Mechanosensitive (MS) channels are universal cellular membrane pores. Bacterial MS channels, as typified by MS channel of small conductance (MscS) from Escherichia coli (EcMscS), release osmolytes under hypoosmotic conditions. MS channels are known to be ion selective to different extents, but the underlying mechanism remains poorly understood. Here we identify an anion-selective MscS channel from Thermoanaerobacter tengcongensis (TtMscS). The structure of TtMscS closely resembles that of EcMscS, but it lacks the large cytoplasmic equatorial portals found in EcMscS. In contrast, the cytoplasmic pore formed by the C-terminal β-barrel of TtMscS is larger than that of EcMscS and has a strikingly different pattern of electrostatic surface potential. Swapping the β-barrel region between TtMscS and EcMscS partially switches the ion selectivity. Our study defines the role of the β-barrel in the ion selection of an anion-selective MscS channel and provides a structural basis for understanding the ion selectivity of MscS channels.crystal structure | anion selection | cytoplasmic region | electrophysiology | single channel recording

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BackgroundThe responses of plant seeds and seedlings to changing atmospheric nitrogen (N) deposition and precipitation regimes determine plant population dynamics and community composition under global change.Methodology/Principal FindingsIn a temperate steppe in northern China, seeds of P. tanacetifolia were collected from a field-based experiment with N addition and increased precipitation to measure changes in their traits (production, mass, germination). Seedlings germinated from those seeds were grown in a greenhouse to examine the effects of improved N and water availability in maternal and offspring environments on seedling growth. Maternal N-addition stimulated seed production, but it suppressed seed mass, germination rate and seedling biomass of P. tanacetifolia. Maternal N-addition also enhanced responses of seedlings to N and water addition in the offspring environment. Maternal increased-precipitation stimulated seed production, but it had no effect on seed mass and germination rate. Maternal increased-precipitation enhanced seedling growth when grown under similar conditions, whereas seedling responses to offspring N- and water-addition were suppressed by maternal increased-precipitation. Both offspring N-addition and increased-precipitation stimulated growth of seedlings germinated from seeds collected from the maternal control environment without either N or water addition. Our observations indicate that both maternal and offspring environments can influence seedling growth of P. tanacetifolia with consequent impacts on the future population dynamics of this species in the study area.Conclusion/SignificanceThe findings highlight the importance of the maternal effects on seed and seedling production as well as responses of offspring to changing environmental drivers in mechanistic understanding and projecting of plant population dynamics under global change.

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Positive resection margin frequently exists in breast‐conserving treatment (BCT) of early‐stage breast cancer, and insufficient therapeutic efficacy is common during radiotherapy (RT) in advanced breast cancer patients. Moreover, a multimodal nanotherapy platform is urgently required for precision cancer medicine. Therefore, a biodegradable cyclic RGD pentapeptide/hollow virus‐like gadolinium (Gd)‐based indocyanine green (R&HV‐Gd@ICG) nanoprobe is developed to improve fluorescence image‐guided surgery and breast cancer RT efficacy. R&HV‐Gd exhibits remarkably improved aqueous stability, tumor retention, and target specificity of ICG, and achieves outstanding magnetic resonance/second near‐infrared (NIR‐II) window multimodal imaging in vivo. The nanoprobe‐based NIR‐II fluorescence image guidance facilitates complete tumor resection, improves the overall mouse survival rate, and effectively discriminates between benign and malignant breast tissues in spontaneous breast cancer transgenic mice (area under the curve = 0.978; 95% confidence interval: 0.952, 1.0). Moreover, introducing the nanoprobe to tumors generated more reactive oxygen species under X‐ray irradiation, improved RT sensitivity, and reduced mouse tumor progression. Notably, the nanoprobe is biodegradable in vivo and exhibits accelerated bodily clearance, which is expected to reduce the potential long‐term inorganic nanoparticle toxicity. Overall, the nanoprobe provides a basis for developing precision breast cancer treatment strategies.

The mechanism of crustal deformation and the development of large offset strike-slip faults during continental collision, such as the India-Eurasia zone, remains poorly understood. Previous mechanical models were simplified which are either (quasi-)2-D approximations or made the a priori assumption that the rheology of the lithosphere was either purely viscous (distributed deformation) or purely localized. Here we present three-dimensional visco-elasto-plastic thermo-mechanical simulations, which can produce both distributed and highly localized deformation, to investigate crustal deformation during continental indentation. Our results show that large-scale shear zones develop as a result of frictional plasticity, which have many similarities with observed shear zones. Yet localized deformation requires both a strong upper crust (>10 22 Pa•s) and a moderately weak middle/lower crust (~10 20 Pa•s) in Tibet. The brittle shear zones in our models develop low viscosity zones directly beneath them, consistent with geological observations of exhumed faults, and geophysical observations across active faults. Plain Language Summary Large offset strike-slip faults are one of the key surface features of continental collision, such as in Tibet. These narrow belts of strike-slip faults accommodate strong deformation, and deciphering their mechanism of formation helps to understand the complex dynamics of India-Eurasia collision. Yet previous models developed to address this either assumed simplified rheologies or employed low numerical resolutions that is insufficient to simulate the spontaneous formation of localized zones. Here, we present high-resolution 3-D visco-elasto-plastic thermo-mechanical models that simulate the formation of large-scale strike-slip faults during Indian indentation, while also taking distributed deformation into account. Our simulations show that a combination of a strong upper crust and a moderately weak middle/lower crust produces faults that are, to first order, consistent with observed ones in the Tibet region. Localized deformation usually initiates at the brittle-ductile transition, and a weak middle/lower crust facilitates subsequent shear localization such that the shear zones cut through the whole crust. The craton-like strong terranes can sustain large stresses and initiate large offset faults along their boundaries.

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Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions. Herein, we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop. The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate (MTX) self-assembles into nanoparticles (VSeM); decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time. Upon reaching tumor sites, acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake. Afterward, the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release; then the released VES could produce extra ROS to accelerate the collapse of VSeM. Finally, the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy. Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.