Phenomenological Muscle Constitutive Model With Actin-Titin Binding for Simulating Active Stretching.

The force produced by a muscle depends on its contractile history, yet human movement simulations typically employ muscle models that define the force-length relationship from measurements of fiber force during isometric contractions. In these muscle models, the total force-length curve can have a negative slope at fiber lengths greater than the fiber length at which peak isometric force is produced. This region of negative stiffness can cause numerical instability in simulations. Experiments have found that the steady-state force in a muscle fiber following active stretching is greater than the force produced during a purely isometric contraction. This behavior is called residual force enhancement. We present a constitutive model that exhibits force enhancement, implemented as a hyperelastic material in the febio finite element software. There is no consensus on the mechanisms responsible for force enhancement; we adopt the assumption that the passive fiber force depends on the sarcomere length at the instant that the muscle is activated above a threshold. We demonstrate the numerical stability of our model using an eigenvalue analysis and by simulating a muscle whose fibers are of different lengths. We then use a three-dimensional muscle geometry to verify the effect of force enhancement on the development of stress and the distribution of fiber lengths. Our proposed muscle material model is one of the few models available that exhibits force enhancement and is suitable for simulations of active lengthening. We provide our implementation in febio so that others can reproduce and extend our results.

Recent advancements in image-enhanced endoscopy in the pancreatobiliary field.

Image-enhanced endoscopy (IEE) has advanced gastrointestinal disease diagnosis and treatment. Traditional white-light imaging has limitations in detecting all gastrointestinal diseases, prompting the development of IEE. In this review, we explore the utility of IEE, including texture and color enhancement imaging and red dichromatic imaging, in pancreatobiliary (PB) diseases. IEE includes methods such as chromoendoscopy, optical-digital, and digital methods. Chromoendoscopy, using dyes such as indigo carmine, aids in delineating lesions and structures, including pancreato-/cholangio-jejunal anastomoses. Optical-digital methods such as narrow-band imaging enhance mucosal details and vessel patterns, aiding in ampullary tumor evaluation and peroral cholangioscopy. Moreover, red dichromatic imaging with its specific color allocation, improves the visibility of thick blood vessels in deeper tissues and enhances bleeding points with different colors and see-through effects, proving beneficial in managing bleeding complications post-endoscopic sphincterotomy. Color enhancement imaging, a novel digital method, enhances tissue texture, brightness, and color, improving visualization of PB structures, such as PB orifices, anastomotic sites, ampullary tumors, and intraductal PB lesions. Advancements in IEE hold substantial potential in improving the accuracy of PB disease diagnosis and treatment. These innovative techniques offer advantages paving the way for enhanced clinical management of PB diseases. Further research is warranted to establish their standard clinical utility and explore new frontiers in PB disease management.

Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

Cause of nocturnal surface ozone enhancement in the North China Plain.

The North China Plain (NCP), known for its dense population, extensive urbanization, and developed industry and agriculture, faces one of the foremost ozone (O3) pollution issues nationwide and even globally. Currently, most studies focus on daytime peak O3 levels, with insufficient understanding of the increase in nighttime O3 concentrations. Based on data from 204 national atmospheric composition monitoring sites in the NCP from 2015 to 2023, we investigated the characteristics of nocturnal surface O3 enhancement (NSOE) events and explored potential formation mechanisms. The mean annual frequencies of single-site and regional NSOE event in the NCP between 2015 and 2023 are 42 % and 21 %, respectively. The daytime peak O3 concentrations before and after NSOE events exceeded those during the corresponding periods of non-NSOE events by 84 ± 19 and 32 ± 15 µg/m3, respectively. The overall effect of the NSOE events was to decelerate the rate of decline in nighttime O3 concentrations and resulted in a reduction of NO2 and CO concentrations from 22:00 onwards. Low level jet (LLJ) and vertical mixing were the main factors affecting NSOE events in the NCP. The proportion of NSOE events affected by LLJ in four representative cities ranged from 57.6 % to 79.5 %. Furthermore, the high concentration of O3 in the residual layer before the NSOE event and the reduction of atmospheric stability during the NSOE event favored downward mixing of upper layer O3. The primary weather systems influencing the four most severe regional NSOE events were LLJ, typhoon, and cold fronts. The first two events were dominated by vertical mixing of O3, while the latter two events were mainly affected by horizontal transport. Our findings provide the first overview of NSOE events in the NCP from characteristics to mechanisms, emphasizing the necessity for future detailed studies based on nocturnal vertical O3 observations.

