Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

An investigation into the present status and influencing factors of nurse retention in grade-a tertiary general hospitals in Shanxi Province within the framework of the magnet hospital concept.

BACKGROUND: The attrition of nursing staff significantly contributes to the shortage of healthcare professionals. This study entailed an examination of the propensity of nurses to sustain employment within Grade-A tertiary general hospitals and the various influencing factors. METHODS: A total of 2,457 nurses from three grade-A tertiary general hospitals were surveyed. The survey instruments included a general information questionnaire, a scale measuring their willingness to continue working, and a Chinese version of the Magnet Hospital Factor scale. RESULTS: The scores of the willingness to continue working scale and the Magnet Hospital Factor scale were 21.53 ± 4.52 and 145.46 ± 25.82, respectively. There were statistically significant differences in the scores of willingness of nurses to continue working across various factors, including the department, age, marital status, family location, length of service as nurses, professional title, position, and employment type, upon comparison (P < 0.001). The correlation analysis showed that there was a positive correlation between the willingness of nurses to continue working and the magnet hospital factors, with a correlation coefficient of 0.523 (P < 0.01). Regression analysis showed that department, length of service as nurses, professional title, position, average monthly income, number of night shifts, medical care relationship, educational support, and nursing manager support among the magnet hospital factors were important predictors of willingness to continue working (P < 0.001). CONCLUSION: The willingness of nurses to continue working in grade-A tertiary general hospitals in Shanxi Province was determined to be at an upper-middle level. The magnet status of grade-A tertiary general hospitals needs to be improved, and there are many factors that influenced willingness of nurses to continue working. To cultivate a more favorable environment and bolster nurse recruitment and retention, all healthcare institutions should strive to establish a magnet nursing environment, thereby fostering the robust development of the nursing team.

Linewidth Measurement of a Narrow-Linewidth Laser: Principles, Methods, and Systems.

Narrow-linewidth lasers mainly depend on the development of advanced laser linewidth measurement methods for related technological progress as key devices in satellite laser communications, precision measurements, ultra-high-speed optical communications, and other fields. This manuscript provides a theoretical analysis of linewidth characterization methods based on the beat frequency power spectrum and laser phase noise calculations, and elaborates on existing research of measurement technologies. In addition, to address the technical challenges of complex measurement systems that commonly rely on long optical fibers and significant phase noise jitter in the existing research, a short-delay self-heterodyne method based on coherent envelope spectrum demodulation was discussed in depth to reduce the phase jitter caused by 1/f noise. We assessed the performance parameters and testing conditions of different lasers, as well as the corresponding linewidth characterization methods, and analyzed the measurement accuracy and error sources of various methods.

Effect of the ratios of estradiol increase on the outcome of in vitro fertilization-embryo transfer with antagonist regimens: a single center retrospective cohort study.

BACKGROUND: The outcome of in vitro fertilization-embryo transfer (IVF) is often determined according to follicle and estradiol levels following gonadotropin stimulation. In previous studies, although most of them analyzed the estrogen level from ovaries or the average estrogen level of a single follicle, there was no study on the ratio of estrogen increase, which was also correlated with pregnancy outcomes in the clinic. This study aimed to make timely adjustments to follow-up medication to improve clinical outcomes based on the potential value of estradiol growth rate. METHODS: We comprehensively analyzed estrogen growth during the entire ovarian stimulation period. Serum estradiol levels were measured on the day of gonadotropin treatment (Gn1), five days later (Gn5), eight days later (Gn8), and on the trigger day (HCG). This ratio was used to determine the increase in estradiol levels. According to the ratio of estradiol increase, the patients were divided into four groups: A1 (Gn5/Gn1 ≤ 6.44), A2 (6.44 < Gn5/Gn1 ≤ 10.62), A3 (10.62 < Gn5/Gn1 ≤ 21.33), and A4 (Gn5/Gn1 > 21.33); B1 (Gn8/Gn5 ≤ 2.39), B2 (2.39 < Gn8/Gn5 ≤ 3.03), B3 (3.03 < Gn8/Gn5 ≤ 3.84), and B4 (Gn8/Gn5 > 3.84). We analyzed and compared the relationship between data in each group and pregnancy outcomes. RESULTS: In the statistical analysis, the estradiol levels of Gn5 (P = 0.029, P = 0.042), Gn8 (P < 0.001, P = 0.001), and HCG (P < 0.001, P = 0.002), as well as Gn5/Gn1 (P = 0.004, P = 0.006), Gn8/Gn5 (P = 0.001, P = 0.002), and HCG/Gn1 (P < 0.001, P < 0.001) both had clinical guiding significance, and lower one significantly reduced the pregnancy rate. The outcomes were positively linked to groups A (P = 0.036, P = 0.043) and B (P = 0.014, P = 0.013), respectively. The logistical regression analysis revealed that group A1 (OR = 0.376 [0.182-0.779]; P = 0.008*, OR = 0.401 [0.188-0.857]; P = 0.018*) and B1 (OR = 0.363 [0.179-0.735]; P = 0.005*, OR = 0.389 [0.187-0.808]; P = 0.011*) had opposite influence on outcomes. CONCLUSION: Maintaining a serum estradiol increase ratio of at least 6.44 on Gn5/Gn1 and 2.39 on Gn8/Gn5 may result in a higher pregnancy rate, especially in young people.

