Search Results (67)

Molecular sensor systems, e.g., implantables and wearables, provide extensive health-related monitoring. Glucose sensor systems have historically prevailed in wearable bioanalysis applications due to their continuous and reliable glucose monitoring, a feat not yet accomplished for other biomarkers. However, the advancement of reagentless detection methodologies may facilitate the creation of molecular sensor systems for multiple analytes. Improving the sensitivity and selectivity of molecular sensor systems is also crucial for biomarker detection under intricate physiological circumstances. The term multidomain molecular sensor systems is utilized to refer, in general, to both biological and chemical sensor systems. This review examines methodologies for enhancing signal amplification, improving selectivity, and facilitating reagentless detection in multidomain molecular sensor devices. The review also analyzes the fundamental components of multidomain molecular sensor systems, including substrate materials, bodily fluids, power, and decision-making units. The review article further investigates how extensive data gathered from multidomain molecular sensor systems, in conjunction with current data processing algorithms, facilitate biomarker detection for precision medicine. Full article

Background/Objectives: The prevalence of dementia among South Asians across India is high among those who are 65 years and older, yet little is known about genetic risk factors for dementia in this population. Methods: Using whole-genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD), we performed a gene-based analysis on the missense/loss-of-function (LoF) and brain-specific promoter/enhancer variants of 84 genes, previously associated with AD in European Ancestry (EA). These analyses were performed separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores), using the variant-Set Test for Association using Annotation infoRmation (STAAR). We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. Results: In the missense/LoF analysis, without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes were associated with at least one measure of cognitive function (FDR q < 0.1). APOE was associated with four measures of cognitive function, PICALM was associated with HMSE score, and TSPOAP1 was associated with executive function. The most strongly associated variants in each gene were rs429358 (APOE ε4), rs779406084 (PICALM), and rs9913145 (TSPOAP1). Rs779406084 is a rare missense mutation that is enriched in LASI-DAD compared to EA (minor allele frequency = 0.075% vs. 0.0015%). Conclusions: Missense/LoF variants in some genes previously associated with AD in EA are associated with measures of cognitive function in South Asians from India. Analyzing genome sequence data allows the identification of potential novel causal variants enriched in South Asians. Full article

Groundbreaking advances in gene editing technologies are transforming modern plant breeding by enabling precise genetic modifications that dramatically accelerate crop improvement. Haploid and diploid induction systems have emerged as particularly powerful tools in this landscape, offering both efficient gene editing capabilities and rapid production of homozygous lines while seamlessly integrating with the advanced genome-editing platforms such as CRISPR-Cas systems. This review synthesizes the current state of knowledge regarding the mechanisms, applications, and recent progress in haploid and diploid induction systems for gene editing. We examine their transformative potential for enhancing genetic gains and compressing breeding timelines, with significant implications for global food security. Additionally, we provide a critical analysis of emerging challenges of genome editing in crops and outline promising future directions for research and development. Full article

Diaryldithiocarbamate complexes, [Fe(S₂CNAr₂)₃], have been prepared and their structure, reactivity, and thermal degradation to afford iron sulfide nanomaterials have been investigated. The addition of three equivalents of LiS₂CNAr₂ to FeCl₂·4H₂O in water-air affords dark red [Fe(S₂CNAr₂)₃] in high yields. All show magnetic measurements consistent with a predominantly high-spin electronic arrangement at room temperature. The molecular structure of [Fe{S₂C(N-p-MeOC₆H₄)₂}₃] reveals the expected distorted octahedral geometry, but Fe-S distances are more consistent with a low-spin electronic configuration, likely a result of the low temperature (120 K) of the data collection. The thermal stability of [Fe{S₂C(N-p-MeC₆H₄)₂}₃] has been investigated. TGA shows that it begins to decompose at a significantly lower temperature (ca. 160 °C) than previously observed for [Fe(S₂CNEt₂)₃], and this is further lowered (to ca. 100 °C) in oleylamine. The decomposition of [Fe{S₂C(N-p-MeC₆H₄)₂}₃] in oleylamine, via either a heat-up or hot injection process, affords nanoparticles of Fe₃S₄ (greigite), while in contrast, dry heating at 450 °C affords FeS (troilite) as large agglomerates. Full article

