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Background: Pediatric pneumonia presents a significant global health challenge, particularly in low- and middle-income countries. This study aimed to investigate the incidence of pneumonia in preschool children in Urumqi and its association with indoor environmental factors. Methods: This case-control study collected data from December 2018 to December 2019 on 1522 preschool children in Urumqi (779 boys and 743 girls) who were diagnosed with pneumonia by a physician. A control group of children who had never had pneumonia was matched in a 1:1 ratio based on gender, age, and ethnicity. Using questionnaires, data were collected on children's general characteristics, passive smoking, types of housing, flooring materials, and indoor dampness, analyzing potential factors associated with the incidence of pediatric pneumonia. Results: Multivariate analysis revealed that cesarean birth (odds ratio [OR] = 1.27; 95 % confidence interval [95%CI] = 1.08-1.48), being an only child (OR = 1.32; 95%CI = 1.13-1.55), antibiotic treatment during the first year of life (OR = 2.51; 95%CI = 1.98-3.19), passive smoking during the mother's pregnancy (OR = 1.62; 95%CI = 1.24-2.13), living in multi-family apartment housing (OR = 1.64; 95%CI = 1.28-2.10) and other types of housing (OR = 1.47; 95%CI = 1.09-1.99), laminate flooring (OR = 1.31; 95%CI = 1.01-1.72), and tile/stone/cement flooring flooring (OR = 1.31; 95%CI = 1.06-1.61), and dampness in dwelling (during first year of mother's pregnancy) (OR = 1.30; 95%CI = 1.04-1.63) were risk factors for pediatric pneumonia. The use of fresh air filtration systems in children's residences (OR = 0.66; 95%CI = 0.50-0.86) was identified as a protective factor. Conclusion: This study underscores the importance of indoor environmental factors in the prevention of pediatric pneumonia. Public health strategies should consider these factors to reduce the incidence of pneumonia in children. Future research needs to be conducted over a broader geographical range and consider a more comprehensive range of factors influencing pediatric pneumonia.
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Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply. However, the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated. This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa. It displayed unprecedented mono- and/or di-malonylation activity toward diverse glucosides with different aglycons. A "one-pot" system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides. Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides. Additionally, it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions. QM/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1, while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167, resulting in its high malonylation regiospecificity. Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates, emphasizing CtMaT1's preference for glucosides. Furthermore, a mutant CtMaT1H36A with notably increased di-malonylation activity was obtained. The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation. This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives, while also providing a versatile tool for enzymatic malonylation applications in pharmacology.
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Biogenic purine crystals can function in vision as light scatters, mirrors, and multilayer reflectors and produce structural colors or depolarization for camouflage. Xanthine crystals form irregular multifocal mirrors in the median ocellus of Archaeognatha. It is important to broaden the study of crystallization strategies to obtain organic crystals with purine rings in the laboratory. In this work, a facile one-step synthesis route to fabricate bio-inspired xanthine crystals is reported for the first time. The obtained rhomboidal xanthine nanoplates have similar morphology and size to biogenic xanthine crystals. Their length and thickness are about 2-4 µm and 50 nm, respectively. Lattice parameters, crystal structure, formation mechanism and optical properties of synthetic single-crystalline xanthine nanoplates were investigated in detail in this work. The obtained xanthine nanoplate crystals are proposed to be anhydrous xanthine with monoclinic symmetry, and the xanthine nanoplates mainly expose the (100) plane. It is proposed that the anhydrous xanthine nanoplates are formed via an amorphous xanthine intermediate precursor. The synthetic anhydrous xanthine nanoplates exhibit excellent optical properties, including high diffuse reflectivity, strong depolarization and pearlescent luster. This work provides a new design to synthesize bio-inspired organic molecular crystals with excellent optical properties.
