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1.
J Am Chem Soc ; 146(19): 12969-12975, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38625041

ABSTRACT

Separation of methanol/benzene azeotrope mixtures is very challenging not only by the conventional distillation technique but also by adsorbents. In this work, we design and synthesize a flexible Ca-based metal-organic framework MAF-58 consisting of cheap raw materials. MAF-58 shows selective methanol-induced pore-opening flexibility. Although the opened pores are large enough to accommodate benzene molecules, MAF-58 shows methanol/benzene molecular sieving with ultrahigh experimental selectivity, giving 5.1 mmol g-1 high-purity (99.99%+) methanol and 2.0 mmol g-1 high-purity (99.97%+) benzene in a single adsorption/desorption cycle. Computational simulations reveal that the preferentially adsorbed, coordinated methanol molecules act as the gating component to selectively block the diffusion of benzene, offering a new gating adsorption mechanism.

2.
Gerontology ; 70(2): 115-124, 2024.
Article in English | MEDLINE | ID: mdl-37926080

ABSTRACT

INTRODUCTION: Previous studies have suggested that the D-dimer to fibrinogen ratio (DD/Fg) could be a potential predictor for deep vein thrombosis, pulmonary embolism, and stroke severity. However, the association between plasma DD/Fg and functional outcome following acute ischemic stroke (AIS) has been unclear. METHODS: Our study followed the STROBE guideline and used a prospective cohort design to investigate this association. A total of 454 patients with AIS were enrolled consecutively in our study, and the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were assessed for stroke severity and functional outcome, respectively. RESULTS: We found a significant difference in DD/Fg values between the three groups based on NIHSS scores at admission. Specifically, the DD/Fg values were higher in the poor functional outcome group (mRS score of 2-6) compared to the favorable functional outcome group (mRS score of 0-1) at the 1-year follow-up (p < 0.001). Additionally, the DD/Fg values were independently associated with poor functional prognosis at 1 year following the onset of stroke, even after adjusting for potential confounders (OR 9.21, 95% CI, 3.68-23.02, p < 0.001). CONCLUSIONS: Our findings suggest that DD/Fg values at admission may serve as risk predictors for poor functional outcomes in patients with AIS 1 year after the stroke.


Subject(s)
Fibrin Fibrinogen Degradation Products , Ischemic Stroke , Stroke , Humans , Fibrinogen , Longitudinal Studies , Prospective Studies , Treatment Outcome , Retrospective Studies
3.
Mar Drugs ; 22(6)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38921589

ABSTRACT

Overwhelming evidence points to an aberrant Wnt/ß-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus Phomopsis asparagi DHS-48 obtained from mangrove plant Rhizophora mangle via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/ß catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G0/G1 phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/ß-catenin signaling by inhibiting ß-catenin transcriptional activity and abrogating ß-catenin translocated to the nucleus; down-regulating the transcription level of ß-catenin-stimulated Wnt target gene and the expression of related proteins including p-GSK3-ß, ß-catenin, LEF1, Axin1, c-Myc, and CyclinD1; and up-regulating GSK3-ß expression, which indicates that DD-9 stabilized the ß-catenin degradation complex, thereby inducing ß-catenin degradation and inactivation of the Wnt/ß-catenin pathway. The possible interaction between DD-9 and ß-catenin and GSK3-ß protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-ß-mediated crosstalk with the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.


