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1.
J Cachexia Sarcopenia Muscle ; 15(3): 1177-1186, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38644549

ABSTRACT

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.


Subject(s)
Body Weight , Neoplasms , Humans , Male , Female , Neoplasms/mortality , Middle Aged , Prognosis , Aged , Cohort Studies , Adult
2.
Int J Biol Sci ; 19(16): 5104-5119, 2023.
Article in English | MEDLINE | ID: mdl-37928269

ABSTRACT

Flotillin-1 (FLOT1) is a member of the flotillin family and serves as a hallmark of lipid rafts involved in the process of signaling transduction and vesicular trafficking. Here, we find FLOT1 promotes gastric cancer cell progression and metastasis by interacting with BCAR1, through ERK signaling. FLOT1 regulates BCAR1 phosphorylation and translocation. Overexpression of FLOT1 increases, while knockdown of FLOT1 decreases gastric cancer cell proliferation, migration and invasion. BCAR1 knockdown could block FLOT1 induced gastric cancer cell proliferation, migration and invasion. Re-expression of wildtype rather than mutant BCAR1 (Y410F) could partially restore FLOT1 knockdown induced gastric cancer cell migration and invasion, while the restore could be inhibited by ERK inhibitor. Furthermore, FLOT1 and BCAR1 expression is closely related to gastric cancer patients' poor outcome. Thus, our findings confirm that BCAR1 mediates FLOT1 induced gastric cancer progression and metastasis through ERK signaling, which may provide a novel pathway for gastric cancer treatment.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Cell Line, Tumor , Signal Transduction/genetics , Membrane Proteins/metabolism , Crk-Associated Substrate Protein/metabolism
3.
Biomater Res ; 27(1): 112, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37941059

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. METHODS: Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. RESULTS: We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. CONCLUSIONS: In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI's properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

4.
World J Surg Oncol ; 21(1): 299, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37735407

ABSTRACT

BACKGROUND: To explore the diagnostic value of Caprini risk assessment model (2005) combined with D-dimer for deep vein thrombosis, and to exclude patients with low incidence of thrombosis who might not need anticoagulation after surgery. METHODS: A total of 171 colorectal cancer patients who underwent surgery from January 2022 to August 2022 were enrolled in this study. Caprini risk assessment model was used to evaluate patients the day before surgery, and full-length venous ultrasonography of lower extremity was used to assess whether patients had thrombosis one day before surgery and the sixth day after surgery. The value of D-dimer was measured by enzyme-linked immunosorbent assays on the first day after surgery, and clinical data of patients were collected during hospitalization. RESULTS: A total of 171 patients were divided into IPC Group and IPC + LMWH Group according to whether low molecular weight heparin (LMWH) were used to prevent thrombus after surgery. Eventually, 17.6% (15/85) patients in IPC Group and 7% (6/86) patients in IPC + LMWH Group developed DVT. Through separate analysis of IPC Group, it is found that Caprini score and D-dimer were independent risk factors for DVT (Caprini OR 3.39 [95% CI 1.38-8.32]; P = 0.008, D-Dimer OR 6.142 [95% CI 1.209-31.187]; P = 0.029). The area under ROC curve of Caprini risk assessment model is 0.792 (95% CI 0.69-0.945, P < 0.01), the cut-off value is 9.5, and the area under ROC curve of D-dimer is 0.738 (95%CI 0.555-0.921, P < 0.01), the cut-off value is 0.835 µg/mL, and the area under the ROC curve was 0.865 (95% CI 0.754-0.976, P < 0.01) when both of them were combined. Based on decision curve analysis, it is found that Caprini risk assessment model combined with D-dimer can benefit patients more. All patients are divided into four groups. When Caprini score < 10 and D-dimer < 0.835 µg/mL, only 1.23% (1/81) of patients have thrombosis and LMWH has little significance. When Caprini score > 10 and D-dimer > 0.835 µg/mL, the incidence of DVT is 38.7% (12/31) and LMWH should be considered. CONCLUSIONS: The Caprini risk assessment model and D-dimer can provide more accurate risk stratification for patients after laparoscopic radical resection of colorectal cancer.


