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1.
Heliyon ; 8(4): e09273, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35497040

RESUMO

This paper systematically analyzes the impact mechanism of bank competition on stability. We select the balanced panel data of 4,631 non-failure banks from 2002 to 2017 released by FDIC to do the estimation and then make an appraisal on bank competition with Lerner index and two kinds of Z-score to measure bank stability respectively. The 2SLS with fixed effect is applied for estimation. Our results suggest that: (1) Competition is a living environment for all industries and bank competition mainly affects stability through franchise value, the cost of borrowing and operating behavior. (2)According to the overall regression, we find that there is an inverted U-shaped relationship between bank competition and stability with an inflection point where the Lerner index is about 0.35. Generally, the US banking industry has always been in a state of excessive competition during the observed period. The further analysis of 3 stages indicates that excessive bank competition, an 'invisible hand', may be one of the most important factors triggering the financial crisis. (3) According to the regression on regions, the inverted U-shaped relationship between bank competition and stability is also existing and the inflection point of Lerner index is between 0.3 and 0.37. However, there is also some regional heterogeneity in terms of the degree of competition, the level of stability and the ability to resist risks and maintain stability when facing competition. This paper may help financial regulators and commercial banks formulate differentiate regulatory policies and business strategies so that banks can control risks better and enhance stability in different competitive environments.

2.
iScience ; 25(4): 104114, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35391832

RESUMO

The laryngeal echolocation is regarded as one of the conspicuous traits that play major roles in flourishing bats. Whether the laryngeal echolocation in bats originated once, however, is still controversial. We here address this question by performing molecular convergence analyses between ancestral branches of bats and toothed whales. Compared with controls, the molecular convergences were enriched in hearing-related genes for the last common ancestor of bats (LCAB) and extant echolocating bats, but not for the LCA of Old World fruit bats (LCAP). And the convergent hearing gene prestin of the LCAB and the extant echolocating bats functionally converged. More importantly, the high-frequency hearing of the LCAP-prestin knock-in mice decreased with lower cochlear outer hair cell function compared with the LCAB-prestin knock-in mice. Together, our findings provide multiple lines of evidence suggesting a single origin of laryngeal echolocation in the LCAB and the subsequent loss in the LCAP.

3.
BMC Ophthalmol ; 22(1): 156, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35379202

RESUMO

BACKGROUND: Transforming growth factor (TGF) is a cytokine that acts on the proliferation, migration, differentiation, and apoptosis of cells and the accumulation of extracellular matrix components. Very few studies have precisely evaluated the concentration of TGF-ß in the aqueous humour (AH) of diabetic and cataract (DMC) eyes due to the low expression of proteins in the AH or other reasons. The concentrations of TGF-ß1, -ß2, and -ß3 in the AH of the DMC group were compared with those of the age-related cataract (ARC) group. METHODS: We collected AH and lens epithelium samples from 33 DMC patients and 36 ARC patients. Luminex liquid suspension chip detection was applied to detect the concentration of TGF-ß1, -ß2, and -ß3 in the AH samples. The expression of TGFB1/2/3 in lens epithelium samples was determined by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The concentrations of TGF-ß1 and TGF-ß2 in AH samples of DMC eyes were higher than those of ARC eyes. The differences in TGF-ß1 and TGF-ß2 between the two groups were statistically significant (P value = 0.001 for TGF-ß1, P value = 0.023 for TGF-ß2). The difference of the correlation between TGF-ß1 and glycosylated haemoglobin was significant (P value = 0.011, and Pearson correlation coefficient = 0.306). The difference of the correlation between TGF-ß2 and glycosylated haemoglobin was significant (P value = 0.026, and Pearson correlation coefficient = 0.269). The mRNA expression levels of TGFB1 and TGFB2 were upregulated in DMC epithelium samples compared with ARC epithelium samples. The differences in TGFB1 and TGFB2 between the two groups were statistically significant (P value for TGFB1 = 0.041, P value for TGFB2 = 0.021). CONCLUSIONS: The concentrations of TGF-ß1 and TGF-ß2 in AH samples were significantly higher in DMC eyes than in ARC eyes. The higher the glycosylated haemoglobin was, the higher the concentrations of TGF-ß1 and -ß2 were. The mRNA expression of TGFB1 and TGFB2 was significantly upregulated in DMC epithelial samples compared with ARC epithelial samples, suggesting the proinflammatory status of the anterior chamber of DMC eyes.


