Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Dysregulation of glutamine/glutamate metabolism in COVID-19 patients: A metabolism study in African population and mini meta-analysis.

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; -log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs = 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17-3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14-4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20-0.44), and 0.44 (95% CI: 0.19-0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.

Siamese Unet Network for Waterline Detection and Barrier Shape Change Analysis from Long-Term and Large Numbers of Satellite Imagery.

Barrier islands are vital dynamic landforms that not only host ecological resources but often protect coastal ecosystems from storm damage. The Waisanding Barrier (WSDB) in Taiwan has suffered from continuous beach erosion in recent decades. In this study, we developed a SiamUnet network compared to three basic DeepUnet networks with different image sizes to effectively detect barrier waterlines from 207 high-resolution satellite images. The evolution of the barrier waterline shape is obtained to present two special morphologic changes at the southern end and the evolution of the entire waterline. The time periods of separation of the southern end from the main WSDB are determined and discussed. We also show that the southern L-shaped end has occurred recently from the end of 2017 until 2021. The length of the L-shaped end gradually decreases during the summer, but gradually increases during the winter. The L-shaped end obviously has a seasonal and jagged change. The attenuation rate of the land area is analyzed as -0.344 km2/year. We also explore two factors that affect the analysis results, which are the number of valid images selected and the deviation threshold from the mean sea level.

Multiple stimulus-response berberine plus baicalin micelles with particle size-charge-release triple variable properties for breast cancer therapy.

OBJECTIVE: The aim was to develop a nanoscale drug delivery system with enzyme responsive and acid sensitive particle size and intelligent degradation aiming to research the inhibitory effect on breast cancer. SIGNIFICANCE: The delivery system addressed the problems of tissue targeting, cellular internalization, and slow drug release at the target site, which could improve the efficiency of drug delivery and provide a feasible therapeutic approach for breast cancer. METHODS: The acid sensitive functional material DSPE-PEG2000-dyn-PEG-R9 was synthesized by Michael addition reaction. Then, the berberine plus baicalin intelligent micelles were prepared by thin-film hydration. Subsequently, we characterized the physical and chemical properties of berberine plus baicalin intelligent micelles, evaluated its anti-tumor effects in vivo and in vitro. RESULTS: The target molecule was successfully synthesized, and the intelligent micelles showed excellent chemical and physical properties, delayed drug release and high encapsulation efficiency. In vitro and in vivo experiments also confirmed that the intelligent micelles could effectively target tumor sites, penetrate tumor tissues, enrich in tumor cells, inhibit tumor cell proliferation, inhibit tumor cell invasion and migration, and induce tumor cell apoptosis. CONCLUSION: Berberine plus baicalin intelligent micelles have excellent anti-tumor effects and no toxicity to normal tissues, which provides a new potential drug delivery strategy for the treatment of breast cancer.

The transcription factor NAC102 confers cadmium tolerance by regulating WAKL11 expression and cell wall pectin metabolism in Arabidopsis.

Cadmium (Cd) toxicity severely limits plant growth and development. Moreover, Cd accumulation in vegetables, fruits, and food crops poses health risks to animals and humans. Although the root cell wall has been implicated in Cd stress in plants, whether Cd binding by cell wall polysaccharides contributes to tolerance remains controversial, and the mechanism underlying transcriptional regulation of cell wall polysaccharide biosynthesis in response to Cd stress is unknown. Here, we functionally characterized an Arabidopsis thaliana NAC-type transcription factor, NAC102, revealing its role in Cd stress responses. Cd stress rapidly induced accumulation of NAC102.1, the major transcript encoding functional NAC102, especially in the root apex. Compared to wild type (WT) plants, a nac102 mutant exhibited enhanced Cd sensitivity, whereas NAC102.1-overexpressing plants displayed the opposite phenotype. Furthermore, NAC102 localizes to the nucleus, binds directly to the promoter of WALL-ASSOCIATED KINASE-LIKE PROTEIN11 (WAKL11), and induces transcription, thereby facilitating pectin degradation and decreasing Cd binding by pectin. Moreover, WAKL11 overexpression restored Cd tolerance in nac102 mutants to the WT levels, which was correlated with a lower pectin content and lower levels of pectin-bound Cd. Taken together, our work shows that the NAC102-WAKL11 module regulates cell wall pectin metabolism and Cd binding, thus conferring Cd tolerance in Arabidopsis.

OrMKK3 Influences Morphology and Grain Size in Rice.

