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Yuan-yuan Wu,1 Wen-Hui Liao,1 Zong-ling Niu,1 Si-Han Zhou,1 Tian-Tian Wu,1 Zhe Li,2 Qi-Hua Zhao,1 Jing-Yuan Xu,2 Ming-jin Xie1 1School of Chemical Science and Technology, Yunnan University, Kunming, People’s Republic of China; 2Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Ming-jin Xie, Email mjxie@ynu.edu.cnBackground: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach.Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex.Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models.Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.Graphical Abstract: Keywords: gallium complex, nanomedicine, anticancer, colorectal cells, drug delivery, in vivo imaging

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE., (© 2024. The Author(s).)

Background: Patients with systemic sclerosis (SSc) are known to have higher incidence of atherosclerosis (AS). Mitochondrial injuries in SSc can cause endothelial dysfunction, leading to AS; thus, mitochondria appear to be hubs linking SSc to AS. This study aimed to identify the mitochondria-related biomarkers of SSc and AS., Methods: We identified common differentially expressed genes (DEGs) in the SSc (GSE58095) and AS (GSE100927) datasets of the Gene Expression Omnibus (GEO) database. Considering the intersection between genes with identical expression trends and mitochondrial genes, we used the least absolute shrinkage and selection operator (LASSO) as well as random forest (RF) algorithms to identify four mitochondria-related hub genes. Diagnostic nomograms were then constructed to predict the likelihood of SSc and AS. Next, we used the CIBERSORT algorithm to evaluate immune infiltration in both disorders, predicted the transcription factors for the hub genes, and validated these genes for the two datasets., Results: A total of 112 genes and 13 mitochondria-related genes were identified; these genes were then significantly enriched for macrophage differentiation, collagen-containing extracellular matrix, collagen binding, antigen processing and presentation, leukocyte transendothelial migration, and apoptosis. Four mitochondria-related hub DEGs (IFI6, FSCN1, GAL, and SGCA) were also identified. The nomograms showed good diagnostic values for GSE58095 (area under the curve (AUC) = 0.903) and GSE100927 (AUC = 0.904). Further, memory B cells, γδT cells, M0 macrophages, and activated mast cells were significantly higher in AS, while the resting memory CD4 + T cells were lower and M1 macrophages were higher in SSc; all of these were closely linked to multiple immune cells. Gene set enrichment analysis (GSEA) showed that IFI6 and FSCN1 were involved in immune-related pathways in both AS and SSc; GAL and SGCA are related to mitochondrial metabolism pathways in both SSc and AS. Twenty transcription factors (TFs) were predicted, where two TFs, namely BRCA1 and PPARγ, were highly expressed in both SSc and AS., Conclusion: Four mitochondria-related biomarkers were identified in both SSc and AS, which have high diagnostic value and are associated with immune cell infiltration in both disorders. Hence, this study provides new insights into the pathological mechanisms underlying SSc and AS. The specific roles and action mechanisms of these genes require further clinical validation in SSc patients with AS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Lyu, Qin and Xie.)

There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH 2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 μg mL -1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The study of facile-synthesis and low-cost X-ray scintillators with high light yield, low detection limit and high X-ray imaging resolution plays a vital role in medical and industrial imaging fields. However, the optimal balance between X-ray absorption, decay lifetime and excitonic utilization efficiency of scintillators to achieve high-resolution imaging is extremely difficult due to the inherent contradiction. Here two thermally activated delayed fluorescence (TADF)-actived coinage-metal clusters M 6 S 6 L 6 (M=Ag or Cu) were synthesized by simple solvothermal reaction, where the cooperation of heavy atom-rich character and TADF mechanism supports strong X-ray absorption and rapid luminescent collection of excitons. Excitingly, Ag 6 S 6 L 6 (SC-Ag) displays a high photoluminescence quantum yield of 91.6 % and scintillating light yield of 17420 photons MeV -1 , as well as a low detection limit of 208.65 nGy s -1 that is 26 times lower than the medical standard (5.5 μGy s -1 ). More importantly, a high X-ray imaging resolution of 16 lp/mm based on SC-Ag screen is demonstrated. Besides, rigid core skeleton reinforced by metallophilicity endows clusters M 6 S 6 L 6 strong resistance to humidity and radiation. This work provides a new view for the design of efficient scintillators and opens the research door for silver clusters in scintillation application., (© 2023 Wiley-VCH GmbH.)

In recent years， ozone （O 3 ） has become an increasingly important air pollutant in China. Identifying the sensitivity of O 3 to the precursors volatile organic compounds （VOCs） and nitrogen oxides （NO x ） can help make effective abatement strategies. This study compared three methods for determining O 3 -VOCs-NO x sensitivity： simulated photochemical indicator values and sensitivity coefficients derived from a three-dimensional air quality model and an observation-based model （OBM）， with a case study involving an O 3 pollution event that occurred in Nanjing in late July 2017. The results showed that O 3 sensitivity based on the photochemical indicator and sensitivity coefficients demonstrated similar spatial variations （over 50% of the grid cells of Nanjing exhibiting identical O 3 sensitivity）. However， sensitivity coefficients identified a larger number of areas within a transitional O 3 sensitivity regime， as opposed to the VOCs- or NO x -limited regime identified by the photochemical indicator. The determination of the latter was affected by the adopted threshold values. The OBM relied on the quality of the observational data. For example， positive biases in observed NO 2 could lead to an underestimation of O 3 sensitivity to NO x with the OBM. During the high pollution period， the three methods exhibited significant disparities. The photochemical indicator tended to suggest the VOCs-limited condition， whereas the OBM and sensitivity coefficients indicated the NO x -limited or transitional regimes.

The redox-active metal ions, especially Cu 2+ , are highly correlated to Alzheimer's disease (AD) by causing metal ion-mediated oxidative stress and toxic metal-bound β-amyloid (Aβ) aggregates. Numerous pieces of evidence have revealed that the regulation of metal homeostasis could be an effective therapeutic strategy for AD. Herein, in virtue of the interaction of both amino-containing silane and ethylenediaminetetraacetic acid disodium salt for Cu 2+ , the silicon-carbon dots (SiCDs) are deliberately prepared using these two raw materials as the cocarbon source; meanwhile, to realize the local enrichment of SiCDs and further maximize the chelating ability to Cu 2+ , the SiCDs are feasibly loaded to the biocompatible mesoporous silica nanoparticles (mSiO 2 ) with the interaction between residual silane groups on SiCDs and silanol groups of mSiO 2 . Thus-obtained nanocomposites (i.e., mSiO 2 @SiCDs) could serve as an efficient Cu 2+ chelator with satisfactory metal selectivity and further modulate the enzymic activity of free Cu 2+ and the Aβ 42 -Cu 2+ complex to alleviate the pathological oxidative stress with an anti-inflammatory effect. Besides, mSiO 2 @SiCDs show an inspiring inhibitory effect on Cu 2+ -mediated Aβ aggregation and further protect the neural cells against the toxic Aβ 42 -Cu 2+ complex. Moreover, the transgenic Caenorhabditis elegans CL2120 assay demonstrates the protective efficacy of mSiO 2 @SiCDs on Cu 2+ -mediated Aβ toxicity in vivo , indicating its potential for AD treatment.

