RNA localization and co-translational interactions control RAB13 GTPase function and cell migration.

Numerous RNAs exhibit specific distribution patterns in mammalian cells. However, the functional and mechanistic consequences are relatively unknown. Here, we investigate the functional role of RNA localization at cellular protrusions of migrating mesenchymal cells, using as a model the RAB13 RNA, which encodes a GTPase important for vesicle-mediated membrane trafficking. While RAB13 RNA is enriched at peripheral protrusions, the expressed protein is concentrated perinuclearly. By specifically preventing RAB13 RNA localization, we show that peripheral RAB13 translation is not important for the overall distribution of the RAB13 protein or its ability to associate with membranes, but is required for full activation of the GTPase and for efficient cell migration. RAB13 translation leads to a co-translational association of nascent RAB13 with the exchange factor RABIF. Our results indicate that RAB13-RABIF association at the periphery is required for directing RAB13 GTPase activity to promote cell migration. Thus, translation of RAB13 in specific subcellular environments imparts the protein with distinct properties and highlights a means of controlling protein function through local RNA translation.

Gray matter atrophy and white matter lesions burden in delayed cognitive decline following carbon monoxide poisoning.

Gray matter (GM) atrophy and white matter (WM) lesions may contribute to cognitive decline in patients with delayed neurological sequelae (DNS) after carbon monoxide (CO) poisoning. However, there is currently a lack of evidence supporting this relationship. This study aimed to investigate the volume of GM, cortical thickness, and burden of WM lesions in 33 DNS patients with dementia, 24 DNS patients with mild cognitive impairment, and 51 healthy controls. Various methods, including voxel-based, deformation-based, surface-based, and atlas-based analyses, were used to examine GM structures. Furthermore, we explored the connection between GM volume changes, WM lesions burden, and cognitive decline. Compared to the healthy controls, both patient groups exhibited widespread GM atrophy in the cerebral cortices (for volume and cortical thickness), subcortical nuclei (for volume), and cerebellum (for volume) (p < .05 corrected for false discovery rate [FDR]). The total volume of GM atrophy in 31 subregions, which included the default mode network (DMN), visual network (VN), and cerebellar network (CN) (p < .05, FDR-corrected), independently contributed to the severity of cognitive impairment (p < .05). Additionally, WM lesions impacted cognitive decline through both direct and indirect effects, with the latter mediated by volume reduction in 16 subregions of cognitive networks (p < .05). These preliminary findings suggested that both GM atrophy and WM lesions were involved in cognitive decline in DNS patients following CO poisoning. Moreover, the reduction in the volume of DMN, VN, and posterior CN nodes mediated the WM lesions-induced cognitive decline.

Association between metabolic syndrome and the risk of Parkinson's disease: a meta-analysis.

BACKGROUND: There is still a lack of knowledge about the relationship between metabolic syndrome (MetS) and Parkinson's disease (PD). This study aimed to determine whether MetS increases PD risk. METHODS: To identify relevant clinical studies, databases such as PubMed, Embase, and the Cochrane Library were searched in depth from the inception of databases until March 31, 2024. The study evaluated the correlation between MetS and the likelihood of developing PD through the computation of aggregated relative risks (RR) and their respective 95% confidence intervals (CIs) utilizing selnRR and lnRR. RESULTS: Seven studies were included in our systematic review. The meta-analysis revealed that patients with MetS have a 0.3-fold increased risk of developing PD (p = 0.001). Furthermore, the analysis revealed a positive correlation between central obesity and the incidence of PD, with an RR of 1.19 (95% CI, 1.16-1.22; p = 0.001), as well as a greater risk of PD in patients with elevated blood pressure, with an RR of 1.13 (95% CI, 1.07-1.19; p = 0.001); elevated serum triglyceride levels, with an RR of 1.09 (95% CI, 1.02-1.15; p = 0.001); lower serum HDL cholesterol levels, with an RR of 1.21 (95% CI, 1.15-1.28; p = 0.001); and elevated plasma fasting glucose levels, with an RR of 1.18 (95% CI, 1.11-1.26; p = 0.001). CONCLUSION: MetS can contribute to the incidence of Parkinson's disease, with individual components of MetS demonstrating comparable effects.

