NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment.

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

1-Naphthaleneacetic Acid Improved the In Vitro Cell Culturing by Inhibiting Apoptosis.

In vitro cell culturing witnessed its applications in scientific research and industrial activities. Attempts to shorten the doubling time of cultured cells have never ceased. In plants, auxin is applied to promote plant growth, the synthetic derivative 1-Naphthaleneacetic acid (NAA) is a good example. Despite the auxin's naturally occurring receptors are not present in mammalian cells, studies suggested they may affect cell culturing. Yet the effects and mechanisms are still unclear. Here, an up to 2-fold increase in the yield of in vitro cultured human cells is observed. Different types of human cell lines and primary cells are tested and found that NAA is effective in all the cells tested. The PI staining followed by FACS suggested that NAA do not affect the cell cycling. Apoptosis-specific dye staining analysis implicated that NAA rescued cell death. Further bulk RNA sequencing is done and it is identified that the lipid metabolism-engaging and anti-apoptosis gene, ANGPTL4, is enhanced in expression upon NAA treatment. Studies on ANGPTL4 knockout cells indicated that ANGPTL4 is required for NAA-mediated response. Thus, the data identified a beneficial role of NAA in human cell culturing and highlighted its potency in in vitro cell culturing.

Numerical studies of indoor particulate and gaseous micropollutant transport and its impact on human health in densely-occupied spaces.

Micropollutants (MPs) have increasingly become a matter of concern owing to potential health risks associated with human inhalation exposure, particularly in densely-occupied indoor environments. This study employed numerical simulations in a traditional built indoor workspace and a public transport cabin to elucidate the transport dynamics and health impacts of particulate and gaseous type of indoor MPs on varying groups of occupants. The risk of infection from pathogen-bearing MPs was evaluated in the workspace using the integrated Eulerian-Lagrangian and modified Wells-Riley model. In the cabin environment, the health impact of inhaled TVOC within the human nasal system was assessed via the integrated nasal-involved manikin model and cancer/non-cancer risk model. The results demonstrated that when ventilation layout was in favour of restricting particulate MPs spread, considerably high health risks (up to 17.22% infection possibility) were generally found in near-fields of emission source (< 2.25 m). Conversely, if the ventilated flow interacts robustly with emission source, every occupant has a minimum 5% infection risk. Incorporating the nasal cavity in the human model offers a nuanced understanding of gaseous MP distributions post-inhalation. Notably, the olfactory and sinus regions displayed heightened vulnerability to TVOC exposure, with a 62.5%-108% concentration increase compared to other nasal areas. Cancer risk assessment plausibly explained the rising occurrence of brain and central nervous system cancer for aircrew members. Non-cancer risk was found acceptable. This study was expected to advance the understanding of environmental pollution and the health risks tied to indoor MPs in densely-populated environments.

Semi-surrogate modelling of droplets evaporation process via XGBoost integrated CFD simulations.

The applications of machine learning (ML) based approach are emerging as possible tools to accelerate CFD simulations. This study proposed a semi-surrogate model for CFD with integration of the cutting-edge ML algorithm, eXtreme Gradient Boosting (XGB), which enlightened a possible pathway to effectively and efficiently solve and predict those costly but highly repetitive fluid dynamics-related problems. Droplet evaporation, a complex but essential phenomenon in respiratory droplets transport, was studied as the practical case using the proposed model. Droplets evaporation and dynamic size distributions were firstly tracked under various combinations of indoor humidity and temperature using traditional Eulerian-Lagrangian CFD framework, followed by generating several datasets for XGB training. The trained XGB was then used to interpret the evaporated droplets size over time under new combinations of indoor conditions. Outcomes revealed that well-trained XGB-base semi-surrogate model was capable of interpreting complex non-linear relationships between droplets dynamic parameters (diameter and time) and indoor parameters (humidity and temperature). For each specific parameter, the predictive error of well-trained XGB could retain below 5 % and its prediction speed was found nearly 1 million times faster than that of new CFD simulations. Successful applications of XGB in conjunction with CFD demonstrated its great potential on providing rapid and more efficient predictions of complex, costly and repetitive fluid dynamics-related phenomenons (e.g. droplets evaporation). Also, the XGB predicted droplets evaporation data from this study could be further applied as initial conditions into new simulations via the User-defined function (UDF).

