Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that ...tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB activation, thus upregulating IL-6 and CCL3 for neutrophil recruitment. In addition, the CTSC-PR3-IL-1β axis induces neutrophil reactive oxygen species production and formation of NETs, which degrade thrombospondin-1 and support metastatic growth of cancer cells in the lungs. CTSC expression and secretion are associated with NET formation and lung metastasis in human breast tumors. Importantly, targeting CTSC with compound AZD7986 effectively suppresses lung metastasis of breast cancer in a mouse model. Overall, our findings reveal a mechanism of how tumor cells regulate neutrophils in metastatic niches and support CTSC-targeting approaches for cancer treatment.
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•Tumor-secreted CTSC promotes breast-to-lung metastasis by regulating neutrophils•CTSC activates membrane-bound PR3 of neutrophils to upregulate IL-1β secretion•CTSC enhances neutrophil recruitment into metastatic niches and induces NETosis•Targeting CTSC with AZD7986 effectively inhibits lung metastasis in mice
Neutrophils play critical roles in cancer metastasis. Xiao et al. report the dual role of a tumor-secreted protease, CTSC, in recruiting neutrophils to metastatic niches and inducing neutrophils to form extracellular traps (NETs). These promote lung colonization of breast cancer and targeting CTSC inhibits lung metastasis in mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Direct detection of circularly polarized light (CPL) is a challenging task due to limited materials and ambiguous structure–property relationships that lead to low distinguishability of the light ...helicities. Perovskite ferroelectric semiconductors incorporating chirality provide new opportunities in dealing with this issue. Herein, a pair of 2D chiral perovskite ferroelectrics is reported, which have enhanced CPL detection performance due to interplays among lattice, photon, charge, spin, and orbit. The chirality‐transfer‐induced chiral&polar ferroelectric phase enhances the asymmetric nature of the photoactive sublattice and achieves a switchable self‐powered detection via the bulk photovoltaic effect. The single‐crystal‐based device exhibits a CPL‐sensitive detection performance under 430 nm with an asymmetric factor of 0.20 for left‐ and right‐CPL differentiation, about two times that of the pure chiral counterparts. The enhanced CPL detection performance is ascribed to the Rashba–Dresselhaus effect that originates from the bulk inversion asymmetry and strong spin–orbit coupling, shown with a large Rashba coefficient, which is demonstrated by density functional theory calculation and circularly polarized light excited photoluminescence measurement. These results provide new perspectives on chiral Rashba ferroelectric semiconductors for direct CPL detection and ferroelectrics‐based chiroptics and spintronics.
A pair of 2D chiral perovskite Rashba ferroelectric semiconductors is reported. The fabricated single‐crystal device responds to circularly polarized light (CPL) under 430 nm with an anisotropy factor of 0.20 for the left‐ and right‐CPL differentiation, about two times of reported pure chiral counterparts. The enhanced performance is ascribed to the Rashba–Dresselhaus effect with a large Rashba coefficient of 0.93 eV Å.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
An ideal bone repair scaffold is expected to possess superior architectural characteristics to facilitate the adhesion, proliferation, and migration of bone‐repair‐related cells, while excluding ...nonosteogenic cells and fibrous tissues from interfering with normal bone regeneration. Unfortunately, such scaffold material has rarely been reported. Herein, nanocomposite scaffolds with a radially ordered porous structure are presented, manufactured using a modified directional freeze‐casting method, and are promising bone defect repair materials to satisfy this requirement. The prepared nanocomposite scaffolds consist of a natural bio‐macromolecule, chitosan, and bioactive hydroxyapatite nanoparticles derived from porcine cortical bone, demonstrating favorable biocompatibility and biological functions. Both in vitro cell studies and in vivo animal studies reveal the great superiority of the radially oriented porous structure of the scaffolds in guiding bone regeneration, while simultaneously preventing the invasion of surrounding nonosteogenic cells and fibrous tissue, compared to the axially oriented porous structure. This work indicates the distinctive potential of radially oriented porous scaffolds for repairing tabular and lacunar bone defects.
