Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor Signaling in B1 but Not B2 B Cells.

B1 and B2 B cells differ in their ability to respond to T-cell-independent (TI) antigens. Here we report that the Src-family kinase (SFK) regulator CD148 has a unique and critical role in the initiation of B1 but not B2 cell antigen receptor signaling. CD148 loss-of-function mice were found to have defective B1 B-cell-mediated antibody responses against the T-cell-independent antigens NP-ficoll and Pneumovax 23 and had impaired selection of the B1 B cell receptor (BCR) repertoire. These deficiencies were associated with a decreased ability of B1 B cells to induce BCR signaling downstream of the SFK Lyn. Notably, Lyn appeared to be selectively regulated by CD148 and loss of this SFK resulted in opposite signaling phenotypes in B1 and B2 B cells. These findings reveal that the function and regulation of Lyn during B1 cell BCR signaling is distinct from other B cell subsets.

Rapid Visual Detection of Elite Erect Panicle Dense and Erect Panicle 1 Allele for Marker-Assisted Improvement in Rice (Oryza sativa L.) Using the Loop-Mediated Isothermal Amplification Method.

Molecular-assisted breeding is an effective way to improve targeted agronomic traits. dep1 (dense and erect panicle 1) is a pleiotropic gene that regulates yield, quality, disease resistance, and stress tolerance, traits that are of great value in rice (Oryza sativa L.) breeding. In this study, a colorimetric LAMP (loop-mediated isothermal amplification) assay was developed for the detection of the dep1 allele and tested for the screening and selection of the heavy-panicle hybrid rice elite restorer line SHUHUI498, modified with the allele. InDel (Insertion and Deletion) primers (DEP1_F and DEP1_R) and LAMP primers (F3, B3, FIP, and BIP) for genotyping were designed using the Primer3 Plus (version 3.3.0) and PrimerExplore (version 5) software. Our results showed that both InDel and LAMP markers could be used for accurate genotyping. After incubation at a constant temperature of 65 °C for 60 min with hydroxynaphthol blue (HNB) as a color indicator, the color of the LAMP assay containing the dep1 allele changed to sky blue. The SHUHUI498 rice line that was detected in our LAMP assay displayed phenotypes consistent with the dep1 allele such as having a more compact plant architecture, straight stems and leaves, and a significant increase in the number of effective panicles and spikelets, demonstrating the effectiveness of our method in screening for the dep1 allele in rice breeding.

Dielectrophoresis: Measurement technologies and auxiliary sensing applications.

Dielectrophoresis (DEP), which arises from the interaction between dielectric particles and an aqueous solution in a nonuniform electric field, contributes to the manipulation of nano and microparticles in many fields, including colloid physics, analytical chemistry, molecular biology, clinical medicine, and pharmaceutics. The measurement of the DEP force could provide a more complete solution for verifying current classical DEP theories. This review reports various imaging, fluidic, optical, and mechanical approaches for measuring the DEP forces at different amplitudes and frequencies. The integration of DEP technology into sensors enables fast response, high sensitivity, precise discrimination, and label-free detection of proteins, bacteria, colloidal particles, and cells. Therefore, this review provides an in-depth overview of DEP-based fabrication and measurements. Depending on the measurement requirements, DEP manipulation can be classified into assistance and integration approaches to improve sensor performance. To this end, an overview is dedicated to developing the concept of trapping-on-sensing, improving its structure and performance, and realizing fully DEP-assisted lab-on-a-chip systems.

Significance of hepatitis B virus capsid dephosphorylation via polymerase.

BACKGROUND: It is generally believed that hepatitis B virus (HBV) core protein (HBc) dephosphorylation (de-P) is important for viral DNA synthesis and virion secretion. HBV polymerase contains four domains for terminal protein, spacer, reverse transcriptase, and RNase H activities. METHODS: HBV Polymerase mutants were transfected into HuH-7 cells and assayed for replication and HBc de-P by the Phos-tag gel analysis. Infection assay was performed by using a HepG2-NTCP-AS2 cell line. RESULTS: Here, we show that a novel phosphatase activity responsible for HBc de-P can be mapped to the C-terminal domain of the polymerase overlapping with the RNase H domain. Surprisingly, while HBc de-P is crucial for viral infectivity, it is essential for neither viral DNA synthesis nor virion secretion. The potential origin, significance, and mechanism of this polymerase-associated phosphatase activity are discussed in the context of an electrostatic homeostasis model. The Phos-tag gel analysis revealed an intriguing pattern of "bipolar distribution" of phosphorylated HBc and a de-P HBc doublet. CONCLUSIONS: It remains unknown if such a polymerase-associated phosphatase activity can be found in other related biosystems. This polymerase-associated phosphatase activity could be a druggable target in clinical therapy for hepatitis B.

