Efficacy and safety of nanoparticle albumin-bound paclitaxel in taxane-pretreated metastatic breast cancer patients.

BACKGROUND: Taxanes are the basic components of breast cancer chemotherapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows improved antitumor effects because of more targeted delivery. However, the effects of nab-paclitaxel have not been systematically studied in patients with metastatic breast cancer (MBC) pretreated with taxanes. Considering the limited treatment options for MBC, this study retrospectively evaluated the clinical efficacy and adverse effects of nab-paclitaxel in patients with taxane-pretreated MBC. METHODS: Patients who had previously received taxanes and subsequently received nab-paclitaxel chemotherapy for MBC at Jiangsu Cancer Hospital between October 2014 and April 2022 were included for analysis. The primary end point was progression-free survival (PFS), and the secondary end points were the objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and side effects. RESULTS: A total of 236 female patients with MBC were included. The median PFS was 7.20 months (95% confidence interval [CI], 6.63-7.80 months), and the ORR, DCR, and CBR were 29.55% (95% CI, 23.50%-35.60%), 83.64% (95% CI, 78.70%-88.60%), and 56.36% (95% CI, 49.80%-63.00%), respectively. Following nab-paclitaxel treatment, the median PFS of patients who were sensitive to taxanes during previous treatments was significantly longer than that of patients who were resistant to taxanes (7.57 months vs. 4.43 months, p < .001). The most common adverse events were sensory neuropathy (89.83%), neutropenia (48.73%), leukopenia (46.61%), and anemia (35.59%). CONCLUSION: Nab-paclitaxel demonstrated clinical activity in taxane-pretreated patients with MBC. This beneficial effect was observed both in patients who were sensitive and resistant to taxanes during previous treatments. These results suggest nab-paclitaxel as the preferred chemotherapy regimen in patients with MBC, regardless of their sensitivity to taxanes during previous treatments.

Vimentin protein is a factor for decreasing breast cancer cell proliferation co-culture with human bone marrow-derived mesenchymal stem cells pre-treated with thiazolidinedione solutions.

BACKGROUND: Our previous study investigated the levels of soluble growth factors in the conditioned media of bone marrow-derived mesenchymal stem cells (BMSCs) pre-treated with thiazolidinedione solutions. The present study aimed to investigate the complex intracellular proteins extracted from BMSCs pre-treated with pioglitazone and/or rosiglitazone using proteomics. METHODS: The proliferative effect of the identified protein on MCF-7 cells that interacted non-adhesively with BMSCs pre-treated with pioglitazone and/or rosiglitazone was evaluated using cell culture inserts and conditioned media. The mRNA expression of proliferation and lipid accumulation markers was also evaluated in the interacted MCF-7 cells by reverse transcription-quantitative PCR. Finally, the correlation between the identified protein and fibroblast growth factor 4 (FGF-4) protein in the conditioned media of the pre-treated BMSCs was evaluated by ELISA. RESULTS: The present study identified vimentin as the specific protein among the complex intracellular proteins that likely plays a role in MCF-7 cell proliferation when the breast cancer cells interacted non-adhesively with BMSCs pre-treated with a combination of pioglitazone and rosiglitazone. The inhibition of this protein promoted the proliferation of MCF-7 cells when the breast cancer cells interacted with pre-treated BMSCs. Gene expression analysis indicated that pre-treatment of BMSCs with a combination of pioglitazone and rosiglitazone decreased the mRNA expression of Ki67 and proliferating cell nuclear antigen in MCF-7 cells. The pre-treatment did not induce mRNA expression of PPARγ, which is a sign of lipid accumulation. The level of vimentin protein was also associated with the FGF-4 protein expression level in the conditioned media of the pre-treated BMSCs. Bioinformatics analysis revealed that vimentin regulated the expression of FGF-4 through its interaction with SRY-box 2 and POU class 5 homeobox 1. CONCLUSIONS: The present study identified a novel intracellular protein that may represent the promising target in pre-treated BMSCs to decrease the proliferation of breast cancer MCF-7 cells for human health and wellness.

Copper recovery from low-grade copper sulfides using bioleaching and its community structure succession in the presence of Sargassum.