Although morphology and grain size are important to rice growth and yield, the identity of abundant natural allelic variations that determine agronomically important differences in crops is unknown. Here, we characterized the function of mitogen-activated protein kinase 3 from Oryza officinalis Wall. ex Watt encoded by OrMKK3. Different alternative splicing variants occurred in OrMKK3. Green fluorescent protein (GFP)-OrMKK3 fusion proteins localized to the cell membrane and nuclei of rice protoplasts. Overexpression of OrMKK3 influenced the expression levels of the grain size-related genes SMG1, GW8, GL3, GW2, and DEP3. Phylogenetic analysis showed that OrMKK3 is well conserved in plants while showing large amounts of variation between indica, japonica, and wild rice. In addition, OrMKK3 slightly influenced brassinosteroid (BR) responses and the expression levels of BR-related genes. Our findings thus identify a new gene, OrMKK3, influencing morphology and grain size and that represents a possible link between mitogen-activated protein kinase and BR response pathways in grain growth. Supplementary Information: The online version contains supplementary material available at 10.1007/s12374-020-09290-2.

Targeting cancer stemness mediated by BMI1 and MCL1 for non-small cell lung cancer treatment.

Lung cancer is the leading cause of cancer-associated death, with a global 5-year survival rate <20%. Early metastasis and recurrence remain major challenges for lung cancer treatment. The stemness property of cancer cells has been suggested to play a key role in cancer plasticity, metastasis and drug-resistance, and is a potential target for drug development. In this study, we found that in non-small cell lung cancer (NSCLC), BMI1 and MCL1 play crucial roles of cancer stemness including invasion, chemo-resistance and tumour initiation. JNK signalling serves as a link between oncogenic pathway or genotoxicity to cancer stemness. The activation of JNK, either by mutant EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3-ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small-molecule, BI-44, was developed, which effectively suppressed BMI1/MCL1 expressions and inhibited tumour formation and progression in preclinical models. Targeting cancer stemness mediated by BMI1/MCL1 with BI-44 provides the basis for a new therapeutic approach in NSCLC treatment.

Expansion of granulocytic myeloid-derived suppressor cells in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV), is a hemorrhagic fever with a high mortality rate of over 10%. We have previously shown that granulocytic myeloid-derived suppressor cell (gMDSC) might affect arginine metabolism, which was associated with decreased platelet count and T lymphocyte dysfunction in this disease. The study was designed to investigate the expression of the gMDSCs subsets in SFTS patients, and to evaluate its association with disease severity. A prospective study was performed on 166 confirmed SFTSV infected patients. Sequential blood samples were collected during hospitalization and after recovery. SFTSV RNA was quantified by real-time RT-PCR. The gMDSCs and NK cells were determined by flow cytometry analysis, which were associated with disease severity. Elevation of the activated gMDSC was observed in SFTS patients at the acute phase, with a significantly higher level of gMDSC attained in 79 severe and 29 fatal SFTS patients than in the mild patients. The NK cells were depleted at the early infection and not restored to normal level until 4 months after the disease. The expansion of gMDSC was accompanied by the elevated expressions of CD3-ζ of NK and Arginase-1, in contrast with the decreased reactive oxygen species (ROS) in gMDSC. The levels of NK, CD3-ζ of NK, viral load, and platelet count were significantly associated with the level of gMDSC. Expansion of gMDSC was demonstrated in SFTS, which was associated with severe disease and suppressed antiviral NK cell via other mechanisms than Arginase-1 or ROS.

The number of cycles of adjuvant chemotherapy in stage III and high-risk stage II rectal cancer: a nomogram and recursive partitioning analysis.

OBJECTIVE: The prognostic role of the number of cycles of adjuvant chemotherapy (ACT) after total mesorectal excision in stage III and high-risk stage II rectal cancer is unknown. As a result of this, our study was designed to assess the effect of the number of cycles of ACT on the prediction of cancer-specific survival. METHODS: Four hundred patients that were diagnosed as stage III and high-risk stage II rectal cancer from January 2012 to January 2018 and who had received total mesorectal excision were enrolled in this study. A nomogram incorporating the number of cycles of ACT was also developed in this study. For internal validation, the bootstrap method was used and the consistency index was used to evaluate the accuracy of the model. The patients were stratified into risk groups according to their tumor characteristics by recursive partitioning analysis. RESULTS: We found that the risk of death was decreased by 26% (HR = 0.74, 95% CI: 0.61-0.89, P = 0.0016) with each increasing ACT cycle. The N stage, positive lymph node ratio (PLNR), carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, and the number of cycles of ACT were chosen and entered into the nomogram model. Recursive partitioning analysis-based risk stratification revealed a significant difference in the prognosis in rectal cancer patients with high-risk, intermediate-risk, and low-risk (3-year cancer-specific survival: 0.246 vs. 0.795 vs. 0.968, P < 0.0001). Seven or more cycles of ACT yielded better survival in patients with PLNR ≥ 0.28 but not in patients with PLNR < 0.28. CONCLUSION: In conclusion, the nomogram prognosis model based on the number of cycles of ACT predicted individual prognosis in rectal cancer patients who had undergone total mesorectal excision. These findings further showed that in patients with PLNR ≥ 0.28, no fewer than 7 cycles of ACT are needed to significantly reduce the patient's risk of death.