Subject(s)
Colorectal Neoplasms , Laparoscopy , Venous Thrombosis , Humans , Heparin, Low-Molecular-Weight , Risk Assessment , Laparoscopy/adverse effects , Venous Thrombosis/diagnosis , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology , Colorectal Neoplasms/surgery
5.
Heliyon ; 9(7): e17630, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37483691

ABSTRACT

Background: Bowel volume loss during anus-preserving surgery (APS) may result in low anterior resection syndrome (LARS). We conducted this prospective observational cohort study to measure the incidence of LARS after surgery and evaluate the relationship between bowel volume loss and bowel function. Methods: Patients with R0 resectable rectal cancer who consented to several bowel function surveys through telephone interviews after the operation were included. Enrolled patients underwent standard APS for rectal cancer, and three length indexes, viz. length of excised bowel, length of the distal margin and length of the proximal margin (LPM) of fresh bowel specimens, were measured in vitro. Results: The three measured variables of the specimens showed a positively skewed distribution. Patient interviews revealed a trend of gradual improvement in bowel function. Univariate analyses revealed that longer LPM was associated with a significantly negative impact on bowel function at all time points. In multivariate analysis, LPM was found to be a significant risk factorstatistically significant, but its impact was not as strong as that of radiotherapy and low-middle tumour. Furthermore, there was no significant difference in the lymph node detection rate between <10-cm and ≥10-cm LPM groups. Conclusion: In APS for rectal cancer, bowel volume loss is an important factor causing postoperative bowel dysfunction. Controlling LPM to <10 cm may help improve postoperative bowel function.

6.
J Hazard Mater ; 459: 132029, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37499501

ABSTRACT

An innovative thermal desorption method, propylene glycol (PG)-mixed steam enhanced extraction, is proposed for a highly efficient remediation of polycyclic aromatic hydrocarbons (PAHs)-contaminated soil. It is found that injecting PG-mixed steam into soil column could obtain > 99% removal efficiencies of PAHs either for the pyrene-spiked soil, or for the contaminated field soil with high-molecular-weight PAHs. PG is a safe and low-cost dihydric alcohol with a boiling point higher than water. When the PG-mixed steam penetrated the contaminated soil, the PG vapor preferentially condensed to form a hot liquid with concentrated PG (e.g., from 30 wt% PG in gas phase to 90 wt% PG in the liquid phase), which would significantly solubilize the PAHs and enhance their desorption from soils. The results also revealed that the effluents derived from the PG-mixed steam could be purified by removing the desorbed PAHs using a simple coagulation treatment, and the recovered PG solution could be reused. The plant assay using wheat seeds showed that the remediated soil had a good regreening potential. Our results demonstrate that PG-mixed steam injection is a promising thermal desorption method for an efficient and sustainable remediation of PAHs-contaminated soil.

