Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs. ibrutinib to treat relapsed/refractory (R/R) CLL/SLL. Here we report results from the subgroup of Chinese patients. Adults with R/R CLL/SLL were randomized 1:1 to receive zanubrutinib (160 mg twice-daily) or ibrutinib (420 mg once-daily) until disease progression or unacceptable toxicity. Endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Data were analyzed descriptively. Ninety patients were randomized in China (zanubrutinib, n = 47; ibrutinib, n = 43). Baseline characteristics were balanced between groups, with fewer male patients in the zanubrutinib vs. ibrutinib group (55.3% vs. 69.8%). Median age was 60.5 years, 11% had del(17p) mutation, and 32% had tumor protein 53 (TP53) mutation. With median 25.3 months follow-up, ORR was 80.9% with zanubrutinib vs. 72.1% with ibrutinib. PFS was improved with zanubrutinib vs. ibrutinib (HR = 0.34 [95% CI, 0.15, 0.77]), and the HR for OS was 0.45 (95% CI, 0.14, 1.50). Rates of Grade ≥ 3 treatment-emergent adverse events (TEAEs; 64.4% vs. 72.1%), AEs leading to discontinuation (6.4% vs. 14.0%), and serious TEAEs (35.6% vs. 51.2%) were lower with zanubrutinib vs. ibrutinib. Zanubrutinib demonstrated improved ORR, PFS, and OS vs. ibrutinib and a more favorable safety profile in patients with R/R CLL/SLL in China. These results are consistent with the full global population of ALPINE. ClinicalTrials.gov: NCT03734016, registered November 7, 2018.

Zanubrutinib is effective in non-germinal-center B-cell-like diffuse large B-cell lymphoma with mutated CD79B, high TCL1A expression, or over- expressed MYC/BCL-2.

To evaluate the effects of gene mutations on Bruton tyrosine kinase inhibitor, zanubrutinib's effectiveness in patients with diffuse large B-cell lymphoma (DLBCL), we examined pooled data from four single-arm studies (BGB-3111-AU-003 [NCT02343120], BGB-3111-207 [NCT03145064], BGB-3111_GA101_Study_001 [NCT02569476], BGB-3111-213 [NCT03520920]; n = 121). Objective response rate (ORR) was higher, though not statistically significant, in patients with activated B-cell-like (ABC)- and unclassified DLBCL (42.9% [21/49]) versus those with germinal-center B-cell-like DLBCL (14.3% [1/7]; p = 0.15). Patients with CD79B mutations had better ORR (60%) versus patients with wild-type alleles (25.9%, p < 0.01). Higher TCL1A expression correlated with better zanubrutinib response (p = 0.03), longer progression-free survival (p = 0.01), and longer overall survival (p = 0.12). TCL1A expression was higher in ABC-DLBCL (p < 0.001) and MYD88/CD79B-mutated subtypes (p < 0.0001). Eighteen patients with high MYC/BCL-2 expression responded better to zanubrutinib (ORR = 61 vs. 29%, p = 0.02). Our results support assessing CD79B mutations, co-expressor DLBCL, and TCL1A expression status to identify patients with DLBCL who will benefit from zanubrutinib.

An antibacterial biologic patch based on bacterial cellulose for repair of infected hernias.