A spatiotemporal assessment of occupants' infection risks in a multi-occupants space using modified Wells-Riley model.

Escalating demands of assessing airborne disease infection risks had been awakened from ongoing pandemics. An inhalation index linked to biomedical characteristics of pathogens (e.g. TCID 50 for coronavirus delta variant) was proposed to quantify human uptake dose. A modified Wells-Riley risk-assessment framework was then developed with enhanced capability of integrating biological and spatiotemporal features of infectious pathogens into assessment. The instantaneous transport characteristics of pathogens were traced by Eulerian-Lagrangian method. Droplets released via speaking and coughing in a conference room with three ventilation strategies were studied to assess occupants' infection risks using this framework. Outcomes revealed that speaking droplets could travel with less distance (0.5 m) than coughing droplets (1 m) due to the frequent interaction between speaking flow and thermal plume. Quantified analysis of inhalation index revealed a higher inhalation possibility of droplets with nuclei size smaller than 5 µ m , and this cut-off size was found sensitive to ventilation. With only 60-second exposure, occupants in the near-field of host started to have considerable infection risks (approximately 20%). This risk was found minimising over distance exponentially. This modified framework demonstrated the systematic analysis of airborne transmission, from quantifying particle inhalation possibility, targeting specific disease's TCID 50 , to ultimate evaluation of infection risks.

Epigenetics alternation in lung fibrosis and lung cancer.

Respiratory disease including interstitial lung diseases (ILDs) and lung cancer is a group of devastating diseases that linked with increased morbidity and healthcare burden. However, respiratory diseases cannot be fully explained by the alternation of genetic information. Genetic studies described that epigenetic mechanisms also participate to transmit genetic information. Recently, many studies demonstrated the role of altered epigenetic modification in the pathogenesis of lung cancer and pulmonary fibrosis. Due to lacking effective medication, the underlying pathophysiological processes and causal relationships of lung diseases with epigenetic mechanisms still need to be better understood. Our present review provided a systematic revision of current knowledge concerning diverse epigenetic aberrations in major lung diseases, with special emphasis on DNA methylation, histone modifications, lncRNAs profiles, telomere patterns, as well as chromatin-remodelling complexes. We believed that a new target therapy for lung disease based on findings of the involved epigenetic pathway is a promising future direction.

The Relation between Immunological Features and the Positive SARS-CoV-2 Nucleic Acid in Patients with Nonsevere COVID⁃19.

Objective: The novel coronavirus nucleic acid results are the core indicators of illness monitoring. This study aimed to evaluate the relationship between immunological features and positive SARS-CoV-2 nucleic acid by analyzing the clinical and immunological features in nonsevere COVID-19 cases. Methods: Data from nonsevere COVID-19 patients admitted to Haihe Hospital from May 2020 to June 2021 were retrospectively reviewed and analyzed. Results: (1) A total of 122 cases were reviewed in the present study, including 38 mild and 84 moderate cases. The average age of mild cases was significantly different from moderate cases (P < 0.001). Eight patients complained of hyposmia and it was more frequent in mild cases (P < 0.001). The nucleic acid positive duration (NPD) of nonsevere novel coronavirus was 20.49 (confidence interval (CI) 17.50-3.49) days. (2) The levels of specific IgM and IgG for COVID-19 were higher in mild cases than in moderate cases (P=0.023 and P=0.047, respectively). (3) The correlation analysis with antibodies and T-cell subtypes showed that the lymphocyte (LYM) count, T cells, CD4+T cells, and CD8+T cells had a linear correlation with NPD. (4) Among the 93 patients monitored, 62 COVID-19 cases presented a progressive rise of specific IgM and IgG. The daily increase rates of IgM and IgG were 38.42% (CI 28.22-48.61%) and 24.90% (CI 0.23-29.58%), respectively. Conclusion: The levels and daily increase rates of specific IgM and IgG against the virus can vary between cases. The NPD presented a linear correlation with the LYM, T cells, CD4+T cells, and CD8+T cells. Hence, more attention should be paid to these indicators in clinical practice.

Analysis of occupants' exposure risk of cough-expelled droplets in the workspace with various mixing ventilation layouts.