Solvent-induced modulation of sensitivity and selectivity in the self-assembly of tetracationic cyclophanes with cholesterol sulphate, sodium dodecyl sulfate, and sodium dodecyl benzene sulfonate: Observations of significant shifts.

Cyclophane CP-1 demonstrates markedly distinct sensitivities toward Cholesterol sulfate (CH-S), Sodium Dodecyl Sulfate (SDS), and Sodium Dodecyl Benzene Sulfonate (SDBS) when the solvent is shifted minimally from a 95 % to a 98 % HEPES-DMSO mixture. In a 98:2 HEPES-DMSO mixture, CP-1 engages in highly selective self-assembly with CH-S, which is characterized by aggregation-induced emission enhancement (AIEE) in contrast to other steroidal sulfates such as pregnenolone sulfate (PRG-S), dehydroisoandrosterone sulfate (DIAND-S), taurocholic acid (TACH-S), and the surfactants SDS and SDBS. This assembly results in an approximate 40-fold increase in fluorescence intensity with three equivalents of CH-S and allows for the detection of concentrations as low as 200 nM under physiological conditions. Dynamic light scattering (DLS) studies illustrate the aggregation of CP-1 and CH-S, with the zeta potential of each shifting from negative values to nearly zero in a 1:2 CP-1:CH-S mixture, indicating self-assembly. This aggregation behavior is reversible, as demonstrated by a corresponding decrease and then increase in fluorescence intensity with temperature variations from 25 °C to 70 °C and back to 25 °C. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) analyses show that CP-1 forms aggregates ranging from 100 to 180 nm, which increase to 150-250 nm upon interaction with CH-S. In a 95:5 HEPES-DMSO mixture, CP-1 exhibits a stronger AIEE response with SDS and SDBS compared to CH-S. Cyclophane CP-2, when dissolved in binary DMSO-water mixtures with water content exceeding 80 %, shows similar AIEE phenomena and undergoes selective fluorescence quenching with SDS and only a 50 % increase in fluorescence intensity with CH-S, irrespective of the HEPES concentration (95 % or 98 %).

More is Less: Image Enhancement Technology Reduces Radiation Exposure During Anterior Lumber Interbody Fusion.

BACKGROUND CONTEXT: Fluoroscopy and radiation exposure occur during anterior lumbar interbody fusion (ALIF). Image enhancement technology is available that can potentially reduce radiation exposure. PURPOSE: The purpose of this study is to evaluate radiation exposure and fluoroscopy times comparing standard fluoroscopy (FL) with a low dose image enhancement platform (LD). STUDY DESIGN: Retrospective review of prospectively maintained database PATIENT SAMPLE: Consecutive patients undergoing ALIF with either standard fluoroscopy or low dose image enhancement technology OUTCOME MEASURES: Radiation dispersion and fluoroscopy times in ALIF patients with standard fluoroscopy and low dose image enhancement technology METHODS: A retrospective review of a prospective database on consecutive patients who have undergone ALIF, stratified into two groups: subjects with standard fluoroscopy (FL), and low dose fluoroscopy with image enhancement technology (LD). RESULTS: A total of 487 ALIF patients were included (FL: 372 vs LD: 115). LD patients were significantly older (66 vs 60 years), with more deformity cases (28% vs 12%), and less degenerative cases (71% vs 87%), all p<0.05; no differences in sex, BMI, or the number of levels operated on between groups. Fluoroscopy time (sec) was significantly higher in LD (51.4 vs 45.5), with a statistically significant reduction in radiation (mGy) compared to FL (23.3 vs 48.2), both p<0.05. Furthermore, the results showed that radiation dispersion is increasingly reduced as fluoroscopy time increases in LD compared to FL (12%, 56%, and 65% reduction in radiation dispersion for fluoroscopy time < 30 sec, between 30 to 60 sec, and > 60 sec, respectively). CONCLUSIONS: The use of low dose fluoroscopy with image enhancement technology significantly reduces the cumulative dose of radiation during ALIF compared to standard dose fluoroscopy. Also, radiation dispersion increasingly decreases as fluoroscopy time increases using low dose image enhancement technology. Low dose image enhancement technology improves the safety profile of ALIF for patients and operating room staff.

Contrast-Enhanced Micro-CT Imaging of Murine Mandibles: A Multi-Method Approach for Simultaneous Hard and Soft Tissue Analysis.

