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1.
FASEB J ; 38(1): e23395, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38149880

RESUMO

Neutrophils accumulate in the inflammatory mucosa of patients with inflammatory bowel disease (IBD), and excessive release of NETs (neutrophil extracellular traps may be one of the important factors that cause IBD progression. However, the specific mechanism underlying vascular injury caused by NETs remains unclear. Immunofluorescence, ELISA, and flow cytometry were used in this study to detect the expression of NETs and DNase in the tissue and peripheral blood samples of patients with IBD. DSS mouse model was used to detect colon injury and vascular permeability. We found that NETs and DNase levels increased in the colon of patients with IBD. We found an increase in the activity of NET-related MPO released by DNase. DNase released NET-related proteins and damaged vascular endothelial cells in vitro. In DSS mouse model, the synchronous increase of DNase and NETs in the colon leads to an increase in vascular injury markers (CD44, sTM). DNase aggravated colon injury and increased vascular permeability in vivo, which was inhibited by gentamicin sulfate (GS). GS does not reduce the expression of DNase, but rather reduces the release of NET-related proteins to protect vascular endothelium by inhibiting DNase activity. MPO and histones synergistically damaged the vascular endothelium, and vascular injury can be improved by their active inhibitors. We further found that H2 O2 is an important substrate for MPO induced vascular damage. In conclusion, in IBD, DNase, and NET levels increased synchronously in the lesion area and released NET-related proteins to damage the vascular endothelium. Therefore, targeting DNase may be beneficial for the treatment of IBD.


Assuntos
Traumatismos Abdominais , Armadilhas Extracelulares , Doenças Inflamatórias Intestinais , Lesões do Sistema Vascular , Animais , Camundongos , Humanos , Desoxirribonucleases , Células Endoteliais , Modelos Animais de Doenças
2.
Ren Fail ; 46(1): 2334406, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38575341

RESUMO

A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. In vitro, transforming growth factor-ß1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts-macrophages communication may provide a novel therapeutic target for kidney fibrosis.


Assuntos
Exossomos , Nefropatias , Animais , Camundongos , Miofibroblastos/metabolismo , Exossomos/metabolismo , Exossomos/patologia , Macrófagos/metabolismo , Nefropatias/patologia , Rim/patologia , Fibrose
3.
J Am Chem Soc ; 145(24): 13326-13334, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37279071

RESUMO

Many optoelectronic processes in colloidal semiconductor nanocrystals (NCs) suffer an efficiency decline under high-intensity excitation. This issue is caused by Auger recombination of multiple excitons, which converts the NC energy into excess heat, reducing the efficiency and life span of NC-based devices, including photodetectors, X-ray scintillators, lasers, and high-brightness light-emitting diodes (LEDs). Recently, semiconductor quantum shells (QSs) have emerged as a promising NC geometry for the suppression of Auger decay; however, their optoelectronic performance has been hindered by surface-related carrier losses. Here, we address this issue by introducing quantum shells with a CdS-CdSe-CdS-ZnS core-shell-shell-shell multilayer structure. The ZnS barrier inhibits the surface carrier decay, which increases the photoluminescence (PL) quantum yield (QY) to 90% while retaining a high biexciton emission QY of 79%. The improved QS morphology allows demonstrating one of the longest Auger lifetimes reported for colloidal NCs to date. The reduction of nonradiative losses in QSs also leads to suppressed blinking in single nanoparticles and low-threshold amplified spontaneous emission. We expect that ZnS-encapsulated quantum shells will benefit many applications exploiting high-power optical or electrical excitation regimes.

4.
Angew Chem Int Ed Engl ; 62(26): e202303433, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37083026

RESUMO

A homogeneous manganese-catalyzed cross-coupling of two secondary alcohols for the divergent synthesis of γ-disubstituted alcohols and ß-disubstituted ketones is reported. Employing the well-defined Mn-MACHOPh as the catalyst, this novel protocol has a broad substrate scope with good functional group tolerance and affords a diverse library of valuable disubstituted alcohols and ketones in moderate to good yields. The strong influence of the reaction temperature on the selective formation of alcohol products was theorized in preliminary DFT studies. Studies have shown that the Gibbs free energy of the formation of alcohols is thermodynamically more favourable than corresponding ketones at a lower temperature.