Emerging Effects of Resveratrol on Wound Healing: A Comprehensive Review.

Resveratrol (RSV) is a natural extract that has been extensively studied for its significant anti-inflammatory and antioxidant effects, which are closely associated with a variety of injurious diseases and even cosmetic medicine. In this review, we have researched and summarized the role of resveratrol and its different forms of action in wound healing, exploring its role and mechanisms in promoting wound healing through different modes of action such as hydrogels, fibrous scaffolds and parallel ratio medical devices with their anti-inflammatory, antioxidant, antibacterial and anti-ageing properties and functions in various cells that may play a role in wound healing. This will provide a direction for further understanding of the mechanism of action of resveratrol in wound healing for future research.

[Primary squamous cell carcinoma of the prostate: Clinical features and therapeutic strategies].

OBJECTIVE: To analyze the clinicopathological and imaging features of primary squamous cell carcinoma of the prostate (PSCC) and provide some new ideas for exploring suitable diagnostic and treatment strategies for the disease. METHODS: We retrieved and analyzed the studies published at home and abroad between 1976 and 2022 and reviewed the clinical data of our Department of Medical Oncology on 70 cases of PSCC, as well as the survival statistics of another 58 cases. RESULTS: Clinically, PSCC was characterized by normal PSA and increased squamous cell carcinoma antigen. Overall survival of the patients was evidently correlated to the PSCC stage, chemotherapy and radiotherapy, significantly longer in those treated by chemotherapy with platinum than in those without platinum (P = 0.001). Univariate analysis suggested that the overall survival of the patients was significantly correlated with chemotherapy. CONCLUSION: PSCC has a poor prognosis. A deep insight into the clinical characteristics of PSCC is important for timely detection and suitable treatment of the malignancy.

Circularly polarized optical microscope using a low aberration liquid crystal lens.

We demonstrate a circularly polarized optical microscope (POM) by incorporating a hole-patterned electrode (HPE) liquid crystal (LC) lens fabricated by photoalignment. The focal plane is controlled by voltages on the HPE LC lens with a tuning range of 2.2 mm without any mechanical movement. The diopter can be controlled from 0 to -5.0D, and the wavefront optical path difference is less than 0.25λ for our proposed HPE LC lens. Such a low aberration is obtained, because the LC directors are well aligned along with the axially symmetrical electrical field, and there is no observed twist deformation of the LC directors. Finally, we applied our circularly polarized POM to inspect the reflectance properties of several beetles, and we find that the "Chrysochroa toulgoeti" beetle exhibits right circularly polarized reflectance from some small areas on its wings.

Expression and purification of a recombinant ELRL-MAP30 with dual-targeting anti-tumor bioactivity.

MAP30 (Momordica antiviral protein 30kD) is a single-chain Ⅰ-type ribosome inactivating protein with a variety of biological activities, including anti-tumor ability. It was reported that MAP30 would serve as a novel and relatively safe agent for prophylaxis and treatment of liver cancer. To determine whether adding two tumor targeting peptides could improve the antitumor activities of MAP30, we genetically modified MAP30 with an RGD motif and a EGFRi motif, which is a ligand with high affinity for αvß3 integrins and with high affinity for EGFR. The recombinant protein ELRL-MAP30 (rELRL-MAP30) containing a GST-tag was expressed in E. coli. The rELRL-MAP30 was highly expressed in the soluble fraction after induction with 0.15 mM IPTG for 20 h at 16 °C. The purified rELRL-MAP30 appeared as a band on SDS-PAGE. It was identified by western blotting. Cytotoxicity of recombinant protein to HepG2, MDA-MB-231, HUVEC and MCF-7 cells was detected by MTT analysis. Half maximal inhibitory concentration (IC50) values were 54.64 µg/mL, 70.13 µg/mL, 146 µg/mL, 466.4 µg/mL, respectively. Proliferation inhibition assays indicated that rELRL-MAP30 could inhibit the growth of Human liver cancer cell HepG2 effectively. We found that rELRL-MAP30 significantly induced apoptosis in liver cancer cells, as evidenced by nuclear staining of DAPI. In addition, rELRL-MAP30 induced apoptosis in human liver cancer HepG2 cells by up-regulation of Bax as well as down-regulation of Bcl-2. Migration of cell line were markedly inhibited by rELRL-MAP30 in a dose-dependent manner compared to the recombinant MAP30 (rMAP30). In summary, the fusion protein displaying extremely potent cytotoxicity might be highly effective for tumor therapy.