The effectiveness of the doxorubicin-etoposide-methylprednisolone regimen for adult HLH secondary to rheumatic disease.

To investigate the efficacy of the doxorubicin-etoposide-methylprednisolone, DEP) regimen as an effective treatment for adult Hemophagocytic Lymphohistiocytosis secondary to rheumatic disease and analyze prognosis in these patients. Fifty-eight adult patients diagnosed with Hemophagocytic Lymphohistiocytosis secondary to rheumatic disease admitted to Beijing Friendship Hospital from 1st Jan. 2018 to 31st Dec. 2022 were retrospectively included in this study. Patients were grouped according to previous treatment. Clinical data and laboratory characteristics of patients were retrospectively analyzed. The efficacy was evaluated every 2 weeks after initiating the first course of the DEP regimen and until the last inpatient or 31st Dec. 2023. 26 patients were included in Group A and 32 patients were included in Group B due to the previous treatment. After the first course of the DEP regimen, the overall response rate of all patients was 82.8%, with 13.8% in complete response and 69% in partial response. There was no significant statistical objective response rate between the two groups after the DEP regimen, except at 2-week. Serum ferritin, sCD25, ALT, AST, and DBIL concentrations were significantly lower at 2, 4 and 6-week than pre-treatment (P < 0.05). The overall mortality rate is 20.7% (12/58). Importantly, advanced age, initial level of HB and PLT, and central nervous system (CNS) involvement were independent poor risk factors affecting OS in bivariate analysis. The DEP regimen is effective for adult HLH secondary rheumatic disease with a high overall rate and accepted side effects.

Agronomic potential of plant-specific Gγ proteins.

The vascular plant-specific type III Gγ proteins have emerged as important targets for biotechnological applications. These proteins are exemplified by Arabidopsis AGG3, rice Grain Size 3 (GS3), Dense and Erect Panicle 1 (DEP1), and GGC2 and regulate plant stature, seed size, weight and quality, nitrogen use efficiency, and multiple stress responses. These Gγ proteins are an integral component of the plant heterotrimeric G-protein complex and differ from the canonical Gγ proteins due to the presence of a long, cysteine-rich C-terminal region. Most cereal genomes encode three or more of these proteins, which have similar N-terminal Gγ domains but varying lengths of the C-terminal domain. The C-terminal domain is hypothesized to give specificity to the protein function. Intriguingly, many accessions of cultivated cereals have natural deletion of this region in one or more proteins, but the mechanistic details of protein function remain perplexing. Distinct, sometimes contrasting, effects of deletion of the C-terminal region have been reported in different crops or under varying environmental conditions. This review summarizes the known roles of type III Gγ proteins, the possible action mechanisms, and a perspective on what is needed to comprehend their full agronomic potential.

Influence of the filter grain morphology on separation efficiency in dielectrophoretic filtration.

Recovery of noble materials from waste is essential for industries around the globe. Dielectrophoretic (DEP) filtration, an electrically switchable particle separation technique, can be applied to tackle this challenge. It is highly selective regarding particle size, material or shape. Expanding the scope of DEP towards high throughput and improving the trapping efficiency are vital to make DEP a viable robust alternative to conventional separation methods. DEP filtration works by selective immobilisation of particles in a porous medium by the action of an inhomogeneous electric field. The field inhomogeneity comes from scattering an electric field at the phase boundary between the particle suspension and the filter surface. In this article, we show how the filter structure affects the DEP separation. We study fixed bed filters of three different grain types and find that the morphology of the grains highly influences the DEP filter efficiency. Specifically, grains with irregular surface structure and high perceived angularity show high separation efficiency. We believe these insights into the design of DEP filtration will pave the way towards its application in, for example, the recovery of valuable materials from electronic waste dust.