Adaptive methods of generating complex light arrays.

Structured light arrays of various shapes have been a cornerstone in optical science, driven by the complexities of precise and adaptable generation. This study introduces an approach using a spatial light modulator (SLM) as a generator for these arrays. By projecting a holographic mask onto the SLM, it functions simultaneously as an optical convolution device, focusing mechanism, and structured light beam mask. Our approach offers unmatched versatility, allowing for the experimental fabrication of traditional beam arrays like azimuthal Laguerre-Gaussian (LG), Bessel-Gaussian (BG), and Hermite-Gauss (HG) in the far-field. Notably, it has enabled a method of generating Ince-Gauss (IG) and LG radial mode beam arrays using a convolution solution. Our system provides exceptional control over array periodicity and intensity distribution, bypassing the Talbot self-imaging phenomenon seen in traditional setups. We provide an in-depth theoretical discussion, supported by empirical evidence, of our far-field results. This method has vast potential for applications in optical communication, data processing, and multi-particle manipulation. It paves the way for rapid generation of structured light with high spatial frequencies and complex shapes, promising transformative advances in these domains.

Insight into efficient degradation of pentacyclic and hexacyclic sulfonamide antibiotics by synthetic trivalent copper: Performance and mechanism.

High valent metal species, including Mn(III), Fe(IV) and Cu(III), have been identified as key intermediates in the degradation of pollutants in many advanced oxidation processes. However, unlike Mn(III) and Fe(IV), the current exploration of the reaction activity and selective oxidation mechanism of Cu(III) towards pollutants with different structures is still quite limited. Herein, the copper(III) periodate was synthesized to investigate the reactivity towards six sulfonamide antibiotics (SAs) including typical two pentacyclic structures (sulfamethoxazole (SMX) and sulfathiazole (STZ)) and four hexacyclic structures (sulfadiazine (SDZ), sulfamerazine (SMR), sulfamonomethoxine (SMM) and sulfapyridine (SPD)). The results indicated that all SAs almost completely removed by Cu(III) system after 10 min with the molar ratio of approximately 3:1 (Cu(III):SAs) and Cu(III) direct oxidation played the most important role. SAs with 6-ring substituents were more readily degraded by Cu(III) than SAs with 5-ring substituents, and the presence of electron-rich group such as -CH3 and -S in ring substituent increased the reactivity towards Cu(III). The introduction of coexisting anions (Cl-, SO42- and HCO3-) hardly affected the degradation of SAs by Cu(III) oxidation, while the addition of HA to some extent inhibited SAs degradation. The solution pH greatly affected the degradation of SAs by Cu(III) and the removal efficiencies of SAs roughly followed the rule of neutral > acidic > alkaline. The degradation mechanism of SAs with 5-ring and 6-ring substituents in Cu(III) system mainly included amino nitration, self-coupling, hydroxylation, S-N cleavage in SAs with 5-ring substituents and SO2 extrusion in SAs with 6-ring substituents. Although the real water matrix inhibited the degradation of SAs to varying degrees, Cu(III) still played a satisfactory performance on SAs degradation especially for electron-rich structure.

The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions.

RNA localization and local translation are important for numerous cellular functions. In mammals, a class of mRNAs localize to cytoplasmic protrusions in an APC-dependent manner, with roles during cell migration. Here, we investigated this localization mechanism. We found that the KIF1C motor interacts with APC-dependent mRNAs and is required for their localization. Live cell imaging revealed rapid, active transport of single mRNAs over long distances that requires both microtubules and KIF1C. Two-color imaging directly revealed single mRNAs transported by single KIF1C motors, with the 3'UTR being sufficient to trigger KIF1C-dependent RNA transport and localization. Moreover, KIF1C remained associated with peripheral, multimeric RNA clusters and was required for their formation. These results reveal a widespread RNA transport pathway in mammalian cells, in which the KIF1C motor has a dual role in transporting RNAs and clustering them within cytoplasmic protrusions. Interestingly, KIF1C also transports its own mRNA, suggesting a possible feedback loop acting at the level of mRNA transport.

