Association of the live microbe intake from foods with all-cause and cardiovascular disease-specific mortality: a prospective cohort study.

BACKGROUND: Live dietary microbes have been hypothesized to promoting human health. However, there has been lacking perceptions to crystallize nexus between consumption of foods with live microbes and mortality. OBJECTIVE: To investigate the association of consumption of foods with medium to high amounts of live microbes with all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. METHODS: The data were obtained from the National Health and Nutrition Examination Survey 1999-2018 at baseline linked to the 2019 National Death Index records. Based on consumption of foods that were categorized as either having medium or high microbial content (MedHi foods), participants were classified into three groups. Kaplan-Meier survival curves and multivariable Cox regression models were used to estimate the association of consumption of MedHi foods with mortality. Population-attributable fractions (PAFs) of consumption of MedHi foods in relation to mortality risk were also estimated. RESULTS: A total of 35,299 adults aged ≥ 20 years were included in this study. During a median follow-up of 9.67 years, compared with adults in G1, those in G3 had 16% (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.77-0.90) reduced risk of all-cause mortality, and 23% (HR, 0.77; 95% CI, 0.67-0.89) reduced risk of CVD-specific mortality. The PAF of high (G3) vs. intermediate or low consumption of MedHi foods (G1 + G2) with all-cause and CVD-specific mortality was 3.4% and 4.3%, respectively. CONCLUSIONS: Consumption of foods with higher microbial concentrations is associated with a reduced risk of all-cause and CVD-specific mortality in US adults.

Physical activity attenuates the excess mortality risk from prolonged sitting time among adults with osteoporosis or osteopenia.

PURPOSE: Osteoporosis is a common generalized skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. This study aims to crystallize associations of physical activity (PA) and sedentary behaviour with the survival of adults with osteoporosis or osteopenia. METHODS: A total of 3103 participants aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) were included in the study. All participants were diagnosed with osteopenia or osteoporosis. Multivariable Cox proportional hazards regression models were used to assess the association of PA and sedentary behaviour with overall mortality, cancer-related mortality, and cardiovascular disease (CVD)-related mortality. RESULTS: During 21349 person-years of follow-up, 675 deaths were documented. Highly active participants had a lower risk of all-cause (hazard ratios [HR] = 0.61; 95% confidence interval [CI], 0.42-0.87; P for trend = 0.004), cancer-specific (HR = 0.64; 95%CI, 0.35-1.17; P for trend = 0.132), CVD-specific (HR = 0.75; 95%CI, 0.45-1.25; P for trend = 0.452), and other (HR, 0.51; 95%CI, 0.29-0.88; P for trend = 0.005) mortality than inactive participants. And sitting time was not associated with mortality among physically active participants; while among those who were insufficiently active or inactive, longer sitting time was associated with increased risks of all-cause (HR per 1-h increase = 1.05; 95% CI, 1.01-1.09), cancer-specific (HR per 1 h increase = 0.98; 95% CI, 0.90-1.07), CVD-specific (HR per 1-h increase = 1.11; 95% CI = 1.04-1.18), and other (HR per 1-h increase = 1.05; 95% CI, 0.98-1.13) mortality in a dose-response manner. CONCLUSIONS: PA can attenuate the excess mortality risk from prolonged sitting for individuals with osteoporosis and/or osteopenia. The combination of prolonged sedentary behaviour with inactive (participants without any PA during a week) PA was associated with an increased risk of mortality. The all-cause mortality risk of individuals who engage in less than 150 min/wk PA and sit more than 8 h/d is 2.02 (95% CI, 1.37-2.99) times higher than that of individuals who engage in more than 150 min/wk PA and sit less than 4 h/d.

Association between glyphosate exposure and osteoarthritis in US adults: Especially in people who are obese and inactive in leisure time physical activity.

