Search

Abstract Both Alzheimer's disease (AD) and osteoporosis (OP) are common age‐associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung‐EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung‐EVs are diminished in aged osteocyte‐derived EVs (OCYAged‐EVs). Based on the self‐constructed OCY‐EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY‐EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a‐shRNA adenovirus inhibits OCYYoung‐EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCYYoung‐EVs, compared to OCYAged‐EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY‐EV as a regulator of brain health, suggesting a novel mechanism in bone‐brain communication.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus‐specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS‐CoV‐2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post‐BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2‐ and CH.1.1‐spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus‐specific memory T cells, even among the non‐seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS‐CoV‐2 variants among adolescents. [ABSTRACT FROM AUTHOR]

Waveform design for integrated radar and jamming is generally based on the concept of shared waveform, which uses jamming signals without typical radar signal characteristics for detection. Existing waveforms have shown limited design flexibility, high levels of sidelobe in detection results, and overall ordinary performance. We propose an integrated radar and jamming waveform based on smart modulation and complementary coding. Unlike traditional integrated radar and jamming waveform based on smart modulation, the phase angle of the binary phase-coded sequence is adjustable in this smart modulation method, allowing for a controllable jamming effect, achieving true smart modulation. However, this smart modulation waveform also suffers from high sidelobes in detection. To address this issue, we take a complementary coding approach and design a smart modulation waveform with complementary characteristics. This waveform can synthesize a complete linear frequency modulation (LFM) signal by adding two pulses together, thereby reducing the sidelobes in the smart modulation waveform and enhancing its detection performance. Theoretical analysis indicates that the detection and jamming effects of this integrated waveform can be flexibly controlled by adjusting the phase angles of the coding sequences. Simulation analysis and experimental results confirm the significant advantages of this waveform. [ABSTRACT FROM AUTHOR]

Methadone maintenance treatment is effective for managing opioid use disorder, but it can have many adverse effects that result in dose reduction. Patients often report persistent withdrawal symptoms after the dose reduction, which can decrease their adherence to treatment and increase the risk for relapse. Acupuncture has been recognized as an appropriate nonpharmacologic treatment for substance dependence. This multicenter, randomized, sham-controlled trial assessed the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Visual Abstract. Effect of Acupuncture for Methadone Reduction: Methadone maintenance treatment is effective for managing opioid use disorder, but it can have many adverse effects that result in dose reduction. Patients often report persistent withdrawal symptoms after the dose reduction, which can decrease their adherence to treatment and increase the risk for relapse. Acupuncture has been recognized as an appropriate nonpharmacologic treatment for substance dependence. This multicenter, randomized, sham-controlled trial assessed the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Background: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. Objective: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. Design: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123) Setting: 6 MMT clinics in China. Participants: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. Intervention: Acupuncture or sham acupuncture 3 times a week for 8 weeks. Measurements: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). Results: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P  < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of −11.7 mm VAS (CI, −18.7 to −4.8 mm; P  < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. Limitation: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. Conclusion: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. Primary Funding Source: National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]

Due to the heterogeneity of cancer, precision medicine has been a major challenge for cancer treatment. Determining medication regimens based on patient genotypes has become a research hotspot in cancer genomics. In this study, we aim to identify key biomarkers for targeted therapies based on single nucleotide variants (SNVs) and copy number variants (CNVs) of genes. The experiment is carried out on 7 cancers on the Encyclopedia of Cancer Cell Lines (CCLE) dataset. Considering the high mutability of driver genes which result in abundant mutated samples, the effect of data sparsity can be eliminated to a large extent. Therefore, we focus on discovering the relationship between driver mutation patterns and three measures of drug response, namely area under the curve (AUC), half maximal effective concentration (EC50), and log2-fold change (LFC). First, multiple statistical methods are applied to assess the significance of difference in drug response between sample groups. Next, for each driver gene, we analyze the extent to which its mutations can affect drug response. Based on the results of multiple hypothesis tests and correlation analyses, our main findings include the validation of several known drug response biomarkers such as BRAF, NRAS, MAP2K1, MAP2K2, and CDKN2A, as well as genes with huge potential to infer drug responses. It is worth emphasizing that we identify a list of genes including SALL4, B2M, BAP1, CCDC6, ERBB4, FOXA1, GRIN2A, and PTPRT, whose impact on drug response spans multiple cancers and should be prioritized as key biomarkers for targeted therapies. Furthermore, based on the statistical p-values and correlation coefficients, we construct gene-drug sensitivity maps for cancer drug recommendation. In this work, we show that driver mutation patterns could be used to tailor therapeutics for precision medicine. [ABSTRACT FROM AUTHOR]