Human milk-derived extracellular vesicles (HMEVs) are key components in breast milk, promoting infant health and development. Maternal conditions could affect HMEV cargo; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study investigated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. The median duration from SARS-CoV-2 test positivity to milk collection was 3 months. After defatting and casein micelle disaggregation, HMEVs were isolated from milk samples of nine mothers with prenatal SARS-CoV-2 and six controls by sequential centrifugation, ultrafiltration, and qEV-size exclusion chromatography. The presence of HMEV was confirmed via transmission electron microscopy. Nanoparticle tracking analysis demonstrated particle diameters of <200 nm and yields of >1 × 10¹¹ particles per mL of milk. Western immunoblots detected ALIX, CD9, and HSP70, supporting the presence of HMEVs in the isolates. Cargo from thousands of HMEVs were analyzed using a multi-omics approach, including proteomics and microRNA sequencing, and predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming, mucosal tissue development, and immunomodulation. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era. Full article

Employing vehicle telematics data, this study investigates the transport environment across urban and major road networks during a two-week period encompassing the Easter holidays, considered as a case study. The analysis spans four distinct years: 2016, 2018, 2021, and 2022. Geospatial and Temporal Mapping captured the dependencies of vehicle speed, acceleration, vehicle-specific power (VSP), and emission factors (EFs) for air pollutants (CO₂ and NO_x) on the studied calendar period. The results showed that during the Easter holiday, the median vehicle speeds exceeded annual averages by roughly 5%, indicating a clear deviation from regular traffic patterns. This deviation was particularly stark during the 2021 lockdown, with a significant drop in vehicle presence, leading to less congestion and thus higher speeds and vehicle acceleration. The emissions analyses revealed that individual cars emit higher levels of CO₂ and NO_x during Easter. Specifically, the median values of CO₂ EF and NO_x EF were 9% and 11% higher than the annual norm. When combined with road occupancy data, the results demonstrate that the Easter holidays in 2022 had a variable impact on NO_x and CO₂ emissions, with significant reductions on major roads during weekday rush hours (15–25%) but slight increases on urban roads during weekend periods. Full article

The optimum germination conditions for foxtail millet sprouts enriched with γ-aminobutyric acid (GABA) and antioxidant polyphenols were investigated. From single-factor experimental results, both the GABA level and total phenolic content (TPC) were more significantly affected by soaking temperature and time, and concentration of sucrose culture solution. Response surface methodology (RSE) was used to optimize the germination conditions of foxtail millet sprouts, where the interaction between soaking temperature and sucrose concentration exhibited a significant (p < 0.05) effect on TPC, and the interaction between soaking time and sucrose concentration displayed a significant (p < 0.05) effect on GABA content. The optimal germination conditions for TPC and GABA enrichment of foxtail millet sprouts were soaking at 31 °C for 4.5 h and germinating at 35 °C with 4.5 g/L sucrose solution for 5 days. Under the optimized conditions, the TPC and GABA content of foxtail millet sprouts were 926.53 milligrams of ferulic acid equivalents per 100 g dry weight (mg FAE/100 g DW) and 259.13 mg/kg, separately, with less difference from the predicted values of 929.44 mg FAE/100 g DW and 263.60 mg/kg, respectively. Collectively, all the individual phenolic compounds increased significantly (p < 0.05) by optimization, except for cis-p-coumaric acid and cis-ferulic acid in bound. The results provide a practical technology for suitable germination conditions to improve the health components of foxtail millet sprouts and increase their added value. Full article

