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1.
Antonie Van Leeuwenhoek ; 117(1): 102, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012584

ABSTRACT

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.


Subject(s)
Chickens , Polymerase Chain Reaction , Poultry Diseases , RNA, Ribosomal, 16S , RNA, Ribosomal, 16S/genetics , Animals , Chickens/microbiology , Polymerase Chain Reaction/methods , Poultry Diseases/microbiology , Poultry Diseases/diagnosis , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , DNA, Bacterial/genetics , Sequence Analysis, DNA , Phylogeny
2.
Org Lett ; 26(28): 5917-5922, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38958598

ABSTRACT

Rh-catalyzed asymmetric hydrogenation of 2-substituted 4H-thiochromenes and 4H-chromenes was successfully developed. This method provided highly efficient access to a series of chiral 2-substituted thiochromanes and chromanes in high yields with excellent enantioselectivities (up to 99% yield, 86-99% ee). The obtained chiral 2-substituted thiochromane products were also successfully transformed to corresponding chiral α-substituted sulfoxides and sulfones with excellent enantioselectivities. Furthermore, this highly enantioselective hydrogenation process could be successfully applied to the concise and practical synthesis of the chiral pharmaceutical BW683C.

3.
Arab J Gastroenterol ; 25(2): 125-128, 2024 May.
Article in English | MEDLINE | ID: mdl-38705812

ABSTRACT

BACKGROUND AND STUDY AIMS: There are limited data regarding indeterminate acute liver failure (ALF). The study aims to perform a post hoc analysis using genetic methods for the ALF cases with indeterminate etiology. PATIENTS AND METHODS: Stored blood samples from these patients with indeterminate ALF were collected. Whole-exome sequencing (WES) was used to evaluate the pathogenesis of indeterminate ALF. RESULTS: A total of 16 samples from 11 adult patients and 5 pediatric patients with indeterminate ALF were available. Among the adult patients, one female patient was identified with two heterozygous variants (c.2333G > T (p.Arg778Leu) and c.2310C > G (p.Leu770 = )) in the adenosine triphosphatase copper-transporting beta (ATP7B) gene, and two male patients were found to harbor heterozygous and homozygous variants (c.686C > A (p.Pro229Gln) plus homozygousvariantA(TA)6TAAinsTA (-), andc.1456 T > G (p.Tyr486Asp) plus c.211G > A (p.Gly71Arg)) in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. For the pediatric patients, single heterozygous variant (c.2890C > T (p.Arg964Cys)) in the polymerase gamma (POLG) gene was found in 1 male child, and two heterozygous variants (c.1909A > G (p.Lys637Glu) and c.3646G > A (p.Val1216Ile)) in the tetratricopeptide repeat domain 37 (TTC37) gene were found in 1 female child. No variants clinically associated with known liver diseases were revealed in the remaining patients. CONCLUSION: These results expand the knowledge of ALF with indeterminate etiology. WES is helpful to reveal possible candidate genes for indeterminate ALF, but incomplete consistency between the genotype and phenotype in some cases still challenge the accurate diagnosis.


Subject(s)
Copper-Transporting ATPases , Exome Sequencing , Glucuronosyltransferase , Liver Failure, Acute , Humans , Liver Failure, Acute/genetics , Liver Failure, Acute/diagnosis , Male , Female , Adult , Glucuronosyltransferase/genetics , Child , Copper-Transporting ATPases/genetics , Heterozygote , Adolescent , Middle Aged , Child, Preschool , Young Adult , Mutation , Homozygote
4.
Sci Rep ; 14(1): 11374, 2024 05 18.
Article in English | MEDLINE | ID: mdl-38762652

ABSTRACT

Collaborative innovation between hospitals and biomedical enterprises is crucial for ensuring breakthroughs in their development. This study explores the structural characteristics and examines the main roles of associated key actors of collaborative innovation between hospitals and biomedical enterprises in China. Using the jointly owned patent data within the country's healthcare industry, a decade-long collaborative innovation network between hospitals and biomedical enterprises in China was established and analyzed through social network analysis. The results revealed that the overall levels of collaborative innovation network density, collaborative frequency, and network connectivity were significantly low, especially in less-developed regions. In terms of actors with higher degree centrality, hospitals accounted for the majority, whereas a biomedical enterprise in Shenzhen had the highest degree centrality. Organizations in underdeveloped and northwest regions and small players were more likely to implement collaborative innovation. In conclusion, a collaborative innovation network between hospitals and biomedical enterprises in China demonstrated high dispersion and poor development levels. Stimulating organizations' initiatives for collaborative innovation may enhance quality and quantity of such innovation. Policy support and economic investments, strategic collaborative help, and resource and partnership optimization, especially for small players and in less-developed and northwest regions, should be encouraged to enhance collaborative innovation between hospitals and the biomedical industry in China and other similar countries or regions.


