Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.

Continuous-variable quantum key distribution robust against environmental disturbances.

Continuous variable quantum key distribution (CV-QKD) can guarantee that two parties share secure keys even in the presence of an eavesdropper. However, the polarization direction of the coherent state transmitted in CV-QKD is susceptible to environmental disturbances during channel transmission, making it difficult to share keys consistently over long periods of time. Therefore, a CV-QKD system that can resist environmental disturbance is very urgent. In this paper, we propose a new optical architecture for CV-QKD based on the Faraday-Michelson interference (FMI) structure, and finally form an all-single-mode (SM) fiber-based stable CV-QKD system which employs transmitted local oscillator (TLO) scheme and discrete modulation coherent state (DMCS) protocol. Specifically, since the Faraday mirror rotates the polarization direction of light by 90o, the birefringence effect of light can be effectively dealt with, thus ensuring the same polarization state of light before and after reflection. The final simulation results show that the theoretical secret key rate of this scheme can reach 139 kbps at 70 km, which can further improve the stability and robustness of CV-QKD in the real environment, and provide technical support for the next-generation high-stability QKD system.

Preliminary characterization of chemical and sensory attributes for grapes and wines of different cultivars from the Weibei Plateau region in China.

Chemical and sensory attributes play a vital role in evaluating the quality of grapes and wines. This study compared basic physicochemical parameters, organic acids, phenolic compounds, and aroma profiles of grapes and wines of six cultivars using chemometrics. The results showed that the reducing sugar contents of Beibinghong, Gongniang, and Granoir grapes were significantly higher than those of others cultivars, whereas their juice yields were significantly lower. The phenolic compound contents in Moldova, Beibinghong, and Gongniang grape skins and wines were higher than those in others cultivars. The organic acid contents in Beibinghong grape and Dunkelfelder wine were highest. Beibinghong and Gongniang grapes and wines showed richer aldehyde and ester concentrations. Beibinghong wine obtained the highest sensory scores. Ethyl decanoate, coumaric acid, and methyl dodecanoate were characteristic variables distinguishing wine cultivars, exhibiting important contributions to their sensory characteristics. These findings were useful for viticulturists and winemakers to select grape varieties.

High-speed information reconciliation with syndrome-based early termination for continuous-variable quantum key distribution.

Information reconciliation (IR) is an indispensable component in the post-processing stage of continuous-variable quantum key distribution (CV-QKD), which adopts error-correcting codes to address the asymmetry of secret keys. Currently, low-density parity-check (LDPC) decoding in IR is a post-processing bottleneck in high-speed CV-QKD systems since the upper bound on secret key rate is higher than the information throughput delivered by decoder. In this paper, we study the relationship between the syndrome variation pattern (SVP) in iterative decoding and reconciliation frame error rate. An early termination scheme based on SVP is proposed and applied to multidimensional reconciliation, which can increase information throughput by adaptively adjusting the iteration number of iterative decoding to real-time decoding status. Furthermore, we show that only the resulting syndrome of the highest-rate code part in Raptor-like LDPC codes needs to be calculated to verify whether the reconciliation is successful by studying the convergency of resulting syndrome, which can save a large fraction of computational resources for syndrome calculation. Simulation results show that information throughput of the proposed scheme can be improved by 617.1% compared to the existing scheme when the IR efficiency reaches 97.09%. The proposed scheme points out a new direction for breaking the post-processing bottleneck in high-speed CV-QKD systems.

Association of Adipokines with Alzheimer's Disease in a Chinese Cohort.

BACKGROUND: The correlation between plasma adipose factor levels and Alzheimer's patients is not entirely clear. OBJECTIVE: We aimed to investigate associations between AD and plasma levels of three adipokines including plasma adiponectin, leptin, and resistin. METHODS: A single-center, cross-sectional study recruited AD patients (n = 148) and cognitively normal (CN) controls (n = 110). The multivariate logistic regression analysis was applied to determine associations of adiponectin, leptin, and resistin with the presence of AD. The receiver operating characteristic (ROC) analysis was employed to determine the diagnostic power of adiponectin, leptin and resistin for AD. RESULTS: After adjusted for the conventional risk factors, plasma levels of leptin (OR = 0.417, 95% CI: 0.272-0.638, p < 0.0001) and adiponectin (OR = 1.249, 95% CI: 1.151-1.354, p < 0.0001) were associated with the presence of AD. In total participants, the plasma adiponectin level was negatively correlated with MMSE scores (p < 0.0001) and was positively with CDR scores (p < 0.0001) and age (p < 0.0001). The plasma level of leptin was negatively correlated with CDR scores (p < 0.0001) and positively correlated with MMSE scores (p < 0.0001). Both adiponectin (p < 0. 0001) and leptin (p < 0. 0001) featured higher AUC than the random chance. CONCLUSIONS: Plasma adiponectin and leptin were associated with the presence, symptomatic severity, and diagnostic power of AD, suggesting a potential role of adipokines in the pathogenesis of AD.

