Unified Near-field and Far-field Localization with Holographic MIMO

Localization which uses holographic multiple input multiple output surface such as reconfigurable intelligent surface (RIS) has gained increasing attention due to its ability to accurately localize users in non-line-of-sight conditions. However, existing RIS-enabled localization methods assume the users at either the near-field (NF) or the far-field (FF) region, which results in high complexity or low localization accuracy, respectively, when they are applied in the whole area. In this paper, a unified NF and FF localization method is proposed for the RIS-enabled localization system to overcome the above issue. Specifically, the NF and FF regions are both divided into grids. The RIS reflects the signals from the user to the base station~(BS), and then the BS uses the received signals to determine the grid where the user is located. Compared with existing NF- or FF-only schemes, the design of the location estimation method and the RIS phase shift optimization algorithm is more challenging because they are based on a hybrid NF and FF model. To tackle these challenges, we formulate the optimization problems for location estimation and RIS phase shifts, and design two algorithms to effectively solve the formulated problems, respectively. The effectiveness of the proposed method is verified through simulations

An Outbreak of a Novel Recombinant Coxsackievirus A4 in a Kindergarten, Shandong Province, China, 2021

In 2021, twenty children exhibiting influenza-like illnesses were reported from a kindergarten in Shandong Province, China. Eleven genomes of Coxsackievirus A4 (CV-A4) were obtained from the pediatric cases, sharing \u3c93% genome sequence identities with known CV-A4 strains. Further analyses suggested potential genetic recombination in the P3 region of the novel strains

Clinical and genetic characteristics of adult cerebral adrenoleukodystrophy

Objective·To summarize and analyze the clinical and genetic characteristics of adult cerebral adrenoleukodystrophy(ACALD ).Methods·The data of eight patients with ACALD who attended the Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2018 to September 2022 were collected and comprehensively analyzed. Clinical data included age at onset, duration of disease, family history, present history and physical examination. Imaging examinations included magnetic resonance imaging (MRI) of the cranial, cervical spine and thoracic spine. Laboratory tests included serum very-long-chain fatty acids (VLCFA), adrenal cortical function and genetic test. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (Moca) were used to assess patients′ cognitive function.Results·A total of 8 male patients with ACALD were included in this study. Ageat onset ranged from 23 to 40 years old with an average age of (32.75±5.80) years, and the disease duration ranged from 4 to 59 months. Patients′ first symptoms were highly variable. Three patients showed memory loss and cognitive dysfunction, two showed irritability and personality change, one showed mental and behavioral abnormalities, one showed dysarthria and ataxia, and one showed persistent dizziness, occipital numbness and insomnia. All the patients had multiple white matter demyelination lesions, and white matter demyelination in parietal occipital lobe and posterior corpus callosum was the most common. Enhancement MRI showed patchy Gd-enhancement of partial lesions in three cases. In two patients, magnetic resonance spectroscopy showed that choline (Cho) peak increased and N-acetyl-aspartate (NAA) peak decreased. Serum VLCFA levels of C26, C24/C22 and C26/C22 were elevated in six patients who underwent serum VLCFA examination. Seven patients underwent adrenal cortical function testing, of which six experienced adrenal cortical dysfunction. Six patients were cognitively impaired, four of whom had decreased MMSE and MoCA scores, and two of whom were unable to cooperate with the assessment due to severe cognitive impairment. Eight different ABCD1 gene mutations were identified, among which c.1750delC (p.H584Tfs*52) and c.160_170delACGCAGGAGGC (p.T54Lfs*137) were novel mutations.Conclusion·The initial symptoms of ACALD vary, among which memory loss and cognitive dysfunction are the most common. White matter demyelination lesions in the parietal and corpus callosum pressure are the most common, and imaging abnormalities precede neurological symptoms. The clinical features of the disease are hair thinning and skin pigmentation, and the biochemical features are elevated serum VLCFA and adrenal insufficiency. Missense mutations are more common in the ABCD1 gene, and exons 1 and 6 are the hot mutant exons in Chinese

Concentration, source, and health risk assessment of polycyclic aromatic hydrocarbons: a pilot study in the Xuanwei lung cancer epidemic area, Yunnan Province, China