A nanocomposite scaffold with a radially oriented porous structure is engineered via a modified freeze‐casting method. The unique structural feature renders the nanocomposite scaffold with great superiority in guiding the infiltration and migration of bone‐repair‐related cells into the scaffold, while preventing the invasion of surrounding nonosteogenic cells and fibrous tissues from interfering with the normal bone regeneration process.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The relatively low capacity and capacity fade of spinel LiMn2O4 (LMO) limit its application as a cathode material for lithium‐ion batteries. Extending the potential window of LMO below 3 V to access ...double capacity would be fantastic but hard to be realized, as it will lead to fast capacity loss due to the serious Jahn–Teller distortion. Here using experiments combined with extensive ab initio calculations, it is proved that there is a cooperative effect among individual Jahn–Teller distortions of Mn3+O6 octahedrons in LMO, named as cooperative Jahn–Teller distortion (CJTD) in the text, which is the difficulty to access the capacity beyond one lithium intercalation. It is further proposed that the cationic disordering (excess Li at Mn sites and Li/Mn exchange) can intrinsically suppress the CJTD of Mn3+O6 octahedrons. The cationic disordering can break the symmetry of Mn3+ arrangements to disrupt the correlation of distortions arising from individual JT centers and prevent the Mn3+O bonds distorting along one direction. Interestingly, with the suppressed CJTD, the original octahedral vacancies in spinel LMO are activated and can serve as extra Li‐ion storage sites to access the double capacity with good reversible cycling stability in microsized LMO.
Using experiments and ab initio calculations, the capacity is doubled by suppressing the cooperative Jahn–Teller distortion (CJTD) in spinel LiMn2O4 (LMO). It is further shown that the cationic disordering can intrinsically suppress CJTD because it can break the symmetry of Mn3+ arrangements to disrupt the correlation of distortions arising from individual JT centers and prevent the Mn3+O bonds distorting along one direction.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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•Low-degree-polymerized (DP = 2–6) COS were obtained by enzymatic hydrolysis.•COS treatment obstructed cell proliferation, inhibited metastasis, and induced cell apoptosis.•COS ...treatment increased the levels of autophagy markers.•COS treatment triggered pro-apoptosis autophagy through p53/mTOR signaling pathway.•COS increased the sensitivity of the osteosarcoma cells to cisplatin.
Osteosarcoma is the most common primary sarcoma of bone. The use of Chitooligosaccharide (COS) as a drug carrier is an emerging new strategy for cancer therapy. However, the application of COS in osteosarcoma has not been reported. Here, we investigated the influence of COS on osteosarcoma, and suggested the underlying mechanism. Initially, we obtained COS with a low-degree-polymerized (DP = 2–6) by enzymatic hydrolysis. Using these COS materials, in vitro assays showed that COS elicited the anti-tumor activity against osteosarcoma cells. We found that COS had significant effects on cell growth, metastasis inhibition, apoptosis and autophagy induction, and triggered pro-apoptosis autophagy through p53/mTOR signaling pathway in osteosarcoma cells. In addition, the COS also inhibited tumor growth and metastasis in an osteosarcoma xenograft model in vivo. Finally, we showed that COS could increase sensitivity to chemotherapy of cisplatin in vitro. Thus, we provide experimental evidence to demonstrate that COS has anti-tumor effect on osteosarcoma, and COS can be a new potential therapeutic candidate for the treatment of osteosarcoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The process of nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and shown to be mediated by "Candidatus Methylomirabilis oxyfera" (M. oxyfera). Here, evidence for n-damo ...in three different freshwater wetlands located in southeastern China was obtained using stable isotope measurements, quantitative PCR assays, and 16S rRNA and particulate methane monooxygenase gene clone library analyses. Stable isotope experiments confirmed the occurrence of n-damo in the examined wetlands, and the potential n-damo rates ranged from 0.31 to 5.43 nmol CO2 per gram of dry soil per day at different depths of soil cores. A combined analysis of 16S rRNA and particulate methane monooxygenase genes demonstrated that M. oxyfera-like bacteria were mainly present in the deep soil with a maximum abundance of 3.2 × 107 gene copies per gram of dry soil. It is estimated that ∼0.51 g of CH4 m-2 per year could be linked to the n-damo process in the examined wetlands based on the measured potential n-damo rates. This study presents previously unidentified confirmation that the n-damo process is a previously overlooked microbial methane sink in wetlands, and n-damo has the potential to be a globally important methane sink due to increasing nitrogen pollution.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Hybrid metal halides (HMHs) based phase transition materials have received widespread attention due to their excellent performance and potential applications in energy harvesting, optoelectronics, ...ferroics, and actuators. Nevertheless, effectively regulating the properties of phase transitions is still a thorny problem. In this work, two chiral lead‐free HMHs (R‐3FP)2SbCl5 (1; 3FP=3‐fluoropyrrolidinium) and (R‐3FP)2SbBr5 (2) were synthesized. By replacing the halide ions in the inorganic skeleton, the phase transition temperature of 2 changes with an increase of about 20 K, compared with 1. Meanwhile, both compounds display reversible dielectric switching properties. Through crystal structure analysis and Hirshfeld surface analysis, their phase transitions are ascribed to the disorder of the cations and deformation of the inorganic chains.