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Pancreatoblastoma (PB) is a rare malignant pancreatic epithelial tumor that mostly occurs in children and occasionally occurs in adults. The tumor has acinar cell differentiation and squamous corpuscles/squamous epithelial islands, which are frequently separated by fibrous bundles. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of numerous adenomatous polyps in the colon and rectum. Cases of pancreatoblastoma combined with familial adenomatous polyposis (FAP) are rarely reported. A review of a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis is presented herein. In this case, the patient was first diagnosed with familial adenomatous polyposis and subsequently found to have pancreatoblastoma 1 year and 3 months later. This suggests pancreatoblastoma may occur in patients with familial adenomatous polyposis or a family history of the condition, indicating a possible association between the two tumors. Therefore, pancreatoblastoma should be included in a differential diagnosis for FAP patients with a pancreatic mass. The final diagnosis of pancreatoblastoma depends on the pathological diagnosis. Acinar-like cells and squamous corpuscles/squamous epithelial cell islands under light microscopy are the key diagnostic points. This case report also can improve the awareness of clinicians, radiologists, and pathologists on the presence of rare tumor-adult pancreatoblastoma in patients with familial adenomatous polyposis.
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Objective: The aim of this report was to comprehensively investigate the clinicopathological features, histological characteristics, and differential diagnosis of tall cell carcinoma with reversed polarity of the breast (TCCRP) to enhance the understanding of this tumour for precise therapeutic interventions. Methods: The clinicopathological characteristics and differential diagnosis of a patient with TCCRP were retrospectively analysed, and a systematic literature review was extracted from relevant published studies on PubMed. Results: All patients included in the study were female, with a median age of 51 years. Microscopically, the tumour cells exhibited a solid papillary growth pattern with tall columnar morphology and reversed nuclear polarity. Immunohistochemistry revealed that the tumours were triple-negative breast cancer (negative for ER, PR, and HER-2), with a low Ki-67 proliferation index. Different degrees of expression were observed for CK7, Calretinin, and S-100 markers; however, CK5/6 showed high expression levels. Conclusions: TCCRP is an uncommon invasive carcinoma subtype found in the breast. Its histological morphology resembles that of tall cell subtype papillary thyroid carcinoma. Accurate diagnosis requires the integration of histomorphological assessment along with immunohistochemistry and molecular genetics analysis.
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OBJECTIVES: To predict the probability of occult lymph node metastasis (OLNM) in the central cervical by analyzing the dual-energy computed tomography (DECT) parameters derived from papillary thyroid carcinoma (PTC). METHODS: Data were retrospectively collected from patients with pathologically confirmed PTC who underwent arterial and venous phases of enhanced DECT with concurrent central neck lymph node dissection (CLND). Three clinical features, three shape-related features, and twenty-six DECT-derived parameters were measured. The univariate and multivariate analyses were applied to select the relevant parameters and develop the nomogram. RESULTS: A total 140 cases with negative diagnosis of cervical central lymph node metastases by preoperative evaluation were included, among which 88 patients with metastasis (OLNM +) and 52 patients without metastasis (OLNM -) were finally confirmed by pathology. (1) Anteroposterior/transverse diameter ratio (A/T) derived from the PTC focus had significant difference between the OLNM + and OLNM - groups (p < 0.05). (2) In the arterial phase, iodine concentration (ICarterial), normalized iodine concentration (NICarterial), effective atomic number (Zeff-arterial), electron density (EDarterial), and slope of energy curve (karterial) from PTC focus showed significant difference (all p < 0.05) between the two groups. In the venous phase, only the CT value under the 40 keV (HU40keVvenous) had differences (p < 0.05). (3) The nomogram was produced to predict the probability of OLNM, and the AUC, sensitivity, and specificity in the training and test cohort were 0.830, 75.0%, 76.9%, and 0.829, 65.9%, 84.6%, respectively. CONCLUSIONS: DECT parameters combined with shape-related feature derived from PTC might be used as predictors of OLNM in the central neck. CLINICAL RELEVANCE STATEMENT: Preoperative imaging evaluation combining shape-related features and dual-energy CT parameters could serve as a reference to discern occult lymph node metastasis in central neck during the surgically planning of papillary thyroid carcinoma. KEY POINTS: ⢠Papillary thyroid carcinoma (PTC) patients may have occult lymph node metastasis (OLNM) in the central neck, which is extremely difficult to find by preoperative imaging examination. ⢠Dual-energy CT quantitative evaluation has higher accuracy than conventional CT and can predicting OLNM in the central neck of PTC. ⢠Dual-energy CT quantitative parameters and morphology of PTC can serve as a useful tool in predicting OLNM in the central neck, and as a guide for personalized treatment.
