Two microalgae,
Chlorella pyrenoidosa and
Chlamydomonas snowiae, were isolated from a high ammonia leachate pond in Li Keng Landfill, Guangzhou, China. Their growth and nutrient removal rates were ...determined in a serial dilution of landfill leachate under laboratory conditions, and their growth rates were compared with that of a
C. pyrenoidosa strain isolated from a clean river. The results indicated the growth of all three algae was inhibited by high leachate concentrations, and the inhibition appears linked to high ammonia (ammoniacal-N
⩾
670
mg
L
−1). Significant amounts of ammoniacal-N, ortho-P and COD in the leachate were removed by the algae, with a positive correlation between algal growth and nutrient consumption. Not enough data are available to conclude that one strain was less inhibited by ammoniacal nitrogen or more effective at treating it. Phytotoxicity of leachate was reduced after algal growth, as demonstrated by a seed germination experiment with
Brassica chinensis. The germination rates in 10%, 30% and 50% concentrations of algal-treated leachate were significantly higher than those in the same concentration but algal-free leachate.
Abstract Context Robot-assisted surgery is increasingly used for radical cystectomy (RC) and urinary reconstruction. Sufficient data have accumulated to allow evidence-based consensus on key issues ...such as perioperative management, comparative effectiveness on surgical complications, and oncologic short- to midterm outcomes. Objective A 2-d conference of experts on RC and urinary reconstruction was organized in Pasadena, California, and the City of Hope Cancer Center in Duarte, California, to systematically review existing peer-reviewed literature on robot-assisted RC (RARC), extended lymphadenectomy, and urinary reconstruction. No commercial support was obtained for the conference. Evidence acquisition A systematic review of the literature was performed in agreement with the PRISMA statement. Evidence synthesis Systematic literature reviews and individual presentations were discussed, and consensus on all key issues was obtained. Most operative, intermediate-term oncologic, functional, and complication outcomes are similar between open RC (ORC) and RARC. RARC consistently results in less blood loss and a reduced need for transfusion during surgery. RARC generally requires longer operative time than ORC, particularly with intracorporeal reconstruction. Robotic assistance provides ergonomic value for surgeons. Surgeon experience and institutional volume strongly predict favorable outcomes for either open or robotic techniques. Conclusions RARC appears to be similar to ORC in terms of operative, pathologic, intermediate-term oncologic, complication, and most functional outcomes. RARC consistently results in less blood loss and a reduced need for transfusion during surgery. RARC can be more expensive than ORC, although high procedural volume may attenuate this difference. Patient summary Robot-assisted radical cystectomy (RARC) is an alternative to open surgery for patients with bladder cancer who require removal of their bladder and reconstruction of their urinary tract. RARC appears to be similar to open surgery for most important outcomes such as the rate of complications and intermediate-term cancer-specific survival. Although RARC has some ergonomic advantages for surgeons and may result in less blood loss during surgery, it is more time consuming and may be more expensive than open surgery.
High cellular heterogeneity within neuroblastomas (NBs) may account for the non-uniform response to treatment. c-KIT(+) cells are frequently detected in NB, but how they influence NB behavior still ...remains elusive. Here, we used NB tumor-initiating cells to reconstitute NB development and demonstrated that c-KIT(+) cells are de novo generated and dynamically maintained within the tumors to sustain tumor progression. c-KIT(+) NB cells express higher levels of neural crest and stem cell markers (SLUG, SOX2 and NANOG) and are endowed with high clonogenic capacity, differentiation plasticity and are refractory to drugs. With serial transplantation assays, we found that c-KIT expression is not required for tumor formation, but c-KIT(+) cells are more aggressive and can induce tumors ninefold more efficiently than c-KIT(-/low) cells. Intriguingly, c-KIT(+) cells exhibited a long-term in vivo self-renewal capacity to sustain the formation of secondary and tertiary tumors in mice. In addition, we showed that Prokineticin signaling and mitogen-activated protein kinase pathways are crucial for the maintenance of c-KIT(+) cells in tumor to promote NB progression. Our results highlight the importance of this de novo population of NB cells in sustainable growth of NB and reveal specific signaling pathways that may provide targets leading to more effective NB therapies.
Lesbian and gay older adults have health disparities that are risk factors for Alzheimer's disease, yet little is known about the neurocognitive aging of sexual minority groups.
To explore ...cross-sectional and longitudinal dementia outcomes for adults in same-sex relationships (SSR) and those in mixed-sex relationships (MSR).
This prospective observational study utilized data from the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) collected from contributing Alzheimer's Disease Research Centers. Participants were adults aged 55+ years at baseline with at least two visits in NACC UDS (from September 2005 to March 2021) who had a spouse, partner, or companion as a co-participant. Outcome measures included CDR® Dementia Staging Instrument, NACC UDS neuropsychological testing, and the Functional Activities Questionnaire. Multivariable linear mixed-effects models accounted for center clustering and repeated measures by individual.
Both MSR and SSR groups experienced cognitive decline regardless of baseline diagnosis. In general, MSR and SSR groups did not differ statistically on cross-sectional or longitudinal estimates of functioning, dementia severity, or neuropsychological testing, with two primary exceptions. People in SSR with mild cognitive impairment showed less functional impairment at baseline (FAQ M = 2.61, SD = 3.18 vs. M = 3.97, SD = 4.53, respectively; p < 0.01). The SSR group with dementia had less steep decline in attention/working memory (β estimates = -0.10 versus -0.18; p < 0.01).
Participants in SSR did not show cognitive health disparities consistent with a minority stress model. Additional research into protective factors is warranted.
