Associations of long-term exposure to air pollution with prevalence of pulmonary nodules: A cross-sectional study in Shijiazhuang, China.

A complete understanding of the associations of ambient air pollution with prevalence of pulmonary nodule is lacking. We aimed to investigate the associations of ambient air pollutants with prevalence of pulmonary nodule. A total of 9991 health examination participants was enrolled and 3166 was elected in the final in Shijiazhuang between April 1st, 2018, and December 31st, 2018. 107 participants were diagnosed in pulmonary nodule while 3059 participants were diagnosed in non-pulmonary (named control). The individual exposure of participants was evaluation by Empirical Bayesian Kriging model according to their residential or work addresses. The pulmonary nodules were found and diagnosed by health examination through chest x-ray detection. Our results suggested that there were positive associations between prevalence of pulmonary nodules and PM2.5 (OR = 1.06, 95% CI: 1.02, 1.11) as well as O3 (OR = 1.49, 95% CI: 1.35, 1.66) levels. The platelet count (PLT) acted as the mediator of pulmonary nodules related with the PM2.5 exposure, while the neutrophil-to-lymphocyte ratio (NLR) as well as platelet-to-lymphocyte ratio (PLR) were the mediators of pulmonary nodules related with the O3 exposure. This study suggests that long-term exposure to PM2.5 and O3 may significantly associated with prevalence of pulmonary nodules, and the above associations are mediated by PLT, NLR and PLR.

The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.

BACKGROUND: Autophagy has been found to be involved in the multidrug resistance (MDR) of cancers, but whether it is associated with resistance of small cell lung cancer (SCLC) has not been studied. Here, we hypothesized that a potential autophagy-regulating miRNA, miR-199a-5p, regulated cisplatin-resistant SCLC. METHODS: We validated the MDR of H446/EP using CCK-8 and LDH. We tested the binding of miR-199a-5p to p62 using the Dual-Luciferase assay and validated the association of miR-199a-5p and p62 in SCLC samples. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. These results were validated in an orthotopic H446 mouse model of SCLC. RESULTS: H446/EP was resistant to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Exposure of cisplatin at 5 µg/ml for 24 h increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells. The expression of miR-199a-5p was up-regulated in H446/EP compared to H446. MiR-199a-5p directly targeted the p62 gene. The expression of miR-199a-5p and p62 were correlated in SCLC samples. In H446 and H69PR, the OE of miR-199a-5p increased LC3II/LC3I, p62, and the formation of autophagolysosomes, but not ATG5, while the KD of miR-199a-5p decreased p62, but did not affect LC3II/LC3I, ATG5, and the formation of autophagolysosomes. In H446/EP, the OE of miR-199a-5p decreased p62 only. These results were generally consistent to results in the animal tumor samples. CONCLUSIONS: The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.

Dispersal network heterogeneity promotes species coexistence in hierarchical competitive communities.

Understanding the mechanisms of biodiversity maintenance is a fundamental issue in ecology. The possibility that species disperse within the landscape along differing paths presents a relatively unexplored mechanism by which diversity could emerge. By embedding a classical metapopulation model within a network framework, we explore how access to different dispersal networks can promote species coexistence. While it is clear that species with the same demography cannot coexist stably on shared dispersal networks, we find that coexistence is possible on unshared networks, as species can surprisingly form self-organised clusters of occupied patches with the most connected patches at the core. Furthermore, a unimodal biodiversity response to an increase in species colonisation rates or average patch connectivity emerges in unshared networks. Increasing network size also increases species richness monotonically, producing characteristic species-area curves. This suggests that, in contrast to previous predictions, many more species can co-occur than the number of limiting resources.

Preparation and identification of an anti-idiotypic antibody antagonist (FG8) for EGFR that shows potential activity against liver cancer cells.

