Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation.

BACKGROUND: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. METHODS: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. RESULTS: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-ß/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. CONCLUSION: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway.

BACKGROUND: Neutrophilic airway inflammation is a challenge in asthma management and is associated with poor patient prognosis. Mucin 1 (MUC1), which contains a cytoplasmic tail (MUC1-CT), has been found to mediate glucocorticoid sensitivity in asthma; however, its role in modulating neutrophilic airway inflammation in asthma remains unknown. METHODS: Human-induced sputum cells were collected from healthy participants (n = 12), patients with mild-to-moderate asthma (n = 34), and those with severe asthma (n = 18). In vitro human lung bronchial 1 epithelial cell line (BEAS-2B) was transfected with small interfering RNA against MUC1 (MUC1-siRNA) and then stimulated by lipopolysaccharide (LPS), where some cells were pretreated with a TLR4 inhibitor (TAK-242). In vivo mouse model of asthmatic neutrophil airway inflammation was induced by ovalbumin (OVA)/LPS. Some groups were intraperitoneally injected with MUC1-CT inhibitor (GO-203) and/or TAK-242 . RESULTS: The mRNA expression of MUC1 was downregulated in the induced sputum of patients with asthma and correlated with asthmatic neutrophilic airway inflammation. The mRNA expressions of TLR4, MyD88, nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3), caspase-1, interleukin (IL)-18, and IL-1ß in induced sputum cells of patients with asthma were upregulated and related to the mRNA expression of MUC1. LPS activated the TLR4 pathway and NLRP3-mediated pyroptosis in BEAS-2B cells in vitro, which were significantly aggravated after MUC1-siRNA transfection. Furthermore, MUCl-CT interacted with TLR4, and the interaction between TLR4 and MyD88 was significantly increased after MUCl-siRNA transfection. Moreover, TAK-242 ameliorated TLR4/MyD88/nuclear factor kappa B (NF-κB) pathway activation, NLRP3 inflammasome-mediated pyroptosis, and neutrophilic inflammation exacerbated by MUC1 downregulation. GO-203 exacerbated TLR4/MyD88/NF-κB pathway activation in vivo, and NLRP3 inflammasome-mediated pyroptosis reduced in a mouse model of asthmatic neutrophil airway inflammation induced by OVA/LPS; these pathological changes were partially alleviated after TAK-242 application. CONCLUSION: This study revealed that MUC1 downregulation plays an important role in asthmatic neutrophilic airway inflammation. MUC1-CT reduces NLRP3 inflammasome-mediated pyroptosis by inhibiting the activation of the TLR4/MyD88/NF-κB pathway, thereby attenuating neutrophil airway inflammation in patients with asthma.

Repurposed Tocilizumab in Patients with Severe COVID-19.

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25-0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11-0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

Clinical characteristics of COVID-19 patients with asthma in Wuhan, China: a retrospective cohort study.

OBJECTIVE: Although it is reported that patients with coronavirus disease 2019 (COVID-19) disease who have comorbidities are at higher risk to suffer adverse clinical outcomes, there are inadequate evidence to clarify the association between COVID-19 and asthma. On this ground, this study aims to systematically analyze the clinical characteristics of COVID-19 patients with asthma. METHODS: In this single-center, retrospective and observational cohort study, 21 COVID-19 patients with asthma and 100 non-asthma COVID-19 patients were statistically matched by propensity score based on age, sex and comorbidities. Meanwhile, a collection and comparison concerning demographic indicators, clinical and laboratory examinations, treatments and outcomes were conducted between two groups to specify their differences. RESULTS: Statistically, the COVID-19 patients with asthma had a higher proportion of ICU admission (14.3% [3/21] vs. 2.1% [2/96] p = 0.040) than those who do not have. On top this, a higher level of inflammatory responses, such as interleukin 6, interleukin 8, procalcitonin, leukocytes, neutrophils and CD4+ T cells was presented in asthma patients. Moreover, the increase of organ damage indices like D-dimer, lactate dehydrogenase and high-sensitivity cardiac troponin I, were more pronounced in COVID-19 patients with asthma. CONCLUSIONS: Exacerbated inflammatory responses and multiple organ damages were triggered in COVID-19 patients with asthma, which highlights more intensive surveillance and supportive treatment.