AIM: To develop and evaluate a novel multi-method micro-computed tomography (µCT) imaging protocol for enhanced visualization of both hard and soft tissues in murine mandibles, addressing the limitations of traditional imaging techniques in dental research. MATERIALS AND METHODS: We employed a contrast-enhanced (CE) µCT imaging technique using Lugol's iodine as a contrast agent to visualize the intricate structures of murine mandibles. The protocol involved the combination of conventional µCT imaging as well as CE-µCT, including decalcification with EDTA, allowing for simultaneous assessment of hard and soft tissues. The method is compared with standard imaging modalities, and the ability to visualize detailed anatomical features is discussed. RESULTS: The CE-µCT imaging technique provided superior visualization of murine mandibular structures, including dental pulp, periodontal ligaments and the surrounding soft tissues, along with conventional µCT imaging of alveolar bone and teeth. This method revealed detailed anatomical features with high specificity and contrast, surpassing traditional imaging approaches. CONCLUSION: Our findings demonstrate the potential of CE-µCT imaging with Lugol's iodine as a powerful tool for dental research. This technique offers a comprehensive view of the murine mandible, facilitating advanced studies in tissue engineering, dental pathology and the development of dental materials.

Regulate catalytic performance by engineering non-regular structure of extradiol dioxygenase: An entrance to bottom strategy.

Extradiol dioxygenase Tcu3516 is a home-sourced enzyme demonstrating potent aromatic phenol degradation capacity. To add to the advantageous modifications inside active cavity, this work reported a novel strategy to engineer rarely concerned non-regular structures around the entrance towards the active site at the bottom of cavity. Three structures, Loop region 1 (Loop1: Met173-Arg185), Loop region 2 (Loop2: Ala201-Val212) and C-terminal (C-tail: His290-Lys306) were therefore identified through structural flexibility analysis. Highly rigid prolines within the structures were mutated into smaller alanine, glycine, or serine to improve structural flexibilities; while only P183S on Loop1 showed 3-fold activity enhancement vs the WT when subjected to cleavage of mono-cyclic catechol analogues. The analysis of Root Mean Square Fluctuation showed that P183S presents certain enhancement on Loop1 flexibility without dramatic changes of other domains. Furthermore, the synergetic effects from mutation P183S and cavity-based mutations V186L, V212N and D285A were evaluated by characterizing combinatorial mutants. Temperature dependence and thermostability of the combined mutants showed a more flexible catalytic domain without sacrificing structural integrity and stability. kcat value of P183S/V186L (SL) towards monocyclic catechols significantly surpasses any other combinatorial mutants around Tcu3516 active sites. Moreover, the synergetic effects on conformational plasticity were analyzed by molecular dynamic simulations to shed light into the interplay between structural changes and catalytic performance.

Species differences in carbon drawdown during marine phytoplankton growth.

Ocean alkalinity enhancement (OAE) has been proposed as a mitigation method for negative carbon emission. Its effects on marine phytoplankton communities would depend on species differences in tolerance to high pH, which results from phytoplankton photosynthetic drawdown of dissolved inorganic carbon (DIC). In this study, 20 marine phytoplankton species were grown in sealed batch cultures and DIC, pH and chlorophyll a (Chl-a) were measured at the peaks of biomass. These results revealed a wide range of species differences. The drawdown DIC (ΔDIC) vs. increases in pH (ΔpH) graph resembled a Michaelis-Menten curve: significantly linear for ΔDIC < ~1000 µM and starting to plateau at ΔDIC > 1000 µM. This indicated that two mechanisms were operating: CO2 limitation at ΔpH < 1.41 and biologically-mediated precipitation-CO2 released carbon uptake at ΔpH > 1.41. These findings suggest that the potential effects of OAE on the phytoplankton communities would depend on the species differences in oceans.

Alteration of cardiac structure and function and its prognostic value in patients with Takayasu arteritis: a cardiac magnetic resonance study.