Infection-associated complications and repair failures and antibiotic resistance have emerged as a formidable challenge in hernia repair surgery. Consequently, the development of antibiotic-free antibacterial patches for hernia repair has become an exigent clinical necessity. Herein, a GBC/Gel/LL37 biological patch (biopatch) with exceptional antibacterial properties is fabricated by grafting 2-Methacryloyloxyethyl trimethylammonium chloride (METAC), a unique quaternary ammonium salt with vinyl, onto bacterial cellulose (GBC), followed by compounding with gelatin (Gel) and LL37. The GBC/Gel/LL37 biopatch exhibits stable swelling capacity, remarkable mechanical properties, flexibility, and favorable biocompatibility. The synergistic effect of METAC and LL37 confers upon the GBC/Gel/LL37 biopatch excellent antibacterial efficacy against Staphylococcus aureus and Escherichia coli, effectively eliminating invading bacteria without the aid of exogenous antibiotics in vivo while significantly reducing local acute inflammation caused by infection. Furthermore, the practical efficacy of the GBC/Gel/LL37 biopatch is evaluated in an infected ventral hernia model, revealing that the GBC/Gel/LL37 biopatch can prevent the formation of visceral adhesions, facilitate the repair of infected ventral hernia, and effectively mitigate chronic inflammation. The prepared antibacterial GBC/Gel/LL37 biopatch is very effective in dealing with the risk of infection in hernia repair surgery and offers potential clinical opportunities for other soft injuries, exhibiting considerable clinical application prospects.

Bronchopulmonary foregut malformation with severe hemoptysis in advanced age: a case report and literature review.

Bronchopulmonary foregut malformation (BPFM) is a rare developmental malformation disease due to embryonic defects, with an even rarer occurrence in adults. We report a diagnosed case in an adult patient, and notably, this is the first reported case of such advanced age. Additionally, she experienced coughing up approximately 1 liter of blood and partial lung tissue, accompanied by respiratory failure and shock. Following treatment with transcatheter arterial embolization, her condition improved, and she has remained stable during follow-up. We present a case report and conducted a systematic review on this particular case.

Assessment of the Relationship Between Genetic Determinants of Obesity, Unhealthy Eating Habits and Chronic Obstructive Pulmonary Disease: A Mendelian Randomisation Study.

Background: Clinical studies have shown that the onset and exacerbation of chronic obstructive pulmonary disease (COPD) are related to obesity and dietary behaviours, but the genetic relationship between them is not clear.Aims: To investigate the relationship between the genetic determinants of obesity, dietary habits (alcohol consumption, intake of sweets, salt intake) and COPD.Methods: Exposure and outcome datasets were obtained from the IEU Open GWAS project. The exposure dataset includes dietary habits (Salt added to food, Sweets intake, Alcohol consumption), obesity level (represented by body mass index (BMI) and body fat percentage (BFP) data sets.). The outcome dataset includes COPD and acute COPD admissions. The collected data were imported into the RStudio software and conducted Mendelian randomisation analysis. Additionally, heterogeneity and horizontal pleiotropy tests were conducted on the data to ensure the veracity of the results.Results: The results showed that BMI was positively correlated with the risk of acute COPD admission (OR = 1.74, 95% CI 1.39-2.18) and COPD (OR = 1.81, 95%CI 1.41-2.33). In addition, BFP was also a risk factor for COPD (OR = 1.98, 95% CI 1.42-2.77) and acute exacerbation of COPD admission (OR = 1.99, 95%CI 1.43-2.77). The increase of salt, sugar and alcohol consumption will not increase the risk of COPD and the risk of hospitalisation due to COPD.Conclusion: Therefore, we should strengthen the guidance of diet and living habits of obese patients. For patients with heavier weight and higher body fat rate, they should be instructed to lose weight and fat to prevent the occurrence of COPD. For obese patients with COPD, more attention should be paid to prevent the occurrence of acute exacerbation of COPD in advance.

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis.

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

Effects of accelerated rehabilitation surgical care on the surgical site wound infection and postoperative complications in patients of lung cancer: A meta-analysis.