This study numerically investigated the transport characteristics of the cough-expelled droplets and their corresponding exposure risk of each occupant under various mixing ventilation layouts. Transient simulations were conducted in a conference room, while pathogen-bearing droplets were released by a standing speaker. The results showed that droplet residues (< 40 µm) had a high potential to reach occupant's breathing zone, among which the number fraction of aerosol residues (< 10 µm) could be nearly doubled compared with that of the rest droplet residues in the breathing zone. Occupants' exposure risks were found very sensitive to the ventilation layouts. The strong ventilated flow could significantly promote droplet dispersions when those inlets were closely located to the infectious speaker, resulting in all occupants exposed to a considerable fraction of aerosols and droplets within a given exposure time of 300 s. The mixing ventilation layout did not have a consistent performance on restricting the pathogen spread and controlling the occupant's exposure risk in an enclosed workspace. Its performance could be highly sensitive to the location of the infectious agent. Centralized vent layouts could provide relatively more consistent performance on removing droplets, whilst some local airflow recirculation with locked droplets were noticed.

Chemical reagents modulate nucleic acid-activated toll-like receptors.

Nucleic acid-mediated interferon signaling plays a pivotal role in defense against microorganisms, especially during viral infection. Receptors sensing exogenous nucleic acid molecules are localized in the cytosol and endosomes. Cytosolic sensors, including cGAS, RIG-I, and MDA5, and endosome-anchored receptors are toll-like receptors (TLR3, TLR7, TLR8, and TLR9). These TLRs share the same domain architecture and have similar structures, facing the interior of endosomes so their binding to nucleic acids of invading pathogens via endocytosis is possible. The correct function of these receptors is crucial for cell homeostasis and effective response against pathogen invasion. A variety of endogenous mechanisms modulates their activities. Nevertheless, naturally occurring mutations lead to aberrant TLR-mediated interferon (IFN) signaling. Furthermore, certain pathogens require a more robust defense against control. Thus, manipulating these TLR activities has a profound impact. High-throughput virtual screening followed by experimental validation led to the discovery of numerous chemicals that can change these TLR-mediated IFN signaling activities. Many of them are unique in selectivity, while others regulate more than one TLR due to commonalities in these receptors. We summarized these nucleic acid-sensing TLR-mediated IFN signaling pathways and the corresponding chemicals activating or deactivating their signaling.

High-resolution computed tomography (HRCT) analysis in anti-synthase antibody syndrome with organizing pneumonia.

OBJECTIVE: The organizing pneumonia (OP) pattern is the second most common finding in anti-synthase antibody syndrome (ASS), and nonspecific interstitial pneumonia (NSIP) is the most common finding. This study analysed the OP score changes by semiquantitative and quantitative analysis methods and the correlation between the high-resolution computed tomography (HRCT) indexes and the pulmonary function test parameters (PFTs) in ASS patients. METHODS: Data from ASS-OP patients admitted to the respiratory department of Ping Jin Hospital from October 2014 to June 2020 were retrospectively reviewed and analysed. RESULTS: Fourteen ASS-OP patients were recruited for this study. (1) In method-1, the consolidation (CO) score and the mean lung attenuation (MA) of poorly aerated and fibrosis lung fields (MAfibrosis) (r=0.56, P=0.04), the ground-glass opacity (GGO) score and the MA of non-aerated lung fields (MAnonaerated) (r=-0.64, P=0.01), and the CO plus the GGO (CG) score and the MAnonaerated (r=-0.59, P=0.03) of the lung fields had liner correlations. In method-2, the GGO score to the MAnonaerated (r=-0.58, P=0.03), and the CG (r=-0.68, P=0.01) score to the MAnonaerated had liner correlations. The FVC% (r=0.68, P=0.01) and FEV1% (r=0.64, P=0.01) to the MAfibrosis had good linear correlations. (2) Compared to the values before treatment, the CO pattern score, volume and weight percentages of the extracted whole lung volume with attenuation values of the nonaerated area (Vnonated%, Wnonaerated%), the volume of poorly aerated and fibrosis lung tissue (Vfibrosis%, Wfibrosis%), the weight percentages of normal aerated lung (Wnormal%), and the MAfibrosis exhibited significant differences during the 3-6 month follow-up period. CONCLUSION: The GGO and CO scored by the semiquantitative or quantitative analysis methods was similar. The HRCT quantitative analysis parameters showed a good correlation with the PFTs in ASS-OP patients, can provide an accurate OP pattern interpretation, and may be used as a monitoring and therapeutic indicator for ASS-OP patients.

