Inhibitory Effect of Lactobacillus Paracasei CMU-Pb-L5 In a Subcutaneous Transplanted Tumor Model of Colorectal Cancer.

Lactobacillus paracasei (L.p) is a prevalent probiotic strain within the Lactobacillus genus, which has robust intestinal colonization capabilities. Previous studies have demonstrated the anticancer properties of L.p both in vivo and in vitro. However, the mechanisms underlying its anticancer activity in vivo remain unclear. This study established a subcutaneous transplanted tumor model of colorectal cancer (CRC) in mice to investigate the impact of L.p CMU-Pb-L5. Various parameters including tumor volume, tumor weight, histological alterations in tumor tissue, levels of polyamines and immune-related cytokines in serum, as well as the expression of polyamine metabolism-related and apoptosis-related proteins were evaluated. The results suggested that L.p CMU-Pb-L5 exhibited inhibitory effects on tumor cell proliferation, promotion of tumor cell apoptosis, reduction in polyamine levels, and enhancement of the immune response in CRC mice. To sum up, these results suggested that L.p CMU-Pb-L5 holds promise for potential clinical applications in the treatment of CRC.

A novel approach for perfusion process design based on a "Grey-Box" kinetic model.

Perfusion cell-culture mode has caught industrial interest in the field of biomanufacturing in recent years. Thanks to new technology, perfusion-culture processes can support higher cell densities, higher productivities and longer process times. However, due to the inherent operational complexity and high running costs, the development and design of perfusion-culture processes remain challenging. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells. Initially, four batches of bench-top reactor continuous-perfusion-culture data were used to fit the model parameters. Then, we proposed the model-based process design approach, aiming to quickly find out the "theoretically optimal" operational parameters combinations (perfusion rate and the proportion of feed medium in perfusion medium) which could achieve the target steady-state VCD while minimizing both medium cost and perfusion rate during steady state. Meanwhile, we proposed a model-based dynamic operational parameters-adjustment strategy to address the issue of cell-growth inhibition due to the high osmolality of concentrated perfusion medium. In addition, we employed a dynamic feedback control method to aid this strategy in preventing potential nutrient depletion scenarios. Finally, we test the feasibility of the model-based process design approach in both shake flask semi-perfusion culture (targeted at 5 × 107 cells/ml) and bench-top reactor continuous perfusion culture (targeted at 1.1 × 108 cells/ml). This approach significantly reduces the number of experiments needed for process design and development, thereby accelerating the advancement of perfusion-mode cell-culture processes.

Research and Implementation of Indoor Positioning Algorithm Based on Bluetooth 5.1 AOA and AOD.

With the addition of Bluetooth AOA/AOD direction-finding capabilities in the Bluetooth 5.1 protocol and the introduction of antenna array technology into the Bluetooth platform to further enhance positioning accuracy, Bluetooth has gradually become a research hotspot in the field of indoor positioning due to its standard protocol specifications, rich application ecosystem, and outstanding advantages such as low power consumption and low cost compared to other indoor positioning technologies. However, current indoor positioning based on Bluetooth AOA/AOD suffers from overly simplistic core algorithm implementations. When facing different application scenarios, the standalone AOA or AOD algorithms exhibit weak applicability, and they also encounter challenges such as poor positioning accuracy, insufficient real-time performance, and significant effects of multipath propagation. These existing problems and deficiencies render Bluetooth lacking an efficient implementation solution for indoor positioning. Therefore, this paper proposes a study on Bluetooth AOA and AOD indoor positioning algorithms. Through an analysis of the principles of Bluetooth's newly added direction-finding functionality and combined with research on array signal DOA estimation algorithms, the paper ultimately integrates the least squares algorithm to optimize positioning errors in terms of accuracy and incorporates an anti-multipath interference algorithm to address the impacts of multipath effects in different scenarios. Experimental testing demonstrates that the indoor positioning algorithms applicable to Bluetooth AOA and AOD can effectively mitigate accuracy errors and overcome multipath effects, exhibiting strong applicability and significant improvements in real-time performance.

Investigating the mechanism of antioxidants as egg white powder flavor modifiers.

