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Abstract We recently achieved the first-in-human transfusion of induced pluripotent stem cell-derived platelets (iPSC-PLTs) as an alternative to standard transfusions, which are dependent on donors and therefore variable in supply. However, heterogeneity characterized by thrombopoiesis-biased or immune-biased megakaryocytes (MKs) continues to pose a bottleneck against the standardization of iPSC-PLT manufacturing. To address this problem, here we employ microRNA (miRNA) switch biotechnology to distinguish subpopulations of imMKCLs, the MK cell lines producing iPSC-PLTs. Upon miRNA switch-based screening, we find imMKCLs with lower let-7 activity exhibit an immune-skewed transcriptional signature. Notably, the low activity of let-7a-5p results in the upregulation of RAS like proto-oncogene B (RALB) expression, which is crucial for the lineage determination of immune-biased imMKCL subpopulations and leads to the activation of interferon-dependent signaling. The dysregulation of immune properties/subpopulations, along with the secretion of inflammatory cytokines, contributes to a decline in the quality of the whole imMKCL population.

Introduction Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).Methods and analysis The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 μs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events.Ethics and dissemination This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.Trial registration number ChiCTR2300073950.

Abstract Abnormal functional brain connectivity could be considered an endophenotype of psychosis in schizophrenia. Identifying candidate endophenotypes may serve as a tool for elucidating its biological and neural mechanisms. The present study investigated the similarities and differences of features of brain network connectivity between patients and their first-degree relatives. Independent component analysis was conducted on imaging data collected from 34 healthy controls, 33 schizophrenia patients, and 30 unaffected first-degree relatives. The correlation between functional connectivity with neurocognitive performance and clinical symptoms were calculated. Abnormalities of between-network connectivity largely overlapped in patients and first-degree relatives, but the extent of such abnormalities was relatively minor in relatives. Negative connectivity between language networks and executive control networks was impaired in schizophrenia patients and their first-degree relatives, and this decreased connectivity was correlated with performance in language processing. Similar impairments were found in high-visual network and executive network coupling, and this decreased connection was correlated with the severity of positive symptoms in patients. The results indicated that abnormal functional connectivity within and between perceptual systems (i.e., high-visual and language) and executive control networks was related to the generic risk of schizophrenia, which makes it a potential endophenotype for schizophrenia.

Virtual reality (VR) technology has been employed in a wide range of fields, from entertainment to medicine and engineering. Advances in VR also provide new opportunities in art exhibitions. This study discusses the experience of art appreciation through desktop virtual reality (Desktop VR) or head-mounted display virtual reality (HMD VR) and compares it with appreciating a physical painting. Seventy-eight university students participated in the study. According to the findings of this study, painting evaluation and the emotions expressed during the appreciation show no significant difference under these three conditions, indicating that the participants believe that paintings, regardless of whether they are viewed through VR, are similar. Owing to the limitation of the operation, the participants considered HMD VR to be a tool that hinders free appreciation of paintings. In addition, attention should be paid to the proper projected size of words and paintings for better reading and viewing. The above indicates that through digital technology, we can shorten the gap between a virtual painting and a physical one; however, we must still improve the design of object size and the interaction in the VR context so that a virtual exhibition can be as impressive as a physical one.

Background: Polydrug abuse is common among opioid users. Individuals who use both heroin and methamphetamine (MA) have been shown to experience a wide range of cognitive deficits. Previous research shows that repetitive transcranial magnetic stimulation (rTMS) can change cerebral cortical excitability and regulate neurotransmitter concentration, which could improve cognitive function in drug addiction. However, the stimulation time, location, and possible mechanisms of rTMS are uncertain. Methods: 56 patients with polydrug use disorder were randomized to receive 20 sessions of 10 Hz rTMS (n = 19), iTBS (n = 19), or sham iTBS (n = 18) to the left DLPFC. All patients used MA and heroin concurrently. Cognitive function was assessed and several related proteins including EPI, GABA-Aα5, IL-10, etc. were quantified by ELISA before and after the treatment. Results: Baseline RBANS scores were lower than normal for age (77.25; IQR 71.5-- 85.5). After 20 treatment sessions, in the iTBS group, the RBANS score increased by 11.95 (95% CI 0.02--13.90, p = 0.05). In particular, there were improvements in memory and attention as well as social cognition. Following treatment, serum EPI and GABA-Aα5 were reduced and IL-10 was elevated. The improvement of immediate memory was negatively correlated with GABA-Aα5 (r = --0.646, p = 0.017), and attention was positively correlated with IL-10 (r = 0.610, p = 0.027). In the 10 Hz rTMS group, the improvement of the RBANS total score (80.21 ± 14.08 before vs.84.32 ± 13.80 after) and immediate memory (74.53 ± 16.65 before vs.77.53 ± 17.78 after) was statistically significant compared with the baseline (p < 0.05). However, compared with the iTBS group, the improvement was small and the difference was statistically significant. There was no statistically significant change in the sham group (78.00 ± 12.91 before vs.79.89 ± 10.92 after; p > 0.05). Conclusion: Intermittent theta burst stimulation to the left DLPFC may improve cognitive function in polydrug use disorder patients. Its efficacy appears to be better than that of 10 Hz rTMS. The improvement of cognitive function may be related to GABA-Aα5 and IL-10. Our findings preliminarily demonstrate the clinical value of iTBS to the DLPFC to augment neurocognitive recovery in polydrug use disorders. [ABSTRACT FROM AUTHOR]