Subject(s)
Cooperative Behavior , Hospitals , Social Network Analysis , China , Humans , Health Care Sector/organization & administration
5.
Yi Chuan ; 46(4): 333-345, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38632095

ABSTRACT

China has a high dependence on soybean imports, yield increase at a faster rate is an urgent problem that need to be solved at present. The application of heterosis is one of the effective ways to significantly increase crop yield. In recent years, the development of an intelligent male sterility system based on recessive nuclear sterile genes has provided a potential solution for rapidly harnessing the heterosis in soybean. However, research on male sterility genes in soybean has been lagged behind. Based on transcriptome data of soybean floral organs in our research group, a soybean stamen-preferentially expressed gene GmFLA22a was identified. It encodes a fasciclin-like arabinogalactan protein with the FAS1 domain, and subcellular localization studies revealed that it may play roles in the endoplasmic reticulum. Take advantage of the gene editing technology, the Gmfla22a mutant was generated in this study. However, there was a significant reduction in the seed-setting rate in the mutant plants at the reproductive growth stage. The pollen viability and germination rate of Gmfla22a mutant plants showed no apparent abnormalities. Histological staining demonstrated that the release of pollen grains in the mutant plants was delayed and incomplete, which may due to the locule wall thickening in the anther development. This could be the reason of the reduced seed-setting rate in Gmfla22a mutants. In summary, our study has preliminarily revealed that GmFLA22a may be involved in regulating soybean male fertility. It provides crucial genetic materials for further uncovering its molecular function and gene resources and theoretical basis for the utilization of heterosis in soybean.


Subject(s)
Glycine max , Infertility, Male , Male , Humans , Plants , Pollen/genetics , Fertility , Plant Infertility/genetics , Gene Expression Regulation, Plant
6.
J Med Virol ; 96(3): e29530, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38529528

ABSTRACT

Integration of hepatitis B virus (HBV) DNA into the human genome is recognized as an oncogenic factor and a barrier to hepatitis B cure. In the study, biopsy liver tissues were collected from adolescents and young adults with acute HBV infection younger than or equal to 35 years of age and from HBV-infected infant patients younger than or equal to 6 months of age. A high-throughput sequencing method was used to detect HBV DNA integration. Totally, 12 adolescents, young adults, and 6 infants were included. Among the 12 patients with acute HBV infection, immunohistochemical staining of intrahepatic hepatitis B surface antigen for all displayed negative results, and no HBV DNA integrants in the hepatocyte DNA were confirmed. All infant patients had elevated levels of alanine aminotransferase and high levels of serum HBV DNA. Numerous gene sites of hepatocyte DNA were integrated by HBV DNA for each infant patient, ranging from 120 to 430 integration sites. The fragile histidine triad gene was the high-frequency integrated site in the intragenic region for infant patients. In conclusion, hepatocyte DNA is integrated by HBV DNA in babies with active hepatitis B but seems seldom affected among adolescents and young adults with acute HBV infection. Infantile hepatitis B should be taken seriously considering abundant HBV DNA integration events.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Infant , Adolescent , Humans , Young Adult , Hepatitis B virus/genetics , DNA, Viral/genetics , Liver/pathology , Hepatitis B Surface Antigens/genetics , Hepatitis B e Antigens , Genomics
8.
J Pediatr Nurs ; 75: 180-186, 2024.
Article in English | MEDLINE | ID: mdl-38163421