To comprehensively evaluate the effect of accelerated rehabilitation surgical care on perioperative wound infections and complications in patients undergoing lung cancer surgery. A comprehensive computerised search for randomised controlled trials (RCTs) of accelerated rehabilitative surgical care applied to patients undergoing lung cancer surgery was conducted using the Web of Science, PubMed, Cochrane Library, Embase, Wanfang and China National Knowledge Infrastructure databases from inception to September 2023. The literature was screened and evaluated by two investigators, and data were extracted from the final included literature. Stata software (version 17.0) was used for data analysis. Overall, 21 RCTs involving 2187 patients were included, including 1093 cases in the accelerated rehabilitation surgical care group and 1094 cases in the conventional care group. The analyses revealed that patients with lung cancer surgery who implemented accelerated rehabilitation surgical care were significantly less likely to develop postoperative wound infections (odds ratio [OR] = 0.29, 95% confidence interval [CI]: 0.17-0.49, p < 0.001) and postoperative complications (OR = 0.26, 95% CI: 0.20-0.34, p < 0.001) and shortened the hospital length of stay (standardised mean differences [SMD] = -1.93, 95% CI: -2.32 to -1.53, and p < 0.001) compared with conventional care. The effect of accelerated rehabilitation surgical care intervention in the perioperative period of lung cancer surgery patients is remarkable, as it can effectively reduce the incidence of wound infection and complications, shorten hospitalisation time and promote patient recovery.

Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a research study called ALPINE. The study involved people who had been diagnosed with, and previously treated at least once for, relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Lymphocytes help to find and fight off viruses and infections in the body, but when someone has CLL or SLL, the body creates abnormal lymphocytes, leaving the patient with a weakened immune system and susceptible to illness. In CLL, these lymphocytes are in the bone marrow and bloodstream, whereas for SLL, they are mostly found in the lymph nodes, such as those in the neck. HOW WAS THE RESEARCH DONE?: The ALPINE study was designed to directly compare the cancer-fighting effects and side effects of zanubrutinib and ibrutinib as treatment for patients with relapsed or refractory CLL/SLL. WHAT WERE THE RESULTS?: After 30 months, zanubrutinib was more effective than ibrutinib at reducing and keeping the cancer from coming back. Clinical Trial Registration: NCT03734016 (ClinicalTrials.gov).

Microneedle-based cell delivery and cell sampling for biomedical applications.

Cell-based therapeutics are novel therapeutic strategies that can potentially treat many presently incurable diseases through novel mechanisms of action. Cell therapies may benefit from the ease, safety, and efficacy of administering therapeutic cells. Despite considerable recent technological and biological advances, several barriers remain to the clinical translation and commercialization of cell-based therapies, including low patient compliance, personal handling inconvenience, poor biosafety, and limited biocompatibility. Microneedles (MNs) are emerging as a promising biomedical device option for improved cell delivery with little invasion, pain-free administration, and simplicity of disposal. MNs have shown considerable promise in treating a wide range of diseases and present the potential to improve cell-based therapies. In this review, we first summarized the latest advances in the various types of MNs developed for cell delivery and cell sampling. Emphasis was given to the design and fabrication of various types of MNs based on their structures and materials. Then we focus on the recent biomedical applications status of MNs-mediated cell delivery and sampling, including tissue repair (wound healing, heart repair, and endothelial repair), cancer treatment, diabetes therapy, cell sampling, and other applications. Finally, the current status of clinical application, potential perspectives, and the challenges for clinical translation are also highlighted.

Application of a novel and green temperature-responsive deep eutectic solvent system to simultaneously extract and separate different polar active phytochemicals from Schisandra chinensis (Turcz.) Baill.

In the present study, a novel and green temperature-responsive deep eutectic solvent (TRDES) system was developed and applied for the simultaneous extraction and separation of different polar active phytochemicals from Schisandra chinensis (Turcz.) Baill. The TRDES, consisting of amino alcohols and phenolic compounds, was chosen as the switching medium, and an upper critical solution temperature (UCST) type switchable solvent was obtained by adding an inorganic salt solution. The switchable phase diagram was plotted based on the relationship between the phase change temperature, the concentration and the amount of sodium chloride solution. Under optimal parameters, the yields with TRDES for different polar active phytochemicals (lignanoids and polysaccharides) from the dried fruit of Schisandra chinensis (DFSC) were 1.62 âˆ¼ 1.17-fold and 1.39-fold to those with conventional solvents. Also, the TRDES system was still effective on extraction of DFSC lignanoids and polysaccharides after four cycles of extraction. The separated polysaccharides and lignanoids both had strong antioxidant activities with IC50 values of 1.92 mg/ mL and 0.10 mg/ mL against 2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), respectively. The extraction mechanism of TRDES was postulated by Density functional theory (DFT) calculations the hydrogen bonding in TRDES was the main factor to the higher extraction yield. This temperature-responsive deep eutectic solvent could be widely used for the efficient extraction and separation of multi-polar components. As a green and recyclable solvents, TRDES has great potential for the lower cost production from plants.