Radiographic patterns and characteristics of sagittal profiles in normal spinopelvic curvatures: An explicit depiction of the distribution of lumbar vertebral bodies and discs.

The current study aimed to investigate the sagittal morphology of the spinopelvic complex and the components of the lumbar spine in the normal population. In total, 132 adult volunteers were retrospectively evaluated and divided into four groups according to the Roussouly classification. Statistical analysis of radiological parameters, including lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, LL-TK, lumbar vertebral lordosis from L1 to L5 (L1L-L5L), the intervertebral angle from L1-L2 to L5-S1 (IVA1-2-IVA5-1), segmental lordosis from L1 to L5 (S1L-S5L), the proportion of L1-L5 (L1%-L5%), the proportion of the intervertebral angle from L1-L2 to L5-S1 (IVA1-2%-IVA5-1%), and proportion of segmental lordosis from L1 to L5 (S1L%-S5L%), was performed. Based on the classification, type II (n = 46) was the most common, followed by type I (n = 39), type III (n = 36), and type IV (n = 11). The quantitative values of the sagittal parameters of the four groups were obtained. Results showed a significant difference in terms of LL, PI, SS, and LL-TK. Further, L1%, L2%, L3%, IVA1-2%, IVA2-3%, S1L%, S2L%, and S3L% had an increasing trend. PI was positively correlated with LL, S1L, S2L, S3L, S4L, S1L%, and S2L%, but not with S5L%. In conclusion, pelvic parameters had a significant effect on lumbar curvature and lordosis distribution. Further, the abovementioned results were beneficial for individual surgical decision-making regarding targeted intervertebral angle, screw-insertion dimension, and rod contouring.

Fermi-Level Depinning in Metal/Ge Junctions by Inserting a Carbon Nanotube Layer.

Germanium (Ge)-based devices are recognized as one of the most promising next-generation technologies for extending Moore's law. However, one of the critical issues is Fermi-level pinning (FLP) at the metal/n-Ge interface, and the resulting large contact resistance seriously degrades their performance. The insertion of a thin layer is one main technique for FLP modulation; however, the contact resistance is still limited by the remaining barrier height and the resistance induced by the insertion layer. In addition, the proposed depinning mechanisms are also controversial. Here, the authors report a wafer-scale carbon nanotube (CNT) insertion method to alleviate FLP. The inserted conductive film reduces the effective Schottky barrier height without inducing a large resistance, leading to ohmic contact and the smallest contact resistance between a metal and a lightly doped n-Ge. These devices also indicate that the metal-induced gap states mechanism is responsible for the pinning. Based on the proposed technology, a wafer-scale planar diode array is fabricated at room temperature without using the traditional ion-implantation and annealing technology, achieving an on-to-off current ratio of 4.59 × 104 . This work provides a new way of FLP modulation that helps to improve device performance with new materials.

Micropore Regulation in Ultrastable [Sc3O]-Organic Frameworks for Acetylene Storage and Purification.