ABSTRACT

BACKGROUND: Nursing translational research (TR) begins with clinical discovery and medical research and leads to clinical application in patients. TR is key to improving nursing quality and developing the nursing profession. However, its development in China remains limited, and the reasons for this are unclear. We aim to enhance the recognition of nursing TR among nursing practitioners in China by exploring their cognition about nursing TR and associated influences. METHODS: We distributed an internet-based questionnaire to 683 nursing practitioners between February 13 and March 15, 2023. We analyzed the characteristics and cognition of nursing TR using descriptive statistics, the chi-squared test, Fisher's exact test, the Wilcoxon rank-sum test, Kruskal-Wallis H test, and stepwise logistic regression analysis. The majority (79.65%) of nursing practitioners who responded to the questionnaire were willing to participate in nursing TR. FINDINGS: Nursing practitioners with a higher educational level, stronger recognition of the importance of nursing TR, and stronger recognition of transdisciplinary nursing TR were more willing to participate in nursing TR. DISCUSSION: The results of this study can accelerate nursing practitioners' willingness to participate in nursing TR. APPLICATION TO PRACTICE: We identified strategies to promote TR: provide further education, optimize courses in higher education, disseminate information, provide guidance on the importance of nursing TR, and establish a nursing TR platform with appropriate potential collaborators.


Subject(s)
Nursing Research , Translational Research, Biomedical , Humans , Surveys and Questionnaires , China , Cognition
9.
Rev Sci Instrum ; 94(9)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37695115

ABSTRACT

This paper tackles the problem of noise suppression during vital sign signal monitoring. Physiological signal monitoring is a significant and promising medical monitoring method, and wearable medical monitoring devices based on piezoelectric polymer sensors are a trending way for their advantages of being flexible in the shape, portable to use, and comfortable to wear. However, this raises the question that the measured signal contains much more noise components. To avoid the following shortcoming of low signal to noise ratio (SNR), a noise suppression method based on improved wavelet threshold and empirical mode decomposition combined with singular value decomposition (SVD) screening the intrinsic mode function (IMF) components is proposed. A wavelet transform is first used under the combination of hard and soft thresholds to focus the target range in the low-frequency region where the energy of the physiological signal is concentrated. Then, a complete ensemble empirical mode decomposition is used to decompose the signal effectively, which can resist the influence of random noises. Meanwhile, a SVD decomposition procedure was used to filter out the lower correlated IMF components to retain the validity of the original signal. We verified the effectiveness of the proposed method through simulated and measured experiments as well as the advantages and disadvantages of the algorithm compared with other physiological signal denoising algorithms through SNR filtering results, power spectrum distribution, and other perspectives. The results proved that the proposed method could effectively remove more detailed noise and improve the SNR of the signal efficiently, which is more conducive to the demand for auxiliary medical diagnosis in the future.

10.
Sensors (Basel) ; 23(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37571536

ABSTRACT

In this paper, we present the properties of a communication channel used for implantable devices. The human-body communication (HBC) channel was proposed for data communication in implantable devices. The impulse response was measured using a channel-mimicking model, which mimics electrical losses caused by human body tissues. Furthermore, we compared two types of channel-mimicking models to evaluate their applicability depending on the measurement environment. The resultant impulse responses of the HBC channel showed that HBC does not cause severe changes in the channel properties even when the implantable device is rotated.


Subject(s)
Human Body , Wireless Technology , Humans , Prostheses and Implants , Communication , Electricity
11.
Children (Basel) ; 10(8)2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37628388

ABSTRACT

This study explored the ambiguous characteristics and influencing factors of parental anxiety, practices, and parent-child relationships among families with young children during a sudden COVID-19 lockdown in Shanghai, China. An online survey was conducted from 1 June to 10 November 2022, with 477 valid responses. Parental anxiety, practices, and parent-child relationships were evaluated. During this lockdown, 72.6% caregivers felt anxious about parenting to different degrees, with only a small proportion experiencing extreme anxiety. Parental anxiety was mainly influenced by whether the caregivers faced parenting issues and external parenting difficulties. The frequency of two-parent-child activities of reading books or looking at picture books with their children and telling stories to them significantly increased. Caregivers' occupations of either professional or technical personnel and working from home were the most significant influencing factors. Mother-child relationships were relatively good. In conclusion, parental anxiety, practices, and parent-child relationships were relatively good and stable among families with young children during this lockdown. In the context of public health emergencies like COVID-19, more parenting support and knowledge should be provided to caregivers from professionals in CHCs or hospitals to decrease parental anxiety and improve parent-child relationships. Full advantage should be taken of working from home to promote parent-child activities.

