Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease.

Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer's disease and related dementias.

Optimized design of a gravitational wave telescope system based on pupil aberration.

The telescope is vital for accurate gravitational wave detection in the TianQin project. It must meet criteria like a geometric tilt-to-length (TTL) coupling noise c o e f f i c i e n t≤0.02√2n m/µr a d and wavefront R M S≤λ/30. Analyzing the pupil aberration's impact on geometric TTL noise, we devised an optimization method using the chief ray spot diagram's standard deviation. Implementing this in Zemax with a ZPL macro, we designed an optical system meeting TianQin's requirements. The system has a maximum geometric TTL noise coefficient of 0.0250 nm/µrad over the science FOV and a wavefront RMS of 0.0111λ, confirming the method's feasibility.

Analysis of alignment requirements for off-axis resonant cavity based on coupling efficiency.

The optical path length stability of the off-axis four-reflection telescope is one of the key technical indicators for the TianQin gravitational wave detection system. In the MHz observation band, the telescope must exhibit an optical path length stability of 0.4p m/H z 1/2. As a feasible solution, the optical path length stability measurement of the off-axis four-reflection telescope based on the Pound-Drever-Hall (PDH) technique imposes stringent requirements on the alignment of the off-axis resonant cavity (ORC). Taking the off-axis two-reflection prototype as the research object, we propose a Monte Carlo analysis-based method for ORC alignment precision analysis. By considering misalignment as an intermediate function, we establish a relationship between the coupling efficiency of the ORC and the wavefront aberration of the telescope. The research results show that by considering the combined effects of multiple misalignment couplings of the primary and secondary mirrors, when the detected telescope wavefront aberration is better than 0.068λ (λ=1064n m) with a probability of 98%, the ORC coupling efficiency can achieve greater than 40% with a probability of 97.13%, which can be used as the main reference indicator for system misalignment analysis. This method simplifies the alignment difficulty of the target under test and can provide alignment reference for subsequent resonant cavities with internal off-axis telescopes.

Chloroform-infiltrated photonic crystal fiber with high-temperature sensitivity.

The temperature sensor is the core part of the temperature measurement instrument, and its performance directly determines the temperature measurement accuracy. Photonic crystal fiber (PCF) is a new type of temperature sensor with extremely high potential. In this paper, we propose a high-performance, structurally simple, liquid-filled PCF temperature sensor, which is based on a SMF-PCF-SMF (single mode fiber, SMF) sandwich structure. By adjusting the structural parameters of the the PCF, it is possible to obtain optical properties that are superior to those of ordinary optical fibers. This allows for more obvious responsive changes of the fiber transmission mode under small external temperature changes. By optimizing the basic structure parameters, a new PCF structure with a central air hole is designed, and its temperature sensitivity is -0.04696 nm/°C. When filling the air holes of PCFs with temperature-sensitive liquid materials, the response of the optical field against the temperature fluctuations can be effectively enhanced. The Chloroform solution is used to selectively infiltrate the resulting PCF owing to its large thermo-optical coefficient. After comparing various filling schemes, the calculation results show that the highest temperature sensitivity of -15.8 nm/°C is finally realized. The designed PCF sensor has a simple structure, high-temperature sensitivity, and good linearity showing great application potential.

Rapid calculation method for backscattered light of a space gravitational-wave detection telescope.

Stray light is a key issue that must be considered in the TianQin telescope. To solve the problem of a long simulation time and the inability of the simulation results to be fed back to guide the optical design, we propose a fast estimation method for stray light based on the FOV with high accuracy. Compared to other models, the error between our model and the software simulation results is smaller, within one order of magnitude. Based on this method, we obtain the optical component target of the TianQin telescope and propose an optimization method to reduce stray light, which can be verified by analyzing the optimized optical design.

Measuring vessel underwater radiated noise in shallow water.

