Tumor necrosis factor (TNF) superfamily member 11 (TNFSF11, also known as RANKL) regulates multiple physiological or pathological functions, including osteoclast differentiation and osteoporosis. ...TNFRSF11A (also called RANK) is considered to be the sole receptor for RANKL. Herein we report that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL. LGR4 competes with RANK to bind RANKL and suppresses canonical RANK signaling during osteoclast differentiation. RANKL binding to LGR4 activates the Gαq and GSK3-β signaling pathway, an action that suppresses the expression and activity of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (NFATC1) during osteoclastogenesis. Both whole-body (Lgr4(-/-)) and monocyte conditional knockout mice of Lgr4 (Lgr4 CKO) exhibit osteoclast hyperactivation (including elevation of osteoclast number, surface area, and size) and increased bone erosion. The soluble LGR4 extracellular domain (ECD) binds RANKL and inhibits osteoclast differentiation in vivo. Moreover, LGR4-ECD therapeutically abrogated RANKL-induced bone loss in three mouse models of osteoporosis. Therefore, LGR4 acts as a second RANKL receptor that negatively regulates osteoclast differentiation and bone resorption.
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IJS, NUK, SBMB, UL, UM, UPUK
A Pd/Y heterobimetallic MOF (denoted as Pd/Y-MOF) catalyst is synthesized by coordination of Pd(II) and Y(III) with 2,2′-bipyridine-5,5′-dicarboxylate acid (bpydc) under microwave irradiation ...condition and is characterized by XRD Rietveld refinement, FTIR, Raman, TG-DTA, and XPS. It is shown that the 3D extended framework is constructed by linking Pd(bpydc)Cl2 building blocks via Y(III) coordinating to carboxylic groups. Pd/Y-MOF exhibits higher catalytic activity than Pd(bpydc)Cl2 in Suzuki-Miyaura coupling reaction and Sonogashira reaction owing to the highly dispersed Pd(II) sites in the layered structure of Pd/Y-MOF and the cooperative effect between Pd(II) and Y(III). The heterogeneity studies provide mechanistic evidence that the reaction proceeds on the surface of Pd(II) ions in the crystal framework. Thus, Pd/Y-MOF exhibits impressive size selectivity toward substrates. With the small-sized reactants, it displays comparable activities with Pd(OAc)2 homogeneous catalyst. However, extremely poor activity in Suzuki-Miyaura coupling reaction with bulk substrates 1-iodonaphthalene and 4-(tert-butyl) iodobenzene is observed due to the inhibition of diffusion into the micropore channels. In addition, Pd/Y-MOF can be easily recycled and reused owing to the high stability of the framework formed by coordination of Y(III) with carboxylic group. The incorporation of Pd(II) into the crystal framework of Pd/Y-MOF prohibits the leaching of Pd(II) active species.
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IJS, KILJ, NUK, PNG, UL, UM
Hepatocellular carcinoma (HCC) is a solid tumor prone to chemotherapy resistance, and combined immunotherapy is expected to bring a breakthrough in HCC treatment. However, the tumor and tumor ...microenvironment (TME) of HCC is highly complex and heterogeneous, and there are still many unknowns regarding tumor cell stemness and metabolic reprogramming in HCC. In this study, we combined single-cell RNA sequencing data from 27 HCC tumor tissues and 4 adjacent non-tumor tissues, and bulk RNA sequencing data from 374 of the Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) samples to construct a global single-cell landscape atlas of HCC. We analyzed the enrichment of signaling pathways of different cells in HCC, and identified the developmental trajectories of cell subpopulations in the TME using pseudotime analysis. Subsequently, we performed transcription factors regulating different subpopulations and gene regulatory network analysis, respectively. In addition, we estimated the stemness index of tumor cells and analyzed the intercellular communication between tumors and key TME cell clusters. We identified novel HCC cell clusters that specifically express HP (HCC_HP), which may lead to higher tumor differentiation and tumor heterogeneity. In addition, we found that the HP gene expression-positive neutrophil cluster (Neu_AIF1) had extensive and strong intercellular communication with HCC cells, tumor endothelial cells (TEC) and cancer-associated fibroblasts (CAF), suggesting that clearance of this new cluster may inhibit HCC progression. Furthermore, ErbB signaling pathway and GnRH signaling pathway were found to be upregulated in almost all HCC tumor-associated stromal cells and immune cells, except NKT cells. Moreover, the high intercellular communication between HCC and HSPA1-positive TME cells suggests that the immune microenvironment may be reprogrammed. In summary, our present study depicted the single-cell landscape heterogeneity of human HCC, identified new cell clusters in tumor cells and neutrophils with potential implications for immunotherapy research, discovered complex intercellular communication between tumor cells and TME cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: This review assesses the associations of interleukin‐8 gene (IL‐8) −251A/T (rs4073) and −845T/C (rs2227532) polymorphisms with susceptibility to periodontitis.
