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Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and how the two systems interact with each other during hepatitis B virus (HBV) infections and, if so, which mechanisms are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using a series of pharmacological and genetic approaches, we provide in vitro and in vivo evidence indicating that HBV suppresses RLR signaling via lactate dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS preventing its aggregation and mitochondrial localization during HBV infection. Therefore, we show that HK2 and glycolysis-derived lactate have important functions in the immune escape of HBV and that energy metabolism regulates innate immunity during HBV infection. RIG-I is a cytosolic antiviral nucleic acid sensor that signals via MAVS to produce type 1 interferons. Here the authors show that hepatits B virus can repress this pathway by activating glycolysis and lactate production, enabling accumulated lactate to bind MAVS and prevent its mitochondrial localization.

In the era of climate change, global agricultural systems are facing numerous, unprecedented challenges. In order to achieve food security, advanced nano-engineering is a handy tool for boosting crop production and assuring sustainability. Nanotechnology helps to improve agricultural production by increasing the efficiency of inputs and minimizing relevant losses. Nanomaterials offer a wider specific surface area to fertilizers and pesticides. In addition, nanomaterials as unique carriers of agrochemicals facilitate the site-targeted controlled delivery of nutrients with increased crop protection. Due to their direct and intended applications in the precise management and control of inputs (fertilizers, pesticides, herbicides), nanotools, such as nanobiosensors, support the development of high-tech agricultural farms. The integration of biology and nanotechnology into nonosensors has greatly increased their potential to sense and identify the environmental conditions or impairments. In this review, we summarize recent attempts at innovative uses of nanotechnologies in agriculture that may help to meet the rising demand for food and environmental sustainability.

Mental health is a significant concern for teenagers. Given that about 80% of Chinese high school students spend the majority of their time indoors on campus, school environments present opportunities not just for learning but also for reducing students’ stress and promoting their well‐being. Previous research has shown that direct interactions with natural elements such as green plants have restorative effects, but limited attention has been given to indirect interactions with nature. We investigated the impact of three design forms—nonbiophilic, curved, and biomimicry—within school corridors and classrooms on Chinese high school students’ stress and cognitive functions. We employed a combination of subjective assessments and objective measurements to examine the protective and restorative impacts of these three design forms and utilized virtual 3D models in order to control confounding environmental variables during a visual experience. Through virtual reality simulations involving 96 participants, we collected physiological responses, including skin conductance level, heart rate, indicators of heart rate variability, and cognitive responses, including creativity and attention test scores, to evaluate participants’ changes in stress levels and cognitive performance. Our results indicated that indirect exposure to nature, particularly curved forms, facilitates greater cognitive improvement and stress reduction, whereas nonbiophilic forms offer enhanced stress protection benefits. Therefore, learning environments with nonbiophilic design may be more suitable for tasks that induce stress, such as classes and examinations. Learning environments that feature curved biophilic forms may be better suited for promoting relaxation, creativity, and attention.

Top emission can enhance luminance, color purity, and panel-manufacturing compatibility for emissive displays. Still, top-emitting quantum-dot light-emitting diodes (QLEDs) suffer from poor stability, low light outcoupling, and non-negligible viewing-angle dependence because, for QLEDs with non-red emission, the electrically optimum device structure is incompatible with single-mode optical microcavity. Here, we demonstrate that by improving the way of determining reflection penetration depths and creating refractive-index-lowering processes, the issues faced by green QLEDs can be overcome. This leads to advanced device performance, including a luminance exceeding 1.6 million nits, a current efficiency of 204.2 cd A −1 , and a T 95 operational lifetime of 15,600 hours at 1000 nits. Meanwhile, our design does not compromise light outcoupling as it offers an external quantum efficiency of 29.2% without implementing light extraction methods. Lastly, an angular color shift of Δ u’v’  = 0.0052 from 0° to 60° is achieved by narrowing the emission linewidth of quantum dots. By improving the method of determining the penetration depth, lowering film refractive indices, and narrowing emission linewidth, Li et al. report single mode top-emitting green QLEDs with EQE of 29.2%, luminance of 1.6 million nits, T95 of 15,600 h at 1000 nits, and negligible angular colour shift.

AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity.

