Four column-type sequential aerobic sludge blanket reactors were fed with phenol as the sole carbon and energy source and operated at loading rates of 1.0, 1.5, 2.0 and 2.5 kg phenol m(-3) day(-1). ...The results indicated that phenol loading exerted a profound influence on the structure, activity and metabolism of the aerobic granules. Compact granules with good settling ability were maintained at loadings up to 2.0 kg phenol m(-3) day(-1), and structurally weakened granules with enhanced production of extracellular polymers and proteins and significantly lower hydrophobicities were observed at the highest loading of 2.5 kg phenol m(-3) day(-1). Specific oxygen uptake rate, catechol 2,3-dioxygenase (C23O) and catechol 1,2-dioxygenase (C12O) activities peaked at a loading of 2.0 kg phenol m(-3) day(-1), and declined thereafter. Granules degraded phenol completely in all four reactors, mainly through the meta cleavage pathway as C23O activities were significantly higher than C12O activities. At the highest loading applied, the anabolism and catabolism of microorganisms were regulated such that phenol degradation proceeded exclusively via the meta pathway, apparently to produce more energy for overstimulation of protein production against phenol toxicity. This work contributes to a better understanding of the ability of aerobic granules to handle high-strength industrial wastewaters containing chemicals that are normally inhibitory to microbial growth.
Over the past decade, chemists have embraced visible-light photoredox catalysis due to its remarkable ability to activate small molecules. Broadly, these methods employ metal complexes or organic ...dyes to convert visible light into chemical energy. Unfortunately, the excitation of widely utilized Ru and Ir chromophores is energetically wasteful as ∼25% of light energy is lost thermally before being quenched productively. Hence, photoredox methodologies require high-energy, intense light to accommodate said catalytic inefficiency. Herein, we report photocatalysts which cleanly convert near-infrared (NIR) and deep red (DR) light into chemical energy with minimal energetic waste. We leverage the strong spin–orbit coupling (SOC) of Os(II) photosensitizers to directly access the excited triplet state (T1) with NIR or DR irradiation from the ground state singlet (S0). Through strategic catalyst design, we access a wide range of photoredox, photopolymerization, and metallaphotoredox reactions which usually require 15–50% higher excitation energy. Finally, we demonstrate superior light penetration and scalability of NIR photoredox catalysis through a mole-scale arene trifluoromethylation in a batch reactor.
The unfolded protein response (UPR) is a stress response program that reprograms cellular translation and gene expression in response to proteotoxic stress in the endoplasmic reticulum (ER). One of ...the primary means by which the UPR alleviates this stress is by reducing protein flux into the ER via a general suppression of protein synthesis and ER-specific mRNA degradation. We report here an additional UPR-induced mechanism for the reduction of protein flux into the ER, where mRNAs that encode signal sequences are released from the ER to the cytosol. By removing mRNAs from the site of translocation, this mechanism may serve as a potent means to transiently reduce ER protein folding load and restore proteostasis. These findings identify the dynamic subcellular localization of mRNAs and translation as a selective and rapid regulatory feature of the cellular response to protein folding stress.
Collision tumor consists of two tumors occurring in the same organ without intermixture of the two cell types. The most common type of collision tumor in ovary is between teratoma and surface ...epithelial tumor. A 38-year-old woman presented with complained of lower abdominal pain and tightness, and a solid partially cystic left ovarian mass with minimal ascites was detected. Left salpingo-oophorectomy was performed. The ovarian mass measured 15 × 12 × 7 cm with a pedunculated mass on its surface which measured 6 × 2.5 × 2.5 cm. Histologically, it was a collision tumor of fibroma and mature cystic teratoma. Fibroma becomes more edematous as their size increases, which is frequently accompanied by the escape of increasing quantities of fluid from the tumor surfaces. Ascites is often detected when the fibroma is more than a diameter of 10 cm. It is important to identify the different components of a collision tumor for proper management.
