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Abstract Background and aims Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein‐associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms. Methods JCAD knockout (JCAD‐KO), liver‐specific JCAD‐KO (Jcad△Hep) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination‐based cell cycle indicator (FUCCI) live‐imaging system was used to visualise the phases of cell cycle. Results Both global and liver‐specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD‐KO cell line was indicated by a FUCCI live‐imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD‐KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes‐associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle‐associated genes. Conclusion JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo–YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation. Key Points JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage. JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle‐associated genes. Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living‐donor liver transplantation.

Background: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant therapy (FASCINATE-N) trial, we classify breast cancer patients using multiomic characteristics into different subtypes to evaluate the efficacy of precision-based targeted therapies compared to standard neoadjuvant chemotherapy. Methods and design: The FASCINATE-N trial is a prospective, randomized, precision-based umbrella trial that plans to enroll 716 women with early breast cancer. After enrollment, patients will first be divided into three groups: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HER2+, and HR−/HER2−. The HR+/HER2− patients are further stratified using fusion and clustering of similarity network fusion (SNF) algorithm into four subtypes; HER2+ patients are divided into HR+/HER2+ and HR−/HER2+ subtypes; and HR−/HER2− patients are stratified using the Fudan University Shanghai Cancer Center classification. For the assignment of drugs to patients, Bayesian methods of adaptive randomization will be used. The primary endpoint is pathological complete response rate; secondary endpoints include 3-year invasive disease-free survival, overall response rate, and toxicities according to common terminology criteria for adverse events (CTCAE) scale version 4.0 and the ratio of patients with complete cell cycle arrest (Ki67 < 2.7%) in HR+/HER2+ breast cancer. Discussion: The goal of our trial is to test the efficacy of our subtyping-based treatment in a neoadjuvant setting and to conduct a pilot study into the efficacy of targeted therapies within each precision-based subtype. The precision-based treatment arm can be updated with the refinement of our subtyping method, the discovery of new targets, and the development of novel targeted drugs. Our trial offers a unique opportunity to provide patients with individualized neoadjuvant therapy and test promising novel treatments that may further benefit patients. Trial registration: ClinicalTrials.gov identifier: NCT05582499 ( https://classic.clinicaltrials.gov/ct2/show/NCT05582499 ).

Abstract Background Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients. Methods We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes. Results CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2–92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4–18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival. Conclusion This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments. Trial registration ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.

Purpose Ultrasound-guided thermal ablation (including microwave ablation [MWA] and radiofrequency ablation [RFA]) has emerged as a remarkable technology for the treatment of benign and malignant diseases. The objective of this multicenter study was to assess the efficacy and safety of thermal ablation in a large cohort of patients with papillary thyroid microcarcinoma (PTMC). Materials and methods Retrospective study of 725 patients who underwent MWA/RFA at 11 centers between March 2015 and March 2020. The mean age of patients was 46 ± 11 years (range, 22–81); the mean follow-up time was 21 ± 13 months (range, 6–60). Changes in size of tumor, the rates of tumor disappearance, disease progression, and complications were assessed. Results From 6 months post-ablation, the size of tumors was significantly reduced compared with those recorded pre-ablation (p

Chinese breast cancer patients have not been well represented in clinical sequencing studies. Here the authors analyse the mutational landscape of 1,134 Chinese breast cancer patients, finding actionable targets and a higher prevalence of p53 and Hippo pathway mutations compared to Western cohorts.

BackgroundThe prognostic value of low-density lipoprotein cholesterol (LDL-C) in elderly patients is controversial. This study aimed to elucidate the relationship between the preoperative LDL-C and adverse outcomes in elderly patients undergoing valve replacement surgery (VRS).MethodsA total of 2,552 aged patients (age ≥ 60 years) undergoing VRS were retrospectively recruited and divided into two groups according to LDL-C level on admission: low LDL-C ( 0.05).ConclusionOur study did not support the negative relationship between LDL-C level and mortality risk in elderly patients undergoing VRS.