Performing reproducible vessel source level (SL) measurements is complicated by seabed reflections in shallow water. In deep water, with a hydrophone far from the seabed, it is straightforward to estimate propagation loss (PL) and convert sound pressure level (SPL) into SL using the method codified in the international standard ISO 17208-2 [International Organization for Standardization (ISO), Geneva, Switzerland (2019)]. Estimating PL is more difficult in shallow water because of the way that sound reflects from the seabed such that multiple propagation paths contribute to SPL. Obtaining reproducible SL measurements in shallow water requires straightforward and robust methods to estimate PL. From May to July 2021, a field experiment evaluated different methods of measuring vessel SL in shallow water. The same vessels were measured many times in water depths of 30, 70, and 180 m. In total, 12 079 SL measurements were obtained from 1880 vessel transits and 16 hydrophones, distributed across 3 moored vertical line arrays and 2 moored horizontal line arrays. The experiment confirmed that it is possible to obtain reproducible vessel SL estimates in shallow water comparable to within ±2.5 dB of ISO-compliant measurements in deep water and repeatable to within ±1.5 dB.

Repetitive Low-Level Blast Exposure via Akt/NF-κB Signaling Pathway Mediates the M1 Polarization of Mouse Alveolar Macrophage MH-S Cells.

Repetitive low-level blast (rLLB) exposure is a potential risk factor for the health of soldiers or workers who are exposed to it as an occupational characteristic. Alveolar macrophages (AMs) are susceptible to external blast waves and produce pro-inflammatory or anti-inflammatory effects. However, the effect of rLLB exposure on AMs is still unclear. Here, we generated rLLB waves through a miniature manual Reddy-tube and explored their effects on MH-S cell morphology, phenotype transformation, oxidative stress status, and apoptosis by immunofluorescence, real-time quantitative PCR (qPCR), western blotting (WB) and flow cytometry. Ipatasertib (GDC-0068) or PDTC was used to verify the role of the Akt/NF-κB signaling pathway in these processes. Results showed that rLLB treatment could cause morphological irregularities and cytoskeletal disorders in MH-S cells and promote their polarization to the M1 phenotype by increasing iNOS, CD86 and IL-6 expression. The molecular mechanism is through the Akt/NF-κB signaling pathway. Moreover, we found reactive oxygen species (ROS) burst, Ca2+ accumulation, mitochondrial membrane potential reduction, and early apoptosis of MH-S cells. Taken together, our findings suggest rLLB exposure may cause M1 polarization and early apoptosis of AMs. Fortunately, it is blocked by specific inhibitors GDC-0068 or PDTC. This study provides a new treatment strategy for preventing and alleviating health damage in the occupational population caused by rLLB exposure.

Optical properties and application potential of a hybrid cavity compound grating structure.

In this paper, we propose a new type of metal-insulator-metal (MIM) hybrid cavity compound grating micro-structure array, which can achieve dual narrowband super-absorption in the near-infrared window. The thin plasmonic microstructure effectively modulates coupling and hybridization effects between surface plasmon polaritons of different transmission resonance cavities to form designable dual narrowband resonance states to achieve near-infrared operation proving manipulation of the optical characteristics in the near-infrared light field. Furthermore, we conduct an in-depth theoretical exploration of the structure's unique properties, such as its high-quality factor, low noise, super-absorption, precise control, and the physical mechanism of its excellent performance in ambient refractive index sensing and detection. This study provides developmental insights for the miniaturization, easy modulation, and multi-function development of surface plasmon superabsorbers while broadening their application in near-infrared environment refractive index detection. The proposed microstructure is also suitable for integration with optical elements.

Multi-layered all-dielectric grating visible color filter with a narrow band and high-quality factor.

In this paper, we proposed a double-layer all-dielectric grating. Under the premise of ensuring the strength of the resonance peak, the upper SiO2 grating layer suppresses the tendency of high-order dipole resonance excitation and improves the transmittance at the non-resonant position (T > 99%). The distribution of chromaticity coordinates on the CIE 1931 chromaticity diagram also proves that suppressing side peaks can effectively increase the saturation of structural colors, which is essential for a high precision imaging system. The cyclic displacement current excites the magnetic dipole resonance, which causes the magnetic field to be confined in the high refractive index material HfO2 grating layer. By adjusting the duty cycle of the grating structure, a reflection spectrum with low full width half maximum (FWHM) (∼2 nm) and high-quality factor Q (∼424.5 nm) can be obtained. And the spectral intensity is more sensitive to the polarization angle. This work is of great significance to the development of sensors, display imaging and other fields. At the same time, the material of the grating filter meets the requirements of high damage threshold of the high-power laser system, and its high-power laser application potential is inestimable.

