Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer.

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.

Identification of a bile acid and bile salt metabolism-related lncRNA signature for predicting prognosis and treatment response in hepatocellular carcinoma.

Bile acids and salts have been shown to play a role in liver carcinogenesis through DNA damage, inflammation, and tumor proliferation. However, the correlation between bile acid metabolism and hepatocellular carcinoma (HCC) prognosis remains unclear. This study aimed to identify a predictive signature of bile acid and bile salt metabolism-related long non-coding RNAs (lncRNAs) for HCC prognosis and treatment response. The study used HCC RNA-sequencing data and corresponding clinical and prognostic data from The Cancer Genome Atlas. A prognostic model consisting of five bile acid and bile salt metabolism-related lncRNAs was developed and evaluated in a training set, a validation set and an external set. The model demonstrated good performance in predicting HCC prognosis and was shown to be an independent biomarker for prognosis. Additionally, our study revealed a significant association between the signature and immune cell infiltration, as well as its predictive value for therapeutic responses to both immunotherapy and chemotherapy. Furthermore, three LncRNAs (LUCAT1, AL031985.3 and AC015908.3) expression levels in our signature were validated through qRT-PCR in a cohort of 50 pairs of HCC patient tumor samples and corresponding adjacent non-tumor samples, along with 10 samples of normal liver tissue adjacent to benign lesions. These findings suggest that this novel bile acid and bile salt metabolism-related lncRNA signature can independently predict the prognosis of patients with HCC and may be utilized as a potential predictor of response to treatment in this setting.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission.

PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Synthesis of Upper-Rim Sulfanylpropyl- and p-Methoxyphenylazo-Substituted Calix[4]arenes as Chromogenic Sensors for Hg2+ and Ag+ Ions.

A series of calix[4]arenes with upper-rim sulfanylpropyl and p-methoxyphenylazo groups (compounds 8-10) were synthesized and found to be effective chromogenic sensors for selectively detecting Hg2+, Hg+, and Ag+ ions among 18 screened metal perchlorates. In comparison to previously reported diallyl- and dithioacetoxypropyl-substituted calix[4]arenes (5, 6, 14, 15, and 16) and the newly synthesized compound 7, the distal (5,17)-disulfanylpropyl-substituted di-p-methoxyphenylazocalix[4]arene 9 demonstrated superior performance with a limit of detection of 0.028 µM for Hg2+ ions in a chloroform/methanol (v/v = 399/1) cosolvent. Job's plot revealed 1:1 binding stoichiometry for all these upper-rim sulfanylpropyl- and p-methoxyphenylazo-substituted calix[4]arenes 8-10 with Hg2+ ions, and Benesi-Hildebrand plots from ultraviolet/visible (UV-vis) titration spectra were used for the determination of their association constants. Our findings indicated that the distal orientation of two p-methoxyphenylazo and two sulfanylpropyl groups in calix[4]arenes 8-10 is more favorable for binding Hg2+ ions than the proximal (5,11-) orientation; moreover, the adjacent sulfanylpropyl groups exhibited superior coordination as ligands compared to the allyl and thioacetoxypropyl groups. Notably, compounds 8-10 displayed a comparable trend in their association with Ag+ ions, albeit with 1 order of magnitude lower binding constants and a distinct binding mode compared to Hg2+ ions. UV-vis spectroscopy, Job's plots, high-resolution mass spectrometry, and 1H nuclear magnetic resonance titration studies are presented and discussed.

Emerging Functional Polymer Composites for Tactile Sensing.

In recent years, extensive research has been conducted on the development of high-performance flexible tactile sensors, pursuing the next generation of highly intelligent electronics with diverse potential applications in self-powered wearable sensors, human-machine interactions, electronic skin, and soft robotics. Among the most promising materials that have emerged in this context are functional polymer composites (FPCs), which exhibit exceptional mechanical and electrical properties, enabling them to be excellent candidates for tactile sensors. Herein, this review provides a comprehensive overview of recent advances in FPCs-based tactile sensors, including the fundamental principle, the necessary property parameter, the unique device structure, and the fabrication process of different types of tactile sensors. Examples of FPCs are elaborated with a focus on miniaturization, self-healing, self-cleaning, integration, biodegradation, and neural control. Furthermore, the applications of FPC-based tactile sensors in tactile perception, human-machine interaction, and healthcare are further described. Finally, the existing limitations and technical challenges for FPCs-based tactile sensors are briefly discussed, offering potential avenues for the development of electronic products.