Subject(s)
Carcinoma, Papillary , Iodine , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/diagnostic imaging , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Retrospective Studies , Carcinoma, Papillary/diagnostic imaging , Carcinoma, Papillary/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Tomography, X-Ray Computed , Neck/pathologyABSTRACT
Various naphthalenediimide (NDI) based electron donor-acceptor coordination polymers (D-A CPs) have been constructed and used to explore charge transfer (CT) and electron transfer (ET) behaviors. Up to now, significant progress has been made in the interface contact and electron donor-acceptor ability matching mechanism, while the electronic density effect of the electron donors on the CT and ET behaviors is still not known. Herein, two NDI-based D-A CPs, [Cd2(H2NDI)(IPA)2(H2O)2] (1) and [Cd2(H2NDI)(IPA-OH)2(H2O)2] (2), are constructed using an NDI-based ligand and two aromatic carboxylic acid ligands (H2NDI = 2,7-bis(3,5-dimethyl) dipyrazol-1,4,5,8-naphthalene tetracarboxydiimide, H2IPA = isophthalic acid; and H2IPA-OH = 5-hydroxyisophthalic acid). UV-vis and EPR spectroscopy and DFT calculations analyses reveal that the occurrence of themal electron transfer (TET) in 1 and 2 results from the HOMO of the IPA and IPA-OH lying higher than the LUMO of the NDI. Meanwhile, compared to 1, the UV-vis absorption spectrum of 2 exhibits a significant red shift, which suggests higher electron density of the donor and more electron transfer pathways are beneficial for the occurrence of intermolecular CT. After UV light irradiation, the comparison of the photochromic behavior of 1 and 2 confirms the negative effect of the stronger CT on photoinduced electron transfer (PET). The present study illustrates the delicate modulating effect of electron density on the CT and ET behaviors in D-A CPs.
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Insulin resistance plays an important role in the pathogenesis of polycystic ovarian syndrome (PCOS). Calpain10 (CAPN10) gene was the first identified susceptibility gene for type 2 diabetes mellitus and closely related to insulin sensitivity. A lot of research attention has been attracted on the relationship between CAPN10 polymorphisms and PCOS risk, but they didn't reach a consistent conclusion. We therefore performed this systematic review and meta-analysis to assess the association of CAPN10 common variants with PCOS susceptibility. A total of 21 studies were eligible for inclusion. Meta-analyses were done for 5 variants that had at least two data sources: UCSNP-19, -43, -44, -56 and -63. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under five genetic models. Subgroup analyses by ethnicity, PCOS diagnostic criteria, and source of controls were conducted. Moreover, false-positive report probability (FPRP) test and trial sequential analysis (TSA) were performed to assess the significant associations. The results showed a possible negative association between UCSNP-19 and PCOS risk (ins/ins vs. del/del + del/ins: OR = 0.84, 95% CI: 0.72-0.98). In subgroup analyses, FPRP test indicated that noteworthy associations were observed in mixed ethnicities for UCSNP-43 (A vs. G: OR = 1.81, 95% CI: 1.17-2.79; AA + AG vs. GG: OR = 2.14, 95% CI: 1.20-3.80) and in Asians for UCSNP-44 (CC vs. TT: OR = 2.07, 95% CI: 1.21-3.51; CC vs. CT + TT: OR = 2.19, 95% CI: 1.31-3.69), but TSA plots showed that the accumulated sample sizes of these associations were insufficient to draw firm conclusions. In summary, our study suggested that UCSNP-19, UCSNP-43, and UCSNP-44 in CAPN10 gene may be involved in PCOS susceptibility. These findings warrant further studies.