Subject(s)
Apoptosis , Cell Proliferation , Wnt Signaling Pathway , Humans , HeLa Cells , Apoptosis/drug effects , Wnt Signaling Pathway/drug effects , Cell Proliferation/drug effects , Hep G2 Cells , beta Catenin/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Liver Neoplasms/drug therapy , Xanthones/pharmacology , Xanthones/chemistry , Xanthones/isolation & purification , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Movement/drug effects , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology
4.
J Am Chem Soc ; 145(1): 487-497, 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36572645

ABSTRACT

This work demonstrates an effective and robust approach to regulate phase behaviors of a block copolymer by programming local features into otherwise homogeneous linear chains. A library of sequence-defined, isomeric block copolymers with globally the same composition but locally different side chain patterns were elaborately designed and prepared through an iterative convergent growth method. The precise chemical structure and uniform chain length rule out all inherent molecular defects associated with statistical distribution. The local features are found to exert surprisingly pronounced impacts on the self-assembly process, which have yet to be well recognized. While other molecular parameters remain essentially the same, simply rearranging a few methylene units among the alkyl side chains leads to strikingly different phase behaviors, bringing about (i) a rich diversity of nanostructures across hexagonally packed cylinders, Frank-Kasper A15 phase, Frank-Kasper σ phase, dodecagonal quasicrystals, and disordered state; (ii) a significant change of lattice dimension; and (iii) a substantial shift of order-to-disorder transition temperature (up to 40 °C). Different from the commonly observed enthalpy-dominated cases, the frustration due to the divergence between the native molecular geometry originating from side chain distribution and the local packing environment mandated by lattice symmetry is believed to play a pivotal role. Engineering the local chain feature introduces another level of structural complexity, opening up a new and effective pathway for modulating phase transition without changing the chemistry or composition.

5.
Acc Chem Res ; 55(20): 2966-2977, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36067359

ABSTRACT

Chemical separations, mostly based on heat-driven techniques such as distillation, account for a large portion of the world's energy consumption. In principle, differential adsorption is a more energy-efficient separation method, but conventional adsorbent materials are still not effective for many industry-relevant mixtures. Porous coordination polymers (PCPs), or metal-organic frameworks (MOFs), are attractive for their well-defined, designable, modifiable, and flexible structures connecting to various potential applications. While the importance of the structural flexibility of MOFs in adsorption-based functions has been demonstrated, the understanding of this special feature is still in its infancy and mostly stays at the periodic structural transformation at the equilibrium state and the special shapes of single-component adsorption isotherms. There are many confusions about the categorization and roles of various types of flexibility. This Account discusses the role of flexibility of MOFs for adsorptive separation, mainly from the thermodynamic and kinetic points of view.As the classic type of framework flexibility, guest-driven structural transformations and the corresponding adsorption isotherms can be thermodynamically described by the energies of the host-guest system. The highly guest-specific pore-opening action showing contrasting single-component adsorption isotherms is regarded as a strategy for achieving molecular sieving without the need for aperture size control, but its effect and role for mixture separation are still controversial. Quantitative mixture adsorption/separation experiments showed that the common periodic (cooperative) pore-opening action leads to coadsorption of molecules smaller than the opened aperture, while the aperiodic (noncooperative) one can achieve inversed molecular sieving under a thermodynamic mechanism.The energy barrier and structure in the nonequilibrium state are also important for flexibility and adsorption/separation. With suitable energy barriers between metastable structures, new types of framework flexibility such as aperture gating can be realized. While kinetically controlled gating flexibility is usually ignored because of the difficulty of characterization or considered as disadvantageous for separation because of the variable aperture size, it plays a critical role in most kinetic separation systems, including adsorbents conventionally regarded as rigid. With the concept of gating flexibility, the meanings of aperture and guest sizes for judging molecular sieving need to be reconsidered. Gating flexibility depends on not only the host itself but also the guest, the host-guest interaction, and the external environment such as temperature, which can be rationally tuned to achieve special adsorption/separation behaviors such as inversed temperature dependence, molecular sieving, and even inversed thermodynamic selectivity. The comprehensive understanding of the thermodynamic and kinetic bases of flexibility will give a new horizon for next-generation separation materials beyond MOFs and adsorbents.


