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The question of how to mine safely in close multi coal seams is the main concern for coal operators, in particular for large-dip coal seams with complex geological and mechanical conditions. This paper presents a detailed similarity simulation on the movement characteristics of the overburden and the stress distribution of underlying strata in terms of a specific coal mine in the Tielieke mining area of the Kubai coalfield via a three-dimensional photogrammetry system and a high-speed static resistance analyzer. The results show that the overburden strata are asymmetrically deformed around the coal pillar and the fracture area is perpendicular to the longwall with an “M” shape when deeper coal is mined. Moreover, the asymmetric movement of overburden results in the non-uniform distribution of stress on the floor of the coal pillar and ribs. In particular, stress is closely related to the location of the longwall, and stress of the coal pillar is much larger when it is closer to the deep side. The floor stress relief degree of the longwall in the deep zone is higher than that of its counterparts, providing a theoretical foundation for a reasonable layout and a support technique for roadways. The main contribution of this research that it can be used as a reference in maintaining the integrity of surrounding rock for large-dip coal seams with close distances.

Members of the cofilin/ADF family of proteins sever actin filaments, increasing the number of filament ends available for polymerization or depolymerization. Cofilin binds actin filaments with positive cooperativity, forming clusters of contiguously bound cofilin along the filament lattice. Filament severing occurs preferentially at boundaries between bare and cofilin-decorated (cofilactin) segments and is biased at 1 side of a cluster. A molecular understanding of cooperative binding and filament severing has been impeded by a lack of structural data describing boundaries. Here, we apply methods for analyzing filament cryo-electron microscopy (cryo-EM) data at the single subunit level to directly investigate the structure of boundaries within partially decorated cofilactin filaments. Subnanometer resolution maps of isolated, bound cofilin molecules and an actin-cofilactin boundary indicate that cofilin-induced actin conformational changes are local and limited to subunits directly contacting bound cofilin. An isolated, bound cofilin compromises longitudinal filament contacts of 1 protofilament, consistent with a single cofilin having filament-severing activity. An individual, bound phosphomimetic (S3D) cofilin with weak severing activity adopts a unique binding mode that does not perturb actin structure. Cofilin clusters disrupt both protofilaments, consistent with a higher severing activity at boundaries compared to single cofilin. Comparison of these structures indicates that this disruption is substantially greater at pointed end sides of cofilactin clusters than at the barbed end. These structures, with the distribution of bound cofilin clusters, suggest that maximum binding cooperativity is achieved when 2 cofilins occupy adjacent sites. These results reveal the structural origins of cooperative cofilin binding and actin filament severing.

Actin cytoskeleton force generation, sensing, and adaptation are dictated by the bending and twisting mechanics of filaments. Here, we use magnetic tweezers and microfluidics to twist and pull individual actin filaments and evaluate their response to applied loads. Twisted filaments bend and dissipate torsional strain by adopting a supercoiled plectoneme. Pulling prevents plectoneme formation, which causes twisted filaments to sever. Analysis over a range of twisting and pulling forces and direct visualization of filament and single subunit twisting fluctuations yield an actin filament torsional persistence length of ~10 μm, similar to the bending persistence length. Filament severing by cofilin is driven by local twist strain at boundaries between bare and decorated segments and is accelerated by low pN pulling forces. This work explains how contractile forces generated by myosin motors accelerate filament severing by cofilin and establishes a role for filament twisting in the regulation of actin filament stability and assembly dynamics.

Arp2/3 complex nucleates branched actin filaments for cell and organelle movements. Here we report a 2.7 Å resolution cryo-EM structure of the mature branch junction formed by S. pombe Arp2/3 complex that provides details about interactions with both mother and daughter filaments. We determine a second structure at 3.2 Å resolution with the phosphate analog BeF x bound with ADP to Arp3 and ATP bound to Arp2. In this ADP-BeF x transition state the outer domain of Arp3 is rotated 2° toward the mother filament compared with the ADP state and makes slightly broader contacts with actin in both the mother and daughter filaments. Thus, dissociation of P i from the ADP-P i transition state reduces the interactions of Arp2/3 complex with the actin filaments and may contribute to the lower mechanical stability of mature branch junctions with ADP bound to the Arps. Our structures also reveal that the mother filament in contact with Arp2/3 complex is slightly bent and twisted, consistent with the preference of Arp2/3 complex binding curved actin filaments. The small degree of twisting constrains models of actin filament mechanics. Arp2/3 complex forms branched actin filaments for cell movements. Here, the authors report cryo-EM structures of branch junctions with ADP or ADPBeF x (to mimic γ-phosphate) bound to Arp3 to explain why γ-phosphate dissociation destabilizes branches.