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2-(2-Phenylethyl)chromones (PECs) are the main bioactive components of agarwood which showed diverse pharmaceutical activities. Glycosylation is a useful structural modification method to improve compounds' druggability. However, PEC glycosides were rarely reported in nature which largely limited their further medicinal investigations and applications. In this study, the enzymatic glycosylation of four naturally separated PECs 1-4 was achieved using a promiscuous glycosyltransferase UGT71BD1 identified from Cistanche tubulosa. It could accept UDP-Glucose, UDP-N-acetylglucosamine and UDP-xylose as sugar donors and conduct the corresponding O-glycosylation of 1-4 with high conversion efficiencies. Three O-glucosylated products 1a (5-hydroxy-2-(2-phenylethyl)chromone 8-O-ß-D-glucopyranoside), 2a (8-chloro-2-(2-phenylethyl)chromone 6-O-ß-D-glucopyranoside) and 3a (2-(2-phenylethyl)chromone 6-O-ß-D-glucopyranoside) were prepared and structurally elucidated as novel PEC glucosides based on NMR spectroscopic analyses. Subsequent pharmaceutical evaluation found that 1a showed remarkably improved cytotoxicity against HL-60 cells, whose cell inhibition rate was 19 times higher than that of its aglycon 1. The IC50 value of 1a was further determined to be 13.96 ± 1.10 µM, implying its potential as a promising antitumor-leading candidate. To improve the production of 1, docking, simulation and site-directed mutagenesis were performed. The important role of P15 in the glucosylation of PECs was discovered. Besides, a mutant K288A with a two-fold increased yield for 1a production was also afforded. This research reported the enzymatic glycosylation of PECs for the first time, and also provide an eco-friendly pathway for the alternative production of PEC glycosides for leading compounds discovery.
Subject(s)
Chromones , Glycosides , Humans , Chromones/pharmacology , Glycosyltransferases/genetics , Glycosyltransferases/metabolism , Pharmaceutical Preparations , Catalysis , Uridine Diphosphate , Molecular StructureABSTRACT
COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of â3)-ß-d-Gal-(1 â 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α-l-Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibite the infection with an EC50 of 37.52 µg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19.
Subject(s)
Antiviral Agents , COVID-19 , SARS-CoV-2 , Humans , Molecular Docking Simulation , SARS-CoV-2/drug effects , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Sulfates , Antiviral Agents/pharmacology , Rhodophyta/chemistryABSTRACT
As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.
Subject(s)
Alkaloids , Biological Products , Biological Products/chemistry , Catalysis , BiocatalysisABSTRACT
OBJECTIVE: To explore the clinicopathological features of solitary fibrous tumors (SFTs) of the lung. METHODS: We collected the clinical data of 52 patients with SFTs of the lung confirmed by pathology, and summarized the clinical, radiological, and morphological features, the immunophenotypes, and the prognosis of SFTs. RESULTS: Fifty-two cases of SFTs of the lung were enrolled in this study, including 51 cases of borderline and 1 case of malignancy, 22 males and 30 females. The average onset age was 52.7 years. The lower lobe of the left lung was the preferred site of SFTs, accounting for 30.77% (16/52). Chest CT showed regular and well-demarcated soft tissue density mass, and the tumor size of most cases (46/52, 88.46%) was 1-10 cm. Morphological features: The distribution of tumor cells showed sparse and dense areas. Tumor cells were spindle-shaped, in whorls or hemangiopericytoma-like conformation. Atypia, mitotic figures, and necrosis were found. Immunohistochemistry showed positive expression of CD34, STAT6, Vimentin, BCL2, and CD99. Ki-67 was ≤ 5% in borderline SFTs and >20% in a malignant SFT. CONCLUSIONS: Solitary fibrous tumors of the lung occur more frequently in middle-aged and elderly people, and there is no significant difference in gender. The lower lobe of the left lung is the preferred site of SFTs. The size of most SFTs is 1-10 cm. Chest CT shows morphologically regular and well-demarcated soft tissue density mass. Pathologically, SFTs of the lung are mostly borderline and occasionally malignant. Immunohistochemistry shows the positive expression of CD34, STAT6, Vimentin, BCL2, and CD99.