Subject(s)
Metal-Organic Frameworks , Adsorption , Metal-Organic Frameworks/chemistry , Porosity , Temperature , Thermodynamics
6.
BMC Cancer ; 23(1): 564, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37340357

ABSTRACT

BACKGROUND AND AIM: Although antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA. METHODS: A total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan-Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created. RESULTS: This study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase < 50 IU/L and cirrhosis groups, primary nonresponse was related to poor overall survival and progression-free survival. Based on multivariate risk analysis, primary non-response (hazard ratio (HR) = 1.883, 95% CI 1.289-2.751, P = 0.001), tumor multiplicity (HR = 1.488, 95% CI 1.036-2.136, P = 0.031), portal vein tumor thrombus (HR = 2.732, 95% CI 1.859-4.015, P < 0.001), hemoglobin < 120 g/L (HR = 2.211, 95% CI 1.548-3.158, P < 0.001) and tumor size ≥ 5 cm (HR = 2.202, 95% CI 1.533-3.163, P < 0.001) were independent risk factors for 1-year OS. According to the scoring chart, patients were divided into three risk groups (high-, medium-, and low-risk groups) with mortality rates of 61.7%, 30.5%, and 14.1%, respectively. CONCLUSIONS: The level of viral decline at 3 months post-antiviral treatment may predict the OS of patients with HBV-related HCC, and primary non-response may shorten the median survival time of patients with high HBV-DNA levels.


Subject(s)
Antiviral Agents , Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Antiviral Agents/therapeutic use , Humans , Hepatitis B/complications , Hepatitis B/drug therapy , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/virology , Liver Neoplasms/drug therapy , Liver Neoplasms/virology , Prognosis , Survival Rate , Retrospective Studies , China , DNA, Viral/blood , Male , Female , Middle Aged , Aged
7.
Chirality ; 35(6): 376-386, 2023 06.
Article in English | MEDLINE | ID: mdl-36924145

ABSTRACT

Studies on the differences between chiral pesticide enantiomers have caused widespread concern in the last decade. In the current work, the selective behaviors and different biological activities of paclobutrazol enantiomers during Chinese cabbage pickling process were evaluated. Results of degradation kinetics indicated that when paclobutrazol reside in raw material (Chinese cabbage) and was introduced into the pickling process, the degradation rates of the two paclobutrazol enantiomers were significantly different, the half-lives of (2R, 3R)-paclobutrazol (R-paclobutrazol) and (2S, 3S)-paclobutrazol (S-paclobutrazol) were 18.24 and 6.19 d, respectively. Besides, the conversion between the two enantiomers could also be observed, and the conversion rate of R-paclobutrazol to S-paclobutrazol was slower than that of reverse process. In addition, from the analysis of 16S rRNA and ITS sequencing, we inferred that the degradation of paclobutrazol was probably due to the presence of Pseudomonas and Serratia. Moreover, there has a significant difference in biological activity between R-paclobutrazol and S-paclobutrazol and shown an obviously enantiomeric effects on microbial community composition of pickling system. Besides, the analysis of microbial community displayed R-paclobutrazol might inhibit the growth of Erwinia (a sort of plant pathogens). Results from this study served to enhance our understanding of chiral pesticide residues on food safety and the potential risks to human health.


Subject(s)
Brassica , Pesticides , Humans , RNA, Ribosomal, 16S , Stereoisomerism
8.
Int J Psychiatry Clin Pract ; 27(2): 118-126, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35980319

ABSTRACT

OBJECTIVES: We investigated the differences in serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) levels and clinical symptoms with first-episode depression at different ages. METHODS: Ninety patients (15-60 years old) diagnosed with first-episode depression were enrolled as the study group, and they were divided into early-onset, adult and late-onset groups. The age-matched control groups were healthy volunteers. Serum BDNF and GDNF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 9 was used for t tests, one-way ANOVAs, chi-square tests, and correlation analyses. p < 0.05 indicated significant differences. RESULTS: Serum BDNF and GDNF levels were lower in the whole study group and the three subgroups than in the healthy groups. Illness severity, anxiety and education were higher in the early-onset than late-onset patients. Serum BDNF levels were lower in the adult than late-onset patients. Serum BDNF levels were negatively correlated with patient CGI-SI scores. After the LSD test for multiple comparisons, the results were also significant. CONCLUSIONS: Low serum BDNF and GDNF levels may be involved in the pathophysiology of first-episode depression, and there were differences in serum BDNF levels at different ages, verifying that serum BDNF and GDNF could serve as potential biomarkers of depression. KEY POINTSDepression is often conceptualised as a systemic illness with different biological mechanisms, but satisfactory explanations have not been provided thus far.The aim of our study was to investigate differences in serum BDNF and GDNF levels and their relationships with clinical symptoms in patients with first-episode depression at different ages.The potential of the neurotrophic factor hypothesis to advance the diagnosis and treatment of depression will be a very exciting new strategy for future research.