Abstract Background Endocrine therapy is the preferred treatment for patients with hormone receptor ‐positive metastatic breast cancer (MBC). While visceral metastasis is a negative prognostic factor, few studies have distinguished between the prognoses of patients with metastases at different visceral sites. Patients and methods In total, 398 patients receiving fulvestrant 500 mg at a single center over a 6‐year period were analyzed. Logistic regression models were used to identify the prognostic factors associated with progression‐free survival (PFS). Kaplan‐Meier analysis was used to compare the PFS of patients with lung and liver metastases. Results Baseline visceral metastases were present in 233 patients, including 138 with lungw/o liver metastases (lung metastases without liver involvement), 51 with liverw/o lung metastases (liver metastases without lung involvement) and 41 with lung and liver metastases. The median PFS was 6.8 months (5.6 and 9.2 months for visceral and nonvisceral metastases, respectively, P = .028). PFS was longer in patients with lungw/o liver metastases than in those with liverw/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P

Background and PurposeAlthough tumor size and nodal status are the most important prognostic factors, it is believed that nodal status outperforms tumor size as a prognostic factor. In particular, when patients have a nodal stage greater than N2 (more than nine positive lymph nodes), it is well accepted that tumor size does not retain its prognostic value. Even in the newest American Joint Committee on Cancer (AJCC) prognostic staging system, which includes molecular subtype as an important prognostic factor, T1-3N2 patients are categorized as the same population. The same is true for T1-4N3 patients. Moreover, some physicians have speculated that for tumors staged N2 or greater, the smaller the tumor is, the more aggressive the tumor. Thus, this study aims to investigate the prognostic value of tumor stage (T stage) in patients with extensive nodal involvement and to compare the survival of T4N × M0 and T × N3M0.Patients and MethodsFemale breast cancer patients with nine or more positive lymph nodes or with T4 tumors were identified in the SEER registry between 2010 and 2015. The effect of T stage on breast cancer-specific survival (BCSS) was assessed using the Kaplan–Meier survival curve method and risk-adjusted Cox proportional hazard regression modeling. Survival comparison of T4NxM0 and TxN3M0 patients was also achieved using the Kaplan–Meier survival curve method and risk-adjusted Cox proportional hazard regression model.ResultsOverall, 21,696 women with N2-3 tumors were included from 284,073 patients.T stage, nodal stage (N stage), ER, PR, HER2 and grade were all independent prognostic factors (p

Background: The prognostic nutritional index (PNI) has been described as a simple risk-stratified tool for several diseases. We explored the predictive role of the PNI on coronavirus disease 2019 (COVID-19) severity.Methods: A total of 101 patients with COVID-19 were included in this retrospective study from January 2020 to March 2020. They were divided into two groups according to COVID-19 severity: non-critical (n = 56) and critical (n = 45). The PNI was calculated upon hospital admission: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). Critical COVID-19 was defined as having one of the following features: respiratory failure necessitating mechanical ventilation; shock; organ dysfunction necessitating admission to the intensive care unit (ICU). The correlation between the PNI with COVID-19 severity was analyzed.Results: The PNI was significantly lower in critically ill than that in non-critically ill patients (P < 0.001). The receiver operating characteristic curve indicated that the PNI was a good discrimination factor for identifying COVID-19 severity (P < 0.001). Multivariate logistic regression analysis showed the PNI to be an independent risk factor for critical illness due to COVID-19 (P = 0.002).Conclusions: The PNI is a valuable biomarker that could be used to discriminate COVID-19 severity.

BackgroundThe therapeutic role of neuromuscular blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) remains controversial.MethodsWe systematically reviewed randomized controlled trials investigating the use of NMBA in ARDS patients from inception to July 2019. Relative risk (RR) was calculated for the incidence of barotrauma and mortality using the random-effect or fixed-effect model according to heterogeneity analysis.ResultsData were combined from five randomized controlled trials that included 1,461 patients (724 in the NMBA group and 737 in the control group). Pooled analysis showed that NMBA infusion did not reduce 28-day mortality (RR = 0.72, 95% confidence interval (CI) 0.44 to 1.17, P=0.180, I-squared = 62.8%), but was associated with lower intensive care unit (ICU) mortality (RR = 0.60, 95% CI 0.41 to 0.88, P = 0.009, I-squared = 9.2%). In addition, the incidence of barotrauma was significantly lower in patients treated with NMBA (RR = 0.53, 95% CI 0.33 to 0.84, P = 0.007, I-squared = 0). However, infusion of NMBA might increase the risk of ICU-acquired weakness (RR = 1.34, 95% CI 0.97 to 1.84, P = 0.066, I-squared = 0).ConclusionInfusion of NMBA could reduce ICU mortality and the incidence of barotrauma. The risk of ICU-acquired weakness was higher in moderate-to-severe ARDS patients treated with NMBA. The real effects of NMBA need to be further evaluated and confirmed by a study with a stricter design.

