The world's tropical reef ecosystems, and the people who depend on them, are increasingly 60 impacted by climate change [1][2][3][4][5][6][7] Reef, as well as the potential influence of water quality and fishing pressure on the severity of 71 bleaching. 72The geographic footprints of mass bleaching of corals on the Great Barrier Reef have varied 73 strikingly during three major events in 1998 , 2002 and 2016). In 1998, bleaching was 74 primarily coastal and most severe in the central and southern regions. In 2002, bleaching was 75 more widespread, and affected offshore reefs in the central region that had escaped in 1998 8 . 76In 2016, bleaching was even more extensive and much more severe, especially in the 77 northern, and to a lesser extent the central regions, where many coastal, mid-shelf and 78 offshore reefs were affected (Fig. 1a, b). In 2016, the proportion of reefs experiencing 79 extreme bleaching (>60% of corals bleached) was over four times higher compared to 1998 80 or 2002 (Fig. 1f) The severity and distinctive geographic footprints of bleaching in each of the three 88 years can be explained by differences in the magnitude and spatial distribution of sea-surface 89 temperature anomalies (Fig. 1a, b 102The geographic pattern of bleaching also demonstrates how marine heatwaves can be (Fig. 2a) (Fig. 1g). largely escaped bleaching in the two earlier events (Fig. 1a). Thirty-five percent of the reefs (Fig. 1b, e). We conclude that the overlap of disparate geographic bleaching at the scale of both individual reefs and the entire Great Barrier Reef (Fig. 1a, b). 134We found a similar strong relationship between the amount of bleaching measured 135 underwater, and the satellite-based estimates of heat exposure on individual reefs (Fig. 3). 136Low levels of bleaching was observed at some locations when DHW values were only 2-3 137 o C-weeks. Typically, 30-40% of corals bleached on reefs exposed to 4 o C-weeks, whereas an 138 average of 70-90% of corals bleached on reefs that experience 8 o C-weeks or more (Fig. 3). 139Resistance and adaptation to bleaching 140 Once we account for the amount of heat stress experienced on each reef, adding 141 chlorophyll-a, a proxy for water quality, to our statistical model yielded no support for the 142 hypothesis that good water quality confers resistance to bleaching 13 . Rather, the estimated 143 effect of chlorophyll-a was to significantly reduce the DHW threshold for bleaching 144 (Extended Data Table 1). However, despite the statistical significance, the effect in real terms 145 beyond heat stress alone is very small (Extended Data Fig. 1). Similarly, we found no effect 146 of the level of protection (in fished or protected zones) on bleaching (P > 0.1: Extended Data 147 Table 1). These results are consistent with the broad-scale pattern of severe bleaching in the 148 northern Great Barrier Reef, which affected hundreds of reefs across inshore-offshore 149 gradients in water quality, and regardless of their zoning (protection) status (Fig. 1a, b). 150Simila...

Global warming is rapidly emerging as a universal threat to ecological integrity and function, highlighting the urgent need for a better understanding of the impact of heat exposure on the resilience of ecosystems and the people who depend on them . Here we show that in the aftermath of the record-breaking marine heatwave on the Great Barrier Reef in 2016 , corals began to die immediately on reefs where the accumulated heat exposure exceeded a critical threshold of degree heating weeks, which was 3-4 °C-weeks. After eight months, an exposure of 6 °C-weeks or more drove an unprecedented, regional-scale shift in the composition of coral assemblages, reflecting markedly divergent responses to heat stress by different taxa. Fast-growing staghorn and tabular corals suffered a catastrophic die-off, transforming the three-dimensionality and ecological functioning of 29% of the 3,863 reefs comprising the world's largest coral reef system. Our study bridges the gap between the theory and practice of assessing the risk of ecosystem collapse, under the emerging framework for the International Union for Conservation of Nature (IUCN) Red List of Ecosystems , by rigorously defining both the initial and collapsed states, identifying the major driver of change, and establishing quantitative collapse thresholds. The increasing prevalence of post-bleaching mass mortality of corals represents a radical shift in the disturbance regimes of tropical reefs, both adding to and far exceeding the influence of recurrent cyclones and other local pulse events, presenting a fundamental challenge to the long-term future of these iconic ecosystems.