Subtype-specific circadian clock dysregulation modulates breast cancer biology, invasiveness, and prognosis.

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular rhythms in non-cancerous and cancerous human breast tissues are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For non-cancerous tissue, the inferred order of core-circadian genes matches established physiology. Inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of Luminal A samples exhibit continued, albeit disrupted rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among Luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude Luminal A tumors. Patients with high-magnitude tumors had reduced 5-year survival. Correspondingly, 3D Luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.

Timing of endoscopy for acute variceal bleeding in patients with cirrhosis (CHESS1905): A nationwide cohort study.

BACKGROUND: Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS: Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS: A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS: The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.

The top 100 most cited articles on COVID-19 vaccine: a bibliometric analysis.

This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.

Statin Use and Delirium Risk: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Findings on the association of statin use with delirium risk are inconsistent. THE STUDY QUESTION: Is statin use associated with delirium risk? STUDY DESIGN: We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles in English published until December 31, 2021. The effect size and 95% confidence interval (CI) were defined as the odds ratio (OR) and 95% CI, respectively, to indicate the difference in the incidence of delirium between statin use and nonuse groups. A random-effects model was selected in the case of high heterogeneity of study populations. We used funnel plots, Egger test, Duval and Tweedie trim-and-fill approach, and the classic fail-safe N to assess publication bias. RESULTS: Of a total of 264 identified studies, 13 were selected for the qualitative review-4 RCTs and 9 observational cohort studies. Statin use was not associated with low delirium risk (pooled OR, 0·82; 95% CI, 0·64-1·04; P = 0·09). Substantial statistical heterogeneity was observed ( I2 , 90%). Visual inspection of the funnel plot of ORs from the studies revealed symmetry. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, we assigned the evidence a rating of C and a weak recommendation for this review. CONCLUSIONS: Statin use is not associated with delirium risk. More comprehensive RCTs are required to confirm the results.

Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Mechanism of effect of Zhuang medicine Semiliquidambar cathayen. Sis Chang on depression inflammation based on network pharmacology, molecular docking and animal experiments / 中国药理学通报

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen. sis Chang (JLBFH) by network pharmacology and molecular docking,etc, then to explore the mechanism of JLBFH' s effect on inflammatory response to depression through reserpine-induced depression rat model. Methods The target of drug and disease was predicted by network pharmacological database, protein interaction network diagram was constructed, biofunctional enrichment and pathways were analyzed, and molecular docking prediction was performed by AGFR software. Based on reserpine-induced depression, the role of JLBFH in depression inflammation was verified by behavior, molecular biology and pathological examination, and so on. Results A total of 13 active ingredients were screened, 11 key targets of JLBFH modulation of depression were selected, and the bioenrichment results were mainly related to cognition, prominent plasticity regulation, etc. The pathways were mainly related to Rapl signaling pathway, Toll-like receptor signaling pathways. The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice, markedly reduced the retention time in the circle of rats, increased serum levels of 5-HT and DA, decreased serum levels of IL-6, improved inflammatory infiltration in the prefrontal cortex, decreased brain tissue levels of IL-6,IL-1β ,TNF-α mRNA expression,and increased AKT1 mRNA expression in brain tissue. Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component, multi-target and multi-pathway, and the experimental validation results show that JLBFH can improve the d¬pression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission

ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Pseudopollen in Camellia oleifera and its implications for pollination ecology and taxonomy.