Assuntos
Catarata , Diabetes Mellitus , Humor Aquoso/metabolismo , Catarata/metabolismo , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1 , Fator de Crescimento Transformador beta2/genética
4.
Microbiol Spectr ; : e0249321, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35446115

RESUMO

Mycoplasma hyorhinis is a widespread pathogen in pig farms worldwide. Although the majority of M. hyorhinis-colonized pigs have no apparent clinical disease, the pathogen can induce diseases such as polyserositis, arthritis, and eustachitis in some cases. To explore the mechanisms for the occurrence of these diseases, we challenged 4 groups of Bama miniature pigs with M. hyorhinis isolated from pigs without clinical symptoms (non-clinical origin [NCO] strain) or with typical clinical symptoms (clinical origin [CO] strain) and investigated the impacts of different strains and inoculation routes (intranasal [IN], intravenous [IV] + intraperitoneal [IP], and IV+IP+IN) on disease induction. Another group of pigs was set as a negative control. Pigs inoculated with the CO strain through a combined intravenous and intraperitoneal (IV+IP) route showed a significant decrease in average daily weight gain (ADWG), serious joint swelling, and lameness compared with the pigs in the negative-control group. Furthermore, this group developed moderate-to-severe pericarditis, pleuritis, peritonitis, and arthritis, as well as high levels of IgG and IgM antibodies. Pigs inoculated IV+IP with the NCO strain developed less marked clinical, pathological changes and a weaker specific antibody response compared with the pigs inoculated with the CO strain. The challenging results of the NCO strain via different routes (IV+IP, IV+IP+IN, and IN) indicated that the combined route (IV+IP) induced the most serious disease compared to the other inoculation routes. Intranasal inoculation induced a smaller decrease in ADWG without obvious polyserositis or arthritis. These data suggest that differences in both strain virulence and inoculation route affect the consequences of M. hyorhinis infection. IMPORTANCE Mycoplasma hyorhinis is a widespread pathogen in pig farms worldwide. The mechanisms or conditions that lead to the occurrence of disease in M. hyorhinis-infected pigs are still unknown. The objective of this study was to evaluate the impact of differences in the virulence of strain and the inoculation route on the consequences of M. hyorhinis infection.

5.
J Food Sci ; 87(5): 2229-2244, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35446445

RESUMO

Sichuan pickle is one of popular traditional fermented foods in China. However, the contamination of heavy metals in Sichuan pickle, particularly home-made Sichuan pickle and aged pickle brine, is little known. Therefore, the content of trace (Cr, Cu, and Zn) and toxic elements (As, Pb, and Cd) in Sichuan industrial pickle (SIP), Sichuan home-made pickle (SHP), and aged pickle brine collected from local markets and families in Sichuan province, respectively, was detected by inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) and the health risk was assessed by target hazard quotients including target hazard quotient (THQ) and total target hazard quotient (TTHQ). Consequently, the mean concentrations of Cr, Cu, Zn, As, Pb, and Cd were 0.122, 0.540, 2.516, 0.023, 0.015, and 0.106 mg/kg in SIP and 0.071, 0.364, 2.698, 0.014, 0.015, and 0.289 mg/kg in SHP, respectively, lower than the maximum allowable concentrations set by Chinese regulations, except for Cr and Cd in few samples. Principal component analysis of the heavy metal content could obviously distinguish between SIP and SHP. The content of As, Pb, and Cd in leaf pickles was significantly higher than that in pickles fermented with other types of vegetables. A significant enrichment of heavy metals in aged pickle brine over 10 years was observed, but pickle jars had no significant effect on heavy metal content in aged pickle brine. The intake of heavy metals through daily consumption of SIP and SHP was at a safe level, whereas the TTHQ of leaf pickle was 1.006, indicating a potential health risk. In conclusion, this study provided fundamental data for food safety assurance of Sichuan pickle. PRACTICAL APPLICATION: Sichuan pickle is one of popular traditional fermented foods in China. In the present study, we investigated the contamination of heavy metals in Sichuan pickles by detecting the content of Cr, Cu, Zn, As, Cd, and Pb in Sichuan industrial pickle, Sichuan home-made pickle, and aged pickle brine, and estimated the health risk to local residents. This study can provide a reference for the safety risk of Sichuan industrial and home-made pickle in terms of heavy metal contamination, and enhance the food safety in the processing, production, and consumption of Sichuan pickle in local families and pickle industry.