A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms.

BACKGROUND: There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. METHODS: Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes. RESULTS: Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. CONCLUSIONS: Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.

Early gray matter atrophy and neurological deficits in patients with carbon monoxide poisoning.

PURPOSE: To investigate early neurological deficits-related change patterns in gray matter (GM) volume in patients with carbon monoxide poisoning (COP) and GM volume differences between patients with and without delayed neurological sequelae (DNS) and those with and without T2 hyperintense lesions after COP. METHODS: Forty-one COP patients (24 patients with DNS) and 36 sex- and age-matched healthy controls (HC) were enrolled in this study. The neurological assessments were administered within 24 h after MRI scans. Voxel-based morphometry analysis was used to detect regional GM volume change. RESULTS: The COP group had statistically significant GM atrophy in the bilateral prefrontal and temporal lobes, anterior cingulate (ACC), thalamus, posterior cerebellum, and right hippocampus compared to the HC group. Atrophy in the left medial orbital superior frontal gyrus (SFG), bilateral ACC, and bilateral thalamus were related to lower Mini-Mental State Examination (MMSE) scores and higher Unified Parkinson's Disease Rating Scale subsection III and neuro-psychiatric inventory scores. Atrophy in the hippocampus and posterior cerebellum were also related to decrease MMSE scores. The DNS subgroup had greater GM atrophy in the limbic system than the non-DNS subgroup. Compared to the subgroup without T2 hyperintense lesions, greater GM atrophy in the limbic system, motor and visual cortex, and default network was observed in the subgroup with T2 hyperintense lesions. CONCLUSION: GM atrophy in the medial orbital SFG, ACC, thalamus, hippocampus, and posterior cerebellum is associated with early neurological deficits in patients with COP. Greater atrophy occurred in patients with DNS and those with T2 hyperintense lesions.

Collective cancer cell invasion requires RNA accumulation at the invasive front.

Localization of RNAs at protrusive regions of cells is important for single-cell migration on two-dimensional surfaces. Protrusion-enriched RNAs encode factors linked to cancer progression, such as the RAB13 GTPase and the NET1 guanine nucleotide exchange factor, and are regulated by the tumor-suppressor protein APC. However, tumor cells in vivo often do not move as single cells but rather utilize collective modes of invasion and dissemination. Here, we developed an inducible system of three-dimensional (3D) collective invasion to study the behavior and importance of protrusion-enriched RNAs. We find that, strikingly, both the RAB13 and NET1 RNAs are enriched specifically at the invasive front of leader cells in invasive cell strands. This localization requires microtubules and coincides with sites of high laminin concentration. Indeed, laminin association and integrin engagement are required for RNA accumulation at the invasive front. Importantly, perturbing RNA accumulation reduces collective 3D invasion. Examination of in vivo tumors reveals a similar localization of the RAB13 and NET1 RNAs at potential invasive sites, suggesting that this mechanism could provide a targeting opportunity for interfering with collective cancer cell invasion.

The new Haemaphysalis longicornis genome provides insights into its requisite biological traits.