OBJECTIVE: Currently, there are two categories of epidermal growth factor receptor (EGFR) antagonists, small molecule antagonists and anti-EGFR antibodies. In the current study, we developed a new EGFR antagonist employing the anti-idiotypic antibodies strategy. RESULTS: First, using EGF as an antigen, through a series of immunological protocols and hybridoma technology, we obtained an anti-idiotypic antibody against EGF receptor-binding epitopes. On this basis, we screened and characterized the anti-idiotype antibodies against EGFR through competitive ELISA, co-localization analysis, competitive receptor binding analysis, and immunofluorescence. Finally, an internal image anti-idiotype antibody called FG8 was successfully prepared. Experiment result shows that FG8 inhibits EGFR-mediated signaling pathways in vitro. Additionally, FG8 inhibits liver tumor cell proliferation as well as induces tumor cell apoptosis. CONCLUSIONS: The present study suggests that FG8 is a potential therapeutic agent for liver cancer. In addition, this study provides a novel method for the preparation of EGFR antagonists.

Long Non-coding RNA MIAT Mediates Non-small Cell Lung Cancer Development Through Regulating the miR-128-3p/PELI3 Axis.

In this study, we set out to characterize the expression status of long non-coding RNA (lncRNA) Myocardial Infarction Associated Transcript (MIAT) in non-small cell lung cancer (NSCLC) and elucidate its mechanistic contribution to this disease. Relative expression levels of MIAT, Pellino E3 Ubiquitin Protein Ligase Family Member 3 (PELI3), and microRNA (miR)-128-3p were analyzed by real-time polymerase chain reaction. PELI3 protein level was determined by immunoblotting. Cell viability and proliferation were evaluated by the MTT assay and colony formation assay, respectively. Cell invasion and migration were assessed by wound-healing closure and transwell assays, respectively. The regulatory actions of miR-128-3p on both MIAT and PELI3 were interrogated by luciferase reporter assay. We demonstrated the aberrant upregulation of MIAT in NSCLC and its association with tumor progression. We further uncovered the negative correlation among MIAT, PELI3, and miR-128-3p. MIAT deficiency significantly compromised cell viability, proliferation, invasion, and migration, while increased miR-128-3p and decreased PELI3 expressions. Application of miR-128-3p inhibitor significantly stimulated luciferase activities driven by both MIAT and PELI3 promoter and phenotypically promoted cell viability, proliferation, migration, and invasion. Our study highlighted the mechanistic contribution of the MIAT/miR-128-3p/PELI3 signaling cascade in NSCLC.

PELI3 mediates pro-tumor actions of down-regulated miR-365a-5p in non-small cell lung cancer.

BACKGROUND: To analyze the relative expression of PELI3 and its mechanistic involvement in the non-small cell lung cancer (NSCLC). METHODS: PELI3 expression in NSCLC tissue samples was determined by the immunohistochemistry. The transcripts abundance of PELI3 was measured with real-time PCR. The protein intensity was analyzed by western blot. The overall survival in respect to PELI3 or miR-365a-5p expression was plotted by the Kaplan-Meier's analysis. Cell growth was determined by colony formation assay. Cell viability was measured by MTT assay. The migration and invasion were evaluated by wound healing and transwell assay respectively. The regulatory effect of miR-365a-5p on PELI3 was interrogated with luciferase reporter assay. The direct binding between miR-365a-5p and PELI3 was analyzed by pulldown assay. RESULTS: PELI3 was aberrantly up-regulated in NSCLC both in vivo and in vitro. High level of PELI3 associated with poor prognosis. PELI3-deficiency significantly inhibited cell viability, colony formation, migration and invasion. We further identified that miR-365a-5p negatively regulated PELI3 in this disease. Ectopic expression of miR-365a-5p in both A549 and H1299 phenocopied PELI3-deficiency. Meanwhile, PELI3-silencing significantly abolished the pro-tumoral effect elicited by miR-365a-5p inhibition. CONCLUSION: Our results highlighted the importance of dysregulated miR-365a-5p-PELI3 signaling axis in NSCLC.

Habitat amount modulates biodiversity responses to fragmentation.