12.
Plant Biotechnol J ; 21(11): 2322-2332, 2023 11.
Article in English | MEDLINE | ID: mdl-37475199

ABSTRACT

A complete and genetically stable male sterile line with high outcrossing rate is a prerequisite for the development of commercial hybrid soybean. It was reported in the last century that the soybean male sterile ms2 mutant has the highest record with seed set. Here we report the cloning and characterization of the MS2 gene in soybean, which encodes a protein that is specifically expressed in the anther. MS2 functions in the tapetum and microspore by directly regulating genes involved in the biosynthesis of secondary metabolites and the lipid metabolism, which is essential for the formation of microspore cell wall. Through comparison of the field performance with the widely used male sterile mutants in the same genetic background, we demonstrated that the ms2 mutant conducts the best in outcrossing rate and makes it an ideal tool in building a cost-effective hybrid system for soybean.


Subject(s)
Glycine max , Plant Infertility , Glycine max/genetics , Glycine max/metabolism , Plant Infertility/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Pollen/genetics , Plant Breeding , Fertility/genetics , Gene Expression Regulation, Plant
13.
Curr Probl Cardiol ; 48(12): 101910, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37422038

ABSTRACT

Cardiac aging is accompanied by changes in the heart at the cellular and molecular levels, leading to alterations in cardiac structure and function. Given today's increasingly aging population, the decline in cardiac function caused by cardiac aging has a significant impact on quality of life. Antiaging therapies to slow the aging process and attenuate changes in cardiac structure and function have become an important research topic. Treatment with drugs, including metformin, spermidine, rapamycin, resveratrol, astaxanthin, Huolisu oral liquid, and sulforaphane, has been demonstrated be effective in delaying cardiac aging by stimulating autophagy, delaying ventricular remodeling, and reducing oxidative stress and the inflammatory response. Furthermore, caloric restriction has been shown to play an important role in delaying aging of the heart. Many studies in cardiac aging and cardiac aging-related models have demonstrated that Sestrin2 has antioxidant and anti-inflammatory effects, stimulates autophagy, delays aging, regulates mitochondrial function, and inhibits myocardial remodeling by regulation of relevant signaling pathways. Therefore, Sestrin2 is likely to become an important target for antimyocardial aging therapy.


Subject(s)
Myocardium , Quality of Life , Humans , Aged , Myocardium/metabolism , Aging , Oxidative Stress , Resveratrol/metabolism , Resveratrol/pharmacology
14.
Mol Breed ; 43(6): 47, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37309310

ABSTRACT

Hybrid breeding can help us to meet the challenge of feeding a growing world population with limited agricultural land. The demand for soybean is expected to grow; however, the hybrid soybean is still in the process of commercialization even though considerable progress has been made in soybean genome and genetic studies in recent years. Here, we summarize recent advances in male sterility-based breeding programs and the current status of hybrid soybean breeding. A number of male-sterile lines with cytoplasmic male sterility (CMS), genic-controlled photoperiod/thermo-sensitive male sterility, and stable nuclear male sterility (GMS) have been identified in soybean. More than 40 hybrid soybean varieties have been bred using the CMS three-line hybrid system and the cultivation of hybrid soybean is still under way. The key to accelerating hybrid soybean breeding is to increase the out-crossing rate in an economical way. This review outlines current problems with the hybrid soybean breeding systems and explores the current efforts to make the hybrid soybean a commercial success.

15.
Sci Rep ; 13(1): 299, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36609446

ABSTRACT

How to allocate the existing medical resources reasonably, alleviate hospital congestion and improve the patient experience are problems faced by all hospitals. At present, the combination of artificial intelligence and the medical field is mainly in the field of disease diagnosis, but lacks successful application in medical management. We distinguish each area of the emergency department by the division of medical links. In the spatial dimension, in this study, the waitlist number in real-time is got by processing videos using image recognition via a convolutional neural network. The congestion rate based on psychology and architecture is defined for measuring crowdedness. In the time dimension, diagnosis time and time-consuming after diagnosis are calculated from visit records. Factors related to congestion are analyzed. A total of 4717 visit records from the emergency department and 1130 videos from five areas are collected in the study. Of these, the waiting list of the pediatric waiting area is the largest, including 10,436 (person-time) people, and its average congestion rate is 2.75, which is the highest in all areas. The utilization rate of pharmacy is low, with an average of only 3.8 people using it at the one time. Its average congestion rate is only 0.16, and there is obvious space waste. It has been found that the length of diagnosis time and the length of time after diagnosis are related to age, the number of diagnoses and disease type. The most common disease type comes from respiratory problems, accounting for 54.3%. This emergency department has congestion and waste of medical resources. People can use artificial intelligence to investigate the congestion in hospitals effectively. Using artificial intelligence methods and traditional statistics methods can lead to better research on healthcare resource allocation issues in hospitals.