OBJECTIVE: Little has been known on the effect of chronic glyphosate exposure on osteoarthritis (OA). The aim of this study was to investigate the association between glyphosate exposure and OA and to further investigate the different moderating effects of leisure time physical activity (LTPA) and body mass index (BMI) types on the association between glyphosate exposure and OA. METHODS: Cross-sectional data from 2540 participants in the 2015-2018 National Health and Nutrition Examination Survey (NHANES) were used to explore the association between glyphosate exposure and OA. Multivariate logistic regression models and restricted cubic spline models were used to investigate the association between glyphosate exposure and OA, and further analyses were conducted to determine the association between glyphosate exposure and OA under different LTPA and BMI types. RESULTS: Of the 2540 participants, 346 had OA. Participants with the highest glyphosate concentration (Q4) had a higher incidence of OA compared to participants with the lowest glyphosate concentration (Q1) (OR, 1.88; 95 % confidence interval [CI]: 1.13, 3.13), there was no nonlinear association between glyphosate and OA (non-linear P = 0.343). In the no LTPA group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.65; 95%CI: 1.27, 5.51). In the obese group, glyphosate concentration in the Q4 group was correlated with OA (OR, 2.74; 95 % CI: 1.48, 5.07). Among people with high BMI and inactive in LTPA, glyphosate concentrations in Q4 were associated with OA (OR, 2.19; 95 % CI: 1.07, 4.48). CONCLUSIONS: Glyphosate is associated with OA odd, and physical activity and moderate weight loss can mitigate this association to some degree. This study provides a scientific basis for rational prevention of OA by regulation of LTPA and BMI under glyphosate exposure.

Exploration of Personalized Treatment for Advanced Hepatocellular Carcinoma: Combination Therapy of Selinexor, Palbociclib, and Pembrolizumab with Umbilical Cord Blood NK Cells.

Objective: To report the efficacy and safety of combination therapy with selinexor, palbociclib, pembrolizumab, and umbilical cord blood NK cells for advanced hepatocellular carcinoma (HCC).Advanced HCC has a poor prognosis and limited effective treatment options. Exploring personalized combination treatment strategies is critically important for improving outcomes in patients with advanced HCC. This study aims to provide preliminary evaluation of the clinical effectiveness and safety of this combination regimen in this high-risk population, and lay the groundwork for larger studies to bring more treatment choices to patients with advanced HCC. Methods: A 67-year-old male patient with advanced HCC and multiple metastases was treated with palbociclib 75mg on days 1-14 of a 28-day cycle, pembrolizumab 200mg intravenous infusion, selinexor 40mg weekly, and umbilical cord blood NK cell (12×109 cells) infusion on days 1, 14, 28 and 42. Imaging examinations and tumor marker detection were performed before and after two cycles of treatment to evaluate response. Results: After two cycles of combination treatment, follow-up PET-CT showed partial response with the liver tumors reduced in size by approximately 60%, lung metastases reduced by approximately 90%, and FDG uptake decreased more than 90% in lymph nodes and bone metastases. The AFP level decreased compared to baseline. Liver function tests including albumin, bilirubin and prothrombin time improved. The patient's performance status also improved from ECOG 2 to ECOG 1. Conclusions: This case report describes preliminary signals that the combination of selinexor, palbociclib, pembrolizumab, and umbilical cord blood NK cells may warrant further investigation for the treatment of advanced HCC. Objective response was observed based on standardized response criteria. However, due to the limitations of a single-arm case study design, definitive conclusions cannot be drawn regarding the efficacy or safety profile of this personalized combination approach. Larger and more robust clinical trials are needed to fully validate if this treatment strategy can achieve clinical benefit for advanced HCC. Future studies should aim to elucidate potential biomarkers that may help identify patients most likely to respond to this combination regimen. Exploring optimal patient selection criteria could also help maximize clinical benefit. Further research is warranted to continue exploring precision medicine combinations involving immunotherapy, targeted agents and cellular therapies for advanced HCC.

Expert consensus on microtransplant for acute myeloid leukemia in elderly patients -report from the international microtransplant interest group.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment.