Assuntos
Metais Pesados , Idoso , Cádmio , Humanos , Chumbo , Medição de Risco , Espectrometria de Massas em Tandem , Verduras
6.
Cell Death Discov ; 8(1): 225, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461343

RESUMO

Angiopoietin-like-4 (ANGPTL4), a secreted glycoprotein that is mainly known as a regulator in lipid metabolism, now, is also indicated to be involved in the regulation of cancer progression and metastasis. However, little is known about not only biological functions, but also underlying mechanism of ANGPTL4 in the progression of osteosarcoma (OS). Here, we discovered that ANGPTL4 is downregulated in OS, and is associated with branched-chain amino acid (BCAA) metabolism. The BCAAs (valine, leucine, and isoleucine) are essential amino acids that play an important role in metabolic regulation. Aberrant BCAA metabolism is also found in various cancers and is associated with tumor progression, including proliferation, invasion, and metastasis. In this study, we indicated that the negative relation between the expression of ANGPTL4 and BCAA catabolism in OS samples and cell lines. The knockdown of ANGPTL4 in OS cells resulted in the accumulation of BCAAs, which in turn activated the mTOR signaling pathway, enhancing OS cell proliferation. Thus, reduced expression of ANGPTL4 is associated with the progression of OS. Taken together, our results demonstrated that the ANGPTL4/BCAA/mTOR axis is an important pathway in OS progression and may be a potential therapeutic target to slow OS progression.

7.
Front Psychiatry ; 13: 848849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463534

RESUMO

Objective: Prefrailty and frailty are two common conditions among older individuals. Recent studies have reported the association between frailty and depressive symptoms, but whether those conditions could predict depressive symptoms is still inconsistent in a few longitudinal studies. In our study, we aimed to estimate the cross-sectional and longitudinal associations between frailty and incident depressive symptoms in a nationally representative sample of community-dwelling middle-aged and older Chinese adults. Method: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged ≥ 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed the baseline surveys were 2,579 and follow-up surveys were 839 for the short-term (2 years from 2011 to 2013) and 788 for the long-term (4 years from 2011 to 2015). In addition, Frailty was measured by the Fried criteria and depressive symptoms were estimated by the Chinese version of the Center for Epidemiologic Studies-Depression scale (CES-D). Logistic regression was used to analyze the odds ratio (OR), and 95% confidence interval (CI) for the cross-sectional associations of frailty and its components with depressive symptoms in the participants at baseline. Cox proportional hazards analysis was conducted using the hazard ratio (HR), and 95% confidence interval (CI) for the prospective associations of baseline frailty and pre-frailty and its component in the participants without depressive symptoms at baseline. Results: At baseline, 57.93% of participants had depressive symptoms and 55.84% had pre-frail and 11.63% had frailty. In the cross-sectional analysis, both pre-frailty (OR = 5.293, 95%CI 4.363-6.422) and frailty (OR = 16.025, 95%CI 10.948-23.457) were associated with depressive symptoms. In the longitudinal analysis, frailty [HR = 1.395 (0.966-2.013)] and pre-frailty [HR = 2.458 (0.933, 6.479)] were not significantly associated with incident depressive symptoms in a full-adjusted model among participants free of baseline depressive symptoms during the short-term. However, frailty [HR = 1.397 (1.017, 1.920)] and pre-frailty [HR = 2.992 (1.210, 7.397)] were significantly associated with incident depressive symptoms during the short term. In the components of frailty, slowness [HR = 1.597 (1.078, 2.366)] was associated with an increased risk of depressive symptoms onset during the short-term. Weakness [HR = 2.08 (1.055, 4.104)] and exhaustion [HR = 1.928 (1.297, 2.867)] were associated with increased risk of depressive symptoms onset during the short-term. Conclusion: Among the middle-aged and older adults, frailty, pre-frailty did not predict depressive symptoms during 2 years of follow-up, when accounting for the potential confounders, slowness considered alone predicted depressive symptoms. Additionally, frailty, pre-frailty predicted depressive symptoms during 4 years of follow-up, when accounting for the potential confounders, weakness and exhaustion considered alone predicted depressive symptoms.