Assuntos
Álcoois , Manganês , Cetonas , Oxirredução , Estrutura Molecular , Catálise
5.
J Cell Mol Med ; 26(7): 2089-2103, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35146909

RESUMO

Neutrophils release neutrophil extracellular traps (NETs) to capture and kill pathogens, but excessive NET release can damage the surrounding tissues. Myeloperoxidase (MPO) and neutrophil elastase (NE) are thought to be important in promoting histone depolymerization and DNA breakage in the nucleus. However, the detailed path by which MPO and NE enter the nucleus is unknown. In the present study, we observed that delayed fusion of azurophilic granules with the nuclear membrane 15-20 min after extracellular degranulation in activated neutrophils. In a subsequent experiment, we further demonstrated that this fusion leads to MPO entry into the nucleus and promotes nuclear histone depolymerization and DNA breakage, a process called 'targeted nuclear degranulation'. This process can be effectively inhibited by dexamethasone and accompanied by the continuous low levels of MPO in the nucleus after PMA stimulation. Meanwhile, we found that 'targeted nuclear degranulation' is dependent on the CD44 translocation and subsequent redistribution of CD44 / ERM (Ezrin/Radixin/Moesin) / F-actin complexes, which guides the movement of azurophilic granules towards the nucleus. Application of ERM phosphorylation inhibitors and importin activity inhibitors significantly reduced the complexes formation and redistribution. Taken together, these findings indicate for the first time that delayed 'targeted nuclear degranulation' after neutrophil activation is a key mechanism of NET formation. CD44/ERM/F-actin complex mediates this process, which providing targets with promising prospects for the precise regulation of NET formation.


Assuntos
Armadilhas Extracelulares , Sepse , Actinas , Animais , Humanos , Receptores de Hialuronatos , Camundongos , Ativação de Neutrófilo , Neutrófilos , Peroxidase
6.
Opt Express ; 30(20): 37101-37111, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258627

RESUMO

A pulse compressing technology of single-frequency Q-switched laser based on the cascaded four-wave mixing (CFWM) effect is demonstrated theoretically and experimentally, for the first time to the best of our knowledge. A theoretical model of the pulse compression is established through deconstructing the pulse duration evolution in the high-order Stokes and anti-Stokes lights of CFWM. A pulse compression ratio of (2|m|+1)1/2 is quantificationally obtained with m corresponding to the order number of the CFWM light. Utilizing dual-wavelength (DW) single-frequency Q-switched laser injected into a highly nonlinear fiber (HNLF), the pulse compression and the spectral broadening phenomenon are observed simultaneously. As the order number of the CFWM light increases from 0-order to 3-order, the pulse duration has reduced from 115 ns to 47 ns with a compression ratio of 2.45, which is essentially consistent with the theoretical analysis. The pulse compressing technique by CFWM is conducive to promoting the performance development of the single-frequency Q-switched laser, which can improve the system precision in the Lidar, trace gas detection, and high-precision ranging. Furthermore, this technology based on time-frequency transformation dynamics may be generally applicable to other single-frequency pulsed fiber lasers.