Background: While the association between physical activity (PA) and depression has been established, there is limited research on the effect of PA on the risk of depression among Chinese individuals. Thus, this study aimed to investigate the relationship between PA and depression among Chinese individuals. Methods: We used a stratified random sampling approach to recruit participants from five urban districts in Wuhan, China. A total of 5,583 permanent residents aged 18 years or older completed questionnaires, which included the International Physical Activity Questionnaire Short Form (IPAQ-SF) to measure PA, and the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. To control for potential confounders, multiple logistic regression was employed to assess the association of PA with depression. Results: The depression group had significantly lower weekly PA levels, measured in metabolic equivalent of task-minutes per week (MET-min/w), compared to the non-depression group [1,770 (693-4,200) MET-min/w vs. 2,772 (1,324-4,893) MET-min/w, p < 0.001]. In the fully adjusted model, the moderate and high PA level groups had lower odds ratios (ORs) for depressive symptoms compared to the low PA level group [OR (95% confidence interval (CI)) = 0.670 (0.523-0.858), 0.618 (0.484-0.790), respectively]. Among males, moderate and high levels of PA were associated with lower risk of depression compared to low PA levels [OR (95% CI) = 0.417 (0.268-0.649), 0.381 (0.244-0.593), respectively]. However, this association was not observed in females [OR (95% CI) = 0.827 (0.610-1.121), 0.782 (0.579-1.056), respectively]. The study found a significant interaction between PA levels and gender in relation to depression (P for interaction = 0.019). Conclusion: The findings suggest a negative association between PA and risk of depressive symptoms, indicating that moderate to high levels of PA may serve as a protective factor against depressive symptoms. [ABSTRACT FROM AUTHOR]

Quantum cryptography holds the promise to establish an information-theoretically secure global network. All field tests of metropolitan-scale quantum networks to date are based on trusted relays. The security critically relies on the accountability of the trusted relays, which will break down if the relay is dishonest or compromised. Here, we construct a measurement-device-independent quantum key distribution (MDIQKD) network in a star topology over a 200-square-kilometer metropolitan area, which is secure against untrustful relays and against all detection attacks. In the field test, our system continuously runs through one week with a secure key rate 10 times larger than previous results. Our results demonstrate that the MDIQKD network, combining the best of both worlds—security and practicality, constitutes an appealing solution to secure metropolitan communications.

Abstract Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.

Measurement-device-independent quantum key distribution (MDIQKD) protocol is immune to all attacks on detection and guarantees the information-theoretical security even with imperfect single-photon detectors. Recently, several proof-of-principle demonstrations of MDIQKD have been achieved. Those experiments, although novel, are implemented through limited distance with a key rate less than 0.1 bit/s. Here, by developing a 75 MHz clock rate fully automatic and highly stable system and superconducting nanowire single-photon detectors with detection efficiencies of more than 40%, we extend the secure transmission distance of MDIQKD to 200 km and achieve a secure key rate 3 orders of magnitude higher. These results pave the way towards a quantum network with measurement-device-independent security. [ABSTRACT FROM AUTHOR]

Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: −0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children’s sleep-wake patterns and sleep problems.

Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface. [ABSTRACT FROM AUTHOR]

A correction to the article "Measurement-Device-Independent Quantum Key Distribution over 200 km," published in a 2014 issue is presented.

Measurement-device-independent quantum key distribution (MDIQKD) with the decoy-state method negates security threats of both the imperfect single-photon source and detection losses. Lengthening the distance and improving the key rate of quantum key distribution (QKD) are vital issues in practical applications of QKD. Herein, we report the results of MDIQKD over 404 km of ultralow-loss optical fiber and 311 km of a standard optical fiber while employing an optimized four-intensity decoy-state method. This record-breaking implementation of the MDIQKD method not only provides a new distance record for both MDIQKD and all types of QKD systems but also, more significantly, achieves a distance that the traditional Bennett-Brassard 1984 QKD would not be able to achieve with the same detection devices even with ideal single-photon sources. This work represents a significant step toward proving and developing feasible long-distance QKD. [ABSTRACT FROM AUTHOR]

Quantum communication has historically been at the forefront of advancements, from fundamental tests of quantum physics to utilizing the quantum-mechanical properties of physical systems for practical applications. In the field of communication complexity, quantum communication allows the advantage of an exponential reduction in the transmitted information over classical communication to accomplish distributed computational tasks. However, to date, demonstrating this advantage in a practical setting continues to be a central challenge. Here, we report a proof-of-principle experimental demonstration of a quantum fingerprinting protocol that for the first time surpasses the ultimate classical limit to transmitted information. Ultralow noise superconducting single-photon detectors and a stable fiber-based Sagnac interferometer are used to implement a quantum fingerprinting system that is capable of transmitting less information than the classical proven lower bound over 20 km standard telecom fiber for input sizes of up to 2 Gbits. The results pave the way for experimentally exploring the advanced features of quantum communication and open a new window of opportunity for research in communication complexity and testing the foundations of physics. [ABSTRACT FROM AUTHOR]