Insufficient Oligodendrocyte Turnover in Optic Nerve Contributes to Age-Related Axon Loss and Visual Deficits.

Age-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available up-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13-18 months) and old (20-22 months) mice of either sex compared with adult mice (3-8 months), accompanied by functional deficits. Oligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL turnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis displayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and visual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice. Genetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual function. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clemastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine treatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved visual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and visual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function.SIGNIFICANCE STATEMENT Oligodendrocyte (OL) turnover has been reported in adult optic nerves (ONs), but the longitudinal change and functional significance of OL turnover during aging remain largely unknown. Using cell-lineage tracing and oligodendroglia-specific manipulation, this study reported that OL generation was active in adult ONs and the efficiency decreased in an age-dependent manner. Genetically dampening OL generation by Olig2 ablation resulted in significant axon loss and retinal degeneration, along with delayed visual signal transmission. Conversely, pro-myelination approaches significantly increased new myelin generation in aging ONs, and consequently preserved retinal integrity and visual function. Our findings indicate that promoting OL generation might be a promising strategy to preserve visual function from age-related decline.

Exploring the link between walking and lung cancer risk: a two-stage Mendelian randomization analysis.

BACKGROUND: Previous observational research showed a potential link between physical activities such as walking and the risk of lung cancer. However, Mendelian randomization (MR) studies suggested there was no association between moderate to vigorous physical activity and lung cancer risk. We speculated that specific physical activities may be associated with lung cancer risk. Consequently, we conducted an MR study to examine the potential relationship between walking and the risk of lung cancer. METHODS: We collected genetic summary data from UK Biobank. After excluding SNPs with F values less than 10 and those associated with confounding factors, we conducted a MR analysis to assess the causal effects between different types of walk and lung cancer. We also performed sensitivity analysis to validate the robustness of our findings. Finally, we analyzed the possible mediators. RESULTS: MR analysis showed number of days/week walked for 10 + minutes was associated with a reduced risk of lung cancer risk (OR = 0.993, 95% CI = 0.987-0.998, P = 0.009). Additionally, usual walking pace was identified as a potentially significant factor in lowering the risk (OR = 0.989, 95% CI = 0.980-0.998, P = 0.015). However, duration of walks alone did not show a significant association with lung cancer risk (OR = 0.991, 95%CI = 0.977-1.005, P = 0.216). The sensitivity analysis confirmed the robustness of these findings. And number of days/week walked for 10 + minutes could affect fed-up feelings and then lung cancer risk. There was a bidirectional relationship between usual walking pace and sedentary behaviors (time spent watching TV). CONCLUSION: The study unveiled a genetically predicted causal relationship between number of days/week walked for 10 + minutes, usual walking pace, and the risk of lung cancer. The exploration of potential mediators of walking phenotypes and their impact on lung cancer risk suggests that specific physical activities may reduce the risk of lung cancer.

Deletion of BACH1 alleviates ferroptosis and protects against LPS-triggered acute lung injury by activating Nrf2/HO-1 signaling pathway.

Multiple lines of evidences have unraveled the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI). In this study, we aimed to decipher the role of BACH1 in the onset and progression of ALI with a focus on ferroptosis and elucidated potential molecular mechanism. We observed that BACH1 expression was drastically elevated in BEAS-2B cells upon exposure to LPS. In the functional aspect, BACH1 deletion exerted an anti-inflammatory property, featured by decreased the secretion of several cytokines including TNF-α, IL-1ß and IL-6 in the face of LPS challenge. What's more important, BACH1 knockout evidently repressed LPS-triggered oxidative stress damage, as evidenced by reduced reactive oxygen species (ROS) production and malondialdehyde (MDA) generation, accompanied with the elevated the activities of superoxide dismutase (SOD), GSH-Px and CAT. Meanwhile, ablation of BACH1 restrained LPS-elicited ferroptosis, as characterized by decreased iron content and PTGS2 expression, accompanied with increased expression of SLC7A11 and GPX4. In terms of mechanism, Nrf2/HO-1 signaling inhibitor effectively abrogated the beneficial effects of BACH1 inhibition on LPS-stimulated inflammation, oxidative damage and ferroptosis. Taken together, these preceding outcomes strongly illuminated that BACH1 was a novel regulator of LPS-evoked injury through regulation of inflammation response, oxidative stress and ferroptosis via activation Nrf2/HO-1 signaling, indicating that BACH1 may represent as a promising novel therapeutic candidate for ALI treatment.