7.
Inflamm Res ; 71(1): 81-91, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34841450

RESUMO

BACKGROUND: Despite many advances in treatment, the prognosis of patients with sepsis still remains poor. Polymorphonuclear leukocytes (PMNs) are the first line of defense against infection. This study aimed to reveal the reason and mechanism of the production of PD-L1+ PMNs in sepsis. METHODS: Cecal ligation and perforation mouse model was established to simulate sepsis. And PMNs were treated for 4 h, 12 h with or without 100 ng/mL (IFN-γ) for further gene sequencing. PD-L1, PD-1, Ly6G, and CD3 were detected by multiplexed immunofluorescence. In addition, expression of PD-L1 and function of PMNs were assessed by flow cytometry. Serum and cell culture supernatant were measured with ELISA assays. Western blot was used to verify the JAK2/STAT1 pathway. RESULTS: Our study demonstrates that PMNs are the main immune cells with high expression of PD-L1 during sepsis, and these cells, therefore, play a critical role in immunosuppression. In vivo studies demonstrated a specific interaction between PD-L1+ PMNs and PD-1+ T cells. In vitro studies further demonstrated that IFN-γ induced the production of PD-L1+ PMNs through the JAK2/STAT1 pathway. In addition, Fedratinib, an inhibitor of Jak2, was shown to significantly reduce the expression of PD-L1 in neutrophils. CONCLUSIONS: These data demonstrate that secretion of IFN-γ by splenic T lymphocytes induces the production of PD-L1 + PMNs through the JAK2/STAT1 pathway in sepsis.


Assuntos
Neutrófilos , Sepse , Animais , Humanos , Interferon gama/metabolismo , Camundongos , Baço/metabolismo , Linfócitos T
8.
BMC Anesthesiol ; 22(1): 127, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488192

RESUMO

BACKGROUND: In clinical practice, sufentanil has a stronger sedative effect on patients than fentanyl at equivalent doses. This study hypothesized that, at equivalent doses, patients undergoing gynaecologic laparoscopic surgery (GLS) receiving fentanyl would have an earlier emergence from anaesthesia (EA), a shorter time to extubation (TE), and a better degree of wakefulness. Therefore, this study evaluated the effects of equipotent doses of fentanyl and sufentanil on the quality of emergence in patients undergoing GLS. METHODS: One hundred seven patients scheduled for GLS under general anaesthesia were randomly divided into two groups and were induced with 0.35 µg/kg sufentanil (Group S; n = 55) or 3.5 µg/kg fentanyl (Group F; n = 52). When the GLS was almost over, the patient's abdominal cavity was flushed with warm saline, and 5 µg of sufentanil or 50 µg of fentanyl in a double-blind manner was intravenously injected into the patients. The primary outcomes of the study included EA, TE, the rate of leaving the surgical bed voluntarily and the incidence of endotracheal tube tolerance. The Ramsay Sedation Scale (RSS), and Verbal Rating Scale (VRS) scores at 15 and 30 min in the postanaesthesia care unit (PACU), as well as other adverse events, including nausea and vomiting, itching, delirium, dizziness, chills, and respiratory depression (SpO2 < 95%) in the PACU, were evaluated as secondary outcomes. RESULTS: There were no statistically significant dissimilarities between the two groups with respect to baseline characteristics. For recovery, the EA (9.0 ± 4.8 min vs. 8.9 ± 3.0 min; P = 0. 146), TE (9.5 ± 4.7 min vs. 9.0 ± 3.0 min; P = 0.135), rate of leaving the surgical bed voluntarily (31.18% vs. 38.46%; P = 0.976), and incidence of endotracheal tube tolerance (94.55% vs. 96.15%; P = 0.694) were not significantly different between the two groups. In the PACU, the 15-min RSS score (2.07 ± 0.38 vs. 2.15 ± 0.36; P = 0.125), the 30-min RSS score (2.02 ± 0.13 vs. 2.04 ± 0.19; P = 0.207), the 15-min VRS score (0.50 ± 0.57 vs. 0.67 ± 0.55; P = 0.295), and the 30-min VRS score (0.45 ± 0.50 vs. 0.75 ± 0.52; P = 0.102) were not significantly different between Groups S and F. No adverse events, such as nausea, vomiting, pruritus, delirium, and tremors, occurred in either group. The rates of respiratory depression (1.82% vs. 1.92%; P = 0.968) and dizziness (0.00% vs. 4.85%; P = 0.142) were not different between Groups S and F in the PACU. CONCLUSIONS: The majority of patients scheduled for GLS were able to rapidly and smoothly emerge from anaesthesia. After surgery, similar outcomes, including EA, TE, the incidence of endotracheal tube tolerance, the rate of leaving the surgical bed voluntarily, RSS scores, VRS scores, and adverse events in the PACU, were achieved for the patients between the two anaesthetic protocols.