7.
Clin Nutr ; 42(6): 1048-1058, 2023 06.
Article in English | MEDLINE | ID: mdl-37178592

ABSTRACT

BACKGROUND & AIMS: The present study aimed to compare the ability of the GLIM criteria, PG-SGA and mPG-SGA to diagnose malnutrition and predict survival among Chinese lung cancer (LC) patients. METHODS: This was a secondary analysis of a multicenter, prospective, nationwide cohort study, 6697 LC inpatients were enrolled between July 2013 and June 2020. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and quadratic weighted Kappa coefficients were calculated to compare the ability to diagnose malnutrition. There were 754 patients who underwent follow-up for a median duration of 4.5 years. The associations between the nutritional status and survival were analyzed by the Kaplan-Meier method and multivariable Cox proportional hazard regression models. RESULTS: The median age of LC patients was 60 (53, 66), and 4456 (66.5%) were male. There were 617 (9.2%), 752 (11.2%), 1866 (27.9%), and 3462 (51.7%) patients with clinical stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ LC, respectively. Malnutrition was present in 36.1%-54.2% (as evaluated using different tools). Compared with the PG-SGA (used as the diagnostic reference), the sensitivity of the mPG-SGA and GLIM was 93.7% and 48.3%; the specificity was 99.8% and 78.4%; and the AUC was 0.989 and 0.633 (P < 0.001). The weighted Kappa coefficients were 0.41 for the PG-SGA vs. GLIM, 0.44 for the mPG-SGA vs. GLIM, and 0.94 for the mPG-SGA vs PG-SGA in patients with stage Ⅰ-Ⅱ LC. These values were respectively 0.38, 0.39, and 0.93 in patients with stage Ⅲ-Ⅳ of LC. In a multivariable Cox analysis, the mPG-SGA (HR = 1.661, 95%CI = 1.348-2.046, P < 0.001), PG-SGA (HR = 1.701, 95%CI = 1.379-2.097, P < 0.001) and GLIM (HR = 1.657, 95%CI = 1.347-2.038, P < 0.001) showed similar death hazard ratios. CONCLUSIONS: The mPG-SGA provides nearly equivalent power to predict the survival of LC patients as the PG-SGA and the GLIM, indicating that all three tools are applicable for LC patients. The mPG-SGA has the potential to be an alternative replacement for quick nutritional assessment among LC patients.


Subject(s)
Lung Neoplasms , Malnutrition , Humans , Male , Female , Cohort Studies , Prospective Studies , Malnutrition/diagnosis , Inpatients , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Nutritional Status , Nutrition Assessment
8.
Foods ; 12(5)2023 Mar 04.
Article in English | MEDLINE | ID: mdl-36900618

ABSTRACT

In a previous study, we demonstrated that the hydro extract of Mao Jian Green Tea (MJGT) promotes gastrointestinal motility. In this study, the effect of MJGT ethanol extract (MJGT_EE) in treating irritable bowel syndrome with constipation (IBS-C) in a rat model constructed via maternal separation combined with an ice water stimulation was investigated. First, a successful model construction was confirmed through the determination of the fecal water content (FWC) and the smallest colorectal distension (CRD) volume. Then, the overall regulatory effects of MJGT_EE on the gastrointestinal tract were preliminarily evaluated through gastric emptying and small intestinal propulsion tests. Our findings indicated that MJGT_EE significantly increased FWC (p < 0.01) and the smallest CRD volume (p < 0.05) and promoted gastric emptying and small intestinal propulsion (p < 0.01). Furthermore, mechanistically, MJGT_EE reduced intestinal sensitivity by regulating the expression of proteins related to the serotonin (5-hydroxytryptamine; 5-HT) pathway. More specifically, it decreased tryptophan hydroxylase (TPH) expression (p < 0.05) and increased serotonin transporter (SERT) expression (p < 0.05), thereby decreasing 5-HT secretion (p < 0.01), activating the calmodulin (CaM)/myosin light chain kinase (MLCK) pathway, and increasing 5-HT4 receptor (5-HT4R) expression (p < 0.05). Moreover, MJGT_EE enhanced the diversity of gut microbiota, increased the proportion of beneficial bacteria, and regulated the number of 5-HT-related bacteria. Flavonoids may play the role of being active ingredients in MJGT_EE. These findings suggest that MJGT_EE could serve as a potential therapeutic pathway for IBS-C.

9.
J Cell Mol Med ; 27(3): 392-402, 2023 02.
Article in English | MEDLINE | ID: mdl-36647700

ABSTRACT

Flotillin-1(FLOT1) has long been recognized as a tumour-promoting gene in several types of cancer. However, the expression and function of FLOT1 in glioblastomas (GBM) has not been elucidated. Here, in this study, we find that the expression level of FLOT1 in GBM tissue was much higher than that in normal brain, and the expression was even higher in the more aggressive subtypes and IDH status of glioma. Kaplan-Meier survival revealed that high FLOT1 expression is closely associated with poor outcome in GBM patients. FLOT1 knockdown markedly reduced the proliferation, migration and invasiveness of GBM cells, while FLOT1 overexpression significantly increases GBM cell proliferation, migration and invasiveness. Mechanistically, FLOT1 expression may play a potential role in the microenvironment of GBM. Therefore, FLOT1 promotes GBM proliferation and invasion in vitro and in vivo and may serve as a biomarker of prognosis and therapeutic potential in the fight against GBM.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/pathology , Prognosis , Tumor Microenvironment/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Brain Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Neoplasm Invasiveness/genetics , Cell Movement/genetics
11.
Inorg Chem ; 61(44): 17855-17863, 2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36282015

