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Metal–organic frameworks (MOFs) are excellent candidates for water harvesting from desert air. MOF-303 (Al(OH)(PZDC), where PZDC is 1- H -pyrazole-3,5-dicarboxylate), a robust and water-stable MOF, is a particularly promising water-harvesting sorbent that can take up water at low relative humidity and release it under mild heating. Accordingly, development of a facile, high-yield synthesis method for its production at scale is highly desirable. Here we report detailed protocols for the green, water-based preparation of MOF-303 on both gram and kilogram scales. Specifically, four synthetic methods (solvothermal, reflux, vessel and microwave), involving different equipment requirements, are presented to guarantee general accessibility. Typically, the solvothermal method takes ~24 h to synthesize MOF-303, while the reflux and vessel methods can reduce the time to 4–8 h. With the microwave-assisted method, the reaction time can be further reduced to just 5 min. In addition, we provide guidance on the characterization of MOF-303, as well as water-harvesting MOFs in general, to ensure high quality of the product in terms of its purity, crystallinity, porosity and water uptake. Furthermore, to address the need for future commercialization of this material, we demonstrate that our protocol can be employed to produce 3.5 kg per batch with a yield of 91%. MOF-303 synthesized at this large scale shows similar crystallinity and water uptake capacity compared to the respective material produced at a small scale. Our synthetic procedure is green and water-based, and can produce the MOF within hours. MOF-303 is a promising water-harvesting sorbent that can take up water at low relative humidity and release it under mild heating. This metal–organic framework can be made at different scales using the four green synthetic methods described in this protocol.

Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation. Treatment of young mice with low levels of antibiotics results in increases in adiposity and causes both a change in the composition of the intestinal microbial community and an alteration in the activity of microbial metabolic pathways, leading to increased short-chain fatty acid production. How low-dose antibiotics add body mass Continuous treatment with low levels of antibiotics has for decades been used to enhance body weight in livestock, yet the mechanisms underlying this effect are unclear. Using a similar approach in young mice, these authors show that subtherapeutic doses of antibiotic increase the body's fat mass, cause changes in the composition of the intestinal microbial community and alter the activity of microbial metabolic pathways that lead to short-chain fatty-acid production. These findings highlight the importance of certain microbes in maintaining normal metabolic activity.

The differentiation of human memory CD8 T cells is not well understood. Here we address this issue using the live yellow fever virus (YFV) vaccine, which induces long-term immunity in humans. We used in vivo deuterium labelling to mark CD8 T cells that proliferated in response to the virus and then assessed cellular turnover and longevity by quantifying deuterium dilution kinetics in YFV-specific CD8 T cells using mass spectrometry. This longitudinal analysis showed that the memory pool originates from CD8 T cells that divided extensively during the first two weeks after infection and is maintained by quiescent cells that divide less than once every year (doubling time of over 450 days). Although these long-lived YFV-specific memory CD8 T cells did not express effector molecules, their epigenetic landscape resembled that of effector CD8 T cells. This open chromatin profile at effector genes was maintained in memory CD8 T cells isolated even a decade after vaccination, indicating that these cells retain an epigenetic fingerprint of their effector history and remain poised to respond rapidly upon re-exposure to the pathogen. In vivo deuterium labelling reveals a quiescent population of long-lived human virus-specific memory CD8 T cells that maintain the epigenetic landscape of effector cells, which facilitates rapid responses to pathogen re-exposure. A pathogen to remember Memory cells protect against reinfection, or protect against infection after vaccination, but whether they are derived from naive or effector T cells is unknown. Rafi Ahmed and colleagues study the generation, maintenance and characteristics of long-lived memory CD8 T cells in humans after yellow fever vaccination and deuterium labelling. The study demonstrates that long-lived memory CD8 T cells are derived from cells that have divided extensively during the effector phase of the infection. Quiescent memory cells appear to revert to a naive phenotype but maintain an upregulated pattern of gene regulation that resembles effector T cells. In a second paper in this issue, Rafi Ahmed and colleagues examine changes in DNA methylation during effector and memory CD8 T cell differentiation, providing support for a model in which long-lived memory cells arise from a precursor of effector cells.

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, costs, and consequences of calcium supplementation on osteoporosis/osteoporotic fractures, cardiovascular events, kidney stones, gastrointestinal diseases, and other important diseases. In the end, we suggest that calcium supplementation should be prescribed and taken cautiously, accounting for individual patients' risks and benefits. Clearly, further studies are needed to examine the health effects of calcium supplementation to make any solid recommendations for people of different genders, ages, and ethnicities.

Analyses of the taxonomic diversity associated with the human microbiome continue to be an area of great importance. The study of the nature and extent of the commonly shared taxa (\"core\"), versus those less prevalent, establishes a baseline for comparing healthy and diseased groups by quantifying the variation among people, across body habitats and over time. The National Institutes of Health (NIH) sponsored Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine and better define what constitutes the taxonomic core within and across body habitats and individuals through pyrosequencing-based profiling of 16S rRNA gene sequences from oral, skin, distal gut (stool), and vaginal body habitats from over 200 healthy individuals. A two-parameter model is introduced to quantitatively identify the core taxonomic members of each body habitat's microbiota across the healthy cohort. Using only cutoffs for taxonomic ubiquity and abundance, core taxonomic members were identified for each of the 18 body habitats and also for the 4 higher-level body regions. Although many microbes were shared at low abundance, they exhibited a relatively continuous spread in both their abundance and ubiquity, as opposed to a more discretized separation. The numbers of core taxa members in the body regions are comparatively small and stable, reflecting the relatively high, but conserved, interpersonal variability within the cohort. Core sizes increased across the body regions in the order of: vagina, skin, stool, and oral cavity. A number of \"minor\" oral taxonomic core were also identified by their majority presence across the cohort, but with relatively low and stable abundances. A method for quantifying the difference between two cohorts was introduced and applied to samples collected on a second visit, revealing that over time, the oral, skin, and stool body regions tended to be more transient in their taxonomic structure than the vaginal body region.