The less improvement of ambient visibility suspects the government’s efforts on alleviating PM 2.5 pollution. The COVID-19 lockdown reduced PM 2.5 and increased visibility in Wuhan. Compared to pre-lockdown period, the PM 2.5 concentration decreased by 39.0 μg m −3 , dominated by NH 4 NO 3 mass reduction (24.8 μg m −3 ) during lockdown period. The PM 2.5 threshold corresponding to visibility of 10 km (PTV 10 ) varied in 54–175 μg m −3 and an hourly PM 2.5 of 54 μg m −3 was recommended to prevent haze occurrence. The lockdown measures elevated PTV 10 by 9–58 μg m −3 as the decreases in PM 2.5 mass scattering efficiency and optical hygroscopicity. The visibility increased by 107%, resulted from NH 4 NO 3 extinction reduction. The NH 4 NO 3 mass reduction weakened its mutual promotion with aerosol water and increased PM 2.5 deliquescence humidity. Controlling TNO 3 (HNO 3  + NO 3 − ) was more effective to reduce PM 2.5 and improve visibility than NH x (NH 3  + NH 4 + ) unless the NH x reduction exceeded 11.7–17.5 μg m −3 .

The organization of actin filaments into higher-ordered structures governs eukaryotic cell shape and movement. Global actin network size and architecture are maintained in a dynamic steady state through regulated assembly and disassembly. Here, we used experimentally defined actin structures in vitro to investigate how the activity of myosin motors depends on network architecture. Direct visualization of filaments revealed myosin-induced actin network deformation. During this reorganization, myosins selectively contracted and disassembled antiparallel actin structures, while parallel actin bundles remained unaffected. The local distribution of nucleation sites and the resulting orientation of actin filaments appeared to regulate the scalability of the contraction process. This \"orientation selection\" mechanism for selective contraction and disassembly suggests how the dynamics of the cellular actin cytoskeleton can be spatially controlled by actomyosin contractility.

Cofilin family proteins have essential roles in remodeling the cytoskeleton through filamentous actin depolymerization and severing. The short, unstructured N-terminal region of cofilin is critical for actin binding and harbors the major site of inhibitory phosphorylation. Atypically for a disordered sequence, the N-terminal region is highly conserved, but specific aspects driving this conservation are unclear. Here, we screen a library of 16,000 human cofilin N-terminal sequence variants for their capacity to support growth in S. cerevisiae in the presence or absence of the upstream regulator LIM kinase. Results from the screen and biochemical analysis of individual variants reveal distinct sequence requirements for actin binding and regulation by LIM kinase. LIM kinase recognition only partly explains sequence constraints on phosphoregulation, which are instead driven to a large extent by the capacity for phosphorylation to inactivate cofilin. We find loose sequence requirements for actin binding and phosphoinhibition, but collectively they restrict the N-terminus to sequences found in natural cofilins. Our results illustrate how a phosphorylation site can balance potentially competing sequence requirements for function and regulation. Here the authors screen a saturation mutagenesis library of the disordered N-terminal tail of the actin severing protein cofilin. Their results reveal how a key phosphorylation site can balance competing sequence constraints on function and regulation.

Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg’s sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PP i ). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification. Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al . show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.

This study, conducted in the geological context of the Yixin coalfield, systematically performed indoor mechanical tests to analyze the impact of different stress conditions on the permeability of weakly cemented sandstone. The results were used to establish numerical simulations of permeability curves, revealing the following key findings. (1) After saturation, weakly cemented sandstone transitions from brittle to plastic failure. Numerical simulations closely matched experimental results, ensuring the accuracy of subsequent permeability simulations using the Hoek–Brown method. (2) Indoor permeability experiments identified a unique “√” shaped permeability curve for weakly cemented sandstone, differing from traditional sandstone. Numerical simulations confirmed this pattern and provided a basis for modeling weakly cemented strata under varying confining pressures. (3) The mesoscopic analysis of numerical simulation shows that that confining pressure limits the expansion of microcracks, while pore pressure causes cracks to develop from high- to low-pressure areas. Increasing pore pressure gradually raises permeability, and elevated confining pressure initially reduces, then increases permeability. (4) A damage parameter “D” was introduced to monitor fractures during compression simulations, showing that with increasing confining pressure, the damage parameter decreases and then sharply increases. Hydraulic pressure differentials directly correlated with the damage. This comprehensive study enhances our understanding of weakly cemented sandstone’s hydrological behavior under varying stress conditions and parameters.