Evaluation of cough-jet effects on the transport characteristics of respiratory-induced contaminants in airline passengers' local environments.

Urgent demands of assessing respiratory disease transmission in airliner cabins had awakened from the COVID-19 pandemics. This study numerically investigated the cough flow and its time-dependent jet-effects on the transport characteristics of respiratory-induced contaminants in passengers' local environments. Transient simulations were conducted in a three-row Boeing 737 cabin section, while respiratory contaminants (2 µm-1000 µm) were released by different passengers with and without coughing and were tracked by the Lagrangian approach. Outcomes revealed significant influences of cough-jets on passengers' local airflow field by breaking up the ascending passenger thermal plumes and inducing several local airflow recirculation in the front of passengers. Cough flow could be locked in the local environments (i.e. near and intermediate fields) of passengers. Results from comparative studies also revealed significant increases of residence times (up to 50%) and extended travel distances of contaminants up to 200 µm after considering cough flow, whereas contaminants travel displacements still remained similar. This was indicating more severe contaminate suspensions in passengers' local environments. The cough-jets was found having long and effective impacts on contaminants transport up to 4 s, which was 8 times longer than the duration of cough and contaminants release process (0.5 s). Also, comparing to the ventilated flow, cough flow had considerable impacts to a much wider size range of contaminants (up to 200 µm) due to its strong jet-effects.

Blood purification in two patients with clinically amyopathic dermatomyositis associated with interstitial lung disease with anti-melanoma differentiation-associated gene-5 antibody (MDA-5).

Patients of clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia (CADM-RFIP) with positive anti-MDA5 antibody usually presents rapid deterioration and traditional therapy such as cyclophosphamide combined with high-dose prednisone pulse therapy shows no clear benefit at whiles. However, blood purification combined with traditional therapy works according to the literature. We herein report two CADM-RFIP patients administered with DNA immunoadsorption combined with traditional therapy and then reviewed the literature of blood purification in CADM-RFIP patients at home and abroad to date. We emphasize blood purification such as DNA immunoadsorption could apply in the early stage of CADM-RFIP, which can decrease inflammation and allow us more time to control the condition better.

[A comparison study of diagnostic value between the old and revised guidelines in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To compare the strengths and limitations of the old and revised guidelines for the diagnosis in patients with idiopathic pulmonary fibrosis(IPF). METHODS: Patients who were admitted and diagnosed as interstitial lung diseases (ILDs) in our hospital from 2009 to 2014 were enrolled in our study.Eachpatient was reevaluated respectively according to the old and revised guidelines of IPF. RESULTS: A total of 553 cases were initially reviewed, among whom 355 cases were excluded for pulmonary fibrosis secondary to definite underlying diseases, 28 excluded due to high resolution computed tomography(HRCT) not done, 26 excluded because serum immunology examination was not available.The remaining 144 cases were finally enrolled in this study including 92 males and 52 females with median age 21-92 (68 ± 11) years old. Twenty five patients (17.4%, 25/144) met the diagnostic criteria of IPF by the old guideline.While by the revised guideline, 53 patients (36.8%, 53/144) were diagnosed as classical IPF, 29 patients(20.1%, 29/144) as probable cases, another 69 non-IPF patients accounting for 43.1% (62/144). The result revealed that there's a significant difference between the two guidelines in the diagnosis of IPF. CONCLUSIONS: The revised guideline favors an early diagnosis of IPF and simplifies the diagnostic process.However the possibility of over diagnosis or missed diagnosis by the revised guideline does exist.On the other hand, despite of the delayed diagnosis by the old guideline, it may reduce the misdiagnosis of IPF in some circumstance.

Nonspecific interstitial pneumonia overlaps organizing pneumonia in lung-dominant connective tissue disease.

Here, we reported two cases of nonspecific interstitial pneumonia overlap organizing pneumonia (NSIP/OP) with lung-dominant connective tissue disease (LD-ILD). The first case is a patient with hands of chapped skin, right-sided pleuritic chest discomfort, weakness, positive ANA and antibodies to Ro/SS-A (+++) and Ro-52 (++). In the second case, there were Reynaud's disease, and nucleolus-ANA increased (1:800). Chest high resolution CT scan in both cases showed ground-glass opacifications, predominantly in basal and subpleural region and the pathologic manifestation were correlated with NSIP/OP, which were previously discovered in Sjogren syndrome, PM/DM and other rheumatic diseases. The two cases of NSIP/OP with LD-CTD we reported expand disease spectrum of NSIP/OP pathological types in ILD. However, it is necessary to process large-scale studies.