Bioleaching characteristics and bacterial community structure were studied during low-grade copper sulfide ores bioleaching in the presence of pretreated Sargassum (PSM). Results indicated that proportion of attached bacteria and copper recovery were improved by using appropriate-dosage PSM. High copper recovery (82.99%) and low Fe3+ concentration were obtained when 150 mg L-1 PSM was used. Precipitation, such as KFe3(SO4)2(OH)6 and (H3O)Fe3(SO4)2(OH)6, was not found in samples used PSM according to XRD, FTIR and TG analyses, which may result from less passivation layer formed by Fe3+ hydrolysis. I- contained in PSM can act as the reductant to convert Fe3+ into Fe2+, which can reduce Fe3+ hydrolysis and adjust Eh value. Bacterial community structure was influenced significantly by PSM according to the 16 S rDNA analysis. Acidithiobacillus ferrooxidans dominated proportion of bacterial community throughout bioleaching process, whose proportion reached 89.1091% after 14 days in sample added 150 mg L-1 PSM.

Melatonin-pretreated human umbilical cord mesenchymal stem cells improved endometrium regeneration and fertility recovery through macrophage immunomodulation in rats with intrauterine adhesions†.

Intrauterine adhesions (IUA) are a common gynecological problem. Stem cell therapy has been widely used in the treatment of IUA. However, due to the complex and harsh microenvironment of the uterine cavity, the effectiveness of such therapy is greatly inhibited. This study aimed to investigate whether melatonin pretreatment enhances the efficacy of human umbilical cord mesenchymal stem cells (HucMSCs) in IUA treatment in rats. First, we explored the effect of melatonin on the biological activity of HucMSCs in vitro through a macrophage co-culture system, Cell Counting Kit 8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, immunofluorescence staining, and qRT-PCR. Subsequently, we established the IUA rat model and tracked the distribution of HucMSCs in this model. In addition, we observed the number of M1 and M2 macrophages through immunofluorescence staining and detected the levels of inflammatory cytokines. Four weeks after cell transplantation, HE, Masson, and immunohistochemical staining were performed. In vitro experiments showed that melatonin pretreatment of HucMSCs promoted proliferation, reduced apoptosis, up-regulated the stemness gene, and regulated macrophage polarization. In vivo, melatonin pretreatment caused more HucMSCs to remain in the uterine cavity. Melatonin-pretreated HucMSCs recruited more macrophages, regulated macrophage polarization, and reduced inflammation. Melatonin-pretreated HucMSCs relieved fibrosis, increased endometrium thickness, and up-regulated CD34, vimentin, proliferating cell nuclear antigen (PCNA), and alpha small muscle antigen (α-SMA) expression. Fertility tests showed that melatonin-pretreated HucMSCs increased the number of embryos. In summary, pretreatment with melatonin was beneficial for HucMSC treatment because it enhanced the cell's ability to recruit macrophages and regulate macrophage polarization, which led to the regeneration of the endometrium and improved pregnancy outcomes.

The Evolving Treatment Landscape of Medullary Thyroid Cancer.

OPINION STATEMENT: Genetic assessment is crucial to address the correct treatment for advanced medullary thyroid cancer (MTC). Multi tyrosine kinase inhibitors (mTKIs) cabozantinib and vandetanib are good first line options, even vandetanib prescription is currently limited to RET mutated patients. Selective RET inhibitors such as pralsetinib could be a preferred upfront treatment in case of RET mutated MTC presenting common or gatekeeper RET mutations (e.g. M918T; V804L/M). Selpercatinib, otherwise, can be prescribed as the second line after disease progression to mTKIs. The best option for subsequent lines is to consider inclusion in clinical trials or alternatively other mTKIs such as sunitinib, sorafenib, lenvatinib, or pazopanib could be evaluated. New perspectives include next-generation RET inhibitors able to overcome resistance mechanisms responsible for disease progression to standard mTKIs and RET inhibitors, and immunotherapy for MTC presenting with high tumor mutational burden.

Effects of calcination on the environmental behavior of sediments by phosphorus speciation and interface characterization.