Glucose starvation activates AMPK via an AMP/ADP-independent mechanism that involves fructose-1,6-bisphosphate and aldolase. New insights into AMPK activation AMPK is a central regulator of metabolic homeostasis, and its dysfunction may result in various diseases including diabetes, obesity, and cancer. AMPK is known to be activated under stressful conditions, including glucose starvation. It has been assumed that upon glucose deprivation AMPK activation occurs in the canonical AMP/ADP-dependent manner, with reduced metabolism of glucose causing falling ATP and increasing AMP and ADP. Here, Sheng-Cai Lin and colleagues show that this is not the case, and that glucose starvation activates AMPK via a different route, in an AMP/ADP-independent manner. During glycolysis, glucose is converted to fructose-1,6-bisphosphate (FBP), which is then processed by FBP aldolases. The authors show that the absence of glucose results in a reduction of FBP-bound aldolase, which triggers LKB1 phosphorylation and activation of AMPK. This study thus uncovers FBP as the critical metabolite that signals glucose availability and FBP aldolases as the sensors that relay the information to AMPK. The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK) 1 , but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK 2 , 3 , 4 , 5 . Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation 6 , 7 . Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.

Subendothelial macrophage internalization of modified lipids and foam cell formation are hallmarks of atherosclerosis. Deubiquitinating enzymes (DUBs) are involved in various cellular activities; however, their role in foam cell formation is not fully understood. Here, using a loss-of-function lipid accumulation screening, we identified ubiquitin-specific peptidase 9 X-linked (USP9X) as a factor that suppressed lipid uptake in macrophages. We found that USP9X expression in lesional macrophages was reduced during atherosclerosis development in both humans and rodents. Atherosclerotic lesions from macrophage USP9X-deficient mice showed increased macrophage infiltration, lipid deposition, and necrotic core content than control apolipoprotein E-KO (Apoe-/-) mice. Additionally, loss-of-function USP9X exacerbated lipid uptake, foam cell formation, and inflammatory responses in macrophages. Mechanistically, the class A1 scavenger receptor (SR-A1) was identified as a USP9X substrate that removed the K63 polyubiquitin chain at the K27 site. Genetic or pharmacological inhibition of USP9X increased SR-A1 cell surface internalization after binding of oxidized LDL (ox-LDL). The K27R mutation of SR-A1 dramatically attenuated basal and USP9X knockdown-induced ox-LDL uptake. Moreover, blocking binding of USP9X to SR-A1 with a cell-penetrating peptide exacerbated foam cell formation and atherosclerosis. In this study, we identified macrophage USP9X as a beneficial regulator of atherosclerosis and revealed the specific mechanisms for the development of potential therapeutic strategies for atherosclerosis.

Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects 1 – 4 . For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action 4 , 5 ; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation 6 . We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase 7 , as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase 8 , which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects. The molecular target of the antidiabetic medicine metformin is identified as PEN2, a subunit of γ-secretases, and the PEN2–ATP6AP1 axis offers potential targets for screening for metformin substitutes.

Real-time monitoring of large marine structures’ health, including drilling platforms, submarine pipelines, dams, and ship hulls, is greatly needed. Among the various kinds of monitoring methods, optical fiber sensors (OFS) have gained a lot of concerns and showed several distinct advantages, such as small size, high flexibility and durability, anti-electromagnetic interference, and high transmission rate. In this paper, three types of OFS used for marine structural health monitoring (SHM), including point sensing, quasi-distributed sensing, and distributed sensing, are reviewed. Emphases are given to the applicability of each type of the sensors by analyzing the operating principles and characteristics of the OFSs. The merits and demerits of different sensing schemes are discussed, as well as the challenges and future developments in OFSs for the marine SHM field.

Using the near-space platform to conduct radiometric calibrations of ocean color sensors is a promising method for refining calibration precision, but there is knowledge gap about the radiance contributions above near-space over the open ocean. We used the radiative transfer (RT) model (PCOART) to assess the contributions (LR) of the upwelling radiance received at the near-space balloons to the total radiance (Lt) measured at the top of the atmosphere (TOA). The results indicated that the LR displayed distinct geometric dependencies with exceeding 2% across most observation geometries. Moreover, the LR increased with wavelengths under the various solar zenith angles, and the LR values fell below 1% only for the two near-infrared bands. Additionally, the influences of variations in oceanic constituents on LR were negligible across various azimuth angles and spectral bands, except in nonalgal particle (NAP)-dominated waters. Furthermore, the influences of aerosol optical thicknesses (AOTs) and atmospheric vertical distributions on LR were examined. Outside glint-contaminated areas, the atmosphere-associated LR variations could exceed 2% but declined substantially as AOTs increased under most observation geometries. The mean height of the vertically inhomogeneous layer (hm) significantly influenced LR, and the differences in Lt could exceed 5% when comparing atmospheric vertical distributions following homogeneous versus Gaussian-like distributions. Finally, the transformability from near-space radiance to Lt was examined based on a multiple layer perceptron (MLP) model, which exhibited high agreement with the RT simulations. The MAPD averaged 0.420% across the eight bands, ranging from 0.218% to 0.497%. Overall, the radiometric calibration utilizing near-space represents a significant innovation method for satellite-borne ocean color sensors.