BACKGROUND: The uses of egg white powder (EWP) are restricted because of its odor. It is necessary to find a method to improve its flavor. In this paper, three different antioxidants - green tea extract (GTE), sodium ascorbate (SA), and glutathione (GSH) - were selected to modify the flavor. The physicochemical and structural properties of EWP were investigated to study the mechanism of the formation and release of volatile compounds. RESULTS: Antioxidants can modify the overall flavor of EWP significantly, inhibiting the generation or release of nonanal, 3-methylbutanal, heptanal, decanal, geranyl acetone, and 2-pemtylfuran. A SA-EWP combination showed the lowest concentration of 'off' flavor compounds; GTE-EWP and GSH-EWP could reduce several 'off' flavor compounds but increased the formation of geranyl acetone and furans. The changes in the carbonyl content and the amino acid composition confirmed the inhibition of antioxidants with the oxidative degradation of proteins or characteristic amino acids. The results of fluorescence spectroscopy and Fourier transform infrared (FTIR) spectroscopy provided structural information regarding EWP, which showed the release of volatile compounds decreased due to structural changes. For example, the surface hydrophobicity increased and the protein aggregation state changed. CONCLUSIONS: Antioxidants reduce the 'off' flavor of EWP in two ways: they inhibit protein oxidation and Maillard reactions (they inhibit formation of 3-methylbutanal and 2-pemtylfuran) and they enhance the binding ability of heat-denatured proteins (reducing the release of nonanal, decanal, and similar compounds). © 2023 Society of Chemical Industry.

A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice.

Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO-) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO- level during DILI in vivo. Therefore, ONOO--activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ. Herein, we report a novel ONOO--responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO--mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended conjugated π-electron system and ∼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous and exogenous ONOO- concentration changes in living cells. Importantly, in vivo fluorescence imaging tests demonstrated that the probe can effectively detect the endogenous generation of ONOO- in an acetaminophen (APAP)-induced liver injury mouse model. This study provides insight into the design of highly selective NIR fluorescent probes suitable for spatiotemporal monitoring of ONOO- under different pathological conditions.

Serum lipids concentration on prognosis of high-grade glioma.

OBJECTIVE: To investigate the effect of serum lipids concentration on the prognosis of high-grade glioma patients undergoing postoperative radiotherapy. METHODS: Retrospective analysis of the patients with high-grade glioma who received postoperative Intensity Modulated Radiotherapy between 13 May 2013 and 12 September 2018 was performed. The patients were grouped according to the average values of serum total cholesterol, LDL, and HDL concentration in peripheral blood (before surgery, 6 months after therapy). Cox proportional hazards model was performed to determine whether the total cholesterol concentration, LDL concentration, and HDL concentration in peripheral blood before therapy and their changes after therapy were factors influencing the prognosis. RESULTS: The results of COX regression analysis showed that the independent prognostic factors of high-grade glioma patients were pathological grade, the extent of resection, serum cholesterol concentration pre-surgery, and the change of LDL concentration from pre-surgery to post-therapy. The prognosis of patients with high serum total cholesterol concentration before therapy was worse than those of patients with low total cholesterol concentration. The 5-year survival rate and the median survival time of patients with high serum total cholesterol concentration before therapy were 4.9% and 23.6 months, but the low cholesterol concentration group were 19.6% and 24.5 months, respectively. Besides, the average serum LDL concentration in high-grade glioma patients gradually increased after therapy. The 5-year survival rate of patients and the median survival time with elevated LDL concentration after therapy is 11.8% and 20.4 months, but the reduced LDL concentration group was 16.7% and 28.4 months, respectively. The total cholesterol and LDL concentration increased significantly after therapy in Grade IV patients while Grade III patients did not. CONCLUSIONS: The cholesterol concentration before therapy and LDL concentration change from pre-surgery to post-therapy are the factors that affect the prognosis of high-grade glioma patients who have undergone postoperative radiotherapy. In the final analysis, the high serum cholesterol pre-surgery and the increased in serum LDL concentration from pre-surgery to post-therapy were associated with worse survival of patients.

