Gene therapy by virus-like self-spooling toroidal DNA condensates for revascularization of hindlimb ischemia.

Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and the current therapeutic strategies including antiplatelet medication or intervene surgery are reported to not clinically benefit the patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted for the potential treatment of critical PAD. Aiming for transcellular delivery of VEGF-encoding plasmid DNA (pDNA), we proposed to elaborate intriguing virus-like DNA condensates, wherein the supercoiled rigid micrometer-scaled plasmid DNA (pDNA) could be regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process with the aid of cationic block copolymer poly(ethylene glycol)-polylysine at an extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking was proposed between the polylysine segments with the aim of stabilizing these intriguing toroidal condensates. Pertaining to the critical hindlimb ischemia, our proposed toroidal VEGF-encoding pDNA condensates demonstrated high levels of VEGF expression at the dosage sites, which consequently contributed to the neo-vasculature (the particularly abundant formation of micro-vessels in the injected hindlimb), preventing the hindlimb ischemia from causing necrosis at the extremities. Moreover, excellent safety profiles have been demonstrated by our proposed toroidal condensates, as opposed to the apparent immunogenicity of the naked pDNA. Hence, our proposed virus-like DNA condensates herald potentials as gene therapy platform in persistent expressions of the therapeutic proteins, and might consequently be highlighted in the management of a variety of intractable diseases.

Magnetic/Acoustic Dual-Controlled Microrobot Overcoming Oto-Biological Barrier for On-Demand Multidrug Delivery against Hearing Loss.

Multidrug combination therapy in the inner ear faces diverse challenges due to the distinct physicochemical properties of drugs and the difficulties of overcoming the oto-biologic barrier. Although nanomedicine platforms offer potential solutions to multidrug delivery, the access of drugs to the inner ear remains limited. Micro/nanomachines, capable of delivering cargo actively, are promising tools for overcoming bio-barriers. Herein, a novel microrobot-based strategy to penetrate the round window membrane (RWM) is presented and multidrug in on-demand manner is delivered. The tube-type microrobot (TTMR) is constructed using the template-assisted layer-by-layer (LbL) assembly of chitosan/ferroferric oxide/silicon dioxide (CS/Fe3O4/SiO2) and loaded with anti-ototoxic drugs (curcumin, CUR and tanshinone IIA, TSA) and perfluorohexane (PFH). Fe3O4 provides magnetic actuation, while PFH ensures acoustic propulsion. Upon ultrasound stimulation, the vaporization of PFH enables a microshotgun-like behavior, propelling the drugs through barriers and driving them into the inner ear. Notably, the proportion of drugs entering the inner ear can be precisely controlled by varying the feeding ratios. Furthermore, in vivo studies demonstrate that the drug-loaded microrobot exhibits superior protective effects and excellent biosafety toward cisplatin (CDDP)-induced hearing loss. Overall, the microrobot-based strategy provides a promising direction for on-demand multidrug delivery for ear diseases.

Dual Roles of the Photooxidation of Organic Amines for Enhanced Triplet-Triplet Annihilation Upconversion in Nanoparticles.

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

Percutaneous coronary intervention leads to microplastics entering the blood: Interventional devices are a major source.

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.

The output of cataract surgery performed by trained non-ophthalmologist physicians in rural areas: study of cataract outcomes and up-take of services report 7.