Identification and Pathogenicity of a New Entomopathogenic Fungus, Mucor hiemalis (Mucorales: Mucorales), on the Root Maggot, Bradysia odoriphaga (Diptera: Sciaridae).

Bradysia odoriphaga Yang and Zhang (Diptera: Sciaridae), the Chinese chive root maggot, is a destructive pest of Allium vegetables and flowers that causes severe losses in northern China. Novel biological control technologies are needed for controlling this pest. We identified a new entomopathogenic fungus isolated from infected B. odoriphaga larvae and evaluated the susceptibility of the biological stages of B. odoriphaga and the effects of temperature on fungus growth and pathogenicity. Based on morphological characteristics and molecular phylogeny, the fungus was identified as Mucor hiemalis BO-1 (Mucorales: Mucorales). This fungus had the strongest virulence to B. odoriphaga larvae followed by eggs and pupae, while B. odoriphaga adults were not susceptible. A temperature range of 18-28°C was optimum for the growth and sporulation of M. hiemalis BO-1 and virulence to B. odoriphaga larvae. At 3 and 5 d after inoculation with 105 spores/ml at 23°C, the survival rates were 24.8% and 4.8% (2nd instar larvae), respectively, and 49.6% and 12.8% (4th instar larvae), respectively. The potted plant trials confirmed that M. hiemalis BO-1 exerted excellent control efficiency against B. odoriphaga larvae, and the control exceeded 80% within 5 d when the spore concentration applied exceeded 107 spores/ml. In conclusion, these findings supported the hypotheses that this fungus could serve as an effective control agent against B. odoriphaga larvae and is worth being further tested to determine its full potential as a biocontrol agent.

Linewidth reduction effect of a cavity-coupled dual-passband plasmonic filter.

We propose a novel cavity-coupled MIM nano-hole array structure that exhibits a tunable dual passband in the near-infrared regime. When compared with the traditional single metal film, the designed structure provides a coupling effect between Gspp and SPP to significantly reduce the linewidths of the two transmission peaks. We also reveal the physical origin of the positive and negative influence of the cavity effect on the transmission of high-frequency and low-frequency peaks. This work supplies a new modulation theory for plasmonic devices based on the EOT phenomenon and has a wide application prospect in the fields of infrared sensor, plasmonic filter, and hyperspectral imaging.

Cavity-driven hybrid plasmonic ultra-narrow bandpass filter.

We propose a novel compound grating structure that exhibits a tunable ultra-narrowband transmission in the near infrared regime. The thin microstructure can realize a steep wave form through a Fano-like resonance by coupling different propagation-type SPP modes and with a narrow line width formed by the energy band gap. Additionally, the out-of-band suppression is remarkably enhanced. It effectively solves the constraint relationship between high transmittance, narrow line width, and weak side peak of the plasmonic filter, and the structure is suitable for integration with detectors in the near infrared regime.

Slowing deep-sea commercial vessels reduces underwater radiated noise.

During 2017, the Vancouver Fraser Port Authority's Enhancing Cetacean Habitat and Observation program carried out a two-month voluntary vessel slowdown trial to determine whether slowing to 11 knots was an effective method for reducing underwater radiated vessel noise. The trial was carried out in Haro Strait, British Columbia, in critical habitat of endangered southern resident killer whales. During the trial, vessel noise measurements were collected next to shipping lanes on two hydrophones inside the Haro Strait slowdown zone, while a third hydrophone in Strait of Georgia measured vessels noise outside the slowdown zone. Vessel movements were tracked using the automated identification system (AIS), and vessel pilots logged slowdown participation information for each transit. An automated data processing system analyzed acoustical and AIS data from the three hydrophone stations to calculate radiated noise levels and monopole source levels (SLs) of passing vessels. Comparing measurements of vessels participating in the trial with measurements from control periods before and after the trial showed that slowing down was an effective method for reducing mean broadband SLs for five categories of piloted commercial vessels: containerships (11.5 dB), cruise vessels (10.5 dB), vehicle carriers (9.3 dB), tankers (6.1 dB), and bulkers (5.9 dB).

