Periodontal diseases like gingivitis and periodontitis are primarily caused by dental plaque. Several antiplaque and anti-microbial agents have been successfully incorporated into toothpastes and ...mouthwashes to control plaque biofilms and to prevent and treat gingivitis and periodontitis. The aim of this article was to review recent developments in the antiplaque, anti-gingivitis, and anti-periodontitis properties of some common compounds in toothpastes and mouthwashes by evaluating basic and clinical studies, especially the ones published in the past five years. The common active ingredients in toothpastes and mouthwashes included in this review are chlorhexidine, cetylpyridinium chloride, sodium fluoride, stannous fluoride, stannous chloride, zinc oxide, zinc chloride, and two herbs-licorice and curcumin. We believe this comprehensive review will provide useful up-to-date information for dental care professionals and the general public regarding the major oral care products on the market that are in daily use.
Alzheimer's disease (AD) is one of the most common aging-related progressive neurodegenerative disorders, and can result in great suffering for a large portion of the aged population. Although the ...pathogenesis of AD is being elucidated, the exact mechanisms are still unclear, thereby impeding the development of effective drugs, supplements, and other interventional strategies for AD. In recent years, impaired autophagy associated with microRNA (miRNA) dysfunction has been reported to be involved in aging and aging-related neurodegenerative diseases. Therefore, miRNA-mediated regulation for the functional status of autophagy may become one of the potent interventional strategies for AD. Mounting evidence from in vivo AD models has demonstrated that physical activity can exert a neuroprotective role in AD. In addition, autophagy is strictly regulated by the mTOR signaling pathway. In this article, the regulation of the functional status of autophagy through the mTOR signaling pathway during physical activity is systematically discussed for the prevention and treatment of AD. This concept will be beneficial to developing novel and effective targets that can create a direct link between pharmacological intervention and AD in the future.
Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including ...immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.
Display omitted
•ScRNA-seq reveals a distinct immune ecosystem in early-relapse HCC•Decreased Tregs, increased DCs, and CD8+ T cells were observed in early-relapse HCC•CD8+ T cells have an innate-like, low cytotoxic, and low clonal expansion phenotype•Recurrent malignant cells mediate the compromised antitumor immune response
Single-cell analysis of primary and relapsed hepatocellular carcinoma tumors from patients reveal innate-like CD8+ T cells with low cytotoxicity and clonal expansion in the latter that may explain the compromised antitumor immunity and poor prognosis associated with liver cancer.
The S. cerevisiae plasma membrane H
-ATPase, Pma1, is a P3A-type ATPase and the primary protein component of the membrane compartment of Pma1 (MCP). Like other plasma membrane H
-ATPases, Pma1 ...assembles and functions as a hexamer, a property unique to this subfamily among the larger family of P-type ATPases. It has been unclear how Pma1 organizes the yeast membrane into MCP microdomains, or why it is that Pma1 needs to assemble into a hexamer to establish the membrane electrochemical proton gradient. Here we report a high-resolution cryo-EM study of native Pma1 hexamers embedded in endogenous lipids. Remarkably, we found that the Pma1 hexamer encircles a liquid-crystalline membrane domain composed of 57 ordered lipid molecules. The Pma1-encircled lipid patch structure likely serves as the building block of the MCP. At pH 7.4, the carboxyl-terminal regulatory α-helix binds to the phosphorylation domains of two neighboring Pma1 subunits, locking the hexamer in the autoinhibited state. The regulatory helix becomes disordered at lower pH, leading to activation of the Pma1 hexamer. The activation process is accompanied by a 6.7 Å downward shift and a 40° rotation of transmembrane helices 1 and 2 that line the proton translocation path. The conformational changes have enabled us to propose a detailed mechanism for ATP-hydrolysis-driven proton pumping across the plasma membrane. Our structures will facilitate the development of antifungal drugs that target this essential protein.
T-cell exhaustion refers to a state of T-cell dysfunction commonly observed in chronic infections and cancer. Immune checkpoint molecules blockading using PD-1 and TIM-3 antibodies have shown ...promising results in reversing exhaustion, but this approach has several limitations. The treatment of T-cell exhaustion is still facing great challenges, making it imperative to explore new therapeutic strategies. With the development of nanotechnology, nanoparticles have successfully been applied as drug carriers and delivery systems in the treatment of cancer and infectious diseases. Furthermore, nanoparticle-based immunotherapy has emerged as a crucial approach to reverse exhaustion. Here, we have compiled the latest advances in T-cell exhaustion, with a particular focus on the characteristics of exhaustion that can be targeted. Additionally, the emerging nanoparticle-based delivery systems were also reviewed. Moreover, we have discussed, in detail, nanoparticle-based immunotherapies that aim to reverse exhaustion, including targeting immune checkpoint blockades, remodeling the tumor microenvironment, and targeting the metabolism of exhausted T cells, etc. These data could aid in comprehending the immunopathogenesis of exhaustion and accomplishing the objective of preventing and treating chronic diseases or cancer.