BACKGROUND: Cataract is the leading cause of blindness worldwide and surgery can restore vision in most patients. Some patients have little access to surgical services due to lack of cataract surgeons and the unaffordable costs. In 2005 we built a service model that trained rural non-ophthalmologist physicians to perform cataract surgeries in rural China. This study evaluates the long-term impacts of this model. METHODS: We conducted a retrospective cohort study to analyze patients' hand-written medical records and electronic outpatient record between January 2005 and December 2019 at two rural health clinics in Southern China. RESULTS: In total, 34,601 patients (49,942 eyes) underwent cataract surgery by non-ophthalmologist physicians from 2005 to 2019.Visual acuity was clearly documented in 38,251 eyes. Before surgery, the unaided distance visual acuity (UDVA) of 60.7% (23,205/38,251) eyes was less than 0.05 decimal. On the first day after surgery, the percentage of UDVA < 0.05 eyes was reduced to 6.0%, and 96.7% (36,980/38,251) of the eyes achieved a better UDVA compared to pre-operation. Surgical-related complications occurred in 218 eyes. The most common complication was posterior capsule rupture (114, 0.23%). 44.3% (15,341/34,601) of the patients chose to have a second eye cataract surgery (SECS) in the same clinic. At one of the outpatient clinics, 21,595 patients received basic eye care apart from cataract surgery between 2018 and 2020. CONCLUSIONS: Non-ophthalmologist physicians trained for cataract surgeries in rural clinics can improve cataract related visual acuity and basic eye care to the local population.

Highly flexible yet strain-insensitive conjugated polymer.

Imparting excellent electrical properties, mechanical robustness, suppleness, conduction stability during deformation, and self-healing to intrinsic conducting polymers is a challenging endeavor. The reversibly interlocked macromolecular networks (RILNs) approach is utilized to tackle this problem. Specifically, poly(3,4-ethylenedioxythiophene) (PEDOT) is mixed with flexible polysulfonic acid networks crosslinked by reversible Diels-Alder bonds, while rigid polyaniline networks crosslinked by reversible Schiff base bonds act as molecular staples. Owing to the joint actions of the doping effect of polyaniline on PEDOT, the specific interlocking architecture and synergy between the component materials, the electrical conductivity (59.3-980.5 S cm-1), tensile strength (8.4-81.6 MPa) and elongation at break (44.5-411.0%) of the resultant PEDOT/RILNs films is significantly tunable according to different usage scenarios by adjusting the PEDOT content from 1.48 to 22.24 wt%. More importantly, the electrical resistance of PEDOT/RILNs remains constant during not only a single large extension and deflection but also repeated stretching (up to 1500 cycles) and bending (up to 106 cycles). The built-in reversible covalent bonds enable the PEDOT/RILNs to autonomously restore damaged mechanical and electrical performance. These record-breaking results and the demonstration of self-powered sensor made of PEDOT/RILNs suggest that the proposed approach successfully satisfies various conflicting requirements of flexible electronics regarding the properties of conducting polymers.

Optimizing anaerobic digestion: Benefits of mild temperature transition from thermophilic to mesophilic conditions.

Anaerobic digestion (AD) plays a significant role in renewable energy recovery. Upgrading AD from thermophilic (50-57 °C) to mesophilic (30-38 °C) conditions to enhance process stability and reduce energy input remains challenging due to the high sensitivity of thermophilic microbiomes to temperature fluctuations. Here we compare the effects of two decreasing-temperature modes from 55 to 35 °C on cell viability, microbial dynamics, and interspecies interactions. A sharp transition (ST) is a one-step transition by 20 °C d-1, while a mild transition (MT) is a stepwise transition by 1 °C d-1. We find a greater decrease in methane production with ST (88.8%) compared to MT (38.9%) during the transition period. ST mode overproduced reactive oxygen species by 1.6-fold, increased membrane permeability by 2.2-fold, and downregulated microbial energy metabolism by 25.1%, leading to increased apoptosis of anaerobes by 1.9-fold and release of intracellular substances by 2.9-fold, further constraining methanogenesis. The higher (1.6 vs. 1.1 copies per gyrA) metabolic activity of acetate-dependent methanogenesis implied more efficient methane production in a steady mesophilic, MT-mediated system. Metagenomic binning and network analyses indicated that ST induced dysbiosis in keystone species and greatly enhanced microbial functional redundancy, causing loss of microbial syntrophic interactions and redundant metabolic pathways. In contrast, the greater microbial interconnections (average degrees 44.9 vs. 22.1) in MT at a steady mesophilic state suggested that MT could better maintain necessary system functionality and stability through microbial syntrophy or specialized pathways. Adopting MT to transform thermophilic digesters into mesophilic digesters is feasible and could potentially enhance the further optimization and broader application of practical anaerobic engineering.