8.
Diabetes Metab Syndr Obes ; 15: 1197-1206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469341

RESUMO

Objective: Data are limited regarding how body composition is linked to insulin resistance in elderly patients with type 2 diabetes mellitus (T2DM). We examined the association between body composition and insulin resistance in elderly T2DM patients. Methods: The cross-sectional study included 488 Chinese elderly patients wth T2DM. Subjects were classified into four groups based on body composition: normal body composition (NBC), low muscle mass alone (LMM), high body fat alone (HBF), both low muscle mass and high body fat (LMMHBF). Results: The percentage of subjects with LMMHBF was 14.5% (11.9% in men and 17.7% in women). Homeostasis model assessment of insulin resistance (HOMA2-IR) was higher in the LMMHBF group than in the HBF group (p = 0.045), and was also significantly higher in the LMMHBF or HBF group than in the NBC or LMM group. The HBF group showed the highest body mass index (BMI) of the four groups of different body compositions, and the LMMHBF group showed lower BMI than the HBF group; however, there was no significant difference in BMI or waist to hip ratio (WHR) between the LMMHBF group and the NBC group. The LMMHBF and HBF groups were significantly associated with increased risk of insulin resistance compared to the NBC group, with odds ratios (ORs) of 4.47 [95% confidence interval (CI) 2.06-9.68, p < 0.001] and 1.76 (95% CI 1.02-3.02, p = 0.041) respectively, even after the adjustment for covariates. Conclusion: In China, though elderly T2DM patients with the body composition of sarcopenic obesity (as defined by coexistence of low muscle mass and high body fat) seemed to have normal body size, they exhibited the most severe degree and the highest risk of insulin resistance.

9.
World J Psychiatry ; 12(2): 338-347, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35317336

RESUMO

BACKGROUND: Frontline nurses in Wuhan directly fighting severe acute respiratory syndrome coronavirus-2 diseases are at a high risk of infection and are extremely susceptible to psychological stress, especially due to the global coronavirus disease 2019 (COVID-19) pandemic. The psychological after-effects of this public health emergency on frontline nurses will last for years. AIM: To assess factors influencing post-traumatic stress disorder (PTSD) among frontline nurses in Wuhan 6 mo after the COVID-19 pandemic began. METHODS: A total of 757 frontline nurses from five hospitals in Wuhan, China, participated in an online survey from July 27 to August 13, 2020. This cross-sectional online study used a demographic information questionnaire, the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, the Connor-Davidson Resilience Scale, and the Patient Health Questionnaire-4. The chi-square test and logistic regression were used to analyze the association of demographics, COVID-19-related variables, and PTSD. Logistic regression was also conducted to investigate which variables were associated with PTSD outcomes. RESULTS: A total of 13.5%, 24.3%, and 21.4% of the frontline nurses showed symptoms of PTSD, depression, and anxiety, respectively. The multivariate logistic regression analysis showed that the following factors were strongly associated with PTSD: Having a relative, friend, or colleague who died of COVID-19; experiencing stigma; or having psychological assistance needs, depressive symptoms or anxiety. Showing resilience and receiving praise after the COVID-19 outbreak were protective factors. CONCLUSION: Frontline nurses still experienced PTSD (13.5%) six months after the COVID-19 outbreak began. Peer support, social support, official recognition, reward mechanisms, exercise, better sleep, and timely provision of information (such as vaccine research progress) by the government via social media, and adequate protective supplies could mitigate the level of PTSD among nurses responding to COVID-19. Stigmatization, depression, and anxiety might be associated with a greater risk of PTSD among nurses.