ABSTRACT

Deep-ultraviolet (DUV; <200 nm) nonlinear optical crystals arouse a great research interest in modern optical material science as they are key parts of solid-state lasers. Since KBe2BO3F2 (KBBF) still is the only crystal which can generate DUV coherent light practically, exploring other available structures in the DUV region by revising KBBF-family structure templates is necessary. In this paper, two KBBF-family structures are designed by adjusting the directions of BO3 groups or docking B and F atoms in known ß-Be2BO3F (BBF). The first BBF structure with a P6322 space group is designed by strictly aligning the BO3 groups of even layers and odd layers in ß-BBF. It is very interesting that docking B and F atoms forms novel B-F bonds, which destroy the inversion symmetry of the structure, making the centrosymmetric ß-BBF structure with the R3̅c space group convert to a noncentrosymmetric BBF structure having the R3c space group. This noncentrosymmetric BBF structure exhibits a DUV cutoff edge shorter than 150 nm and a second harmonic generation effect comparable to that of KH2PO4 (KDP; d36 = 0.39 pm/V), indicating its feasibility as a frequency-doubling crystal in the DUV region. Our conversion design provides an effective way for uncovering noncentrosymmetric structures in KBBF-family structures.

12.
Dalton Trans ; 51(33): 12432-12435, 2022 Aug 23.
Article in English | MEDLINE | ID: mdl-35943027

ABSTRACT

Cuproussiloxane (1) was prepared from the reaction of silanediol R(Me)Si(OH)2 (R = N(SiMe3)(2,6-iPr2C6H3)) and (CuMes)4 (Mes = 2,4,6-Me3C6H2). The prepared compound crystalizes into two self-assemblies: Cu24O24Si12Me12R12 ([(CuO)2Si(Me)R]12, 1a) and Cu20O20Si10Me10R10 ([(CuO)2Si(Me)R]10, 1b). 1a and 1b feature dodecagonal and decagonal prism X-ray structures, respectively. 1 was found to exhibit good to excellent activity for catalyzing the aerobic C-P cross-coupling reaction of terminal alkynes with H-phosphonates to form alkynylphosphonates (70-99% yields).

13.
Nanomicro Lett ; 14(1): 161, 2022 Aug 09.
Article in English | MEDLINE | ID: mdl-35943631

ABSTRACT

With the aging of society and the increase in people's concern for personal health, long-term physiological signal monitoring in daily life is in demand. In recent years, electronic skin (e-skin) for daily health monitoring applications has achieved rapid development due to its advantages in high-quality physiological signals monitoring and suitability for system integrations. Among them, the breathable e-skin has developed rapidly in recent years because it adapts to the long-term and high-comfort wear requirements of monitoring physiological signals in daily life. In this review, the recent achievements of breathable e-skins for daily physiological monitoring are systematically introduced and discussed. By dividing them into breathable e-skin electrodes, breathable e-skin sensors, and breathable e-skin systems, we sort out their design ideas, manufacturing processes, performances, and applications and show their advantages in long-term physiological signal monitoring in daily life. In addition, the development directions and challenges of the breathable e-skin are discussed and prospected.