Rituximab plus cladribine versus R-CHOP in frontline management of marginal zone lymphoma in China: a propensity-score matched multicenter study.

Marginal zone lymphoma (MZL) is an uncommon subtype of non-Hodgkin lymphoma (NHL). Combination of rituximab and cladribine (R-2CdA) is a potential option for indolent NHL (iNHL) and mantle cell lymphoma (MCL) patients. The goal of this multicenter retrospective study was to assess the efficacy and safety of R-2CdA in MZL to support consensus-reaching in first-line therapy in advanced-stage patients. We searched electronic medical records databases of eight centers in China. Between November 2014 and December 2019, 183 symptomatic advanced MZL patients (42 treated with R-2CdA and 141 with rituximab plus cyclophosphamide, adriamycin, vincristine, and prednisone [R-CHOP]) were identified. After propensity score matching (PSM) (1:1) to adjust for clinical characteristics, 39 patients from each treatment arm were selected. The overall response rate (ORR) (84.6% vs. 94.9%, P = 0.263) and complete response rate (59.0% vs. 66.7%, P = 0.487) were comparable between two protocols. Neither progression-free survival (PFS), including the 5-year PFS (67.7% vs. 56.1%, P = 0.352), nor overall survival was improved by R-2CdA versus R-CHOP. However, R-2CdA was more tolerable than R-CHOP in MZL patients regarding grade 3/4 hematological adverse events (odds ratio [OR] 0.565, 95% confidence interval [CI] neutropenic fever (OR 0.795, 95% CI 0.678-0.932), and infections (OR 0.800, 95% CI 0.640-1.000). Overall, our study demonstrated that R-2CdA is potentially as effective as but safer than R-CHOP in advanced MZL.

MiR-140 targets lncRNA FAM230B to suppress cell proliferation in acute myeloid leukemia running title: MiR-140 targets FAM230B in AML.

BACKGROUND: FAM230B serves as an oncogenic lncRNA in both gastric cancer and papillary thyroid cancer, while its role in acute myeloid leukemia (AML) is unclear. We predicted that FAM230B could be a target of miR-140, a well-characterized tumor suppressor, and analyzed their interaction in AML. METHODS: Differential expressions of FAM230B and miR-140 in bone marrow mononuclear cells (BMMNCs) were determined by RT-qPCR. Correlations were analyzed by Pearson's correlation coefficient. Subcellular FAM230B location was determined using cellular fractionation assay. The direct interaction between FAM230B and miR-140 was confirmed by RNA pull-down assay. The roles of FAM230B and miR-140 in cell proliferation were explored using BrdU assay. RESULTS: High FAM230B expression level and low miR-140 expression level were observed in AML. FAM230B and miR-140 were inversely correlated and directly interacted with each other. FAM230B could be detected in both cytoplasm and nuclear samples. MiR-140 overexpression downregulated FAM230B expression and suppressed the enhancing effects of FAM230B overexpression on cell proliferation. CONCLUSION: MiR-140 may target FAM230B to suppress cell proliferation in AML.

Ibrutinib as monotherapy versus combination therapy in Chinese patients with relapsed/refractory mantle cell lymphoma: A multicenter study.

BACKGROUND: Ibrutinib has revolutionized the treatment of mantle cell lymphoma (MCL). Both ibrutinib monotherapy and ibrutinib-based combination therapy are important salvage options for patients with relapsed/refractory (R/R) MCL. The real-world efficacy and safety profile of the two strategies in Chinese patients with R/R MCL remain unclarified. METHODS: In the present study, data of 121 R/R MCL patients who received either ibrutinib monotherapy (N = 68) or ibrutinib combination therapy (N = 53) in 13 medical centers in China were retrospectively reviewed. RESULTS: With a median follow-up of 20.5 months, the overall response rate was 60.3% versus 84.9% (p = 0.003), complete remission rate was 16.2% versus 43.4% (p < 0.001), and median progression-free survival (PFS) was 18.5 months (95% confidence interval [CI], 12.1-21.8) vs. 30.8 months (95% CI, 23.5-NR) (hazard ratio, 0.53 [95% CI, 0.30-0.93]; p = 0.025), with ibrutinib monotherapy and ibrutinib-based combination therapy, respectively. Subgroup analysis showed that patients with male gender, no refractory disease, Ki67 <30%, previous line of therapy = 1, non-blastoid subtype, and the number of extranodal sites involved <2 might benefits more from the combination therapy. Treatment-emergent adverse events were similar, except for a higher incidence of all grade neutropenia in the ibrutinib combination group (12.7% vs. 32.0%, p = 0.017). CONCLUSIONS: Ibrutinib combination therapy demonstrated potentially superior efficacy and comparable tolerability to ibrutinib monotherapy. Ibrutinib-based combination therapy could be one of the prominent treatment options for R/R MCL patients.