Methods: Several electronic ...databases were searched for eligible articles. Twelve studies involving 2,233 cases and 2,655 controls were retrieved and analyzed. Odds ratios (ORs) along with 95% confidence intervals (CIs) were calculated to assess the strength of relationship between the IL‐8 polymorphisms and periodontitis risk.
Results: No significant association was found for IL‐8 −251A/T polymorphism with periodontitis in the overall analysis and stratification by periodontitis type and smoking status. Subgroup analysis by ethnicity revealed that −251A/T T allele and TT genotype were associated with decreased risk of periodontitis in a Brazilian mixed population (T allele versus A allele: OR 0.80, 95% CI 0.68 to 0.94, Pheterogeneity = 0.30; TT versus AA: OR 0.65, 95% CI 0.46 to 0.93, Pheterogeneity = 0.39; TT versus AA/AT: OR 0.58, 95% CI 0.35 to 0.98, Pheterogeneity = 0.01). In addition, −251A/T T allele was associated with increased periodontitis risk in Asians. Pooled estimates showed that the −845T/C polymorphism was associated with periodontitis susceptibility in overall analysis and the chronic periodontitis subgroup. In addition, marginal associations were observed between −845T/C polymorphism and periodontitis in a Brazilian mixed population. Moreover, this association was also confirmed to be significant in Brazilian non‐smokers.
Conclusion: This meta‐analysis indicated that both IL‐8 −251A/T and −845T/C polymorphisms may be involved in the development of periodontitis in a Brazilian mixed population, whereas the −251A/T allele T appeared to be a risk factor for periodontitis in Asians.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The effect of alkali-metal ions on the local structure and luminescence properties for alkali-metal europium double tungstate compounds AEu(WO4)2 (A = Li, Na, K) has been investigated by a dual-space ...structural technique, atomic pair distribution function (PDF) analysis, and the Rietveld method of powder X-ray diffraction. The compounds AEu(WO4)2 (A = Li, Na) crystallize in the isostructure with the tetragonal space group I41/a (No. 88) and show the same luminescence properties in spite of the different doped alkali metals. However, KEu(WO4)2 crystallizes in monoclinic symmetry with the space group C2/c (No. 15). Compared with the two other counterparts, KEu(WO4)2 exhibits a more effective charge-transfer excitation, a larger Stokes shift, and a broader 612 nm emission band. This phenomenon is ascribed to the lower crystal symmetry in KEu(WO4)2, which influences bond distances and the coordination number of Eu3+. Two complementary methods, the Rietveld method and PDF analysis, reveal that both LiEu(WO4)2 and NaEu(WO4)2 afford the same local surroundings of Eu3+. The local structure determined by the Rietveld and PDF methods well account for the observed luminescent properties.
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IJS, KILJ, NUK, PNG, UL, UM
Urethane has little effect on nervous system and is often used in neuroscience studies. However, the effect of urethane in neurons is not thoroughly clear. In this study, we investigated changes in ...neuron responses to tones in inferior colliculus during urethane anesthesia. As urethane was metabolized, the best and characteristic frequencies did not obviously change, but the minimal threshold (MT) remained relatively stable or was elevated. The frequency tuning bandwidth at 60 dB SPL (BW
60dBSPL
) remained unchanged or decreased, and the average evoked spike of effective frequencies at 60 dB SPL (ES
60dBSPL
) gradually decreased. Although the average evoked spike of effective frequencies at a tone intensity of 20 dB SPL above MT (ES
20dBSPLaboveMT
) decreased, the frequency tuning bandwidth at a tone intensity of 20 dB SPL above MT (BW
20dBSPLaboveMT
) did not change. In addition, the changes in MT, ES
60dBSPL
, BW
60dBSPL
, and ES
20dBSPLaboveMT
increased with the MT in pre-anesthesia awake state (MT
pre−anesthesiaawake
). In some neurons, the MT was lower, BW
60dBSPL
was broader, and ES
60dBSPL
and ES
20dBSPLaboveMT
were higher in urethane anesthesia state than in pre-anesthesia awake state. During anesthesia, the inhibitory effect of urethane reduced the ES
20dBSPLaboveMT
, but did not change the MT, characteristic frequency, or BW
20dBSPLaboveMT
. In the recording session with the strongest neuron response, the first spike latency did not decrease, and the spontaneous spike did not increase. Therefore, we conclude that urethane can reduce/not change the MT, increase the evoked spike, or broaden/not change the frequency tuning range, and eventually improve the response of auditory neurons to tone with or without “pushing down” the tonal receptive field in thresholding model. The improved effect increases with the MT
pre−anesthesiaawake
of neurons. The changes induced by the inhibitory and improved effects of urethane abide by similar regularities, but the change directions are contrary. The improvement mechanism may be likely due to the increase in the ratio of excitatory/inhibitory postsynaptic inputs to neurons.