Despite the ubiquity of ferrihydrite in natural sediments and its importance as an industrial sorbent, the nanocrystallinity of this iron oxyhydroxide has hampered accurate structure determination by traditional methods that rely on long-range order. We uncovered the atomic arrangement by real-space modeling of the pair distribution function (PDF) derived from direct Fourier transformation of the total x-ray scattering. The PDF for ferrihydrite synthesized with the use of different routes is consistent with a single phase (hexagonal space group P6(3)mc; a = approximately 5.95 angstroms, c = approximately 9.06 angstroms). In its ideal form, this structure contains 20% tetrahedrally and 80% octahedrally coordinated iron and has a basic structural motif closely related to the Baker-Figgis delta-Keggin cluster. Real-space fitting indicates structural relaxation with decreasing particle size and also suggests that second-order effects such as internal strain, stacking faults, and particle shape contribute to the PDFs.

The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy. Here we report the discovery of a highly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.

The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host's immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation. Moreover, this review provides new insight regarding the influence of the gut microbiota on Trp metabolism. Additional comprehensive analyses of targeted Trp metabolites (including endogenous and bacterial metabolites) are essential for experimental preciseness, as the influence of the gut microbiota cannot be neglected, and may explain contradictory results in the literature.

SummaryAging is a result of gradual and overall functional deteriorations across the body; however, it is unknown if an individual tissue works to primarily mediate aging progress and lifespan control. Here we found that the hypothalamus is important for the development of whole-body aging in mice, and the underlying basis involves hypothalamic immunity mediated by IKKβ/NF-κB and related microglia-neuron immune crosstalk. Several interventional models were developed showing that aging retardation and lifespan extension are achieved in mice through preventing against aging-related hypothalamic or brain IKKβ/NF-κB activation. Mechanistic studies further revealed that IKKβ/NF-κB inhibits GnRH to mediate aging-related hypothalamic GnRH decline, and GnRH treatment amends aging-impaired neurogenesis and decelerates aging. In conclusion, the hypothalamus has a programmatic role in aging development via immune-neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating aging-related health problems.

Graphene has the potential for high-speed, wide-band photodetection, but only with very low external quantum efficiency and no spectral selectivity. Here we report a dramatic enhancement of the overall quantum efficiency and spectral selectivity that enables multicolour photodetection, by coupling graphene with plasmonic nanostructures. We show that metallic plasmonic nanostructures can be integrated with graphene photodetectors to greatly enhance the photocurrent and external quantum efficiency by up to 1,500%. Plasmonic nanostructures of variable resonance frequencies selectively amplify the photoresponse of graphene to light of different wavelengths, enabling highly specific detection of multicolours. Being atomically thin, graphene photodetectors effectively exploit the local plasmonic enhancement effect to achieve a significant enhancement factor not normally possible with traditional planar semiconductor materials.

Trace chemical detection is important for a wide range of practical applications. Recently emerged two-dimensional (2D) crystals offer unique advantages as potential sensing materials with high sensitivity, owing to their very high surface-to-bulk atom ratios and semiconducting properties. Here, we report the first use of Schottky-contacted chemical vapor deposition grown monolayer MoS2 as high-performance room temperature chemical sensors. The Schottky-contacted MoS2 transistors show current changes by 2-3 orders of magnitude upon exposure to very low concentrations of NO2 and NH3. Specifically, the MoS2 sensors show clear detection of NO2 and NH3 down to 20 ppb and 1 ppm, respectively. We attribute the observed high sensitivity to both well-known charger transfer mechanism and, more importantly, the Schottky barrier modulation upon analyte molecule adsorption, the latter of which is made possible by the Schottky contacts in the transistors and is not reported previously for MoS2 sensors. This study shows the potential of 2D semiconductors as high-performance sensors and also benefits the fundamental studies of interfacial phenomena and interactions between chemical species and monolayer 2D semiconductors.