Polycyclic aromatic hydrocarbons (PAHs) are toxic and hazardous volatile environmental pollutants that have been studied as possible major causative agents of lung cancer in Xuanwei. In this paper, indoor and outdoor PM2.5 samples were collected from two homes at different time periods in Hutou, the lung cancer epidemic area in Xuanwei. The results showed that PAH pollution levels from coal combustion in Xuanwei lung cancer epidemic area were significant. The mass concentrations of total PAHs, major carcinogenic compounds, and benzo[a]pyrene-based equivalent concentration (BaPeq) were significantly higher in the coal-using home than in the electricity-using home. For the coal-using home, the PAHs were mainly derived from coal combustion. For the electricity-using home, the PAHs might have been a combination of traffic and coal combustion sources. The human health risk due to inhalation exposure to the PAHs was represented by the incremental lifetime cancer risk (ILCR) of the inhalation exposure. The results showed that the indoor cancer risk for the coal-using home in Xuanwei is higher than that of the electricity-using home and much higher than that of Chinese megacities such as Beijing and Tianjin. Long-term exposure to indoor coal-burning environments containing high levels of PAHs may be one of the main reasons for the high incidence of lung cancer in Xuanwei

Vitamin D and suicidality: a Chinese early adolescent cohort and Mendelian randomization study

Abstract Aims Previous cross-sectional and case–control studies have proposed that decreased vitamin D levels are positively correlated with the risk of suicidality in adults. However, limited studies have examined the association between vitamin D and suicidality in adolescents. This study aimed to investigate the relationship between serum vitamin D and suicidality risk among early adolescents. Methods Data were obtained from a Chinese early adolescent cohort. In this cohort, seventh-grade students from a middle school in Anhui Province were invited to voluntarily participate in the baseline assessments and provide peripheral blood samples (in September 2019). The participants were followed up annually (in September 2020 and September 2021). Serum 25-hydroxyvitamin D [25(OH)D] and vitamin D–related single-nucleotide polymorphisms at baseline were measured in November 2021. Traditional observational and Mendelian randomization (MR) analyses were performed to examine the relationship between serum 25(OH)D at baseline and the risk of baseline and incident suicidality (i.e., suicidal ideation [SI], plans and attempts). Results Traditional observational analysis did not reveal a significant linear or non-linear association of serum 25(OH)D concentration with the risks of baseline and 2-year incident suicidality in the total sample (P > .05 for all). Sex-stratified analysis revealed a non-linear association between the 25(OH)D concentration and the risk of baseline SI in women (Poverall = .002; Pnon-linear = .001). Moreover, the risk of baseline SI in the 25(OH) insufficiency group was lower than that in the 25(OH) deficiency group in the total sample (odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.51–0.92, P = .012). This difference remained significant in women (OR = 0.59, 95% CI = 0.40–0.87, P = .008) but not in men (OR = 0.78, 95% CI = 0.53–1.15, P = .205). Additionally, both linear and non-linear MR analyses did not support the causal effect of serum 25(OH)D concentration on the risk of baseline, 1-year and 2-year incident suicidality (P > .05 for all). Conclusions This study could not confirm the causal effect of vitamin D on suicidality risk among Chinese early adolescents. Future studies must confirm these findings with a large sample size

A Synthetic Plasmid Toolkit for Shewanella oneidensis MR-1

Shewanella oneidensis MR-1 is a platform microorganism for understanding extracellular electron transfer (EET) with a fully sequenced and annotated genome. In comparison to other model microorganisms such as Escherichia coli, the available plasmid parts (such as promoters and replicons) are not sufficient to conveniently and quickly fine-tune the expression of multiple genes in S. oneidensis MR-1. Here, we constructed and characterized a plasmid toolkit that contains a set of expression vectors with a combination of promoters, replicons, antibiotic resistance genes, and an RK2 origin of transfer (oriT) cassette, in which each element can be easily changed by fixed restriction enzyme sites. The expression cassette is also compatible with BioBrick synthetic biology standards. Using green fluorescent protein (GFP) as a reporter, we tested and quantified the strength of promoters. The copy number of different replicons was also measured by real-time quantitative PCR. We further transformed two compatible plasmids with different antibiotic resistance genes into the recombinant S. oneidensis MR-1, enabling control over the expression of two different fluorescent proteins. This plasmid toolkit was further used for overexpression of the MtrCAB porin-c-type cytochrome complex in the S. oneidensis ΔmtrA strain. Tungsten trioxide (WO3) reduction and microbial fuel cell (MFC) assays revealed that the EET efficiency was improved most significantly when MtrCAB was expressed at a moderate level, thus demonstrating the utility of the plasmid toolkit in the EET regulation in S. oneidensis. The plasmid toolkit developed in this study is useful for rapid and convenient fine-tuning of gene expression and enhances the ability to genetically manipulate S. oneidensis MR-1