Subject(s)
Brain-Derived Neurotrophic Factor , Glial Cell Line-Derived Neurotrophic Factor , Adolescent , Adult , Humans , Middle Aged , Young Adult , Anxiety , Depression
9.
Angew Chem Int Ed Engl ; 62(24): e202303374, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37040094

ABSTRACT

The ethanol/water separation challenge highlights the adsorption capacity/selectivity trade-off problem. We show that the target guest can serve as a gating component of the host to block the undesired guest, giving molecular sieving effect for the adsorbent possessing large pores. Two hydrophilic/water-stable metal azolate frameworks were designed to compare the effects of gating and pore-opening flexibility. Large amounts (up to 28.7 mmol g-1 ) of ethanol with fuel-grade (99.5 %+) and even higher purities (99.9999 %+) can be produced in a single adsorption process from not only 95 : 5 but also 10 : 90 ethanol/water mixtures. More interestingly, the pore-opening adsorbent possessing large pore apertures showed not only high water adsorption capacity but also exceptionally high water/ethanol selectivity characteristic of molecular sieving. Computational simulations demonstrated the critical role of guest-anchoring aperture for the guest-dominated gating process.

10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(11): 1678-1685, 2023 Nov 28.
Article in English, Zh | MEDLINE | ID: mdl-38432858

ABSTRACT

OBJECTIVES: Childhood traumatic experiences greatly influenced the brain network activities of patients with depression, and there is an urgent need to explore the temporal dynamics for these changes. This study aims to investigate the abnormalities of resting-state electroencephalogram (EEG) microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. METHODS: Using resting-state EEG microstate analysis, we explored the temporal dynamics of brain activity in patients with adolescent depression. This study selected 66 adolescents with depression as a patient group, and 27 healthy adolescents as a healthy control group. A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates. Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. RESULTS: In this study, significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group. Notably, there was a statistically significant difference (P<0.05) in the occurrence of microstate A across 2 groups, exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores (Spearman's rho=-0.31, P=0.013). Furthermore, patient-specific, non-random transitions from microstate B to A (Spearman's rho=-0.30, P=0.015) and C to A (Spearman's rho=-0.31, P=0.013) were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group, showing statistically significant differences when comparing to the healthy controls (P<0.05). Upon stratification into quartiles based on the emotional abuse factor scores, the occurrence of microstate A, as well as the transition rates from microstates B to A and C to A, retained statistical significance following adjustment for multiple comparisons (all P<0.05). CONCLUSIONS: The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse. Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks. EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.


Subject(s)
Depression , Emotional Abuse , Humans , Adolescent , Algorithms , Brain , Electroencephalography
11.
Nat Mater ; 20(8): 1113-1120, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33859384

ABSTRACT

Metastable 1T'-phase transition metal dichalcogenides (1T'-TMDs) with semi-metallic natures have attracted increasing interest owing to their uniquely distorted structures and fascinating phase-dependent physicochemical properties. However, the synthesis of high-quality metastable 1T'-TMD crystals, especially for the group VIB TMDs, remains a challenge. Here, we report a general synthetic method for the large-scale preparation of metastable 1T'-phase group VIB TMDs, including WS2, WSe2, MoS2, MoSe2, WS2xSe2(1-x) and MoS2xSe2(1-x). We solve the crystal structures of 1T'-WS2, -WSe2, -MoS2 and -MoSe2 with single-crystal X-ray diffraction. The as-prepared 1T'-WS2 exhibits thickness-dependent intrinsic superconductivity, showing critical transition temperatures of 8.6 K for the thickness of 90.1 nm and 5.7 K for the single layer, which we attribute to the high intrinsic carrier concentration and the semi-metallic nature of 1T'-WS2. This synthesis method will allow a more systematic investigation of the intrinsic properties of metastable TMDs.