Deletional α-thalassemia is characterized by reduced hemoglobin A 2 and involves the deletion of a few nucleotides, which is a rare hereditary disease. However, the detection of rare mutations using commonly used genetic tests is highly challenging. In the present study, next-generation sequencing (NGS) was used to identify a novel 7-bp deletion α-thalassemia in one individual from a Chinese family. Hematological parameters of the family members were determined using an automated cell counter, and hemoglobin electrophoresis was performed using a capillary electrophoresis system. Subsequently, NGS was performed on the genomic DNA of the patient and her family members. The 7-bp deletion (named Hb Honghe [ HBA1 : c.401_407delGCACCGT]) of α-thalassemia in the α-globin gene was confirmed using Sanger sequencing. The patient's father was also a heterozygous carrier of HBA1 : c.401_407delGCACCGT deletion, but not her mother or sister. The application of the combined molecular approach is essential for the accurate diagnosis of rare thalassemia. This study reports a novel case of α- thalassemia. The characterization of the mutation might provide new insights into genetic counseling and accurate diagnosis of thalassemia.

Reduced activity of the enzymes encoded by PHGDH, PSAT1, and PSPH causes a set of ultrarare, autosomal recessive diseases known as serine biosynthesis defects. These diseases present in a broad phenotypic spectrum: at the severe end is Neu-Laxova syndrome, in the intermediate range are infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end is childhood disease with intellectual disability. However, L-serine supplementation, especially if started early, can ameliorate and in some cases even prevent symptoms. Therefore, knowledge of pathogenic variants can improve clinical outcomes. Here, we use a yeast-based assay to individually measure the functional impact of 1,914 SNV-accessible amino acid substitutions in PSAT. Results of our assay agree well with clinical interpretations and protein structure-function relationships, supporting the inclusion of our data as functional evidence as part of the ACMG variant interpretation guidelines. We use existing ClinVar variants, disease alleles reported in the literature and variants present as homozygotes in the primAD database to define assay ranges that could aid clinical variant interpretation for up to 98% of the tested variants. In addition to measuring the functional impact of individual variants in yeast haploid cells, we also assay pairwise combinations of PSAT1 alleles that recapitulate human genotypes, including compound heterozygotes, in yeast diploids. Results from our diploid assay successfully distinguish the genotypes of affected individuals from those of healthy carriers and agree well with disease severity. Finally, we present a linear model that uses individual allele measurements to predict the biallelic function of ~1.8 million allele combinations corresponding to potential human genotypes. Taken together, our work provides an example of how large-scale functional assays in model systems can be powerfully applied to the study of ultrarare diseases., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:: AMD is a scientific advisor with a financial interest in Fenologica Biosciences, Inc., a company that develops instrumentation and analytical tools for the analysis of microbial colonies. Aimée Dudley, Gareth Cromie, and Michael Xie are listed as inventors on US patents or patent applications that may be relevant to this work. The remaining authors declare that they have no competing interests., (Copyright: © 2023 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anisotropic charge transport plays a pivotal role in clarifying the conductivity mechanism in direct X-ray detection to improve the detection sensitivity. However, the anisotropic photoelectric effect of semiconductive single crystal responsive to X-ray is still lacking of theoretical and experimental proof. The semiconductive coordination polymers (CPs) with designable structures, adjustable functions, and high crystallinity provide a suitable platform for exploring the anisotropic conductive mechanism. Here,the study first reveals a 1D conductive transmission path for direct X-ray detection from the perspective of structural chemistry. The semiconductive copper(II)-based CP 1 single crystal detector exhibits unique anisotropic X-ray detection performance. Along the 1D π-π stacking direction, the single crystal device (1-SC-a) shows a superior sensitivity of 2697.15 µCGy air -1  cm -2 and a low detection limit of 1.02 µGy air  s -1 among CPs-based X-ray detectors. This study provides beneficial guidance and deep insight for designing high-performance CP-based X-ray detectors., (© 2023 Wiley-VCH GmbH.)

A series of O-phenanthroline silver(I) complexes were synthesized and characterized by infrared (IR) spectroscopy, mass spectrometry (MS), 1 H nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The cytotoxicity of the silver(I) complex (P-131) was evaluated in the cancer cell lines HCT-116, HeLa, and MDA-MB-231 and the normal cell line LO2 via MTT assays. The 50% inhibition concentration (IC 50 ) of P-131 on HCT116 cell line is 0.86 ± 0.03 μM. It is far lower than the IC 50 value of cisplatin (9.08 ± 1.10 μM), the IC 50 value of normal cell LO2 (76.20 ± 0.48 μM) is much higher than that of cisplatin (3.99 ± 0.74 μM), indicating that its anticancer effect is stronger than that of cisplatin, and its biological safety is greater than that of cisplatin. Furthermore, anticancer mechanistic studies showed that P-131 inhibited cell proliferation by blocking DNA synthesis and acted temporally on the nucleus in dividing HCT-116 cells. Moreover, P-131 increased intracellular reactive oxygen species (ROS) levels in a dose-dependent manner. Notably, 10 mg/kg P-131 showed better antitumor effects than oxaliplatin in an HCT116 human colorectal xenograft mouse model without inducing toxicity. Moreover, the microdilution broth method was used to evaluate the antimicrobial properties of P-131 against Pseudomonas aeruginosa and Candida albicans. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Histone deacetylases (HDACs) not only regulate histone acetylation but also participate in many pathophysiologic processes, especially the development of cancer, including breast cancer. However, whether Histone deacetylase 11 can influence breast cancer is still unknown. This study investigated the relationship between HDAC11 expression in breast cancers and clinicopathologic parameters, and used small interference RNA (siRNA) to determine the biological behavioural changes after knockdown of HDAC11., Methods: Immunohistochemical (IHC) staining was employed to detect the expression of HDAC11 in a tissue microarray (TMA) of 145 patients with invasive ductal breast carcinoma. Transwell and wound healing assays were employed to analyze cell invasion and migration. The proliferation ability of cells was determined by Cell Counting Kit (CCK8)., Results: The results show that the expression of HDAC11 was positively correlated with the overall survival (OS) of breast cancer patients. Specific HDAC11 knockdown enhanced MDA-MB-231 cell proliferation, migration, and invasion., Conclusion: In conclusion, this study found that HDAC11 expression is positively correlated with the overall survival rate of patients. HDAC11 can inhibit the invasion and proliferation of breast cancer cells to a certain extent and can be used as a good prognosis marker., Competing Interests: None., (IJCEP Copyright © 2023.)

Luminescent metal halides have been exploited as a new class of X-ray scintillators for security checks, nondestructive inspection, and medical imaging. However, the charge traps and hydrolysis vulnerability are always detrimental to the three-dimensional ionic structural scintillators. Here, the two zero-dimensional organic-manganese(II) halide coordination complexes 1-Cl and 2-Br were synthesized for improvements in X-ray scintillation. The introduction of a polarized phosphine oxide can help to increase the stabilities, especially the self-absorption-free merits of these Mn-based hybrids. The X-ray dosage rate detection limits reached up to 3.90 and 0.81 μGy air /s for 1-Cl and 2-Br , respectively, superior to the medical diagnostic standard of 5.50 μGy air /s. The fabricated scintillation films were applied to radioactive imaging with high spatial resolutions of 8.0 and 10.0 lp/mm, respectively, holding promise for use in diagnostic X-ray medical imaging.