COVID-19 mortality and exposure to airborne PM2.5: A lag time correlation

COVID-19 has escalated into one of the most serious crises in the 21st Century. Given the rapid spread of SARS-CoV-2 and its high mortality rate, here we investigate the impact and relationship of airborne PM2.5 to COVID-19 mortality. Previous studies have indicated that PM2.5 has a positive relationship with the spread of COVID-19. To gain insights into the delayed effect of PM2.5 concentration (μgm−3) on mortality, we focused on the role of PM2.5 in Wuhan City in China and COVID-19 during the period December 27, 2019 to April 7, 2020. We also considered the possible impact of various meteorological factors such as temperature, precipitation, wind speed, atmospheric pressure and precipitation on pollutant levels. The results from the Pearson's correlation coefficient analyses reveal that the population exposed to higher levels of PM2.5 pollution are susceptible to COVID-19 mortality with a lag time of >18 days. By establishing a generalized additive model, the delayed effect of PM2.5 on the death toll of COVID-19 was verified. A negative correction was identified between temperature and number of COVID-19 deaths, whereas atmospheric pressure exhibits a positive correlation with deaths, both with a significant lag effect. The results from our study suggest that these epidemiological relationships may contribute to the understanding of the COVID-19 pandemic and provide insights for public health strategies

Comprehensive genomic profiling reveals prognostic signatures and insights into the molecular landscape of colorectal cancer

BackgroundColorectal cancer (CRC) is a prevalent malignancy with diverse molecular characteristics. The NGS-based approach enhances our comprehension of genomic landscape of CRC and may guide future advancements in precision oncology for CRC patients.MethodIn this research, we conducted an analysis using Next-Generation Sequencing (NGS) on samples collected from 111 individuals who had been diagnosed with CRC. We identified somatic and germline mutations and structural variants across the tumor genomes through comprehensive genomic profiling. Furthermore, we investigated the landscape of driver mutations and their potential clinical implications.ResultsOur findings underscore the intricate heterogeneity of genetic alterations within CRC. Notably, BRAF, ARID2, KMT2C, and GNAQ were associated with CRC prognosis. Patients harboring BRAF, ARID2, or KMT2C mutations exhibited shorter progression-free survival (PFS), whereas those with BRAF, ARID2, or GNAQ mutations experienced worse overall survival (OS). We unveiled 80 co-occurring and three mutually exclusive significant gene pairs, enriched primarily in pathways such as TP53, HIPPO, RTK/RAS, NOTCH, WNT, TGF-Beta, MYC, and PI3K. Notably, co-mutations of BRAF/ALK, BRAF/NOTCH2, BRAF/CREBBP, and BRAF/FAT1 correlated with worse PFS. Furthermore, germline AR mutations were identified in 37 (33.33%) CRC patients, and carriers of these variants displayed diminished PFS and OS. Decreased AR protein expression was observed in cases with AR germline mutations. A four-gene mutation signature was established, incorporating the aforementioned prognostic genes, which emerged as an independent prognostic determinant in CRC via univariate and multivariate Cox regression analyses. Noteworthy BRAF and ARID2 protein expression decreases detected in patients with their respective mutations.ConclusionThe integration of our analyses furnishes crucial insights into CRC’s molecular characteristics, drug responsiveness, and the construction of a four-gene mutation signature for predicting CRC prognosis

Conception et évaluation d’assemblages d’aptamères et médicaments pour cibler les maladies infectieuses et cancéreuses