This article reports a pair of 1D lead‐free hybrid metal halides: (R‐3FP)2SbCl5 (1; 3FP=3‐fluoropyrrolidinium) and (R‐3FP)2SbBr5 (2) exhibit high temperature triggered structural phase transition and dielectric switching properties. By halogen substitution in the inorganic framework, the dielectric switch temperature of 2 increased about 20 K, compared with 1.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Multiferroics refer to materials with two or more ferroic orders in one phase within a specific temperature range, including ferroelectricity, ferroelasticity, and ferromagnetism which have been ...widely used in sensors, actuators, and memory devices. Among them, hybrid perovskites exhibiting multiferroicity are generally limited to low dimensions (0D–2D). Designing 3D lead‐free perovskite multiferroics remains a challenge due to Goldschmidt's tolerance factor limitation. Here, a multiferroic perovskite (R‐3AP)RbBr3 (1; 3AP = 3‐ammoniopyrrolidinium) is successfully synthesized by introducing homochirality to the 3D ferroelectric (Rac‐3AP)RbBr3, achieving both ferroelasticity and ferroelectricity. Compound 1 undergoes a structure phase transition at 401 K belonging to Aizu notation 432F2(s), which has 12 ferroelectric equivalent polarization directions and 6 polar axes. Furthermore, 1 exhibits reversible second harmonic generation switching effects. Moreover, while the temperature varies, the reversible and rapid changes of ferroelastic domains in 1 are observed using a polarizing microscope, indicating that it is a ferroelastic material. This work provides a practical method for designing and synthesizing molecule‐based multiferroics.
The work reports a 3D perovskite multiferroics (R‐3AP)RbBr3 (1) based on the 3D rubidium‐based ferroelectric (Rac‐3AP)RbBr3 by using the homochirality strategy. Compound 1 exhibits 432F2(s) ferroelectric–ferroelastic phase transition at 401 K. In addition, 1 exhibits a second harmonic generation (SHG) switch and multi‐axis ferroelectricity with a saturation polarization (Ps) value of 1.21 µC·cm−2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Martensitic transformation, usually accompanied by ferroelastic and thermoelastic behaviors, is an interesting and useful mechanical-related property upon external stimuli. For molecular ...crystals, however, martensitic systems to show reversible stimuli-actuation behaviors are still limited because of a lack of designability and frequent crystal collapse due to large stress releases during the transformations. Here, a one-dimensional hybrid perovskite semiconductor (NMEA)PbI
3
(NMEA =
N
-methylethylammonium) was prepared by following a dimensionality reduction design principle. The crystal undergoes reversible ferroelastic and thermoelastic martensitic transformations, which are attributed to weak intermolecular interactions among the chains that easily trigger the interchain shearing movement. The actuation behavior occurring during the phase transition is very close to room temperature and demonstrated to behave as a mechanical actuator for switching. This work provides an effective approach to designing molecular actuators with promising applications in next-generation intelligence devices.
High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is present in almost all cells and regulates the activity of innate immune responses in both intracellular and extracellular ...settings. Current evidence suggests that HMGB1 plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response, immune reactions, cell migration, aging, and cell death. Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs in hosts in response to microbial infections with a proven or suspected infectious etiology and is the leading cause of death in intensive care units worldwide, particularly in the aging population. Dysregulated systemic inflammation is a classic characteristic of sepsis, and suppression of HMGB1 may ameliorate inflammation and improve patient outcomes. Here, we focus on the latest breakthroughs regarding the roles of HMGB1 in sepsis and sepsis-related organ injury, the ways by which HMGB1 are released, and the signaling pathways and therapeutics associated with HMGB1. This review highlights recent advances related to HMGB1: the regulation of HMBG1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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