Subject(s)
Severe Fever with Thrombocytopenia Syndrome , Solitary Fibrous Tumors , Aged , Middle Aged , Male , Female , Humans , Vimentin , Biomarkers, Tumor/analysis , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/metabolism , Solitary Fibrous Tumors/pathology , Lung/pathology , Proto-Oncogene Proteins c-bcl-2ABSTRACT
The cytochrome P450 17α-hydroxylase (P450c17) enzyme, encoded by Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) gene, catalyzes both the 17a-hydroxylation and 17,20-lyase reactions required for the production of cortisol and sex steroids. 17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive disease caused by homozygous or compound heterozygous mutations in CYP17A1 gene. 17OHD can be classified into complete form and partial form based on the phenotypes resulting from P450c17 enzyme defects of different severities. Here we report two unrelated girls diagnosed with 17OHD at the age of 15 and 16 respectively. Both patients presented with primary amenorrhea, infantile female external genitalia and absent axillary or pubic hair. Hypergonadotropic hypogonadism was detected in both patients. Besides, Case 1 showed undeveloped breast, primary nocturnal enuresis, hypertension, hypokalemia and reduced 17α-hydroxyprogesterone and cortisol levels, while Case 2 had growth spurt, spontaneous breast development, elevated corticosterone and decreased aldosterone. The chromosome karyotype for both patients was 46, XX. Clinical exome sequencing was used to detect the underlying genetic defect in the patients, and the potential pathogenic mutations were validated by Sanger sequencing of the patients and their parents. The homozygous p.S106P mutation of CYP17A1 gene detected in Case 1 has been reported previously. Although the p.R347C and p.R362H mutations have been reported separately before, their compound heterozygote was firstly identified in Case 2. Based on the clinical, laboratory and genetic findings, Case 1 and Case 2 were definitely diagnosed as complete and partial form of 17OHD respectively. Both patients received estrogen and glucocorticoid replacement therapy. Their uterus and breasts developed gradually, and first menstruation occurred. Hypertension, hypokalemia and nocturnal enuresis in Case 1 were relieved. In conclusion, we described a case of complete 17OHD accompanied by nocturnal enuresis for the first time. Moreover, we identified a new compound heterozygote (p.R347C and p.R362H) of CYP17A1 gene in the case with partial 17OHD.
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Organic matter is a critical factor which regulates nitrogen loss pathways of denitrification and anammox for microbes in marine ecosystems. However, only a little attention has been paid to contrasting studies on denitrification and anammox in sandy and muddy sediments, especially in the coastal continental shelf dominated by sandy sediments. This study determined the bulk properties and associated microbial nitrogen transformation processes of surface sediments in the East China Sea coastal shelf, with the aim of gaining insight into the interaction of nitrogen loss with organic matter at the molecular level. The results illustrate that nitrogen loss dominates in organic-rich muddy sediments, and its denitrification rate (14.39 nmol N g-1 h-1) and anammox rate (2.73 nmol N g-1 h-1) are greater than those of sandy sediments (denitrification rate = 5.55 nmol N g-1 h-1, anammox rate = 1.57 nmol N g-1 h-1). Furthermore, determination of the mean summed ladderanes shows higher anammox generated in the muddy sediments with a value of 167.78 ng g-1dw. Quantitative analysis demonstrated that organic-rich muddy sediments enhanced the copy number of the denitrifying functional gene nosZ and anammox functional gene hzsB. We inferred that the greater rate of nitrogen loss in muddy sediments was due to the coupling relationship between anammox and denitrification. Overall, the community distribution and abundance of denitrifying bacteria and anammox bacteria changed intricately under the influence of organic matter. Moreover, this study further improves the understanding of nitrogen loss pathways and mechanistic factors from sediments.
Subject(s)
Denitrification , Geologic Sediments , Geologic Sediments/microbiology , Ecosystem , Nitrogen/metabolism , Oxidation-ReductionABSTRACT
The overuse of antibiotics in the past decades has led to the emergence of a large number of drug-resistant microorganisms. In recent years, the infection rate caused by multidrug-resistant microorganisms has been increasing, which has become one of the most challenging problems in modern medicine. Plant-derived secondary metabolites and their derivatives have been identified to display significant antimicrobial abilities with good tolerance and less adverse side effects, potentially having different action mechanisms with antibiotics of microbial origin. Thus, these phyto-antimicrobials have a good prospect in the treatment of multidrug-resistant microorganisms. Terpenoids, alkaloids, and flavonoids made up the predominant part of the currently reported phytochemicals with antimicrobial activities. Synthetic biology research around these compounds is one of the hotspot fields in recent years, which not only has illuminated the biosynthesis pathways of these phyto-antimicrobials but has also offered new methods for their production. In this review, we discuss the biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents-using artemisinin and oleanolic acid (terpenoids), berberine and colchicine (alkaloids), and baicalin (flavonoids) as examples-around their antimicrobial action mechanisms, biosynthesis pathway elucidation, key enzyme identification, and heterologous production, in order to provide useful hints for plant-derived antimicrobial agent discovery and development.