N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC. AIM: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC. METHODS: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines. RESULTS: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC (P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher (P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC (P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased (P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) (P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS. CONCLUSION: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis.

Prodrug-inspired adenosine triphosphate-activatable celastrol-Fe(III) chelate for cancer therapy.

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.

Fast Low-Sidelobe Pattern Synthesis Using the Symmetry of Array Geometry.

Array pattern synthesis with low sidelobe levels is widely used in practice. An effective way to incorporate sensor patterns in the design procedure is to use numerical optimization methods. However, the dimension of the optimization variables is very high for large-scale arrays, leading to high computational complexity. Fortunately, sensor arrays used in practice usually have symmetric structures that can be utilized to accelerate the optimization algorithms. This paper studies a fast pattern synthesis method by using the symmetry of array geometry. In this method, the problem of amplitude weighting is formulated as a second-order cone programming (SOCP) problem, in which the dynamic range of the weighting coefficients can also be taken into account. Then, by utilizing the symmetric property of array geometry, the dimension of the optimization problem as well as the number of constraints can be reduced significantly. As a consequence, the computational efficiency is greatly improved. Numerical experiments show that, for a uniform rectangular array (URA) with 1024 sensors, the computational efficiency is improved by a factor of 158, while for a uniform hexagonal array (UHA) with 1261 sensors, the improvement factor is 284.

Bearing-DETR: A Lightweight Deep Learning Model for Bearing Defect Detection Based on RT-DETR.

Detecting bearing defects accurately and efficiently is critical for industrial safety and efficiency. This paper introduces Bearing-DETR, a deep learning model optimised using the Real-Time Detection Transformer (RT-DETR) architecture. Enhanced with Dysample Dynamic Upsampling, Efficient Model Optimization (EMO) with Meta-Mobile Blocks (MMB), and Deformable Large Kernel Attention (D-LKA), Bearing-DETR offers significant improvements in defect detection while maintaining a lightweight framework suitable for low-resource devices. Validated on a dataset from a chemical plant, Bearing-DETR outperformed the standard RT-DETR, achieving a mean average precision (mAP) of 94.3% at IoU = 0.5 and 57.5% at IoU = 0.5-0.95. It also reduced floating-point operations (FLOPs) to 8.2 G and parameters to 3.2 M, underscoring its enhanced efficiency and reduced computational demands. These results demonstrate the potential of Bearing-DETR to transform maintenance strategies and quality control across manufacturing environments, emphasising adaptability and impact on sustainability and operational costs.

Recognition of an extralobar pulmonary sequestration during lung resection.

BACKGROUND: Extralobar pulmonary sequestration is located outside the lung parenchyma and is covered by a separated pleural sac, which comprises approximately 25% of all pulmonary sequestration. CASE PRESENTATION: This article reported one case of an extralobar pulmonary sequestration originated from the mesoesophagus, which was recognized and excised during a lung resection. Histologic examination revealed an ectopic lung tissue with hyperplasia of bronchioles, which was accord with an extralobar pulmonary sequestration. CONCLUSIONS: CT angiogram, ultrasound and MRI can be used to clarify the diagnosis and detect the abnormal feeding arteries of extralobar pulmonary sequestration. Carefulness should be taken while dissecting and ligating the potential feeding arteries. Endovascular occlusion might be an alternative option to surgery.

Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.

Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here we employed an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk locus 19q13.2. Notably, we found that RPS19 exhibited the most significant effect among the identified genes and acted as a critical oncogene facilitating CRC cell proliferation. Subsequently, combining integrative fine-mapping analysis and a large-scale population study consisting of 6027 cases and 6099 controls, we prioritized rs1025497 as a potential causal candidate for CRC risk, demonstrating that rs1025497[A] allele significantly reduced the risk of CRC (OR 0.70, 95% confidence interval = 0.56-0.83, P = 1.12 × 10-6), which was further validated in UK Biobank cohort comprising 5,313 cases and 21,252 controls. Mechanistically, we experimentally elucidated that variant rs1025497 might acted as an allele-specific silencer, inhibiting the expression level of oncogene RPS19 mediated by the transcription suppressive factor HBP1. Taken together, our sturdy unveils the significant role of RPS19 during CRC pathogenesis and delineates its distal regulatory mechanism mediated by rs1025497, advancing our understanding of the etiology of CRC and provided new insights into the personalized medicine of human cancer.

Evaluating the accuracy of Raman spectroscopy in differentiating leukemia patients from healthy individuals: A systematic review and meta-analysis.

PURPOSE: To assess the accuracy of Raman spectroscopy in distinguishing between patients with leukemia and healthy individuals. METHOD: PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases were searched for relevant articles published from inception of the respective database to November 1, 2023. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), were calculated along with their corresponding 95 % confidence intervals (CI). A summary comprehensive receiver operating characteristic curve (SROC) was constructed and the area under the curve (AUC) was calculated. The degree of heterogeneity was tested and analyzed. RESULTS: Fifteen groups of original studies from 13 articles were included. The pooled SEN and SPE were 0.93 (95 % CI, [0.92 -0.93]) and 0.91(95 % CI, [0.90-0.92]), respectively. The DOR was 613.01 (95 %CI, [270.79-1387.75]), and the AUC was 0.99. The Deeks' funnel plot asymmetry test indicated no significant publication bias among the included studies (bias coefficient, 40.80; P = 0.13 < 0.10). The meta-regression analysis findings indicated that the observed heterogeneity could be attributed to variations in sample categories and Raman spectroscopy techniques. CONCLUSION: We confirmed that Raman spectroscopy has good accuracy in differentiating patients with leukemia from healthy individuals, and may become a means of leukemia screening in clinical practice. In the case of analysis based on live cells using surface-enhanced Raman spectroscopy (SERS) improved diagnostic efficacy was observed.

Mapping of 10-km daily diffuse solar radiation across China from reanalysis data and a Machine-Learning method.

Diffuse solar radiation (DSR) plays a critical role in renewable energy utilization and efficient agricultural production. However, there is a scarcity of high-precision, long-term, and spatially continuous datasets for DSR in the world, and particularly in China. To address this gap, a 41-year (1982-2022) daily diffuse solar radiation dataset (CHDSR) is constructed with a spatial resolution of 10 km, based on a new ensemble model that combines the clear-sky irradiance estimated by the REST2 model and a machine-learning technique using precise cloud information derived from reanalysis data. Validation against ground-based measurements indicates strong performance of the new hybrid model, with a correlation coefficient, root mean square error and mean bias error (MBE) of 0.94, 13.9 W m-2 and -0.49 W m-2, respectively. The CHDSR dataset shows good spatial and temporal continuity over the time horizon from 1982 to 2022, with a multi-year mean value of 74.51 W m-2. This dataset is now freely available on figshare to the potential benefit of any analytical work in solar energy, agriculture, climate change, etc ( https://doi.org/10.6084/m9.figshare.21763223.v3 ).

Corrosion Behavior of Al-Containing CoNiV Medium Entropy Alloy Coating Fabricated by Laser Cladding.