Association of phthalate exposure with pulmonary function in adults: NHANES 2007-2012.

BACKGROUND: Epidemiological evidence for the adverse effect of phthalate exposure on respiratory health is on the rise, but cross-sectional studies regarding its effects on lung function are limited and contradictory, especially in adults. OBJECTIVE: To assess the associations between individual and a mixture of urinary phthalate metabolites and adult pulmonary function in the United States, and to identify which ones were primarily responsible for impaired respiratory function. METHODS: We obtained a cross-sectional data on 3788 adults aged 20 years and older from the National Health and Nutrition Examination Survey (2007-2012). Respiratory function was evaluated using spirometry, and phthalate exposure was assessed by measuring the levels of ten urinary phthalate metabolites. The effects of individual and mixed phthalate metabolites exposure on lung function were assessed using multivariate linear regression models and the repeated holdout weighted quantile sum (WQS) regression models, respectively, after adjusting for potential confounders including age, gender, family poverty income ratio, body mass index, and serum cotinine. RESULTS: When modeled as continuous variables or quantiles, urinary phthalate metabolites, including mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(3-carboxypropyl) phthalate, and mono-carboxyoctyl phthalate, were identified to be negatively associated with forced vital capacity in percent predicted values (ppFVC) and forced expiratory volume in the first second in percent predicted values (ppFEV1). In addition, per each decile increase in the WQS index, ppFVC (ß = -2.87, 95% CI: -3.56, -2.08) and ppFEV1 (ß = -2.53, 95% CI: -3.47, -1.54) declined significantly, primarily due to the contribution of MEP and MECPP. Furthermore, there were no significant interactions between co-exposure to urinary phthalate metabolites and each covariate. CONCLUSION: Our findings reveal that urinary phthalate metabolites are significantly associated with adult respiratory decrements, with diethyl and di-(2-ethylhexyl) phthalate contributing the most to the impaired lung function.

ADE-CycleGAN: A Detail Enhanced Image Dehazing CycleGAN Network.

The preservation of image details in the defogging process is still one key challenge in the field of deep learning. The network uses the generation of confrontation loss and cyclic consistency loss to ensure that the generated defog image is similar to the original image, but it cannot retain the details of the image. To this end, we propose a detail enhanced image CycleGAN to retain the detail information during the process of defogging. Firstly, the algorithm uses the CycleGAN network as the basic framework and combines the U-Net network's idea with this framework to extract visual information features in different spaces of the image in multiple parallel branches, and it introduces Dep residual blocks to learn deeper feature information. Secondly, a multi-head attention mechanism is introduced in the generator to strengthen the expressive ability of features and balance the deviation produced by the same attention mechanism. Finally, experiments are carried out on the public data set D-Hazy. Compared with the CycleGAN network, the network structure of this paper improves the SSIM and PSNR of the image dehazing effect by 12.2% and 8.1% compared with the network and can retain image dehazing details.

Modified diffusive epidemic process on Apollonian networks.

We present an analysis of an epidemic spreading process on an Apollonian network that can describe an epidemic spreading in a non-sedentary population. We studied the modified diffusive epidemic process using the Monte Carlo method by computational analysis. Our model may be helpful for modeling systems closer to reality consisting of two classes of individuals: susceptible (A) and infected (B). The individuals can diffuse in a network according to constant diffusion rates [Formula: see text] and [Formula: see text], for the classes A and B, respectively, and obeying three diffusive regimes, i.e., [Formula: see text], [Formula: see text], and [Formula: see text]. Into the same site i, the reaction occurs according to the dynamical rule based on Gillespie's algorithm. Finite-size scaling analysis has shown that our model exhibits continuous phase transition to an absorbing state with a set of critical exponents given by [Formula: see text], [Formula: see text], and [Formula: see text] familiar to every investigated regime. In summary, the continuous phase transition, characterized by this set of critical exponents, does not have the same exponents of the mean-field universality class in both regular lattices and complex networks.

Culturally Appropriate Assessment of Depression and Anxiety in Older Torres Strait Islanders: Limitations and Recommendations.