Background and aims: In 1997, Tsou described the special differentiation of the connective tissues of some species of Theaceae to produce single-celled powders with unique patterns called pseudopollen. The purpose of this study was to investigate the morphological structure of the pseudopollen of Camellia oleifera (Theaceae) and to study the morphology of pseudopollen in seven other Camellia species. Methods: Scanning electron microscopy, paraffin section, light microscopy, transmission electron microscopy, histochemistry. Key result: C. oleifera pseudopollen was similar to normal pollen in macroscopic morphology but different microscopically. The normal pollen was starch-rich and yellow, with mostly reticulate exine ornamentation. In contrast, the pseudopollen was a white powder, single-celled and rich in protein, with parallel unbranched ridge lines on the outer wall, and originated from the parenchyma of the connective tissues. There are also differences in the micro-characteristics of normal and pseudopollen among different species in Camellia. Conclusion: There are great differences in morphological structure between C. oleifera and other species in Camellia normal pollen and pseudopollen; these results may indicate that the pseudopollen can be used as a taxonomic basis for Camellia, and the macroscopic similarity between pseudopollen and pollen and histochemical characteristics of pseudopollen can be a pollination strategy.

In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy in children.

BACKGROUND: Molluscum contagiosum (MC), milia, keratosis pilaris (KP), verruca plana (VP), seborrheic keratosis (SK), and juvenile xanthogranuloma (JXG) are common papule dermatoses on the face of children that have a similar appearance. In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. The purpose of this study was to clarify the RCM characteristics of MC, milia, KP, VP, SK, and JXG and explore the clinical application value of RCM for these common facial papule dermatoses. METHODS: We recruited 113 patients referred for unequivocal facial papule dermatosis, including 21 patients with MC, 17 patients with milia, 19 patients with KP, 36 patients with VP, 8 patients with SK, and 12 patients with JXG. We evaluated the characteristics and distinguishing features of the six kinds of facial papule dermatoses using RCM. RESULTS: The main RCM features of the six dermatoses included a well-demarcated border of the lesion area. MC, milia and KP all manifested cyst-like structures, and their distinguishing features were the location of the cystic structures and the refractive index of the contents. Although VP, SK, and JXG did not have obvious cystoid structures, VP was typically characterized by uniformly distributed petal-like structures with a medium-to-high refractive index in the epidermis. With regard to SK, the characteristic features were an obviously thickened epidermis and cobblestone-like structures. JXG was mainly characterized by multiple large round and ovoid cells with a foamy cytoplasm, and discoid-shaped multinucleated large cells were diffusely distributed in the dermis. CONCLUSION: RCM allows the real-time visualization of major key diagnostic and distinguishing features of common facial papule dermatoses in children, including MC, milia, KP, VP, SK, and JXG.

Treatment Strategies in Emergency Endoscopy for Acute Esophageal Variceal Bleeding (CHESS1905): A Nationwide Cohort Study.

Background and Aims: Emergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB. Methods: Cirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed. Results: A total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively). Conclusion: The nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

Gene delivery strategies for therapeutic proteins production in plants: Emerging opportunities and challenges.

There are sharply rising demands for pharmaceutical proteins, however shortcomings associated with traditional protein production methods are obvious. Genetic engineering of plant cells has gained importance as a new strategy for protein production. But most current genetic manipulation techniques for plant components, such as gene gun bombardment and Agrobacterium mediated transformation are associated with irreversible tissue damage, species-range limitation, high risk of integrating foreign DNAs into the host genome, and complicated handling procedures. Thus, there is urgent expectation for innovative gene delivery strategies with higher efficiency, fewer side effect, and more practice convenience. Materials based nanovectors have established themselves as novel vehicles for gene delivery to plant cells due to their large specific surface areas, adjustable particle sizes, cationic surface potentials, and modifiability. In this review, multiple techniques employed for plant cell-based genetic engineering and the applications of nanovectors are reviewed. Moreover, different strategies associated with the fusion of nanotechnology and physical techniques are outlined, which immensely augment delivery efficiency and protein yields. Finally, approaches that may overcome the associated challenges of these strategies to optimize plant bioreactors for protein production are discussed.

Characteristics of multicystic biliary hamartoma: A case report.