Dredged sediments derived from eutrophicated lakes poses hardness of sludge disposal and ecological risks. The proper pretreatment and utilization of dredged sediments presented a challenge. In this study, Dianchi Lake sediments were dredged, thermally treated and utilized as particle capping material in batch experiments. The effects of calcination on phosphorus speciation and sediment-water interface environment as well as P immobility mechanism were predominantly explored. The microstructures and chemical compositions of calcined sediments were investigated, indicating the porosity and mineralization components were greatly enhanced. The fractional analysis of phosphorus revealed that the calcination process reduced the percentage of unsteady phosphorus, transforming into stable inert phosphorus fractions (Al-P, Ca-P and Res-P), respectively, thereby minimized its mobility and eutrophication risk. Interestingly, calcination temperatures of 700 °C and 800 °C resulted in smaller releasing potentials and equilibrium phosphorus concentrations, despite having lower adsorption capacities than 550 °C. Furthermore, the results of redox potential monitoring showed that the thermally treated Dianchi Lake sediments could enhance the redox potential and dissolved oxygen in the surface sediment, indicating the amelioration of interfacial environment. The practical monitoring experiments confirmed the capping depressed the DTP to 0.031 mg L-1. The investigation of this study provided explicit evidence of Ca coupled P and aerobic Fe bound P strengthened the immobilization effects, and the development of sediment calcination demonstrates a promising strategy for alleviating the burden of endogenous pollution and improving aerobic environment, which are of great significance for lake ecological remediation.

Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS).

No standard options existed for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer that progresses after second-line trastuzumab emtansine therapy before 2020. The purpose of this study was to examine the efficacy of pertuzumab retreatment after disease progression following pertuzumab-containing therapy for HER2-positive locally advanced or metastatic breast cancer for the first time. This randomized, open-label, multicenter phase III trial was undertaken in 93 sites in Japan. Eligible patients with HER2-positive breast cancer who had received pertuzumab, trastuzumab, and chemotherapy as first- and/or second-line therapy were randomly assigned (1:1) to: (i) pertuzumab, trastuzumab, and physician's choice chemotherapy (PTC), or (ii) trastuzumab and physician's choice chemotherapy (TC). The primary end-point was investigator-assessed progression-free survival (PFS). Between August 1, 2015 and December 31, 2018, 219 patients were randomized to PTC (n = 110) or TC (n = 109). Median follow-up was 14.2 months (interquartile range, 9.0-22.2), and median PFS was 5.3 months (95% confidence interval [CI], 4.0-6.6) with PTC and 4.2 months (95% CI, 3.2-4.8) with TC (stratified hazard ratio 0.76 [95% CI upper limit 0.967]; p = 0.022). Progression-free survival was improved by adding pertuzumab in all prespecified subgroups. The PTC arm showed a trend towards better overall survival and duration of response, but similar objective response and health-related quality of life. The incidence of treatment-related adverse events was similar between groups except for diarrhea. Pertuzumab retreatment contributes to disease control for HER2-positive locally advanced or metastatic breast cancer previously treated with pertuzumab-containing regimens.

Long-term water quality response to increased hydraulic loadings in a field-scale free water surface constructed wetland treating domestic effluent.

There is limited understanding of how constructed wetland (CW) water quality may change over time in response to increased wastewater nutrient and hydraulic loadings. We evaluated long-term water quality trends and drivers for a full-scale (8.19 ha) free water surface CW that was developed in 2001 for the treatment of increasing amounts of pre-treated domestic wastewater from the township of Mount Barker, South Australia. Water quality parameter concentrations and loads, hydraulic loadings rates, trend direction assessments (TDAs), and water quality parameter removal efficiencies were analysed over the study period. The wetland received an annual average loading rate of 947, 19644, 31039, 18140, 2985, and 807 kg year-1 for BOD5, TN, NH4-N, TKN-N, NOx-N, and TP respectively and removed on average 8%, 72%, 73%, 78%, 12% and -246% of these loadings respectively. The average influent concentrations for the study period were 2.6, 42.3, 40.6, 35.9, 9.0, and 1.9 mg L-1 for BOD5, TN, NH4-N, TKN-N, NOx-N, and TP respectively. Average concentration removal rates over the study period were 50%, 39%, 40%, 15%, -216% and -600.5% for TN, NH4-N, TKN-N, NOx-N, BOD5 and TP respectively, suggesting that nitrogen was only partly assimilated by the wetland and it was a source of organic material and phosphorus. Using seasonally and inflow rate adjusted data, TDAs predicted virtually certain increases in TN, NH4-N, and TKN-N influent concentrations over time, a decline in NOx-N, no trend in BOD5, and a possible decreasing trend in TP. The inflow explained variance accounted for approximately 50% of the variation in TN, NH4-N and TKN-N effluent concentrations. Annual removal efficiencies of N declined with increasing hydraulic loads, and hydraulic loading rates varied with management practices. Seasonal analysis showed that N removal was greater during summer and lower in winter. Due to local population growth and various management practices, hydraulic loading is variable and has often exceeded design targets. Our findings indicate the long-term performance of CWs need to be closely monitored, as water quality can deteriorate due to increased hydraulic loadings.