OBJECTIVES: The aim of the study was to assess the prevalence of anxiety and depression in older Aboriginal and Torres Strait Islander adults. METHODS: A modified version of the PHQ-9 (KICA-dep) and the Geriatric Anxiety Inventory (GAI) were administered as part of a wider dementia prevalence study conducted in the Torres Strait. Results were compared to diagnoses obtained on Geriatric review to evaluate their applicability in the region. RESULTS: A total of 236 participants completed the KICA-dep and 184 completed the GAI short form. Of these, 10.6% were identified with depression and 15.8% with anxiety. Some participants found questions about suicide ideation and self-harm offensive and others had difficulty understanding concepts on the GAI. The KICA-dep performed poorly in comparison to diagnosis on geriatric clinical review, so results are unlikely to reflect the true prevalence of depression in the region. CONCLUSIONS: Further research is required to explore the underlying dimensions of depression and anxiety and terminology used to express mood symptoms in the Torres Strait. CLINICAL IMPLICATIONS: • Current mental health screening tools are not applicable for the Torres Strait• More work is required to determine how symptoms of depression and anxiety are expressed within Torres Strait communities.

In vitro characterisation of murine pre-adipose nucleated cells reveals electrophysiological cycles associated with biological clocks.

Adipocytes are energy stores of the body which also play a role in physiological regulation and homeostasis through their endocrine activity. Adipocyte circadian clocks drive rhythms in gene expression, and dysregulation of these circadian rhythms associates with pathological conditions such as diabetes. However, although the role of circadian rhythms in adipose cells and related tissues has been studied from phsyiological and molecular perspectives, they have not yet been explored from an electrical perspective. Research into electro-chronobiology has revealed that electrical properties have important roles in peripheral clock regulation independently of transcription-translation feedback loops. We have used dielectrophoresis to study electrophysiological rhythms in pre-adipocytes - representing an adipocyte precursor and nucleated cell-based model, using serum shocking as the cellular method of clock entrainment. The results revealed significant electrophysiological rhythms, culminating in circadian (ca. 24 hourly) cycles in effective membrane capacitance and radius properties, whereas effective membrane conductance was observed to express ultradian (ca. 14 hourly) rhythms. These data shed new light into pre-adipocyte electrical behaviour and present a potential target for understanding and manipulation of metabolic physiology.

L-DEP regimen is effective as an initial therapy for adult EBV-HLH.

We performed a single-center, prospective trial to investigate the efficacy of PEG- asparaginase combined with liposomal doxorubicin, etoposide, and methylprednisolone (L-DEP) as an initial therapy for Epstein-Barr virus driven hemophagocytic lymphohistiocytosis (EBV-HLH). None of the patients received any chemotherapy after the diagnosis of EBV-HLH between September 2019 and September 2021. The efficacy was evaluated 2 weeks and 4 weeks after initiating L-DEP primary therapy. Forty-seven eligible patients with EBV-HLH were enrolled. The overall response rate (ORR) was 80.9% (38/47, 12 in clinical CR, 26 in clinical PR) at 2 weeks after the L-DEP regimen; at 4 weeks, the ORR was 75.6% (34/45, 21 in clinical CR, 13 in clinical PR). EBV-DNA loads in blood and plasma were significantly decreased 2 and 4 weeks after the L-DEP regimen (P < 0.001). Ferritin, soluble CD25 (sCD25), triglycerides (TGs), and ultrasonic spleen longitude, and thickness were all decreased significantly 2 and 4 weeks after the L-DEP regimen (P < 0.001). Thus, the L-DEP regimen is an effective initial therapy for EBV-HLH. However, the L-DEP regimen was poor in terms of long-term prognosis and that allo-HSCT should be received as soon as possible once a complete response is achieved.

SIRT1 enhances oxaliplatin resistance in colorectal cancer through microRNA-20b-3p/DEPDC1 axis.