Introduction: Multicystic biliary hamartoma (MCBH) is a very rare hepatic benign neoplasm that manifests as a localized cystic-solid mass. Only 17 cases have been described in the literature to date. MCBH diagnosis is currently dependent on imaging and pathology following surgical resection and no precise standards are in place. Case Presentation: This case study involves a middle-aged male patient with a history of drinking but no other liver diseases. A routine ultrasound examination showed a 6.0 × 5.5 cm inhomogeneous echo mass in the right lobe of the liver. The patient experienced no discomfort or other symptoms, and blood tests were normal. Imaging revealed a localized cystic-solid neoplasm in segment 6 of the liver that did not have the features of a malignant tumor. Surgical resection was performed. Based on imaging, macroscopic examination, and histological results, a final diagnosis of MCBH was made. Conclusion: The imaging and pathological features of MCBH were summarized based on the published case reports to date. As a non-invasive examination, the imaging features will aid in the diagnosis of MCBH. Furthermore, these features, along with tumor size and patient symptoms, will facilitate clinicians in selecting surgical resection or follow-up for individual patients.

Combined Biosynthetic Pathway Engineering and Storage Pool Expansion for High-Level Production of Ergosterol in Industrial Saccharomyces cerevisiae.

Ergosterol, a terpenoid compound produced by fungi, is an economically important metabolite serving as the direct precursor of steroid drugs. Herein, ergsosterol biosynthetic pathway modification combined with storage capacity enhancement was proposed to synergistically improve the production of ergosterol in Saccharomyces cerevisiae. S. cerevisiae strain S1 accumulated the highest amount of ergosterol [7.8 mg/g dry cell weight (DCW)] among the wild-type yeast strains tested and was first selected as the host for subsequent metabolic engineering studies. Then, the push and pull of ergosterol biosynthesis were engineered to increase the metabolic flux, overexpression of the sterol acyltransferase gene ARE2 increased ergosterol content to 10 mg/g DCW and additional overexpression of a global regulatory factor allele (UPC2-1) increased the ergosterol content to 16.7 mg/g DCW. Furthermore, considering the hydrophobicity sterol esters and accumulation in lipid droplets, the fatty acid biosynthetic pathway was enhanced to expand the storage pool for ergosterol. Overexpression of ACC1 coding for the acetyl-CoA carboxylase increased ergosterol content from 16.7 to 20.7 mg/g DCW. To address growth inhibition resulted from premature accumulation of ergosterol, auto-inducible promoters were employed to dynamically control the expression of ARE2, UPC2-1, and ACC1. Consequently, better cell growth led to an increase of ergosterol content to 40.6 mg/g DCW, which is 4.2-fold higher than that of the starting strain. Finally, a two-stage feeding strategy was employed for high-density cell fermentation, with an ergosterol yield of 2986.7 mg/L and content of 29.5 mg/g DCW. This study provided an effective approach for the production of ergosterol and other related terpenoid molecules.

Facile Synthesis of Uniform Mesoporous Nb2O5 Micro-Flowers for Enhancing Photodegradation of Methyl Orange.

The removal of organic pollutants using green environmental photocatalytic degradation techniques urgently need high-performance catalysts. In this work, a facile one-step hydrothermal technique has been successfully applied to synthesize a Nb2O5 photocatalyst with uniform micro-flower structure for the degradation of methyl orange (MO) under UV irradiation. These nanocatalysts are characterized by transmission and scanning electron microscopies (TEM and SEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method, and UV-Vis diffuse reflectance spectroscopy (DRS). It is found that the prepared Nb2O5 micro-flowers presents a good crystal phases and consist of 3D hierarchical nanosheets with 400-500 nm in diameter. The surface area is as large as 48.6 m2 g-1. Importantly, the Nb2O5 micro-flowers exhibit superior catalytic activity up to 99.9% for the photodegradation of MO within 20 mins, which is about 60-fold and 4-fold larger than that of without catalysts (W/O) and commercial TiO2 (P25) sample, respectively. This excellent performance may be attributed to 3D porous structure with abundant catalytic active sites.

[The Genome-Wide Changes in Expression Profile of CML T Cells After Up-regulation of TCRζ Chain Expression].

OBJECTIVE: To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ. METHODS: The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3+ T cells were obtained by MACS method. The TCRζ-IRES2-EGFP (experimental group) and pIRES2-EGFP (control group) plasmids were transfected into T cells by nuclear transfection technique. The gene expression profiles of CML T cells up-regulated TCRζ chain and control cells were detected by Affymetrix GeneChip Human Gene 2.0 ST Array. The differentially expressed genes were analyzed by GO functional annotation analysis and KEGG pathway enrichment analysis. RESULTS: A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated. CONCLUSION: The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.