Purpose: To investigate the prevalence and characteristics of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) and its prognostic value in patients with Takayasu arteritis (TA). Materials and methods: Sixty TA patients with a CMR examination were retrospectively included. All TA patients were divided into with LGE-positive and LGE-negative groups. Bi-ventricular function and location, distribution, and pattern of left ventricular (LV) LGE were evaluated in both LGE-positive and LGE-negative groups. Primary outcome was defined as a composite of cardiovascular death, hospitalization for heart failure, coronary artery revascularization, and stroke. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between variables and primary outcomes. Results: Sixty consecutive TA patients were enrolled in this study. The mean age was 38.2 ± 13.8 years and 54 patients (54/60, 90.0%) were female. LGE-positive was observed in twenty-one (21/60, 35%) patients in the total patients with TA. LGE was predominantly distributed in the middle wall and subendocardial. The patchy and infarcted LGE patterns were the most common. Compared with the LGE-negative group, the LGE-positive group had reduced LV ejection fraction (P = 0.033), elevated LV end-diastolic volume index (P = 0.008), LV end-systolic volume index (P = 0.012), and LV mass (P = 0.008). During a median follow-up period of 1,892 days (interquartile range: 1,764-1,988 days), the primary outcomes occurred in thirteen patients. In the univariate analysis, LGE-positive (hazard ratio [HR] = 4.478, 95% confidence interval [CI]: 1.376-14.570; P = 0.013) were independently associated with the primary outcomes. However, LGE-positive did not retain its value as an independent predictor of primary outcomes in the multivariate analysis. Instead, LVMI (HR = 1.030, 95%CI: 1.013-1.048; P = 0.001) was the strongest independent predictor of primary outcomes in patients with TA. The Kaplan-Meier plot revealed that patients with LVMI ≥ 57.5 g/m2 have a worse prognosis. Conclusion: LGE-positive detected by CMR was observed in 35% of total TA patients with different distributions and patterns. LGE is associated with adverse LV remodeling and worsen cardiac function. However, LVMI rather than LGE can provide independent prognostic information in patients with TA.

Development and experimental validation of computational methods for human antibody affinity enhancement.

High affinity is crucial for the efficacy and specificity of antibody. Due to involving high-throughput screens, biological experiments for antibody affinity maturation are time-consuming and have a low success rate. Precise computational-assisted antibody design promises to accelerate this process, but there is still a lack of effective computational methods capable of pinpointing beneficial mutations within the complementarity-determining region (CDR) of antibodies. Moreover, random mutations often lead to challenges in antibody expression and immunogenicity. In this study, to enhance the affinity of a human antibody against avian influenza virus, a CDR library was constructed and evolutionary information was acquired through sequence alignment to restrict the mutation positions and types. Concurrently, a statistical potential methodology was developed based on amino acid interactions between antibodies and antigens to calculate potential affinity-enhanced antibodies, which were further subjected to molecular dynamics simulations. Subsequently, experimental validation confirmed that a point mutation enhancing 2.5-fold affinity was obtained from 10 designs, resulting in the antibody affinity of 2 nM. A predictive model for antibody-antigen interactions based on the binding interface was also developed, achieving an Area Under the Curve (AUC) of 0.83 and a precision of 0.89 on the test set. Lastly, a novel approach involving combinations of affinity-enhancing mutations and an iterative mutation optimization scheme similar to the Monte Carlo method were proposed. This study presents computational methods that rapidly and accurately enhance antibody affinity, addressing issues related to antibody expression and immunogenicity.

Lateral flow assay sensitivity and signal enhancement via laser µ-machined constrains in nitrocellulose membrane.

Lateral flow assay (LFA) is a handful diagnostic technology that can identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other common respiratory viruses in one strip, which can be tested at the point-of-care without the need for equipment or skilled personnel outside the laboratory. Although its simplicity and practicality make it an appealing solution, it remains a grand challenge to substantially enhance the colorimetric LFA sensitivity. In this work, we present a straightforward approach to enhance the sensitivity of LFA by imposing the flow constraints in nitrocellulose (NC) membranes via a number of vertical femtosecond laser micromachined microchannels which is important for prolonged specific binding interactions. Porous NC membrane surfaces were structured with different widths and densities µ-channels employing a second harmonic of the Yb:KGW femtosecond laser and sample XYZ translation over a microscope objective-focused laser beam. The influence of the microchannel parameters on the vertical wicking speed was evaluated from the video recordings. The obtained results indicated that µ-channel length, width, and density in NC membranes controllably increased the immunological reaction time between the analyte and the labeled antibody by 950%. Image analysis of the colorimetric indicators confirmed that the flow rate delaying strategy enhanced the signal sensitives by 40% compared with pristine NC LFA.

Neuroimaging feature in identifying acute myelopathy etiologies: comparison between neuromyelitis optica spectrum disorder and cervical spondylotic myelopathy.