Assuntos
Anestesia , Delírio , Laparoscopia , Propofol , Insuficiência Respiratória , Tontura/induzido quimicamente , Feminino , Fentanila , Humanos , Náusea/induzido quimicamente , Propofol/efeitos adversos , Remifentanil , Insuficiência Respiratória/induzido quimicamente , Sufentanil , Vômito/induzido quimicamente
9.
Parasitol Res ; 121(10): 2841-2848, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35939147

RESUMO

Tetratrichomonas gallinarum and Trichomonas gallinae can colonize the alimentary tract of domestic birds. However, little information is available on the epidemiology of the two trichomonad species in domestic free-range poultry in China. In this study, the occurrence and genetic characteristic of T. gallinarum and T. gallinae among free-range chickens, ducks, and geese in Anhui Province, China, were investigated. The 1910 fecal samples collected from 18 free-range poultry farms throughout Anhui Province were examined for the presence of T. gallinarum and T. gallinae by PCR and sequence analysis of the small subunit (SSU) rRNA gene of T. gallinarum and ITS1-5.8S-ITS2 sequence of T. gallinae. The overall occurrence of T. gallinarum in poultry was 1.2% (22/1910), with infection rates of 2.1% (17/829) in chickens, 0.2% (1/487) in ducks, and 0.7% (4/594) in geese. The constructed phylogeny tree using the concatenated ITS1-5.8S-ITS2 region and SSU rRNA indicated the T. gallinarum isolates detected in this study were closely related to previously defined genogroups A, D, and E, respectively. Nine (0.5%) fecal samples were positive for T. gallinae, with infection rates of 0.8% (7/829) in chickens, 0.4% (2/487) in ducks, and 0% (0/594) in geese. Sequence and phylogenetic analysis showed that four T. gallinae ITS1-5.8S-ITS2 sequences obtained from chicken feces and one duck fecal sample belonged to genotype ITS-OBT-Tg-1. This is the first report of the prevalence and genetic characterization of T. gallinarum and T. gallinae in free-range chickens, ducks, and geese in China.


Assuntos
Doenças das Aves , Trichomonadida , Tricomoníase , Trichomonas , Animais , Doenças das Aves/epidemiologia , Galinhas , Patos , Filogenia , Aves Domésticas , Prevalência , Trichomonas/genética , Tricomoníase/epidemiologia , Tricomoníase/veterinária
10.
Crit Care ; 25(1): 50, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549126

RESUMO

BACKGROUND: Although the immune function of neutrophils in sepsis has been well described, the heterogeneity of neutrophils remains unclear during the process of sepsis. METHODS: In this study, we used a mouse CLP model to simulate the clinical scenario of patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS was used to stimulate neutrophils in vitro to simulate sepsis; single-cell gene sequencing technology was used to explore the immunological typing. To explore the immunological function of immunosuppressive neutrophils, PD-L1 knockout neutrophils were cocultured with lymphocytes from wild-type mice. RESULTS: We found that neutrophils presented variant dysfunction at the late stage of sepsis, including inhibition of apoptosis, seriously damaged chemotaxis and extensive infiltration into the tissues. Single-cell RNA sequencing revealed that multiple subclusters of neutrophils were differentiated after LPS stimulation. The two-dimensional spatial distribution analysis showed that Foxp3+ T cells were much closer to Ly-6G than the CD4+ and CD8+ cells, indicating that infiltrated neutrophils may play immunomodulatory effect on surrounding T-regs. Further observations showed that LPS mediates PD-L1 over expression through p38α-MSK1/-MK2 pathway in neutrophils. The subsets of highly expressed PD-L1 exert immunosuppressive effect under direct contact mode, including inhibition of T cell activation and induction of T cell apoptosis and trans-differentiation. CONCLUSIONS: Taken together, our data identify a previously unknown immunosuppressive subset of neutrophils as inhibitory neutrophil in order to more accurately describe the phenotype and characteristics of these cells in sepsis.