Cuticular wax plays an important role in protecting land plant against biotic and abiotic stresses. Cuticular wax production on plant surface is often visualized by a characteristic glaucous appearance. This study identified quantitative trait loci (QTLs) for wheat (Triticum aestivum L.) flag leaf glaucousness (FLG) using a high-density genetic linkage map developed from a recombinant inbred line (RIL) population derived from the cross Heyne×Lakin by single-seed descent. The map consisted of 2 068 single nucleotide polymorphism (SNP) markers and 157 simple sequence repeat (SSR) markers on all 21 wheat chromosomes and covered a genetic distance of 2 381.19 cM, with an average marker interval of 1.07 cM. Two additive QTLs for FLG were identified on chromosomes 3AL and 2DS with the increasing FLG allele contributed from Lakin. The major QTL on 3AL, QFlg.hwwgr-3AL, explained 17.5–37.8% of the phenotypic variation in different environments. QFlg.hwwgr-3AL was located in a 4.4-cM interval on chromosome 3AL that was flanked by two markers IWA1831 and IWA8374. Another QTL for FLG on 2DS, designated as QFlg.hwwgr-2DS which was identified only in Yangling in 2014 (YL14), was flanked by IWA1939 and Xgwm261 and accounted for 11.3% of the phenotypic variation for FLG. QFlg.hwwgr-3AL and QFlg.hwwgr-2DS showed Additive×Environment (AE) interactions, explaining 3.5 and 4.4% of the phenotypic variance, respectively. Our results indicated that different genes/QTLs may contribute different scores of FLG in a cultivar and that the environment may play a role in FLG.

H2O2 was adopted to oxidize NO in simulated flue gas at 100-500°C. The effects of the H2O2 evaporation conditions, gas temperature, initial NO concentration, H2O2 concentration, and H2O2:NO molar ratio on the oxidation efficiency of NO were investigated. The reason for the narrow NO oxidation temperature range near 500°C was determined. The NO oxidation products were analyzed. The removal of NOx using NaOH solution at a moderate oxidation ratio was studied. It was proven that rapid evaporation of the H2O2 solution was critical to increase the NO oxidation efficiency and broaden the oxidation temperature range. the NO oxidation efficiency was above 50% at 300-500°C by contacting the outlet of the syringe needle and the stainless-steel gas pipe together to spread H2O2 solution into a thin film on the surface of the stainless-steel gas pipe, which greatly accelerated the evaporation of H2O2. The NO oxidation efficiency and the NO oxidation rate increased with increasing initial NO concentration. This method was more effective for the oxidation of NO at high concentrations. H2O2 solution with a concentration higher than 15% was more efficient in oxidizing NO. High temperatures decreased the influence of the H2O2 concentration on the NO oxidation efficiency. The oxidation efficiency of NO increased with an increase in the H2O2:NO molar ratio, but the ratio of H2O2 to oxidized NO decreased. Over 80% of the NO oxidation product was NO2, which indicated that the oxidation ratio of NO did not need to be very high. An 86.7% NO removal efficiency was obtained at an oxidation ratio of only 53.8% when combined with alkali absorption.

To investigate the expression of microRNA-155 (miRNA-155) in the livers of mice with lipopolysaccharide (LPS)-induced sepsis and to determine the role of dexamethasone (DXM) in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. Moreover, DXM alone inhibited the expression of miRNA-155 to below the baseline level, but did not impact the expression of inflammatory factors, suggesting that the down-regulation of miRNA-155 by DXM may partially, but not completely, depend on the suppression of pro-inflammatory cytokines by DXM. Our data indicate that the overexpression of miRNA-155 in the livers of mice with LPS-induced sepsis may play an important role in the pathological processes of sepsis and that the down-regulation of miRNA-155 by DXM may be a novel mechanism regulating inflammation and immunity.