Intramedullary spinal cord glioblastoma (ISCG) is lethal due to lack of effective treatment. We previously established a rat C6-ISCG model and the antitumor effect of F3.CD-TK, an hNSC line expressing CD and TK, via producing cytocidal 5FU and GCV-TP. However, the neurotherapeutic potential of this hNSC approach has remained uninvestigated. Here for the first time, cultured F3.CD-TK cells were found to have a markedly higher oncolytic effect, which was GJIC-dependent, and BDNF expression but less VEGF secretion than F3.CD. In Rowett athymic rats, F3.CD-TK (1.5 × 10⁶ cells/10 µL × 2), injected near C6-ISCG (G55 seeding 7 days earlier: 10 K/each) and followed by q.d. (×5/each repeat; i.p.) of 5FC (500 mg/kg/5 mL/day) and GCV (25 mg/kg/1 mL/day), robustly mitigated cardiorespiratory, locomotor, and sensory deficits to improve neurofunction and overall survival compared to animals receiving either F3.CD or F3.CD-TK+F3.CD debris formula. The F3.CD-TK regimen exerted greater tumor penetration and neural inflammation/immune modulation, reshaped C6-ISCG topology to increase the tumor’s surface area/volume ratio to spare/repair host axons (e.g., vGlut1+ neurites), and had higher post-prodrug donor self-clearance. The multimodal data and mechanistic leads from this proof-of-principle study suggest that the overall stronger anti-ISCG benefit of our hNSC-based GDEPT is derived from its concurrent oncolytic and neurotherapeutic effects. Full article

The identification of four potential nonstructural 5 (NS5) residues—K28, K45, V335, and S749—that share the same amino acid preference in STAT2-interacting flaviviruses [Dengue virus (DENV) and Zika virus (ZIKV)], but not in STAT2-non-interacting flaviviruses [West Nile virus (WNV) and/or Yellow fever virus (YFV)] from an alignment of multiple flavivirus NS5 sequences, implied a possible association with the efficiency of ZIKV to antagonize the human signal transducer and activator of transcription factor 2 (STAT2). Through site-directed mutagenesis and reverse genetics, mutational impacts of these residues on ZIKV growth in vitro and STAT2 antagonism were assessed using virus growth kinetics assays and STAT2 immunoblotting. The results showed that mutations at the residue K28 significantly reduced the efficiency of ZIKV to antagonize STAT2. Further investigation involving residue K28 demonstrated its additional effects on the phenotypes of ZIKV-NS5 nuclear bodies. These findings demonstrate that K28, identified from sequence alignment, is an important determinant of replication and STAT2 antagonism by ZIKV. Full article

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion. Full article

A comparative karyotype analysis of four species of yellow-flowered Eranthis sect. Eranthis, i.e., E. bulgarica, E. cilicica, E. hyemalis, and E. longistipitata from different areas, has been carried out for the first time. All the studied specimens had somatic chromosome number 2n = 16 with basic chromosome number x = 8. Karyotypes of the investigated plants included five pairs of metacentric chromosomes and three pairs of submetacentric/subtelocentric chromosomes. The chromosome sets of the investigated species differ mainly in the ratio of submetacentric/subtelocentric chromosomes, their relative lengths, and arm ratios. A new oligonucleotide probe was developed and tested to detect 45S rDNA clusters. Using this probe and an oligonucleotide probe to 5S rDNA, 45S and 5S rDNA clusters were localized for the first time on chromosomes of E. cilicica, E. hyemalis, and E. longistipitata. Major 45S rDNA clusters were identified on satellite chromosomes in all the species; in E. cilicica, minor clusters were also identified in the terminal regions of one metacentric chromosome pair. The number and distribution of 5S rDNA clusters is more specific. In E. cilicica, two major clusters were identified in the pericentromeric region of a pair of metacentric chromosomes. Two major clusters in the pericentromeric region of a pair of submetacentric chromosomes and two major clusters in the interstitial region of a pair of metacentric chromosomes were observed in E. longistipitata. E. hyemalis has many clusters of different sizes, localized mainly in the pericentromeric regions. Summarizing new data on the karyotype structure of E. sect. Eranthis and previously obtained data on E. sect. Shibateranthis allowed conclusions to be formed about the clear interspecific karyological differences of the genus Eranthis. Full article