14.
Curr Oncol ; 29(5): 3138-3148, 2022 04 29.
Article in English | MEDLINE | ID: mdl-35621645

ABSTRACT

BACKGROUND: Invasive neoplasia (Tis-T1) are increasingly being encountered in the daily routine of endoscopic polypectomy. However, the need for salvage surgery following endoscopic therapy for invasive neoplasia is controversially discussed. PATIENTS AND METHODS: Patients with endoscopic removal of invasive neoplasia were identified from the national Surveillance Epidemiology and End Results (SEER) Database 2005 to 2015. Survival analysis and Cox proportional hazard regression analysis in cancer-specific mortality and overall survival rate was used, which were stratified by T stage and polyp size. RESULTS: A total of 5805 patients with endoscopic removal of invasive neoplasia were included in the analysis, of whom 1214 (20.9%) underwent endoscopic treatment alone and 4591 (79.1%) underwent endoscopic resection plus surgery. The survival analysis revealed that patients undergoing salvage surgery had a significantly better cancer-specific survival (97.4% vs. 95.8%, p-value = 0.017). In patients with T1 stage, additional salvage surgery led to a significantly higher cancer-specific survival (92.1% vs. 95.0%, p value = 0.047). CONCLUSION: Salvage surgery following endoscopic polypectomy may improve the oncological survival of patients with invasive neoplasia, especially in patients with T1 stage. Furthermore, the T stage, size, and localization of polyps, as well as the level of CEA, could be identified as significant predictors for lymphonodal and distant metastases.


Subject(s)
Colonic Polyps , Neoplasms , Colonic Polyps/pathology , Colonic Polyps/surgery , Colonoscopy , Humans , Survival Analysis
15.
Inorg Chem ; 61(13): 5215-5223, 2022 Apr 04.
Article in English | MEDLINE | ID: mdl-35312318

ABSTRACT

Two borylaminoamidinatosilylenes (L)[(1,5-C8H14)B(Ar)N]Si (L = PhC(NtBu)2, Ar = 2,6-iPr2C6H3 (1)) and (L)[(1,5-C8H14)B(Ar')N]Si (Ar' = 2,4,6-Me3C6H2 (2)) have been prepared and utilized to investigate the reaction toward isocyanide. Reactions of 1 with the respective CN-2,6-Me2C6H3 and CNCy (Cy = cyclo-C6H11) produced compounds (L)Si(NAr)C(N-2,6-Me2C6H3)B(1,5-C8H14)(CN-2,6-Me2C6H3) (3) and (L)Si(NAr)C(NCy)C(NCy)B(1,5-C8H14)(CNCy) (4). Reactions of 2 with the respective CNCy and CN-2,6-Me2C6H3 yielded compounds cyclo-(L)SiN(Ar')C(NCy)B(1,5-C8H14)C(NCy) (5) and cyclo-(L)[(1,5-C8H14)B(Ar')N]SiC(CN-2,6-Me2C6H3)N(2,6-Me2C6H3)C(N-2,6-Me2C6H3) (6). Compounds 3-6 have different compositions and structures from each other. Density functional theory (DFT) calculations suggest initial formation of (L)[(1,5-C8H14)B(←:CN-2,6-Me2C6H3)(Ar)N]Si (A), (L)[(1,5-C8H14)B(←:CNCy)(Ar)N]Si (A'), (L)[(1,5-C8H14)B(←:CNCy)-(Ar')N]Si (A″), and (L)[(1,5-C8H14)B(←:CN-2,6-Me2C6H3)(Ar')N]Si (A‴) as the respective intermediates. The as-followed transition states TS, TS1', TS1″, and TS‴ all feature probable Si:→C(═N):→B bonding with different Gibbs energies of 7.24, 2.46, 3.86, and 6.59 kcal/mol, respectively, due to variation among the Ar, Ar', 2,6-Me2C6H3, and Cy groups in these species, and reacted in different ways.