OBJECTIVE: The clinical symptoms of neuromyelitis optica spectrum disorder (NMOSD) and acute cervical spondylotic myelopathy (CSM) may overlap in some cases. This study aimed to investigate the differences in imaging features between NMOSD and CSM in acute myelopathy. METHODS: We included 78 patients in this retrospective study, including 28 NMOSD patients and 50 CSM patients. The demographic characteristics and clinical symptoms of the two groups of patients were compared. The T1 signal intensity, length of the spinal cord involved by T2 hyperintensity, degree of intervertebral disc degeneration, proportion of thoracic and lumbar cord involvement, proportion of brain involvement and lesion enhancement rate in magnetic resonance imaging (MRI) were compared between the two groups of patients. The number, length, location on the sagittal image, pattern on the sagittal image, and distribution on the axial image of the lesions in the contrast-enhanced MRI of the two groups were evaluated. RESULTS: There were differences between NMOSD and CSM patients in the proportion of women, the proportion of bowel and bladder symptoms, mRS levels, the length of the spinal cord involved by T2 hyperintensity, degree of intervertebral disc degeneration, the proportion of thoracic and lumbar cord involvement, the proportion of brain involvement, the enhancement rate and number of lesions (p < 0.05). Among NMOSD patients, linear, patchy and ring or semi-ring enhancement were present in 8(30.8%) ,14 (53.8%) and 4(15.4%)patients, respectively, and axial gray and white matter were involved in 17 (65.4%) patients. Among patients with CSM, 9(36.0%) patients showed longitudinal oriented flake, 16 (64.0%) patients showed pancake-like enhancement, and 21 (84.0%) patients showed axial white matter involvement only. The differences in enhancement pattern on sagittal images and axial involvement were statistically significant (p < 0.05). CONCLUSIONS: Early differential diagnosis of NMOSD and CSM in acute myelopathy can be made by analyzing images and the number, length, sagittal enhancement pattern, and axial involvement of gadolinium-enhanced lesions.

Immediate effects of different feedback methods on running jump height and motion improvement in male college basketball players.

The study aimed to assess the validity and accuracy of estimating running jump (RJ) height using the high-speed camera of a smartphone and to evaluate the effectiveness of oral and visual feedback via a smartphone in enhancing RJ movements and height in skilled athletes. Twenty male college basketball players were randomly assigned to either the Oral Feedback (OF) or Oral and Visual Feedback (OVF) group. Initially, participants performed RJs on force plates while being recorded with an iPhone (240 fps). Jump heights were estimated using the video, force plate data, and position data from pelvic markers (JHiPhone, JHFP, and JHRM, respectively). Subsequently, each group received tailored feedback based on the RJ video. After feedback, participants performed RJs again, and jump heights were re-estimated. The JHiPhone measurements were systematically higher but showed acceptable random errors compared to JHRM, with excellent reproducibility and strong positive correlations with JHFP and JHRM. Only the OVF group showed significant improvements in jump height post-feedback. Our results indicate that JHiPhone is a valuable and accurate tool for sports settings. Additionally, the results demonstrated that visual feedback using a smartphone is effective and should complement oral feedback to enhance RJ jump height in real sports settings.

Structural-modulated substrate of MXene for surface-enhanced Raman scattering sensing.

The distinctive structure of MXene offers exceptional electron transport properties, abundant surface chemistry, and robust mechanical attributes, thereby bestowing it with remarkable advantages and promising prospects in the realm of surface-enhanced Raman scattering (SERS). This review comprehensively outlines the evolution, synthesis methodologies, and characterization techniques employed for MXene-based SERS substrates. It delves into the intricacies of its SERS enhancement mechanism, substrate variants, and performance metrics, alongside showcasing its diverse applications spanning molecular detection, biosensing, and environmental monitoring. Furthermore, it endeavors to pinpoint the research bottlenecks and chart the future research trajectories for MXene-based SERS substrates.

Liquisolid Technique for Solubility Enhancement of Poorly Soluble Drug - A Brief Review.

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.

Functional genomics screens reveal a role for TBC1D24 and SV2B in antibody-dependent enhancement of dengue virus infection.