Anthropogenic habitat destruction leads to habitat loss and fragmentation, both of which interact to determine how biodiversity changes at the landscape level. While the detrimental effects of habitat loss are clear, there is a long-standing debate about the role of habitat fragmentation per se. We identify the influence of the total habitat amount lost as a modulator of the relationship between habitat fragmentation and biodiversity. Using a simple metacommunity model characterized by colonization-competition (C-C) trade-offs, we show that the magnitude of habitat loss can induce a unimodal response of biodiversity to habitat fragmentation. When habitat loss is low, habitat fragmentation promotes coexistence by suppressing competitively dominant species, while habitat fragmentation at high levels of habitat loss can shape many smaller isolated patches that drive extinctions of superior competitors. While the C-C trade-off is not the only mechanism for biodiversity maintenance, the modulation of habitat fragmentation effects by habitat loss is probably common. Reanalysis of a globally distributed dataset of fragmented animal and plant metacommunities shows an overall pattern that supports this hypothesis, suggesting a resolution to the debate regarding the relative importance of positive versus negative fragmentation effects.

Trajectory of mid-arm subcutaneous fat, muscle mass predicts mortality in hemodialysis patients independent of body mass index.

Although decreasing body mass index (BMI) is associated with higher mortality risk in patients undergoing hemodialysis (HD), BMI neither differentiates muscle and fat mass nor provides information about the variations of fat distribution. It remains unclear whether changes over time in fat and muscle mass are associated with mortality. We examined the prognostic significance of trajectory in the triceps skinfold (TSF) thickness and mid-upper arm circumference (MUAC). In this multicenter prospective cohort study, 972 outpatients (mean age, 54.5 years; 55.3% men) undergoing maintenance HD at 22 treatment centers were included. We calculated the relative change in TSF and MUAC over a 1-year period. The outcome was all-cause mortality. Kaplan-Meier, Cox proportional hazard analyses, restricted cubic splines, and Fine and Gray sub-distribution hazards models were performed to examine whether TSF and MUAC trajectories were associated with all-cause mortality. During follow-up (median, 48.0 months), 206 (21.2%) HD patients died. Compared with the lowest trajectory group, the highest trajectories of TSF and MUAC were independently associated with lower risk for all-cause mortality (HR = 0.405, 95% CI 0.257-0.640; HR = 0.537; 95% CI 0.345-0.837; respectively), even adjusting for BMI trajectory. Increasing TSF and MUAC over time, measured as continuous variables and expressed per 1-standard deviation decrease, were associated with a 55.7% (HR = 0.443, 95% CI 0.302-0.649), and 97.8% (HR = 0.022, 95% CI 0.005-0.102) decreased risk of all-cause mortality. Reduction of TSF and MUAC are independently associated with lower all-cause mortality, independent of change in BMI. Our study revealed that the trajectory of TSF thickness and MUAC provides additional prognostic information to the BMI trajectory in HD patients.

Pan-Cancer Analysis Shows that KIFC2 is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Bladder Cancer.

KIFC2 plays an important role in prostate cancer progression and chemotherapy resistance, but the mechanism of its involvement in other malignancies remains unclear. Therefore, this study aimed to analyze and validate the mechanism of effect of KIFC2 in multiple tumors. Bioinformatic analysis was performed in conjunction with multiple databases (The Cancer Genome Atlas, Genotype-Tissue Expression Project, Human Protein Atlas, etc.) to fully explore the potential role of KIFC2 within individual tumors and to analyze the correlation with major research components such as prognosis, mutations, and the tumor microenvironment. The expression of KIFC2 demonstrates a significant correlation with the prognosis, clinical phenotype, tumor mutational burden, microsatellite instability, and tumor microenvironment across various malignancies and is associated with the modulation of diverse functional and signaling pathways. The differences in the expression of KIFC2 in the bladder cancer tissues (14 pairs) were statistically significant. The pan-cancer analysis in this study revealed the multifunctionality of KIFC2 in a variety of tumors, indicating a possible prognostic predictor and potential therapeutic target for tumors.

Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling.

BACKGROUND: Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear. METHODS: Lrp4f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4-/-) and pyramidal neuron specific knockout mice (Nex-Lrp4-/-). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored. RESULTS: We found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE. CONCLUSION: These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

Complex nonmonotonic responses of biodiversity to habitat destruction.

