0.001) in patients who denied a history of diabetes. Multivariable Cox regression analysis showed that FBG ≥ 7.0 mmol/L was an independent risk factor for the mortality of COVID-19 regardless of the presence or deny a history of diabetes (hazard atio [HR] = 10.63, 95% confidence interval [CI]: 7.15-15.83, p < 0.001; HR = 3.9, 95% CI: 1.56-9.77, p = 0.004, respectively). Our study shows that FBG ≥ 7.0 mmol/L can be a predictive factor of 1-year all-cause mortality in COVID-19 patients, independent of diabetes history. FBG ≥ 7.0 mmol/L has an advantage in predicting the severity, clinical sequelae, and pulmonary absorption in COVID-19 patients without a history of diabetes. Early detection, timely treatment, and strict control of blood glucose when finding hyperglycemia in COVID-19 patients (with or without diabetes) are critical for their prognosis.

Experimental demonstration of all-optical aggregation and de-aggregation for a QPSK signal in an elastic optical network.

The aggregation and de-aggregation between one QPSK and two BPSK signals are experimentally demonstrated based on cross-phase modulation (XPM) effects and phase-sensitive amplification (PSA), aiming to improve flexible spectral efficiency in the elastic optical network. Benefiting from the nonlinear-optical loop mirror (NOLM), the two BPSK signals can be extracted without any information redundancy for the de-aggregation scheme. The wavelength of the extracted signals stay the same as the input signal in the NOLM. Moreover, the aggregation from two BPSK signals to one QPSK signal is also successfully achieved. The feasibility of the two schemes can be confirmed by the transfer functions and the input-output constellation. The bit-error-rate (BER) and error vector magnitude(EVM) performance of the two schemes are also investigated and the corresponding OSNRs for error-free signal recovery are obtained respectively. The proposed schemes contribute to the realization of flexible optical networks and can be applied in the future gateway node between optical sub-networks.

Channel characteristics estimation based on a secure optical transmission system with deep neural networks.

Optical transmission security has attracted much attention. In recent years, many secure optical transmission systems based on channel characteristics are proposed. However, there are many drawbacks with these systems, such as separated plaintext and key transmission, low key generation rate (KGR), insecurity when the eavesdropper has acquired the lengths of the local fibers utilized by legal parties. To solve the above problems, we propose a novel secure optical transmission system based on neural networks (NNs), which are employed to estimate channel characteristics. By training NNs locally and transmitting pseudo-keys, the proposed system can transmit the plaintext together with key, transforming the key dynamically. Moreover, since the channel characteristics for legal parties and eavesdropper are not completely identical, the NNs trained by legal parties and eavesdropper are inconsistent. Even though the eavesdropper has attained the lengths of local fibers wielded by legal parties, the NN model trained by the legal parties is still unavailable to illegal eavesdropper. The final key is generated by the trained NN and pseudo-key, so the keys generated by legal parties and eavesdropper are dissimilar. The simulation results prove the feasibility of the proposed system with the transmission distance of 100 km and the bit rate of 100 Gbps. Meanwhile, if plaintext and key have equivalent code length, the KGR of 50 Gbps for legal parties and the key disagreement rate (KDR) of 50% for illegal eavesdropper will be realized.

A time-delay signature elimination and broadband electro-optic chaotic system with enhanced nonlinearity by deep learning.

In this paper, a novel electro-optic chaotic system with enhanced nonlinearity by deep learning (ENDL) is proposed to achieve time-delay signature (TDS) elimination. A long-short term memory network (LSTM) is trained by a specially designed loss function to enhance the nonlinear effect that can hide the TDS of the system. For the first time, the trained deep learning module is put into a single feedback loop to participate in chaos generation. Simulation results show that the ENDL system can eliminate TDS and increase the bandwidth to more than 31GHz when the feedback intensity is very low (α = 4V). Moreover, the complexity of the chaotic output can be improved with permutation entropy (PE) reaching 0.9941. The synchronization result shows that the ENDL system has high sensitivity to TDS but has low sensitivity to the feedback intensity, thus the system has both high security and high robustness. This system has an uncomplicated synchronization structure and high flexibility, and it opens up a new direction for high-quality chaos generation.

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs. We found that late passage (P25 or later) UCMSCs (LP-UCMSCs) exhibited impaired proangiogenic abilities. Treatment of P25 UCMSCs with rapamycin (900 nM) reversed the senescent phenotype and notably enhanced the proangiogenic activity of senescent UCMSCs. In a nude mouse model of hindlimb ischemia, intramuscular injection of rapamycin-treated P25 UCMSCs into the ischemic limb significantly promoted neovascularization and ischemic limb salvage. We further analyzed the changes in the expression of angiogenesis-associated genes in rapamycin-primed MSCs and found higher expression of several genes related to angiogenesis, such as VEGFR2 and CTGF/CCN2, in primed cells than in unprimed MSCs. Taken together, our data demonstrate that rapamycin is a potential drug to restore the proangiogenic activity of senescent MSCs, which is of importance in treating ischemic diseases and tissue engineering.