12.
BMC Cancer ; 22(1): 185, 2022 Feb 18.
Article in English | MEDLINE | ID: mdl-35180841

ABSTRACT

BACKGROUND: The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. METHODS: A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. RESULTS: After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p < 0.05). In BCLC stages 0-B, HCC-related and non-HCC-related deaths significantly differed between younger and older individuals (p = 0.0019). CONCLUSION: In stage BCLC 0-B, age affects the long-term prognosis of patients.


Subject(s)
Age Factors , Carcinoma, Hepatocellular/mortality , Hepatectomy/mortality , Liver Neoplasms/mortality , Risk Assessment/statistics & numerical data , Adult , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
13.
Psychol Med ; 52(1): 48-56, 2022 01.
Article in English | MEDLINE | ID: mdl-32501194

ABSTRACT

BACKGROUND: Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months. RESULTS: Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an 'enriched' randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization. CONCLUSIONS: The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.


Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/prevention & control , Bayes Theorem , Antidepressive Agents/therapeutic use , Recurrence , Chronic Disease
14.
Ann Hepatol ; 27(2): 100672, 2022.
Article in English | MEDLINE | ID: mdl-35065261

ABSTRACT

INTRODUCTION: Among all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). METHODS: To develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. RESULTS: The model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor-lymph node-metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. CONCLUSIONS: Our study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.


Subject(s)
Carcinoma, Hepatocellular , End Stage Liver Disease , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Cell Count , Humans , Liver Neoplasms/pathology , Neoplasm Staging , Nomograms , Prognosis , Retrospective Studies , Severity of Illness Index
15.
Mar Drugs ; 20(2)2022 Feb 05.
Article in English | MEDLINE | ID: mdl-35200654

ABSTRACT

Demethylincisterol A3 (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation and migration of human liver (HepG2) and cervical cancer (HeLa) cells in vitro and it can induce cell apoptosis and arrest the cell cycle in the G1-phase. Mechanistically, we demonstrated that Sdy-1 executes its function via inhibition of the Wnt/ß-catenin signaling pathway. Sdy-1 may not inhibit the Wnt signaling pathway through the cascade reaction from upstream to downstream, but directly acts on ß-catenin to reduce its transcription level, thereby reducing the level of ß-catenin protein and further reducing the expression of downstream related proteins. The possible interaction between Sdy-1 and ß-catenin protein was further confirmed by molecular docking studies. In the nude mouse xenograft model, Sdy-1 can also significantly inhibit tumor growth. These results indicated that Sdy-1 is an efficient inhibitor of the Wnt signaling pathway and is a promising antitumor candidate for therapeutic applications.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Sterols/pharmacology , Uterine Cervical Neoplasms/drug therapy , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Female , HeLa Cells , Hep G2 Cells , Humans , Mice , Mice, Nude , Molecular Docking Simulation , Rhizophoraceae/chemistry , Sterols/isolation & purification , Wnt Signaling Pathway/drug effects , Xenograft Model Antitumor Assays
16.
Mar Drugs ; 20(8)2022 Aug 18.
Article in English | MEDLINE | ID: mdl-36005528

ABSTRACT

Three new cytochalasins, phomoparagins A-C (1-3), along with five known analogs (4-8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4-6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.


