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"Liu, Long"
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Microbial response to acid stress: mechanisms and applications
Microorganisms encounter acid stress during multiple bioprocesses. Microbial species have therefore developed a variety of resistance mechanisms. The damage caused by acidic environments is mitigated through the maintenance of pH homeostasis, cell membrane integrity and fluidity, metabolic regulation, and macromolecule repair. The acid tolerance mechanisms can be used to protect probiotics against gastric acids during the process of food intake, and can enhance the biosynthesis of organic acids. The combination of systems and synthetic biology technologies offers new and wide prospects for the industrial applications of microbial acid tolerance mechanisms. In this review, we summarize acid stress response mechanisms of microbial cells, illustrate the application of microbial acid tolerance in industry, and prospect the introduction of systems and synthetic biology to further explore the acid tolerance mechanisms and construct a microbial cell factory for valuable chemicals.
Journal Article
Asymmetric magnetization switching and programmable complete Boolean logic enabled by long-range intralayer Dzyaloshinskii-Moriya interaction
After decades of efforts, some fundamental physics for electrical switching of magnetization is still missing. Here, we report the discovery of the long-range intralayer Dzyaloshinskii-Moriya interaction (DMI) effect, which is the chiral coupling of orthogonal magnetic domains within the same magnetic layer via the mediation of an adjacent heavy metal layer. The effective magnetic field of the long-range intralayer DMI on the perpendicular magnetization is out-of-plane and varies with the interfacial DMI constant, the applied in-plane magnetic fields, and the magnetic anisotropy distribution. Striking consequences of the effect include asymmetric current/field switching of perpendicular magnetization, hysteresis loop shift of perpendicular magnetization in the absence of in-plane direct current, and sharp in-plane magnetic field switching of perpendicular magnetization. Utilizing the intralayer DMI, we demonstrate programable, complete Boolean logic operations within a single spin-orbit torque device. These results will stimulate investigation of the long-range intralayer DMI effect in a variety of spintronic devices.
The authors find a magnetization switching mechanism and the long-range intralayer Dzyaloshinskii-Moriya interaction effect, which enables asymmetric magnetization switching and complete Boolean logic operations.
Journal Article
Investigation of free surface effect on the cavity expansion and contraction in high-speed water entry
The evolution of the water-entry cavity affects the impact load and the motion of the body. This paper adopts the Eulerian finite element method for multiphase flow for simulations of the high-speed water-entry process. The accuracy and convergence of the numerical method are verified by comparing it with the experimental data and the results of the transient cavity dynamics theory. Based on the results, the representative characteristics of the cavity are discussed from the perspective of the cavity cross-section. It is found that the asymmetry of the cavity expansion and contraction durations is related to the motion of the free surface and the closure of the cavity. The uplift of the free surface suppresses cavity expansion, while the jet generated from free surface closure accelerates cavity contraction. The duration of the contraction of the cavity near the free surface is shorter than the expansion duration due to the change in the velocity distribution caused by the free surface motion. The necking phenomenon during deep closure leads to an increase in the internal pressure of the cavity, prolonging cavity contraction near the deep closure area. This work provides new insights into the cavity dynamics in high-speed water entry.
Journal Article
Superconductivity above 100 K in single-layer FeSe films on doped SrTiO3
Monolayer iron selenide grown on SrTiO
3
has recently gained attention due to suggestive evidence it superconducts at high temperature.
In situ
electrical transport measurements now reveal a transition temperature above 100 K.
Recent experiments on FeSe films grown on SrTiO
3
(STO) suggest that interface effects can be used as a means to reach superconducting critical temperatures (
T
c
) of up to 80 K (ref.
1
). This is nearly ten times the
T
c
of bulk FeSe and higher than the record value of 56 K for known bulk Fe-based superconductors
2
. Together with recent studies of superconductivity at oxide heterostructure interfaces
3
,
4
,
5
,
6
, these results rekindle the long-standing idea that electron pairing at interfaces between two different materials can be tailored to achieve high-temperature superconductivity
7
,
8
,
9
,
10
,
11
,
12
. Subsequent angle-resolved photoemission spectroscopy measurements of the FeSe/STO system revealed an electronic structure distinct from bulk FeSe (refs
13
,
14
), with an energy gap vanishing at around 65 K. However,
ex situ
electrical transport measurements
1
,
15
have so far detected zero resistance—the key experimental signature of superconductivity—only below 30 K. Here, we report the observation of superconductivity with
T
c
above 100 K in the FeSe/STO system by means of
in situ
four-point probe electrical transport measurements. This finding confirms FeSe/STO as an ideal material for studying high-
T
c
superconductivity.
Journal Article
Cytomembrane nanovaccines show therapeutic effects by mimicking tumor cells and antigen presenting cells
Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.