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study.

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Continuous Porous Aromatic Framework Membranes with Modifiable Sites for Optimized Gas Separation.

Continuous microporous membranes are widely studied for gas separation, due to their low energy premium and strong molecular specificity. Porous aromatic frameworks (PAFs) with their exceptional stability and structural flexibility are suited to a wide range of separations. Main-stream PAF-based membranes are usually prepared with polymeric matrices, but their discrete entities and boundary defects weaken their selectivity and permeability. The synthesis of continuous PAF membranes is still a major challenge because PAFs are insoluble. Herein, we successfully synthesized a continuous PAF membrane for gas separation. Both pore size and chemistry of the PAF membrane were modified by ion-exchange, resulting in good selectivity and permeance for the gas mixtures H2 /N2 and CO2 /N2 . The membrane with Br- as a counter ion in the framework exhibited a H2 /N2 selectivity of 72.7 with a H2 permeance of 51844 gas permeation units (GPU). When the counter ions were replaced by BF4 - , the membrane showed a CO2 permeance of 23058 GPU, and an optimized CO2 /N2 selectivity of 60.0. Our results show that continuous PAF membranes with modifiable pores are promising for various gas separation situations.

Association between miR-212-3p and SOX11, and the effects of miR-212-3p on cell proliferation and migration in mantle cell lymphoma.

To the best of our knowledge, the effect of miR-212-3p on sex-determining region Y-box 11 (SOX11) expression has not been previously investigated and how this effect affects cell proliferation and migration in lymphoma remains unclear. The present study aimed to assess the association between microRNA-212-3p (miR-212-3p) and SOX11, and the effects of miR-212-3p on cell proliferation and migration in mantle cell lymphoma. Cancer tissue and corresponding paracancerous tissue samples were collected from 65 patients with mantle cell lymphoma. The mRNA expression levels of miR-212-3p and SOX11 were analyzed using quantitative PCR, and SOX11 protein expression was determined using western blotting. Following transfection, the miR-212-3p mimic group exhibited a significantly lower SOX11 mRNA and protein expression than the miR-NC group. After 48-72 h of transfection, cell proliferation in the miR-212-3p mimic group was significantly lower than that in the miR-NC group. Furthermore, the miR-212-3p mimic group exhibited significantly lower cell invasion and significantly higher apoptosis than the miR-NC group. The current results suggested that miR-212-3p inhibited lymphoma cell proliferation and migration, and promoted their apoptosis by specifically regulating SOX11. Therefore, miR-212-3p may serve as a novel therapeutic target and marker for lymphoma.

lncRNA SNHG14 promotes oncogenesis and immune evasion in diffuse large-B-cell lymphoma by sequestering miR-152-3p.

