Development of central nervous system (CNS) is regulated by both intrinsic and peripheral signals. Previous studies have suggested that environmental factors affect neurological activities under both ...physiological and pathological conditions. Although there is anatomical separation, emerging evidence has indicated the existence of bidirectional interaction between gut microbiota, i.e., (diverse microorganisms colonizing human intestine), and brain. The cross-talk between gut microbiota and brain may have crucial impact during basic neurogenerative processes, in neurodegenerative disorders and tumors of CNS. In this review, we discuss the biological interplay between gut-brain axis, and further explore how this communication may be dysregulated in neurological diseases. Further, we highlight new insights in modification of gut microbiota composition, which may emerge as a promising therapeutic approach to treat CNS disorders.
We examine the cross-sectional variation in the marginal value of corporate cash holdings that arises from differences in corporate financial policy. We begin by providing semi-quantitative ...predictions for the value of an extra dollar of cash depending upon the likely use of that dollar, and derive a set of intuitive hypotheses to test empirically. By examining the variation in excess stock returns over the fiscal year, we find that the marginal value of cash declines with larger cash holdings, higher leverage, better access to capital markets, and as firms choose greater cash distribution via dividends rather than repurchases.
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T （Provenge）, ...ipilimumab （Yervoy, anti-CT- LA-4）, and more recently, the programmed cell death （PD）-I antibody （pembroliznmab, Keytruda）, for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-l-specific T cell receptor （TCR） or CD19-chimeric antigen re- ceptor （CAR）, have shown promising clinical results for patients with metastatic cancer. Current success of cancer immunotherapy is built upon the work of cancer antigens and co-inhibitory signaling molecules identified 20 years ago. Among the large numbers of target antigens, CD19 is the best target for CAR T cell therapy for blood cancer, but CAR-engineered T cell immunotherapy does not yet work in solid cancer. NY-ESO-1 is one of the best targets for TCR-based immunotherapy in solid cancer. Despite the great success of checkpoint blockade therapy, more than 50% of cancer patients fail to respond to blockade therapy. The advent of new technologies such as next-generation sequencing has enhanced our ability to search for new immune targets in onco-immunology and accelerated the de- velopment of immunotherapy with potentially broader coverage of cancer patients. In this review, we will discuss the recent progresses of cancer immunotherapy and novel strategies in the identification of new immune targets and mu- tation-derived antigens （neoantigens） for cancer immunotherapy and immunoprecision medicine.
6G is envisioned to empower wireless communication and computation through the digitalization and connectivity of everything, by establishing a digital representation of the real network environment. ...Mobile edge computing (MEC), as one of the key enabling factors, meets unprecedented challenges during mobile offloading due to the extremely complicated and unpredictable network environment in 6G. The existing works on offloading in MEC mainly ignore the effects of user mobility and the unpredictable MEC environment. In this paper, we present a new vision of Digital Twin Edge Networks (DITEN) where digital twins (DTs) of edge servers estimate edge servers' states and DT of the entire MEC system provides training data for offloading decision. A mobile offloading scheme is proposed in DITEN to minimize the offloading latency under the constraints of accumulated consumed service migration cost during user mobility. The Lyapunov optimization method is leveraged to simplify the long-term migration cost constraint to a multi-objective dynamic optimization problem, which is then solved by <inline-formula><tex-math notation="LaTeX">Actor</tex-math></inline-formula>-<inline-formula><tex-math notation="LaTeX">Critic</tex-math></inline-formula> deep reinforcement learning. Simulations results show that our proposed scheme effectively diminishes the average offloading latency, the offloading failure rate, and the service migration rate, as compared with benchmark schemes, while saving the system cost with DT assistance.