Background: The aim of this study was to assess curative effect of hysteroscopic and laparoscopic myomectomy for type II submucous myomas between 3 and 5 cm in diameter and explore the optimal surgical indications.Methods: A retrospective analysis was performed of those who underwent hysteroscopic or laparoscopic myomectomy from January 2008 to January 2013. The patients were divided into three subgroups according to the myomas diameter (namely, 30 mm ≤ myomas diameter <40 mm; 40 mm ≤ myomas diameter <50 mm; and myomas diameter ≥ 50 mm). Clinical data such as operation time, amount of bleeding, postoperative anal exsufflation time, hospital stay, and complications were collected.Results: There was no significant difference regarding operation time and amount of bleeding in two groups. We found significant difference in hysteroscopic group (within-subgroup) difference regarding operation time and amount of bleeding, whereas no significant difference in the laparoscopic group, while significant differences between-subgroup differences regarding operation time. Complete removal of myoma was seen in all patients.Conclusions: Both techniques are feasible for type II submucous myomas. Laparoscopic operation has higher advantages in type II submucous myomas of greater than 4 cm in diameter whereas hysteroscopic operation has higher advantages in type II submucous myomas of lower than 4 cm in diameter. [ABSTRACT FROM AUTHOR]

To evaluate the effects of chelated Zn/Cu/Mn on redox status, immune responses and hoof health in lactating Holstein cows, 48 head in early lactation were divided into healthy or lame groups according to their gait score. Cows were fed the same amount of Zn/Cu/Mn as sulfate salts or in chelated forms for 180 days, and foot-and-mouth disease (FMD) vaccine was injected at day 90. The results showed that lame cows had lower antioxidant function, serum Zn/Mn levels, hair Cu levels, and hoof hardness. Moreover, increased antioxidant status, FMD antibody titers, serum and hair levels of Zn/Cu/Mn, and hoof hardness and decreased milk fat percent and arthritis biomarkers were observed in cows fed chelated Zn/Cu/Mn. In summary, supplementation with chelated Zn/Cu/Mn improved antioxidant status and immune responses, reduced arthritis biomarkers, and increased accumulation of Zn/Cu/Mn in the body and hoof hardness in dairy cows. [ABSTRACT FROM AUTHOR]

Background: Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human tumor cells and tumors to cytotoxic molecules. The aim of this pilot study was to investigate the efficacy of PPI in improving the clinical outcome of docetaxel + cisplatin regimen in patients with metastatic breast cancer (MBC). Methods: Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m² followed by cisplatin 75 mg/mm² on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate. Results: Ninety-four patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, B and C were 46.9, 71.0, and 64.5 %, respectively. Median TTP for arm A (n = 32), B (n =31), C (n =31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was observed between patients who had taken PPI and who not with ORR (46.9 % vs. 67.7 %, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p = 0.045). Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively (p = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity was observed with PPI. Conclusions: The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial. [ABSTRACT FROM AUTHOR]

Background: Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. Methods: 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. Results: In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. Conclusions: SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype. [ABSTRACT FROM AUTHOR]

The article presents information on a study on the construction and immunogenicity of eukaryotic plasmid expressing F gene of duck paramyxovirus strain DPI/02. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify Fusion glycoprotein (F) gene of paramyxovirus strain DPI/02 isolated from duck and cloned into genetic vector pMD18-T. The results conclude that to construction of eukaryotic plasmid which expressed F gene is useful to develop nucleate vaccine.

Plant microRNAs (miRNAs) play crucial regulatory roles in various developmental processes. In this study, we characterize the miRNA profile of the shoot apical meristem (SAM) of an important legume crop, soybean, by integrating high-throughput sequencing data with miRNA microarray analysis. A total of 8423 non-redundant sRNAs were obtained from two libraries derived from micro-dissected SAM or mature leaf tissue. Sequence analysis allowed the identification of 32 conserved miRNA families as well as 8 putative novel miRNAs. Subsequent miRNA profiling with microarrays verified the expression of the majority of these conserved and novel miRNAs. It is noteworthy that several miRNAs* were expressed at a level similar to or higher than their corresponding mature miRNAs in SAM or mature leaf, suggesting a possible biological function for the star species. In situ hybridization analysis revealed a distinct spatial localization pattern for a conserved miRNA, miR166, and its star speciessuggesting that they serve different roles in regulating leaf development. Furthermore, localization studies showed that a novel soybean miRNA, miR4422a, was nuclear-localized. This study also indicated a novel expression pattern of miR390 in soybean. Our approach identified potential key regulators and provided vital spatial information towards understanding the regulatory circuits in the SAM of soybean during shoot development. [ABSTRACT FROM PUBLISHER]