Novel aluminum plasmonic absorber enhanced by extraordinary optical transmission.

We report a theoretical and experimental study on a novel type of aluminum super absorber which exhibits a near perfect absorption based on the surface plasmon resonance in the visible and near-infrared spectrum. The absorber consists of Ag/SiO2/Al triple layers in which the top Al layer is patterned by a periodic nano hole array. The absorption spectrum can be easily controlled by adjusting the structure parameters including the radius of the nano hole and the maximal absorption can reach 99.0% in theory. We completely analyze the SPP and LSP modes supported by the metal-dielectric-metal structure and their contribution to the ultrahigh absorption. On this basis, we find a novel method to enhance the absorption via the simultaneous excitation of SPP at different interfaces theoretically and experimentally. Moreover, for the first time we clarify the EOT caused by the nano hole array can enhance the absorption by experiment, which is not reported in previous works. This kind of absorber can be fabricated by low-cost colloidal sphere lithography and the use of stable Al overcomes the disadvantages brought by the noble metal, which make it a more appropriate candidate for photovoltaics, spectroscopy, photodetectors, sensing, and surface enhanced Raman scattering.

Roughness reduction of large-area high-quality thick Al films for echelle gratings by multi-step deposition method.

Generally, echelle grating ruling is performed on a thick Al film. Consequently, high-quality large-area thick Al films preparation becomes one of the most important factors to realize a high-performance large-size echelle grating. In this paper, we propose a novel multi-step deposition process to improve thick Al films quality. Compared with the traditional single-step deposition process, it is found that the multi-step deposition process can effectively suppress large-size grains growth resulting in a low surface roughness and high internal compactness of thick Al films. The differences between single- and multi-step deposition processes are discussed in detail. By using multi-step deposition process, we prepared high-quality large-area Al films with a thickness more than 10 µm on a 520 mm × 420 mm neoceramic glass substrate.

Marine mammal audibility of selected shallow-water survey sources.

Most attention about the acoustic effects of marine survey sound sources on marine mammals has focused on airgun arrays, with other common sources receiving less scrutiny. Sound levels above hearing threshold (sensation levels) were modeled for six marine mammal species and seven different survey sources in shallow water. The model indicated that odontocetes were most likely to hear sounds from mid-frequency sources (fishery, communication, and hydrographic systems), mysticetes from low-frequency sources (sub-bottom profiler and airguns), and pinnipeds from both mid- and low-frequency sources. High-frequency sources (side-scan and multibeam) generated the lowest estimated sensation levels for all marine mammal species groups.

Comparative key aroma compounds and sensory correlations of aromatic coconut water varieties: Insights from GC × GC-O-TOF-MS, E-nose, and sensory analysis.

Aroma is a key criterion in evaluating aromatic coconut water. A comparison regarding key aroma compounds and sensory correlations was made between Thailand Aromatic Green Dwarf (THD) and Cocos nucifera L. cv. Wenye No. 4 coconut water using E-nose and GC × GC-O-TOF-MS combined with chemometrics. Twenty-one volatile components of coconut water were identified by GC × GC-O-TOF-MS, and 5 key aroma compounds were analyzed by relative odor activity value and aroma extract dilution analysis. Moreover, the combination of the E-nose with orthogonal partial least squares was highly effective in discriminating between the two coconut water samples and screened the key sensors responsible for this differentiation. Additionally, the correlation between volatile compounds and sensory properties was established using partial least squares. The key aroma compounds of coconut water exhibited positive correlations with the corresponding sensory properties.