High storage capacity, high separation selectivity, and high structure stability are essential for an idea gas adsorbent. However, it is not easy to achieve all three at the same time, even for the promising metal-organic framework (MOF) adsorbents. We demonstrate herein that robust [Sc3O]-organic frameworks could be regulated by a micropore combination strategy for high-performance acetylene adsorption. Under the same solvent system with formic acid as a modulator, similar tritopic ligands extend [Sc3O(COO)6] trigonal-prismatic clusters to generate SNNU-5-Sc and SNNU-150-Sc adsorbents. Notably, the two Sc-MOFs can keep their architectures over 24 h in water at different pH values (2-12) or at 90 °C. Modulated by the linker symmetry, the final stacking metal-organic polyhedral cages produce open window sizes of about 10 Å for SNNU-5-Sc and 5 Å + 7 Å for SNNU-150-Sc. Due to such micropore combinations, SNNU-5-Sc exhibits a top-level C2H2 uptake of 211.2 cm3 g-1 (1 atm and 273 K) and SNNU-150-Sc shows high C2H2/CH4, C2H2/C2H4, and C2H2/CO2 selectivities of 80.65, 4.03, and 8.19, respectively, under ambient conditions. Dynamic breakthrough curves obtained on a fixed-bed column and grand canonical Monte Carlo (GCMC) simulations further support their prominent acetylene storage and purification performance. High framework stability, storage capacity, and separation selectivity make SNNU-5-Sc and SNNU-150-Sc ideal acetylene adsorbents in practical applications.

A 1-µm-Band Injection-Locked Semiconductor Laser with a High Side-Mode Suppression Ratio and Narrow Linewidth.

We demonstrate a narrow-linewidth, high side-mode suppression ratio (SMSR) semiconductor laser based on the external optical feedback injection locking technology of a femtosecond-apodized (Fs-apodized) fiber Bragg grating (FBG). A single frequency output is achieved by coupling and integrating a wide-gain quantum dot (QD) gain chip with a Fs-apodized FBG in a 1-µm band. We propose this low-cost and high-integration scheme for the preparation of a series of single-frequency seed sources in this wavelength range by characterizing the performance of 1030 nm and 1080 nm lasers. The lasers have a maximum SMSR of 66.3 dB and maximum output power of 134.6 mW. Additionally, the lasers have minimum Lorentzian linewidths that are measured to be 260.5 kHz; however, a minimum integral linewidth less than 180.4 kHz is observed by testing and analyzing the power spectra of the frequency noise values of the lasers.

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.

Comparison of outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal GIST: An inverse probability of treatment weighting analysis.

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. METHODS: Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. RESULTS: The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). CONCLUSIONS: In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

Tailoring the Pore Environment of a Robust Ga-MOF by Deformed [Ga3O(COO)6] Cluster for Boosting C2H2 Uptake and Separation.

The construction of superstable metal-organic frameworks (MOFs) for selective gas uptake is urgently demanded but remains a great challenge. Herein, a unique bifunctional deformed [Ga3O(COO)6] inorganic secondary building unit (SBU) generated from the desymmetrical evolution of typical triangular prismatic trinuclear cluster was first introduced, which was extended by an isosceles triangular organic linker to produce a robust Ga-MOF (SNNU-63). Remarkably, SNNU-63 can stabilize in water at 25 °C for 96 h and at 80 °C for more than 24 h, which surpasses nearly all other Ga-MOFs. The combined effects of open metal sites and hydrophobic pore environment provided by deformed [Ga3O] SBUs render SNNU-63 with high C2H2 storage capacity and efficient C2H2 and natural gas purification performance. The ideal adsorbed solution theory calculation, column breakthrough tests, and grand canonical Monte Carlo simulations demonstrate that SNNU-63 is a potential material for addressing the challenge of C2H2/CO2 and C2H2/CH4 mixture separation under ambient conditions.

Identification of novel STAT3 inhibitors bearing 2-acetyl-7-phenylamino benzofuran scaffold for antitumour study.

Signal transducer and activator of transcription 3 (STAT3) is identified as a promising target for multiple cancer therapy and attracts widespread concern. Herein, we reported the discovery of a series of 2-acetyl-7-phenylamino benzofuran derivatives as STAT3 inhibitors using scaffold fusion strategy. Further structure activity relationship study led to the discovery of compound C6, which displayed the most potent anti-proliferation activities against MDA-MB-468 cells (IC50 = 0.16 µM). Western blot assay demonstrated that C6 inhibited the activation of STAT3 (Tyr705) without influencing the phosphorylation of STAT1 (Tyr701). Further mechanistic studies indicated that C6 caused a notable G2/M cycle-arresting and early apoptosis in a concentration-dependent manner in MDA-MB-468 cells. Finally, molecular modelling study elucidated the binding mode of C6 in STAT3 SH2 domain.