Objectives: Whether age or menopause per se influences fat distribution remains controversial. This study aimed to investigate the change of body composition, particularly body fat distribution, in ...relation to menopausal transition in a 30-month prospective study of perimenopausal women. Methods: A total of 438 community-based healthy women aged 44–55 years participated in the Hong Kong Perimenopausal Women Osteoporosis Study. Data were obtained at baseline, and at 9-, 18- and 30-month during the follow-up. Soft tissue measurements consisting of fat mass and lean muscle mass of the trunk and whole body were obtained by the dual energy X-ray absorptiometry. Percentage change of body measurements over the follow-up period was compared between women who remained premenopausal, those who went through menopausal transition, and those who were menopausal since baseline. Results: A slight decrease in the lean mass but an increase in the total fat mass and trunk fat mass (TFM) over the follow-up period were noted. Multivariate linear regression analysis showed that age was negatively associated with an increase in central obesity. Adjusted for the important predictors--age, age of menarche and education level, menopausal status was a significant and independent predictor of the decrease in lean mass and the increase in percent of body fat, TFM and trunk–leg fat mass ratio. Conclusion: Our 30-month longitudinal study showed that menopause has an independent effect on an increase in fat mass, and an increase in central obesity in perimenopausal Chinese women.
Abstract Background Comprehensive and standardized reporting of adverse events after robot-assisted radical cystectomy (RARC) and urinary diversion for bladder cancer is necessary to evaluate the ...magnitude of morbidity for this complex operation. Objective To accurately identify and assess postoperative morbidity after RARC using a standardized reporting system. Design, setting, and participants A total of 241 consecutive patients underwent RARC, extended pelvic lymph node dissection, and urinary diversion between 2003 and 2011. In all, 196 patients consented to a prospective database, and they are the subject of this report. Continent diversions were performed in 68% of cases. Outcome measurements and statistical analysis All complications within 90 d of surgery were defined and categorized by a five-grade and 10-domain modification of the Clavien system. Univariable and multivariable logistic regression analyses were used to identify predictors of complications. Grade 1–2 complications were categorized as minor, and grade 3–5 complications were categorized as major. All blood transfusions were recorded as grade ≥2. Results and limitations Eighty percent of patients (156 of 196 patients) experienced a complication of any grade ≤90 d after surgery. A total of 475 adverse events (113 major) were recorded, with 365 adverse events (77%) occurring ≤30 d after surgery. Sixty-eight patients (35%) experienced a major complication within the first 90 d. Other than blood transfusions given (86 patients 43.9%), infectious, gastrointestinal, and procedural complications were the most common, at 16.2%, 14.1%, and 10.3%, respectively. Age, comorbidity, preoperative hematocrit, estimated blood loss, and length of surgery were predictive of a complication of any grade, while comorbidity, preoperative hematocrit, and orthotopic diversion were predictive of major complications. The 90-d mortality rate was 4.1%. The main limitation is lack of a control group. Conclusions Analysis of postoperative morbidity following RARC demonstrates a considerable complication rate, though the rate is comparable to contemporary open series that followed similar reporting guidelines. This finding reinforces the need for complete and standardized reporting when evaluating surgical techniques and comparing published series.
Targeted proteomics is a convenient method determining enzyme expression levels, but a quantitative analysis of these proteomic data has not been fully explored yet. Here, we present and demonstrate ...a computational tool (principal component analysis of proteomics, PCAP) that uses quantitative targeted proteomics data to guide metabolic engineering and achieve higher production of target molecules from heterologous pathways. The method is based on the application of principal component analysis to a collection of proteomics and target molecule production data to pinpoint specific enzymes that need to have their expression level adjusted to maximize production. We illustrated the method on the heterologous mevalonate pathway in Escherichia coli that produces a wide range of isoprenoids and requires balanced pathway gene expression for high yields and titers. PCAP-guided engineering resulted in over a 40% improvement in the production of two valuable terpenes. PCAP could potentially be productively applied to other heterologous pathways as well.
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•We report quantitative analysis method for proteomics data using PCA.•Principal component analysis of proteomics (PCAP) can direct metabolic engineering.•PCAP provides information not apparent by the simple observation of proteomics data.•PCAP was successfully applied to improve the mevalonate pathway (MEV) in E. coli.•Limonene and bisabolene production increased about 40% using PCAP-based strategy.
In this Phase 2b study, 331 low‐to‐moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of ...tofacitinib (CP‐690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy‐proven acute rejection (BPAR) with a serum creatinine increase of ≥0.3 mg/dL and ≥20% (clinical BPAR) at Month 6 and measured GFR at Month 12. Similar 6‐month incidences of clinical BPAR (11%, 7% and 9%) were observed for MI, LI and CsA. Measured GFRs were higher (p < 0.01) at Month 12 for MI and LI versus CsA (65 mL/min, 65 mL/min vs. 54 mL/min). Fewer (p < 0.05) patients in MI or LI developed chronic allograft nephropathy at Month 12 compared with CsA (25%, 24% vs. 48%). Serious infections developed in 45%, 37% and 25% of patients in MI, LI and CsA, respectively. Anemia, neutropenia and posttransplant lymphoproliferative disorder occurred more frequently in MI and LI compared with CsA. Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side‐effects at the doses evaluated.
The authors present the results of a phase 2b trial of tofacitinib in renal transplantation.
Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome ...degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy. Proteomics measurements discover a host factor in need of protection to improve resource redistribution activity. A computational model demonstrates that the MazF mRNA-decay feedback loop enables proportional control of MazF in an optimal operating regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic shifts in transcript abundance and discovers regulatory design elements. Altogether, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.