The Effects of Drug Exposure and Single Nucleotide Polymorphisms on Aaptinib-Induced Severe Toxicities in Solid Tumors.

To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. SIGNIFICANCE STATEMENT: Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

Unexpected Parabolic Temperature Dependency of CH4 Emissions from Rice Paddies.

Global warming is expected to affect methane (CH4) emissions from rice paddies, one of the largest human-induced sources of this potent greenhouse gas. However, the large variability in warming impacts on CH4 emissions makes it difficult to extrapolate the experimental results over large regions. Here, we show, through meta-analysis and multi-site warming experiments using the free air temperature increase facility, that warming stimulates CH4 emissions most strongly at background air temperatures during the flooded stage of ∼26 °C, with smaller responses of CH4 emissions to warming at lower and higher temperatures. This pattern can be explained by divergent warming responses of plant growth, methanogens, and methanotrophs. The effects of warming on rice biomass decreased with the background air temperature. Warming increased the abundance of methanogens more strongly at the medium air temperature site than the low and high air temperature sites. In contrast, the effects of warming on the abundance of methanotrophs were similar across the three temperature sites. We estimate that 1 °C warming will increase CH4 emissions from paddies in China by 12.6%─substantially higher than the estimates obtained from leading ecosystem models. Our findings challenge model assumptions and suggest that the estimates of future paddy CH4 emissions need to consider both plant and microbial responses to warming.

Designing a novel E2-IFN-γ fusion protein against CSFV by immunoinformatics and structural vaccinology approaches.

Subunit vaccines with high purity and safety are gradually becoming a main trend in vaccinology. However, adjuvants such as interferon-gamma (IFN-γ) are required to enhance immune responses of subunit vaccines due to their poor immunogenicity. The conjugation of antigen with adjuvant can induce more potent immune responses compared to the mixture of antigen and adjuvant. At the same time, the selection of linker, indispensable in the construction of the stable and bioactive fusion proteins, is complicated and time-consuming. The development of immunoinformatics and structural vaccinology approaches provides a means to address the abovementioned problem. Therefore, in this study, a E2-IFN-γ fusion protein with an optimal linker (E2-R2-PIFN) was designed by bioinformatics approaches to improve the immunogenicity of the classical swine fever virus (CSFV) E2 subunit vaccine. Moreover, the E2-R2-PIFN fusion protein was expressed in HEK293T cells and the biological effects of IFN-γ in E2-R2-PIFN were confirmed in vitro via Western blotting. Here, an alternative method is utilized to simplify the design and validation of the antigen-adjuvant fusion protein, providing a potential subunit vaccine candidate against CSFV. KEY POINTS: • An effective and simple workflow of antigen-adjuvant fusion protein design and validation was established by immunoinformatics and structural vaccinology. • A novel E2-IFN-γ fusion protein with an optimal linker was designed as a potential CSFV vaccine. • The bioactivity of the newly designed fusion protein was preliminarily validated through in vitro experiments.

Metformin alleviates cisplatin-induced ototoxicity by autophagy induction possibly via the AMPK/FOXO3a pathway.

Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Unfortunately, patients are often troubled by serious side effects, especially hearing loss. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We explored the role of autophagy and the efficacy of metformin in cisplatin-induced ototoxicity in cells, zebrafish, and mice. Furthermore, the underlying molecular mechanism of how metformin affects cisplatin-induced ototoxicity was examined. In in vitro experiments, autophagy levels in HEI-OC1 cells were assessed using fluorescence and Western blot analyses. In in vivo experiments, whether metformin had a protective effect against cisplatin ototoxicity was validated in zebrafish and C57BL/6 mice. The results showed that cisplatin induced autophagy activation in HEI-OC1 cells. Metformin exerted antagonistic effects against cisplatin ototoxicity in HEI-OC1 cells, zebrafish, and mice. Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), whereas cells with AMPK silencing displayed otherwise. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.NEW & NOTEWORTHY Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We investigated the protective effect of metformin on cisplatin ototoxicity in vitro and in vivo. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.

Effects of physical therapy on lung function in children with asthma: a systematic review and meta-analysis.