Assuntos
Heterogeneidade Genética , Neutrófilos/classificação , Sepse/sangue , Animais , Modelos Animais de Doenças , Contagem de Leucócitos/métodos , Contagem de Leucócitos/estatística & dados numéricos , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/fisiologia , Reação em Cadeia da Polimerase/métodos , Sepse/genética
11.
Exp Cell Res ; 386(2): 111735, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751554

RESUMO

Activation of coagulation occurs in sepsis and contributes to the development of thrombosis. Platelet α-granule exocytosis plays an important role in septic coagulation abnormalities. The present study aimed to investigate the effects and the underlying mechanisms of exogenous carbon monoxide, carbon monoxide-releasing molecules II (CORM-2)-liberated CO, on suppressing platelet α-granule exocytosis in sepsis. It was shown that CORM-2 weakened α-granule membrane fusion with platelet plasma membrane and attenuated α-granule contents exocytosis in LPS-Induced platelet. Further studies revealed that CORM-2 suppressed the expression of integrin αIIbß3 in platelets stimulated by LPS. This was accompanied by a decrease in production and phosphorylation of PKCθ and Munc18a, SNARE complex assembly and subsequently platelet α-granule exocytosis. Taken together, we suggested that the potential mechanism of suppressive effect of CORM-2 on LPS-induced platelet SNAREs complex assembly and α-Granule Exocytosis might involve integrin αIIbß3-mediated PKCθ/Munc18a pathway activation.


Assuntos
Plaquetas/efeitos dos fármacos , Monóxido de Carbono/farmacologia , Proteínas Munc18/genética , Compostos Organometálicos/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética , Proteína Quinase C-theta/genética , Proteínas SNARE/genética , Plaquetas/citologia , Plaquetas/metabolismo , Monóxido de Carbono/química , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/metabolismo , Exocitose , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Fusão de Membrana/efeitos dos fármacos , Modelos Biológicos , Proteínas Munc18/metabolismo , Compostos Organometálicos/química , Ativação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Cultura Primária de Células , Proteína Quinase C-theta/metabolismo , Proteínas SNARE/metabolismo , Sepse/genética , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais
12.
Parasitol Res ; 120(10): 3519-3527, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34417865

RESUMO

Free-range chickens might mediate the spread of Cryptosporidium oocysts to humans and other animals. Few studies have evaluated the prevalence of Cryptosporidium species in domestic free-range poultry in China. Here, we characterized the prevalence and distribution of species and genotypes of Cryptosporidium in domestic free-range chickens, ducks, and geese in Anhui Province, China. A total of 1910 fresh fecal samples from three poultry species were examined from 18 free-range poultry farms by nested PCR and analysis of the Cryptosporidium SSU rRNA gene. The overall prevalence of Cryptosporidium species was 2.9% (55/1910), with infection rates of 1.3% (11/829) in chickens, 7.3% (36/487) in ducks, and 1.4% (8/594) in geese. C. baileyi (0.6%), C. meleagridis (0.2%), C. galli (0.2%), and C. xiaoi-like genotype (0.2%) were identified in chickens, and only C. baileyi was identified in ducks and geese, with infection rates of 7.4% and 1.3%, respectively. C. baileyi was the most prevalent species. Sequencing of the GP60 gene revealed that the C. meleagridis isolates belonged to the IIIbA26G1R1b subtype. This is the first study to document C. galli and C. xiaoi-like genotype in domestic free-range chickens in China. These findings expand the range of avian hosts known for Cryptosporidium and highlight the need for additional studies to characterize the diversity of Cryptosporidium in avian species.


Assuntos
Criptosporidiose , Cryptosporidium , Doenças das Aves Domésticas , Animais , Galinhas , China/epidemiologia , Criptosporidiose/epidemiologia , Cryptosporidium/genética , Fezes , Genótipo , Humanos , Aves Domésticas , Doenças das Aves Domésticas/epidemiologia , Prevalência
13.
Int J Mol Sci ; 22(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805371

RESUMO

As an evolutionarily conserved pathway, mitogen-activated protein kinase (MAPK) cascades function as the key signal transducers that convey information by protein phosphorylation. Here we identified PlMAPK2 as one of 14 predicted MAPKs encoding genes in the plant pathogenic oomycete Peronophythora litchii. PlMAPK2 is conserved in P.litchii and Phytophthora species. We found that PlMAPK2 was up-regulated in sporangium, zoospore, cyst, cyst germination and early stage of infection. We generated PlMAPK2 knockout mutants using the CRISPR/Cas9 method. Compared with wild-type strain, the PlMAPK2 mutants showed no significant difference in vegetative growth, oospore production and sensitivity to various abiotic stresses. However, the sporangium release was severely impaired. We further found that the cleavage of the cytoplasm into uninucleate zoospores was disrupted in the PlMAPK2 mutants, and this developmental phenotype was accompanied by reduction in the transcription levels of PlMAD1 and PlMYB1 genes. Meanwhile, the PlMAPK2 mutants exhibited lower laccase activity and reduced virulence to lychee leaves. Overall, this study identified a MAPK that is critical for zoosporogenesis by regulating the sporangial cleavage and pathogenicity of P.litchii, likely by regulating laccase activity.


Assuntos
Litchi/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oomicetos/patogenicidade , Doenças das Plantas , Litchi/microbiologia , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Proteínas de Plantas/metabolismo , Virulência
14.
Entropy (Basel) ; 23(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922613

RESUMO

Complex modeling has received significant attention in recent years and is increasingly used to explain statistical phenomena with increasing and decreasing fluctuations, such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which results in a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID databases, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains from Wuhan, Beijing, New York, German, and the UK variant B.1.1.7) which were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2, which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses, suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolution of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS > SARS-CoV-1 > SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

15.
BMC Microbiol ; 20(1): 4, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906854

RESUMO

BACKGROUND: Harpins are proteins secreted by the type III secretion system of Gram-negative bacteria during pathogen-plant interactions that can act as elicitors, stimulating defense and plant growth in many types of non-host plants. Harpin-treated plants have higher resistance, quality and yields and, therefore, harpin proteins may potentially have many valuable agricultural applications. Harpins are characterized by high thermal stability at 100 °C. However, it is unknown whether harpins are still active at temperatures above 100 °C or whether different temperatures affect the activity of the harpin protein in different ways. The mechanism responsible for the heat stability of harpins is also unknown. RESULTS: We identified a novel harpin, HpaXpm, from the cassava blight bacteria Xanthomonas phaseoli pv. manihotis HNHK. The predicted secondary structure and 3-D structure indicated that the HpaXpm protein has two ß-strand domains and two major α-helical domains located at the N- and C-terminal regions, respectively. A phylogenetic tree generated using the maximum likelihood method grouped HpaXpm in clade I of the Hpa1 group along with harpins produced by other Xanthomonas spp. (i.e., HpaG-Xag, HpaG-Xcm, Hpa1-Xac, and Hpa1Xm). Phenotypic assays showed that HpaXpm induced the hypersensitive response (HR), defense responses, and growth promotion in non-host plants more effectively than Hp1Xoo (X. oryzae pv. oryzae). Quantitative real-time PCR analysis indicated that HpaXpm proteins subjected to heat treatments at 100 °C, 150 °C, or 200 °C were still able to stimulate the expression of function-related genes (i.e., the HR marker genes Hin1 and Hsr203J, the defense-related gene NPR1, and the plant growth enhancement-related gene NtEXP6); however, the ability of heat-treated HpaXpm to induce HR was different at different temperatures. CONCLUSIONS: These findings add a new member to the harpin family. HpaXpm is heat-stable up to 200 °C and is able to stimulate powerful beneficial biological functions that could potentially be more valuable for agricultural applications than those stimulated by Hpa1Xoo. We hypothesize that the extreme heat resistance of HpaXpm is because the structure of harpin is very stable and, therefore, the HpaXpm structure is less affected by temperature.