This study aimed to explore the role of small nucleolar RNA host gene 14 (SNHG14) in the pathogenesis of diffuse large-B-cell lymphoma (DLBCL). DLBCL cell lines (OCI-Ly7 and OCI-Ly3) and specimens from patients were collected to evaluate the roles of SNHG14 in DLBCL pathogenesis. The results showed that SNHG14 expression increased and miR-152-3p expression decreased in DLBCL tissues and cell lines, indicating a negative correlation between miR-152-3p and SNHG14 expression. Moreover, SNHG14 was found to promote DLBCL growth, migration, and EMT-like processes in vitro, and directly inhibits miR-152-3p gene expression via sequestration of the miR-152-3p transcripts in DLBCL. Additionally, SNHG14/miR-152-3p inhibits apoptosis and promotes cell proliferation on cytotoxic T lymphocytes (CTLs) in DLBCL via the PD-1/PD-L1 checkpoint. Furthermore, both the immune escape and progression of DLBCL are advanced by SNHG14 expression via its interactions with miR-152-3p. Collective, this suggests that SNHG14 is a potential diagnostic, prognostic, and therapeutic target for DLBCL.

Oxaliplatin-induced peripheral neuropathy: clinical features, mechanisms, prevention and treatment.

Oxaliplatin (OXA) is a commonly used platinum-based chemotherapy drug for colorectal cancer. OXA-induced peripheral neurotoxcity (OIPN) is a comprehensive adverse reaction of OXA. OIPN can be divided into acute and chronic types according to clinical features and different mechanisms. The main clinical features of acute OIPN are cold-sensitive sensory symptoms and neuropathic pain in limbs. In addition to the above symptoms, chronic OIPN also produces autonomic nerve dysfunction. The most important mechanism involved in acute OIPN is the alteration of voltage-gated Na + channels, and nuclear DNA damage in chronic OIPN. There are some methods like reducing exposure to cold, calcium and magnesium salts, amifostine could be beneficial in acute OIPN prevention and dose modification, changing in schedule glutathione, duloxetine, selective serotonin reuptake inhibitors, carbonic anhydrase inhibitor in chronic OIPN prevention. Recent updates are provided in this article in relation to the clinical features, potential mechanisms, prevention and treatment of OIPN.

Potential pathways of zinc deficiency-promoted tumorigenesis.

Zinc (Zn) is the second most abundant necessary trace element in the human body. It is reported that zinc deficiency (ZD) promotes many types of cancer progression through multiple signal pathways. It is well known that oxidative stress, DNA damage, DNA repair, cell cycle, cell apoptosis, metabolic alterations, microRNAs abnormal expression, and inflammation level are closely related to cancer development. Cumulative evidence suggests that ZD influences these biological functions. This review explores the latest advances in understanding the role of ZD in tumorigenesis. Fully comprehending the potential mechanisms of ZD-induced tumors may provide novel clues for prevention and clinical treatment of cancers.

Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thyroid cancer (TC) is the most common endocrine system tumour. Several studies had revealed the potential of circulating microRNAs (miRNAs) as novel biomarkers for the diagnosis of TC. The purpose of this meta-analysis is to summarize published studies and evaluate the diagnostic accuracy of circulating miRNAs in TC detection. METHODS: In this meta-analysis, we systematically searched three databases: PubMed, EMBASE and Cochrane Library. We used the bivariate mixed-effects regression model to calculate the pooled diagnostic parameters and conduct the summary receiver operator characteristic curve (SROC). All calculations were performed using stata software. RESULTS: Thirty-five studies from 9 articles, including 663 TC patients, 519 patients with benign thyroid nodules (BTNs), and 84 healthy controls were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were 0.81 (95% CI 0.75-0.86), 0.81 (95% CI 0.75-0.86), 4.3 (95% CI 3.2-5.6), 0.24 (95% CI 0.18-0.31), 18 (95% CI 12-28) and 0.88 (95% CI 0.85-0.90), respectively in BTN controls, and 0.81 (95% CI 0.75-0.86), 0.85 (95% CI 0.75-0.91), 5.3 (95% CI 3.3-8.7), 0.23 (95% CI 0.18-0.29), 24 (95% CI 14-39), 0.89 (95% CI 0.86-0.91) in healthy controls. The subgroup analysis found that multiple miRNA assays had higher diagnostic accuracy than single miRNA assays with sensitivity of 0.88, specificity of 0.89 and AUC of 0.94. CONCLUSION: Circulating miRNAs have good values to diagnose TC and distinguish TC patients from BTN patients. MiRNAs can assist in the diagnosis of malignancy and avoid unnecessary surgery. In summary, circulating miRNAs should be added to our current clinical tools.