A periodic boundary value problem of fractional differential equation involving p(t)-Laplacian operator.

The purpose of this article is to research the existence of solutions for fractional periodic boundary value problems with p(t)-Laplacian operator. In this regard, the article needs to establish a continuation theorem corresponding to the above problem. By applying the continuation theorem, a new existence result for the problem is obtained, which enriches existing literature. In addition, we provide an example to verify the main result.

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.

BACKGROUND: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available. METHODS: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05. RESULTS: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P = 0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death. CONCLUSIONS: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, NCT03734016.).

Do carbon emission trading scheme policies induce green technology innovation? New evidence from provincial green patents in China.

Carbon emission trading scheme (ETS) policy is a quota-based market-motivated environmental regulation policy that by transforming environmental responsibility of enterprises into self-consciousness behavior induces green innovation behavior in enterprises and influences the level of regional green innovation. Based on panel data on green patents in 30 Chinese provinces from 2010 to 2019, the paper uses six Chinese pilot provinces for ETS as the treatment group to investigate the induced effects of Chinese ETS policy on the quantity and quality of green technology innovation using difference in difference model and analyzes the effects of Chinese ETS policy on green technology innovation in different pilot regions using a synthetic control method. The findings indicate that (1) compared with non-pilot areas, the carbon emission trading policies in pilot areas can induce green technology innovation activities. (2) In all pilot regions, ETS policies significantly promoted the quantity and quality of green technology innovation, but the quantity promotion effect was significantly better than the quality promotion effect, and the low-quality promotion effect was better than the high-quality promotion effect. (3) In terms of individual pilot region, ETS policies in Guangdong, Hubei and Tianjin significantly promoted the quantity of green technology innovation and low-quality green technology innovation, but significantly inhibited or suppressed high-quality green technology innovation in a short term. This paper not only enriches the research on environmental equity trading policies and green technology innovation theoretically, but also provides empirical evidence for the effectiveness of carbon emission trading schemes pilots program in China.

Decreased circulating levels of free triiodothyronine in Sepsis children and correlation analysis.

BACKGROUND: Intensive physical stress in sepsis can induce the disorder of endocrine function and impact the clinical course and prognosis. Low T3 syndrome has been verified to be the predictive indicator of poor prognosis in several researches. Reports on the influence factors of thyroid hormonal levels in children with severe sepsis are rare. We aim to investigate the thyroid hormonal variations in the course of sepsis and analyze that how to be affected by clinical data and inflammatory biomarkers. METHODS: In the case-control study, 184 children with sepsis and 323 controls were included in Tongji Hospital, Wuhan, China, in 2019. Data on clinical and inflammatory parameters were collected from all participants. Circulating FT3(Free Triiodothyronine) levels were measured by Electrochemiluminescence immunoassay. Finally, we investigated the correlation between FT3 and related variables with linear regression analysis. RESULTS: Serum FT3 was lower in the sepsis group than in control group(2.59 + 1.17 vs 2.83 + 1.01 pg/mL, p < 0.05). Significant moderately negative correlations(|r| > 0.3) of FT3 levels with ferritin, PCT, duration of symptoms, SOFA score, and mortality were revealed. Moreover, we observed that FT3 had the positive correlation with albumin, as well as white blood cell count. CONCLUSIONS: Concentrations of serum FT3 are dramatically declined in sepsis children than in control children. Our results demonstrate that recognizing the potential abnormality of thyroid hormones in sepsis patients and examine timely through abnormal common clinical data and inflammatory biomarkers is a fine option.