The nano metallic-based material has received the particular attention of scientists in H2 storage. Herein, an efficient air-stable nano metallic magnesium (Mg)-Polymethyl methacrylate (PMMA) system, ...in which methyl magnesium chloride (MeMgCl) as organic Mg precursor is in-situ reduced to metallic Mg particles (Mg NPs) by lithium naphthalene (Li-naphthalene) in soluble PMMA/THF system, exhibits an excellent H2 storage performance and do not require harsh operation condition. In order to form well-distributed Mg NPs (co. 5 nm) in PMMA gel framework, it is an important procedure to mix Mg ion and Li-naphthalene completely, as well the restriction effect of polymer molecular chain. The synthesized mechanism of nanocomposite and the optimal reaction conditions were ascertained by designing a series of experiments. Notably, PMMA can not confined the size of metallic Mg by blending method, and the mixed β/γ-Mg presents nearly no ability to adsorb hydrogen. Here, the air stable Mg NPs is in-situ reduced in PMMA can be reacted with H2, and O2 and H2O molecules can not be infiltrated into PMMA. The correlation between the size of Mg NPs, the amount of PMMA and hydrogen storage performance for the PMMA-Mg NPs composite (PMC) is studied. We have found that hydrogen storage capacity of PMC could be enhanced as decreasing the size of Mg NPs by adjusting the amount of PMMA. The Mg NPs in PMMA might release the higher amount of H2 at below 300 °C with a rapid absorption/desorption kinetics than the reported material in literature. The obtained nanocomposite are able to deliver dense hydrogen in demanding environments.
•Organic Mg was in-situ reduced to well-dispersed metallic Mg NPs in porous PMMA.•PMMA played an important role on the formation of Mg nanocrystal.•The hydrogen storage capacity could be enhanced as decreasing the size of NPs.•Mg NPs were completely dependent on PMMA for air stability more than 30 days.•The nanocomposite has a wide operating temperature range and excellent performance.
Highlights
A novel interface design of producing interfacial voids is proposed for CsPbIBr
2
perovskite solar cells (PSCs), which is free of any extra modification layer.
Interfacial voids improve ...absorption of CsPbIBr
2
film, reduce saturation current density, and enlarge built-in potential of the PSCs.
The PSC yields a superior efficiency of 10.20% with a record-high photovoltage of 1.338 V.
A novel interface design is proposed for carbon-based, all-inorganic CsPbIBr
2
perovskite solar cells (PSCs) by introducing interfacial voids between TiO
2
electron transport layer and CsPbIBr
2
absorber. Compared with the general interfacial engineering strategies, this design exempts any extra modification layer in final PSC. More importantly, the interfacial voids produced by thermal decomposition of 2-phenylethylammonium iodide trigger three beneficial effects. First, they promote the light scattering in CsPbIBr
2
film and thereby boost absorption ability of the resulting CsPbIBr
2
PSCs. Second, they suppress recombination of charge carriers and thus reduce dark saturation current density (
J
0
) of the PSCs. Third, interfacial voids enlarge built-in potential (
V
bi
) of the PSCs, awarding increased driving force for dissociating photo-generated charge carriers. Consequently, the PSC yields the optimized efficiency of 10.20% coupled with an open-circuit voltage (
V
oc
) of 1.338 V. The
V
oc
achieved herein represents the best value among CsPbIBr
2
PSCs reported earlier. Meanwhile, the non-encapsulated PSCs exhibit an excellent stability against light, thermal, and humidity stresses, since it remains ~ 97% or ~ 94% of its initial efficiency after being heated at 85 °C for 12 h or stored in ambient atmosphere with relative humidity of 30–40% for 60 days, respectively.
