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Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.The increasing global prevalence of myopia calls for elaboration of the pathogenesis of this disease. Here, we show that selective ablation and activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in developing mice induced myopic and hyperopic refractive shifts by modulating the corneal radius of curvature (CRC) and axial length (AL) in an opposite way. Melanopsin- and rod/cone-driven signals of ipRGCs were found to influence refractive development by affecting the AL and CRC, respectively. The role of ipRGCs in myopia progression is evidenced by attenuated form-deprivation myopia magnitudes in ipRGC-ablated and melanopsin-deficient animals and by enhanced melanopsin expression/photoresponses in form-deprived eyes. Cell subtype-specific ablation showed that M1 subtype cells, and probably M2/M3 subtype cells, are involved in ocular development. Thus, ipRGCs contribute substantially to mouse eye growth and myopia development, which may inspire novel strategies for myopia intervention.Spatiotemporal patterns of gene expression are instrumental to morphogenesis. A stable pattern interface, often between reciprocal-inhibiting morphogens, must be robustly maintained after initial patterning cues diminish, organ growth, or organ geometry changes. In plants, floral and leaf primordia obtain the adaxial-abaxial pattern at the shoot apical meristem periphery. However, it is unknown how the pattern is maintained after primordia have left the shoot apex. Here, through a combination of computational simulations, time-lapse imaging, and genetic analysis, we propose a model in which auxin simultaneously promotes both adaxial and abaxial domains of expression. Furthermore, we identified multilevel feedback regulation of auxin signaling to refine the spatiotemporal patterns. Our results demonstrate that coactivation by auxin determines and stabilizes antagonistic adaxial-abaxial patterning during aerial organ formation.In 1995, journalist Gary Taubes published an article in Science titled "Epidemiology faces its limits," which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.Recently, nanoscale light manipulation using surface plasmon polaritons (SPPs) has received considerable research attention. The conventional method of detecting SPPs is through light scattering or using bulky Si or Ge photodetectors. However, these bulky systems limit the application of nanophotonic circuits. In this study, the light-matter interaction between graphene and SPP was investigated. For realizing an improved integration in nanocircuits, single-layer graphene was added to asymmetric SPP nanoantenna arrays for nonscattering detection in the near field. The developed device is capable of detecting the controlled propagation of SPPs with a photoresponsivity of 15 mA/W, which paves the way for the new-generation on-chip optical communication.Exposure of a solution of the square pyramidal tungstacyclopentane complex W(NAr)(OSiPh3)2(C4H8) (Ar = 2,6-i-Pr2C6H3) to ethylene at 22 °C in ambient (fluorescent) light slowly leads to the formation of propylene and the square pyramidal tungstacyclobutane complex W(NAr)(OSiPh3)2(C3H6). No reaction takes place in the dark, but the reaction is >90% complete in ∼15 min under blue LED light (∼450 nm λmax). The intermediates are proposed to be (first) an α methyl tungstacyclobutane complex (W(NAr)(OSiPh3)2(αMeC3H5)), and then from it, a β methyl version. The TBP versions of each can lose propylene and form a methylene complex, and in the presence of ethylene, the unsubstituted tungstacyclobutane complex W(NAr)(OSiPh3)2(C3H6). The W-Cα bond in an unobservable TBP W(NAr)(OSiPh3)2(C4H8) isomer in which the C4H8 ring is equatorial is proposed to be cleaved homolytically by light. A hydrogen atom moves or is moved from C3 to the terminal C4 carbon in the butyl chain as the bond between W and C3 forms to give the TBP α methyl tungstacyclobutane complex. Essentially, the same behavior is observed for W(NCPh3)(OSiPh3)2(C4H8) as for W(NAr)(OSiPh3)2(C4H8), except that the rate of consumption of W(NCPh3)(OSiPh3)2(C4H8) is about half that of W(NAr)(OSiPh3)2(C4H8). In this case, an α methyl-substituted tungstacyclobutane intermediate is observed, and the overall rate of formation of W(NCPh3)(OSiPh3)2(C3H6) and propylene from W(NCPh3)(OSiPh3)2(C4H8) is ∼20 times slower than in the NAr system. These results constitute the first experimentally documented examples of forming a metallacyclobutane ring from a metallacyclopentane ring (ring contraction) and establish how metathesis-active methylene and metallacyclobutane complexes can be formed and reformed in the presence of ethylene. They also raise the possibility that ambient light could play a role in some metathesis reactions that involve ethylene and tungsten-based imido alkylidene olefin metathesis catalysts, if not others.