Low phosphate represses histone deacetylase complex1 to regulate root system architecture remodeling in Arabidopsis.

The mechanisms involved in the regulation of gene expression in response to phosphate (Pi) deficiency have been extensively studied, but their chromatin-level regulation remains poorly understood. We examined the role of histone acetylation in response to Pi deficiency by using the histone deacetylase complex1 (hdc1) mutant. Genes involved in root system architecture (RSA) remodeling were analyzed by quantitative real-time polymerase chain reaction (qPCR) and chromatin immunoprecipitation qPCR. We demonstrate that histone H3 acetylation increased under Pi deficiency, and the hdc1 mutant was hypersensitive to Pi deficiency, with primary root growth inhibition and increases in root hair number. Concomitantly, Pi deficiency repressed HDC1 protein abundances. Under Pi deficiency, hdc1 accumulated higher concentrations of Fe3+ in the root tips and had higher expression of genes involved in RSA remodeling, such as ALUMINUM-ACTIVATED MALATE TRANSPORTER1 (ALMT1), LOW PHOSPHATE ROOT1 (LPR1), and LPR2 compared with wild-type plants. Furthermore, Pi deficiency enriched the histone H3 acetylation of ALMT1 and LPR1. Finally, genetic evidence showed that LPR1/2 was epistatic to HDC1 in regulating RSA remodeling. Our results suggest a chromatin-level control of Pi starvation responses in which HDC1-mediated histone H3 deacetylation represses the transcriptional activation of genes involved in RSA remodeling in Arabidopsis.

A NAC-type transcription factor confers aluminium resistance by regulating cell wall-associated receptor kinase 1 and cell wall pectin.

Transcriptional regulation is important for plants to respond to toxic effects of aluminium (Al). However, our current knowledge to these events is confined to a few transcription factors. Here, we functionally characterized a rice bean (Vigna umbellata) NAC-type transcription factor, VuNAR1, in terms of Al stress response. We demonstrated that rice bean VuNAR1 is a nuclear-localized transcriptional activator, whose expression was specifically upregulated by Al in roots but not in shoot. VuNAR1 overexpressing Arabidopsis plants exhibit improved Al resistance via Al exclusion. However, VuNAR1-mediated Al exclusion is independent of the function of known Al-resistant genes. Comparative transcriptomic analysis revealed that VuNAR1 specifically regulates the expression of genes associated with protein phosphorylation and cell wall modification in Arabidopsis. Transient expression assay demonstrated the direct transcriptional activation of cell wall-associated receptor kinase 1 (WAK1) by VuNAR1. Moreover, yeast one-hybrid assays and MEME motif searches identified a new VuNAR1-specific binding motif in the promoter of WAK1. Compared with wild-type Arabidopsis plants, VuNAR1 overexpressing plants have higher WAK1 expression and less pectin content. Taken together, our results suggest that VuNAR1 regulates Al resistance by regulating cell wall pectin metabolism via directly binding to the promoter of WAK1 and induce its expression.

CXCR5+ CD4+ T cell subsets and their relationship to immune dysfunction in chronic hepatitis B-associated liver cirrhosis.

BACKGROUND AND AIM: Hepatitis B-associated liver cirrhosis (HBC) leads to profound alterations of immune systems, especially disruptions of B cell immune responses. CXCR5+ CD4+ T cells (including T follicular helper [Tfh] cells and T follicular regulatory [Tfr] cells) are responsible for the regulation of B cell functions. The aim of this study was to dissect the roles of CXCR5+ CD4+ T cell subset in B cell disruption caused by HBC. METHODS: Forty-one patients with HBC and 15 healthy controls were enrolled in this study. ELISA, flow cytometric analysis, and cell coculture were performed to analyze the properties of Tfh and Tfr. RESULTS: We observed significantly decreased memory B cells and increased plasma B cells in HBC patients, as well as significant upregulation of lipopolysaccharide binding protein and soluble CD14 in plasma of decompensated HBCs patients. The downregulation of Tfh17 was observed in HBC patients with spontaneous bacterial peritonitis compared with those without. The decrease of Tfh17 was paralleled with Child-Pugh grade and negatively correlated with plasma B cells and soluble CD14 in HBC patients. Interleukin (IL)-21+ Tfh of HBC patients was also downregulated compared with healthy controls, and it was positively correlated with memory B cells and the upregulation of IL-10+ Tfr. It was then revealed that Tfr could inhibit the secretion of IL-21 by Tfh, and the blocking of IL-10 could diminish this effect. CONCLUSIONS: The changes of the frequency and function of Tfh and Tfr may play an important role in disease progression and immune dysfunction of HBC.

