Despite the critical role of microRNA in inflammatory response, little is known about its function in inflammation-induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). To investigate the potential role of microRNA146a (miR-146a) in ALI, we used lipopolysaccharide (LPS)-induced ALI rat model. Our data revealed that LPS-induced lung injury in rats resulted in significant upregulation of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, and miR-146a expression. LPS treatment also leads to higher expression of miR-146a as well as increase in secretion of TNF-α, IL-6, and IL-1β in alveolar macrophage (AM) NR8383 cells in a time-dependent manner. Manipulation with miR146a mimic significantly suppressed LPS-mediated TNF-α, IL-6, and IL-1β induction in NR8383 cells by repressing expression of IRAK-1 and TRAF-6. These data clearly indicate that the upregulation of miR146a suppresses inflammatory mediators in LPS induced-ALI model. Therefore, miR-146a may be therapeutically targeted as a mean to repress inflammatory response following ALI.

Background The emerging infectious disease, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a serious threat in China and worldwide. Challenged by this serious situation, China has taken many measures to contain its transmission. This study aims to systematically review and record these special and effective practices, in hope of benefiting for fighting against the ongoing worldwide pandemic. Methods The measures taken by the governments was tracked and sorted on a daily basis from the websites of governmental authorities (e.g. National Health Commission of the People’s Republic of China). And the measures were reviewed and summarized by categorizations, figures and tables, showing an ever-changing process of combating with an emerging infectious disease. The population shift levels, daily local new diagnosed cases, daily mortality and daily local new cured cases were used for measuring the effect of the measures. Results The practices could be categorized into active case surveillance, rapid case diagnosis and management, strict follow-up and quarantine of persons with close contacts, and issuance of guidance to help the public understand and adhere to control measures, plus prompt and effective high-level policy decision, complete activation of the public health system, and full involvement of the society. Along with the measures, the population shift levels, daily local new diagnosed cases, and mortality were decreased, and the daily local new cured cases were increased in China. Conclusions China’s practices are effective in controlling transmission of SARS-CoV-2. Considering newly occurred situations (e.g. imported cases, work resumption), the control measures may be adjusted.

Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early stage resectable NSCLC remains unclear. Here, we studied PD-L1 expression and tumor infiltrating lymphocytes (TILs) in surgically resectable NSCLC and correlate the finding with clinicopathological features and patient outcomes. Total of 170 archival samples of resectable NSCLC were probed for PD-L1 expression using the clone 22C3 pharmDx kit. The PD-L1 expression was determined by the Tumor Proportion Score (TPS) and classified into TPS <1%, TPS 1 to 49% and TPS ≥50%. The scoring of TILs was from hematoxylin & eosin stained tissue sections using a system for standardized evaluation of TILs in breast cancer. PD-L1 expression was compared with clinical pathological characteristics and survival outcome. Expression of PD-L1 scores of TPS ≥50%, TPS 1 to 49% and TPS <1% were observed in 10.6%, 24.7% and 64.7% of the 170 archival samples, respectively. Positive PD-L1 expression was significantly higher in patients with squamous carcinoma, in those with higher TNM stage and with the presence of TILs. Neither the PD-L1 expression, TIL status, nor their combination was an independent prognosis biomarker of survival when the data was subjected to either univariate or multivariate analysis. The incidence of PDL1 expression appears to be lower in patient with early stage resectable lung cancer. PD-L1 expression and TILs are not prognostic indicators of survival outcome in this population.

Background and Purpose To demonstrate that gradual and continuous WM change and the associated cognitive decline in type 2 diabetes mellitus (T2DM) patients can be captured by DTI parameters and the DTI parameters can be used to complement neuropsychological test scores in identifying T2DM patients with and without mild cognitive impairment (MCI). Materials and Methods Forty-two T2DM patients, divided into a group with MCI (DM-MCI; n = 20) and a group with normal cognition (DM-NC; n = 22) based on cognitive assessments, were enrolled together with age-, gender-, and education-matched healthy controls (HC; n = 26). DTI was performed at 3 Tesla, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (λ23) among the groups. A receiver operating characteristic (ROC) analysis was used to assess the performance of using DTI parameters for separating the two T2DM groups. Results The whole-brain TBSS analysis revealed that 7.3% and 24.9% of the WM exhibited decreased FA and increased MD (p < 0.05), respectively, between the DM-MCI and the DM-NC groups, while considerably larger WM regions showed FA (36.6%) and MD (58.8%) changes between the DM-MCI and the HC groups. These changes were caused primarily by an elevated radial diffusivity observed in the DM-MCI patients. Radial diffusivity also exhibited subtle but statistically significant changes between the DM-NC and the HC group. Analyses on individual fiber tracts showed pronounced FA reduction and MD elevation in regions related to cognitive functions. The ROC analysis on the right cingulum (hippocampus) showed that FA produced a larger area under the curve (AUC = 0.832) than MD (0.753) for separating MCI from normal cognition among T2DM patients. When FA was combined with MD, the AUC was further improved to 0.857. Conclusion This study demonstrates that the DTI parameters can show a significant difference between the T2DM patients with and without MCI, suggesting their potential use as an imaging marker for detecting cognitive decline in T2DM patients. More importantly, this study also suggests that the DTI parameters may capture gradual and continuous WM changes that can be associated with early stages of cognitive decline in T2DM patients before they can be diagnosed clinically using the conventional neuropsychological tests.

Background: Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. Patients and methods: Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by nextgeneration sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. Results: The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0e11.2). Conclusions: The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.

PD-L1 expression in TMAs correlates moderately well with that in the corresponding surgical specimens, indicating that evaluating PD-L1 expression in diagnostic biopsy specimens could be misleading in defining sensitivity to pembrolizumab treatment yet may be reliable as a way to exclude patients with a PD-L1 TPS less than 50% from first-line pembrolizumab treatment.

Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM) has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues ) that are first imaged (fresh, unfixed, and unstained) with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management.

Roots are widely acknowledged to be major contributors to ecosystem nutrient cycles. However, live roots may have very different effects than dead roots, the quality of the soil surrounding the roots may itself affect the influence of the roots, and the nature of the soil profile may modify all of these interactions. We have used experimental, field-based mesocosms to dissect the differing effects of live and dead roots in organic and mineral horizons of spodosolic forest soils. Mesocosms were constructed in a simple ecosystem dominated by pitch pine (Pinus rigida Mill.) and blueberry (Vaccinium corymbosum L.) in the New Jersey Pinelands. They contained 5 cm deep surface horizons of either organic matter or an inert substitute (vermiculite), placed above 10 cm of mineral material from the E horizon, with defined amounts of live or dead roots added. Sampling was conducted over a 2-yr period. In mineral soil, live roots stimulated ammonification rates but had little effect on extractable N, and the stimulation occurred only if an organic surface horizon was present. In contrast, live roots in organic material reduced both ammonification rates and extractable N. Dead roots increased extractable N in the mineral material, but not the organic material. The presence or absence of an organic horizon had a dominating effect on all aspects of nitrogen dynamics in the mineral soil; not only extractable inorganic N, but also transformation rates, were higher in soils under organic matter. The results showed that the effects of roots on soil nutrients depended on (1) the ratio of live to dead root biomass, (2) the quality of the soil material in which the roots occurred, and (3) the structure of the soil profile. These findings necessitate a revision of the concept of ''rhizosphere effect'' in forest soils.