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1.
Food Chem ; 369: 130923, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455331

RESUMO

Lactic acid bacteria are one of the most pivotal probiotics. Promoting their viability could be an effective method to modulate the balance of intestinal flora, thereby improving human health. The current solution is to take advantage of carbon-sourced prebiotics, while protein and peptides with potential prebiotic functions have not been investigated. Soy proteins and peptides have been proven to enhance the growth and metabolism of Lactobacillus. However, research on the relationship between strains of lactobacilli and the structure of soybean peptides is still limited. In the present study, soybean protein and peptides effectively increased the growth and organic acid secretion of Limosilactobacillus reuteri LR08. Additionally, soybean peptides and fructooligosaccharides showed synergistic effects in modulating Limosilactobacillus reuteri LR08. Fraction 1 acquired from soy peptides using RP-HPLC exhibited the most effectiveness and several novel peptides were identified. These results could theoretically and practically benefit soybean peptide application as a potential prebiotic.


Assuntos
Lactobacillus reuteri , Probióticos , Humanos , Lactobacillus , Peptídeos , Prebióticos , Soja
2.
J Clin Transl Hepatol ; 9(5): 615-625, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722176

RESUMO

Background and Aims: Chronic hepatitis B is the main cause of liver cancer. However, the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase (ALT). People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment. However, the truth is not as optimistic as we thought. We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients. Methods: Medline, Embase, and Cochrane Library were searched up to January 10th 2020, to identify studies of these patients with liver biopsy. The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis. Potential heterogeneity was explored by subgroup analysis and meta-regression. Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis. The secondary outcome was to find the risk factors of significant histological changes. Results: Nineteen eligible studies, with 2,771 participants, were included. The pooled proportion of significant inflammation or fibrosis was 35% [95% confidence interval (CI): 27 to 43] and 30% (95% CI: 25 to 36), respectively. The pooled proportion of cirrhosis was 3% [95% CI: 1 to 5, (12 studies; 1,755 participants)]. In subgroup analysis, old age [vs. young (<40 years-old), 44% vs. 26%, p=0.012] was significantly associated with higher fibrosis stage as well as cirrhosis [vs. young (<40 years-old), 4.8% vs. 1.8%, p<0.001]. Conclusions: About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes, and some even have cirrhosis.

3.
J Food Sci ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730237

RESUMO

Current studies regarding the effect of different nitrogen sources on gut microbiota have thus far disregarded the ability of probiotics and coliforms to compete for protein. This study aimed to investigate the differences in the utilization of soybean protein (SPro) and its derived peptides (SPep) by the gut microbiota of Sprague Dawley (SD) rats. The SPro and SPep prepared in this study showed extensive SPro molecular weight distribution, while that of SPep was minimal, ranging between 150 and 1000 Da and primarily consisting of two to five amino acids. The cecum microflora composition of the rats was determined via 16S rDNA amplicon sequencing, showing that the SPro and SPep significantly increased the abundance and uniformity of the gut microbiota after 35 days of feeding. The Firmicutes/Bacteroidetes (F/B) ratios of the SPep, SPro, and casein groups were 2.49 ± 0.60, 2.98 ± 1.12, and 2.59 ± 0.74, respectively. Although the rats fed with SPro and SPep displayed similar gut microbiome structures, SPep significantly promoted Lactobacillus and Phascolarctobacterium growth. The results showed that SPep significantly increased the diversity of the gut microbiota and elevated the probiotic proportion. PRACTICAL APPLICATION: SPro and SPep are two nutritious and high-quality nitrogen sources. The results showed that SPro and SPep regulated the structure of gut microbiota in rats, and the effect of SPep was better. This study provides a theoretical basis for developing SPep functional foods able to regulate gut microbiota and maintain health.