BACKGROUND: Asthma is a common chronic respiratory disease in children. In addition to medications, physical therapy is considered as a treatment strategy for asthma. We conducted this study to investigate the effects of physical therapy on lung function in children with asthma. METHODS: Three databases were searched. We conducted the meta-analysis for the forced expiratory volume in the first second in percent predicted values [FEV1(%pred)], the forced vital capacity in percent predicted values [FVC(%pred)], and the peak expiratory flow in percent predicted values [PEF(%pred)] by using a random effect model. RESULTS: Of the 6474 identified studies, 18 studies (16 in physical training, 2 in breathing exercise or inspiratory muscle training) were included in the systematic review and 11 studies (all in physical training) were included in the meta-analysis. The meta-analysis showed a significantly improved FVC(%pred) in the experimental group. CONCLUSIONS: Physical training improved FVC(%pred) significantly in children with asthma. Further study is needed, especially on the effects of breathing exercise and inspiratory muscle training in children with asthma. IMPACT: Our study reviewed the physical therapies for children with asthma and clarified whether and how these therapies affect them. Our study found that physical training improved the forced vital capacity in percent predicted values [FVC(%pred)] significantly in asthmatic children. Our study provided evidence that physical training could improve lung function in children with asthma, which is not identical to the Global Initiative for Asthma (GINA) guidelines.

The effect of psychological condition before radiotherapy on prognosis in 390 patients initially treated for nasopharyngeal carcinoma.

PURPOSE: To explore whether anxiety and depression are prognostic indexes for overall survival in patients with nasopharyngeal carcinoma (NPC) who underwent intensity-modulated radiotherapy (IMRT). METHODS: Clinical data were collected for NPC patients who underwent IMRT. Anxiety and depression were investigated before radiotherapy by using the Hospital Anxiety and Depression Scale (HADS). The survival rate was calculated by the Kaplan-Meier method, and survival curves were compared among patients with different levels of anxiety and depression. The Cox risk regression model was used to screen the factors affecting survival. RESULTS: A total of 390 initially treated NPC patients were included in the study. Among them, 166 patients suffered from anxiety, and 95 patients suffered from depression before radiotherapy. The 5-year overall survival rates for patients with and without anxiety before radiotherapy were 71.6% and 81.8% (χ2 = 5.31, P = 0.021), respectively. The 5-year overall survival rates for patients with and without depression before radiotherapy were 74.3% and 78.1% (χ2 = 0.05, P = 0.82), respectively. Cox regression analysis indicated clinical stages (HR = 3.982, 95% CI: 2.365~6.705), anxiety (HR = 1.832, 95% CI: 1.140~2.944), and gender (HR = 0.555, 95% CI: 0.313~0.984) as independent prognostic factors. CONCLUSION: Anxiety before radiotherapy is associated with poor prognosis in NPC patients.

Accelerated atrazine degradation and altered metabolic pathways in goat manure assisted soil bioremediation.

The intensive and long-term use of atrazine in agriculture has resulted in serious environmental pollution and consequently endangered ecosystem and human health. Soil microorganisms play an important role in atrazine degradation. However, their degradation efficiencies are relatively low due to their slow growth and low abundance, and manure amendment as a practice to improve soil nutrients and microbial activities can solve these problems. This study investigated the roles of goat manure in atrazine degradation performance, metabolites and bacterial community structure. Our results showed that atrazine degradation efficiencies in un-amended soils were 26.9-35.7% and increased to 60.9-84.3% in goat manure amended treatments. Hydroxyatrazine pathway was not significantly altered, whereas deethylatrazine and deisopropylatrazine pathways were remarkably enhanced in treatments amended with manure by encouraging the N-dealkylation of atrazine side chains. In addition, goat manure significantly increased soil pH and contents of organic matters and humus, explaining the change of atrazine metabolic pathway. Nocardioides, Sphingomonas and Massilia were positively correlated with atrazine degradation efficiency and three metabolites, suggesting their preference in atrazine contaminated soils and potential roles in atrazine degradation. Our findings suggested that goat manure acts as both bacterial inoculum and nutrients to improve soil microenvironment, and its amendment is a potential practice in accelerating atrazine degradation at contaminated sites, offering an efficient, cheap, and eco-friendly strategy for herbicide polluted soil remediation.