10.
Front Microbiol ; 13: 842058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308339

RESUMO

Mycoplasma hyorhinis is a common pathogen of swine and is also associated with various human tumors. It causes systemic inflammation, typically polyserositis and polyarthritis, in some infected pigs. However, the pathogenic mechanism of M. hyorhinis remains unclear. DnaK is a highly conserved protein belonging to the heat-shock protein 70 family of molecular chaperones, which plays important roles as a moonlighting protein in various bacteria. In the present study, we identified the surface exposure of M. hyorhinis DnaK. Two virulent strains expressed more DnaK on their surface than the avirulent strain. Thereafter, the potential moonlighting functions of DnaK were investigated. Recombinant M. hyorhinis DnaK (rMhr-DnaK) was found to be able to adhere to swine PK-15 cells and human NCI-H292 cells. It also bound to four extracellular matrix components-fibronectin, laminin, type IV collagen, and vitronectin-in a dose-dependent manner. ELISA demonstrated an interaction between rMhr-DnaK and plasminogen, which was significantly inhibited by a lysine analog, ε-aminocaproic acid. rMhr-DnaK-bound plasminogen was activated by tissue-type plasminogen activator (tPA), and the addition of rMhr-DnaK significantly enhanced the activation. Finally, a DnaK-specific antibody was detected in the serum of pigs immunized with inactivated vaccines, which indicated good immunogenicity of it. In summary, our findings imply that DnaK is an important multifunctional moonlighting protein in M. hyorhinis and likely participates extensively in the infection and pathogenesis processes of M. hyorhinis.

11.
BMC Musculoskelet Disord ; 23(1): 201, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241034

RESUMO

AIMS: Intralesional curettage is a commonly used treatment for primary bone tumors. However, local recurrence of tumors after curettage remains a major challenge. QUESTIONS: (1) Is blood pressure related to local recurrence after intralesional curettage for benign or intermediate bone tumors? (2) What's the impact of tourniquet usage on the risk of recurrence from high blood pressure? METHODS: This retrospective study evaluated patients receiving intralesional curettage for primary bone tumors from January 2011 to January 2015. A total of 411 patients with a minimum five-year follow-up were included for analysis. Demographic and disease-related variables were first assessed in univariable analyses for local recurrence risk. When a yielded p-value was < 0.2, variables were included in multivariable analyses to identify independent risk factors for local recurrence. Patients were then stratified by tourniquet usage (use/non-use), and risk from high blood pressure was evaluated in both subgroups. RESULTS: At an average follow-up of 6.8 ± 1.0 years, 63 of 411 patients (15.3%) experienced local recurrence. In multivariable analyses, local recurrence was associated with age (OR, 0.96; 95% CI, 0.94-0.99; p = 0.005); tumor type; lesion size (> 5 cm: OR, 3.58; 95% CI, 1.38-9.33; p = 0.009); anatomical site (proximal femur: OR, 2.49; 95% CI, 1.21-5.15; p = 0.014; proximal humerus: OR, 3.34; 95% CI, 1.61-6.92; p = 0.001); and preoperative mean arterial pressure (> 110 mmHg: OR, 2.61; 95% CI, 1.20-5.67; P = 0.015). In subgroup analyses, after adjusting for age, tumor type, lesion size, and anatomical site, tourniquet use modified the preoperative mean arterial pressure - recurrence relationship: when tourniquet was not used, preoperative mean arterial pressure predicted local recurrence (95-110 mmHg, 4.13, 1.42-12.03, p = 0.009; > 110 mmHg, 28.06, 5.27-149.30, p < 0.001); when tourniquet was used, preoperative mean arterial pressure was not related to local recurrence (all p values > 0.05). CONCLUSIONS: A high preoperative blood pressure was related to local recurrence after intralesional curettage for primary bone tumors in our study. Tourniquet usage and controlling blood pressure might be beneficial for reducing local recurrence in patients scheduled to receive intralesional curettage for primary bone tumor treatment. LEVEL OF EVIDENCE: Level IV, hypothesis-generating study.