Transarterial embolization with hepatectomy for ruptured hepatocellular carcinoma: a meta-analysis.

PURPOSE: To compare the clinical effectiveness between transarterial embolization (TAE) with staged hepatectomy (SH) and emergency hepatectomy (EH) for ruptured hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Pubmed, Embase, and Cochrane Library databases were screened for eligible publications from the inception of the databases till February 2021. RESULTS: This meta-analysis included seven studies comprising 162 patients who underwent TAE with SH and 266 patients who underwent EH. The pooled intraoperative blood loss was less in the TAE with SH cohort, as compared to the EH cohort without significant difference (p = .20). The pooled blood transfer rate (p<.00001), blood transfer volume (p = .002), and 30-day patient death (p = .04) were all markedly reduced in the TAE with SH cohort versus the EH cohort. No significant differences in surgery duration (p = .27), hospital stay period (p = .81), complication rate (p = 0.92), disease-free survival (DFS) (p = .79), and overall survival (OS) (p = 0.28) were found between the two groups. CONCLUSIONS: Compared with EH for ruptured HCC, TAE with SH could effectively decrease intraoperative blood loss and 30-day mortality. However, the long-term DFS and OS might not be beneficial to preoperative TAE.

Dynamical Behavior of SEIR-SVS Epidemic Models with Nonlinear Incidence and Vaccination.

For some infectious diseases such as mumps, HBV, there is evidence showing that vaccinated individuals always lose their immunity at different rates depending on the inoculation time. In this paper, we propose an age-structured epidemic model using a step function to describe the rate at which vaccinated individuals lose immunity and reduce the age-structured epidemic model to the delay differential model. For the age-structured model, we consider the positivity, boundedness, and compactness of the semiflow and study global stability of equilibria by constructing appropriate Lyapunov functionals. Moreover, for the reduced delay differential equation model, we study the existence of the endemic equilibrium and prove the global stability of equilibria. Finally, some numerical simulations are provided to support our theoretical results and a brief discussion is given.

Isolated pulmonary mucormycosis in an immunocompetent patient: a case report and systematic review of the literature.

BACKGROUND: Pulmonary mucormycosis caused by Mucorales is a highly lethal invasive fungal infection usually found in immunocompromised patients. Isolated pulmonary mucormycosis in immunocompetent patients is very rare. Here, we present a case of a 32-year-old male who developed pulmonary mucormycosis without any known immunodeficiency. CASE PRESENTATION: The patient presented to our hospital because of cough and chest pain along with blood in the sputum. He was first treated for community-acquired pneumonia until bronchoalveolar lavage fluid culture confirmed the growth of Absidia. His symptoms were relieved with the use of amphotericin B, and he eventually recovered. We also provide a systematic review of relevant literature to summarize the characteristics of pulmonary mucormycosis in immunocompetent patients. CONCLUSIONS: Pulmonary mucormycosis has variable clinical presentations and is difficult to identify. Due to its high fatality rate, clinicians should make judgements regarding suspected cases correctly and in a timely manner to avoid misdiagnosis and delayed treatment.

Dexamethasone prevents the Epstein-Barr virus induced epithelial-mesenchymal transition in A549 cells.

Clinical data have shown that pulmonary interstitial fibrosis is likely to occur in the later stages of viral pneumonia. While viral infections are thought to cause chronic pulmonary interstitial inflammation and pulmonary fibrosis, it remains unclear if they promote pulmonary fibrosis by epithelial-mesenchymal transition (EMT). In this study, human epithelial cell line A549 has been used to model the infection of the Epstein-Barr virus (EBV) and the respiratory syncytial virus (RSV). Their differences were compared and the possible infection mechanisms analyzed by randomly assigning cells to one of five treatments. Exposure of the LMP1 is thought to be the key gene during EBV-induced EMT in the A549 cells. Enzyme-linked immunosorbent assay analysis revealed that the EBV infection was associated with the induction of a number of cytokines (interleukin-8 [IL-8], IL-13, tumor necrosis factor-α, and transforming growth factor-ß) and dexamethasone (DXM) could significantly prevent the phenotypic changes, and partly the mechanisms related with the IL-13 pathway. Surprisingly, different results were seen with the RSV infection as the A549 cells still displayed an epithelial morphology but the levels of E-cadherin, α-SMA, vimentin, and fibronectin did not change. This is the first study demonstrating the different reactions induced by different viruses, and the protective effects of DXM on the EBV-induced EMT in the A549 cells by partially inhibiting the IL-13 pathway. These findings suggest a novel mechanism, by which DXM or anti-IL-13 may delay the progression of pulmonary fibrosis by preventing the progress of EBV-induced EMT.