Microbial consortia adaptation to substrate changes in anaerobic digestion.

Renewable natural gas (RNG) produced from anaerobic digestion (AD) of agricultural residues is emerging a serious biofuel alternative. Complex nature of lignocellulosic biomass residues coupled with complex biochemical transformations involving a large spectrum of microbial communities make anaerobic digestion of biomass difficult to understand and control. The present work aims at studying adaptation of microbial consortia in AD to substrates changes and correlating these to biogas generation. The double edged study deals with (a) using a common starting culture inoculum on different fractions of pretreated lignocellulosic biomass (LBM) fractions; and (b) using different starter inocula for gas generation from simple glucose substrate. Taxonomic analysis using 16S amplicon sequencing is shown to highlight changes in microbial community structure and predominance, majorly in hydrolytic bacterial populations. Observed variations in the rate of digestion with different starter inocula could be related to differences in microbial community structure and relative abundance. Results with different treated biomass fractions as substrates indicated that AD performance could be related to abundance of substrate-specific microbial communities. The work is a step to a deeper understanding of AD processes that may lead to better control and operation of AD for super-scale production of RNG from biomass feedstocks.

Phase I study of liposomal irinotecan in patients with metastatic breast cancer: findings from the expansion phase.

PURPOSE: Metastatic breast cancer (mBC) remains incurable and is associated with low survival rates. This study assessed the efficacy and safety of liposomal irinotecan in heavily pretreated patients with mBC, with or without active brain metastases (BM). METHODS: Following the dose escalation phase and determination of recommended phase 2 dose, the expansion phase of this phase I, open-label, non-randomized study, assigned adult women to cohorts based on mBC subtype: cohort 1, hormone receptor +/human epidermal growth factor receptor 2-; cohort 2, triple-negative breast cancer; or cohort 3, any mBC subtype with active BM. Patients received liposomal irinotecan 50 or 70 mg/m2 free base every 2 weeks. Here, we report secondary outcomes including best overall response (BOR), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). RESULTS: For non-central nervous system (non-CNS) disease across all cohorts (intent-to-treat population, N = 29), the ORR was 34.5% (95% confidence interval: 17.94-54.33), with a BOR of partial response in 10 patients (34.5%), stable disease in five (17.2%), progressive disease in 10 (34.5%); four patients were unevaluable (13.8%). The ORR for the CNS cohort was 30.0% (95% confidence interval: 6.67-65.25) using modified Response Evaluation Criteria in Solid Tumors. Common grade 3 or higher TEAEs were diarrhea (27.6%), nausea (17.2%), fatigue (13.8%), asthenia (10.3%), and hypokalemia (10.3%). Serious treatment-related TEAEs were reported in six patients (20.7%). No treatment-related TEAEs resulted in death. CONCLUSIONS: Liposomal irinotecan monotherapy demonstrated antitumor activity in heavily pretreated patients with mBC, with or without BM. The observed safety profile was consistent with that in previous studies. CLINICAL TRIAL REGISTRATION: Trial registration ID NCT01770353.

Comparison of performances of different fungal laccases in delignification and detoxification of alkali-pretreated corncob for bioethanol production.

The performance of the alkaline fungal laccase PIE5 (pH 8.5) in the delignification and detoxification of alkali-pretreated corncob to produce bioethanol was evaluated and compared with that of the neutral counterpart (rLcc9, 6.5), with the acidic laccase rLacA (4.0) was used as an independent control. Treatment with the three laccases facilitated bioethanol production compared with their respective controls. The lignin contents of alkali-pretreated corncob reduced from 4.06%, 5.06%, and 7.80% to 3.44%, 3.95%, and 5.03%, after PIE5, rLcc9, and rLacA treatment, respectively. However, the performances of the laccases were in the order rLacA > rLcc9 > PIE5 in terms of decreasing total phenol concentration (0.18, 0.36, and 0.67 g/l), boosting ethanol concentration (8.02, 7.51, and 7.31 g/l), and volumetric ethanol productivity (1.34, 0.94, and 0.91 g/l hr), and shortening overall fermentation time. Our results would inform future attempts to improve laccases for ethanol production. Furthermore, based on our data and the fact that additional procedures, such as pH adjustment, are needed during neutral/alkaline fungal laccase treatment, we suggest acidic fungal laccases may be a better choice than neutral/alkaline fungal laccases in bioethanol production.