4.
J Am Chem Soc ; 143(45): 18907-18916, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34729984

RESUMO

Elpasolite- and cryolite-type oxyfluorides can be regarded as superstructures of perovskite and exhibit structural diversity. While maintaining a similar structural topology with the prototype structures, changes in the size, electronegativity, and charge of cation and/or anion inevitably lead to structural evolution. Therefore, the nominal one-to-one relation suggested by a doubled formula of perovskite does not guarantee a simple 2-fold superstructure for many cases. Herein, the commensurately modulated perovskite-like K3TiOF5 was refined at 100 K from single-crystal X-ray diffraction data by using a pseudotetragonal subcell with lattice parameters of a = b = 6.066(2) Å and c = 8.628(2) Å. The length of the modulation vector was refined to 0.3a* + 0.1b* + 0.25c*. In the commensurate supercell of K3TiOF5, the B-site Ti4+ and K+ cations in [TiOF5]3- and [KOF5]6- octahedral units were found to be significantly displaced from the average atomic positions refined in the subcell. The displacements of the K+ cations are ±0.76 Å, and those for the Ti4+ cations are approximately ±0.13 Å. One- and two-dimensional solid-state 19F NMR measurements revealed two tightly clustered groups of resonances in a ratio of ca. 4:1, assigned to equatorial and axial fluorine, respectively, consistent with local [TiOF5]3- units. S/TEM results confirmed the average structure. Electronic structure calculations of the idealized I4mm subcell indicate the instability to a modulated structure arises from soft optical modes that is controlled by the octahedrally coordinated B-site potassium ions in the cryolite-type structure.

5.
J Transp Geogr ; 96: 103176, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34776657

RESUMO

The outbreak of COVID-19 in China started at the end of December 2019. This led to a series of containment measurements to control the spread of COVID-19. Despite of the widely reported effects of these measures, inadequate attention has gone to their social impacts. The elderly, as one of the most susceptible populations, has experienced a considerable reduction in mobility. This paper explores the role mobility played and how the social environment influenced elderly mobility in the first 2 months of the COVID-19 outbreak. We surveyed 186 families with a total of 248 elderly people in Kunming. The results show that mobility improves the quality of daily living, such as access to grocery shopping, maintenance of outdoor activities for health cultivation and preserving social networks even during the pandemic. Four themes relating to social environment emerged from the data as elements influencing elderly mobility during the pandemic: social pressure, practice of the virtue of Xiao, the social norm of respecting the aged and the impacts of technological advances. Among them, the virtue of Xiao enabled the elderly to stay in place in the early phase of COVID-19 by fulfilling their needs for daily necessities and social interactions, whilst being less technology-savvy further excluded them socially by restraining them from restoring mobility after the lifting of travel restrictions.

6.
Food Funct ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784410

RESUMO

Obesity is a most prevalent human health problem. Several studies showed that appropriate modulation of gut microbiota could help reshape the metabolic profile of obese individuals, thereby altering the development of obesity. A nutritional strategy for treating obesity includes prebiotics. Type 3 Resistant Starch from Canna edulis (Ce-RS3) is a dietary fiber that exerts potential effects on the intestinal microbial community; however, the metabolic landscape and anti-obesity mechanism remain unclear. In the present study, obese mice were treated with Ce-RS3, and 16S rRNA gene sequencing and metabolomics were used to measure changes in gut microbiota and fecal metabolic profiles, respectively. At the end of the treatment (13 weeks), we observed slow weight gain in the mice, and pathological damage and inflammation were substantially reduced. Ce-RS3 constructs a healthy gut microbiota structure and can enhance intestinal immunity and reduce metabolic inflammation. Ce-RS3 increased the diversity of gut microbiota with enrichment of Bifidobacterium and Roseburia. Ce-RS3 regulated the systemic metabolic dysbiosis in obese mice and adjusted 26 abnormal metabolites in amino acids and lipids metabolism, many of which are related to the microbiome. More importantly, we found that the anti-obesity effect of Ce-RS3 can be transferred by fecal transplantation. The beneficial effects of Ce-RS3 might derive from gut microbiota changes, which might improve obesity and metabolic inflammation by altering host-microbiota interactions with impacts on the metabolome. In conclusion, Ce-RS3 can be used as a prebiotic with potential value for the treatment of obesity.

7.
Opt Express ; 29(24): 40310-40322, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809375

RESUMO

We demonstrate a wide viewing angle polarization interference filter (PIF), which consists of two crossed polarizers and double liquid crystal layers with opposite twisted direction. The polarization interference effect of the PIF is achieved by the double liquid crystal layers, and an additional compensation layer between the double liquid crystal layers can further improve the optical performance of the PIF. By using the Jones matrix method, we derive the transmittance formula of the PIF with/without compensation layer, which can be used to design any required color filter by selecting the appropriate twist angle and thickness of the liquid crystal layer. We design blue, green and red PIFs and analyze their optical performance. The proposed PIF has a wider viewing angle (±30°), and the color saturation of the PIF is also considerably high.