Assuntos
Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Pressão Sanguínea , Neoplasias Ósseas/patologia , Curetagem/efeitos adversos , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Torniquetes/efeitos adversos , Resultado do Tratamento
12.
J Clin Med ; 11(6)2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35329906

RESUMO

Muscle biopsy is a fundamental procedure to assist the final diagnosis of myopathy. With the recent advances in molecular diagnosis, serology tests, and mechanism-based classification in myopathy, the précised diagnosis for myopathy required the applications of multiple tools. This study intends to reappraise the benefit of muscle biopsy in adult-onset myopathy under the setting of an optimized muscle biopsy protocol and comprehensive serology tests. A one-group pretest-posttest study design was used. The pre- and post-biopsy diagnoses and treatments in 69 adult patients were compared. Muscle biopsy yielded 85.5% of definitive diagnoses, including changes in pre-biopsy diagnoses (40.6%) and narrowing down the suspicious myopathies (49.3%). The demographic data and clinical parameters between the group "with change" and "without change" after biopsy were not different. Among those with changes in diagnosis, 39.3% also had a corresponding shift in treatment, which benefits the patients significantly. Regarding the most common adult-onset myopathy, idiopathic inflammatory myopathy (IIM), 41% of patients with pre-biopsy diagnosis as IIM had changes in their IIM subtype diagnosis, and 53% was finally not IIM after muscle biopsy. Although there have been advances in molecular diagnosis recently, muscle biopsy still undoubtedly critically guided the diagnosis and treatment of adult-onset myopathy in the era of precision medicine.

14.
J Food Sci ; 87(3): 1342-1354, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35166370

RESUMO

The tadalafil-like compounds have appeared recently as adulterants in drinks and healthcare dietary supplements sourced from medicinal and edible food, which may cause illness and even death. In this work, the rationality of haptens was explored by computational chemistry and molecular simulation theories such as frontier molecular orbital (FMO)-based softness (S), three-dimensional (3D) structure, surface electrostatic potential (ESP), and lipophilic potential (LP). An antiserum from hapten H5 with the highest softness and maintaining the appropriate three-dimensional (3D) structure showed the optimal immunoassay performance, indicating an increasing softness was a critical factor for effective hapten. Based on the antibody induced by hapten H5, an indirect competitive enzyme-linked immunosorbent assay (icELISA) method for detecting multiple tadalafil-like adulterants was established. The icELISA showed a limit of detection (LOD), 50% inhibition concentration (IC50 ), and a working range of 0.004-0.396, 0.89-4.27, and 0.094-16.71 ng/ml for tadalafil, amino tadalafil, acetamino tadalafil, nortadalafil, and N-desmethyl ent-tadalafil, respectively. The spiked recoveries of tadalafil-like adulterants in samples ranged from 84.9% to 116.2%. The results of the icELISA and HPLC-MS/MS methods had a good correlation for real samples with the R2 of 0.9955. Specially, this work not only provided a convenient immunoassay method for measuring tadalafil-like adulterants in spirit drinks and dietary supplements in group-screening manner, but also suggested that softness was likely to be a general theory for rational hapten design. PRACTICAL APPLICATION: Rapid monitoring of tadalafil-like adulterants in food samples is very necessary and important for consumers, regulatory agencies, and the food industry.