Significance of the microRNA­17­92 gene cluster expressed in B­cell non­Hodgkin's lymphoma.

To evaluate the prognostic value of the microRNA (miR)­17­92 gene cluster, the expression of miR­17­92 in B­cell non­Hodgkin's lymphoma (B­NHL) was examined. Patients with B­NHL, who received therapy in the Department of Hematology, Harbin Medical University Cancer Hospital between January 2012 and October 2014, were enrolled in the study. The expression of the miR­17­92 cluster in tumor tissue samples was detected by reverse transcription­quantitative polymerase chain reaction analysis. The overall survival (OS) and event­free survival (EFS) times were also investigated by the Kaplan­Meier method and comparisons between groups were estimated using a log­rank test. Three types of lymphoid cancer cells with wild­type (WT), knockout of miR­17­92 (KO), and overexpression of miR­17­92 (TG), were utilized to establish a tumor xenograft model, and a reactive hyperplasia lymph cell was used as a control. The tumor incubation times and weights were examined. A total of 71 patients with B­NHL were registered. No significant correlations were identified between the expression of miR­17­92 and clinical factors (P>0.05). Members of the miR­17­92 cluster exhibited various expression in the subtypes of B­NHL, and the difference between follicular lymphoma (FL) and germinal center B­cell like (GBC) was most marked. The overexpression of miR­18, miR­19a, and miR­92a induced a marked reduction in the OS of patients with B­NHL, and high­levels of miR­19a and miR­92a led to a decline in EFS. The overexpression of miR­17­92 shortened the duration of incubation required for visualization of the xenograft tumor, whereas knockout led to inhibition of tumor formation. The expression of miR­17­92 in FL differed significantly from that in GBC, and miR­19a may have a crucial effect on the OS and EFS of patients with B­NHL.

A Crystalline Polyimide Porous Organic Framework for Selective Adsorption of Acetylene over Ethylene.

The separation of acetylene from ethylene is a crucial process in the petrochemical industry, as even small acetylene impurities can lead to premature termination of ethylene polymerization. Herein, we present the synthesis of a robust, crystalline naphthalene diimide porous aromatic framework via imidization of linear naphthalene-1,4,5,8-tetracarboxylic dianhydride and triangular tris(4-aminophenyl)amine. The resulting material, PAF-110, exhibits impressive thermal and long-term structural stability, as indicated by thermogravimetric analysis and powder X-ray diffraction characterization. Gas adsorption characterization reveals that PAF-110 has a capacity for acetylene that is more than twice its ethylene capacity at 273 K and 1 bar, and it exhibits a moderate acetylene selectivity of 3.9 at 298 K and 1 bar. Complementary computational investigation of each guest binding in PAF-110 suggests that this affinity and selectivity for acetylene arises from its stronger electrostatic interaction with the carbonyl oxygen atoms of the framework. To the best of our knowledge, PAF-110 is the first crystalline porous organic material to exhibit selective adsorption of acetylene over ethylene, and its properties may provide insight into the further optimized design of porous organic materials for this key gas separation.

miR-26b-5p suppresses proliferation and promotes apoptosis in multiple myeloma cells by targeting JAG1.