To improve the accuracy of discriminating the seismic response of monitoring well water levels and enhance prediction efficiency, this paper conducts a comparative study using different methods on the seismic response of water level in 6 monitoring wells near two faults in the Ya'an area. First, the difference method is used to process and analyze the water level data. Then, the water level data is combined with two parameters of regional seismic activity (energy level and maximum magnitude) to analyze the relationship between regional seismic activity and water level fluctuations. Subsequently, the combined sequence was analyzed and processed in both the time domain and frequency domain. Finally, the prediction efficiency of five methods were tested using the Molchan chart method, and the optimal processing method and the monitoring well with the best prediction efficiency near the faults was identified. The results show that the combination of water level and seismic activity parameters has advantages over using the water level difference method alone, as the former can accurately eliminate the abnormal interference of seismic activity to water level. The optimal prediction methods of the six monitoring wells vary, with the optimal prediction days being within 60 days. Additionally, the study identities the monitoring wells with the optimal prediction efficiency in the fault areas. While the combination of water level and seismic activity parameters is not universally applicable to all monitoring wells, this method can effectively reflect the extent to which water level are influenced by seismic activity. [ABSTRACT FROM AUTHOR]

The integrated detection and jamming system employs integrated signals devoid of typical radar signal characteristics for detection and jamming. This allows for the sharing of resources such as waveform, frequency, time, and aperture, significantly enhancing the overall utilization rate of system resources. However, to achieve effective interference, the integrated waveform must overlap with the adversary radar signal within the frequency band. Consequently, the detection echoes are susceptible to the strong co-frequency direct wave generated by the adversary signals. This paper proposes a co-frequency direct wave interference suppression algorithm based on 2D generalized smoothed- l 0 norm sparse recovery. The algorithm exploits a joint dictionary comprising our integrated signals and adversary signals, along with the sparsity of 2D range-Doppler maps. The direct solution of the sparse decomposition optimization problem, formulated for the entire echo matrix, enhances the target detection performance for integrated signals even in the presence of robust co-frequency direct wave interference. Furthermore, the proposed method achieves robustness to interference of varying intensities through the adaptive updating and adjustment of relevant parameters. The effectiveness of the proposed method is validated through simulation and experimental results. [ABSTRACT FROM AUTHOR]

Abstract A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY.

Resting-state fMRI studies have increasingly focused on multi-contrast techniques, such as BOLD and ASL imaging. However, these techniques may reveal different aspects of brain activity (e.g., static vs. dynamic), and little is known about the similarity or disparity of these techniques in detecting resting-state brain activity. It is therefore important to assess the static and dynamic characteristics of these fMRI techniques to guide future applications. Here we acquired fMRI data while subjects were in eyes-closed (EC) and eyes-open (EO) states, using both ASL and BOLD techniques, at two research centers (NIDA and HNU). Static brain activity was calculated as voxel-wise mean cerebral blood flow (CBF) using ASL, i.e., CBF-mean, while dynamic activity was measured by the amplitude of low frequency fluctuations (ALFF) of BOLD, i.e., BOLD-ALFF, at both NIDA and HNU, and CBF, i.e., CBF-ALFF, at NIDA. We showed that mean CBF was lower under EC than EO in the primary visual cortex, while BOLD-ALFF was higher under EC in the primary somatosensory cortices extending to the primary auditory cortices and lower in the lateral occipital area. Interestingly, mean CBF and BOLD-ALFF results overlapped at the visual cortex to a very small degree. Importantly, these findings were largely replicated by the HNU dataset. State differences found by CBF-ALFF were located in the primary auditory cortices, which were generally a subset of BOLD-ALFF and showed no spatial overlap with CBF-mean. In conclusion, static brain activity measured by mean CBF and dynamic brain activity measured by BOLD- and CBF-ALFF may reflect different aspects of resting-state brain activity and a combination of ASL and BOLD may provide complementary information on the biophysical and physiological processes of the brain.