Obesity predisposes to the risk of higher mortality in young COVID-19 patients.

Although emerging data demonstrated mortality of young COVID-19 patients, no data have reported the risk factors of mortality for these young patients, and whether obesity is a risk for young COVID-19 patients remains unknown. We conducted a retrospective study including 13 young patients who died of COVID-19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID-19 patients. Most of the young deceased COVID-19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by a higher severity of patchy shadows (100.00% vs 48.70%; P = .006), pleural thickening (61.50% vs 12.80%; P = .012), and mild pericardial effusion (76.90% vs 0.00%; P < .001). Most importantly, the deceased patients manifested higher body mass index (odds ratio [OR] = 1.354; 95% confidence interval [CI] = 1.075-1.704; P = .010), inflammation-related index C-reactive protein (OR = 1.014; 95% CI = 1.003-1.025; P = .014), cardiac injury biomarker hs-cTnI (OR = 1.420; 95% CI = 1.112-1.814; P = .005), and increased coagulation activity biomarker D-dimer (OR = 418.7; P = .047), as compared with that of survivors. Our data support that obesity could be a risk factor associated with high mortality in young COVID-19 patients, whereas aggravated inflammatory response, enhanced cardiac injury, and increased coagulation activity are likely to be the mechanisms contributing to the high mortality.

Clinical characteristics of 54 medical staff with COVID-19: A retrospective study in a single center in Wuhan, China.

In December 2019, an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection occurred in Wuhan, and rapidly spread to worldwide, which has attracted many people's concerns about the patients. However, studies on the infection status of medical personnel is still lacking. A total of 54 cases of SARS-Cov-2 infected medical staff from Tongji Hospital between 7 January and 11 February 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method. From 7 January to 11 February 2020, 54 medical staff of Tongji Hospital were hospitalized due to coronavirus disease 2019 (COVID-19). Most of them were from other clinical departments (72.2%) rather than emergency department (3.7%) or medical technology departments (18.5%). Among the 54 patients with COVID-19, the distribution of age had a significant difference between non-severe type and severe/critical cases (median age: 47 years vs 38 years; P = .0015). However, there was no statistical difference in terms of gender distribution and the first symptoms between theses two groups. Furthermore, we observed that the lesion regions in SARS-Cov-2 infected lungs with severe-/critical-type of medical staff were more likely to exhibit lesions in the right upper lobe (31.7% vs 0%; P = .028) and right lung (61% vs 18.2%; P = .012). Based on our findings with medical staff infection data, we suggest training for all hospital staff to prevent infection and preparation of sufficient protection and disinfection materials.

The joint impacts of dispersal delay and dispersal patterns on the stability of predator-prey metacommunities.

A predator-prey metapopulation model over arbitrary number of patches is considered in this paper. The model assumes that only prey move (with a dispersal delay) between all connected patches. Two cases of dispersal patterns are considered. For the case the dispersal of prey is due to random effect only (independent of predator density), we show that either the dispersal delay is harmless in the sense that it does not affect the stability of the metacommunity, or the dispersal delay can induce stability switches with finite number of stability intervals. For the case the dispersal of prey is due to predator-avoidance (dependent on predator density), we show that the interplay of density-dependent dispersal and dispersal delay may also induce finite number of stability switches. This indicates that the combination of the density-dependent dispersal and dispersal delay can exhibit both stabilizing and destabilizing effects on the stability of the coexistence equilibrium. Our results show that the delay and the patterns of prey dispersal jointly affect the stability of predator-prey metacommunities and can induce multiple stability switches.

Epidemic characteristics of two classic SIS models with disease-induced death.