Ticks are a large group of blood-feeding arthropods that transmit multiple human and animal pathogens and are hence of importance to public health. The tick Haemaphysalis longicornis is associated with the transmission of multiple human pathogens in Asia, and recently found invading to the United States. Here, we report the sequencing, assembly and annotation of the 3.16 gigabase genome of this species, which is larger than the previous assembled one. The present Haemaphysalis longicornis genome was characterized by 6519 scaffolds, 24,189 protein-coding genes and a high proportion of simple sequence repeats (54.72%). By genomic assembly and comparative genomic analysis, we characterized the key genes that play essential roles in iron metabolism, detoxification, and freeze tolerance of H. longicornis. Furthermore, a total of 79 endogenous viral elements were identified within the genome, which might have had a considerable impact on its evolution. Decoding the H. longicornis genome not only provides insight into the genetic underpinnings of specific biological processes but also offers the basis for the subsequent integrated control of ticks and tick-borne diseases.

Neurological sequelae in acute carbon monoxide poisoning: A prospective observational study with MRI data.

OBJECTIVES: Acute carbon monoxide (CO) poisoning survivors may experience persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). This study evaluated the clinical features, laboratory results, acute brain lesions (ABLs) on diffusion-weighted imaging (DWI) at presentation, and long-term outcomes and explored differences between patients with PNS and DNS. METHODS: The study included 443 patients who had experienced CO poisoning, underwent DWI and completed 1-year follow-ups. The demographics, comorbidities, symptomatology, laboratory results, ABLs on DWI at presentation, and long-term outcomes were compared between patients with PNS and those with DNS. RESULTS: The 42 (9.5%) and 96 (21.7%) patients with PNS and DNS, respectively, showed no significant differences in demographics, duration of CO exposure, initial conscious level, symptomatology, and laboratory results. ABLs on DWI were observed in 33 patients (33/42) with PNS and 62 patients (62/96) with DNS. The most common region of ABLs was the globus pallidus (60.6% and 56.6% in PNS and DNS, respectively). The proportion of ABLs present and lesion distribution did not differ significantly between the two groups. At 1 year, a significantly higher proportion of patients in the PNS group showed a good outcome (defined as modified Rankin Scale [mRS] scores of 0-2, 81%) compared with the DNS group (81% vs. 56.3%, p = .047). CONCLUSION: Demographics, clinical features, laboratory results, and acute brain lesions on MRI at presentation did not differ between the PNS and DNS groups. However, the long-term outcome of PNS was better than that of DNS.

Object Relocation Visual Tracking Based on Histogram Filter and Siamese Network in Intelligent Transportation.

Target detection and tracking algorithms are one of the key technologies in the field of autonomous driving in intelligent transportation, providing important sensing capabilities for vehicle localization and path planning. Siamese network-based trackers formulate the visual tracking mission as an image-matching process by regression and classification branches, which simplifies the network structure and improves the tracking accuracy. However, there remain many problems, as described below. (1) The lightweight neural networks decrease the feature representation ability. It is easy for the tracker to fail under the disturbing distractors (e.g., deformation and similar objects) or large changes in the viewing angle. (2) The tracker cannot adapt to variations of the object. (3) The tracker cannot reposition the object that has failed to track. To address these issues, we first propose a novel match filter arbiter based on the Euclidean distance histogram between the centers of multiple candidate objects to automatically determine whether the tracker fails. Secondly, the Hopcroft-Karp algorithm is introduced to select the winners from the dynamic template set through the backtracking process, and object relocation is achieved by comparing the Gradient Magnitude Similarity Deviation between the template and the winners. The experiments show that our method obtains better performance on several tracking benchmarks, i.e., OTB100, VOT2018, GOT-10k, and LaSOT, compared with state-of-the-art methods.

Subfemtosecond Wakefield Injector and Accelerator Based on an Undulating Plasma Bubble Controlled by a Laser Phase.

We demonstrate that a long-propagating plasma bubble executing undulatory motion can be produced in the wake of two copropagating laser pulses: a near-single-cycle injector and a multicycle driver. When the undulation amplitude exceeds the analytically derived threshold, highly localized injections of plasma electrons into the bubble are followed by their long-distance acceleration. While the locations of the injection regions are controlled by the carrier-envelope phase (CEP) of the injector pulse, the monoenergetic spectrum of the accelerated subfemtosecond high-charge electron bunches is shown to be nearly CEP independent.