Under some conditions, dengue virus (DENV) can hijack IgG antibodies to facilitate its uptake into target cells expressing Fc gamma receptors (FcgR)-a process known as antibody-dependent enhancement (ADE) of infection. Beyond a requirement for FcgR, host dependency factors for this unusual IgG-mediated infection route remain unknown. To identify cellular factors exclusively required for ADE, here, we performed CRISPR knockout (KO) screens in an in vitro system poorly permissive to infection in the absence of IgG antibodies. Validating our approach, a top hit was FcgRIIa, which facilitates the binding and internalization of IgG-bound DENV but is not required for canonical infection. Additionally, we identified host factors with no previously described role in DENV infection, including TBC1D24 and SV2B, which have known functions in regulated secretion. Using genetic knockout and trans-complemented cells, we validated a functional requirement for these host factors in ADE assays performed with monoclonal antibodies and polyclonal sera in multiple cell lines and using all four DENV serotypes. We show that knockout of TBC1D24 or SV2B impaired the binding of IgG-DENV complexes to cells without affecting FcgRIIa expression levels. Thus, we identify cellular factors beyond FcgR that promote efficient ADE of DENV infection. Our findings represent a first step toward advancing fundamental knowledge behind the biology of a non-canonical infection route implicated in disease.IMPORTANCEAntibodies can paradoxically enhance rather than inhibit dengue virus (DENV) infection in some cases. To advance knowledge of the functional requirements of antibody-dependent enhancement (ADE) of infection beyond existing descriptive studies, we performed a genome-scale CRISPR knockout (KO) screen in an optimized in vitro system permissive to efficient DENV infection only in the presence of IgG. In addition to FcgRIIa, a known receptor that facilitates IgG-mediated uptake of IgG-bound, but not naked DENV particles, our screens identified TBC1D24 and SV2B, cellular factors with no known role in DENV infection. We validated a functional role for TBC1D24 and SV2B in mediating ADE of all four DENV serotypes in different cell lines and using various antibodies. Thus, we identify cellular factors beyond Fc gamma receptors that promote ADE mechanisms. This study represents a first step toward advancing fundamental knowledge beyond a poorly understood non-canonical viral entry mechanism.

Au@Pt nanoparticles-based signal-enhanced lateral flow immunoassay for ultrasensitive naked-eye detection of SARS-CoV-2.

With SARS-CoV-2 N protein as a model target, a signal-enhanced LFIA based on Au@Pt nanoparticles (NPs) as labels is proposed. This Au@Pt NPs combined the distinguished localized surface plasma resonance (LSPR) effect of Au NPs and the ultrahigh peroxidase-like catalytic activity of Pt NPs. Au@Pt NPs could trigger substrate chromogenic reaction, generating a color signal orders of magnitude darker than their intrinsic color. In the detection, after the coloration of the strips, 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 were added, and a dark blue chelate (OxTMB) was produced soon, enhancing the band color significantly. After the signal amplification, the naked-eye detection limit for N protein reached 40 pg/mL. The detection sensitivity enhanced more than 1000 times than that without signal amplification. Compared with mainstream LFIA requiring complex readout instruments, the Au@Pt-based LFIA achieved a comparable sensitivity using naked eyes detection. This point is crucial, especially for unprofessional users or low-resource areas. Hence, this signal-enhanced LFIA may serve as a sensitive, cost-effective, and user-friendly detection method. It can shorten the testing window period and help identify early infections.

Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs.

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.

Perilymphatic enhancement and endolymphatic hydrops: MRI findings and clinical associations.

Objective: In this study, we aimed to summarize magnetic resonance imaging (MRI) findings of perilymphatic enhancement (PE) and endolymphatic hydrops (EH) of the inner ear, which are associated with vestibular and cochlear symptoms. Methods: We analyzed data on ears with definite Meniere's disease (MD), sensorineural hearing loss (SNHL), vertigo, and listening difficulties (LiD) from 508 ears of 254 patients who underwent contrast-enhanced 3-Tesla MRI between April 2021 and March 2023. We evaluated the degree of endolymphatic hydrops (EH), signal intensity ratios (SIRs) between the basal turns of the cochlea and cerebellum, and hearing levels for all ears. Ears with definite MD were also assessed for changes in vestibular and cochlear symptoms within 6 months. Results: Ears with definite MD exhibited significantly higher percentages of EH in both the vestibule and cochlea compared with ears with other diseases. Furthermore, ears with MD or sensorineural hearing loss (SNHL) had significantly higher SIRs of PE compared with ears with other diseases or asymptomatic ears. Among patients with definite MD, those experiencing hearing fluctuations or vertigo attacks within the last 6 months had significantly higher SIRs of PE compared with those who did not experience any symptoms. Conclusion: Significant EH in the vestibule and cochlea was a major finding for the imaging diagnosis of definite MD. A high SIR of PE was a good indicator for assessing MD activity, reflecting vestibular and cochlear symptoms and fluctuations.Level of Evidence: 4.