CoNiV medium entropy alloys (MEAs) have been widely recognized for their superior corrosion resistance. Nonetheless, their extensive application has been hindered by high production costs and complex fabrication processes. In this study, CoNiVAlx MEA coatings were synthesized on AISI 304 stainless steel substrates via laser cladding technology. The microstructure, phase composition, corrosion resistance, and corrosion mechanisms of the coatings were systematically investigated by using advanced characterization techniques, including optical microscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffractometry, and electrochemical workstation analysis. The ratio of O2-/OH- in the passivation film of the coated surface exhibited a gradual increase with the addition of Al. The formation of the Al-containing precipitated phase L21 was observed at x = 0.3 and 0.4. The results demonstrated that moderate Al doping (x ≤ 0.2) enhanced corrosion resistance by improving the stability of the passivation film and reducing the thermodynamic tendency toward corrosion. In contrast, excessive Al doping (x > 0.2) led to the formation of the L21 phase, which increased the susceptibility to localized corrosion, thus compromising the overall corrosion resistance.

Chromothripsis is a novel biomarker for prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms.

This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.

Rapid axial roll test outperforms alternative positional tests in identifying the affected ear in HSC-BPPV: an observational cohort study.

Purpose: To evaluate the utility of supine roll test (SRT) and alternative positional tests, such as head-shaking test (HST), seated supine positioning test (SSPT), bow and lean test (BLT), and rapid axial roll test (RART) in determining the affected semicircular canal of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV). Methods: In an observational cohort study, 553 patients diagnosed with HSC-BPPV were divided into five groups in terms of different positional tests received: SRT group (n = 110), HST+ SRT (n = 112), BLT + SRT (n = 114), SSPT+SRT (n = 108) and RART+SRT (n = 109). The same method was used for the last four groups: The patients were first subjected to different alternative positional tests and then to SRT, and the nystagmus was observed separately to determine the affected side. The primary outcomes compared included the accuracy and sensitivity of these tests in the determination of the affected semicircular canal in HSC-BPPV. Results: Patients with nystagmus elicited by positional tests accounted for 84.99% (470/553). The elicitation rate of nystagmus of SRT was lowest, being 77.27% (85/110). The elicitation rate of nystagmus were higher in the test groups than in the control group, and RART+SRT group yielded the highest elicitation rate of nystagmus (95.41%, 104/109). Among the alternative positional tests, RART attained the highest elicitation rate of nystagmus (101/109, 92.66%). Comparison between alternative positional tests and SRT, RART and SRT showed obviously better agreement in determining the affected semicircular canal (85.45%, 96/109) and eliciting nystagmus (95.41%, Kappa = 0.642), but no difference was found in curative effect when the affected side was accurately determined (χ2 = 1.618, p = 0.655). Conclusion: All alternative positional tests are helpful for eliciting nystagmus in patients with HSC-BPPV, and the significant advantages of RART include high-sensitivity in eliciting nystagmus and high accuracy in determining the affected semicircular canal, which provided objective support for the correct diagnosis of HSC-BPPV and the successful reduction of otolith.

RESC14 and RESC8 cooperate to mediate RESC function and dynamics during trypanosome RNA editing.

Mitochondrial transcripts in Trypanosoma brucei require extensive uridine insertion/deletion RNA editing to generate translatable open reading frames. The RNA editing substrate binding complex (RESC) serves as the scaffold that coordinates the protein-protein and protein-RNA interactions during editing. RESC broadly contains two modules termed the guide RNA binding complex (GRBC) and the RNA editing mediator complex (REMC), as well as organizer proteins. How the protein and RNA components of RESC dynamically interact to facilitate editing is not well understood. Here, we examine the roles of organizer proteins, RESC8 and RESC14, in facilitating RESC dynamics. High-throughput sequencing of editing intermediates reveals an overlapping RESC8 and RESC14 function during editing progression across multiple transcripts. Blue native PAGE analysis demonstrates that RESC14 is essential for incorporation of RESC8 into a large RNA-containing complex, while RESC8 is important in recruiting a smaller ribonucleoprotein complex (RNP) to this large complex. Proximity labeling shows that RESC14 is important for stable RESC protein-protein interactions, as well as RESC-RECC associations. Together, our data support a model in which RESC14 is necessary for assembly of editing competent RESC through recruitment of an RNP containing RESC8, GRBC and gRNA to REMC and mRNA.