Background Group 2 innate lymphoid cells (ILC2) have been implicated in the pathogenesis of allergic lung diseases. However, the upstream signals that regulate ILC2 function during pulmonary ...inflammation remain poorly understood. ILC2s have been shown to respond to exogenous IL-2, but the importance of endogenous IL-2 in ILC2 function in vivo remains unclear. Objective We sought to understand the role of IL-2 in the regulation of ILC2 function in the lung. Methods We used histology, flow cytometry, immunohistochemistry, ELISA, and quantitative PCR with knockout and reporter mice to dissect pulmonary ILC2 function in vivo . We examined the role of ILC2s in eosinophilic crystalline pneumonia, an idiopathic type 2 inflammatory lung condition of mice, and the effect of IL-2 deficiency on this disease. We determined the effect of IL-2 administration on pulmonary ILC2 numbers and function in mice in the steady state and after challenge with IL-33. Results We discovered an unexpected role for innate cell–derived IL-2 as a major cofactor of ILC2 function during pulmonary inflammation. Specifically, we found that IL-2 was essential for the development of eosinophilic crystalline pneumonia, a type 2 disease characterized by increased numbers of activated ILC2s. We show that IL-2 signaling serves 2 distinct functions in lung ILC2s, namely promoting cell survival/proliferation and serving as a cofactor for the production of type 2 cytokines. We further demonstrate that group 3 innate lymphoid cells are an innate immune source of IL-2 in the lung. Conclusion Innate cell–derived IL-2 is a critical cofactor in regulating ILC2 function in pulmonary type 2 pathology.
Iodine deficiency is one of the major causes of brain damage in childhood. However, iodine supplementation during early pregnancy and lactation can prevent the ill effects of iodine deficiency. This ...study evaluated maternal and infant thyroid function and infant visual information processing (VIP) in the context of maternal iodine supplementation. A community-based, randomized, supplementation trial was conducted. Mother infant dyads (n = 106) were enrolled within the first 10 days after delivery to participate in this study. Mothers were randomly assigned either to receive a potassium iodide capsule (225 μg iodine) daily for 26 weeks or iodized salt weekly for 26 weeks. Maternal thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), thyroglobulin (Tg), urinary iodine concentration (UIC), breast milk iodine concentration (BMIC) and infant T4, TSH, UIC and VIP were measured as outcome variables. At baseline, neither mothers nor infants in the two groups were significantly different in any of the biomarkers or anthropometric measurements. Maternal TSH and goiter prevalence significantly decreased following iodine supplementation. The percentage of infants who preferentially remembered the familiar face was 26% in the capsule and 51% in the I-salt groups. Infant sex, length for age Z score, BMIC, maternal education and household food security were strong predictors of novelty quotient. In conclusion supplementation daily for six months with an iodine capsule or the use of appropriately iodized salt for an equivalent time was sufficient to reduce goiter and TSH in lactating women. Higher BMIC and LAZ as well as better household food security, maternal education, and male sex predicted higher novelty quotient scores in the VIP paradigm.
With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. ...This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones insulin-like growth factor-1 (IGF-1), free testosterone (males only) and catabolic markers inflammatory markers (interleukin-6, C-reactive protein) and myostatin. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95 % CI 1.13–28.84.44,
p
= 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95 % CI 0.00–0.52,
p
= 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95 % CI 1.00–1.24,
p
= 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1 % decline in odds of sarcopenia in women (
p
= 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.
Owing to a fast growth rate, aerobic granules display a wide range of sizes, approximately 0.3-5.0 mm in diameter. As the diameter increases, the aerobic granule undergoes serial morphological and ...physical changes that could cause problems to the reactor operation, a phenomenon which, however, has not been fully studied hitherto. In this study, aerobic granules from a sequencing batch reactor were mechanically separated into various size-categories in order to investigate their physical properties, including sludge volumetric index (SVI), settling velocity (sv), specific surface hydrophobicity, granule strength, total solids, percentage volatile solids and other structural properties. Also, the live and dead biomass distribution was examined under a confocal laser scanning microscope after treatment with nucleic acid viability stains. Regardless of size, the biomass (both live and dead) was densest in the outer layer of the granule, which was about 600+/-50 microm thick. The live cells appeared only in the peripheral zone, while dead biomass spread into the inner zone. The biomass distribution pattern justified the changing physical properties of the granules as they grew bigger. As size increased, the sv, granule total density and biomass density increased but not in parallel with the size increment, while the granule strength, specific surface hydrophobicity and SVI decreased. Nonetheless, beyond a threshold size (4.0 mm diameter), the granules presented peculiar values in those properties, deviating from the initial trends. This was due to both inner and outer structural changes. The physical properties associated significantly with the size factor, for which the correlation coefficients were above 0.67. In view of biological viability and physical properties, the operational size-range suggested for optimal performance and economically effective aerobic SBR granular sludge is a diameter of 1.0-3.0 mm.
Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus ...nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.
Highlights • Dpysl3 was expressed in ameboid microglia and diminished in ramified microglia with progressing age. • Dpysl3 expression was increased in activated microglia in vivo and in vitro. • ...siRNA-mediated knockdown of Dpysl3 suppressed the proinflammatory mediators in activated microglia. • Knockdown of Dpysl3 inhibited migration, phagocytosis of activated microglia coupled with deranged actin configuration.
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