Modern adjuvant systemic therapies (STs) have revolutionized the management of stage III melanoma. Currently, the role of adjuvant radiotherapy (RT) remains unclear. In this single-center retrospective study, patients with clinically detectable stage III melanoma with high-risk features for lymph node basin (LNB) recurrence and whose tumors were fully resected with complete lymphadenectomy (CLD) between 2010 and 2019 were assessed. We determined the cumulative incidence (CIF) of LNB recurrence and any disease recurrence or progression using competing risk analysis. A total of 108 patients were identified; the median age was 59 years (24–92), and 74 (69%) were men. A total of 51 (42%) received adjuvant RT, 22 (20%) received adjuvant ST, and 35 (32%) received no adjuvant therapy. The advent of ST changed clinical practice, with a significant increase in the use of adjuvant ST and a decrease in the use of RT when comparing practice patterns before and after 2015 (p < 0.001). The 3-year CIF of LNB recurrence was similar in patients treated with adjuvant RT (6.3%) and adjuvant ST (9.8%). The 3-year CIF of any disease recurrence or progression was lower in patients receiving adjuvant ST (24%) compared to those receiving adjuvant RT (52%) or no adjuvant therapy (55%, p = 0.06). Three-year overall survival (OS) was not significantly different in patients treated with ST compared to those not treated with any ST (p = 0.118). Despite ST replacing RT as the dominant adjuvant treatment modality, this change in practice has not resulted in increased LNB recurrence for patients at high risk of LNB recurrence following CLD. Full article

Locomotor recovery after spinal cord injury (SCI) remains an unmet challenge. Nerve transfer (NT), the connection of a functional/expendable peripheral nerve to a paralyzed nerve root, has long been clinically applied, aiming to restore motor control. However, outcomes have been inconsistent, suggesting that NT-induced neurological reinstatement may require activation of mechanisms beyond motor axon reinnervation (our hypothesis). We previously reported that to enhance rat locomotion following T13-L1 hemisection, T12-L3 NT must be performed within timeframes optimal for sensory nerve regrowth. Here, T12-L3 NT was performed for adult female rats with subacute (7–9 days) or chronic (8 weeks) mild (SCI_mi: 10 g × 12.5 mm) or moderate (SCI_mo: 10 g × 25 mm) T13-L1 thoracolumbar contusion. For chronic injuries, T11-12 implantation of adult hMSCs (1-week before NT), post-NT intramuscular delivery of FGF2, and environmentally enriched/enlarged (EEE) housing were provided. NT, not control procedures, qualitatively improved locomotion in both SCI_mi groups and animals with subacute SCI_mo. However, delayed NT did not produce neurological scale upgrading conversion for SCI_mo rats. Ablation of the T12 ventral/motor or dorsal/sensory root determined that the T12-L3 sensory input played a key role in hindlimb reanimation. Pharmacological, electrophysiological, and trans-synaptic tracing assays revealed that NT strengthened integrity of the propriospinal network, serotonergic neuromodulation, and the neuromuscular junction. Besides key outcomes of thoracolumbar contusion modeling, the data provides the first evidence that mixed NT-induced locomotor efficacy may rely pivotally on sensory rerouting and pro-repair neuroplasticity to reactivate neurocircuits/central pattern generators. The finding describes a novel neurobiology mechanism underlying NT, which can be targeted for development of innovative neurotization therapies. Full article