(2R,3R)-3-((1R)-1-[tert-Butyl(dimethyl)siloxy]ethyl)- 4-oxoazetidin-2-yl acetate was efficiently prepared from L-ascorbic acid. The key steps were the a highly diastereoselective [2 + 2] cycloaddition of diketene with an (S)-glyceraldehyde-derived aldimine to give the ketone, stereoselective titanium tetrachloride mediated asymmetric reduction to give the corrsponding S-configured alcohol, and Mitsunobu inversion of the latter to give the desired R-configured alcohol. [ABSTRACT FROM AUTHOR]

We analyzed the effect of fungal infection on dye decolorization in continuous and sequential white rot fungus bioreactors. Biological samples of biofilm were collected to determine the ability of these bioreactors to degrade dye in synthetic wastewater. Polymerase chain reaction–denaturing gradient gel electrophoresis was used to analyze the taxonomy of the fungal community. Decolorization rate and manganese peroxidase activity were analyzed. Scanning electron microscopy was used to examine the physical structure of the biofilm. At an influent concentration of 50 mg/L, decolorization rates and chemical oxygen demand (COD) removal rates were as high as 88.7% and 53.7% in the sequential reactor and 85.5% and 54.6% in the continuous reactor on day 6 of the studies, respectively. The quantity of foreign fungi in the reactors increased over time and negatively affected Phanerochaete chrysosporium (PC) growth by competitively absorbing nutrients from the culture medium, resulting in a decline in PC-mediated dye decolorization. Changes in manganese peroxidase activity corresponded to dye decolorization rate. Decolorization capacity of the reactor was dependent on multiple factors including operation mode, operating period, and dye concentration, the latter being the most critical. Polymerase chain reaction–denaturing gradient gel electrophoresis analysis revealed the presence of multiple fungal taxa in some samples. The fungal community was dominated by PC in both reactors. Variations in the makeup of the fungal community corresponded to changes in dye biodegradation. In the sequential reactor, fungal diversity was initially low and progressively increased as treatment progressed, whereas in the continuous reactor the diversity was initially high and then decreased with time. Diversity of foreign fungi was higher in the sequential reactor than in the continuous reactor, suggesting that the latter is more suitable for dye decolorization. [ABSTRACT FROM AUTHOR]

Abstract  The biological function and stability of a cytochrome P450 (CYP) mainly depend on the subtle properties of the residues in the active site cavity, which are generally more divergent among proteins than other parts of the protein. As the most unique member of human CYP2C family, CYP2C8 has an isoleucine (Ile) 476 instead of phenylalanine (Phe) in substrate recognizing site 6 (SRS6). However, the role of Ile476 of CYP2C8 is still unknown. Therefore, six site-directed mutants of CYP2C8 were constructed to better define this. By UV–visible and circular dichroism spectroscopy studies, we studied for the first time the structural stability and all-trans-retinoic acid binding capability of the CYP2C8 variants. We found that the ferric CYP2C8 went through three states during thermal unfolding. Combined with substrate binding studies, our data revealed that residue 476 was involved in contact with substrate and was important for maintaining the thermal stability of CYP2C8. [ABSTRACT FROM AUTHOR]

facile and efficient enantioselective synthesis of florfenicol starting from commercially available 4-methylthiobenzaldehyde is described. Key features of the synthesis include a onestep oxidation of allyl and thioether groups in allylic alcohol to form (2S,3S)-epoxide under Sharpless epoxidation conditions and a highly efficient conversion of (1R,2R)-azide into amino alcohol via debenzylation and reduction of an azido moiety in one-pot operation. [ABSTRACT FROM AUTHOR]