It has typically been assumed that habitat destruction, characterized by habitat loss and fragmentation, has consistently negative effects on biodiversity. While numerous empirical studies have shown the detrimental effects of habitat loss, debate continues as to whether habitat fragmentation has universally negative effects. To explore the effects of habitat fragmentation, we developed a simple model for site-occupancy dynamics in fragmented landscapes. With the model, we demonstrate that a competition-colonization trade-off can result in nonlinear oscillatory responses in biodiversity to both habitat loss and fragmentation. However, the overall pattern of habitat loss reducing species richness is still established, in line with empirical observations. Interestingly, the existence of localized oscillations in biodiversity can explain the mixed responses of species richness to habitat fragmentation per se observed in nature, thereby reconciling the debate on the fragmentation-diversity relationship. Therefore, this study offers a parsimonious mechanistic explanation for empirically observed biodiversity patterns in response to habitat destruction.

Genetic instability of lung induced by carbon black nanoparticles is related with Plk1 signals changes.

As a possible carcinogen, carbon black has threatened public health. However, the evidences are insufficient and the mechanism of carcinogenesis is still not specified. Thirty rats were randomly divided into 3 groups, namely 0, 5 and 30 mg/m3 Carbon Black nanoparticles (CBNPs) groups, respectively. Rats were treated with CBNPs by nose-only inhalation for 28 days, 6 h/day. The human bronchial epithelial (16HBE) cells were treated with 0, 50, 100 and 200 µg/mL CBNPs for 24 h. Polo-like kinase 1 (PLK1) overexpression cell line was established by pcDNA3.1-PLK1 stable transfection. Our results showed that CBNPs exposure could induce DNA damage and genetic changes as well as apoptosis in vivo and in vitro. The DNA repair ability increased after CBNPs exposure. Cell cycle process was retarded at the G2/M phases in 16HBE cells after CBNPs treatment. The PLK1, ChK2 GADD45α and XRCC1 expression levels changed in rat lung and 16HBE cells after CBNPs treatment. Compared with NC 16HBE cells, DNA damage and repair, numbers of apoptotic cells and micronucleus (MN) rates, as well as the ChK2, GADD45α, XRCC1 expression levels decreased, whereas cytokinesis block proliferation index (CBPI) and replicative index (RI) increase in PLK overexpression (PLK+/+) cells after CBNPs treatment. This study highlighted that PLK1 related with the genetic toxicity of CBNPs in vitro and in vivo. Our results provided evidences supporting reclassification of carbon black as a human possible carcinogen.

PEG-rhG-CSF for prophylaxis of neutropenia after chemotherapy in patients with non-small cell lung cancer: A multicenter, prospective, randomized study.

BACKGROUND: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during multiple cycles of chemotherapy in patients with non-small cell lung cancer (NSCLC). METHOD: In a multicenter, prospective, randomized trial, patients with NSCLC were randomly assigned in a 2:1 ratio to treatment group (PEG-rhG-CSF as primary prophylactic therapy) or control group. Patients in the control group were administered rhG-CSF when white blood cell count was <2.0 × 109 /L or absolute neutrophil count <1.0 × 109 /L. The primary endpoint was the incidence of grade 3/4 neutropenia. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia in each cycle, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, and safety. RESULTS: Between January 2019 and July 2021, 130 patients were enrolled (treatment group: n = 87, control group: n = 43). The incidence of grade 3/4 neutropenia in the treatment group was significantly lower than that in the control group (1.15% vs. 11.63%, p < 0.05). The mean duration of grade 3/4 neutropenia for the treatment and control group was 2.00 and 3.75 days, respectively. There were no statistical differences in the incidence of FN, delay rate of chemotherapy, prolonged time of chemotherapy, and antibiotic use between the two groups (all p > 0.05). Adverse events were reported in 47.13% of patients in the treatment group and 48.84% patients in the control group. CONCLUSIONS: Primary prophylactic treatment with PEG-rhG-CSF could reduce the incidence of neutropenia in patients with NSCLC during multiple cycles of chemotherapy, with acceptable safety and tolerability.