Size-segregated particulate matter (PM) samples were collected in different seasons from 2016 to 2017 at the Xianlin Campus of Nanjing University. Mass concentrations of water-soluble inorganic ions, carbonaceous components, and elements were analyzed for PM with an aerodynamic diameter ≤ 1.1 μm (PM 1.1 ; <0.4 μm, 0.4-0.7 μm, and 0.7-1.1 μm). The results showed that PM 1.1 , OC, NO 3 - , SO 4 2- , and NH 4 + exhibited higher ambient levels in fall-winter than those in spring-summer, which was attributed to the changes in local diffusion conditions, evaporation, and decomposition of non-refractory components. Elemental carbon (EC) reached its maximum concentration[(1.87±0.98) μg·m -3 ]in spring due to the increase in industrial and road dust resuspension. According to the characteristic ratio between bulk components, the anions in PM 1.1 were dominated by NO 3 - , SO 4 2- , and Cl - in Nanjing, and the carbonaceous components were mainly from fossil fuel combustions and associated aging processes. As the ambient temperature increased, the size distributions of thermo-unstable components including NH 4 + , NO 3 - , and OC shifted towards finer particles, whereas EC became more enriched in coarse particles, possibly due to the increase in emission intensity of motor vehicles and fugitive dust contributions. Since high relative humidity (>70%) is often accompanied by high temperature (>20℃) and improved diffusion conditions, a relative humidity of 60%-70% was more conducive to the formation of secondary inorganic ions in PM 1.1 . Source apportionment results based on the speciation data of PM 1.1 showed that secondary formation processes[(66.6±18.3)%]and dust resuspension[(16.8±14.8)%]were the main contributors to PM 1.1 in Nanjing, and further control of the emissions of gaseous precursors and dust is necessary.

Background: Exercise training significantly improves cardiorespiratory fitness (CRF) in heart failure with reduced ejection fraction (HFrEF) patients, but high-intensity interval training (HIIT) is not superior to moderate-intensity interval training (MIIT). Whether HIIT is more beneficial than MIIT in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear., Methods: On August 29, 2021, we conducted a comprehensive computerized literature search of the Medline, EMBASE, Web of Science, and Cochrane databases using the following keywords: "HF or diastolic HF or HFpEF or HF with normal ejection fraction and exercise training or aerobic exercise or isometric exercises or physical activity or cardiac rehabilitation." Only randomized controlled trials (RCTs) reporting comparisons between HIIT and MIIT in HFpEF were included in the final analysis to maintain consistency and obtain robust pooled estimates. Methodological quality was assessed based on the ratings of individual biases. To generate an overall test statistic, the data were analyzed using the random-effects model for a generic inverse variance. Outcome measures were reported as an odds ratio, and confidence intervals (CIs) were set at 95%. The study followed PRISMA guidelines., Results: This meta-analysis included only RCTs comparing the efficacy of HIIT and MIIT in HFpEF patients. This study included 150 patients from 3 RCTs. In the current pooled data analysis, HIIT significantly improves diastolic function measured by E/A ratio (WMD, 0.13; 95% CI, 0.03-0.23, P = .009). However, no significant change was observed in the diastolic function measured by E/e' ratio (WMD, 0.39; 95% CI, -2.40 to 3.18, P = .78), and CRF evaluated by both VO2 (mL/kg per min; WMD, -0.86; 95%CI, -5.27 to 3.55, P = .70) and VE/CO2 slope (WMD, 0.15; 95% CI, -10.24 to 10.53, P = .98), and systolic function (EF-WMD, -2.39; 95% CI, -12.16% to 7.38%, P = .63) between HIIT and MIIT in patients with HFpEF., Conclusion: In HFpEF patients, HIIT may be superior to MIIT in improving diastolic function, measured by E/A, but not CRF and left ventricular systolic function., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To understand the changes in chemical composition and sources of PM 2.5 under the extreme reduction background during the COVID-19 epidemic periods in Nanjing, hourly observation results of PM 2.5 components (water-soluble inorganic ions, carbonaceous components, and inorganic elements) of two epidemic events from January to March 2020 and June to August 2021 were analyzed. In comparison to that during pre-epidemic periods, the concentration of NO 3 - during the two epidemic control periods decreased by 52.9% and 43.0%, respectively, which was larger than the decreases in NH 4 + (46.4% and 31.6%) and SO 4 2- (33.8% and 16.5%). Since the observation site was located close to a main road, the decrease in elemental carbon (EC, 35.4% and 20.6%) was higher than that in organic carbon (OC, 11.1% and 16.2%). In reference to the variations in the characteristic ratios of the bulk components mentioned above, the epidemic control showed a more substantial influence on traffic emissions than industrial activities. The concentration time series of PM 2.5 major components over the epidemic periods indicated that NO x from local traffic emissions had substantial contributions to the formation of NO 3 - , which led to local short-term PM 2.5 pollution. In addition, the positive matrix factorization (PMF) model was used to analyze the hourly observation data of PM 2.5 components. The seven identified factors were linked with metallurgy, firework and firecracker combustions, road traffic emissions, coal combustion, dust resuspension, secondary sulfate, and secondary nitrate. Because the nitrate was unstable under high temperature, the contribution of secondary nitrate to PM 2.5 during the epidemic control period of 2021 (summer, 21.2%) was much lower than that during the epidemic control period of 2020 (winter, 60.6%); however, the formation of secondary components always dominated the contribution of PM 2.5 sources. Therefore, emissions of NO x and SO 2 should be further controlled to continuously reduce ambient PM 2.5 concentrations in Chinese cities.

A series of (8-hydroxyquinoline) gallium(III) complexes (CP- 1 - 4 ) was synthesized and characterized by single X-ray crystallography and density functional theory (DFT) calculation. The cytotoxicity of the four gallium complexes toward a human nonsmall cell lung cancer cell line (A549), human colon cancer cell line (HCT116), and human normal hepatocyte cell line (LO2) was evaluated using MTT assays. CP- 4 exhibited excellent cytotoxicity against HCT116 cancer cells (IC 50 = 1.2 ± 0.3 μM) and lower toxicity than cisplatin and oxaliplatin. We also evaluated the anticancer mechanism studies in cell uptake, reactive oxygen species analysis, cell cycle, wound-healing, and Western blotting assays. The results showed that CP- 4 affected the expression of DNA-related proteins, which led to the apoptosis of cancer cells. Moreover, molecular docking tests of CP- 4 were performed to predict other binding sites and to confirm its higher binding force to disulfide isomerase (PDI) proteins. The emissive properties of CP- 4 suggest that this complex can be used for colon cancer diagnosis and treatment, as well as in vivo imaging. These results also provide a foundation for the development of gallium complexes as potent anticancer agents., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach., Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex., Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models., Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy., Competing Interests: There is no conflict to declare., (© 2023 Wu et al.)

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified&#95;Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified&#95;Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.