Assuntos
Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/farmacologia , Desenvolvimento Vegetal/efeitos dos fármacos , Xanthomonas/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Proteínas da Membrana Bacteriana Externa/genética , Regulação Bacteriana da Expressão Gênica , Temperatura Alta , Funções Verossimilhança , Modelos Moleculares , Fenótipo , Filogenia , Domínios Proteicos , Estabilidade Proteica , Estrutura Secundária de Proteína , Nicotiana/efeitos dos fármacos , Nicotiana/crescimento & desenvolvimento
16.
Inflamm Res ; 69(1): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758219

RESUMO

PURPOSE: Sepsis, an intractable clinical syndrome, is often accompanied by severe vascular endothelial injury and barrier dysfunction. Previous evidence has shown that the endogenous repair mechanism of damaged vascular endothelium requires the proliferation of local endothelial cells (ECs), but processes of re-endothelialization and angiogenesis after endothelial injury are also affected by bone marrow-derived endothelial progenitor cells (EPCs). EPC mobilization has been linked to the mechanism of vascular endothelial repair in various chronic diseases. However, the potential value of EPC mobilization in the treatment of sepsis has not been explored. METHODS: Literature review was done to summarize the mobilization mechanism of EPC and to describe the cytokines and treatments related to EPC mobilization. Additionally, we summarize what is known about the mechanisms of endothelial damage and repair in sepsis. RESULTS: During sepsis, many endotoxins and inflammatory factors can damage ECs, resulting in increased vascular permeability and microcirculatory disorders. EPCs can serve as a source of ECs. Increasing evidence suggests that various cytokines and medicines can induce EPC mobilization. CONCLUSION: EPC mobilization plays an important role in endothelial repair; this may guide the discovery of novel methods to treat sepsis.


Assuntos
Células Progenitoras Endoteliais/fisiologia , Sepse/terapia , Animais , Movimento Celular , Humanos
17.
Inflamm Res ; 69(3): 321-330, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32025760

RESUMO

OBJECTIVE: To reveal the systematic response of neutrophils to sepsis and to study the hub lncRNAs in sepsis. MATERIALS AND METHODS: Neutrophils taken from the femur and tibia of male C57 BL/6 mice were used in this study. And neutrophils were treated for 0 h, 0.5 h, 1 h, and 4 h with or without 1 µg/mL lipopolysaccharide (LPS) for further chip detection. In addition, cecal ligation and perforation were used to simulate sepsis. Here, we used different bioinformatics analyses, including differential expression analysis, weighted gene co-expression network analysis (WGCNA), and gene regulatory network analysis, to analyze the systemic response of neutrophils to sepsis. RESULTS: We identified nine modules and found hub lncRNAs in each module. The blue and pink modules were closely related to the inflammatory state of sepsis. Some hub lncRNAs (NONMMUT005259, KnowTID_00004196, and NR_003507) may have functions related to the inflammatory state in sepsis. CONCLUSIONS: Based on a new biological approach, our research results revealed the systemic-level response of neutrophils to sepsis and identified several hub lncRNAs with potential regulatory effects on this condition.