Oxaliplatin (L-OHP) is a standard treatment drug for colorectal cancer (CRC), but acquired drug resistance limits the outcome of patients. We investigated the involvement of sirtuin 1 (SIRT1) in L-OHP resistance in the setting of CRC via microRNA-20b-3p/DEP domain containing 1 (miR-20b-3p/DEPDC1) axis. CRC tissues that were resistant or sensitive to L-OHP were harvested, in which SIRT1, miR-20b-3p, and DEPDC1 levels were tested. L-OHP-resistant-resistant CRC cells were transfected, subsequently, cellular proliferation, invasion, migration, and apoptosis were tested, and tumor resistance to L-OHP was observed. The binding of SIRT1 to miR-20b-3p promoter and the targeting relationship between miR-20b-3p and DEPDC1 were verified. An aberrant elevation in SIRT1 expression was seen in L-OHP-resistant CRC tissues and cells. Knockdown of SIRT1 sensitized CRC cells and xenografted CRC tumors to L-OHP. SIRT1 bound with miR-20b-3p promoter to regulate DEPDC1. Reducing miR-20b-3p or raising DEPDC1 levels weakened the effect of SIRT1 knockdown on L-OHP-resistant-CRC cells. SIRT1 enhances L-OHP resistance in CRC by mediating miR-20b-3p/DEPDC1 axis.

Genome sequencing and genetic analysis of recombinant inbred lines reveals important agronomic traits related loci under different nitrogen fertilization.

BACKGROUND: The intensive application of inorganic nitrogen has contributed to increasing the crop yield with the risk of environmental damage. High nitrogen fertilizer requirements are a long-standing problem in japonica cultivation. MATERIALS AND METHODS: In the present study, 200 recombinant inbred lines derived from two representative japonica varieties of Japanese and Chinese varieties, Akitakomachi and Liaogeng5, respectively, were planted under different nitrogen fertilization conditions. The relationships among nitrogen fertilization, genetic background, and important agronomic traits were surveyed through the phenotypic investigation and next-generation sequencing. RESULTS: The results showed that the yield components of Akitakomachi dramatically decreased along with the nitrogen reduction, whereas those of Liaogeng5 exhibited a slight decrease. The appearance quality and milling quality of both Akitakomachi and Liaogeng5 were improved, especially Liaogeng5. The recombinant inbred lines (RILs) showed similar trends to their parental lines. The QTLs analysis of important agronomic traits detected 17 loci, one QTL clustering located on chromosome 9 that corresponded to the plant height, panicle angle, grain number per panicle, harvest index, and taste value was identified to be synonymous with a previously reported gene, DEP1. The function of DEP1 was verified by a knock-out mutant constructed by CRISPR/Cas9. The dep1 mutant exhibited improved grain quality without severe yield penalty under nitrogen reduction conditions. CONCLUSION: The results of the present study provide useful information for the improvement of food security by enhancing nitrogen use efficiency.

The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.

Phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger 1 (P-Rex1) catalyzes the exchange of GDP for GTP on Rac GTPases, thereby triggering changes in the actin cytoskeleton and in transcription. Its overexpression is highly correlated with the metastasis of certain cancers. P-Rex1 recruitment to the plasma membrane and its activity are regulated via interactions with heterotrimeric Gßγ subunits, PIP3, and protein kinase A (PKA). Deletion analysis has further shown that domains C-terminal to its catalytic Dbl homology (DH) domain confer autoinhibition. Among these, the first dishevelled, Egl-10, and pleckstrin domain (DEP1) remains to be structurally characterized. DEP1 also harbors the primary PKA phosphorylation site, suggesting that an improved understanding of this region could substantially increase our knowledge of P-Rex1 signaling and open the door to new selective chemotherapeutics. Here we show that the DEP1 domain alone can autoinhibit activity in context of the DH/PH-DEP1 fragment of P-Rex1 and interacts with the DH/PH domains in solution. The 3.1 Å crystal structure of DEP1 features a domain swap, similar to that observed previously in the Dvl2 DEP domain, involving an exposed basic loop that contains the PKA site. Using purified proteins, we show that although DEP1 phosphorylation has no effect on the activity or solution conformation of the DH/PH-DEP1 fragment, it inhibits binding of the DEP1 domain to liposomes containing phosphatidic acid. Thus, we propose that PKA phosphorylation of the DEP1 domain hampers P-Rex1 binding to negatively charged membranes in cells, freeing the DEP1 domain to associate with and inhibit the DH/PH module.

Gßγ recruits and activates P-Rex1 via two independent binding interfaces.