Laser-Ion Lens and Accelerator.

Generation of highly collimated monoenergetic relativistic ion beams is one of the most challenging and promising areas in ultraintense laser-matter interactions because of the numerous scientific and technological applications that require such beams. We address this challenge by introducing the concept of laser-ion lensing and acceleration. Using a simple analogy with a gradient-index lens, we demonstrate that simultaneous focusing and acceleration of ions is accomplished by illuminating a shaped solid-density target by an intense laser pulse at ∼10^{22} W/cm^{2} intensity, and using the radiation pressure of the laser to deform or focus the target into a cubic micron spot. We show that the laser-ion lensing and acceleration process can be approximated using a simple deformable mirror model and then validate it using three-dimensional particle-in-cell simulations of a two-species plasma target composed of electrons and ions. Extensive scans of the laser and target parameters identify the stable propagation regime where the Rayleigh-Taylor-like instability is suppressed. Stable focusing is found at different laser powers (from a few to multiple petawatts). Focused ion beams with the focused density of order 10^{23} cm^{-3}, energies in access of 750 MeV, and energy density up to 2×10^{13} J/cm^{3} at the focal point are predicted for future multipetawatt laser systems.

Synergistic Ir/Cu Catalysis for Asymmetric Allylic Alkylation of Oxindoles: Enantio- and Diastereoselective Construction of Quaternary and Tertiary Stereocenters.

3,3-Disubstituted oxindoles bearing quaternary and tertiary stereogenic centers are privileged structural motifs, which widely exist in pharmaceutical and natural products. Herein, a highly regio-, enantio-, and diastereoselective allylic alkylation of 3-alkyl oxindoles through synergistic iridium and copper catalysis is described, which provides a series of 3,3-disubstituted oxindole derivatives containing adjacent quaternary and tertiary stereogenic centers in excellent yields, enantiomeric excess, and diastereomeric ratio (for 30 examples, up to 97 % yield, >99 % ee, and >20 : 1 dr). This method provides exclusive branched selectivity, excellent enantio- and diastereoselectivities, and good functional compatibility. Control experiments suggested that the chiral copper catalyst is required for achieving high reactivities and diastereoselectivities under mild reaction conditions.

Iridium(III)-Catalyzed Diarylation/Annulation of Benzoic Acids: Facile Access to Multi-Aryl Spirobifluorenes as Pure Hydrocarbon Hosts for High-Performance OLEDs.

Herein disclosed is the first example of diarylation/annulation of benzoic acids via an iridium catalyst system. This protocol provides a step-economic and highly efficient pathway to 1-aryl, 1,3-diaryl, 1,7-diaryl and 1,3,7-triaryl spirobifluorenes from readily available starting materials. The applications of multi-aryl spirobifluorenes as pure hydrocarbon (PHC) hosts for red, green, and blue (RGB) phosphorescent organic light-emitting diodes (PhOLEDs) were explored. Due to high triplet energies, 1,3-diaryl spirobifluorenes exhibit the potential as the host material of blue PhOLEDs. 1,7-Diaryl spirobifluorene can serve as the host of green PhOLEDs. 1,3,7-Triaryl spirobifluorene is a high-performance host for red PhOLEDs, which exhibits a high external quantum efficiency (EQE) up to 27.3 %. This work not only exemplifies the great potential of multi-aryl spirobifluorenes as PHC hosts, but also offers a new approach for the synthesis of these PHC hosts.

Polarization-maintaining design for satellite-based quantum communication terminals.