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Clinical Value of Platelets and Coagulation Parameters in Predicting the Severity of Delta Variant SARS-CoV-2.

INTRODUCTION: The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta. METHODS: This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization. RESULTS: Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30-51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta. CONCLUSION: Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.

Copper-Catalyzed 1,2-Dicarbonylative Cyclization of Alkenes with Alkyl Bromides via Radical Cascade Process.

Herein, we developed a new procedure on 1,2-dicarbonylative cyclization of 4-aryl-1-butenes with alkyl bromides. Using simple copper catalyst, two molecules of carbon monoxide were introduced into the double bond with the formation of four new C-C bonds and a new ring. Various α-tetralones and 2,3-dihydroquinolin-4-ones were formed in moderate to good yields.

Downregulation of aromatase plays a dual role in preeclampsia.

Preeclampsia (PE) is a gestational disease, which seriously impairs maternal and infant health. However, the pathogenesis of PE remains unclear. The aromatase (CYP19A1) in placenta converts androgens from maternal and fetal adrenal glands to estrogen. Therefore, this change in the aromatase expression or function and the subsequent change of steroids in the placenta could be related to the pathophysiology of PE. In this study, we first analyzed the expression of CYP19A1 in clinical placental tissues as well as the level of sex hormones in corresponding serum samples. The results showed that the expression of aromatase in the placenta of PE patients was relatively low and accompanied by a sex hormone imbalance. Subsequently, animal experiments showed that ischemia and hypoxia lead to a low expression of CYP19A1, and that PE-like symptoms appear in pregnant mice following decreased or inhibited CYP19A1 expression. It was also found that, with the downregulation of CYP19A1 expression, the invasion and migration abilities of trophoblast cells were enhanced, which benefited placental implantation. However, alongside this, apoptosis and the inflammatory response were also increased, which was detrimental to placental development. Phosphoproteomic analyses revealed that the activation of the PI3K/AKT signaling pathway may play a key role in these processes. In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE.

LncRNA UCA1 remits LPS-engendered inflammatory damage through deactivation of miR-499b-5p/TLR4 axis.

Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPS-injured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1ß, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPS-stimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.

HASPIN is involved in the progression of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) is a common malignant tumor of the biliary system, but the current treatment of GBC is unsatisfactory. Therefore, new treatment targets and strategies are urgently needed. METHODS: The expression of HASPIN in GBC was detected by immunohistochemical staining. HASPIN knockdown cell model was constructed by lentivirus infection, and the infection efficiency of lentivirus and knockdown efficiency of shHASPIN were verified by fluorescence immunoassay, qRT-PCR and Western blot. The effects of HASPIN knockdown on cell proliferation, clone-formation ability and apoptosis were determined by MTT, clone formation assay, flow cytometry and Human Apoptosis Antibody Array in vitro. Besides, the effect of HASPIN knockdown on the growth of GBC solid tumors was demonstrated in vivo. RESULTS: The expression of HASPIN in GBC was up-regulated and positively correlated with the pathological grade of GBC. ShHASPIN significantly down-regulated the mRNA and protein levels of HASPIN, suggesting that HASPIN knockdown cell model was successfully constructed in vitro. After HASPIN knockdown, the proliferation and clone-formation ability of GBC cells were observably inhibited, the apoptotic levels were markedly increased, and the expression of Caspase 3, IGFBP-5, p21 and sTNF-R1 related to apoptotic pathway was up-regulated. Furthermore, HASPIN knockdown inhibited the growth of GBC in vivo. CONCLUSION: HASPIN was up-regulated in GBC and played an important role in promoting the progress of GBC.

Assembling seed dormancy genes into a system identified their effects on seedbank longevity in weedy rice.