Evaluation of nine active components of Lu-Jiao Fang in normal and hypertrophic rat myocardia via LC-MS/MS.

Lu-Jiao Fang (LJF), a traditional Chinese medicine prescription, can improve the cardiac function of chronic heart failure (CHF) patients; however, knowledge about the cardiac distribution of LJF, especially in CHF animal models, is rather limited. This work aimed to explore the cardiac distribution of LJF in pressure overload-induced CHF rats at the last gavage administration of LJF after 30 weeks of treatment. LC-MS/MS methods for analyzing nine active components (i.e. loganin, hesperidin, epimedin C, icariin, psoralen, isopsoralen, baohuoside I, morroniside and specnuezhenide) of LJF in cardiac tissue samples were established, and the components were then analyzed in left ventricular wall (LVW) and right ventricular wall (RVW) in parallel at same time point postdose for three dose groups. The results showed that most analytical component levels in LVW (hypertrophic myocardium) were only 39-74% of those in RVW (normal myocardium); however, psoralen and isopsoralen levels in LVW were equal to or even greater than the levels in RVW, suggesting that the hypertrophic myocardium tissue affinity of psoralen and isopsoralen might overcome the negative effect of decreased blood flow on distribution. This study indicated that the pathological state may influence drug distribution, and the efficacy of psoralen and isopsoralen for improving CHF deserves further investigation.

Supercritical fluid chromatography-a technical overview and its applications in medicinal plant analysis: an update covering 2012-2018.

Medicinal plants with complex matrices are endowed with a wide scope of biological activities. The separation, quantification, characterization and purification of bioactive components from herbal medicine extracts have always challenged analysts. Fortunately, the advancement of various emerging techniques has provided potent support for improving the method selectivity, sensitivity and run speeds in medicinal plant analyses. In recent years, the advent of new-generation supercritical fluid chromatography (SFC) instruments and a wide diversity of column chemistries, coupled with the intrinsic technical features of SFC, have made it an alternative and prominent analytical platform in the medicinal plant research area. This work aims to give a comprehensive overview of the fundamentals, technical advancement and investigating parameters of SFC in combination with three prevalent detectors. Moreover, the latest research progress of SFC applications in medicinal plant analyses is illuminated, with focus on herbal medicine-related SFC papers on the analytical and preparative scale that were published during the period of 2012 to December 2018. The most relevant applications were classified based on the constituents to be analysed. As for the respective research cases, analytical protocols and data processing strategies were provided, along with the indicated restrictions or superiority of the method; thus, the current status of SFC in medicinal plant analysis was presented.

ß-Cell function in obese children and adolescents with metabolic syndrome compared to isolated obesity.

OBJECTIVE: To evaluate ß-cell function in obese children and adolescents meeting clinical criteria for isolated obesity (iOB), isolated components of dysmetabolism (cMD), or metabolic syndrome (MS), and in obese children and adolescents with normal glucose tolerance (NGT), impaired glucose regulation (IGR), or type 2 diabetes (T2DM). STUDY DESIGN: We undertook a prospective study of Han Chinese children and adolescents aged 8-16 years (median 11 ± 1.4) seen in an obesity clinic between May 2013 and 2018. Patients were classified as iOB (53), cMD (139), and MS (139) groups based on clinical criteria. The same patients were also classified as NGT (212), IGR (111), or T2DM (8) based on results of an oral glucose tolerance test (OGTT). The MS patients were classified as NGT [MS](59) and IGR [MS](72) for the further study. All participants also completed a mixed-meal tolerance test (MMTT). RESULTS: Compared with the iOB group, the MS group had significantly higher area under the curve of C-peptide up to the 2 hours (AUC CP) (P = .03) and peak C-peptide (P = .03), adjusted for BMI, age and Tanner stage, on MMTT. However, there was no difference in the insulinogenic index (ΔI30/ΔG30) or oral disposition index (oDI) derived from the OGTT among the three groups. However, 52% of participants with MS had IGR, compared to 28% in the cMD group. Compared with the NGT group, the individuals with IGR had significantly lower ΔI30/ΔG30 (P = .001) and oDI (P < .001). Compared with the iOB group, the NGT[MS] had significantly higher AUC CP (P = .004), peak C-peptide (P = .004) and ΔI30/ΔG30 (P = .007) adjusted for age, but no difference in oDI. Compared with the NGT[MS], the IGR[MS] had significantly lower ΔI30/ΔG30 (P = .005) and oDI (P < .001), but the AUC CP and peak C-peptide had no difference. CONCLUSION: Although the MS youth have ß-cell hyperfunction as a whole, ß-cell dysfunction is present in the early stages of dysmetabolism in obese youth with cMD or MS and worsened across the spectrum from iOB to cMD and MS, contributing to development of T2DM.