Subject(s)
Artificial Intelligence , Delivery of Health Care , Humans , Child , Resource Allocation , Emergency Service, Hospital , Hospitals
16.
PLoS One ; 18(1): e0279879, 2023.
Article in English | MEDLINE | ID: mdl-36656818

ABSTRACT

The current epidemiological status of the new coronary pneumonia epidemic in China is being explored to prevent and control the localized dissemination of aggregated outbreaks. This study analyzed the characteristics of new outbreaks of coronavirus disease 2019 (COVID-19) at three stages of aggregated outbreaks in Jilin Province, China, to provide a reference for the prevention and control of aggregated outbreaks. Case information were collected from all patients in Jilin Province from January 12, 2020 to the present. The epidemic was divided into three stages according to the time of onset. The first stage comprised 97 cases reported from January 12, 2020 to February 19, 2020, during which 17 aggregated outbreaks occurred. The second comprised 43 cases reported from April 25, 2020 and May 23, 2020, involving one aggregated outbreak. The third comprised 435 cases reported on January 10, 2021 and February 9, 2021, involving one aggregated outbreak. The relationship between aggregated and non-aggregated cases in the first phase of the outbreak and the difference between imported and local cases during the aggregated outbreak were assess using statistical analysis, and the differences in the baseline information between the three phases were analyzed. The incubation periods of the three phases were 10 days, 8 days, and 5 days. The number of aggregated epidemic events in Jilin Province tended to increase and then decrease over time. The clustered events in Jilin Province were divided into four categories: household contact (14 times, 51 cases); household contact and public places (one time, three cases); household contact, public places, and gatherings (one time, six cases); and household contact, public places, gatherings, and work (three times, 495 cases). Clustered events occurred mainly between January 22, 2020, and February 4, 2020. Among all cases in the first phase of the outbreak, the method of detection and the time from diagnosis to discharge were longer in aggregated cases than in non-aggregated cases, and that the source of infection and renewal cases were more frequent and more likely to be detected in the outpatient clinics during aggregated outbreaks than the imported cases. The second phase of the epidemic showed significant spatial variability (Moran's I<0, P<0.05). The third stage of the epidemic occurred in a higher proportion of individuals aged 50-90 years and within a shorter incubation period compared with the first two stages. The current focus of prevention and control of the COVID-19 epidemic in Jilin Province is to strictly implement the restrictions on gatherings and to perform timely screening and isolation of close contacts of infectious sources while strengthening the supervision of the inflow of people from outside the region. Simultaneously, more targeted prevention and control measures can be implemented for different age groups and occupations.


Subject(s)
COVID-19 , Epidemics , Humans , COVID-19/epidemiology , SARS-CoV-2 , China/epidemiology , Disease Outbreaks/prevention & control
17.
Foods ; 11(19)2022 Oct 02.
Article in English | MEDLINE | ID: mdl-36230141

ABSTRACT

The Cinnamomum camphora seed kernel (CCSK), with high contents of medium-chain oil (~59%) and protein (~19%), is an excellent source for a plant-based food ingredient. To broaden the application of the protein isolate (PI) from CCSK in the food industry, the Maillard reaction products (MRPs) were prepared by PI and dextran (DX) under mild wet-heating conditions (60 °C, 5 h), and the structural and functional properties of the PI-DX conjugates were investigated. The covalent bond between PI and DX was confirmed by the degree of grafting and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Compared with the heated PI, the PI-DX conjugates had more ordered structure, with the decreased random coil content. The changes in tertiary structure of PI-DX conjugates were reflected by the results of intrinsic fluorescence and surface hydrophobicity. Moreover, PI-DX conjugates showed better solubility, emulsifying properties, thermal stability and antioxidant activities. These results provided a theoretical basis for the development of PI-based MRPs with desirable characteristics.