Seed dormancy (SD) and longevity (SL) may share developmental and genetic mechanisms, as both traits are developed in the same maternal environment and evolved to coordinate the timing of germination and the life span of seedbanks. To test the hypothesis, allelic variants at the SD1-2, 7-1, 7-2, and 12 loci from weedy and cultivated rice (Oryza sativa) were assembled into the same genetic background, and 16 homozygous lines selected as a tetragenic system. These lines were evaluated for SD measured by germination at 7, 21, 35, and 150 days of after-ripening (DAR), and for SL measured by the seed decay rate and survivability in the soil of a rice field for 7 months. Pyramiding the alleles from weedy rice lengthened the dormancy duration, and seeds survived in the soil remained dormant at the excavation. Germination levels at 7 to 150 DAR were correlated positively with the seed decay rate (r = 0.41-0.53) and negatively with the survivability (r = -0.45 to -0.28) in the tetragenic system. All four loci contributed to genotypic variation for each of the SD and SL measurements through main and/or epistatic (two- to four-order interactions) effects. SD7-1 (identical to the pericarp color gene Rc) played a major role in regulating seedbank longevity when interacted with the other SD gene(s). This research provided evidence that natural genes controlling SD are involved in regulation of soil seedbank longevity. Thus, accumulation of SD genes in a population could result in persistence of wild plants and weeds in conventional tillage systems.

The complete mitochondrial genome of Eterusia aedea (Lepidoptera, Zygaenidae) and comparison with other zygaenid moths.

Zygaenidae comprises >1036 species, including many folivorous pests in agriculture. In the present study, the complete mitochondrial genome (mitogenome) of a major pest of tea trees, Eterusia aedea was determined. The 15,196-bp circular genome contained the common set of 37 mitochondrial genes (including 13 protein-coding genes, two rRNA genes, and 22 tRNA genes) and exhibited the similar genomic features to reported Zygaenidae mitogenome. Comparative analyses of Zygaenidae mitogenomes showed a typical evolutionary trend of lepidopteran mitogenomes. In addition, we also investigated the gene order of lepidopteran mitogenomes and proposed that the novel gene order trnA-trnR-trnN-trnE-trnS-trnF from Zygaenidae and Gelechiidae and most other gene rearrangements of this tRNA cluster evolved independently. Finally, the mitogenomic phylogeny of Lepidoptera was reconstructed based on multiple mitochondrial datasets. And all the phylogenetic results revealed the sister relationships of Cossoidea and Zygaenoidea with both BI and ML methods, which is the first stable mitogenomic evidence for this clade.

Controllable Si-C Bond Activation Enables Stereocontrol in the Palladium-Catalyzed [4+2] Annulation of Cyclopropenes with Benzosilacyclobutanes.

A novel and unusual palladium-catalyzed [4+2] annulation of cyclopropenes with benzosilacyclobutanes is reported. This reaction occurred through chemoselective Si-C(sp2 ) bond activation in synergy with ring expansion/insertion of cyclopropenes to form new C(sp2 )-C(sp3 ) and Si-C(sp3 ) bonds. An array of previously elusive bicyclic skeleton with high strain, silabicyclo[4.1.0]heptanes, were formed in good yields with excellent diastereoselectivity under mild conditions. An asymmetric version of the reaction with a chiral phosphoramidite ligand furnished a variety of chiral bicyclic silaheterocycle derivatives with good enantioselectivity (up to 95.5:4.5 er). Owing to the mild reaction conditions, the good stereoselectivity profile, and the ready availability of the functionalized precursors, this process constitutes a useful and straightforward strategy for the synthesis of densely functionalized silacycles.

Management of Persistent Air Leaks Using Endobronchial Autologous Blood Patch and Spigot Occlusion: A Multicentre Randomized Controlled Trial in China.

