Optimal Treatment of Tumor in Upper Human Respiratory Tract Using Microaerosols.

Lung cancer is a frequently diagnosed respiratory disease caused by particulate matter in the environment, especially among older individuals. For its effective treatment, a promising approach involves administering drug particles through the inhalation route. Multiple studies have investigated the flow behavior of inhaled particles in the respiratory airways of healthy patients. However, the existing literature lacks studies on the precise understanding of the transportation and deposition (TD) of inhaled particles through age-specific, unhealthy respiratory tracts containing a tumor, which can potentially optimize lung cancer treatment. This study aims to investigate the TD of inhaled drug particles within a tumorous, age-specific human respiratory tract. The computational model reports that drug particles within the size range of 5-10 µm are inclined to deposit more on the tumor located in the upper airways of a 70-year-old lung. Conversely, for individuals aged 50 and 60 years, an optimal particle size range for achieving the highest degree of particle deposition onto upper airway tumor falls within the 11-20 µm range. Flow disturbances are found to be at a maximum in the airway downstream of the tumor. Additionally, the impact of varying inhalation flow rates on particle TD is examined. The obtained patterns of airflow distribution and deposition efficiency on the tumor wall for different ages and tumor locations in the upper tracheobronchial airways would be beneficial for developing an efficient and targeted drug delivery system.

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction.

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.

Bi-directional neuro-immune dysfunction after chronic experimental brain injury.

BACKGROUND: It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. METHODS: To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests. RESULTS: TBI induced chronic alterations in the transcriptome of BM lineage-c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain. CONCLUSIONS: TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.

The brain-bone marrow axis and its implications for chronic traumatic brain injury.

Traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function which contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham congenic donor mice into otherwise healthy, age-matched, irradiated hosts. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI showed that longer reconstitution periods were associated with increased microgliosis and leukocyte infiltration. Thus, TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in innate immunity and neurological function, as well as altered sensitivity to subsequent brain injury.

Highly Permeable Sulfonated Polydopamine Integrated MXene Membranes for Efficient Surfactant-Stabilized Oil-in-Water Separation.

MXene is an incredibly promising two-dimensional material with immense potential to serve as a high-performing separating or barrier layer to develop advanced membranes. Despite the significant progress made in MXene membranes, two major challenges still exist: (i) effectively stacking MXene nanosheets into defect-free membranes and (ii) the high fouling tendency of MXene-based membranes. To address these issues, we employed sulfonated polydopamine (SPD), which simultaneously serves as a binding agent to promote the compact assembling of Ti3C2Tx MXenes (MX) nanosheets and improves the antifouling properties of the resulting sulfonated polydopamine-functionalized MX (SPDMX) membranes. The SPDMX membrane was tested for challenging surfactant-stabilized oil-in-water separation with an impressive efficiency of 98%. Moreover, an ultrahigh permeability of 1620 LMH/bar was also achieved. The sulfonation of PD helps in improving the antifouling characteristics of SPDMX by developing a strong hydration layer and enhancing the oleophobicity of the membrane. The underwater SPDMX membrane appeared superoleophobic with an oil contact angle of 153°, whereas the ceramic membrane exhibited an oil contact angle of 137°. The SPDMX membranes showed an improved flux recovery (31%) compared to the nonsulfonated counterpart. This work highlights the appropriate functionalization of MXene as a promising approach to developing MXene membranes with high permeation flux and better antifouling characteristics for oily wastewater treatment.

Seismic isolation retrofitting solution for an existing steel cable-stayed bridge.

This paper investigated the seismic retrofitting of an existing cable-stayed bridge through the use of a seismic isolation system. The bridge is situated in a high seismic zone. During the Saguenay earthquake 1988, one of the anchorage plates of the bridge supports failed. Herein, several configurations of seismic isolation system were considered to identify an appropriate solution for the seismic retrofitting of the bridge in both the longitudinal and transverse directions. A three-dimensional model of the bridge was created, and its seismic behavior studied through nonlinear dynamic time-history analysis. The comparative performance study among the five retrofitting configurations showed that the partial seismic isolation of the bridge led to an enhancement of the seismic response of the bridge in one direction only. However, the overall seismic response of the cable-stayed bridge substantially improved in the longitudinal and transverse directions in cases where the isolation systems were utilized between the supports and the deck-tower connection of the bridge.

Favorable outcome after choroidal drainage for postoperative kissing suprachoroidal hemorrhage following trabeculectomy in a high myopic vitrectomised eye.

A 39-year-old lady with past history of vitreoretinal surgery for retinal detachment and cataract surgery with Intraocular lens implantation was diagnosed as uncontrolled glaucoma. She had high myopia. She underwent Trabeculectomy and following which she presented with massive suprachoroidal hemorrhage in the first postoperative day with severe loss of vision. This case depicts the risk of suprachoroidal hemorrhage in a high myopic vitrectomised eye following glaucoma filtration surgery. It also demonstrates a favorable outcome following intervention for postoperative Suprachoroidal hemorrhage. At present, there is no evidence in literature of such event in a high myopic Vitrectomised eye following Trabeculectomy.