8.
Front Pharmacol ; 12: 764669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733163

RESUMO

Background: BuqiTongluo (BQTL) granules are herbal phenotypic drugs for Qi deficiency and blood stasis (QDBS) syndrome. Its discovery relied primarily on knowledge of observable phenotypic changes associated with diseases. Although BQTL granules have been widely advocated by Chinese Medicine (CM) practitioners, its use lacks empirical support. Aim of the study: In this basket trial, the efficacy of BQTL granules in multiple diseases that have the QDBS syndrome in common will be compared with placebo. Materials and Methods: The BuqiTongluo granule for Qi deficiency and blood stasis syndrome (BOSS) study is a basket herbal trial (ClinicalTrials.gov, NCT04408261). It will be a double-blinded, randomized, placebo-controlled, parallel, multicenter, clinical trial. In total, 432 patients (1:1:1 ischemic stroke, stable angina pectoris, and diabetic peripheral neuropathy), who meet the operationalized diagnostic criteria for QDBS syndrome, have been recruited and randomized in a ratio of 1:1 to receive 6 weeks' treatment with BQTL granules or placebo. The primary outcome is the change in the QDBS syndrome score at week 6 from baseline. Secondary outcomes include objective outcome measures for the three diseases and adverse events. Omics will help to understand these responses by molecular events. Conclusion: QDBS syndrome is a common phenotypic marker that was hypothesized to predict whether patients with multiple diseases would respond to this targeted therapy. No previous basket trial has assessed the potential efficacy of an herbal intervention for multiple diseases. The unique promise of the trial is its ability to exploit a disease phenotype to discover novel treatments for three diseases for which the root cause is unknown, complex, or multifactorial, and for which scientific understanding is insufficient to provide valid molecular targets.

9.
Transl Androl Urol ; 10(9): 3566-3578, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733653

RESUMO

Background: Urine-derived stem cells (USCs) have been widely researched as a novel cell source for stem cell therapy, but their immunomodulatory characteristics remain to be investigated. This study aimed to characterize the immunomodulatory properties of human USCs. Methods: Human USCs were isolated from fresh voiding urine samples from healthy male donors and expanded. Their cell surface markers were characterized by flow cytometry analysis and the telomerase activities for several USCs clones were determined. The immunosuppressive potential of USCs was evaluated by the performing the mixed lymphocyte reaction (MLR) [co-culture with peripheral blood mononuclear cells (PBMNCs)] and natural killer cells (NK) cytotoxicity assay. USCs cytokines release profile was determined by using human cytokine proteome array. Results: USCs exhibited high cell surface expression of embryonic/mesenchymal stem cells (MSCs) markers CD29, CD44, CD54, CD73, CD90, CD146, and CD166, while lacked expression of hematopoietic stem cell markers CD11, CD14, CD19, CD31, CD34, CD45, B cell marker CD79, and co-stimulatory factors CD80 and CD86, thus, exhibiting the phenotype of MSCs. MLR indicated that USCs significantly inhibited the proliferation of PBMNCs, as compared to that of the human smooth muscle cells (SMCs). In cell cytotoxicity assays, NK cells displayed less cytotoxicity against USCs than against bone marrow mesenchymal stem cells (BMSCs) and SMCs. Furthermore, upon PBMNCs stimulation, USCs secreted higher levels of immunomodulatory cytokines, including IL-6, IL-8, MCP-1, RANTES, GROα, and GM-CSF, compared to those of BMSCs, especially when directly contact mix-culture with PBMNCs. Conclusions: USCs secreted immunoregulatory cytokines and possessed immunomodulatory properties, comparable to those of BMSCs.