Morphologically dynamic dendritic spines are the major sites of neuronal plasticity in the brain; however, the molecular mechanisms underlying their morphological dynamics have not been fully elucidated. Phldb2 is a protein that contains two predicted coiled-coil domains and the pleckstrin homology domain, whose binding is highly sensitive to PIP 3 . We have previously demonstrated that Phldb2 regulates synaptic plasticity, glutamate receptor trafficking, and PSD-95 turnover. Drebrin is one of the most abundant neuron-specific F-actin-binding proteins that are pivotal for synaptic morphology and plasticity. We observed that Phldb2 bound to drebrin A (adult-type drebrin), but not to drebrin E (embryonic-type drebrin). In the absence of Phldb2, the subcellular localization of drebrin A in the hippocampal spines and its distribution in the hippocampus were altered. Immature spines, such as the filopodium type, increased relatively in the CA1 regions of the hippocampus, whereas mushroom spines, a typical mature type, decreased in Phldb2 -/- mice. Phldb2 suppressed the formation of an abnormal filopodium structure induced by drebrin A overexpression. Taken together, these findings demonstrate that Phldb2 is pivotal for dendritic spine morphology and possibly for synaptic plasticity in mature animals by regulating drebrin A localization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

The recognition and adsorption of silver ions (Ag + ) from industrial wastewater are necessary but still challenging. Herein, we constructed four Zn(II)-based coordination polymers (CPs), namely, [Zn(btap) 2 (NO 3 ) 2 ] n ( 1 ), [Zn(btap)(SO 4 )(H 2 O) 3 ] n ( 2 ), {[Zn(btap) 2 (H 2 O) 2 ]·(ClO 4 ) 2 } n ( 3 ), and [Zn(btap)Cl 2 ] n ( 4 ), by using 3,5-bis(triazol-1-yl)pyridine (btap) with different anionic Zn(II) salts. The crystal structures of 1 - 4 , varying from one-dimensional beaded ( 1 ) and zigzag chain ( 2 ) to two-dimensional sql ( 3 ) and bex ( 4 ) typologies, were regulated by the coordination modes of btap and the counter-anions. The water stability, pH stability, thermostability, and luminescent properties of the CPs were investigated. The luminescence performances in a series of cations and anions were also explored. Considering the high density of chloride groups in the structure, 4 showed luminescence sensing for Ag + [ K SV = 9188.45 M - 1 and a limit of detection (LOD) of 4.9 μM], as well as an excellent ability for Ag + adsorption in aqueous solution (maximum adsorption capacity, 653.3 mg/g). Additionally, anti-interference experiments revealed that 4 had excellent recognition and adsorption capacities for Ag + even when multiple ions coexisted. Moreover, XRD, EDS, and XPS analyses confirmed that the coordination of Ag + with chloride groups in 4 resulted in excellent adsorption capacity and prevented ligand-to-ligand electron transfer, showing excellent detection ability. Suitable coordination sites were introduced to interact strongly with Ag + , along with detection and large adsorption capacity. Our strategy can effectively design and develop multifunctional CP-based materials, which are applicable in removal processes and environmental protection, by regulating anions in the self-assembly and introducing CP functional groups.

Background: Sacubitril/valsartan has been approved for the treatment of heart failure (HF) patients with reduced ejection fraction; since then, it gradually became a new star drug in the therapy of HF. Nevertheless, the effectiveness of sacubitril/valsartan remains under investigation. Thus far, only a few bibliometric studies have systematically analyzed the application of sacubitril/valsartan., Methods: Publications on sacubitril/valsartan were retrieved from the Web of Science Core Collection on April 29, 2021. Data were analyzed using Microsoft Excel 2019 (Redmond, WA), VOS viewer (Redmond, WA), and Cite Space V (Drexel University, Philadelphia, PA)., Results: A total of 1309 publications on sacubitril/valsartan published from 1995 to 2021 were retrieved. The number of publications regarding sacubitril/valsartan increased sharply in the last 6 years (2015-2021), and American scholars authored >40% of those publications. Most were published in the European Journal of Heart Failure, the United States was the bellwether with a solid academic reputation in this area. Solomon published the highest number of related articles and was the most frequently cited author. "Heart failure" was the leading research hotspot. The keywords, "inflammation," "fibrosis," and "oxidative stress" appeared most recently as research fronts., Conclusions: Research attention should be focused on clinical trial outcomes. Considering its effectiveness in HF, the mechanisms and further applications of sacubitril/valsartan may become research hotspots in the future and should be closely examined., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Two examples of efficient cathode-ray scintillation coordination polymers with good stability at high voltage were prepared by conjugating luminescent groups with d 10 metal ions. The synergistic effect of inorganic metal and organic ligand suppresses the self-quenching of the conjugated luminescent groups and enhances the scintillation performance. This work provides new ideas for the design of new field-emission displays and cathode-ray scintillation materials.

Phytochemical investigation of Melodinus fusiformis led to a new aspidosperma-aspidosperma bisindole alkaloid (BIA), bis-19 β -hydroxyvenalstonidine ( 1 ), together with three known BIAs ( 2 - 4 ). The structures were established by extensive analysis of their HRESIMS, NMR data, and comparing with the reported data. BIA 1 is an almost symmetrical structure, linked by C3-C14' bond, while BIAs 2 - 4 are reported for the first time from the plant. The cytotoxic, immunosuppressive and anti-inflammatory activities of BIAs 1 - 4 were evaluated in vitro . BIAs 1 , 3 and 4 showed good toxicity against MOLT-4 cell lines with IC 50 values in the range of 1.5-17.5  - M. BIA 2 exhibited the strongest inhibitory effect against MCF-7 cell lines with an IC 50 value of 7.1 μM. BIA 1 significantly inhibited Con A-stimulated mice splenocytes proliferation equal to that of the positive control (DXM) in a concentration-dependent manner. BIAs 1 and 2 were able to decrease the NO production in LPS-induced RAW 264.7 cells at 30 μM concentration. BIA 2 showed similar inhibition of nitric oxide release, compared to that of DXM. Furthermore, BIA 2 remarkably inhibited the levels of IL-6 and TNF-α compared to the LPS induced group. Interestingly, BIA 2 displayed an inhibitory effect on TNF-α production similar to that of dexamethasone at a concentration of 20 μM.