[Preliminary Experimental Study of Establishing a Lung Development Model with Specific Pathogen Free Preterm Pigs].

OBJECTIVE: To determine the best time for conducting cesarean section for the establishment of an animal model of lung development with specific pathogen free (SPF) preterm Bama minipigs under the condition of not making medical interventions such as hyperoxia, mechanical ventilation, or medication. METHODS: SPF Bama sows at gestational day (GD) 113, GD107, GD104, GD101, and GD98 were selected and cesarean sections were performed. Then, the viability of the preterm piglets were observed. Based on their general data, viability, and paraffin sections stained with hematoxylin and eosin, the best time for performing cesarean section in order to build a SPF preterm pig model of lung development was determined. RESULTS: Cesarean sections were performed on a total of 7 sows and 55 piglets were delivered, among which 25 were still alive 3 hours after delivery. Seven piglets of GD104 and all piglets of GD107 and GD113 survived, while piglets of GD98 and GD101 all died. The survival rate of piglets of GD104 was 33.33% (7/21). Piglets of GD98 already possessed fully developed physical appearance and lung shape. Piglets from GD104 had better lung expansion and higher density of thin-walled alveoli. The lungs of GD107 piglets were basically fully expanded, and the density of thin-walled alveoli was almost the same as that of normal full-term piglets. CONCLUSIONS: Findings of this study suggest that SPF preterm piglets of GD104 with no specific pathogen exposure and no medical intervention can be used to establish a SPF preterm pig model of lung development.

Long noncoding RNA LINC00630 promotes radio-resistance by regulating BEX1 gene methylation in colorectal cancer cells.

This study aimed to analyze the relation between long noncoding RNA (lncRNA) LINCE00630 and radio-resistance and elucidate the underlying mechanism. Relative expression of LINC00630, BEX1, and DNMT3B in colorectal cancer (CRC) cells and clinical samples was determined by real-time PCR. Prognosis in respect of LINC00630 expression was analyzed by Kaplan-Meier survival curve. LINC00630 and BEX1 were specifically silenced by shRNAs. Cell viability and growth were analyzed by MTT and clonogenic assays, respectively. Cell apoptosis was measure by both caspase-3 activity and flow cytometry. Association between EZH2 with LINC00630 and BEX1 promoter was determined by RNA immunoprecipitation and chromatin immunoprecipitation. BEX1 and DNMT3B proteins were quantified by Western blot. We demonstrated the elevated LINC00630 correlated with radio-resistance and poorer prognosis in CRC. Knockdown of LINC00630 significantly improved the sensitivity of CRC cells to irradiation. Mechanistically, LINC00630 in complex with EZH2 negatively regulated BEX1 through promoter DNA methylation. BEX1 silencing greatly restored the cell viability and suppressed cell apoptosis, which were elicited by LINC00630 deficiency in response to irradiation. Our data uncovered the contribution of elevated LINC00630 to radio-resistance in CRC, which was predominately mediated by epigenetically repressed BEX1.

Lower-than-expected CH4 emissions from rice paddies with rising CO2 concentrations.

Elevated atmospheric CO2 (eCO2 ) generally increases carbon input in rice paddy soils and stimulates the growth of methane-producing microorganisms. Therefore, eCO2 is widely expected to increase methane (CH4 ) emissions from rice agriculture, a major source of anthropogenic CH4 . Agricultural practices strongly affect CH4 emissions from rice paddies as well, but whether these practices modulate effects of eCO2 is unclear. Here we show, by combining a series of experiments and meta-analyses, that whereas eCO2 strongly increased CH4 emissions from paddies without straw incorporation, it tended to reduce CH4 emissions from paddy soils with straw incorporation. Our experiments also identified the microbial processes underlying these results: eCO2 increased methane-consuming microorganisms more strongly in soils with straw incorporation than in soils without straw, with the opposite pattern for methane-producing microorganisms. Accounting for the interaction between CO2 and straw management, we estimate that eCO2 increases global CH4 emissions from rice paddies by 3.7%, an order of magnitude lower than previous estimates. Our results suggest that the effect of eCO2 on CH4 emissions from rice paddies is smaller than previously thought and underline the need for judicious agricultural management to curb future CH4 emissions.