Case Report: Glycogen Storage Disease Type Ia in a Chinese Child Treated With Growth Hormone.

Background: Glycogen storage disease type Ia is a rare metabolic disorder that leads to excessive glycogen and fat accumulation in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay, and growth retardation. Here, we report on a patient with glycogen storage disease type Ia treated with growth hormone. Case Presentation: A 10-year-old boy had growth retardation for 6 years, and was admitted to clarify the cause of his short stature. We found that his bone age was 5.5 years, significantly lower than his physical age, while his serum IGF-1 and IGFBP-3 were 23.30 and 1620.0 ng/mL, respectively, both lower than normal. His medical history revealed that he had suffered from steatohepatitis, hyperlipidemia, and hypoglycemia since he was 11 months of age. Whole exome sequencing (WES) showed compound heterozygous mutations in exons 2 and 5 of the glucose-6-phosphatase (G6PC) gene on chromosome 17: c.G248A (p.R83H) and c.G648T (p.L216L). The patient was finally diagnosed with GSD Ia. After growth hormone (GH) treatment and corn starch therapy for 14 months, his height significantly increased (by 13 cm). The serum IGF-1 level increased to the normal range but his lipid levels and liver function did not significantly increase. Conclusion: We describe a young patient with a compound heterozygous G6PC variant in a Chinese family; his height increased significantly after growth hormone and corn starch interventions. This case emphasizes that WES is essential for early diagnosis, and that growth hormone treatment may increase the height of patients with GSD Ia safely.

[Retracted] MicroRNA­744 inhibits tumor cell proliferation and invasion of gastric cancer via targeting brain­derived neurotrophic factor.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Fig. 2D were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 5055­5061, 2017; DOI: 10.3892/mmr.2017.7167].

IL-27 overexpression alleviates inflammatory response in allergic asthma by inhibiting Th9 differentiation and regulating Th1/Th2 balance.

OBJECTIVE: To investigate the effect of IL-27 on Th9 differentiation and Th1/Th2 balance. METHODS: C57BL/6 (B6) mice were treated with ovalbumin to establish an allergic asthma (AA) model and subjected to IL-27 overexpression (OV) and empty vector (EV). Hematoxylin-eosin (HE) staining was performed to observe lung tissue inflammation. Flow cytometry was carried out to evaluate the percentage of Th9, Th1, and Th2 cells. The expression of IL-27, IL-27R, IL-9, T-bet, IFN-γ, and IgE was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Western blot was conducted to observe the expression of pSTAT-1 and pSTAT-3. RESULTS: Compared with the Model group, the number of Th1 cells in the Model + OV group increased significantly (p < .05), while those of Th9 and Th2 cells decreased significantly (p < .05). The expression of IL-27, IL-27R, and IFN-γ in blood serum was increased (p < .05), and that of IL-9 and IgE was significantly decreased in the Model + OV group compared to the Model (p < .05). Western blot revealed that Model + OV exhibited lower expression of pSTAT-3 than that in the Model and Model + EV groups (p < .05), while pSTAT-1 expression was significantly increased (p < .05). Inflammatory infiltration in the Model + OV group was significantly reduced, and there was no significant difference between the Model and Model + EV groups. CONCLUSIONS: IL-27 OV inhibits Th9 differentiation and regulates the imbalance of Th1/Th2, thereby alleviating inflammatory response in AA. The findings suggest that IL-27 OV may be a potential strategy for clinical treatment of AA.

MYB308-mediated transcriptional activation of plasma membrane H + -ATPase 6 promotes iron uptake in citrus.