Inflammatory diseases caused by infectious agents such as the SARS-CoV-2 virus can lead to impaired reductive-oxidative (REDOX) balance and disrupted mitochondrial function. Peripheral blood mononuclear cells (PBMCs) provide a useful model for studying the effects of inflammatory diseases on mitochondrial function but can be limited by the need to store these cells by cryopreservation prior to assay. Here, we describe a method for improving and determining PBMC viability with normalization of values to number of living cells. The approach can be applied not only to PBMC samples derived from patients with diseases marked by an altered inflammatory response such as viral infections., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Tryptophan regulates and participates in various physiological systems in the human body, and its excessive intake has harmful effects. Therefore, detecting and monitoring tryptophan in water and distinguishing it from other amino acids are necessary. In addition to their excellent luminescence, coordination polymer-based sensors have good stability and high sensitivity and selectivity for sensing applications. In this work, two luminescent coordination polymers (CPs), [Zn(ttb)Cl] n (1) and [Zn 2 (ttb) 2 (OH)(NO 3 )] n (2), were obtained through the solvothermal reaction of different Zn(II) salts with a rarely studied multidentate N-donor ligand, 1-(tetrazo-5-yl)-3-(triazo-1-yl) benzene (Httb). Crystallographic investigations revealed that the structure of 1 exhibits a 2D fes net with Cl - anions acting as terminal charge balancers, and that of 2 features a 3D ant net with NO 3 - anions in a rare monodentate bridging (μ 2 -O-η 1 :η 1 ) mode. In terms of stability tests, 2 has better thermal and water stability than 1. Although both show good fluorescence performance, specific tryptophan detection, and excellent anti-interference ability, 2 has higher K SV (111 852.6 M -1 ), a lower limit of detection (LOD = 23.6 nM), and a better recovery rate than 1. Cytotoxicity experiments proved that 2 has extremely low toxicity and thus has great potential for in vivo detection. Therefore, CP 2 is a suitable candidate for advanced practical applications for the efficient sensing of tryptophan in water. The luminescence of the ligands was also calculated using DFT theory and further discussed through experiments. The quenching mechanism that occurs after tryptophan addition was explored through Hirshfeld surface analysis.

Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified N -ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake in vitro . In the present study, we generated Nsf +/- mice and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo . Nsf +/- mice exhibited abnormalities in sociability, communication, repetitiveness, and anxiety. Additionally, Nsf loss led to a decrease in membrane SERT expression in the raphe and accumulation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors at the synaptic membrane surface in the hippocampal CA1 region. We found that postsynaptic density and long-term depression were impaired in the hippocampal CA1 region of Nsf +/- mice. Taken together, these findings demonstrate that NSF plays a role in synaptic plasticity and glutamatergic and serotonergic systems, suggesting a possible mechanism by which the gene is linked to the pathophysiology of autistic behaviors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xie, Iwata, Ishikawa, Nomura, Tani, Murata, Fukazawa and Matsuzaki.)

To explore the application of high-temporal-resolution data in PM 2.5 source apportionment during air pollution events, ambient air PM 2.5 components were continuously monitored in urban Nanjing from January to December, 2017. Commercially available instruments for continuous measurements were deployed to obtain hourly concentrations of elements, water-soluble ions, and carbonaceous components of PM 2.5 . Data for 15 elements and 5 bulk components during three pollution events(firework combustion during the Spring Festival, a spring sandstorm, and a winter haze event) and across the whole year comprised four datasets for source apportionment using positive matrix factorization(PMF), and the distribution of factor/source contributions and estimations of average concentrations of characteristic components were compared based on different input datasets(PMF firework-sand-haze and PMF full-year ). The results showed that the identified factors/sources, factor profiles, and contributions differed largely between PMF firework-sand-haze and PMF full-year solutions. For example, the relative average contribution of the firework combustion factor derived from the PMF full-year solution(was 1.50%) was far less than that of the PMF firework solution. The dust factor had an average contribution of 8.51% in the PMF sand solution, which was approximately double that of the PMF full-year solution. This might be explained by the fact that PMF assumes unvaried source compositions during the measurement campaign, meaning that the source apportionment results based on long-term observations will include bias due to changes in emission sources. Furthermore, during the firework combustion event, the estimated average concentration of K from the PMF firework solution[(1.32±1.17) μg·m -3 , P =0.64]was closer to measured value[(1.36±1.19) μg·m -3 ]than that of the PMF full-year solution[(1.16±1.19) μg·m -3 , P =0.0090]. For the sand storm event, the concentrations of Fe, Si, and Ti were significantly underestimated by the PMF full-year solution[(0.061±0.042)-(1.06±0.65) μg·m -3 , P <0.05], while their peak concentrations agreed well between the PMF sand estimations and the observations. During the winter haze event, all PM 2.5 bulk components were well estimated by both the PMF full-year and PMF haze solutions. Based on these results, PMF source apportionment results based on continuous measurement data during pollution events can reasonably reflect short-term variations in characteristic PM 2.5 components and their sources, which can improve the timeliness of air pollution source apportionment.

Coordination of skilled movements and motor planning relies on the formation of regionally restricted brain circuits that connect cortex with subcortical areas during embryonic development. Layer 5 neurons that are distributed across most cortical areas innervate the pontine nuclei (basilar pons) by protrusion and extension of collateral branches interstitially along their corticospinal extending axons. Pons-derived chemotropic cues are known to attract extending axons, but molecules that regulate collateral extension to create regionally segregated targeting patterns have not been identified. Here, we discovered that EphA7 and EfnA5 are expressed in the cortex and the basilar pons in a region-specific and mutually exclusive manner, and that their repulsive activities are essential for segregating collateral extensions from corticospinal axonal tracts in mice. Specifically, EphA7 and EfnA5 forward and reverse inhibitory signals direct collateral extension such that EphA7 -positive frontal and occipital cortical areas extend their axon collaterals into the EfnA5 -negative rostral part of the basilar pons, whereas EfnA5 -positive parietal cortical areas extend their collaterals into the EphA7 -negative caudal part of the basilar pons. Together, our results provide a molecular basis that explains how the corticopontine projection connects multimodal cortical outputs to their subcortical targets. SIGNIFICANCE STATEMENT Our findings put forward a model in which region-to-region connections between cortex and subcortical areas are shaped by mutually exclusive molecules to ensure the fidelity of regionally restricted circuitry. This model is distinct from earlier work showing that neuronal circuits within individual cortical modalities form in a topographical manner controlled by a gradient of axon guidance molecules. The principle that a shared molecular program of mutually repulsive signaling instructs regional organization-both within each brain region and between connected brain regions-may well be applicable to other contexts in which information is sorted by converging and diverging neuronal circuits., (Copyright © 2021 the authors.)

A new schiff base cobalt(III) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] cobalt(III) (M3) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M3 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 by MTT assays. The IC 50 is in the range of 6.27-22.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M3 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, western blot analysis indicated M3 dramatically decreased the target protein c-Myc and KLF5 expression levels, and activated many signaling pathways including ER stress, apoptosis, cell cycle and DNA damage in HeLa. M3 did not affect proteasomal activity.

Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries., Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca 2+ distribution, inositol 1,4,5-trisphosphate receptor (IP 3 R) abundance, and the activities of voltage-gated K + channels (K V ) and Ca 2+ -activated K + channels (BK Ca ) were examined in rat cerebral vascular smooth muscle cells (VSMCs)., Results: An increase of cytoplasmic Ca 2+ and a decrease of mitochondrial/sarcoplasmic reticulum (SR) Ca 2+ were observed in HU rat cerebral VSMCs. The abundance of fusion proteins (mitofusin 1/2 [MFN1/2]) and fission proteins (dynamin-related protein 1 [DRP1] and fission-mitochondrial 1 [FIS1]) was significantly downregulated and upregulated, respectively in HU rat cerebral VSMCs. The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats, and IP 3 R protein/mRNA levels were significantly upregulated. The current densities and open probabilities of K V and BK Ca decreased and increased, respectively. Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1. It also decreased IP 3 R expression levels and restored the activities of the K V and BK Ca channels. MitoTEMPO restored the Ca 2+ distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries., Conclusion: The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The light absorption of organic components in PM 2.5 was investigated at a suburban site in northern Nanjing from September 2018 to September 2019, and PM 2.5 compositional data and principal component analysis (PCA) were used to identify the sources of light-absorbing organic carbon (brown carbon, BrC). The results showed that the average light absorption coefficients of water-soluble organic carbon (WSOC) and methanol extractable organic carbon (MEOC) were (3.22±2.18) Mm -1 (Abs 365,w ) and (7.69±4.93) Mm -1 (Abs 365,m ), respectively. Significant correlations were observed between Abs 365,w and mass concentrations of WSOC ( r =0.72, P <0.01) and between Abs 365,m and mass concentrations of MEOC ( r =0.62, P =0.04). Both Abs 365,w and Abs 365,m exhibited seasonal variations, with higher values during winter than during summer,and higher diel variations at night than during the day. This can be attributed to meteorological characteristics during the winter and nighttime, i.e., decreased boundary layer height and increased atmospheric stability, enhanced primary emissions in winter,and stronger photobleaching effects during the summer and during the day. The annual average Abs 365,m /Abs 365,w ratio (2.60±0.92) was much larger than the average mass ratio of MEOC/WSOC (1.37±0.30), indicating that the water-insoluble fraction of MEOC had a stronger light absorption effect and dominated BrC absorption. No strong correlation ( r <0.60) was observed between WSOC, MEOC, Abs 365,m , and mass concentrations of K + , indication that biomass burning was not the main source of BrC in the study location. The mass absorption efficiency of WSOC (MAE 365,w ) and MEOC (MAE 365,m ) and their ratios (MAE 365,m /MAE 365,w ) showed similar seasonal variations to Abs 365 . The average MAE 365 value of the water-insoluble fraction of MEOC (4.10±5.15) m 2 ·g -1 was 6.0 and 2.9 times higher than that of MAE 365,w and MAE 365,m , respectively, suggested that BrC absorption was primarily attributable to water-insoluble components. In comparison to the absorption Ångström exponent of WSOC ( Å WSOC ), Å MEOC displayed marked temporal variability, which might be related to the seasonal variation in the emission of water-insoluble chromophores. According to the PCA results, the light absorption of PM 2.5 organic was mainly attributed to secondary formation and anthropogenic primary emissions rather than biomass burning.

Zaoren Anshen prescription preparations(ZRASs), which are prepared from three traditional Chinese herb medicines, namely fried Zizyphi Spinosae Semen, Salvia Miltiorrhizae Radix et Rhizoma and vinegar-processed Schisandrae Chinensis Fructus, are a series of proprietary Chinese medicines for the treatment of insomnia, amnesia and dizzy in clinic. In recent years, pharmacodynamic effect, chemical constituents and quality control of ZRASs had been extensively studied for the purpose of ensuring their safety, efficacy and stability, and a great progress had been made. However, there is no review of the research advance of ZRASs up to date. The present review summarized the research advance of ZRASs in quality control standards, chemical constituents, pharmacodynamic effects, and chemical analysis for the first time, with the aim to provide a reference for further studies on the effective constituents and quality control of ZRASs.

Objective: To detect the long-term response to unilateral anterior crossbite (UAC) in masticatory muscles and in molecular biomarkers of peripheral blood leukocytes., Design: Fifty-six six-week-old Sprague-Dawley rats were used. The gene-fold changes in peripheral blood leukocytes were detected by the microarray analysis to compare the rats that received 20-week UAC treatment with age-matched controls (n = 4). Muscle atrophy-related gene Fbxo32 was selected based on the data of the microarray analysis verified by using real-time PCR. The remaining 36 rats were randomly separated in the UAC and control groups at 12 and 20 weeks (n = 12). The protein expression of Fbxo32 and the muscle injury and myogenesis-related markers, αB-crystallin and desmin, were detected in the masseter and lateral pterygoid muscles by western blot assay., Results: In the 20-week UAC group, the masseter muscle weight was lower than that in the age-matched control group, and the expression level of Fbxo32 gene in peripheral blood leukocytes was increased according to the microarray analysis confirmed by real-time PCR detection. The increased protein expression levels of Fbxo32 were detected in the masseter in the 20-week UAC group, and the protein expression levels of desmin and αB-crystallin were decreased at this time point. No similar changes were detected in the lateral pterygoid muscle., Conclusions: Masseter atrophy is induced by long-term stimulation of UAC. The increased expression of the Fbxo32 gene in peripheral blood leukocytes may be a candidate biological marker of masseter atrophy., (Copyright © 2020. Published by Elsevier Ltd.)

Herein, an anionic metal-organic framework, formulated as {[Zn 3 (OH)(bmipia)(H 2 O) 3 ] 4 ·[Zn(H 2 O)6.5] 2 } n (FCS-3), was prepared from zinc ions and semi-rigid carboxylate ligands of 5-[N,N-bis(5-methylisophthalic acid)amion] isophthalic acid (H 6 bmipia) and was employed as a unique fluorescence turn-on chemical sensor for the ultra-sensitive detection of various antibiotics in the aqueous phase.

Chromosomal abnormalities (CAs) can cause spontaneous miscarriage and increase the incidence of subsequent pregnancy loss and other complications. Presently, CAs are detected mainly by array comparative genomic hybridization (CGH) and single nucleotide polymorphism microarrays. The present study developed a low‑coverage next‑generation sequencing method to detect CAs in spontaneous miscarriage and assess its clinical performance. In total, 1,401 patients who had experienced an abortion were enrolled in the present study and divided into two groups. In group I, 437 samples that had been previously validated by array CGH were used to establish a method to detect CAs using a semiconductor sequencing platform. In group II, 964 samples, which were not verified, were assessed using established methods with respect to clinical significance. Copy number variant (CNV)‑positive and euploidy samples were verified by array CGH and short tandem repeat profiling, respectively, based on quantitative fluorescent PCR. The low‑coverage sequencing method detected CNVs >1 Mb in length and a total of 3.5 million unique reads. Similar results to array CGH were obtained in group I, except for six CNVs <1 Mb long. In group II, there were 341 aneuploidies, 195 CNVs, 25 mosaicisms and 403 euploidies. Overall, among the 1,401 abortion samples, there were 536 aneuploidies, 263 CNVs, 34 mosaicisms, and 568 euploidies. Trisomies were present in all autosomal chromosomes. The most common aneuploidies were T16, monosomy X, T22, T15, T21 and T13. Furthermore, one tetrasomy 21, one CNV associated with Wolf‑Hirschhorn syndrome, one associated with DiGeorge syndrome and one associated with both Prader‑Willi and Angelman syndromes were identified. These four cases were confirmed by short tandem repeat profiling and array CGH. Quantitative fluorescent PCR revealed nine polyploidy samples. The present method demonstrated equivalent efficacy to that of array CGH in detecting CNVs >1 Mb, with advantages of requiring less input DNA and lower cost.