18.
Article in English | MEDLINE | ID: mdl-35457590

ABSTRACT

Focusing on the exploration of the important role of fiscal ecological compensation in green development, this paper incorporates fiscal ecological compensation into the analytical framework of green development. Based on samples of data from county areas in China in 2017 and 2018, this paper empirically examines the shape of the green development routes in county areas in China. On this basis, this paper explores the impact and mechanism of fiscal ecological compensation on the green development path in China. The empirical results show that there is a nonlinear, N-shaped relationship between economic development and the ecological environment in China within the range of the sample examined. Fiscal ecological compensation has a direct governance effect on the ecological environment of deterring ecological damage and providing financial compensation. Fiscal ecological compensation has an indirect impact on the ecological management of different regions by influencing economic development. Therefore, while focusing on transforming the economic development model, local governments should adopt policy instruments such as expanding the coverage of financial ecological compensation, deepening the design of the financial ecological compensation system, and systematically evaluating the effects of financial ecological compensation policies. The government should further improve and optimize the fiscal eco-compensation system in order to help China's green and high-quality development.


Subject(s)
Economic Development , Environment , China , Ecosystem , Policy
19.
Front Pharmacol ; 13: 813087, 2022.
Article in English | MEDLINE | ID: mdl-35359837

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an acute respiratory disease with systemic complications. Therapeutic strategies for COVID-19, including repurposing (partially) developed drugs are urgently needed, regardless of the increasingly successful vaccination outcomes. We characterized two-dimensional (2D) and three-dimensional models (3D) to establish a physiologically relevant airway epithelial model with potential for investigating SARS-CoV-2 therapeutics. Human airway basal epithelial cells maintained in submerged 2D culture were used at low passage to retain the capacity to differentiate into ciliated, club, and goblet cells in both air-liquid interface culture (ALI) and airway organoid cultures, which were then analyzed for cell phenotype makers. Airway biopsies from non-asthmatic and asthmatic donors enabled comparative evaluation of the level and distribution of immunoreactive angiotensin-converting enzyme 2 (ACE2). ACE2 and transmembrane serine proteinase 2 (TMPRSS2) mRNA were expressed in ALI and airway organoids at levels similar to those of native (i.e., non-cultured) human bronchial epithelial cells, whereas furin expression was more faithfully represented in ALI. ACE2 was mainly localized to ciliated and basal epithelial cells in human airway biopsies, ALI, and airway organoids. Cystic fibrosis appeared to have no influence on ACE2 gene expression. Neither asthma nor smoking status had consistent marked influence on the expression or distribution of ACE2 in airway biopsies. SARS-CoV-2 infection of ALI cultures did not increase the levels of selected cytokines. Organotypic, and particularly ALI airway cultures are useful and practical tools for investigation of SARS-CoV-2 infection and evaluating the clinical potential of therapeutics for COVID-19.

20.
Dose Response ; 20(1): 15593258221088092, 2022.
Article in English | MEDLINE | ID: mdl-35392264

ABSTRACT

Background: Ropivacaine is widely used for clinical anesthesia and postoperative analgesia. However, the neurotoxicity induced by ropivacaine in a concentration- and duration-dependent manner, and it is difficult to prevent neurotoxicity. Osthole inhibits phosphodiesterase-4 activity by binding to its catalytic site to prevent cAMP hydrolysis. The aim of this present study is to explore the precise molecular mechanism of osthole-mediated inhibition of neurotoxicity induced by ropivacaine. Methods: SH-SY5Y cell viability and apoptosis were measured in different concentration and duration. Protein concentration was determined in each signaling pathway. The molecular mechanism of osthole-mediated inhibition of ropivacaine-caused neurotoxicity was evaluated. Results: The study demonstrated that osthole inhibits SH-SY5Y cells neurotoxicity in a duration- and concentration-dependent manner. Moreover, ropivacaine significantly increased the expression of caspase-3 by promoting the phosphorylation of p38. Osthole-induced upregulation of cAMP activated cAMP-dependent signaling pathway, sequentially leading to elevated cyclic nucleotide response element-binding protein levels, which inhibits P38-dependent signaling and decreases apoptosis of SH-SY5Y. Conclusions: This study display the evidence confirmed the molecular mechanism by which osthole amplification of cAMP-dependent signaling pathway, and overexpression of cyclic nucleotide response element-binding protein inhibits P38-dependent signaling and decreases ropivacaine-induced SH-SY5Y apoptosis.

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