10.
Nucleic Acid Ther ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797690

RESUMO

Antisense oligonucleotides (ASOs), a novel paradigm in modern therapeutics, modulate cellular gene expression by binding to complementary messenger RNA (mRNA) sequences. While advances in ASO medicinal chemistry have greatly improved the efficiency of cellular uptake, selective uptake by specific cell types has been difficult to achieve. For more efficient and selective uptake, ASOs are often conjugated with molecules with high binding affinity for transmembrane receptors. Triantennary N-acetyl-galactosamine conjugated phosphorothioate ASOs (GalNAc-PS-ASOs) were developed to enhance targeted ASO delivery into liver through the hepatocyte-specific asialoglycoprotein receptor (ASGR). We assessed the kinetics of uptake and subsequent intracellular distribution of AlexaFluor 488 (AF488)-labeled PS-ASOs and GalNAc-PS-ASOs in J774A.1 mouse macrophages and primary mouse or rat hepatocytes using simultaneous coherent anti-Stokes Raman scattering (CARS) and two-photon fluorescence (2PF) imaging. The CARS modality captured the dynamic lipid distributions and overall morphology of the cells; two-photon fluorescence (2PF) measured the time- and dose-dependent localization of ASOs delivered by a modified treatment of suspension cells. Our results show that in macrophages, the uptake rate of PS-ASOs did not significantly differ from that of GalNAc-PS-ASOs. However, in hepatocytes, GalNAc-PS-ASOs exhibited a peripheral uptake distribution compared to a polar uptake distribution observed in macrophages. The peripheral distribution correlated with a significantly larger amount of internalized GalNAc-PS-ASOs compared to the PS-ASOs. This work demonstrates the relevance of multimodal imaging for elucidating the uptake mechanism, accumulation, and fate of different ASOs in liver cells that can be used further in complex in vitro models and liver tissues to evaluate ASO distribution and activity.

11.
Biosens Bioelectron ; 196: 113741, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34736103

RESUMO

In this study, a highly ordered three dimensional (3D) DNA nanostructure was self-assembled by label-free DNA nanotweezers, which was used as recognized probe to interact with target. Once the target was recognized by the 3D DNA nanoprobe (3D DNT), DNA nanotweezers opened to release target analog (T1). This recognition process was proceeded in homogeneous solution, which can avoid complex electrode modification and improve reaction efficiency. Then these target analogs were captured by the signal DNA probes (E1) modified on the electrode. In the assistance of Exo III, E1 was digested and the T1 was released to participate in the next cycle to realize signal amplification. Finally, an ultrasensitive carcinoembryonic antigen (CEA) electrochemical biosensing with a detection limit of 4.88 fg mL-1 was developed.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34783538

RESUMO

The ability to detect multidimensional forces is highly desired for electronic skin (E-skin) sensors. Here, based on single-electrode-mode triboelectric nanogenerators (S-TENGs), fully elastic E-skin that can simultaneously sense normal pressure and shear force has been proposed. With the hemispherical curve-structure design and further structural optimization, the pressure sensor exhibits a high linearity and sensitivity of 144.8 mV/kPa in the low-pressure region. By partitioning the lower tribolayer into two symmetric parts, a multidimensional force sensor has been fabricated in which the output voltage sum and ratio of the two S-TENGs can be used for normal pressure and shear force sensing, respectively. When the multidimensional force sensors are mounted at a two-fingered robotic manipulator, the change of the grabbing state can be recognized, indicating that the sensor may have great application potential in tactile sensing for robotic manipulation, human-robot interactions, environmental awareness, and object recognition.

13.
Oncology ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794142

RESUMO

PURPOSE: The systemic immune-inflammation index (SII) is correlated with patient survival in various solid malignancies including non-small cell lung cancer (NSCLC). However, limited information is available on the prognostic implication of SII in patients undergoing trimodality therapy for stage III Non-Small Cell Lung Carcinoma (NSCLC). METHODS: At our institution, 81 patients underwent curative intent trimodality therapy (neoadjuvant chemoradiotherapy followed by surgical resection) for stage III NSCLC from 2004-2019. SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. Chi-squared analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate disease free survival (DFS), overall survival (OS), and freedom from recurrence (FFR) rates, with Cox regression used to determine absolute hazards. RESULTS: Patients underwent neoadjuvant radiation therapy to a median dose of 4500 cGy concurrent with a median of 3 cycles of chemotherapy (most commonly carboplatin and paclitaxel) followed by surgical resection (86.4% lobectomy and 13.6% pneumonectomy) with mediastinal lymph node dissection. At a median follow-up of 68.4 months, a low SII (<1260) at diagnosis was independently associated with an improved OS (HR: 0.448, p=0.004), DFS (HR: 0.366, p<0.001), and FFR (HR: 0.325, p=0.002). CONCLUSIONS: We identified that a low SII was associated with improved OS, DFS, and FFR in patients undergoing trimodality therapy for stage III NSCLC. The interplay of the immune system and lung cancer outcomes remains an active area of investigation for which further study is warranted.