Effective Excess Noise Suppression in Continuous-Variable Quantum Key Distribution through Carrier Frequency Switching.

Continuous-variable quantum key distribution (CV-QKD) is a promising protocol that can be easily integrated with classical optical communication systems. However, in the case of quantum-classical co-transmissions, such as dense wavelength division multiplexing with classical channels and time division multiplexing with large-power classical signal, a quantum signal is more susceptible to crosstalk caused by a classical signal, leading to signal distortion and key distribution performance reduction. To address this issue, we propose a noise-suppression scheme based on carrier frequency switching (CFS) that can effectively mitigate the influence of large-power random noise on the weak coherent state. In this noise-suppression scheme, a minimum-value window of the channel's noise power spectrum is searched for and the transmission signal frequency spectrum shifts to the corresponding frequency to avoid large-power channel noise. A digital filter is also utilized to filter out most of the channel noise. Simulation results show that compared to the traditional fixed carrier frequency scheme, the proposed noise-suppression scheme can reduce the excess noise to 1.8%, and the secret key rate can be increased by 1.43 to 2.86 times at different distances. This noise-suppression scheme is expected to be applied in scenarios like quantum-classical co-transmission and multi-QKD co-transmission to provide noise-suppression solutions.

Marine Alkaloid Lepadins E and H Induce Ferroptosis for Cancer Chemotherapy.

Induction of ferroptosis emerges as an effective method for cancer treatment. With massive efforts to elucidate the ferroptosis mechanism, the development of new ferroptosis inducers proceeds rather slowly, with only a few small molecules identified. Herein, we report our discovery of marine alkaloid lepadins E and H as a new class of ferroptosis inducers. Our in vitro studies show that lepadins E and H exhibit significant cytotoxicity, promote p53 expression, increase ROS production and lipid peroxides, reduce SLC7A11 and GPX4 levels, and upregulate ACSL4 expression, all of which consistently support induction of ferroptosis through the classical p53-SLC7A11-GPX4 pathway. Our animal model study of lepadin H confirms its in vivo antitumor efficacy with negligible toxicity to normal organs. This work elucidates the mode of action of lepadins (E and H) and verifies their in vivo efficacy as a new class of ferroptosis inducers for anticancer therapy with translational potential.

The Diagnostic Potential of Circulating Autoantibodies to Amyloid-ß in Alzheimer's Disease.

BACKGROUND: The profile of naturally occurring antibodies to amyloid-ß (NAbs-Aß) is altered in patients with Alzheimer's disease (AD). However, the diagnostic potential of NAbs-Aß for AD is not clear yet. OBJECTIVE: This study aims to investigate the diagnostic capacities of NAbs-Aß for AD. METHODS: A total of 40 AD patients and 40 cognitively normal (CN) controls were enrolled in this study. Levels of NAbs-Aß were detected by ELISA. The correlations of NAbs-Aß levels with cognitive function and AD-associated biomarkers were examined by Spearman correlation analysis. Diagnostic abilities of NAbs-Aß were evaluated by the receiver operating characteristic (ROC) curve analyses. The integrative diagnostic models were established by logistic regression models. RESULTS: We found that NAbs-Aß7-18 had the highest diagnostic capability (AUC = 0.72) among all single NAbs-Aß. The combined model (NAbs-Aß7-18, NAbs-Aß19-30, and NAbs-Aß25-36) had a noticeable improvement (AUC = 0.84) in the diagnostic capacity compared with each single NAbs-Aß. CONCLUSION: NAbs-Aßs are promising in the diagnosis of AD. Further investigations are needed to confirm the translational potential of this diagnostic strategy.

Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-ß and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits.

Deficiencies in the clearance of peripheral amyloid ß (Aß) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aß is decreased in AD. However, the exact mechanism of Aß clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aß. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aß in vivo and in vitro. Moreover, enhancing blood monocyte Aß phagocytosis by improving energy metabolism alleviated brain Aß deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aß phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

Associations of Blood and Cerebrospinal Fluid Aß and tau Levels with Renal Function.