Subject(s)
Cytochalasins , Fungi , Cytochalasins/pharmacology , Immunosuppressive Agents/pharmacology , Molecular Structure , Phomopsis
17.
Sensors (Basel) ; 22(21)2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36365891

ABSTRACT

Intelligent manufacturing, defined as the integration of manufacturing with modern information technologies such as 5G, digitalization, networking, and intelligence, has grown in popularity as a means of boosting the productivity, intelligence, and flexibility of traditional manufacturing processes. The steel industry is a necessary support for modern life and economic development, and the Chinese steel industry's capacity has expanded to roughly half of global production. However, the Chinese steel industry is now confronted with high labor costs, massive carbon emissions, a low level of intelligence, low production efficiency, and unstable quality control. Therefore, China's steel industry has launched several large-scale intelligent manufacturing initiatives to improve production efficiency, product quality, manual labor intensity, and employee working conditions. Unfortunately, there is no comprehensive overview of intelligent manufacturing in China's steel industry. We began this research by summarizing the construction goals and overall framework for intelligent manufacturing of the steel industry in China. Following that, we offered a brief review of intelligent manufacturing for China's steel industry, as well as descriptions of two typical intelligent manufacturing models. Finally, some major technologies employed for intelligent production in China's steel industry were introduced. This research not only helps to comprehend the development model, essential technologies, and construction techniques of intelligent manufacturing in China's steel industry, but it also provides vital inspiration for the manufacturing industry's digital and intelligence updates and quality improvement.


Subject(s)
Industry , Steel , Commerce , Quality Control , Intelligence , China
18.
Angew Chem Int Ed Engl ; 61(28): e202204967, 2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35510692

ABSTRACT

Cu-based metal-organic frameworks have attracted much attention for electrocatalytic CO2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO2 reduction to C2 H4 /CH4 . By changing the size of ligand side groups, the C2 H4 /CH4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C2 H4 , CH4 , and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long-term electrocatalysis, they can retain the structures/morphologies without formation of Cu-based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C-C coupling to form C2 H4 . Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C2 H4 pathway is more sensitive than the CH4 one.

19.
J Am Chem Soc ; 143(44): 18744-18754, 2021 11 10.
Article in English | MEDLINE | ID: mdl-34714634

ABSTRACT

Molecular shape is an essential parameter that regulates the self-organization and recognition process, which has not yet been well appreciated and exploited in block polymers due to the lack of precise and efficient modulation methods. This work (i) develops a robust approach to break the intrinsic symmetry of linear polymers by introducing geometric features into otherwise homogeneous chains and (ii) quantitatively highlights the critical contribution of molecular geometry/architecture to the self-assembly behaviors. Iteratively connecting homologous monomers of different side chains according to pre-designed sequences generates discrete polymers with exact chemical structure, uniform chain length, and programmable side-chain gradient along the backbone, which transcribes into diverse shapes. The precise chemistry eliminates all the defects and heterogeneities, providing a delicate platform for fundamental inquiries into the role of molecular geometry. A rich collection of unconventional complex phases, including Frank-Kasper A15 and σ phases, as well as a dodecagonal quasicrystal phase, were captured in these rigorous single-component systems. The self-assembly behaviors are strikingly sensitive to subtle variations of geometry, such that simply migrating a few methylene units among the side chains would generate substantial differences in lattice size or phase stability, or even trigger a phase transition toward distinct structures. The phenomena can be rationalized with a geometric argument that nonuniform side chain distribution leads to conformational mismatch between two immiscible blocks, resulting in varied interfacial curvatures and distinct lattice symmetries. The profound contribution demonstrates that molecular geometry is an effective and robust parameter for structural engineering.

20.
BMC Cancer ; 21(1): 246, 2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33685417

ABSTRACT

BACKGROUND: Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. METHODS: A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. RESULTS: The C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. CONCLUSIONS: Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.


Subject(s)
Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Nomograms , alpha-Fetoproteins/analysis , Biopsy , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/therapy , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Liver/diagnostic imaging , Liver/pathology , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Treatment Outcome
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