14.
Nat Commun ; 12(1): 6711, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795238

RESUMO

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.

15.
BMC Musculoskelet Disord ; 22(1): 951, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781964

RESUMO

BACKGROUND: A variety of bone graft substitutes have been introduced into the treatment of bone non-unions. However, clinical outcomes from current evidences are various and conflicting. This study aimed to present the preliminary outcomes of a treatment protocol in which the combination of demineralized bone matrix (DBM) and platelet rich plasma (PRP) was used as a bone graft substitute for long bone non-unions. METHODS: Data of this retrospective study were reviewed and collected from a consecutive case series involving 43 patients who presented with a long bone non-union and were treated in our department from October 2018 to May 2019. The combination of DMB and PRP was applied as a bone defect filler in 16 patients, whilst the other 27 patients were treated with iliac bone autografting. Patients' demographics, postoperative complications and the result of bone union were compared and evaluated. RESULTS: The demographic data between the two groups were comparable. No significant difference was found with regard to the incidence of postoperative complications. No graft rejection, heterotopic ossification or other complications were noted. The distribution of bony healing time was rather scattered but did not differ significantly between the groups (7.533 ± 3.357 months vs. 6.625 ± 2.516 months; P=0.341). Union was identified radiographically in 15 of 16 patients in the DBM+PRP group and in 24 of 27 patients in autograft group. CONCLUSIONS: The present study identified that low incidence of postoperative complications and satisfactory bony healing rate could be achieved in the treatment of long bone non-unions augmented with the combination of DBM and PRP. Although these findings might indicate the promising future of this treatment protocol, larger and higher quality studies should also be executed to assess its routine use.


Assuntos
Substitutos Ósseos , Plasma Rico em Plaquetas , Matriz Óssea , Transplante Ósseo , Humanos , Estudos Retrospectivos , Transplante Autólogo
16.
Nat Commun ; 12(1): 6437, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750384

RESUMO

As a quantum material, Weyl semimetal has a series of electronic-band-structure features, including Weyl points with left and right chirality and corresponding Berry curvature, which have been observed in experiments. These band-structure features also lead to some unique nonlinear properties, especially high-order harmonic generation (HHG) due to the dynamic process of electrons under strong laser excitation, which has remained unexplored previously. Herein, we obtain effective HHG in type-II Weyl semimetal ß-WP2 crystals, where both odd and even orders are observed, with spectra extending into the vacuum ultraviolet region (190 nm, 10th order), even under fairly low femtosecond laser intensity. In-depth studies have interpreted that odd-order harmonics come from the Bloch electron oscillation, while even orders are attributed to Bloch oscillations under the "spike-like" Berry curvature at Weyl points. With crystallographic orientation-dependent HHG spectra, we further quantitatively retrieved the electronic band structure and Berry curvature of ß-WP2. These findings may open the door for exploiting metallic/semimetallic states as solid platforms for deep ultraviolet radiation and offer an all-optical and pragmatic solution to characterize the complicated multiband electronic structure and Berry curvature of quantum topological materials.

17.
J Healthc Eng ; 2021: 6264447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790344

RESUMO

As the aging continues, China has become the country with the largest older population. In order to ensure the well-being of older adults in their later years, the whole society is increasingly concerned about the mental health of older adults. In 2019, we conduct a questionnaire survey in Shaanxi Province. Stratified random sampling is used to select three representative cities, and 677 samples are selected from the survey results for research. By using the structural equation model, we aim to reveal the mechanism of leisure activities' influence on mental health of the older adults and verify whether social support and perceived stress play a mediating role. The study finds that the older adults' leisure activities have no significant direct impact on mental health. Social support has a significant mediating effect between leisure activities and mental health of the older adults. Leisure activities indirectly affect the mental health of the older adults through social support, and participation in leisure activities can improve the social support of the older adults, thus improving the mental health level of the older adults. Perceived stress plays a significant mediating role between leisure activities and mental health of the older adults. By participating in leisure activities, the perceived stress of the older adults will be reduced, thus improving their mental health. Social support and perceived stress play a sufficient mediating role in the influence of leisure activities on mental health.