Cerebral ischemia-reperfusion (I-R) is a complex pathological process. Although autophagy can be evoked by ischemia, its involvement in the reperfusion phase after ischemia and its contribution to ...the fate of neurons remains largely unknown. In the present investigation, we found that autophagy was activated in the reperfusion phase, as revealed in both mice with middle cerebral artery occlusion and oxygen-glucose deprived cortical neurons in culture. Interestingly, in contrast to that in permanent ischemia, inhibition of autophagy (by 3-methyladenine, bafilomycin A
1
, Atg7 knockdown or in atg5
−/−
MEF cells) in the reperfusion phase reinforced, rather than reduced, the brain and cell injury induced by I-R. Inhibition of autophagy either with 3-methyladenine or Atg7 knockdown enhanced the I-R-induced release of cytochrome c and the downstream activation of apoptosis. Moreover, MitoTracker Red-labeled neuronal mitochondria increasingly overlapped with GFP-LC3-labeled autophagosomes during reperfusion, suggesting the presence of mitophagy. The mitochondrial clearance in I-R was reversed by 3-methyladenine and Atg7 silencing, further suggesting that mitophagy underlies the neuroprotection by autophagy. In support, administration of the mitophagy inhibitor mdivi-1 in the reperfusion phase aggravated the ischemia-induced neuronal injury both in vivo and in vitro. PARK2 translocated to mitochondria during reperfusion and Park2 knockdown aggravated ischemia-induced neuronal cell death. In conclusion, the results indicated that autophagy plays different roles in cerebral ischemia and subsequent reperfusion. The protective role of autophagy during reperfusion may be attributable to mitophagy-related mitochondrial clearance and inhibition of downstream apoptosis. PARK2 may be involved in the mitophagy process.
Abstract
The design of highly stable, selective and efficient electrocatalysts for CO
2
reduction reaction is desirable while largely unmet. In this work, a series of precisely designed ...polyoxometalate-metalloporphyrin organic frameworks are developed. Noted that the integration of {ε-PMo
8
V
Mo
4
VI
O
40
Zn
4
} cluster and metalloporphyrin endows these polyoxometalate-metalloporphyrin organic frameworks greatly advantages in terms of electron collecting and donating, electron migration and electrocatalytic active component in the CO
2
reduction reaction. Thus-obtained catalysts finally present excellent performances and the mechanisms of catalysis processes are discussed and revealed by density functional theory calculations. Most importantly, Co-PMOF exhibits remarkable faradaic efficiency ( > 94%) over a wide potential range (−0.8 to −1.0 V). Its best faradaic efficiency can reach up to 99% (highest in reported metal-organic frameworks) and it exhibits a high turnover frequency of 1656 h
−1
and excellent catalysis stability ( > 36 h).
Innate immunity is the first defense system against invading pathogens. Toll-like receptors (TLRs) are well-defined pattern recognition receptors responsible for pathogen recognition and induction of ...innate immune responses. Since their discovery, TLRs have revolutionized the field of immunology by filling the gap between the initial recognition of pathogens by innate immune cells and the activation of the adaptive immune response. TLRs critically link innate immunity to adaptive immunity by regulating the activation of antigen-presenting cells and key cytokines. Furthermore, recent studies also have shown that TLR signaling can directly regulate the T cell activation, growth, differentiation, development, and function under diverse physiological conditions. This review provides an overview of TLR signaling pathways and their regulators and discusses how TLR signaling, directly and indirectly, regulates cell-mediated immunity. In addition, we also discuss how TLR signaling is critically important in the host's defense against infectious diseases, autoimmune diseases, and cancer.
In the context of carbon neutrality, the paper uses Super Efficiency Data Envelopment Analysis (DEA) to evaluate the level of regional energy efficiency in China, then selects Theil index to analyze ...the difference and change of regional energy efficiency. The results are as follows: (1) The overall level of energy efficiency in China is relatively low, and the average efficiency level from 2007 to 2019 is 0.568. Among them, Beijing is the highest, at 1.261, and Xinjiang is the lowest, at only 0.205. The energy efficiency of the eastern region is the highest in China: the average is 0.812. The central region is lower than the national average, with the value of 0.534. The lowest energy efficiency is in the western region, which is only 0.349. It can be seen that there are significant differences in regional energy efficiency, and from west to east has increased. (2) The Theil coefficient increased before 2012 and began to show a downward trend in 2013. The difference in the eastern region maintained the smallest downward trend among the three regions. The difference in the central region fluctuated and increased before 2011, and dropped sharply after 2012. In the western region, the coefficient is relatively stable and has not changed significantly. (3) Differences within and between regions in China show an overall downward trend. From the perspective of contribution rate, the difference between regions contributes the most to the overall difference.