Cancer vaccines often fail to generate clinically relevant effects. Here, the authors generate a nanosized cytomembrane vaccine based on fusion between dendritic cells and cancer cells, and show them to activate anti-tumor immune responses via their antigen presenting and T-cell activating functions.
Journal Article
Mannose antagonizes GSDME-mediated pyroptosis through AMPK activated by metabolite GlcNAc-6P
Pyroptosis is a type of regulated cell death executed by gasdermin family members. However, how gasdermin-mediated pyroptosis is negatively regulated remains unclear. Here, we demonstrate that mannose, a hexose, inhibits GSDME-mediated pyroptosis by activating AMP-activated protein kinase (AMPK). Mechanistically, mannose metabolism in the hexosamine biosynthetic pathway increases levels of the metabolite
N
-acetylglucosamine-6-phosphate (GlcNAc-6P), which binds AMPK to facilitate AMPK phosphorylation by LKB1. Activated AMPK then phosphorylates GSDME at Thr6, which leads to blockade of caspase-3-induced GSDME cleavage, thereby repressing pyroptosis. The regulatory role of AMPK-mediated GSDME phosphorylation was further confirmed in AMPK knockout and GSDME
T6E
or GSDME
T6A
knock-in mice. In mouse primary cancer models, mannose administration suppressed pyroptosis in small intestine and kidney to alleviate cisplatin- or oxaliplatin-induced tissue toxicity without impairing antitumor effects. The protective effect of mannose was also verified in a small group of patients with gastrointestinal cancer who received normal chemotherapy. Our study reveals a novel mechanism whereby mannose antagonizes GSDME-mediated pyroptosis through GlcNAc-6P-mediated activation of AMPK, and suggests the utility of mannose supplementation in alleviating chemotherapy-induced side effects in clinic applications.
Journal Article
Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer
Long noncoding RNAs (lncRNAs) are recently implicated in modifying immunology in colorectal cancer (CRC). Nevertheless, the clinical significance of immune-related lncRNAs remains largely unexplored. In this study, we develope a machine learning-based integrative procedure for constructing a consensus immune-related lncRNA signature (IRLS). IRLS is an independent risk factor for overall survival and displays stable and powerful performance, but only demonstrates limited predictive value for relapse-free survival. Additionally, IRLS possesses distinctly superior accuracy than traditional clinical variables, molecular features, and 109 published signatures. Besides, the high-risk group is sensitive to fluorouracil-based adjuvant chemotherapy, while the low-risk group benefits more from bevacizumab. Notably, the low-risk group displays abundant lymphocyte infiltration, high expression of CD8A and PD-L1, and a response to pembrolizumab. Taken together, IRLS could serve as a robust and promising tool to improve clinical outcomes for individual CRC patients.
Identification of long non-coding RNA (lncRNA) signatures could be used to improve cancer clinical outcome. Here the authors developed a machine learning-based integrative procedure to construct a consensus immune-related lncRNA signature to predict prognosis, recurrence and treatment benefits in colorectal cancer.
Journal Article
Investigation of hydrodynamics of water impact and tail slamming of high-speed water entry with a novel immersed boundary method
High-speed water entry is a transient hydrodynamic process that is accompanied by strongly compressible flow, free surface splash, cavity evolution and other nonlinear hydrodynamic phenomena. To address these problems, a novel fluid–structure interaction (FSI) scheme based on the immersed boundary method is proposed which is suitable for strongly compressible multiphase flows. In this scheme, considering the multiphase interfaces at the immersed boundary, an improved immersed boundary method for effectively suppressing the non-physical force oscillation is proposed. Additionally, a quaternion-based six degrees of freedom motion system is used to describe rigid body motion, and the multiphase flow Eulerian finite element method is applied as the fluid solver. Using analytical solutions, experimental data and literature data, the accuracy and robustness of the FSI scheme are validated. Finally, the high-speed water entry of the slender body with different noses is investigated, and the hydrodynamic loads including the axial and normal drag forces and the bending moment are extensively discussed. The hydrodynamic load and motion trajectory are determined by the nose configuration. The tail slamming phenomenon is the primary focus, and it is revealed that its formation is primarily related to the pitch moment formed at the stage of crossing the free surface. Tail slamming also causes violent impact loads, especially bending moments, which may cause slender projectiles to break off. Finally, to combine the features of the flat and hemispherical noses, the water entry of the projectile with a truncated hemispherical nose is simulated and discussed.
Journal Article
An immune checkpoint score system for prognostic evaluation and adjuvant chemotherapy selection in gastric cancer
Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISS
GC
) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISS
GC
is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISS
GC
can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.
Expression patterns of immune checkpoints in patients with gastric cancer remain poorly characterized. Here the authors propose an immune scoring system based on the expression of six immunosuppressive ligands to improve the prognostic accuracy in gastric cancer patients and drive the selection of candidates for adjuvant chemotherapy.
Journal Article