A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations.

BACKGROUND: α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-controlled clinical trials in otherwise healthy, overweight adults using LA supplementation are lacking. OBJECTIVES: The primary objective was to evaluate whether LA supplementation decreases elevated plasma triglycerides in overweight or obese adults. Secondary aims examined if LA promotes weight loss and improves oxidative stress and inflammation. METHODS: Overweight adults [n = 81; 57% women; 21-60 y old; BMI (in kg/m2) ≥ 25] with elevated plasma triglycerides ≥100 mg/dL were enrolled in a 24-wk, randomized, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints. RESULTS: R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at 24 wk than the placebo group (-0.8; P = 0.04). The effect of R-LA on BMI was correlated to changes in plasma triglycerides (r = +0.50, P = 0.004). Improvement in body weight was greater at 24 wk in R-LA subgroups than in placebo subgroups. Women and obese participants (BMI ≥ 35) showed greater weight loss (-5.0% and -4.8%, respectively; both P < 0.001) and loss of body fat (-9.4% and -8.6%, respectively; both P < 0.005). Antioxidant gene expression in mononuclear cells at 24 wk was greater in the R-LA group (Heme oxygenase 1 [HMOX1] : +22%; P = 0.02) than in placebo. Less urinary F2-isoprostanes (-25%; P = 0.005), blood leukocytes (-10.1%; P = 0.01), blood thrombocytes (-5.1%; P = 0.03), and ICAM-1 (-7.4%; P = 0.04) at 24 wk were also observed in the R-LA group than in placebo. CONCLUSIONS: Long-term LA supplementation results in BMI loss, greater antioxidant enzyme synthesis, and less potential for inflammation in overweight adults. Improved cellular bioenergetics is also evident in some individuals given R-LA.This trial was registered at clinicaltrials.gov as NCT00765310.

Producing more grain with lower environmental costs.

Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs. Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil-crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha(-1)), 7.2 Mg ha(-1) and 10.5 Mg ha(-1) to 8.5 Mg ha(-1), 8.9 Mg ha(-1) and 14.2 Mg ha(-1), respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil-crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.

Investigation into the impact of tyrosine on the product formation and quality attributes of mAbs in rCHO cell cultures.

Tyrosine (Tyr) is crucial to the maintenance of the monoclonal antibody (mAb) titers and quality attributes in fed-batch cultures of recombinant Chinese hamster ovary (rCHO) cells. However, the relation between tyrosine and these aspects is not yet fully defined. In order to further elucidate such a relation, two groups of fed-batch experiments with high tyrosine (H-T) or low tyrosine (L-T) additions producing an IgG1 monoclonal antibody against CD20 were implemented to investigate the intracellular and extracellular effects of tyrosine on the culture performance. It was found that the scarcity of tyrosine led to the distinctive reduction in both viable cell density and antibody specific production rate, hence the sharply reduced titer, possibly related to the impaired translation efficiency caused by the substrate limitation of tyrosine. In addition, alterations to the critical quality attributes were detected in the L-T group, compared to those in the H-T condition. Notable decrease in the contents of intact antibody was found under the L-T condition because of the elevated reductive level in the supernatant. Moreover, the aggregate content in the L-T condition was also reduced, probably resulting from the accumulation of extracellular cystine. In particular, the lysine variant content noticeably increased with tyrosine limitation owing to the downregulation of two carboxypeptidases, i.e., CpB and CpH. Overall, understanding the role of tyrosine in these aspects is fundamental to the increase of product titers and control of critical quality attributes in the monoclonal antibody production of rCHO cell fed-batch cultures. KEY POINTS: • Tyrosine is essential in the maintenance of product titers and the control of product qualities in high cell density cultivations in rCHO cell. • This study revealed the bottleneck of decreased qmAbupon the deficiency of tyrosine. • The impact of tyrosine on the critical product qualities and the underlying mechanisms were also thoroughly assessed.