Linear temporal stability analysis on the inviscid sheared convective boundary layer flow

A linear temporal stability analysis is conducted for inviscid sheared convective boundary layer flow, in which the sheared instability with stable stratification coexists with and caps over the thermal instability with unstable stratification. The classic Taylor–Goldstein equation is applied with different stratification factors Js and Jb in the Brunt–Väisälä frequency, respectively. Two shear-thermal hybrid instabilities, the hybrid shear stratified (HSS) and hybrid Rayleigh–Bénard (HRB) modes, are obtained by solving the eigenvalue problems. It is found that the temporal growth rates of the HSS and HRB modes vary differently with increased Jb in two distinct wavenumber (~a) regions defined by the intersection point between the stability boundaries of the HSS and HRB modes. Based on Jb,cr where the temporal growth rate of the HSS and HRB are equal, a map of the unique critical boundary, which separates the effective regions of the HSS and HRB modes, is constructed and found to be dependent on Js, Jb, and ~a. The examinations of the subordinate eigenfunctions indicate that the shear instability is well developed in the HSS mode, in which the large vortex structures may prevail and suppress the formation of convective rolls; the shear instability in the HRB mode is either “partly developed” when Jb Jb,cr , thus only plays a secondary role to modify the dominant convective rolls, and as Jb increases, the eigenfunctions of the HSS mode exhibit different transitional behaviors in the two regions, signifying the “shear enhancement” and “shear sheltering” of the entrainment of buoyancy flux

Radiation recall pneumonitis induced by chemotherapy after thoracic radiotherapy for lung cancer

<p>Abstract</p> <p>Background</p> <p>Radiation recall pneumonitis (RRP) describes a rare reaction in previously irradiated area of pulmonary tissue after application of triggering agents. RRP remains loosely characterized and poorly understood since it has so far only been depicted in 8 cases in the literature. The objective of the study is to disclose the general characteristics of RRP induced by chemotherapy after thoracic irradiation for lung cancer, and to draw attention to the potential toxicity even after a long time interval from the previous irradiation.</p> <p>Methods</p> <p>Medical records were reviewed. RRP induced by chemotherapy was diagnosed by the history of chemotherapy after radiotherapy, clinical presentation and radiographic abnormalities including ground-glass opacity, attenuation, or consolidation changes within the radiation field, plus that radiographic examination of the thorax before showed no radiation pneumonitis. RRP was graded according to Common Terminology Criteria for Adverse Events version 3.0. The characteristics of the 12 RRP cases were analyzed.</p> <p>Results</p> <p>Twelve patients were diagnosed of RRP, of who 8 received taxanes. The median time interval between end of radiotherapy and RRP, between end of radiotherapy and beginning of chemotherapy, and between beginning of chemotherapy and RRP was 95 days, 42 days and 47 days, respectively. Marked symptomatic and radiographic improvement was observed in the 12 patients after withdrawal of chemotherapy and application of systemic corticosteroids. Seven patients were rechallenged with chemotherapy, of whom four with the same kind of agents, and showed no recurrence with steroid cover.</p> <p>Conclusions</p> <p>Doctors should pay attention to RRP even after a long time from the previous radiotherapy or after several cycles of consolidation chemotherapy. Taxanes are likely to be associated with radiation recall more frequently. Withdrawal of causative agent and application of steroids are the treatment of choice. Patients may be rechallenged safely with steroid cover and careful observation, which needs to be validated.</p

PHE1-based IgG-like antibody platform provides a novel strategy for enhanced T-cell immunotherapy

IntroductionBispecific antibodies (BsAbs) can simultaneously target two epitopes of different antigenic targets, bringing possibilities for diversity in antibody drug design and are promising tools for the treatment of cancers and other diseases. T-cell engaging bsAb is an important application of the bispecific antibody, which could promote T cell-mediated tumor cell killing by targeting tumor-associated antigen (TAA) and CD3 at the same time.MethodsThis study comprised antibodies purification, Elisa assay for antigen binding, cytotoxicity assays, T cell activation by flow cytometry in vitro and xenogenic tumor model in vivo.ResultsWe present a novel bsAb platform named PHE-Ig technique to promote cognate heavy chain (HC)-light chain (LC) pairing by replacing the CH1/CL regions of different monoclonal antibodies (mAbs) with the natural A and B chains of PHE1 fragment of Integrin β2 based on the knob-in-hole (KIH) technology. We had also verified that PHE-Ig technology can be effectively used as a platform to synthesize different desired bsAbs for T-cell immunotherapy. Especially, BCMA×CD3 PHE-Ig bsAbs exhibited robust anti-multiple myeloma (MM) activity in vitro and in vivo.DiscussionMoreover, PHE1 domain was further shortened with D14G and R41S mutations, named PHE-S, and the PHE-S-based BCMA×CD3 bsAbs also showed anti BCMA+ tumor effect in vitro and in vivo, bringing more possibilities for the development and optimization of different bsAbs. To sum up, PHE1-based IgG-like antibody platform for bsAb construction provides a novel strategy for enhanced T-cell immunotherapy

The expansion of autologous adipose-derived stem cells in vitro for the functional reconstruction of nasal mucosal tissue

BACKGROUND: I t is established that adipose-derived stem cells (ADSCs) produce and secrete cytokines/growth factors that antagonize mucosal injury. However, the exact molecular basis underlying the treatment effects exerted by ADSCs is ill understood, and whether ADSCs cooperate with adipose tissue particles to improve mucosal function in patients with empty nose syndrome (ENS) has not been explored. We investigated the impact of ADSCs on nasal mucosa, the associated mechanisms, and their use in the treatment of patients with ENS. RESULTS: The nasal endoscope and mucociliary clearance assessments were significantly improved (P < 0.05) in patients with (n = 28) and without (n = 2) a rudimentary turbinate that received ADSCs combined with fat granules transplantation. Patients experienced a significant improvement in nasal obstruction and nasal mucociliary clearance after nasal turbinate angioplasty (P < 0.05). H&E staining, Masson’s staining, and AB-PAS staining confirmed that inflammation was significantly reduced, collagenous fibers became aligned, fewer deposits were observed, and the mucosal proteins generated from caliciform cells increased following treatment. After a 14-day incubation period, ADSCs developed a polygonal cobblestone shape characteristic of human epithelial cells. Furthermore, immunohistochemical analysis revealed the presence of epithelial markers such as cytokeratin-7, and cytokeratin-19. Western blot analysis showed the presence of specific epithelial cell markers including cytokeratin-7, cytokeratin-14 and cytokeratin-19 in these epithelial like cells (ELC); these markers had low expression levels of ADSCs. CONCLUSIONS: The reconstruction of mucosal function by nasal turbinate angioplasty combined with ADSCs and autologous adipose tissue particle transplantation significantly improved the symptoms of patients with ENS. This is a new procedure that will improve mucosal restoration treatment options in patients with ENS. Furthermore, we undertook preliminary explorations of the underlying mechanisms involved, and found that transplantation of ADSCs could induce epithelial cells to improve mucosa function in patients with ENS in the micro-environment of injection areas

The role of PALLD-STAT3 interaction in megakaryocyte differentiation and thrombocytopenia treatment

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction