Zonal demand-controlled ventilation strategy to minimize infection probability and energy consumption: A coordinated control based on occupant detection.

Due to the outbreak of COVID-19, an increased risk of airborne transmission has been experienced in buildings, particularly in confined public places. The need for ventilation as a means of infection prevention has become more pronounced given that some basic precautions (like wearing masks) are no longer mandatory. However, ventilating the space as a whole (e.g., using a unified ventilation rate) may lead to situations where there is either insufficient or excessive ventilation in localized areas, potentially resulting in localized virus accumulation or large energy consumption. It is of urgent need to investigate real-time control of ventilation systems based on local demands of the occupants to strike a balance between infection risk and energy saving. In this work, a zonal demand-controlled ventilation (ZDCV) strategy was proposed to optimize the ventilation rates in sub-zones. A camera-based occupant detection method was developed to detect occupants (with eight possible locations in sub-zones denoted as 'A' to 'H'). Linear ventilation model (LVM), dimension reduction, and artificial neural network (ANN) were integrated for rapid prediction of pollutant concentrations in sub-zones with the identified occupants and ventilation rates as inputs. Coordinated ventilation effects between sub-zones were optimized to improve infection prevention and energy savings. Results showed that rapid prediction models achieved an average prediction error of 6 ppm for CO2 concentration fields compared with the simulation under different occupant scenarios (i.e., occupant locations at ABH, ABCFH, and ABCDEFH). ZDCV largely reduced the infection risk to 2.8% while improved energy-saving efficiency by 34% compared with the system using constant ventilation rate. This work can contribute to the development of building environmental control systems in terms of pollutant removal, infection prevention, and energy sustainability.

Bone marrow stromal cells-derived exosomes reduce neurological damage in traumatic brain injury through the miR-124-3p/p38 MAPK/GLT-1 axis.

BACKGROUND: Mounting evidence indicates that stem cell-derived exosomal miRNAs have therapeutic effects on traumatic brain injury (TBI). This research is focused on exploring the molecular processes of miR-124-3p obtained from bone marrow stromal cells-derived exosomes (BMSCs-Exos) in attenuating posttraumatic glutamate-mediated excitotoxicity. METHODS: We created a TBI rat model and analyzed the expression profile of miRNA through miRNA microarray. The miR-124-3p and p38 MAPK levels were analyzed utilizing RT-qPCR and western blotting. Dual-luciferase reporter (DLR) assay showed the targeting relationship between miR-124-3p and p38 MAPK. We subsequently conducted a TUNEL assay and flow cytometry to evaluate the neuronal apoptotic rate in an in vitro glutamate-mediated excitotoxicity model treated with BMSCs-Exos enriched with miR-124-3p (BMSCs-ExosmiR-124-3p). Moreover, the levels of p38 MAPK and glutamate transporter-1 (GLT-1) were measured by western blotting. Furthermore, BMSCs-ExosmiR-124-3p were administered to the TBI rats, and their neuroprotective effects were observed using western blotting, immunohistochemistry, histological staining, magnetic resonance imaging (MRI), and Morris water maze (MWM). RESULTS: The results revealed that the brains of TBI rats exhibited lowered miR-124-3p and enhanced p38 MAPK levels. DLR assay demonstrated miR-124-3p's role in targeting p38 MAPK and negatively regulating its expression. In vitro and in vivo studies confirmed that BMSCs-ExosmiR-124-3p attenuated glutamate-mediated excitotoxicity by downregulating p38 MAPK and upregulating GLT-1 expressions via transferring exosomal miR-124-3p. Moreover, histopathological evaluation and MRI results showed that BMSCs-ExosmiR-124-3p remarkably alleviated neuronal cell death and minimized the lesion volumes post-TBI. MWM outcomes illustrated that BMSCs-ExosmiR-124-3p treatment could substantially improve neurological function post-TBI. Furthermore, the effects of treatment with p38 MAPK inhibitor SB203580 were similar to BMSCs-ExosmiR-124-3p. CONCLUSION: Overall, the outcomes of the current report highlighted that BMSCs-ExosmiR-124-3p can lead to the upregulation of GLT-1 in TBI rat models by inhibiting the p38 MAPK signaling pathway, hence alleviating glutamate-mediated excitotoxicity and attenuating neurological damage post-TBI.

Identification of Prognostic and Tumor Microenvironment by Shelterin Complex-Related Signatures in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the oral cavity. Shelterin complex gene (SG) has an important role in regulating telomere structure and length. SG is considered promising as a novel prognostic marker for cancer and a potential target for tumor therapy. However, SGs have not been systematically studied in OSCC. We analyzed SGs based on public data from OSCC patients and showed that SGs are closely associated with the prognosis of OSCC patients. Two different subtypes of SGs were identified in the TCGA and GEO cohorts, and LASSO regression analysis was used to further construct an SGs-related prognostic model. Randomized cohorts and different clinical subgroups validated the model's accuracy. The assessment of clinical characteristics, tumor mutational burden (TMB), and tumor microenvironment (TME) between high- and low-risk scores groups showed lower TMB, more abundant immune cell infiltration, and better prognosis in the low-risk group. According to the IPS analysis, patients in the low-risk group were more responsive to immunotherapy. This study establishes a foundation for research on SG and confirms that risk scores can predict prognosis and guide clinical treatment in OSCC patients.

2-Methoxyestradiol combined with ascorbic acid facilitates the apoptosis of chronic myeloid leukemia cells via the microRNA-223/Fms-like tyrosine kinase 3/phosphatidylinositol-3 kinase/protein kinase B axis.

Chronic myeloid leukemia (CML) is a malignant myeloproliferative tumor. 2-Methoxyestradiol (2-ME) is an endogenous estrogen metabolite that shows efficacy in human malignancies. Ascorbic acid (AA) possesses antioxidant activity. This study explored the mechanism of 2-ME combined with AA in the apoptosis of CML cells. Firstly, human CML cell lines were treated with 2-ME and AA. The cell viability, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were detected. miR-223 expression in CML cells was detected. In addition, CML cells were transfected with miR-223 inhibitor. The binding relationship between miR-223 and FLT3 was verified. Subsequently, the FLT3 was overexpressed or silenced for the function rescue experiment to confirm the role of FLT3 in CML cell apoptosis. The expression levels of key factors of the PI3K/AKT pathway were detected. Finally, xenograft nude mouse models were established for in vivo verification. 2-ME + AA treatment inhibited CML cell viability and promoted apoptosis, elevated ROS content, and reduced MMP. 2-ME + AA treatment promoted miR-223 expression in CML cells. miR-223 targeted FLT3. Moreover, miR-223 inhibitor or FLT3 overexpression partially annulled the effect of 2-ME + AA on CML cells. 2-ME + AA inhibited the PI3K/AKT pathway via the miR-223/FLT3 axis. Furthermore, 2-ME + AA suppressed CML xenograft growth in mice. Collectively, 2-ME + AA promoted miR-223 expression and suppressed FLT3 and the PI3K/AKT pathway, thereby facilitating the apoptosis of CML cells and inhibiting CML xenograft growth in mice.

Mucormycosis-induced upper gastrointestinal ulcer perforation in immunocompetent patients: a report of two cases.

BACKGROUND: Gastrointestinal mucormycosis (GIM) is a rare, opportunistic fungal infection with poor prognosis. Clinically, it is difficult to diagnose GIM owing to its nonspecific clinical symptoms and poor suspicion. The estimated incidence of GIM is inaccurate, and most cases are diagnosed accidentally during surgery or upon postmortem examination. GIM usually occurs in patients with immune deficiencies or diabetes. Here, we report two cases of immunocompetent young patients with GIM who had good prognosis after treatment. Compared to other case reports on GIM, our cases had unusual infection sites and no obvious predisposing factors, which make it important to highlight these cases. CASE PRESENTATION: The first case was that of a 16-year-old immunocompetent boy who was admitted with gastrointestinal bleeding and perforation due to a gastric ulcer. Strategies used to arrest bleeding during emergency gastroscopy were unsuccessful. An adhesive mass was then discovered through laparoscopy. The patient underwent type II gastric resection. Pathological examination of the mass revealed bacterial infection and GIM. The second case was of a 33-year-old immunocompetent woman with a recent history of a lower leg sprain. The patient subsequently became critically ill and required ventilatory support. After hemodynamic stabilization and extubation, she presented with hematemesis due to exfoliation and necrosis of the stomach wall. The patient underwent total gastrectomy plus jejunostomy. The pathology results revealed severe bacterial infection and fungal infection that was confirmed as GIM. The patient fully recovered after receiving anti-infective and antifungal treatments. CONCLUSIONS: Neither patient was immunosuppressed, and both patients presented with gastrointestinal bleeding. GIM was confirmed via pathological examination. GIM is not limited to immunocompromised patients, and its diagnosis mainly relies on pathological examination. Early diagnosis, timely surgical treatment, and early administration of systemic drug treatment are fundamental to improving its prognosis.