Rosmarinic acid plus deferasirox inhibits ferroptosis to alleviate crush syndrome-related AKI via Nrf2/Keap1 pathway.

BACKGROUND: Myoglobin (Mb) induced death of renal tubular epithelial cells (RTECs) is a major pathological factor in crush syndrome-related acute kidney injury (CS-AKI). It is unclear whether ferroptosis is involved and could be a target for treatment. PURPOSE: This study aimed to evaluate the potential therapeutic effects of combining the natural small molecule rosemarinic acid (RA) and the iron chelator deferasirox (Dfe) on CS-AKI through inhibition of ferroptosis. METHODS: Sequencing data were downloaded from the GEO database, and differential expression analysis was performed using the R software limma package. The CS-AKI mouse model was constructed by squeezing the bilateral thighs of mice for 16 h with 1.5 kg weight. TCMK1 and NRK-52E cells were induced with 200 µM Mb and then treated with RA combined with Dfe (Dfe + RA, both were 10 µM). Functional and pathological changes in mouse kidney were evaluated by glomerular filtration rate (GFR) and HE pathology. Immunofluorescence assay was used to detect Mb levels in kidney tissues. The expression levels of ACSL4, GPX4, Keap1, and Nrf2 were analyzed by WB. RESULTS: We found that AKI mice in the GSE44925 cohort highly expressed the ferroptosis markers ACSL4 and PTGS2. CS-AKI mice showed a rapid decrease in GFR, up-regulation of ACSL4 expression in kidney tissue, and down-regulation of GPX4 expression, indicating activation of the ferroptosis pathway. Mb was found to deposit in renal tubules, and it has been proven to cause ferroptosis in TCMK1 and NRK-52E cells in vitro. We found that Dfe had a strong iron ion scavenging effect and inhibited ACSL4 expression. RA could disrupt the interaction between Keap1 andNrf2, stabilize Nrf2, and promote its nuclear translocation, thereby exerting antioxidant effects. The combination of Dfe and RA effectively reversed Mb induced ferroptosis in RTECs. CONCLUSION: In conclusion, we found that RA combined with Dfe attenuated CS-AKI by inhibiting Mb-induced ferroptosis in RTECs via activating the Nrf2/Keap1 pathway.

Massively parallel jumping assay decodes Alu retrotransposition activity.

The human genome contains millions of retrotransposons, several of which could become active due to somatic mutations having phenotypic consequences, including disease. However, it is not thoroughly understood how nucleotide changes in retrotransposons affect their jumping activity. Here, we developed a novel massively parallel jumping assay (MPJA) that can test the jumping potential of thousands of transposons en masse. We generated nucleotide variant library of selected four Alu retrotransposons containing 165,087 different haplotypes and tested them for their jumping ability using MPJA. We found 66,821 unique jumping haplotypes, allowing us to pinpoint domains and variants vital for transposition. Mapping these variants to the Alu-RNA secondary structure revealed stem-loop features that contribute to jumping potential. Combined, our work provides a novel high-throughput assay that assesses the ability of retrotransposons to jump and identifies nucleotide changes that have the potential to reactivate them in the human genome.

Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, highly heterogeneous neurodegenerative disease, underscoring the importance of obtaining information to personalize clinical decisions quickly after diagnosis. Here, we investigated whether ALS-relevant signatures can be detected directly from biopsied patient fibroblasts. We profiled familial ALS (fALS) fibroblasts, representing a range of mutations in the fused in sarcoma (FUS) gene and ages of onset. To differentiate FUS fALS and healthy control fibroblasts, machine-learning classifiers were trained separately on high-content imaging and transcriptional profiles. "Molecular ALS phenotype" scores, derived from these classifiers, captured a spectrum from disease to health. Interestingly, these scores negatively correlated with age of onset, identified several pre-symptomatic individuals and sporadic ALS (sALS) patients with FUS-like fibroblasts, and quantified "movement" of FUS fALS and "FUS-like" sALS toward health upon FUS ASO treatment. Taken together, these findings provide evidence that non-neuronal patient fibroblasts can be used for rapid, personalized assessment in ALS.