Iron-deficiency chlorosis is a common nutritional disorder in crops grown on alkaline or calcareous soils. Although the acclimation mechanism to iron deficiency has been investigated, the genetic regulation of iron acquisition is still unclear. Here, by comparing the iron uptake process between the iron-poor-soil-tolerant citrus species Zhique (ZQ) and the iron-poor-soil-sensitive citrus species trifoliate orange (TO), we discovered that enhanced root H + efflux is crucial for the tolerance to iron deficiency in ZQ. The H+ efflux is mainly regulated by a plasma membrane-localized H+-ATPase, HA6, the expression of which is upregulated in plants grown in soil with low iron content, and significantly higher in the roots of ZQ than TO. Overexpression of the HA6 gene in the Arabidopsis thaliana aha2 mutant, defective in iron uptake, recovered the wild-type phenotype. In parallel, overexpression of the HA6 gene in TO significantly increased iron content of plants. Moreover, an iron deficiency-induced transcription factor, MYB308, was revealed to bind the promoter and activate the expression of HA6 in ZQ in yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays. Overexpression of MYB308 in ZQ roots significantly increased the expression level of the HA6 gene. However, MYB308 cannot bind or activate the HA6 promoter in TO due to the sequence variation of the corresponding MYB308 binding motif. Taking these results together, we propose that the MYB308 could activate HA6 to promote root H+ efflux and iron uptake, and that the distinctive MYB308-HA6 transcriptional module may be, at least in part, responsible for the iron deficiency tolerance in citrus.

New insights in the chemical profiling of major metabolites in different pigeon pea cultivars using UPLC-QqQ-MS/MS.

As one of the major non-conventional edible legumes, different cultivars of pigeon pea have different uses according to their specificity. For the first time, the main phenotype and plant physiological parameters of ten different pigeon pea cultivars were evaluated in detail, and then a novel method using UPLC-QqQ-MS/MS has been investigated for the qualitative and quantitative analysis of eighteen active constituents originating from pigeon peas. After systematic optimization of MRM parameters, the developed method showed a good precision (RSD < 7.28%) and high recovery (91.27-113.62%) within 6 min. It was found that pigeon pea 11Y21, R7 and R10 exhibited superiority in contents of the unique active compounds of cajaninstilbene acid, cajanuslactone, longistylin A and longistylin C. Moreover, combined with the main plant physiological parameters, we can find that excessive plant growth may affect the metabolites content in pigeon pea. Meanwhile, the gene expression levels indicating that the metabolite profiles of different cultivars can be strongly influenced by genetic variation. Overall, the present work developed a valid method for the detection of various phenolic compounds, which could be applied for applicability and variety breeding of pigeon pea and also providing sufficient evidences for other utilization in the future.

Application value of gray-scale ultrasound and shear wave elastography in differential diagnosis of thyroid nodules.

BACKGROUND: The global prevalence of thyroid cancer has increased significantly in recent years. Ultrasonography is the preferred method for differentiating benign and malignant thyroid nodules preoperatively and is recommended by guidelines. OBJECTIVE: To assess the application value of gray-scale ultrasound and shear wave elastography in distinguishing small thyroid nodules. METHODS: A retrospective analysis of 228 thyroid nodules, all of which were confirmed by pathology after surgery or FNA from January 2019 to January 2020, was carried out. All nodules were divided into a ⩽ 5 mm group and a > 5 mm group according to their maximum size. We compared the differences in the gray scale and elastography of the nodules between the two groups and the accuracy of different diagnostic methods. RESULTS: The accuracies of gray-scale ultrasound and shear wave elastography in the ⩽ 5 mm group were found to be lower than those in the > 5 mm group, and the gray-scale accuracy was slightly higher than that of shear wave elastography in both groups (p< 0.05). The largest AUC (area under the curve) of elastic parameters in the ⩽ 5 mm and > 5 mm groups was found for Emax and Esd, respectively. Based on a combination of these two parameters, the accuracies of the two groups were significantly higher than those of the parameters or gray scale alone (p< 0.05) and were 84.62% and 85.48%, respectively. CONCLUSION: Shear wave elastography is valuable in the diagnosis of benign and malignant thyroid nodules using ultrasonography. When combining gray-scale ultrasound and shear wave elastography, the diagnostic accuracy is obviously improved, especially for ⩽ 5 mm small thyroid nodules.