High-level expression of a ß-mannanase (manB) in Pichia pastoris GS115 for mannose production with Penicillium brevicompactum fermentation pretreatment of soybean meal.

An endo-1,4-ß-mannanase gene (manB) from a Bacillus pumilus Nsic-2 grown in a stinky tofu emulsion was cloned and expressed in Pichia pastoris GS115. After characterized, the endo-1,4-ß-mannanase (manB) show maximum activity at pH 6.0 and 50 °C with LBG as substrate and perform high stability at a range of pH 6-8. After applying for a shake flask fermentation, the specific activity of manB reached 3462 U/mg. To produce mannose, the soybean meal (SBM) was pretreated by biological fermentation for 11 days with Penicillium brevicompactum, and then hydrolyzed by manB. As a result, mannose yield reached 3.58 g per 1 kg SBM which indicated that 0.358% SBM was converted into mannose after hydrolyzation, and mean a total 20% mannan of SBM converting into mannose, while the control group demonstrated only 1.78% conversion. An effective ß-mannanase for the bioconversion of mannan-rich biomasses and an efficient method to produce mannose with soybean meal were introduced.

Quantification of morphochemical changes during in situ enzymatic hydrolysis of individual biomass particles based on autofluorescence imaging.

Enzymatic hydrolysis of biomass is an established method for producing biofuels. Lignocellulosic biomass such as corn stover is very inhomogeneous material with big variation on conversion rates between individual particles therefore leading to variable recalcitrance results. In this study, we used noninvasive optical microscopy techniques, such as two-photon microscopy and fluorescence lifetime imaging microscopy, to visualize and analyze morphological and chemical changes of individual corn stover particles pretreated with sulfuric acid during hydrolysis. Morphochemical changes were interpreted based on the fluorescence properties of isolated building blocks of plant cell wall, such as cellulose, hemicellulose, and lignin. Enzymatic hydrolysis resulted in particle size reduction, side wall collapse, decrease of second harmonic signal from cellulose, redshifting of autofluorescence emission, and lifetime decrease attributed to the relative increase of lignin. Based on these observations, tracking compositional change after hydrolysis of individual particles was accomplished. The methodologies developed offer a paradigm for imaging and analyzing enzymatic hydrolysis in vitro and in situ, which could be used for screening enzymes cocktails targeting specific recalcitrant structures or investigating locally enzyme anti-inhibitory agents.

Experience with eribulin in pretreated patients with advanced liposarcoma: a case series.

Systemic treatments for advanced soft tissue sarcoma are limited. Eribulin showed activity in metastatic soft tissue sarcoma, particularly liposarcomas. Data from six patients with advanced liposarcoma that received eribulin as third- or fourth-line therapy are presented herein. Eribulin treatment was well tolerated; no grade 3-4 toxicity or therapy delay was observed. Two patients had a partial response; four had a prolonged stable disease. The first case, with pre-existing chronic renal dysfunction, achieved a 6-month stable disease with dose-reduced eribulin. The second case became resectable after eribulin treatment, with a 6-month complete surgical remission. The third case obtained a 7-month stable disease with eribulin and stereotactic body radiotherapy. The last three cases were ≥65 years old, and two of them had objective response with eribulin.

Optimization of Yarrowia lipolytica-based consolidated biocatalyst through synthetic biology approach: transcription units and signal peptides shuffling.