Assuntos
Química Computacional , Espectrometria de Massas em Tandem , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática/métodos , Haptenos , Imunoensaio , Tadalafila
15.
Leuk Lymphoma ; : 1-10, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105265

RESUMO

Chimeric antigen receptor T (CAR-T) cells are a promising approach in hematopoietic malignancies. We evaluated the safety and efficacy of a combination of humanized anti-BCMA and murine anti-CD38 CAR-T cell therapy in patients with relapsed or refractory multiple myeloma (R/RMM). Twenty-two R/RMM patients, with a median age of 56 years and a median number of previous therapies of 8, were included in the study. Both CAR-T cells infusion doses were 2.0 × 106/kg. The overall response rate (ORR) was 90.9%, with 12 patients (54.5%) achieving a strict complete response/complete response (sCR/CR). The 24-month overall survival (OS) rate was 56.6%, and the progression-free survival (PFS) rate was 48.7%. Cytokine release syndrome (CRS) of grades 1-2 occurred in 16 patients (72.7%) and of grade ≥3 in six patients (27.3%). Immune effector cell-associated neurotoxic syndrome (ICANS) of grades 1-2 occurred in three patients (13.6%). The combination therapy is potential in R/RMM patients.Trial registration: The patients were enrolled in clinical trials registered as ChiCTR1800017051.

16.
Mol Ther ; 30(3): 1188-1200, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35007759

RESUMO

The effect of immunotherapy is limited by oncometabolite D-2-hydroxyglutarate (D2HG). D2HGDH is an inducible enzyme that converts D2HG into the endogenous metabolite 2-oxoglutarate. We aimed to evaluate the impairment of CD8 T lymphocyte function in the high-D2HG environment and to explore the phenotypic features and anti-tumor effect of D2HGDH-modified CAR-T cells. D2HG treatment inhibited the expansion of human CD8 T lymphocytes and CAR-T cells, increased their glucose uptake, suppressed effector cytokine production, and decreased the central memory cell proportion. D2HGDH-modified CAR-T cells displayed distinct phenotypes, as D2HGDH knock-out (KO) CAR-T cells exhibited a significant decrease in central memory cell differentiation and intracellular cytokine production, while D2HGDH over-expression (OE) CAR-T cells showed predominant killing efficacy against NALM6 cancer cells in high-D2HG medium. In vivo xenograft experiments confirmed that D2HGDH-OE CAR-T cells decreased serum D2HG and improved the overall survival of mice bearing NALM6 cancer cells with mutation IDH1. Our findings demonstrated that the immunosuppressive effect of D2HG and distinct phenotype of D2HGDH modified CAR-T cells. D2HGDH-OE CAR-T cells can take advantage of the catabolism of D2HG to foster T cell expansion, function, and anti-tumor effectiveness.


Assuntos
Glutaratos/metabolismo , Neoplasias , Oxirredutases do Álcool/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/metabolismo , Humanos , Imunoterapia , Imunoterapia Adotiva , Camundongos , Neoplasias/terapia , Linfócitos T/metabolismo , Microambiente Tumoral
18.
Pest Manag Sci ; 78(4): 1749-1758, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35001496

RESUMO

BACKGROUND: Plant virus diseases are difficult to control and severely threaten the productivity of crops, which leads to huge financial losses. To discover the new antiviral drugs, 34 novel ferulic acid derivatives with piperazine moiety were synthesized, and the antiviral activities were systematically screened as well. RESULTS: Bioassay results indicated that most of the target compounds had outstanding antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. In particular, compound E2 exhibited remarkable curative activities to TMV and CMV with EC50 values of 189.0 and 401.7 µg/mL compared to those for ningnanmycin (387.0, 519.3 µg/mL) and ribavirin (542.1, 721.5 µg/mL). And then the mechanisms of compound E2 were studied by chlorophyll content, differentially expressed proteins and genes tests. CONCLUSION: The excellent antiviral activity of compound E2 was closely associated with the increase in host photosynthesis, which was confirmed by chlorophyll content, differentially expressed proteins and genes assays. Compound E2 can be considered as a lead structure for the discovery of new antiviral agents. © 2022 Society of Chemical Industry.