With Remdesivir being approved by FDA as a drug for the treatment of Corona Virus Disease 2019 (COVID-19), nucleoside drugs have once again received widespread attention in the medical community. ...Herein, we summarized modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides, and their bioactivity rules. 2′-“Ara”-substituted by –F or –CN group, and 3′-“ara” substituted by acetylenyl group can greatly influence their anti-tumor activities. Dideoxy dehydrogenation of 2′,3′-sites can enhance antiviral efficiencies. Acyclic nucleosides and L-type nucleosides mainly represented antiviral capabilities. 5-F Substituted uracil analogues exihibit anti-tumor effects, and the substrates substituted by –I, –CF3, bromovinyl group usually show antiviral activities. The sugar coupled with 1-N of triazolid usually displays anti-tumor efficiencies, while the sugar coupled with 2-N of triazolid mainly represents antiviral activities. The nucleoside analogues assembled by cholesterol, polyethylene glycol, fatty acid and phospholipid would improve their bioavailabilities and bioactivities, or reduce their toxicities.
This review mainly summarize the effects of structure modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides on the antiviral/anti-tumor activity. Display omitted
•Nucleosides scaffold feature were summarized.•-F, –CN and Acetylenyl substituent are favorable for their anti-tumor activity.•Dideoxy dehydrogenation of 2′, 3′-sites could enhance antiviral activity.•Acyclic and L-type nucleosides mainly represented antiviral activity.•C–N Glycosidic bond would affect activity of triazolid nucleoside analogues.
Black carbon (BC) is one of the most important climate pollutants due to its strong positive radiative forcing on the climate system. However, long-term observation of BC is inadequate, and its trend ...remains unknown at both regional and global scales. In this study, using quality-controlled ground-based black carbon observations at 34 stations, the climatology of BC mass concentration during 2006–2017 in China was evaluated for the first time. The national annual average BC concentration was 3534 ng/m
3
, and the concentration exhibited large spatial variation, from a minimum of 272 ng/m
3
to a maximum of 10,228 ng/m
3
. Significant seasonal variations were also observed. The peak BC concentration (4763 ± 3380 ng/m
3
) occurred during winter, followed by autumn (3752 ± 2623 ng/m
3
) and spring (3022 ± 2121 ng/m
3
). The lowest BC concentration occurred in summer (2583 ± 1780 ng/m
3
) due to decreased emissions, wet removal by precipitation, and diffusion induced by strong turbulent mixing. Additionally, the diurnal variability at about 80% of the stations in China showed a bimodal pattern. Daily maximum BC concentration during 0000–0600, 0600–1200, 1200–1800, and 1800–2400 local solar time accounted for 0, 41, 12, and 47% of the total, respectively. In particular, the diurnal and monthly variations in BC were explicitly analyzed at seven baseline stations. Surface BC has exhibited a significant declining trend across China, which is partly corroborated by the increase in single scattering albedo during the same period in Beijing. Also, the BC radiative forcing at the top of the atmosphere has declined at the rate of − 0.9 ± 0.1 W/m
2
/10 years over China, which differs from with the trend in the simulation using the CMIP6 emission. The decreasing BC has led to a larger reduction rate in atmospheric heating (− 3.7 ± 0.4 W/m
2
/10 years), implying a less stable atmosphere that facilitates the dispersion of air pollutants. The declining BC burden implies for both the air quality in China and regional climate change.
Autophagy is a major catabolic pathway in eukaryotes associated with a broad spectrum of human diseases. In autophagy, autophagosomes carrying cellular cargoes fuse with lysosomes for degradation. ...However, the molecular mechanism underlying autophagosome maturation is largely unknown. Here we report that TECPR1 binds to the Atg12-Atg5 conjugate and phosphatidylinositol 3-phosphate (PtdIns3P) to promote autophagosome-lysosome fusion. TECPR1 and Atg16 form mutually exclusive complexes with the Atg12-Atg5 conjugate, and TECPR1 binds PtdIns(3)P upon association with the Atg12-Atg5 conjugate. Strikingly, TECPR1 localizes to and recruits Atg5 to autolysosome membrane. Consequently, elimination of TECPR1 leads to accumulation of autophagosomes and blocks autophagic degradation of LC3-II and p62. Finally, autophagosome maturation marked by GFP-mRFP-LC3 is defective in TECPR1-deficient cells. Thus, we propose that the concerted interactions among TECPR1, Atg12-Atg5, and PtdIns(3)P provide the fusion specificity between autophagosomes and lysosomes and that the assembly of this complex initiates the autophagosome maturation process.
Display omitted
► TECPR1 and Atg16 form two mutually exclusive complexes with Atg12-Atg5 ► TECPR1 localizes to and recruits Atg5 to autolysosomes ► Atg12-Atg5-TECPR1 complex binds to PtdIns(3)P specifically ► TECPR1 is required for autophagosome maturation
PDF
