Principle has it that even the most advanced super‐resolution microscope would be futile in providing biological insight into subcellular matrices without well‐designed fluorescent tags/probes. ...Developments in biology have increasingly been boosted by advances of chemistry, with one prominent example being small‐molecule fluorescent probes that not only allow cellular‐level imaging, but also subcellular imaging. A majority, if not all, of the chemical/biological events take place inside cellular organelles, and researchers have been shifting their attention towards these substructures with the help of fluorescence techniques. This Review summarizes the existing fluorescent probes that target chemical/biological events within a single organelle. More importantly, organelle‐anchoring strategies are described and emphasized to inspire the design of new generations of fluorescent probes, before concluding with future prospects on the possible further development of chemical biology.
See below the surface: Fluorescent probes that target individual organelles and elucidate their functionalities are systematically summarized in this Review. The design strategy towards organelle targeting will shed light on basic studies of cell biology.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
AIM To investigate the clinical significance of preoperative systemic immune-inflammation index(SII) in patients with colorectal cancer(CRC). METHODS A retrospective analysis of 1383 cases with CRC ...was performed following radical surgery. SII was calculated with the formula SII =(P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR) in patients with CRC.RESULTS The optimal cut-off point for SII was defined as 340. The overall survival(OS) and disease-free survival(DFS) were better in patients with low NLR, PLR, and SII(P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics(ROC) curve for SII(0.707) was larger than those for NLR(0.602) and PLR(0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.
The strong force which binds hadrons is described by the theory of quantum chromodynamics (QCD). Determining the character and manifestations of QCD is one of the most important and challenging ...outstanding issues necessary for a comprehensive understanding of the structure of hadrons. Within the context of the QCD parton picture, the parton distribution functions (PDFs) have been remarkably successful in describing a wide variety of processes. However, these PDFs have generally been confined to the description of collinear partons within the hadron. New experiments and facilities provide the opportunity to additionally explore the transverse structure of hadrons which is described by generalized parton distributions (GPDs) and transverse-momentum-dependent parton distribution functions (TMD PDFs). In our previous report Lin et al. (2018), we compared and contrasted the two main approaches used to determine the collinear PDFs: the first based on perturbative QCD factorization theorems, and the second based on lattice-QCD calculations. In the present report, we provide an update of recent progress on the collinear PDFs, and also expand the scope to encompass the generalized PDFs (GPDs and TMD PDFs). We review the current state of the various calculations, and consider what new data might be available in the near future. We also examine how a shared effort can foster dialog between the PDF and lattice-QCD communities, and yield improvements for these generalized PDFs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of ...the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
Nuclear factor-E2-related factor 2 (Nrf2) is a key transcription factor known to be involved in maintaining cell redox balance and signal transduction and plays central role in reducing intracellular ...oxidative stress damage, delaying cell senescence and preventing age-related diseases. However, it has been shown that the level of Nrf2 decreases with age and that the silencing of the
Nrf2
gene is associated with the induction of premature senescence. Therefore, a plethora of researchers have focused on elucidating the regulatory mechanism of Nrf2 in the prevention of cell senescence. This complex regulatory mechanism of Nrf2 in the cell senescence process involves coordinated regulation of multiple signaling molecules. After summarizing the function of Nrf2 and its relationship with cell senescence pathway, this review focuses on the recent advances and progress made in elucidating the regulatory mechanism of Nrf2 in the cell senescence process. Additionally, the information collected here may provide insights for further research on Nrf2, in particular, on its regulatory mechanism in the cell senescence process.
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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
In applying large-momentum effective theory, renormalization of the Euclidean correlators in lattice regularization is a challenge due to linear divergences in the self-energy of Wilson lines. Based ...on lattice QCD matrix elements of the quasi-PDF operator at lattice spacing a=0.03fm ∼ 0.12fm with clover and overlap valence quarks on staggered and domain-wall sea, we design a strategy to disentangle the divergent renormalization factors from finite physics matrix elements, which can be matched to a continuum scheme at short distance such as dimensional regularization and minimal subtraction. Our results indicate that the renormalization factors are universal in the hadron state matrix elements. Moreover, the physical matrix elements appear independent of the valence fermion formulations. These conclusions remain valid even with HYP smearing which reduces the statistical errors albeit reducing control of the renormalization procedure. Moreover, we find a large non-perturbative effect in the popular RI/MOM and ratio renormalization scheme, suggesting favor of the hybrid renormalization procedure proposed recently.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigate the transverse momentum dependent parton distributions (TMDs) in the parton quasidistributions framework. The longstanding hurdle of the so-called pinch pole singularity from the ...spacelike gauge links in the TMD definitions can be resolved by the finite length of the gauge link along the hadron moving direction. In addition, with the soft factor subtraction, the quasi-TMD is free of linear divergence. We further demonstrate that the energy evolution equation of the quasi-TMD a.k.a. the Collins-Soper evolution, only depends on the hadron momentum. This leads to a clear matching between the quasi-TMD and the standard TMDs.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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•MXene-derived hierarchical titanate nanostructures (HTNs) were prepared by a mild in situ chemical conversion method.•HTNs can efficiently remove Eu(III) with large adsorption ...capacities (more than 200 mg/g).•The ion-exchange behavior of Eu(III) with Na+ or K+ was confirmed.•The exchanged Eu(III) ions were confined in the nanoscale interlayers of HTNs and then immobilized.
Developing versatile materials that rapidly and efficiently adsorb radionuclides is an urgent objective for environmental remediation in response to radioactive contamination. Herein, we report the preparation of hierarchical titanate nanostructures (HTNs) by a in situ chemical conversion strategy using a two-dimensional MXene crystal precursor. These HTNs are very stable and can efficiently remove Eu(III) with large sorption capacities, owing to well-maintained layered structures and abundantly exchangeable guest cations. The replacement of sodium or potassium ions with Eu(III) in HTN interlayers has been confirmed by X-ray diffraction (XRD), photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). The extended X-ray sorption fine structure (EXAFS) results, in combination with density functional theory (DFT) calculations, further indicate that the sequestration of Eu(III) is realized by forming inner-sphere surface complexes in nano-confined space, evidenced by the decrease of Eu-O distances (R) and coordination numbers (N). The finding of the inner-sphere complexation induced by Ti−O/Ti−OH coordination and confinement effect provides new insights into the interaction mechanism between radionuclides and titanates. Given their extraordinary sorption capacity and facile synthesis under mild conditions, these HTNs are promising candidates for the efficient removal of trivalent lanthanides and actinides from aqueous solutions during the cleanup of radioactive pollution in the environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients ...consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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