Delivering a specific drug to specific tissues or cells remains a great challenge in drug delivery. Aptamers are single strand oligonucleotides with specific folding structures that bind to their target molecules (small molecules, proteins, cells, etc.) with high binding affinities and specificities. They are versatile tools for designing targeted drug delivery systems (DDS) since they could be used as targeting moieties, as well as drug carrier or stimuli-responsive unit. In this work, we used DNA aptamers to construct multifunctional aptamer assemblies to deliver drugs in a specific manner against infectious and cancer diseases.In the first chapter, aptamer-based nanotrains and nanoflowers were designed to carry quinine in a specific and targeted manner against malaria infection. Aptamer-based nanotrains were designed and assembled by hybridization of complementary linkers between malaria targeting sequences and quinine loading aptamers. Aptamer-based nanoflowers were designed by incorporating the targeting aptamers and quinine loading aptamers in the template and were generated by the rolling circle amplification. Both DNA aptamer-based DDS were examined according to their stability, drug loading ability and safety profiles by native gel electrophoresis (PAGE), UV-vis, fluorescence and in vitro cellular tests. Our results demonstrate that nanotrains showed better drug loading selectivity as compared to nanoflowers, and maintain their targeting ability to Plasmodium falciparum Lactate Dehydrogenase (PfLDH) as demonstrated by surface plasmon resonance.In the second chapter, aptamer-posaconazole conjugates were designed to deliver the antifungal drug specifically to fungal species against fungal invasive infections. Posaconazole (POS) was chemically conjugated with the aptamer targeting the β-D-glucan surface of fungi, or physically loaded on a chimeric aptamer recognizing posaconazole on one side and the β-D glycan surface of fungi, on the other side. The formation of the latter was characterized by PAGE and the targeting ability was examined by ultrafiltration and fluorescence microscopy on Aspergillus species.In the third chapter, a dual targeting aptamer was designed to improve the specific targeting of gastric cancer stem cells, and subsequently deliver targeted drugs to tackle cancer resistance. Aptamers targeting epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 44 (CD44) were hybridized thanks to complementary linkers. Their formation was verified by native PAGE and their targeting ability and specificity were investigated by cytometry. The drug loading ability and drug binding affinity was determined by fluorescence method.The diversity of aptamer assemblies presented in this thesis demonstrates the versatility of aptamers as drug delivery carriers since they possessed both drugs loading abilities and targeting abilities. This work enlarges the possibilities of drug loading into aptamer assemblies that was previously restricted to intercalating drugs. This work suggests that using aptamers to build multifunctional aptamer assemblies as drug delivery systems for infectious and cancer diseases.Livrer un médicament précis à un tissu ou une cellule spécifique reste un défi majeur pour la vectorisation de médicaments. Les aptamères sont des oligonucléotides simple brin dont le repliement tridimensionnel permet de lier des molécules cibles (petites molécules, protéines, cellules, etc.) avec une affinité et une sélectivité très élevées. Grâce à leur utilisation polyvalente comme agent de ciblage, comme transporteur ou élément sensible à un stimulus, ils sont très utiles dans la conception de systèmes de vectorisation de médicaments. Dans ce travail, nous avons utilisé des aptamères d'ADN pour construire des assemblages d'aptamères multifonctionnels afin de délivrer des médicaments de manière spécifique contre les maladies infectieuses et cancéreuses.Dans le premier chapitre, des nanotrains et des nanofleurs à base d'aptamères d’ADN sont présentés pour transporter la quinine de manière spécifique et ciblée contre le paludisme. Les nanotrains sont assemblés par hybridation de liens complémentaires entre des aptamères transportant la quinine et un aptamère ciblant une protéine de la malaria, la Plasmodium falciparum lactate deshydrogénase (PfLDH). Les nanofleurs, quant à eux, sont préparées par amplification circulaire continue des séquences d’aptamères transportant la quinine et d’aptamères ciblant PfLDH. La formation, la stabilité, la capacité de chargement de quinine et la biocompatibilité des deux types de nanotransporteurs ont été étudiés et comparés par gel d’électrophorèse natif (PAGE), spectroscopie UV-visible, fluorescence et par des tests cellulaires in vitro. En bref, les nanotrains ont montré une meilleure sélectivité pour la quinine par rapport aux nanofleurs et ont maintenu leur capacité de ciblage pour PfLDH selon des études de résonance de plasma de surface.Dans le deuxième chapitre, des conjugués aptamère-posaconazole sont présentés pour cibler le médicament antifongique posaconazole (POS) spécifiquement vers les souches responsables des infections fongiques invasives. La molécule de posaconazole a été conjuguée chimiquement à l’aptamère ciblant le β-D glucane présent à la surface des champignons, ou bien complexé physiquement à une chimère d’aptamères de posaconazole d’une part, et de β-D-glucane, d’autre part. Leur formation a été caractérisée par PAGE et la capacité de ciblage a été démontrée par ultrafiltration et microscopie de fluorescence sur des souches d’Aspergillus.Dans le troisième chapitre, une chimère d’aptamère à double ciblage est présentée pour reconnaître spécifiquement les cellules souche du cancer gastrique et y vectoriser ensuite un anticancéreux pour combattre la résistance de ce cancer. Les aptamères ciblant la molécule d’adhésion cellulaire épithéliale (EpCAM) et le cluster de différentiation 44 (CD44) ont été hybridées grâce à des séquences complémentaires. Leur formation a été vérifiée par PAGE natif ; leur ciblage et spécificité ont été étudiés par cytométrie de flux. L’affinité et la capacité de chargement de doxorubicine ont été déterminées par fluorescence.Ces diverses stratégies d’assemblages d'aptamères démontrent la polyvalence des aptamères pour construire un vecteur de médicaments, car ils peuvent à la fois transporter des médicaments et les cibler au site d’action. Par rapport à la littérature existante, ce travail élargit la gamme des médicaments pouvant être transportés par ce type de vecteurs, habituellement restreints aux agents intercalants de l’ADN. Ce travail démontre le potentiel des assemblages d'aptamères multifonctionnels comme système de vectorisation ciblée pour les maladies infectieuses et cancéreuses