BACKGROUND: Optimal management of persistent air leaks (PALs) in patients with secondary spontaneous pneumothorax (SSP) remains controversial. OBJECTIVE: To evaluate the efficacy and safety of endobronchial autologous blood plus thrombin patch (ABP) and bronchial occlusion using silicone spigots (BOS) in patients with SSP accompanied by alveolar-pleural fistula (APF) and PALs. METHODS: This prospective multicentre randomized controlled trial compared chest tube-attached water-seal drainage (CTD), ABP, and BOS that were performed between February 2015 and June 2017 in one of six tertiary care hospitals in China. Patients diagnosed with APF experiencing PALs (despite 7 days of CTD) and inoperable patients were included. Outcome measures included success rate of pneumothorax resolution at the end of the observation period (further 14 days), duration of air leak stop, lung expansion, hospital stay, and complications. RESULTS: In total, 150 subjects were analysed in three groups (CTD, ABP, BOS) of 50 each. At 14 days, 60, 82, and 84% of CTD, ABP, and BOS subjects, respectively, experienced full resolution of pneumothorax (p = 0.008). All duration outcome measures were significantly better in the ABP and BOS groups than in the CTD group (p < 0.016 for all). The incidence of adverse events, including chest pain, cough, and fever, was not significantly different. All subjects in the ABP and BOS groups experienced temporary haemoptysis. Spigot displacement occurred in 8% of BOS subjects. CONCLUSION: ABP and BOS resulted in clinically meaningful outcomes, including higher success rate, duration of air leak stop, lung expansion, and hospital stay, with an acceptable safety profile.

MiR-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through TLR2/MyD88/NF-κB pathway by targeting TLR2.

Autophagy plays a pivotal role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M.tb.). The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the influence of miR-23a-5p on the activation of macrophage autophagy during M.tb. infection in bone marrow-derived macrophages (BMDMs) and murine RAW264.7 cells. Here, we demonstrated that M.tb.-infection of macrophages lead to markedly enhanced expression of miR-23a-5p in a time- and dose-dependent manner. Furthermore, forced expression of miR-23a-5p accelerated the survival rate of intracellular mycobacteria, while transfection with miR-23a-5p inhibitors attenuated mycobacterial survival. More importantly, overexpression of miR-23a-5p dramatically prevented M.tb.-induced activation of autophagy in macrophages, whereas inhibitors of miR-23a-5p remarkably accelerated M.tb.-induced autophagy. Mechanistically, miR-23a-5p is able to modulate TLR2/MyD88/NF-κB signaling activity by targeting TLR2 in RAW264.7 cells in response to M.tb.-infection. Collectively, these findings demonstrated that miR-23a-5p modulated the innate host defense by promoting mycobacteria survival and inhibiting the activation of autophagy against M.tb. through TLR2/MyD88/NF-κB pathway by targeting TLR2, which may provide a promising therapeutic target for tuberculosis.

Serum N-glycans outperform CA19-9 in diagnosis of extrahepatic cholangiocarcinoma.

Extensive efforts have been devoted to improve the diagnosis of extrahepatic cholangiocarcinoma (ECCA) due to its silent clinical character and lack of effective diagnostic biomarkers. Specific alterations in N-glycosylation of glycoproteins are considered a key component in cancer progression, which can serve as a distinct molecular signature for cancer detection. This study aims to find potential serum N-glycan markers for ECCA. In total, 255 serum samples from patients with ECCA (n = 106), benign bile tract disease (BBD, n = 60) and healthy controls (HC, n = 89) were recruited. Only 2 µL of serum from individual patients was used in this assay where the N-glycome of serum glycoproteins was profiled by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) technology. Multi-parameter models were constructed by combining the N-glycans and carbohydrate antigen 19-9 (CA19-9) which is currently used clinically. Quantitative analyses showed that among 13 N-glycan structures, the bifucosylated triantennary N-glycan (peak10, NA3F2) presented the best diagnostic performance for distinguishing ECCA from BBD and HC. Two diagnostic models (Glycotest1 and Glycotest2) performed better than single N-glycan or CA19-9. Additionally, two N-glycan structures (peak9, NA3Fb; peak12, NA4Fb) were tightly related to lymph node metastasis in ECCA patients. In conclusion, sera of ECCA showed relatively specific N-glycome profiling patterns. Serum N-glycan markers and models are novel, valuable and noninvasive alternatives in ECCA diagnosis and progression monitoring.

N-glycosylation of serum proteins for the assessment of patients with IgD multiple myeloma.