Propofol-opioids are the most common drug combination and can reduce the dose of propofol and the incidence of adverse events in painless artificial abortion. We hypothesized that butorphanol may ...reduce the median effective dose (ED
) of propofol, propofol injection pain, and postoperative uterine contraction pain.
This was a randomized, double-blind, controlled study. A total of 54 female patients, who had ASA I or II, aged 18-49 years, undergoing painless artificial abortion, were randomly assigned into two groups, namely, Group P (propofol) and Group PB (propofol plus 10 μg/kg butorphanol). According to the pre-experiment, the initial dose of propofol for the P and PB groups was 3 and 2.5 mg/kg, respectively, with a dose gradient of 0.25 mg/kg. The ED
of propofol was analyzed using probit regression analysis. The total propofol dose consumed, recovery time, and anesthesia-related adverse events were also recorded.
There were 25 and 29 patients in the P and PB groups, respectively. The ED
(95% CI) of propofol for artificial abortion were 2.477 (2.186-2.737) and 1.555 (1.173-1.846) mg/kg in the P and PB groups, respectively. The total propofol dose consumed was (150.7 ± 21.7) mg and (110.4 ± 28.2) mg in the P and PB groups, respectively (
< 0.001). Compared with the P group, injection-site pain (76 vs. 20.7%) and uterine contraction pain (72 vs. 6.9%) in the PB group had a significant decrease (
< 0.001).
Combination of propofol with 10 μg/kg butorphanol reduced the ED
of propofol and decreased the incidence of propofol injection-site pain and postoperative uterine contraction pain during painless artificial abortion compared with propofol alone.
https://www.chictr.org.cn/showproj.html?proj=166610, identifier: ChiCTR2200059795.
Previous studies investigating HIV-infected patients suggested a direct link between underweight and the mortality rate of AIDS. However, there was a lack of evidence showing the optimal range of ...initial body mass index (BMI) patients maintain during antiretroviral therapy (ART). We aimed to evaluate associations of the BMI values pre-ART and during the entire ART duration with mortality among HIV-positive individuals. In total, 5101 HIV/AIDS patients, including 1439 (28.2%) underweight, 3047 (59.7%) normal-weight, 548 (10.7%) overweight and 67 (1.3%) obese patients, were included in this cohort. The cumulative mortality of underweight, normal-weight, and overweight were 2.4/100 person-years (95% CI 1.9-2.9), 1.1/100 person-years (95% CI 0.9-1.3), and 0.5/100 person-years (95% CI 0.1-0.9), respectively. Cumulative mortality was lower in both the normal-weight and overweight populations than in the underweight population, with an adjusted hazard ratio (AHR) of 0.5 (95% CI 0.4-0.7, p < 0.001) and 0.3 (95% CI 0.1-0.6, p = 0.002), respectively. Additionally, in the 1176 patients with available viral load data, there was significant difference between the underweight and normal-weight groups after adjustment for all factors, including viral load (p = 0.031). This result suggests that HIV-infected patients in Guangxi maintaining a BMI of 19-28 kg/m
, especially 24-28 kg/m
, have a reduced risk of death.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Herein, a formaldehyde-modified metal-organic framework, FA/NH2-UiO-66 is facilely synthesized via one-pot solvothermal reaction. Under excitation of 365 nm UV light, the drastic fluorescence ...enhancement triggered by Hg2+ ions and the un-interfered signal by the coexisting metal ions renders a sensitive and specific fluorescent detection of Hg2+ ions. A low detection limit (0.0885 nM, M refers to mol L−1) and a wide linear range (0.1 nM∼40 μM) are obtained based on calculation of the fluorescence intensity versus the concentration of Hg2 ions. The mechanism of fluorescence enhancement is ascribed to the intermolecular cyclization when Hg2+ is trapped by imino group on FA/NH2-UiO-66. Moreover, the target- directed adsorption by FA/NH2-UiO-66 leads to an effective mercury separation from contaminative system, which exhibits a satisfactory adsorption efficiency of 95.42% within 50 minutes. This work thus delivers a dual-functional MOFs-based platform for visual and hypersensitive Hg2+ tracking and effective removal of the toxic heavy metal ions, showing promise in tackling the environmental problems with monitoring and remediation synchronously.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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