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Sorghum [Sorghum bicolor (L.) Moench] is an important crop for food security in semiarid and arid regions due to its high tolerance to abiotic and biotic stresses and its good performance in marginal lands with relatively low fertility. To deeply understand the interrelationship among sorghum genotype, environment, sowing dates, and densities in the spring sowing early maturing (SSEM) areas of China, and to provide a basis for specifying scientific and reasonable cultural practices, a two-year field experiment was conducted with six popular varieties at six locations. Combined ANOVA showed that the yield difference between years was significant (P<0.05); the yield differences among locations, varieties, sowing dates, and densities were all highly significant (P<0.01). The variety effect was mainly influenced by location, year, sowing dates and their interactions. The sowing effect was mainly influenced by the location, year, variety and their interactions The plant density effect was significantly influenced by location and location-year interaction. Of the contributions of various test factors to yield variance, the location was the largest one (38.18%), followed by variety (12.31%), sowing date (1.53%), density (0.54%), and year (0.09%), with all these single factors accounting for 52.65%. The total contribution of all two-factor interactions accounted for 14.24%, among which the greatest contributor was location-hybrid interaction (8.07%). The total contribution of all three-factor interactions accounted for 14.58%, of which year-location-hybrid interaction was the largest contributor (9.02%). Sowing dates significantly affected model of sorghum growth and development, especially during the late period. The key climatic factors affecting yield were different among the six locations. Weather factors during the grain filling stages contributed much more than those during the early stage to grain yield. Mid-maturing varieties are recommended other than early maturing varieties for the SSEM areas even when late sowing occurs. Sowing as early as possible is recommended for areas with very short frost-free period (Harbin, Tongliao, and Datong). Proper delayed sowing is recommended for areas with a relative long frost-free period (Gongzhuling, Baicheng and Zhangjiakou). This research will provide a conducive reference for sorghum production in similar areas.
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Objective: To investigate the clinical manifestations, radiologic features, pathological features, and immunophenotype of minute pulmonary meningothelial-like nodules (MPMNs). Method: This is a retrospective observational study. We collected the clinical data of 7 cases of MPMNs, and performed comprehensive characterization using a combination of clinical, morphological, radiologic and immunohistochemical assessments. Results: Of the 7 cases of MPMNs, 6 were female and 1 was male. The median age was 55 years. All MPMNs were multiple in lung with the size from 0,01 to 0,5cm. Chest CT examination showed ground-glass attenuation or solid nodules. Four cases were concomitant with carcinoma and/or pneumonia, and 3 cases occurred alone. Four of the 7 patients had no obvious symptoms; 3 patients had chest pain or cough or shortness of breath or hemoptysis. Multiple white nodules were found macroscopically, and the diseased cells grew along the alveolar septum, with relatively normal morphology, rich cytoplasm, unclear cell boundary, and uniform nucleus with delicate chromatin and without atypia; and the diseased cells showed nest or whorls distribution. EMA, PR, CD56 and vimentin were positive in all cases by immunohistochemistry. Conclusions: MPMNs are rare benign lesions in the lung, often multiple, usually less than 0.5cm in diameter, most of which have no obvious clinical symptoms. MPMNs are often found by chest CT, and occur independently or concomitant with other lesions. The positive immunohistochemical staining of EMA, PR, CD56, vimentin supports the diagnosis.
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Multiple-glycosylated glycosides are a major source of bioactive leads. However, most of the currently reported glycosyltransferases (GTases) mainly catalyze glycosylation of aglycones without sugar group substitution. GTases accepting diverse glycosides as substrates are rarely reported. In this article, a new GTase UGT71BD1 was identified from Cistanche tubulosa, a desert herb plant abundant with various phenylethanoid glycosides (PhGs). Interestingly, UGT71BD1 showed no activity toward the aglycone of PhGs. Instead, it could catalyze the further glycosylation of PhG compounds to produce new phenylethanoid multiglycosylated glycosides, including the natural rarely separated tetraglycoside PhGs. Extensive assays found the unprecedented substrate promiscuity of UGT71BD1 toward diverse glycosides including flavonoid glycosides, stilbene glycosides, and coumarin glycosides, performing further mono- or diglycosylation with efficient conversion rates. Using UGT71BD1, six multiglycosylated glycosides were prepared and structurally identified by NMR spectroscopy. These products showed enhanced pharmacological activities compared with the substrates. Docking, dynamic simulation, and mutagenesis studies identified key residues for UGT71BD1's activity and revealed that the sugar modules in glycosides play crucial roles in substrate recognition, thus partly illuminating the unusual substrate preference of UGT71BD1 toward diverse glycosides. UGT71BD1 could be a potential enzyme tool for glycosylation of diverse glycosides.