Nowadays considerable effort is being pursued towards development of consolidated microbial biocatalysts that will be able to utilize complex, non-pretreated substrates and produce valuable compounds. In such engineered microbes, synthesis of extracellular hydrolases may be fine-tuned by different approaches, like strength of promoter, type of secretory tag, and gene copy number. In this study, we investigated if organization of a multi-element expression cassette impacts the resultant Yarrowia lipolytica transformants' phenotype, presuming that different variants of the cassette are composed of the same regulatory elements and encode the same mature proteins. To this end, Y. lipolytica cells were transformed with expression cassettes bearing a pair of genes encoding exactly the same mature amylases, but fused to four different signal peptides (SP), and located interchangeably in either first or second position of a synthetic DNA construction. The resultant strains were tested for growth on raw and pretreated complex substrates of different plant origin for comprehensive examination of the strains' acquired characteristics. Optimized strain was tested in batch bioreactor cultivations for growth and lipids accumulation. Based on the conducted research, we concluded that the positional order of transcription units (TU) and the type of exploited SP affect final characteristics of the resultant consolidated biocatalyst strains, and thus could be considered as additional factors to be evaluated upon consolidated biocatalysts optimization. KEY POINTS: • Y. lipolytica growing on raw starch was constructed and tested on different substrates. • Impact of expression cassette design and SP on biocatalysts' phenotype was evidenced. • Consolidated biocatalyst process for lipids production from starch was conducted.

Low-dose nab-paclitaxel-based combination chemotherapy in heavily pretreated pancreatic cancer patients.

BACKGROUND: Heavily pretreated pancreatic cancer patients have a grave prognosis. In this case series study, we evaluated the safety and efficacy of nab-paclitaxel-based chemotherapy for such patients. METHODS: The data of pancreatic adenocarcinoma patients (n = 40) treated with nab-paclitaxel after the failure of gemcitabine or fluoropyrimidines at our institution in 2013-2015 were reviewed. RESULTS: The median number of prior chemotherapy regimens was two (range, 1-6). Eighteen patients had an Eastern Cooperative Oncology Group performance status of ≥2. The regimens comprised nab-paclitaxel combined with the following drugs: gemcitabine (n = 28), gemcitabine and fluoropyrimidine (n = 3), platinum and fluoropyrimidine (n = 4), fluoropyrimidine (n = 4), and irinotecan and fluoropyrimidine (n = 1). The median dose of nab-paclitaxel was 63 (range, 51-72) mg/m2/dose, with the schedule of D1/15, D1/8, and D1/8/15 followed in 23, 14, and 3 patients, respectively. The median overall survival was 5.1 (95% CI, 4.6-5.7) months. Among 32 evaluable patients, two partial responses and six stable diseases were observed. The median progression-free survival was 2.6 (95% CI, 1.9-3.2) months. Grade 3/4 leucopenia or neutropenia was observed in three and two patients, respectively. Grade 3/4 anemia was observed in four patients. Other significant (grade 3 or more) nonhematological toxicities were not frequent, except for sepsis/infection (n = 7). However, more severe anemia or sepsis/infection was significantly associated with disease control. CONCLUSION: In heavily pretreated pancreatic adenocarcinoma patients, low-dose nab-paclitaxel-based chemotherapy was fairly tolerable with modest efficacy.

Effect of culture conditions on biomass yield of acclimatized microalgae in ozone pre-treated tannery effluent: A simultaneous exploration of bioremediation and lipid accumulation potential.

Microalgae has huge potential towards biological nutrient removal, but the challenges are remains in maximizing the biomass yield and so nutrient/pollutant removal efficiency. In this study, a response surface methodology-central composite design was applied to investigate the significant process variables (temperature, light intensity, inoculum density and light period) and its interaction effect on biomass yield of effluent acclimatized microalgae Nannochloropsis oculata, Chlorella vulgaris and Chlorella sorokiniana in ozone pre-treated tannery effluent (OPTE). At optimum culture condition N. oculata, C. vulgaris, and C. sorokiniana have yielded 0.67 g/L, 0.85 g/L, and 1.06 g/L biomass. Besides, correlation and regression analysis revealed the strong correlation between microalgal growth and nutrient removal rate. Among the species, C. sorokiniana has shown better remediation potential, at 27.5 °C, 150 µmol m-2 s-1 light intensity, 30% (v/v) inoculum, 16 h light period with the specific growth rate of 0.559 day-1 and nutrient/pollutant removal efficiency of 90% C, 90% N, 100% P, 82% COD, and 100% chromium. But, N. oculata has revealed the better lipid accumulation potential (40%) in OPTE. Thus, the present study established the appropriate strains and conditions required for OPTE treatment along with the value-added biomass production in large scale.

Fe3O4 nanoparticles loading on cow dung based activated carbon as an efficient catalyst for catalytic microbubble ozonation of biologically pretreated coal gasification wastewater.