18.
mBio ; : e0300721, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34781745

RESUMO

The life cycle of filamentous fungi generally comprises hyphal growth and asexual reproduction. Both growth and propagation processes are critical for invasion growth, spore dissemination, and virulence in fungal pathogens and for the production of secondary metabolites or for biomass accumulation in industrial filamentous fungi. The CCAAT-binding complex (CBC) is a heterotrimeric transcription factor comprising three subunits, HapB, HapC, and HapE, and is highly conserved in fungi. Previous studies revealed that CBC regulates sterol metabolism by repressing several genes in the ergosterol biosynthetic pathway in the human fungal pathogen Aspergillus fumigatus. In the present study, we found dysfunction of CBC caused the abnormal asexual reproduction (conidiation) in submerged liquid culture. CBC suppresses the activation of the brlA gene in the central regulatory pathway for conidiation combined with its upstream regulators fluG, flbD, and flbC by binding to the 5'-CCAAT-3' motif within conidiation gene promoters, and lack of CBC member HapB results in the upregulation of these genes. Furthermore, when the expression of brlA or flbC is repressed, the submerged conidiation does not happen in the hapB mutant. Interestingly, deletion of HapB leads to enhanced transient cytosolic Ca2+ levels and activates conidiation-positive inducer Ca2+-CrzA modules to enhance submerged conidiation, demonstrating that CrzA works with CBC as a reverse regulator of fungal conidiation. To the best of our knowledge, the finding of this study is the first report for the molecular switch mechanism between vegetative hyphal growth and asexual development regulated by CBC, in concert with Ca2+-CrzA signaling in A. fumigatus. IMPORTANCE A precisely timed switch between vegetative hyphal growth and asexual development is a crucial process for the filamentous fungal long-term survival, dissemination, biomass production, and virulence. However, under the submerged culture condition, filamentous fungi would undergo constant vegetative growth whereas asexual conidiation rarely occurs. Knowledge about possible regulators is scarce, and how they could inhibit conidiation in liquid culture is poorly understood. Here, we demonstrated that the transcription factor heterotrimeric CBC dominantly maintains vegetative growth in liquid-submerged cultures by directly suppressing the conidiation-inductive signal. In contrast, calcium and the transcription factor CrzA, are positive inducers of conidiation. Our new insights into the CBC and Ca2+-CrzA regulatory system for transition control in the submerged conidiation of A. fumigatus may have broad repercussions for all filamentous fungi. Moreover, our elucidation of the molecular mechanism for submerged conidiation may support new strategies to precisely control vegetative growth and asexual conidiation in aspergilli used in industry.

19.
Exp Ther Med ; 22(6): 1480, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34765021

RESUMO

Fluorescence in situ hybridization (FISH) serves as an ancillary tool for assessing chromosomal abnormalities and is important in differential diagnoses and treatment decisions. In clinical practice, pathologists encounter unsatisfactory formalin-fixed paraffin-embedded (FFPE) sections exhibiting weak fluorescence signals, mostly due to inappropriate tissue processing or preservation, leading to interpretation difficulties. For the present study, FFPE samples for which conventional FISH failed were collected. Instead of a pretreatment step using a commercial kit, heat-induced antigen retrieval (HIAR) was introduced using either citrate buffer or Tris-EDTA buffer, while the subsequent experimental workflow remained unchanged. After HIAR-assisted FISH, the hybridization efficiency and signal intensity were markedly enhanced and no difference in signal adequacy was observed when comparing the effect of the two AR solutions. The present study demonstrated that HIAR is a reliable tool for FISH, particularly for poor-quality FFPE sections yielding weak or no fluorescence signals in the conventional analysis.

20.
Front Pharmacol ; 12: 701886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737697

RESUMO

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2-related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer. Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS. Methods: Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed. Results: SFI treatment efficiently postponed the disease onset (p = 0.022) and extended the overall survival (p = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss (p < 0.001) and astrocytic activation (p < 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde (p < 0.05) and increasing the levels of superoxide dismutase (p < 0.05), Nrf2 (p < 0.05), heme oxygenase-1 (p < 0.05), and glutathione S-transferase (p < 0.05) in the SOD1-G93A mice. Conclusion: The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain via alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.

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