Subject(s)
Cistanche , Cistanche/chemistry , Cistanche/metabolism , Glycosides/chemistry , Glycosylation , Glycosyltransferases/metabolism , SugarsABSTRACT
Helicobacter pylori (H. pylori) infection is the strongest risk factor for the occurrence and development of gastric carcinoma. However, the molecular mechanism underlying H. pylori-induced pathogenesis has not yet been fully characterized. Here, we explored whether H. pylori upregulates semaphorin 5A to promote gastric cancer progression via the extracellular regulated protein kinases/matrix metalloproteinase (ERK/MMP9) signaling pathway. In this study, H. pylori upregulated semaphorin 5A expression in vitro and in vivo. Using the human gastric carcinoma cell lines SGC7901, SGC7901-siScrambled, and SGC7901-siSema 5A, our studies showed that H. pylori increased the proliferation, growth, migration, and invasiveness of gastric cancer cells via its effects on semaphorin 5A and that H. pylori increased the expression of MMP9 in gastric cancer cells via the semaphorin 5A-mediated ERK signaling pathway. Further analysis revealed that the ERK inhibitor PD98059 and MMP9 antibody (Ab) attenuated H. pylori-induced gastric cancer cell invasion and metastasis in vitro through a semaphorin 5A-dependent mechanism. In conclusion, H. pylori could promote gastric cancer progression in a semaphorin 5A-dependent manner via the ERK/MMP9 signaling pathway. Semaphorin 5A and its related signaling molecules potentially represent latent targets for H. pylori-related gastric cancer therapy.
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BACKGROUND: To evaluate the prevalence of myopia in school students in Urumqi, China, and explore the influence of the interaction between parental myopia and poor reading and writing habits on myopia to identify the at-risk population and provide evidence to help school students avoid developing myopia. METHODS: A cross-sectional survey was conducted with 6,883 school students aged 7-20 years in Urumqi in December 2019. The Standard Eye Chart and mydriatic optometry were used to determine whether students had myopia. Falconer's method was used to calculate the heritability of parental myopia. Multivariate unconditional logistic regression models were used to analyze the risk factors for myopia and the additive and multiplicative interaction of parental myopia and poor reading and writing habits. RESULTS: After standardizing the age of the 6,883 students, the overall prevalence rate of myopia was 47.50 %. The heritability of parental myopia was 66.57 % for boys, 67.82 % for girls, 65.02 % for the Han group, and 52.71 % for other ethnicities. There were additive interactions between parental myopia and poor reading and writing habits; among them, parental myopia and poor eye habits when reading and writing (the distance between the eyes and book is less than 30 cm when reading and writing, fingers block the sight of one eye while holding the pen, and leaning one's body when reading and writing; habit 1) increased the risk of myopia by 10.99 times (odds ratio [OR] = 10.99, 95 % confidence interval [CI] = 8.33-14.68), parental myopia and poor reading posture (reading while lying down, walking, or in the car; habit 2) increased the risk of myopia by 5.92 times (OR = 5.92, 95 % CI = 4.84-7.27). There was no multiplicative interaction between parental myopia and habit 1 or habit 2 (OR = 0.69, 95 % CI = 0.44-1.08; OR = 0.89, 95 % CI = 0.66-1.21, respectively). CONCLUSION: The prevalence of myopia among students in Urumqi, Xinjiang is relatively high. The risk of developing myopia is affected by parental myopia and poor reading and writing habits. In addition, parental myopia amplifies the harm caused by poor reading and writing habits, thereby increasing the risk of myopia. Students with parents who have myopia should be targeted during myopia prevention efforts.