•We use super-efficiency DEA to measure China's regional energy efficiency.•We use Theil Index to illustrate regional differences in energy efficiency.•We have reached a conclusion that can provide a theoretical reference for policy making.•We compared the magnitude and trend of energy efficiency in various regions.
The RIG‐I‐like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that ...leucine‐rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR‐mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15‐associated RIG‐I to promote interaction between RIG‐I and the autophagic cargo receptor p62 and to mediate RIG‐I degradation via selective autophagy. Depletion of either LRRC25 or ISG15 abrogates RIG‐I‐p62 interaction as well as the autophagic degradation of RIG‐I. Collectively, our findings identify a previously unrecognized role of LRRC25 in type I IFN signaling activation by which LRRC25 acts as a secondary receptor to assist RIG‐I delivery to autophagosomes for degradation in a p62‐dependent manner.
Synopsis
Upon RNA virus infection, LRRC25 recognizes ISG15‐associated immune receptor RIG‐I and facilitates its degradation via p62‐mediated selective autophagy, thereby limiting RIG‐I‐dependent type I interferon signaling.
LRRC25 negatively regulates type I interferon signaling upon RNA virus infection.
LRRC25 promotes autophagic degradation of RIG‐I in a p62‐dependent manner.
ISG15 serves as a signal for LRRC25‐mediated RIG‐I degradation.
The interaction between RIG‐I, ISG15 and LRRC25 forms a negative feedback loop to avoid prolonged immune activation upon viral infection.
Upon RNA virus infection, LRRC25 recognizes ISG15‐associated immune receptor RIG‐I and facilitates its degradation via p62‐mediated selective autophagy, thereby limiting RIG‐I‐dependent type I interferon signaling.
This study aims at developing an effective method to modify hydrophobic polyvinylidene fluoride (PVDF) membranes for membrane distillation (MD) which is tolerant to salty feed solution containing ...mineral oil. A novel approach was explored to obtain a highly hydrophilic membrane surface via plasma induced grafting of polyethylene glycol (PEG) and subsequent TiO2 particles deposition onto the membrane surface. The mechanism of oil affinity onto a membrane surface was quantitatively investigated by the extended Derjaguin–Landau–Verwey–Overbeek (XDLVO) theory. A series of characterizations were conducted for the virgin and modified membranes. Membrane distillation tests for synthetic seawater containing 0.01wt% of mineral oil were also performed to investigate the influences of membrane hydrophobicity, membrane surface structure, pH value of the feed solution and hydrodynamic conditions on oil fouling behavior.
The SEM and FTIR measurements confirmed the presence of PEG and TiO2 particles on the PVDF membrane substrate. The hydrophilically modified PVDF-PT membrane exhibits a positive interfacial free energy with oil in the feed, indicating the TiO2 deposition effectively improve the anti-fouling property of PVDF-P membrane and PVDF membrane. It was also found that the PVDF-PT membrane presents a stable water flux over 24h of operation without fouling and wetting due to combined effects of enhanced surface hydrophilicity and reduced membrane pore sizes. In addition, the pH value of the feed solution plays an important role in oil fouling. More severe fouling can be observed at the pH which made the membrane surface and oil droplets carry opposite charges. Moreover, a higher flow velocity enhances the shear force exerted on the oil droplets, thus leading to less oil present on the membrane surface and less oil fouling of the membrane.
•A novel approach was explored to obtain a hydrophilic surface for PVDF membrane.•The modified membrane was used for membrane distillation of feed containing oils.•The mechanism of oil affinity onto a membrane surface was studied by the XDLVO theory.•The modified membrane presents a stable water flux over 24h of operation without oil fouling.•The pH value of the feed solution plays an important role in oil fouling.
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