The epidemic characteristics of two classic SIS epidemic models, including the epidemic size, peak and turning point, are investigated. The two SIS models are with bilinear and standard incidences, respectively. For the SIS models, the susceptible individuals generally can be divided into two classes. One consists of the individuals who had not been infected by the infection, the other are individuals who have been infected and recovered from the infection. Based on this fact, the classic SIS epidemic models need to be reformulated in order to analyze the turning points of the epidemic for various cumulative cases in detail. The obtained results illustrate how to determine the epidemic characteristics of the two models, and demonstrate their dependence on the initial conditions and the relative parameters of the models.

Lgr5 regulates the regeneration of lesioned nasal respiratory epithelium.

Nasal respiratory epithelium is a ciliated pseudostratified columnar epithelium. The cellular components of nasal respiratory epithelium include ciliated cells, goblet cells, and basal cells. Until now, our knowledge in the development of nasal respiratory epithelium is still limited and the cellular mechanism of regeneration is still elusive. In this study, we found that adult stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is expressed in the mice nasal respiratory epithelium. Both immunostaining and lineage tracing analysis indicated Lgr5 positive cells in the nasal respiratory epithelium are proliferative stem/progenitor cells. Using the Rosa-Tdtomato and Rosa26-DTR mice, we elucidated that Lgr5+ cells participate in the regeneration of lesioned nasal respiratory epithelium, and this group of cells is necessary in the process of epithelium recovery. Using the in vitro culture system, we observed the formation of spheres from Lgr5+ cells and these spheres have the capacity to generate other types of cells. Above all, this study reported a group of previously unidentified progenitor/stem cells in nasal respiratory epithelium, unveiling the potential cellular mechanism in nasal respiratory epithelium regeneration.

Cloning and characterization of a novel Gladiolus hybridus AFP family gene (GhAFP-like) related to corm dormancy.

Abscisic acid (ABA) is an important phytohormone controlling seed dormancy. AFPs (ABA INSENSITIVE FIVE BINDING PROTEINS) are reported to be negative regulators of the ABA signaling pathway. The involvement of AFPs in dormant vegetative organs remains poorly understood. Here, we isolated and characterized a novel AFP family member from Gladiolus dormant cormels, GhAFP-like, containing three conserved domains of the AFP family. Quantitative PCR analysis revealed that GhAFP-like was expressed in dormant organs and its expression was down-regulated along with corm storage. GhAFP-like was verified to be a nuclear-localized protein. Overexpressing GhAFP-like in Arabidopsis thaliana not only showed weaker seed dormancy with insensitivity to ABA, but also changed the expression of some ABA related genes. In addition, a primary root elongation assay showed GhAFP-like may involve in auxin signaling response. The results in this study indicate that GhAFP-like acts as a negative regulator in ABA signaling and is related to dormancy.

ADP-glucose pyrophosphorylase gene plays a key role in the quality of corm and yield of cormels in gladiolus.

Starch is the main storage compound in underground organs like corms. ADP-glucose pyrophosphorylase (AGPase) plays a key role in regulating starch biosynthesis in storage organs and is likely one of the most important determinant of sink strength. Here, we identify an AGPase gene (GhAGPS1) from gladiolus. The highest transcriptional levels of GhAGPS1 were observed in cormels and corms. Transformation of GhAGPS1 into Arabidopsis rescued the phenotype of aps1 mutant. Silencing GhAGPS1 in gladiolus corms by virus-induced gene silencing (VIGS) decreased the transcriptional levels of two genes and starch content. Transmission electron microscopy analyses of leaf and corm sections confirmed that starch biosynthesis was inhibited. Corm weight and cormel number reduced significantly in the silenced plants. Taken together, these results indicate that inhibiting the expression of AGPase gene could impair starch synthesis, which results in the lowered corm quality and cormel yield in gladiolus.

Utilization of Microcapsule Technology in Foods.

Microencapsulation technology has greatly accelerated the development of food industry and has a bright future for further applications. In this review paper, we introduce the current researches, latest advances and trends of core materials, wall materials, microencapsulation technology, as well as the encapsulation of food additives, bioactive substance, esculent oils, probiotics and other substances, and their application in food industry.

Antibacterial Properties of ZnO/Calcium Alginate Composite and Its Application in Wastewater Treatment.