Topology-Guided Design for Sc-soc-MOFs and Their Enhanced Storage and Separation for CO2 and C2-Hydrocarbons.

Evaluating the effect of ligand substitution on metal ions and/or clusters during the MOF growth process is conducive to rational design of isoreticular MOFs with improved performance. Through topological direction and ligand substitution strategy, we herein constructed two Sc-soc-MOFs (Sc-EBTC and Sc-ABTC) based on two similar rectangular-planar diisophthalate ligands, linear-shaped H4EBTC (1,1'-ethynebenzene-3,3',5,5'-tetracarboxylic acid) and zigzag-shaped H4ABTC (3,3',5,5'-azobenzenetetracarboxylic acid), under solvothermal conditions with formic acid as a modulator. {Sc[(Sc3O)(H2O)3]3(EBTC)6} (Sc-EBTC) possesses two distinct clusters as SBUs, trinuclear [Sc3O(CO2)6] (SBU1) and mononuclear cluster [ScO6] (SBU2), which maintain the soc-topology except for the mononuclear [ScO6] instead of the corresponding trinuclear [Sc3O(CO2)6] in Sc-ABTC ({(Sc3O)(H2O)3(ABTC)1.5(NO3)}). Notably, Sc-EBTC represents a rare soc-MOF with two distinct clusters as SBUs. Due to similar pore spaces, the two Sc-soc-MOF materials both exhibit enhanced and comparable gas sorption and selectivity performances. Specially, their remarkable C2H2, C2H4, and CO2 storage capacity along with prominent CO2/CH4 and C2-hydrocarbons/CH4 separations indicate that these Sc-soc-MOFs are promising adsorbents for natural gas purification under ambient conditions.

Mesoatrial Shunt for Budd-Chiari Syndrome.

BACKGROUND: The long-term efficacy of mesoatrial shunt (MAS) for Budd-Chiari syndrome (BCS) is not well studied. The purpose of our study was to investigate the long-term outcome and efficacy of MAS for BCS. METHODS: We retrospectively evaluated 11 patients who underwent MAS for BCS from April 1986 to November 1995. Records of patients' clinical presentations, laboratorial investigation, Doppler duplex ultrasonography, radiologic image, and treatment outcomes were all retrieved and analyzed. RESULTS: Follow-up intervals ranged from 1 year and 2 months to 30 years and 2 months (mean, 17 years and 8 months). Portal pressure decreased significantly from 35.72 ± 3.52 cm H2O to 27.86 ± 5.83 cm H2O post-MAS (P = 0.001). The 5-year, 10-year, and 20-year patency were 72.7%, 54.5%, 36.4%, respectively; 63.3% of patients had survived for more than 10 years and 45.5% for more than 20 years. A male has been alive with patent shunt for 28 years and 1 month. CONCLUSIONS: The MAS with enforced rings is an effective therapeutic modality for BCS with cautious perioperative management.

hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation.

BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) plays an important role in cancer invasion, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. DESIGN: Proteomics analysis, qPCR and western blotting were used to screen for hTERT-regulated candidate molecules in gastric cancer invasion. Chromatin immunoprecipitation (ChIP) qPCR was performed to identify the binding sites of hTERT at the regulatory region of the integrin ß1 (ITGB1) gene. ChIP assays were further applied to elucidate the transcription factors that bound to the regulatory region. The interactions between hTERT and the transcription factors were tested by co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down experiments. Moreover, the revealed pathway was verified in tumour-bearing nude mice and human gastric cancer tissues. RESULTS: ITGB1 was identified as a downstream gene of hTERT, and there were two hTERT-binding regions within this gene. hTERT alleviated the binding of forkhead box O3 (FOXO3a) to FOXO3a binding element (+9972∼+9978), but it enhanced the binding of forkhead box M1 (FOXM1) to FOXM1 binding element (-1104∼-1109) in ITGB1 gene. Importantly, FOXO3a played a major role in hTERT-induced ITGB1 expression, and the hTERT/murine double minute 2 (MDM2) complex promoted the ubiquitin-mediated degradation of FOXO3a. Moreover, hTERT increased ITGB1 expression in xenograft gastric cancer, and the level of hTERT was positively correlated with that of ITGB1 in human gastric cancer tissues. CONCLUSIONS: The hTERT/MDM2-FOXO3a-ITGB1 pathway markedly contributes to hTERT-promoted gastric cancer invasion, suggesting that this pathway might be a novel target for the prevention and treatment of gastric cancer metastasis.

Ligand Torsion Triggered Two Robust Fe-Tetratopic Carboxylate Frameworks with Enhanced Gas Uptake and Separation Performance.

By regulating the tetratopic carboxylate ligands, two robust Fe-MOFs (MOF=Metal-organic framework) comprising trigonal prismatic building blocks under a DMA/DMSO/HBF4 solvent system, namely, [(CH3 )2 NH2 ][FeII3 (OH)(BPTC)1.5 (DMSO)3 ] (SNNU-60) and [FeIII FeII2 (OH)(ABTC)1.5 (DMSO)3 ] (SNNU-61) (BPTC=3,3',5,5'-biphenyltetracarboxylic acid, ABTC=3,3',5,5'-azobenzenetetracarboxylic acid, SNNU=Shaanxi Normal University) have been successfully synthesized. The torsions between the benzene groups of the ligands result in two MOFs exhibiting completely different (4,6)-connected frameworks, which represent the only two MOF types constructed by [M3 (O/OH)(COO)6 ] trimeric building units and quadrilateral tetratopic carboxylate linkers until now. The robust Fe-MOFs SNNU-60 and SNNU-61 both exhibit high thermal/chemical stability, permanent microporosity, and excellent gas uptake capability for H2 , CO2 , C2 H2 , and C2 H4 under 1 bar. SNNU-60 in particular displays very high C2 H2 capture under low pressure (85 cm3 cm-3 at 0.15 bar and 298 K), which is among the top C2 H2 uptake MOF materials. Also, these two Fe-MOFs display high separation for CO2 and C2 -hydrocarbons over CH4 . Significantly, thanks to the high stability, suitable pore size, open Fe sites, and ion skeleton, SNNU-60 has extremely high C2 H2 /CH4 selectivity (83.6, 298 K), which surpasses most MOFs reported so far under the same conditions.

The FOXM1-induced resistance to oxaliplatin is partially mediated by its novel target gene Mcl-1 in gastric cancer cells.

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that belongs to the Bcl-2 family. The aberrant expression of Mcl-1 is important for sensitivity to chemotherapy drugs in gastric cancer. However, the regulatory mechanism of Mcl-1 in gastric cancer cells remains unclear. In this study, we first found that Forkhead box M1 (FOXM1) and Mcl-1 expression levels were positively correlated in human gastric cancer specimens and that both are associated with poor prognosis of patients treated with oxaliplatin. Second, we demonstrated that the expression level of Mcl-1 was correlated with FOXM1 expression in gastric cancer cells. Third, reporter assays showed that FOXM1 upregulated the promoter activity of the Mcl-1 gene. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays further demonstrated that FOXM1 could bind to a particular site (-635acaaacaa-628) in the promoter region of the Mcl-1 gene. Moreover, CCK-8 assays and analyses of apoptosis revealed that the suppression of the FOXM1/Mcl-1 pathway induced apoptosis and thus increased sensitivity to oxaliplatin in gastric cancer cells, whereas the enhancement of the FOXM1/Mcl-1 pathway inhibited apoptosis and decreased sensitivity to oxaliplatin in gastric cancer cells. Taken together, this study is the first to not only show that Mcl-1 is a novel target gene of FOXM1 but also suggest that targeting FOXM1/Mcl-1 may be a novel strategy to enhance sensitivity to oxaliplatin in gastric cancer.