A new Schiff base copper(II) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] copper (II) (M1) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M1 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 and HUVEC, by MTT (3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazoliumbromide) assays. The IC 50 (50% inhibition concentrations) is in the range of 5.13-11.68 μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M1 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, M1 increased intracellular ROS (Reactive oxygen species) levels in a dose-dependent manner. Western blot analysis indicated M1 dramatically decrease c-Myc transcription factor and KLF5 (Krüppel-like factor 5) protein expression levels in HeLa. M1 did not inhibit proteasomal activity. Finally, M1 induced DNA damages and activated the DNA damage repair pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Postflight orthostatic intolerance has been regarded as a major adverse effect after microgravity exposure, in which cerebrovascular adaptation plays a critical role. Our previous finding suggested that dedifferentiation of vascular smooth muscle cells (VSMCs) might be one of the key contributors to cerebrovascular adaptation under simulated microgravity. This study was aimed to confirm this concept and elucidate the underlying mechanisms., Materials and Methods: Sprague Dawley rats were subjected to 28-day hindlimb-unloading to simulate microgravity exposure. VSMC dedifferentiation was evaluated by ultrastructural analysis and contractile/synthetic maker detection. The role of T-type Ca V 3.1 channel was revealed by assessing its blocking effects. MiR-137 was identified as the upstream of Ca V 3.1 channel by luciferase assay and investigated by gain/loss-of-function approaches. Calcineurin/nuclear factor of activated T lymphocytes (NFAT) pathway, the downstream of Ca V 3.1 channel, was investigated by detecting calcineurin activity and NFAT nuclear translocation., Results: Simulated microgravity induced the dedifferentiation and proliferation in rat cerebral VSMCs. T-type Ca V 3.1 channel promoted the dedifferentiation and proliferation of VSMC. MiR-137 and calcineurin/NFATc3 pathway were the upstream and downstream signalling of T-type Ca V 3.1 channel in modulating the dedifferentiation and proliferation of VSMCs, respectively., Conclusions: The present work demonstrated that miR-137 and its target T-type Ca V 3.1 channel modulate the dedifferentiation and proliferation of rat cerebral VSMCs under simulated microgravity by regulating calcineurin/NFATc3 pathway., (© 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Objective: Dental occlusion are frequently changed in clinic. Molecular responses in jaw muscles to aberrant dental occlusion are changes are attractive, yet remain are obscure., Design: Unilateral anterior crossbite (UAC) prostheses were applied to Sprague-Dawley rats and then ceased after two weeks to detect the reactions of the masseter, a representative jaw elevator, and the lateral pterygoid muscle (LPM), a representative jaw depressor., Results: Two weeks of UAC elicited mild injury of the two muscles. Myogenesis and protective reactions were detected as increases in αB-crystallin expression in the masseter after 3 days and in the LPM after 2 weeks, and increases in desmin expression in both muscles after 2 weeks. A switch in fibre types from IIb to IIx occurred in the LPM but not in the masseter. Inflammatory responses, shown by the infiltration of inflammatory cells and increases in TNF-α mRNA expression, and fibrosis responses, shown by increased mRNA expression of Type I and III collagens, appeared very mild in the two muscles. These responses were partially recovered by the cessation of UAC. During the whole process, no obvious changes were observed in mitochondrial function, as indicated by the levels of proliferator-activated receptor γ coactivator 1α, mitofusin-2 and voltage-dependent anion channel., Conclusions: UAC causes injury and very limited inflammatory and fibrosis adaption in the masseter and LPM. Both muscles respond with myogenesis and protective activity. The LPM responds also with muscle fibre isoform alternations. These alterations were partially recovered by the cessation of dental stimulation at an early stage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to explore the effect of circ MTHFD2 on resistance to pemetrexed (MTA) in gastric cancer by regulating the expression of micro ribonucleic acid (miR)-124., Materials and Methods: Human gastric cancer MGC-803 cells were induced by MTA at an increasing concentration. MGC-803/MTA resistant cell model was successfully established after 5 months. The half-maximal inhibitory concentration (IC50) of MTA on the two kinds of cells was detected via cell counting kit-8 (CCK-8) assay. Differentially expressed circular RNAs (circRNAs) were screened using circRNA microarray analysis. Meanwhile, the target miRNAs of circRNAs were predicted using bioinformatics tool and verified via luciferase reporter assay, respectively. In MGC-803 cells, the effects of overexpression and knockdown of circ MTHFD2 on the expression of miR-124 were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the effects of circ MTHFD2 on the protein expressions of FDZ5 and multidrug resistance gene-1 (MDR-1) were detected via Western blotting., Results: MGC-803/MTA resistant cell lines were successfully constructed via persistent drug exposure to MTA at an increasing concentration for 5 months. Compared with parental cells, MGC-803/MTA resistant cells showed significantly enhanced drug resistance. Subsequently, differentially expressed circRNAs were screened using circRNA microarray analysis. A total of 673 circRNAs were screened out based on Fold Change >3 and adjusted p-value. The results of qRT-PCR showed that the expression levels of all differentially expressed circRNAs were significantly changed when compared with MGC-803/MTA resistant cells. Compared with MGC-803/MTA resistant cells, the drug resistance of cells increased significantly in circ MTHFD2 overexpression group. However, it markedly decreased in circ MTHFD2 knockdown group. According to the results of bioinformatics and luciferase reporter assay, circ MTHFD2 could target bind to miR-124. In MGC-803/MTA cells, miR-124 could remarkably increase the resistance of MGC-803/MTA cells to MTA. Western blotting results revealed that overexpression of circ MTHFD2 significantly increased the protein expressions of FDZ5 and MDR-1. However, miR-124 mimics reversed the inhibitory effect of circ MTHFD2 on FDZ5 and MDR-1., Conclusions: Circ MTHFD2 directly binds to miR-124 through the molecular sponge effect. This may induce increased protein expression of MDR-1, ultimately enhancing the drug resistance of MGC-803/MTA cells.