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice.

The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics.

Relevance analysis of clinical and lung function parameters changing and prognosis of idiopathic pulmonary fibrosis.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia with unknown cause. We analyzed the changed rate of pulmonary function and arterial blood gas in IPF patients, and evaluated their influence of changed rate to IPF prognosis. METHODS: 81 patients with IPF were recruited successfully, they were followed-up at 6 and 12 months. Dyspnea score and respiratory assessment parameters including FVC, FEV1, TLC, SaO2, PA-aO2, and DLCO were evaluated at their 6 and 12 months follow-up. The changed value and changed rate of above parameters were calculated, and their treatment effects were divided into 3 subgroup: improved, stable and deteriorated group. Statistical analysis was performed between groups for survival and hazards regression analysis. RESULTS: 55 of 81 patients were follow-up at 12 months. Dyspnea score and its changed rate, the changed value of FEV1%, FVC%, TLC%, DLCO%, and PaO2, SaO2, PA-aO2 were prognosis effect factors in IPF patients in 6 and 12 months group. The survival analysis of dyspnea scores, FVC%, TLC%, DLCO%, PaO2, SaO2 and PA-aO2 at K-M were all statistical significant (P < 0.05) in improved, stable and deteriorated group. CONCLUSION: FVC% changed rate, dyspnea score changed rate and PaO2 changed rate were IPF patient prognosis associated factors in 6 months group; and FVC% changed rate, DLCO% changed rate and TLC% changed rate were prognosis associated factors for IPF patient in 12 months group.

Resonance phenomenon of the ATP motor as an ultrasensitive biosensor.

We designed a rotary biosensor as a damping effector, with the rotation of the F(0)F(1)-ATPase driven by Adenosine Triphosphate (ATP) synthesis being indicated by the fluorescence intensity and a damping effect force being induced by the binding of an RNA molecule to its probe on the rotary biosensor. We found that the damping effect could contribute to the resonance phenomenon and energy transfer process of our rotary biosensor in the liquid phase. This result indicates that the ability of the rotary motor to operate in the vibration harmonic mode depends on the environmental conditions and mechanism in that a few molecules of the rotary biosensor could induce all of the sensor molecules to fluoresce together. These findings contribute to the theory study of the ATPase motor and future development of biosensors for ultrasensitive detection.

[Screening of potential proteins from patients with idiopathic pulmonary fibrosis by using of surface enhanced laser desorption/ionization time of flight mass spectrum].

OBJECTIVE: To screen potential proteins in bronchoalveolar lavage fluid (BALF) and serum samples obtained from patients with idiopathic pulmonary fibrosis (IPF), for the purpose of discovering candidate biomarkers. METHODS: BALF and serum samples from 34 patients diagnosed IPF (IPF group) and 25 non-smoker healthy controls (control group) were collected. Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) was used to obtain protein fingerprints from BALF and serum samples. Biomarker Wizard and Biomarker Pattern were introduced in bioinformatics analysis. RESULTS: A total of 247 protein peaks were detected in BALF, and 13 peaks with statistical difference compared with control group. Among 13 detected protein peaks, 7 with mass/charge ratio (M/Z) values of 2240.57, 3459.32, 3501.78, 4146.50, 4516.51, 4615.88, 5651.26 were statistically up-regulated (all P < 0.01); and 6 peaks with M/Z values of 4989.91, 5043.68, 6968.76, 11 687.70, 11 782.10, 14 733.30 were significantly down-regulated (all P < 0.01). In addition, 142 protein peaks were differentially expressed in serum samples, and 9 peaks with statistical differences. Among them, 9 peaks with M/Z values of 3382.59, 3453.39, 4608.28, 5825.48, 8936.76, 9164.27, 11 525.30, 11 689.40 and 11 886.00 were significantly up-regulated (P < 0.05 or P < 0.01), compared with control group. CONCLUSIONS: The present work demonstrated that SELDI-TOF-MS technology be capable of detecting differentially expressed protein peaks in BALF and serum samples from IPF patients. Further investigations were guaranteed to elucidate their potential diagnostic value in clinical practice.