16.
Pharmaceutics ; 14(3)2022 Feb 24.
Article in English | MEDLINE | ID: mdl-35335873

ABSTRACT

Androgen deprivation therapy (ADT) is a systemic therapy for advanced prostate cancer (PCa). Although most patients initially respond to ADT, almost all cancers eventually develop castration resistance. Castration-resistant PCa (CRPC) is associated with a very poor prognosis, and the treatment of which is a serious clinical challenge. Accumulating evidence suggests that abnormal expression and activation of various kinases are associated with the emergence and maintenance of CRPC. Many efforts have been made to develop small molecule inhibitors to target the key kinases in CRPC. These inhibitors are designed to suppress the kinase activity or interrupt kinase-mediated signal pathways that are associated with PCa androgen-independent (AI) growth and CRPC development. In this review, we briefly summarize the roles of the kinases that are abnormally expressed and/or activated in CRPC and the recent advances in the development of small molecule inhibitors that target kinases for the treatment of CRPC.

17.
Dalton Trans ; 51(10): 4097-4103, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35179544

ABSTRACT

A new borate, Na2SrB16O26, was synthesized by the high-temperature solution method. It exhibits complicated interpenetrating 3D B-O frameworks composed of the functional building block (FBB) [B8O16]. The UV-vis-NIR diffuse reflectance spectroscopy shows that it has a deep-ultraviolet (DUV) cutoff edge (<200 nm). The relationship between the structures and optical properties was uncovered by theoretical calculations. By the first-principles calculation, the birefringence is estimated to be 0.07 at 1064 nm. The response electron distribution anisotropy (REDA) analysis indicates that the [BO3] units contribute mainly to the generation of the moderate birefringence.

18.
Inorg Chem ; 61(6): 2713-2718, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35107974

ABSTRACT

Three mixed-alkali-metal fluorooxoborates, KNaB3O4F3 (I), K2B3O4F3 (II), and KCsB3O4F3 (III), were acquired in a closed system. I-III are isomorphic and adopt orthorhombic structures [Pbcn (No. 60)] with wavy parallelly arranged pseudolayers composed of ∞1[B3O4F3] chains, which exhibit slight differences in the arrangement modes of the fundamental building blocks. First-principles calculations illustrate that they all have moderate birefringence and large band gaps on the order of 7.0 eV, suggesting deep-ultraviolet (DUV) cutoff edges. In order to investigate the main source of the optical properties, the electronic structure and anisotropy of the response electron distribution were analyzed. Experimental characterizations for I confirm the structure and DUV transparence ability.

20.
Int J Gen Med ; 15: 675-687, 2022.
Article in English | MEDLINE | ID: mdl-35082517

ABSTRACT

PURPOSE: Tumor deposits (TDs) are acknowledged negative prognostic factors in colorectal cancer (CRC), and their pathogenesis remains a puzzle. This study aimed to construct and validate a nomogram available for preoperative TDs prediction in CRC patients. PATIENTS AND METHODS: Patients from the Surveillance, Epidemiology, and End Results (SEER) and the cancer genome atlas (TCGA) databases were randomly divided into training and validation sets according to the sample size ratio of 7:3. Univariate logistic regression was performed for identifying differentially expressed microRNAs between TDs and non-TDs. Nomograms for TDs prediction were developed from the multivariate logistic regression model with least absolute shrinkage and selection operator and were validated internally in terms of accuracy, calibration, and clinical utility. Based on the target genes, pathways tightly associated with TDs were selected using enrichment analysis. RESULTS: Six clinicopathologic factors and expressions of six microRNAs (miR-614, miR-1197, miR-4770, miR-3136, miR-3173, and miR-4636) differed significantly between TDs and non-TDs CRC patients from the SEER and TCGA training sets. We compared potential prediction discrimination between two nomograms: a clinicopathologic nomogram and a six-microRNA signature nomogram. The six-microRNA signature nomogram revealed better accuracy than the clinicopathologic one for TDs prediction (AUC values of 0.96 and 0.93 in the validation cohort). The calibration plots and decision curve analysis demonstrated that the six-microRNA signature nomogram had better validity and a greater prognostic benefit versus the clinicopathologic one for TDs prediction. Calcium signaling pathways were closely associated with roles of the six microRNAs in TDs of CRC patients. CONCLUSION: The six-microRNA signature nomogram can be used as an efficient tool for preoperative TDs prediction in CRC patients.

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