BACKGROUND: Though the levels of diagnosis and treatment of multiple myeloma (MM) have been largely improved recent years, the prognosis of these patients remain unacceptable. It is urgent for us to discover the exact mechanism and determine some new indicators for MM. MiRNAs play a critical role in the occurrence and progression of cancers, including MM. MiR-26b-5p has been reported to be closely related to cells proliferation in human pulmonary cancer, hepatocellular carcinoma and so on. MATERIAL AND METHODS: Here, we measured the expression of miR-26b-5p in MM samples and cell lines by real-time PCR. Then, Kaplan-Meier Curves were applied to assess the effect of miR-26b-5p expression on MM patients prognosis. Functionally, MTT assay and Flow cytometry were conducted to explore the functions of miR-26b-5p in cells proliferation and apoptosis. Furthermore, bioinformatics tools, Pearson's correlation coefficient analysis, gain-and loss of-function experiments and rescue experiment were used to determine the relationship between JAG1 and miR-26b-5p in MM cells. In addition, we also confirmed the role of JAG1 in MM cells proliferation and apoptosis by gain-and loss of-function experiments. RESULTS: Here, we reported for the first time that miR-26b-5p was under-expressed in MM by real-time PCR. Clinically, Kaplan-Meier Curves showed that MM patients with lower miR-26b-5p expression had worse prognosis. Functionally, MTT assay revealed that miR-26b-5p inhibited cells proliferation. Flow cytometry indicated that miR-26b-5p accelerated tumor cells apoptosis. Furthermore, bioinformatics tools, Pearson's correlation coefficient analysis gain-and loss of-function experiments showed that JAG1 was the target of miR-26b-5p in MM cells. And, gain-and loss of-function experiments for JAG1 confirmed that JAG1 was an oncogene in MM cells. What's more, rescue experiment showed that JAG1 mediated the function of miR-26b-5p in MM cells. CONCLUSION: MiR-26b-5p acts as a tumor suppressor through suppressing cells proliferation and inducing cells apoptosis via directly targeting JAG1 in MM. MiR-26b-5p could be a potential and ponderable tumor target for MM in future.

HuR regulates telomerase activity through TERC methylation.

Telomerase consists of the catalytic protein TERT and the RNA TERC. Mutations in TERC are linked to human diseases, but the underlying mechanisms are poorly understood. Here we report that the RNA-binding protein HuR associates with TERC and promotes the assembly of the TERC/TERT complex by facilitating TERC C106 methylation. Dyskeratosis congenita (DC)-related TERC U100A mutation impair the association of HuR with TERC, thereby reducing C106 methylation. Two other TERC mutations linked to aplastic anemia and autosomal dominant DC, G107U, and GC107/108AG, likewise disrupt methylation at C106. Loss-of-HuR binding and hence lower TERC methylation leads to decreased telomerase activity and telomere shortening. Furthermore, HuR deficiency or mutation of mTERC HuR binding or methylation sites impair the renewal of mouse hematopoietic stem cells, recapitulating the bone marrow failure seen in DC. Collectively, our findings reveal a novel function of HuR, linking HuR to telomerase function and TERC-associated DC.

Lentivirus-mediated down-regulation of CK2α inhibits proliferation and induces apoptosis of malignant lymphoma and leukemia cells.

Casein kinase II subunit alpha (CK2α) is highly expressed in many malignant tumor tissues, including lymphomas and leukemia. To investigate the role of CK2α in cell proliferation and apoptosis of malignant lymphomas and leukemia, 2 lymphoma cell lines and one leukemia cell line were infected with CK2α shRNA lentivirus or negative control shRNA lentivirus, and stably infected cell lines were established. Real-time PCR and Western blot results showed that the mRNA and protein levels of CK2α were significantly reduced in CK2α knockdown cells. The tetrazolium-based colorimetric (MTT) assay found that down-regulation of CK2α inhibited the proliferation of these cells. Flow cytometry analysis showed that inhibition of CK2α induced cell cycle arrest and apoptosis of lymphoma and leukemia cells. In accordance with these, down-regulation of CK2α also reduced the protein levels of proliferating cell nuclear antigen (PCNA), cyclinD1, and bcl-2, and increased the protein expression of bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly(ADP ribose) polymerase (PARP). Moreover, knockdown of CK2α impeded the growth of xenograft tumors in vivo. In summary, our study revealed that CK2α may contribute to the development of malignant lymphoma and leukemia, and serve as the therapeutic target of these malignant tumors.