Following surgery, over 50% of cardiac surgery patients report anxiety, stress and/or depression, with at least 10% meeting clinical diagnoses, which can persist for more than a year. Psychological distress predicts post-surgery health outcomes for cardiac patients. Therefore, post-operative distress represents a critical recovery challenge affecting both physical and psychological health. Despite some research identifying key personal, social, and health service correlates of patient distress, a review or synthesis of this evidence remains unavailable. Understanding these factors can facilitate the identification of high-risk patients, develop tailored support resources and interventions to support optimum recovery. This narrative review synthesises evidence from 39 studies that investigate personal, social, and health service predictors of post-surgery psychological distress among cardiac patients. The following factors predicted lower post-operative distress: participation in pre-operative education, cardiac rehabilitation, having a partner, happier marriages, increased physical activity, and greater social interaction. Conversely, increased pain and functional impairment predicted greater distress. The role of age, and sex in predicting distress is inconclusive. Understanding several factors is limited by the inability to carry out experimental manipulations for ethical reasons (e.g., pain). Future research would profit from addressing key methodological limitations and exploring the role of self-efficacy, pre-operative distress, and pre-operative physical activity. It is recommended that cardiac patients be educated pre-surgery and attend cardiac rehabilitation to decrease distress. Full article

A series of Mg-Y-Ni alloys with different volume fractions of long-period stacking-ordered (LPSO) phase were prepared, by controlling the alloy composition, heat treatment, and single-pass extrusion, to assess the influence of increasing LPSO phase volume fraction on the hydrogen absorption and desorption properties of the extruded alloys. The LPSO phase volume fraction in the alloys increased with increasing solute concentration, from ~24% LPSO in Mg₉₇Y₂Ni₁ (at.%) to ~60% LPSO in Mg₉₃Y₄Ni₃ (at.%) up to ~92% LPSO in Mg₉₁Y₅Ni₄ (at.%). The most refined microstructure was obtained in the alloy with highest volume fraction of LPSO phase. After 100 s at 300 °C, the Mg₉₁Y₅Ni₄ alloy absorbed 4.6 ± 0.2 wt.% H while the Mg₉₇Y₂Ni₁ and Mg₉₃Y₄Ni₃ alloys each absorbed 3.8 ± 0.2 wt.% H. After 10,000 s at 300 °C, all three alloys had absorbed a maximum of 5.3 ± 0.2 wt.% H with no further significant difference in hydrogen absorption kinetics. The Mg₉₁Y₅Ni₄ alloy desorbed 1.8 ± 0.2 wt.% H after 100 s at 300 °C against a vacuum while the Mg₉₇Y₂Ni₁ and Mg₉₃Y₄Ni₃ alloys desorbed 0.8 ± 0.2 wt. H and 0.6 ± 0.2 wt.% H, respectively. After 10,000 s at 300 °C, the Mg₉₁Y₅Ni₄ and Mg₉₇Y₂Ni₁ alloys completely desorbed 5.2 ± 0.2 wt.% H and 5.4 ± 0.2 wt.% H, respectively, but the Mg₉₃Y₄Ni₃ alloy desorbed only 3.7 ± 0.2 wt.% H. Hydrogen absorption and desorption kinetics were fastest in the Mg₉₁Y₅Ni₄ alloy with the highest LPSO volume fraction, but no consistent trend with LPSO phase volume fraction was observed with the Mg₉₃Y₄Ni₃ alloy, which showed the slowest absorption and desorption kinetics. The hydrogen pressures corresponding to metal–hydride equilibrium did not vary with LPSO phase volume fraction or alloy composition, indicating that the (de)hydrogenation thermodynamics were not significantly changed in any of the alloys. Hydrogen absorption experiments with thin foils, made of extruded Mg₉₁Y₅Ni₄ alloy with the highest LPSO phase fraction, demonstrated that the LPSO structures decompose into Mg phase, Mg₂Ni phase, lamellar Mg/Mg-Y structures, and YH_x particles. This study shows that hydrogen kinetics can be impacted in Mg-Y-Ni alloys by controlling the LPSO phases using common metallurgical techniques. Full article