Amyloid ß (Aß) and tau play pivotal roles in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that brain-derived Aß and tau can be cleared through transport into the periphery, and the kidneys may be vital organs involved in the clearance of Aß and tau. However, the effects of deficiency in the clearance of Aß and tau by the kidneys on brain AD-type pathologies in humans remain largely unknown. In this study, we first recruited 41 patients with chronic kidney disease (CKD) and 40 age- and sex-matched controls with normal renal function to analyze the associations of the estimated glomerular filtration rate (eGFR) with plasma Aß and tau levels. To analyze the associations of eGFR with cerebrospinal fluid (CSF) AD biomarkers, we recruited 42 cognitively normal CKD patients and 150 cognitively normal controls with CSF samples. Compared with controls with normal renal function, CKD patients had higher plasma levels of Aß40, Aß42 and total tau (T-tau), lower CSF levels of Aß40 and Aß42 and higher levels of CSF T-tau/Aß42 and phosphorylated tau (P-tau)/Aß42. Plasma Aß40, Aß42, and T-tau levels were negatively correlated with eGFR. In addition, eGFR was negatively correlated with CSF levels of T-tau, T-tau/Aß42, and P-tau/Aß42 but positively correlated with Mini-Mental State Examination (MMSE) scores. Thus, this study showed that the decline in renal function was correlated with abnormal AD biomarkers and cognitive decline, which provides human evidence that renal function may be involved in the pathogenesis of AD.

High-precision data acquisition for free-space continuous-variable quantum key distribution.

Data acquisition in a continuous-variable quantum key distribution (CV-QKD) system is a necessary step to obtain secure secret keys. And the known data acquisition methods are commonly based on the assumption that the channel transmittance is constant. However, the channel transmittance in free-space CV-QKD fluctuates during the transmission of quantum signals, and the original methods are not applicable in this scenario. In this paper, we propose a data acquisition scheme based on the dual analog-to-digital converter (ADC). In this scheme, two ADCs with the same sampling frequency as the pulse repetition rate of the system and a dynamic delay module (DDM), which are used to construct a high-precision data acquisition system, eliminate the effect of transmittance fluctuation by a simple division operation of the data from the two ADCs. Simulation and proof-of-principle experimental results show that the scheme is effective for free-space channels and can achieve high-precision data acquisition under the condition of fluctuation of channel transmittance and very low signal-to-noise ratio (SNR). Furthermore, we introduce the direct application scenarios of the proposed scheme for free-space CV-QKD system and verify their feasibilities. This method is of great significance to promote the experimental realization and practical application of free-space CV-QKD.

Experimental free-space continuous-variable quantum key distribution with thermal source.

Passive-state-preparation (PSP) continuous-variable quantum key distribution (CVQKD) protocol explores the intrinsic field fluctuations of a thermal source. Compared with traditional Gaussian-modulated coherent-state CVQKD, it does not need active modulations and has promising applications in chip integration and portable free-space quantum key distribution. In this Letter, we propose and experimentally realize a PSP CVQKD scheme with transmitted local oscillator (LO) through fluctuating transmittance free-space channel using an off-the-shelf amplified spontaneous emission source for the first time. By proposing thermal-state polarization multiplexing transmitted LO, synchronized channel transmittance monitoring and fine-grained phase compensation techniques, secure keys within -15 dB transmittance of simulated free-space channel with turbulence are generated, with a final average secure key rate of 1.015 Mbps asymptotically. Equivalent atmospheric turbulence model analysis shows that the free-space PSP CVQKD scheme provides a promising outlook for high-speed and chip-based CVQKD for kilometer-level atmospheric channel networks.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Associations Between Plasma Klotho with Renal Function and Cerebrospinal Fluid Amyloid-ß Levels in Alzheimer's Disease: The Chongqing Ageing & Dementia Study.

BACKGROUND: The kidney-brain crosstalk has been involved in Alzheimer's disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. OBJECTIVE: To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. METHODS: We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-ß (Aß)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aß, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. RESULTS: We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aß42, Aß40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aß42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aß42. CONCLUSION: Renal function impacts brain Aß metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD.

Toward incompatible quantum limits on multiparameter estimation.

Achieving the ultimate precisions for multiple parameters simultaneously is an outstanding challenge in quantum physics, because the optimal measurements for incompatible parameters cannot be performed jointly due to the Heisenberg uncertainty principle. In this work, a criterion proposed for multiparameter estimation provides a possible way to beat this curse. According to this criterion, it is possible to mitigate the influence of incompatibility meanwhile improve the ultimate precisions by increasing the variances of the parameter generators simultaneously. For demonstration, a scheme involving high-order Hermite-Gaussian states as probes is proposed for estimating the spatial displacement and angular tilt of light at the same time, and precisions up to 1.45 nm and 4.08 nrad are achieved in experiment simultaneously. Consequently, our findings provide a deeper insight into the role of Heisenberg uncertainty principle in multiparameter estimation, and contribute in several ways to the applications of quantum metrology.