Assuntos
Redes Reguladoras de Genes , Neutrófilos/citologia , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Sepse/sangue , Sepse/metabolismo , Animais , Células Cultivadas , Biologia Computacional , Fêmur/metabolismo , Perfilação da Expressão Gênica , Inflamação , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tíbia/metabolismo
18.
Parasitol Res ; 119(2): 637-647, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31823007

RESUMO

The trichomonad species Tetratrichomonas buttreyi and Pentatrichomonas hominis have been reported in the bovine digestive tract in only a few studies, and the prevalence and pathogenicity of these two protists in cattle herds remain unknown. In this study, the prevalence of T. buttreyi and P. hominis in yellow cattle, dairy cattle, and water buffalo in Anhui Province, China, was determined with a PCR analysis of the small subunit ribosomal RNA genes. The overall infection rates for T. buttreyi and P. hominis were 8.1% and 5.4%, respectively. Double infections were found in 15 (1.6%) samples from four farms. The prevalence of P. hominis in cattle with abnormal feces was significantly higher than that in cattle with normal feces (χ2 = 13.0, p < 0.01), and the prevalence of T. buttreyi in the northern region of Anhui Province was also significantly higher than that in the mid region (χ2 = 16.6, p < 0.01). Minor allelic variations were detected in the T. buttreyi isolates from cattle in this study, as in other hosts in previous studies. Morphological observations, together with the PCR analysis, demonstrated that the trichomonads isolated in this study were P. hominis. The presence of T. buttreyi and P. hominis indicated that cattle are natural hosts of these two trichomonads and could be a potential source of P. hominis infections in humans and other animal hosts.


Assuntos
Búfalos/parasitologia , Doenças dos Bovinos/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Trichomonadida/genética , Animais , Bovinos , China/epidemiologia , Fezes , Trato Gastrointestinal/parasitologia , Humanos , Prevalência , RNA Ribossômico 18S/genética , Trichomonadida/classificação , Trichomonadida/isolamento & purificação
19.
Parasitol Res ; 119(7): 2359-2362, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500368

RESUMO

Several Cryptosporidium species that infect reptiles, especially squamates, are well described, but there is limited data about Cryptosporidium species infecting crocodilians. In this study, we assess the occurrence of intestinal parasites using traditional microscopic examination and describe the prevalence and Cryptosporidium species in the captive-bred Chinese alligators (Alligator sinensis) in eastern China using molecular methods. The results of microscopic examination showed that no intestinal parasites were detected among the 491 fecal samples examined from the Chinese alligators. The overall prevalence for Cryptosporidium was 0.41% (2/491) by PCR detection using the SSU rRNA locus. Sequence and phylogenetic analysis of the SSU rRNA, COWP, and actin genes revealed the presence of Cryptosporidium testudinis, which has been isolated primarily from chelonians. This is the first detection of the specific DNA of C. testudinis in the feces of the Chinese alligator. This study expands our knowledge of the Cryptosporidium species involved in crocodiles, and more extensive studies are necessary to confirm the validity of C. testudinis in crocodiles.


Assuntos
Jacarés e Crocodilos/parasitologia , Criptosporidiose/parasitologia , Cryptosporidium/isolamento & purificação , Animais , China/epidemiologia , Criptosporidiose/epidemiologia , Cryptosporidium/classificação , Cryptosporidium/genética , DNA de Protozoário/genética , DNA Ribossômico/genética , Fezes/parasitologia , Genes de Protozoários/genética , Filogenia
20.
Opt Express ; 26(3): 3466-3482, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29401874

RESUMO

We present a backlight module (BLM) employing a photoluminescent quantum-dot microstructure array for flexible/curved liquid crystal displays (LCDs). Differently sized quantum-dot (QD) BLMs were prepared based on the theoretical spectral model and microstructure fabrication process. A 27-inch curved prototype showed a wide color gamut of 122.79% under the National Television Systems Committee standard while achieving high brightness of over 4000 cd/m2 and brightness/color uniformity of 85.21%/9.2 × 10-3. An LCD monitor prototype equipped with the proposed BLM was also assembled and tested, which showed higher visual performance when compared with a common commercial monitor. This method produces QD BLMs without the need of additional optical elements, and has good compatibility with traditional processes.

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