In this study, the antibacterial activities of ZnO with various morphologies were evaluated. A possible mechanism of antibacterial activities of dumbbell like ZnO was proposed based on the microscopic studies of the interaction between bacterial and dumbbell like ZnO, and also based on the antibacterial activity of ZnO enveloped with semi permeable membrane. Monosodium glutamate (MSG) wastewater and soy sauce wastewater were treated by M. purpureus using ZnO/calcium alginate carrier. The attached and suspended biomass in MSG wastewater reached to 228 mg/g and 74 mg/g, while, the attached and suspended biomass in soy sauce wastewater was 130 mg/g and 66 mg/g, respectively. The levels of chemical oxide demand (COD), biological oxide demand (BOD5), SO4(2-) and NH3-N in the treated MSG wastewater were distinctive lower than those detected in the raw wastewater. This ZnO/calcium alginate carrier method could be utilized as an alternative to the traditional anaerobic/aerobic methods in the application of food processing wastewater treatment.

[The Effects of Complex of Benzoquinone on Fermi Resonance].

Fermi resonance phenomenon exists in simple compounds and it also widely exists in vibration spectra of complex. The complex can be formed by adding up simple compounds. As a result, the characteristic parameters of some parts of molecule will make changes, and the molecular spectra have a significant change along with it. Benzoquinone and proline in the solution form charge-transfer complex under certain conditions, but the spectra intensity is weak, our research uses Teflon liquid-core optical fiber technology to gain high quality resonance Raman spectra. We acquire Raman spectra of Benzoquinone and its complex in experiments, and analyze the characteristic parameters of Fermi resonance according to J. F. Bertran quantum theory. The results shows that, because of the formation of complex, Fermi resonance peak of C==0 bond shifts to high wavelength, the spectra intensity decreases, the frequency space increases, the coupling coefficient increases. The explanation is that, in the solution of complex, proline is donor, while benzoquinone is acceptor, the non-bonding electron of N atom which is belong to proline transfers to the pi anti-bonding orbital of benzoquinone, then n-pi* charge transfer complex is produced. That causes the change of molecular energy level, changes the Raman spectra. All these researches provide new idea and clue for spectral line certification and attribution of complex molecules, complexes and polymer.

Forensic discrimination of three common brands of kitchen knives in China by ICP-AES and infrared absorption.

A block of an injury instrument will be left in wounds sometimes, and the suspect instrument can be discriminated by comparison with the block that was left through elemental analysis. In this study, three brands (Shibazi, Zhangxiaoquan, Qiaoxifu) of kitchen knives with forged, chop, and slice application series were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Infrared Absorption to investigate the type, number of elements and the reference range used for comparing. The results show that when regarding one or more element as the discriminative threshold, together with 5% relative standard deviation (RSD) as the reference range, all the samples could be distinguished among different series. Furthermore, within the same series, the discriminative capability could reach up to 88.57% for all samples. In addition, elements with high content, such as Cr, Mn, and C, were useful to discriminate among different series, and trace elements, such as Ni, Si, and Cu, were useful within the same series. However, in practice, it is necessary to evaluate the accuracy of the method by Standard Reference Material (SRM) before an examination is performed.

[Study of Fermi resonance characteristic of CS2 in THF].

In the present paper, an innovative experiment was done. The authors measured the Raman spectra of CS2 mixed with THF at different volume fractions. According to the J. F. Bertran theory, we analyzed the changing regularity of v1-2v2 Fermi resonance along with the different concentration. It was shown that the characteristic parameters of Fermi resonance in solution, such as spectra intensity, frequency space, coupling coefficient and anharmonic constant, will make changes along with solution concentration variation. Because of the existing of solvent effects, the spectra intensity decreases gradually, and the coupling coefficient increases gradually. The explanation of such changes is that the vibration spectra are affected not only by scattering coefficient, but also by more weak hydrogen bond's formation. In addition, the asymmetric frequency shift of the Raman spectra was also found in the paper. The fundamental frequency v1 basically has no shifts, but the overtone frequency 2v2 moves towards the high wave number gradually, which is inconsistent with the theory of symmetrical movement. According to the study of molecular microcosmic action, the formation and mechanism of the weak hydrogen bond can preferably explain the above phenomenon. The research has a major influence on the further study of solvent effects in Fermi resonance. And the paper will also provide certain reference value for the study of molecule vibration spectra in solution.