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.

Illumina sequencing revealed roles of microRNAs in different aluminum tolerance of two citrus species.

Self-germinated seedlings of Citrus sinensis and C. grandis were supplied with nutrient solution with 0 mM AlCl3·6H2O (control, -Al) or 1 mM AlCl3·6H2O (+Al) for 18 weeks. The DW (Dry weights) of leaf, stem, shoot and the whole plant of C. grandis were decreased and the ratio of root DW to shoot DW in C. grandis were increased by Al, whereas these parameters of C. sinensis were not changed by Al. Al treatment dramatically decreased the sulfur (S) content in C. grandis roots and the phosphorus (P) content in both C. sinensis and C. grandis roots. More Al was transported to shoots and leaves in C. grandis than in C. sinensis under Al treatment. Al treatment has more adverse effects on C. grandis than on C. sinensis, as revealed by the higher production of superoxide anion (O2 ·-), H2O2 and thiobarbituric acid reactive substace (TBARS) content in C. grandis roots. Via the Illumina sequencing technique, we successfully identified and quantified 12 and 16 differentially expressed miRNAs responding to Al stress in C. sinensis and C. grandis roots, respectively. The possible mechanism underlying different Al tolerance of C. sinensis and C. grandis were summarized as having following aspects: (a) enhancement of adventitious and lateral root development (miR160); (b) up-regulation of stress and signaling transduction related genes, such as SGT1, PLC and AAO (miR477, miR397 and miR398); (c) enhancement of citrate secretion (miR3627); (d) more flexible control of alternative glycolysis pathway and TCA cycle (miR3627 and miR482); (e) up-regulation of S-metabolism (miR172); (f) more flexible control of miRNA metabolism. For the first time, we showed that root development (miR160) and cell wall components (cas-miR5139, csi-miR12105) may play crucial roles in Al tolerance in citrus plants. In conclusion, our study provided a comprehensive profile of differentially expressed miRNAs in response to Al stress between two citrus plants differing in Al tolerance which further enriched our understanding of the molecular mechanism underlying Al tolerance in plants.

Polymorphism in the EREG gene confers susceptibility to tuberculosis.

BACKGROUND: Host genetic factors affect the immune response to Mycobacterium tuberculosis (Mtb) infection as well as the progression of the disease. Epiregulin (EREG) belongs to the epidermal growth factor (EGF) family, which binds to the epidermal growth factor receptor (EGFR) to regulate the immune response of the host during infections. Our study aimed to compare EREG levels in tuberculosis (TB) patients and healthy controls and assess whether polymorphisms in EREG increase the risk of TB. METHODS: We used ELISA to determine the plasma EREG level from 30 healthy controls and 50 tuberculosis patients. By evaluating the EREG gene from 624 TB patients and 600 healthy controls, we determined the allelic and genotypic frequencies for association with susceptibility to TB infections in this group. RESULTS: This paper shows that the pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) groups showed a significantly higher plasma EREG level (1014 ± 733.9 pg/ml, 700.2 ± 676.6 pg/ml, respectively) than the healthy controls (277 ± 105.4 pg/ml). The rs2367707 polymorphism was associated with a higher risk of PTB and EPTB (P = 0.00051, P = 0.0012). Analyses of haplotype frequencies found that people with the haplotype CACAT had a higher risk of PTB and EPTB (P = 0.00031, OR = 1.43; P = 0.000053, OR = 1.65). Moreover, the rs6446993 polymorphism of the EREG gene was found to be associated with EPTB (P = 0.00087, OR = 1.54; 95% CI = 1.23-1.94). CONCLUSIONS: Compared to that of healthy controls, the level of EREG in the plasma of TB patients increased significantly. Based on these data, we demonstrated that EREG polymorphisms are genetic factors for susceptibility to TB and various forms of TB.

Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking.

BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.