Multi-rate and multi-protocol continuous-variable quantum key distribution.

Quantum key distribution (QKD) is an effective solution to ensure the secure transmission of information. However, for the large-scale application of QKD, the interoperability and flexibility of the transmitter and receiver are urgent issues to be solved. Here, for the first time, to the best of our knowledge, we experimentally verify the feasibility of one continuous-variable (CV) QKD system to achieve multiple protocols and rates. The flexibility of the system comes from the modulator realizing multiple protocols and a broadband coherent detector realizing multiple symbol rates. The results show that this system can switch between different rates and protocols to generate the secure key, and reveal its similarity to classical optical communication. Therefore, It can be adjusted according to user needs and provides a system-level solution for building a flexible quantum network.

Vinasse-based biochar magnetic composites: adsorptive removal of tetracycline in aqueous solutions.

Highly efficient and cost-effective adsorbents for antibiotic removal are the key to mitigate pollution by industrial wastewaters. Pyrolyzing low-cost winemaking waste into biochar is a promising means for waste biomass utilization. This study assembled vinasse-derived biochar with manganese ferrite into vinasse-manganese ferrite biochar-magnetic composites (V-MFB-MCs) through simultaneous pyrolysis of waste biomass and metal (Mn and Fe) hydroxide precipitates. Batch experiments were conducted to evaluate the kinetics and isotherms of tetracycline (TC) adsorption as well as the influence of pH value, humic acid, and ionic strength. Morphological characterization showed that crystalline MnFe2O4 nanoparticles were impregnated within the framework of fabricated V-MFB-MCs. Superior TC adsorption capacity and fast pseudo-second-order kinetics could be achieved by the V-MFB-MCs-800 at pH 3.0. The TC adsorption onto V-MFB-MCs-800 was highly pH-dependent and controlled by the positive influence of ionic strength and humic acid. V-MFB-MCs-800 showed excellent adsorption performance in different natural water. Multiple interaction mechanisms including pore filling effect, π-π stacking interaction, and hydrogen bonding contribute to TC removal by V-MFB-MCs-800, which can be an innovative biowaste-derived material for industrial wastewater treatment.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aß neurotoxicity and promotes Aß clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Anti-noise computational imaging using unsupervised deep learning.

Computational imaging enables spatial information retrieval of objects with the use of single-pixel detectors. By combining measurements and computational methods, it is possible to reconstruct images in a variety of situations that are challenging or impossible with traditional multi-pixel cameras. However, these systems typically suffer from significant loss of imaging quality due to various noises when the measurement conditions are single-photon detecting, undersampling and complicated. Here, we provide an unsupervised deep learning (UnDL) based anti-noise approach to deal with this problem. The proposed method does not require any clean experimental data to pre-train, so it effectively alleviates the difficulty of model training (especially for the biomedical imaging scene which is difficult to obtain training ground truth inherently). Our results show that an UnDL based imaging approach outperforms conventional single-pixel computational imaging methods considerably in reconstructing the target image against noise. Moreover, the well-trained model is generalized to image a real biological sample and can accurately image 64 × 64 resolution objects with a high speed of 20 fps at 5% sampling ratio. This method can be used in various solvers for general computational imaging and is expected to effectively suppress noises for high-quality biomedical imaging in generalizable complicated environments.

Robustness of optic-fiber-based weak-value amplification against amplitude-type noise.

Experiments based on a free-space platform have demonstrated that the weak-value amplification (WVA) technique can provide high sensitivity and precision for optical sensing and metrology. To promote this technique for real-world applications, it is more suitable to implement WVA based on an optical-fiber platform due to the lower cost, smaller scale, and higher stability. In contrast to the free-space platform, the birefringence in optical fiber is strong enough to cause polarization cross talk, and the amplitude-type noise must be taken into account. By theoretical analysis and experimental demonstration, we show that the optic-fiber-based WVA is robust in the presence of amplitude-type noise. In our experiment, even the angular misalignment on optical axes at the interface reaches 0.08 rad, and the sensitivity loss can be maintained at less than 3 dB. Moreover, the main results are valid to a simplified detection scheme that was recently proposed that is more compatible with the future design of optical-fiber-based WVA. Our results indicate the feasibility of implementing WVA based on optical fiber, which provides a possible way for designing optical sensors with higher sensitivity and stability in the future.