Background/aims To determine the topographic variation of macular choroidal and retinal thicknesses (RTs) in normal eyes and their relationship with refractive error. Methods Spectral domain optical coherence tomography with enhanced depth imaging was performed on 124 healthy participants using a standardised imaging protocol. Manual segmentation of choroidal boundaries was performed by trained graders, and mean choroidal thickness (CT) was compared with mean RT in corresponding sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Results Mean central subfield CT was 322.2 µm. The choroid was thickest at the temporal and superior sectors (323.1–338.1 µm), followed by inferior sectors (314.0–321.8 µm), and thinnest at the nasal sectors (232.8–287.8 µm). In contrast, the retina was thicker nasally (343.4 µm) and thinner temporally (287.1 µm). CT was thickest among emmetropes in all ETDRS subfields and became thinner progressively among low, moderate and high myopes (p<0.001). The variation of both choroidal and RTs among refractive error groups resulted in different topographic patterns at the macula. Conclusion There is significant topographic variation of choroidal and RTs at different regions of the macula, with progressive change of choroidal thickness in all sectors based on the refractive status of the eye.

BACKGROUNDHepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes.METHODSAdolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging-proton density fat fraction.RESULTSHepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: -10.6% [95% CI: -19.1%, -2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 μIU/mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P = 0.049), but not hepatic fat (r = 0.13, P = 0.532).CONCLUSIONOur results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD.TRIAL REGISTRYClinicalTrials.gov NCT02513121.FUNDINGThe Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors), the UCSD Altman Clinical and Translational Research Institute, the NIH, Children's Healthcare of Atlanta and Emory University's Children's Clinical and Translational Discovery Core, Children's Healthcare of Atlanta and Emory University Pediatric Biostatistical Core, the Georgia Clinical and Translational Science Alliance, and the NIH National Institute of Diabetes, Digestive, and Kidney Disease.

Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions. Here, the authors profile the oral, lung, and gut microbiota of 479 patients with acute respiratory failure, revealing that reduced diversity and increased pathogen presence can predict survival outcomes, highlighting the potential for microbiota-based approaches in critical care.

During gestation, the female reproductive tract must maintain pregnancy while concurrently preparing for parturition. Here, we explore the transitions in gene expression and protein turnover (fractional synthesis rates [FSR]) by which the cervix implements a transition from rigid to compliant. Shifts in gene transcription to achieve immune tolerance and alter epithelial cell programs begin in early pregnancy. Subsequently, in mid-to-late pregnancy transcriptional programs emerge that promote structural reorganization of the extracellular matrix (ECM). Stable isotope labeling revealed a striking slowdown of overall FSRs across the proteome on gestation day 6 that reverses in mid-to-late pregnancy. An exception was soluble fibrillar collagens and proteins of collagen assembly, which exhibit high turnover in nonpregnant cervix compared with other tissues and FSRs that continue throughout pregnancy. This finding provides a mechanism to explain how cross-linked collagen is replaced by newly synthesized, less cross-linked collagens, which allows increased tissue compliance during parturition. The rapid transition requires a reservoir of newly synthesized, less cross-linked collagens, which is assured by the high FSR of soluble collagens in the cervix. These findings suggest a previously unrecognized form of “metabolic flexibility” for ECM in the cervix that underlies rapid transformation in compliance to allow parturition. Summary sentence Flux proteomics identify a steady reservoir of newly synthesized fibrillar collagens in the pregnant cervix, which in conjunction with pregnancy-specific transcriptional programs ensure increased cervical compliance during the process of birth. Graphical Abstract

Here, we have described and validated a strategy for monitoring skeletal muscle protein synthesis rates in rodents and humans over days or weeks from blood samples. We based this approach on label incorporation into proteins that are synthesized specifically in skeletal muscle and escape into the circulation. Heavy water labeling combined with sensitive tandem mass spectrometric analysis allowed integrated synthesis rates of proteins in muscle tissue across the proteome to be measured over several weeks. Fractional synthesis rate (FSR) of plasma creatine kinase M-type (CK-M) and carbonic anhydrase 3 (CA-3) in the blood, more than 90% of which is derived from skeletal muscle, correlated closely with FSR of CK-M, CA-3, and other proteins of various ontologies in skeletal muscle tissue in both rodents and humans. Protein synthesis rates across the muscle proteome generally changed in a coordinate manner in response to a sprint interval exercise training regimen in humans and to denervation or clenbuterol treatment in rodents. FSR of plasma CK-M and CA-3 revealed changes and interindividual differences in muscle tissue proteome dynamics. In human subjects, sprint interval training primarily stimulated synthesis of structural and glycolytic proteins. Together, our results indicate that this approach provides a virtual biopsy, sensitively revealing individualized changes in proteome-wide synthesis rates in skeletal muscle without a muscle biopsy. Accordingly, this approach has potential applications for the diagnosis, management, and treatment of muscle disorders.