BACKGROUND: Because glycosylation is one of the most common post-translational modifications of proteins and because changes in glycosylation have been shown to have a significant correlation with the development of many cancer types, we investigated the serum N-glycome used to diagnose, stage and evaluate the pathological outcomes in IgD multiple myeloma. METHODS: Serum samples were available for 20 patients with IgD multiple myeloma, 41 patients with light chain multiple myeloma and 42 healthy control subjects. Serum N-glycans were released and analysed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. RESULTS: Characteristic changes were revealed in the serum N-glycome of IgD myeloma. In particular, three N-glycans (NG1(6)A2F, Peak3; NG1(3)A2F, Peak4; NA2FB, Peak7) showed increased clinical value. The best area under the ROC curve of NG1(6)A2F to diagnose IgD myeloma was 0.981, with a 95.0% sensitivity and 95.2% specificity, and that of NG1(3)A2F was 0.936, with a 95.0% sensitivity and 78.6% specificity. The best area under the ROC curve of NA2FB/NG1(3)A2F to differentially diagnose IgD myeloma versus light chain myeloma was 0.744, with a 95.3% sensitivity and 50.0% specificity. The level of NG1(3)A2F was correlated with the international staging system, while the higher abundance of NA2FB presented in IgD myeloma was predictive of a shorter progression-free survival. CONCLUSIONS: The advent of serum N-glycan signatures may play a role in the diagnosis, staging and prognosis of IgD myeloma and will serve as the foundation for a precision medicine approach to this rare subtype of multiple myeloma.

Map-Based Cloning of Seed Dormancy1-2 Identified a Gibberellin Synthesis Gene Regulating the Development of Endosperm-Imposed Dormancy in Rice.

Natural variation in seed dormancy is controlled by multiple genes mapped as quantitative trait loci in major crop or model plants. This research aimed to clone and characterize the Seed Dormancy1-2 (qSD1-2) locus associated with endosperm-imposed dormancy and plant height in rice (Oryza sativa). qSD1-2 was delimited to a 20-kb region, which contains OsGA20ox2 and had an additive effect on germination. Naturally occurring or induced loss-of-function mutations of the gibberellin (GA) synthesis gene enhanced seed dormancy and also reduced plant height. Expression of this gene in seeds (including endospermic cells) during early development increased GA accumulation to promote tissue morphogenesis and maturation programs. The mutant allele prevalent in semidwarf cultivars reduced the seed GA content by up to 2-fold at the early stage, which decelerated tissue morphogenesis including endosperm cell differentiation, delayed abscisic acid accumulation by a shift in the temporal distribution pattern, and postponed dehydration, physiological maturity, and germinability development. As the endosperm of developing seeds dominates the moisture equilibrium and desiccation status of the embryo in cereal crops, qSD1-2 is proposed to control primary dormancy by a GA-regulated dehydration mechanism. Allelic distribution of OsGA20ox2, the rice Green Revolution gene, was associated with the indica and japonica subspeciation. However, this research provided no evidence that the primitive indica- and common japonica-specific alleles at the presumably domestication-related locus functionally differentiate in plant height and seed dormancy. Thus, the evolutionary mechanism of this agriculturally important gene remains open for discussion.

The diagnostic value of serum fucosylated fetuin A in hepatitis B virus-related liver diseases.