Assuntos
Cucumovirus , Vírus do Mosaico do Tabaco , Antivirais/química , Antivirais/farmacologia , Ácidos Cumáricos , Desenho de Fármacos , Piperazina , Relação Estrutura-Atividade
19.
Anal Methods ; 14(8): 781-788, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35083987

RESUMO

Glove-based wearable sensors can offer the potential ability to a fast and on-site environmental threat assessment, which is crucial for timely and informed incident management. In this study, an on-demand surface-enhanced Raman scattering (SERS) array sensor has been patterned on fire-retardant fibre gloves via the screen-printing technique in large batches. The screen-printed ink contains one-pot synthesized silver nanoparticle and molybdenum disulfide nanocomposite (Ag/MoS2), and polyanionic cellulose (PAC) as a new adhesive agent. Rhodamine 6G (R6G) was employed as an initial probe molecule to systematically evaluate the performance of the resulting sensor. The results suggest that the fabricated fire-retardant screen-printed SERS array sensor displays high reproducibility and stability at 250 °C, with the lower detection limit of 10-13 M for R6G. The spot-to-spot SERS signals show that the intensity variation was less than 10%. Besides, the SERS signals can be maintained over 7 weeks. Further investigation was then successfully carried out to detect polycyclic aromatic hydrocarbons (PAHs), which are commonly used as flammable chemicals. In our perception, this wearable fire-retardant screen-printed SERS array sensor would be an ideal candidate for practical on-site environmental emergency monitoring due to its fire-retardant capability and timely measurement on a portable carrier.


Assuntos
Retardadores de Chama , Nanopartículas Metálicas , Dispositivos Eletrônicos Vestíveis , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Prata/química
20.
Food Res Int ; 151: 110846, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34980384

RESUMO

Sichuan pickle is a natural combination of probiotics and dietary fibers, in which a strain Lactiplantibacillus plantarum QS7T was found to be capable of efficiently metabolizing inulin. However, the underlying molecular mechanism of inulin consumption by the strain QS7T is unclear. Therefore, this study firstly investigated the metabolic characteristics of inulin in the strain QS7T, and the results showed it could grow very well on the medium containing inulin as a carbon source (maximum OD600 nm, 1.891 ± 0.028) and degrade both short-chain oligofructose and long-chain fructan components through thin layer chromatography analysis. Genomic sequencing and analysis revealed a high percentage of functional genes associated with carbohydrate transport and metabolism, particularly glycoside hydrolase (GH) genes responsible for hydrolysing carbohydrates, within the genome of the strain QS7T. Furthermore, comparative transcriptomic analysis of L. plantarum QS7T in response to inulin or glucose indicated that functional genes associated with inulin consumption including several genes encoding PTS sugar transporters and two predicted GH32 family genes encoding beta-fructofuranosidase and beta-fructosidase were significantly up-regulated by inulin compared to the gene expression on glucose. In conclusion, we obtained a mechanistic understanding of interplay between probiotic L. plantarum QS7T derived from Sichuan pickle and natural dietary fiber, inulin; totally two operons including a sacPTS1 operon responsible for metabolizing short-chain oligofructose primarily in the cytoplasm and a fos operon responsible for extracellularly degrading all moderate and long-chain fructan components linked to inulin consumption by L. plantarum QS7T.


Assuntos
Inulina , Probióticos , Óperon , Transcriptoma , beta-Frutofuranosidase/metabolismo
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