Objectives: To detect whether early growth response 1 (EGR1) in peripheral blood leucocytes (PBLs) indicates temporomandibular joint (TMJ) osteoarthritis (OA) lesions., Materials and Methods: Egr1 mRNA expression levels in PBLs were detected in eight malocclusion patients without temporomandibular disorder (TMD) signs and 16 malocclusion patients with clinical TMD signs with (eight) or without (eight) imaging signs of TMJ OA. Twelve 6-week-old rats were randomized to a control group and a unilateral anterior crossbite (UAC) group and were sampled at 4 weeks. The Egr1 mRNA expression levels in PBLs and protein expression levels in different orofacial tissues were measured., Results: Patients with TMD signs with/without TMJ OA diagnosis showed lower Egr1 mRNA expression levels in PBLs than patients without TMD signs. The lower Egr1 mRNA expression was also found in the PBLs of UAC rats, which were induced to exhibit early histo-morphological signs of TMJ OA lesions. In subchondral bone of UAC rats, EGR1 protein expression was decreased, co-localization of EGR1 with osterix or dentin matrix protein-1 was identified, and the number of EGR1 and osterix double-positive cells was reduced (all p < .05)., Conclusion: Egr1 reduction in PBLs potentially indicates subchondral bone OA lesions at an early stage., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objective: We aimed to develop a mouse model predominating in a proliferative response in the articular cartilage of the temporomandibular joints., Materials and Methods: Bilateral anterior elevation of occlusion was developed by installing metal tubes onto the incisors of mice with edge-to-edge relation to prevent tooth wear, leading to an increase in the vertical height of the dental occlusion with time. Morphological changes and expression changes in Cyclin D1, Aggrecan, and type II and type X collagen in the mandibular condylar cartilage were detected. In addition, cells were isolated from the mandibular condylar cartilage and exposed to cyclic tensile strain (CTS)., Results: Compared with age-matched controls, the tooth length was longer at 3 weeks, 7 weeks, and 11 weeks in BAE mice (p < 0.05), with increased condylar cartilage thickness, matrix amount, and cell number (p < 0.05). Compared with the deep zone cells, CTS stimulated the superficial zone cells to express a higher level of proliferating cell nuclear antigen, Cyclin D1, Aggrecan, and type II collagen but a lower level of type X collagen and alkaline phosphatase., Conclusion: Bilateral anterior elevation stimulated the proliferative response in the mandibular condylar cartilage, offering a new therapeutic strategy for cartilage degeneration., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty-four six-week-old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene-fold changes in PBLs were detected by a microarray analysis comparing rats that received 20-week unilateral anterior crossbite (UAC) treatment with age-matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA-like lesions. The other twenty-four rats were randomly placed in the UAC and control groups at 12- and 20-week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real-time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1-positive, EXPH1-positive and IL10-positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation., (© 2019 The Authors. Journal of Oral Rehabilitation Published by John Wiley & Sons Ltd.)

The functional and structural adaptations in cerebral arteries could be one of the fundamental causes in the occurrence of orthostatic intolerance after space flight. In addition, emerging studies have found that many cardiovascular functions exhibit circadian rhythm. Several lines of evidence suggest that space flight might increase an astronaut's cardiovascular risks by disrupting circadian rhythm. However, it remains unknown whether microgravity disrupts the diurnal variation in vascular contractility and whether microgravity impacts on circadian clock system. Sprague-Dawley rats were subjected to 28-day hindlimb-unweighting to simulate the effects of microgravity on vasculature. Cerebrovascular contractility was estimated by investigating vasoconstrictor responsiveness and myogenic tone. The circadian regulation of Ca V 1.2 channel was determined by recording whole-cell currents, evaluating protein and mRNA expressions. Then the candidate miRNA in relation with Ca 2+ signal was screened. Lastly, the underlying pathway involved in circadian regulation of cerebrovascular contractility was determined. The major findings of this study are: (1) The clock gene BMAL1 could induce the expression of miR-103, and in turn modulate the circadian regulation of Ca V 1.2 channel in rat cerebral arteries at post-transcriptional level; and (2) simulated microgravity disrupted intrinsic diurnal oscillation in rat cerebrovascular contractility by altering circadian regulation of BMAL1/miR-103/Ca V 1.2 signal pathway.

Background: The temporomandibular joint (TMJ) disc plays a role in joint movement and in load absorbance and distribution. An experimental unilateral anterior crossbite (UAC) prosthesis induces mandibular condylar cartilage degeneration in rats. However, the changes in the articular disc are still unknown., Objective: To describe changes in the TMJ discs of UAC rats., Methods: The discs of fifty-four Sprague-Dawley rats, equally distributed into a UAC group and an age-matched sham-operated control group at 4, 12 and 20 weeks (n = 9), were evaluated by gross and histomorphological observation and by detection at the mRNA or protein expression levels of the markers related to the matrix elements., Results: No macro- or micro-morphological differences were observed between groups. However, there were catabolic degradative changes at the molecular level in the UAC group, showing a significant reduction in the mRNA and/or protein expression levels of many molecules. The reduction became worse with time (P < 0.05). The reduced molecules included: (a) those related to the extracellular matrix, such as type I collagen, decorin and fibromodulin; (b) those related to chondrogenesis, such as type II collagen and aggrecan; and (c) those related to osteogenesis, such as alkaline phosphatase and runt-related transcription factor 2. The mRNA expression of vascular endothelial growth factor did not change. In contrast, fibronectin, which can promote wound healing, and its N-terminal fragment, which can induce cartilage degradation, were accumulated (P < 0.05)., Conclusion: TMJ discs were stimulated to catabolic changes by the aberrant dental occlusion and seemed to go to inanimate with time., (© 2018 John Wiley & Sons Ltd.)

The essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding their signalling cascades completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP 3 , functions as a phosphoinositide-signalling mediator for synaptic plasticity. BDNF application caused Phldb2 recruitment toward postsynaptic membrane in dendritic spines, whereas PI3K inhibition resulted in its reduced accumulation. Phldb2 bound to postsynaptic scaffolding molecule PSD-95 and was crucial for localization and turnover of PSD-95 in the spine. Phldb2 also bound to GluA1 and GluA2. Phldb2 was indispensable for the interaction between NMDA receptors and CaMKII, and the synaptic density of AMPA receptors. Therefore, PIP 3 -responsive Phldb2 is pivotal for induction and maintenance of LTP. Memory formation was impaired in our Phldb2 -/- mice.

A manganese Schiff base complex with N,N'-1,2-phenylenediamine-bis(salicyladimine) was synthesized and characterized by X-ray crystallography. This complex was administered intragastrically to alloxan-diabetic mice 3 weeks. In vivo tests showed that the complex significantly lowered serum glucose levels in alloxan-diabetic mice at doses of 77 mg V kg -1 . Meanwhile, this complex was investigated as dipeptidyl peptidase IV (DPP-IV) inhibitor for the treatment of type 2 diabetes. The compound exhibit moderate inhibition against DPP-IV and possessed an IC 50 value of 30 μM. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that it was a noncompetitive inhibitor of DPP-IV and Ki value was 136.3 μM. Moreover, molecular modeling studies suggested that the complex could fit well within the active-site cleft of DPP-IV. An acute toxicity study showed that animals treated intragastically with complex 1 at a dose of 5.0 g/kg did not show any significantly abnormal signs. These preliminary results suggest that the manganese Schiff base complex can induce a hypoglycemic effect in alloxan-diabetic mice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Multiple cellular components, including neuronal, glial and endothelial cells, are involved in the sophisticated pathological processes following central nervous system injury. The pathological process cannot reduce damage or improve functional recovery by merely targeting the molecular mechanisms of neuronal cell death after central nerve system injuries. Eph receptors and ephrin ligands have drawn wide attention since the discovery of their extensive distribution and unique bidirectional signaling between astrocytes and neurons. The roles of Eph/ephrin bidirectional signaling in the developmental processes have been reported in previous research. Recent observations suggest that Eph/ephrin bidirectional signaling continues to be expressed in most regions and cell types in the adult central nervous system, playing diverse roles. The Eph/ephrin complex mediates neurogenesis and angiogenesis, promotes glial scar formation, regulates endocrine levels, inhibits myelin formation and aggravates inflammation and nerve pain caused by injury. The interaction between Eph and ephrin is also considered to be the key to angiogenesis. This review focuses on the roles of Eph/ephrin bidirectional signaling in the repair of central nervous system injuries., Competing Interests: The authors declare no competing financial interests