BACKGROUND: Some changes of glycoproteins have been identified in the serum of patients with different liver diseases, which provided potential glycan biomarkers for diagnosis, prognosis and monitoring of disease progression. METHODS: We established a lectin-antibody sandwich ELISA method to detect fucosylated fetuin A (fuc-fetuin A) level in serum, in which biotinylated Aleuria aurantia lectin (AAL) was used for specific recognition. Then serum fuc-fetuin A level was detected in 108 healthy controls and 548 hepatitis B virus (HBV)-infected patients, including 232 hepatocellular carcinoma (HCC) patients, 114 liver cirrhosis (LC) patients, 86 liver fibrosis (LF) patients, and 116 asymptomatic HBV carriers, to assess its diagnostic and prognostic value in HBV-related liver diseases. RESULTS: Serum fetuin A level decreased in LC patients as compared to HCC patients or healthy controls, while it decreased further according to the increasing Child-Pugh grades. The fuc-fetuin A level was in a decreasing order in LC, HCC, LF, HBV-carriers and healthy controls. For distinguishing LC and HCC patients from LF, HBV-carriers and healthy controls, the area under the receiver operating characteristic (ROC) curve is 0.871, with a sensitivity of 0.818 and specificity of 0.819. The survival analysis revealed that higher fuc-fetuin A level was significantly associated with worse recurrence-free survival in HCC patients (p=0.018). CONCLUSIONS: The results indicated that the serum fuc-fetuin A might serve as a potential glycan biomarker for distinguishing LC and HCC from LF, HBV-carriers and healthy controls. Furthermore, the preoperative fuc-fetuin A level could be a useful prognostic biomarker for HCC patients.

Analysis on the Complete Mitochondrial Genome of Andraca theae (Lepidoptera: Bombycoidea).

The bombycid moth, Andraca theae (Matsumura) (Lepidoptera: Bombycoidea) is an important pest of tea in southeastern China. In the present study, the mitochondrial genome (mitogenome) of A. theae was amplified by polymerase chain reaction and sequenced. The complete mitogenome of A. theae, encoding 37 genes, was 15,737 bp in length (Genbank no. KX365419), and consisted of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 ribosomal RNA genes and an adenine (A) + thymine (T)-rich region (AT-rich region). The gene order of A. theae mitogenome was typical for Lepidoptera mitogenomes. Except for cox1, which started with CGA, all other 12 PCGs started with ATN. Eleven of the 13 PCGs ended with TAA, expect for cox1 and cox2, which ended with a single T. The maximum likelihood method and the Bayesian method were used to analyze the phylogenetic relationship among 22 representative bombycoid species with a matrix consisting of the 13 PCGs of the mitogenomes of the 22 species. The topological structures of the two phylogenetic trees we constructed were almost identical, with the results indicating that the bombycid species, including A. theae, clustered into a single clade with a bootstrap value of 58% and a posterior probability of 0.98. The phylogenetic relationship among the Bombycoidea species analyzed was Lasiocampidae + (Bombycidae + (Saturniidae + Sphingidae)) which was supported by a high bootstrap value of 100% and a posterior probability of 1.00.

[Abnormal expression of circulating nuclear factor-κB in hepatocellular carcinoma and reversal of multidrug resistance through intervening its gene transcription].

OBJECTIVE: To investigate the expressions of nuclear factor-κB (NF-κB) and P-glycoprotein (P-gp) in patients with liver diseases and the effects and mechanism of intervening NF-κB activation on multiple drug resistance (MDR) reversal. METHODS: The levels of circulating NF-κB and P-gp expression were quantitatively detected in 294 patients with liver diseases by using enzyme-linked immunosorbent assay. NF-κB gene transcription in human HepG2 cells was intervened by specific siRNA with/without doxorubicin treatment. Levels of protein or gene expression were analyzed by Western blotting or fluorescence quantitative polymerase chain reaction (PCR). RESULTS: The dynamic increase of circulating NF-κB and P-gp expressions were observed during patients from chronic hepatitis to cirrhosis to hepatocellular carcinoma (HCC) development. The levels of serum NF-κB and P-gp expression in HCC were significantly higher (P<0.001) than those in cirrhosis, chronic hepatitis, and normal controls. The expression levels of serum NF-κB and P-gp were significantly associated with HBV infection (P<0.05), elevated after interventional chemotherapy with higher frequency or prolonged therapy, and significantly decreased in the post-operative HCC (P<0.001). Both expressions in HepG2 cells were significantly higher after adding doxorubicin in the cell cultures. After the cells were transfected with siRNA, the NF-κB expression was down-regulated at mRNA or protein level with higher sensitivity to doxorubicin. CONCLUSION: The over-expressions of NF-κB and P-gp are closely associated with MDR formation; intervention of NF-κB activation can inhibit P-gp expression, and enhance the sensitivity to anti-cancer drug and reverse MDR of HCC.