Gßγ marks the inner side of the plasma membrane where chemotactic GPCRs activate Rac to lead the assembly of actin filaments that push the cell to move forward. Upon dissociation from heterotrimeric Gi, Gßγ recruits and activates P-Rex1, a Rac guanine nucleotide exchange factor (RacGEF). This cytosolic chemotactic effector is kept inactive by intramolecular interactions. The mechanism by which Gßγ stimulates P-Rex1 has been debated. We hypothesized that Gßγ activates P-Rex1 by a two-step mechanism based on independent interaction interfaces to recruit and unroll this RacGEF. Using pulldown assays, we found that Gßγ binds P-Rex1-DH/PH as well as PDZ-PDZ domains. These domains and the DEP-DEP tandem interact among them and dissociate upon binding with Gßγ, arguing for a stimulatory allosteric effect. In addition, P-Rex1 catalytic activity is inhibited by its C-terminal domain. To discern P-Rex1 recruitment from activation, we studied Q-Rhox, a synthetic RhoGEF having the PDZ-RhoGEF catalytic DH/PH module, insensitive to Gßγ, swapped into P-Rex1. Gßγ recruited Q-Rhox to the plasma membrane, indicating that Gßγ/PDZ-PDZ interaction interface plays a role on P-Rex1 recruitment. In conclusion, we reconcile previous findings and propose a mechanistic model of P-Rex1 activation; accordingly, Gßγ recruits P-Rex1 via the Gßγ/PDZ-PDZ interface followed by a second contact involving the Gßγ/DH/PH interface to unleash P-Rex1 RacGEF activity at the plasma membrane.

Theory for hierarchical assembly with dielectrophoresis and the role of particle anisotropy.

Nonuniform electric fields cause polarizable particles to move through an effect known as dielectrophoresis (DEP). Additionally, the particles themselves create nonuniform fields due to their induced dipoles. When the nonuniform field of one particle causes another to move, it represents a path to hierarchical assembly termed mutual DEP (mDEP). Anisotropic particles potentially provide further opportunities for assembly through intense and intricate local field profiles. Here, we construct a theoretical framework for describing anisotropic particles as templates for assembly through mDEP by considering the motion of small nanoparticles near larger anisotropic nanoparticles. Using finite element analysis, we study eight particle shapes and compute their field enhancement and polarizability in an orientation-specific manner. Strikingly, we find a more than tenfold enhancement in the field near certain particle shapes, potentially promoting mDEP. To more directly relate the field intensity to the anticipated assembly outcome, we compute the volume experiencing each field enhancement versus particle shape and orientation. Finally, we provide a framework for predicting how mixtures of two distinct particle species will begin to assemble in a manner that allows for the identification of conditions that kinetically bias assembly toward specific hierarchical outcomes.

Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis.

BACKGROUND: This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR). METHODS: Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR). RESULTS: The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs. CONCLUSIONS: The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.

Separation of circulating tumor cells from blood using dielectrophoretic DLD manipulation.

Circulating Tumor Cells (CTCs) play a prominent role in early cancer detection. Emerging label-free techniques can be promising to CTC detection due to advantages in preserving cell integrity and minimal sample consumption. Deterministic Lateral Displacement (DLD) is a size-based label-free technique employing laminar flow for continuous sorting of suspended cells. However, separation based solely on size is challenging as the size distributions of CTCs tend to overlap with blood cells. Moreover, the rarity of CTCs in blood requires high throughput processing of samples for clinical utility. In this work, a dielectrophoretic DLD technique is presented to segregate CTCs from blood. This technique utilizes the cell size and dielectric properties as well as particle movement caused by polarization effect to accomplish continuous separation at high flow rates. A numerical model is developed and validated to investigate the effects of various parameters related to the fluid flow, micro-post array, and electric field. It is demonstrated that the dielectrophoretic DLD with specific post arrangement can continuously separate A549 lung CTCs from WBCs by applying a field frequency close to the crossover frequency of CTCs. The analysis further indicates that such a device can perform well despite uncertainties of CTC crossover frequencies. Additionally, efficient separation with minimum clogging can be achieved by setting the electric field perpendicular to fluid flow. The presented platform offers distinct advantages and can be potentially combined with techniques such as antibody-based immune-binding methods for rapid detection of CTCs.