Cow dung based activated carbon was successfully modified by Fe3O4 nanoparticles as the novel catalyst (Fe3O4 nanoparticles@CDAC) to improve the microbubble ozonation treating biologically pretreated coal gasification wastewater (BPCGW). When the pH, ozone dosage, ozone bubble diameter and catalyst dosage of the ozonation were 7, 0.4 L/min, 5 µm and 3 g/L, the chemical oxygen demand (COD) removal efficiency reached 74% and the ratio of biochemical oxygen demand in five days/COD (BOD5/COD) increased from 0.04 to 0.52, which were attributed to the electron transfer of Fe2+ and Fe3+ in Fe3O4 and enhanced hydroxyl radicals generation by the reaction of iron ions and ozone. Meanwhile, benzene derivatives, naphthalene and aromatic proteins were significantly removed while multiple chain hydrocarbons and their derivatives composed the main residual organic matters. The catalytic activity was slightly decreased even the catalyst has been reused for five times. Therefore, catalytic microbubble ozonation using Fe3O4 nanoparticles@CDAC represented excellent performance treating BPCGW and it is a promising process for wastewater advanced treatment.

Effects of Biosurfactants on Enzymatic Saccharification and Fermentation of Pretreated Softwood.

The enzymatic hydrolysis of cellulose is inhibited by non-productive adsorption of cellulases to lignin, and that is particularly problematic with lignin-rich materials such as softwood. Although conventional surfactants alleviate non-productive adsorption, using biosurfactants in softwood hydrolysis has not been reported. In this study, the effects of four biosurfactants, namely horse-chestnut escin, Pseudomonas aeruginosa rhamnolipid, and saponins from red and white quinoa varieties, on the enzymatic saccharification of steam-pretreated spruce were investigated. The used biosurfactants improved hydrolysis, and the best-performing one was escin, which led to cellulose conversions above 90%, decreased by around two-thirds lignin inhibition of Avicel hydrolysis, and improved hydrolysis of pretreated spruce by 24%. Red quinoa saponins (RQS) addition resulted in cellulose conversions above 80%, which was around 16% higher than without biosurfactants, and it was more effective than adding rhamnolipid or white quinoa saponins. Cellulose conversion improved with the increase in RQS addition up to 6 g/100 g biomass, but no significant changes were observed above that dosage. Although saponins are known to inhibit yeast growth, no inhibition of Saccharomyces cerevisiae fermentation of hydrolysates produced with RQS addition was detected. This study shows the potential of biosurfactants for enhancing the enzymatic hydrolysis of steam-pretreated softwood.

Palbociclib and endocrine therapy in heavily pretreated hormone receptor-positive HER2-negative advanced breast cancer: the UK Compassionate Access Programme experience.

PURPOSE: Palbociclib is approved in 1st line for hormone receptor (HR)-positive HER2-negative advanced breast cancer (ABC). A Compassionate Access Programme previously allowed patients to receive it in 4th line. However, Palbociclib has not been specifically tested in this population. We aimed to determine the safety and efficacy profile of Palbociclib within the Programme across ten institutions in the United Kingdom. METHODS: We retrospectively identified HR-positive HER2-negative ABC patients on the Programme between December 2015 and September 2017. Demographics, disease characteristics, prior treatments, blood tests, toxicities, treatment delays and responses were recorded. Simple statistics, Fisher's exact test, χ2 method and Cox regression were used. RESULTS: 118 patients identified had a median age of 59. 82.2% were postmenopausal and 92.4% performance status 0-1. 81.4% had visceral involvement and 6.8% bone-only disease after a median of 5 prior treatments and 3 prior chemotherapies. Clinical benefit rate was 47.5%, overall response rate 15.8%, median PFS 4.5 months and median OS 15.8 months. Longer progression-free survival on prior endocrine therapy was a predictor of longer PFS and OS. 89.7% developed neutropenia (grade ≥ 3 in 56.8%). 5.1% experienced febrile neutropenia. 48.3% had dose reductions and 3.4% discontinued Palbociclib following toxicity. No statistically significant difference in grade ≥ 3 neutropenia was observed according to metastatic sites nor previous treatments. CONCLUSIONS: This is the most extensive analysis of palbociclib in ≥ 4th-line setting. Clinical benefit was confirmed particularly for endocrine-sensitive, predominantly bony disease and in earlier lines of treatment. Safety was similar to PALOMA trials with higher febrile neutropenia rate.