We report the polarization preservation of quantum light in the optical systems of the terminals of the world's first quantum communication satellite, Micius. The main scientific experimental goals and polarization requirements of the satellite and ground station are introduced firstly. Three optical terminals are equipped on Micius to achieve our scientific goals, including a quantum entanglement source (QES), quantum entanglement transmitter (QET) and quantum key distribution transmitter (QKDT), and the function of each optical terminal is described briefly. A polarization-maintaining design for the terminals on Micius is critical for quantum communication, and the optical structure of the QKDT and QET is determined by using three polarization-maintaining methods. The optical configurations of the QKDT and QET are introduced, and the polarization-maintaining methods are described in detail. The final polarization extinction ratios of the QKDT and QET at wavelengths of 850 nm and 810 nm are better than 500:1, which provides critical technical support for realizing the scientific goals of Micius.

The Chinese Herb Codonopsis pilosula Isolate Isorhapontigenin protects against oxidative stress injury by inhibiting the activation of PI3K/Akt signaling pathway.

We investigated the effects of the Chinese herb Codonopsis pilosula isolate isorhapontigenin on antioxidant factor and the PI3K/Serine/Akt signaling pathway in Parkinson's disease. This research was, therefore, carried out to explore a possible protective mechanism of isorhamnetin in Parkinson's disease. The results support that isorhapontigenin could effectively inhibit isorhapontigenin restored myeloperoxidase + induced reduction of antioxidant levels. Also, 1-Methyl-4-phenylpyridine up-regulated the expression of phosphorylated-Akt, phosphorylated-PI3K, and phosphorylated mammalian target of rapamycin, while isorhapontigenin inhibited the expression of phosphorylated-Akt, phosphorylated-PI3K, and phosphorylated- mammalian target of rapamycin. Furthermore, LY294002 improved the antioxidant effect of isorhapontigenin in PC12 cells, and insulin-like growth factor 1 inhibited the antioxidant effect of isorhapontigenin in PC12 cells. Our results support the finding that isorhamnetin enhanced the antioxidant effect induced by 1-Methyl-4-phenylpyridine in PC12 cells by suppressing the activation of the PI3K/Akt signaling pathway.

Botanical acaricides and repellents in tick control: current status and future directions.

Ticks are obligate blood-sucking ectoparasites and notorious as vectors of a great diversity of, in many instances, zoonotic pathogens which can cause considerable damage to animal and human health. The most commonly used approach for the control of ticks is the application of synthetic acaricides. However, the negative impacts of synthetic acaricides on the treated animals and the environment, in addition to its documented role in the development of resistance has led to the search for safer and more environmentally friendly alternative methods without compromising efficacy. An emerging promising approach for the control of ticks which has attracted much attention in recent years is the use of botanicals. Indeed, botanicals have been widely reported to show diverse effects and great potential as tick repellent and control. Although several excellent reviews have previously focused on this topic, studies on the exploration and application of botanicals to control ticks have expanded rapidly. Herein, we provide an update on the current understanding and status of botanical acaricides and repellents in tick control using recently published articles between 2017 and 2019. We also discuss the challenges and future directions in the application of botanicals in tick control, with a view of providing important clues for designing new integrated tick control methods.

Modification, Biological Evaluation and SAR Studies of Novel 1H-Pyrazol Derivatives Containing N,N'-Disubstituted Urea Moiety as Potential Anti-melanoma Agents.

Malignant melanomas are amongst the most aggressive cancers. BRAF Inhibitors have exhibited therapeutic effects against BRAF-mutant melanoma. In continuation of our earlier studies on anti-melanoma agents based on 1H-pyrazole skeleton, two sets of novel compounds that include 1H-pyrazole-4-amines FA1 - FA13 and corresponding urea derivatives FN1 - FN13 have been synthesized and evaluated for their BRAFV600E inhibitory and antiproliferation activities. Compound FN10 displayed the most potent biological activity against BRAFV600E (IC50 = 0.066 µm) and the A375 human melanoma cell line (GI50 = 0.81 µm), which was comparable to the positive control vemurafenib, and more potent than our previously reported 1H-pyrazole-3-amines and their urea derivatives. The results of SAR studies and molecular docking can guide further optimization and may help to improve potency of these pyrazole-based anti-melanoma agents.