In colorectal cancer, surgical resection is fundamental for curative treatment. Epidural analgesia mitigates the perioperative physiologic stress response caused by surgery, and reduction in perioperative stress may reduce postoperative complications. Vismodegib Nevertheless, epidural analgesia also causes hypotension and lower limb motor weakness that can impair postoperative recovery. Here, we aimed to assess the association between epidural analgesia and postoperative complications after colorectal cancer surgery.

We identified patients undergoing colorectal cancer surgery 2008-2018 in Denmark in the Danish Colorectal Cancer Group Database and obtained anaesthesia data from the Danish Anaesthesia Database. The Danish National Prescription Registry was used to obtain data on prescriptions filled preoperatively reflecting current comorbidities. Databases were linked using the Danish Central Person Registry number and the operation day. Patients were classified according to preoperative insertion of an epidural catheter for analgesia. Confounders were adjusted by propensity score matching. Logistic regression was used to compute effect estimates of epidural analgesia on postoperative complications.

We identified 19 932 individuals undergoing colorectal cancer surgery with available anaesthesia data. Propensity score matching yielded 5691 individuals in each group with balanced preoperative covariates. In the epidural analgesia group 1400 (24.6%) experienced complications compared with 1453 (25.5%) without epidural analgesia. We found no statistically significant association between epidural use and postoperative complications (OR 0.95, 95% CI 0.87-1.04).

In total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery.

In total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery.We report the fully fledged photophysical characterization of isomerically pure, empty-caged, tubular fullerenes D5h-C90 and D5d-C100 and compare their key properties. In particular, the focus was on cage sizes between 60 and 150 carbon atoms with D3, D3d/h, and D5d/h symmetry. The optical band gap of D5d-C100 is 1.65 eV, which is larger than 1.37 eV of D5h-C90. In stark contrast to the nonluminescent D5h-C90, D5d-C100 luminesces at room temperature. Transient absorption spectroscopy shows that photoexcited D5d-C100 is subject to a slow intersystem crossing that generates a triplet excited state. In contrast, a fast, nonradiative internal conversion governs the deactivation of D5h-C90 In this case, exploring the corresponding triplet excited state required triplet-triplet sensitization experiments with anthracene. Density functional theory calculations revealed the electronic structure of the fullertubes, and calculations are consistent with our experimental findings. The calculated band gap systematically decreases with the number of carbon atoms within the D3 and D3d/h series. In contrast, an oscillating behavior is noted within the series of D5d/h fullertubes. Finally, photoexcited D5d-C100 was found to undergo hole transfer with electron-donating triethylamines readily but not electron transfer with electron-accepting methyl viologens.There is a well-established complex interaction between vitamin D metabolism and bone and gonad functions. In this study, we aimed to investigate the potential effects of vitamin D therapy on testosterone and osteocalcin (OC) levels in aged male rats. Forty-five adult male rats were divided into three groups in this study. Unlike the control group, the two experimental groups received 50 IU/kg/day and 100 IU/kg/day of vitamin D3 (cholecalciferol), respectively, for a 4-week period using the gavage method. Testicular tissue and blood samples from rats were collected under general anesthesia at the end of the 4-week period. Testicular tissue samples were examined using light and electron microscopy. Additionally, serum testosterone and OC levels were measured in blood samples. The 50 IU/kg dose of cholecalciferol increased testosterone and OC levels, which were lower than normal due to aging, and regulated the organization of the seminiferous tubule epithelium and interstitium more effectively than the 100 IU/kg dose of cholecalciferol. Male fertility functions and bone health, which degrade due to aging, were increased due to the use of exogenous vitamin D, although the higher dose was not associated with more effective results.

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