LINC00958 may be a new prognostic biomarker in various cancers: A meta-analysis and bioinformatics analysis.

Background: There have been many studies on long non-coding RNAs (lncRNAs) as tumor markers. LINC00958 is a lncRNA that has been studied in a variety of tumor types. This meta-analysis aims to explore the relationship between LINC00958 and clinical prognosis and pathological characteristics in various cancers. Methods: We searched for related studies from PubMed, Web of Science, The Cochrane Library and Embase (up to October 2021). The association of LINC00958 expression with clinicopathological characteristics and prognosis was evaluated using the pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). Results: 16 studies (1,121 patients) were included in this meta-analysis, we found that overexpression of LINC00958 was associated with poor overall survival (OS) (HR = 1.84; 95% CI: 1.36-2.49; p < 0.001). We also found that LINC00958 overexpression was correlated with positive lymph node metastasis (LNM) (OR = 1.91; 95% CI: 1.39-2.63; p < 0.001), advanced degree of infiltration (OR = 1.64; 95% CI: 1.11-2.41; p = 0.013), advanced tumor-node-metastasis (TNM) stage (OR = 2.80; 95% CI: 1.48-5.33; p = 0.002). Other clinicopathological characteristics have no obvious correlation, such as age, sex, tumor size, distant metastasis, and differentiation grade (p > 0.05). Conclusion: In summary, the overexpression of LINC00958 is significantly correlated with poor OS, positive LNM, advanced degree of infiltration, and advanced TNM stage. LINC00958 might serve as a potential prognostic biomarker and therapeutic target for a variety of cancers. However, rigorous studies with large sample sizes are still needed for further research and demonstration.

HOXA-AS2 may be a potential prognostic biomarker in human cancers: A meta-analysis and bioinformatics analysis.

Background: Dysregulation of long non-coding (lncRNA) has been reported in various solid tumors. HOXA cluster antisense RNA 2 (HOXA-AS2) is a newly identified lncRNA with abnormal expression in several human malignancies. However, its prognostic value remains controversial. This meta-analysis synthesized available data to clarify the association between HOXA-AS2 expression levels and clinical prognosis in multiple cancers. Methods: Four public databases (Embase, PubMed, Web of Science, The Cochrane Library) were used to identify eligible studies. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined to assess the correlation of HOXA-AS2 expression with survival outcomes and clinicopathological features of cancer patients. Publication bias was measured using Begg's funnel plot and Egger's regression test, and the stability of the combined results was measured using sensitivity analysis. Additionally, multiple public databases were screened and extracted to validate the results of this meta-analysis. Results: The study included 20 studies, containing 1331 patients. The meta-analysis showed that the overexpression of HOXA-AS2 was associated with poor overall survival (HR = 2.06, 95% CI 1.58-2.69, p < 0.001). In addition, the high expression of HOXA-AS2 could forecast advanced tumor stage (OR = 3.89, 95% CI 2.90-5.21, p < 0.001), earlier lymph node metastasis (OR = 3.48, 95% CI 2.29-5.29, p < 0.001), larger tumor size (OR = 2.36, 95% CI 1.52-3.66, p < 0.001) and earlier distant metastasis (OR = 3.54, 95% CI 2.00-6.28, p < 0.001). However, other clinicopathological features, including age (OR = 1.09, 95% CI 0.86-1.38, p = 0.467), gender (OR = 0.92, 95% CI 0.72-1.18, p = 0.496), depth of invasion (OR = 2.13, 95% CI 0.77-5.90, p = 0.146) and differentiation (OR = 1.02, 95% CI 0.65-1.59, p = 0.945) were not significantly different from HOXA-AS2 expression. Conclusion: Our study showed that the overexpression of HOXA-AS2 was related to poor overall survival and clinicopathological features. HOXA-AS2 may serve as a potential prognostic indicator and therapeutic target for tumor treatment.

Integrative pan-cancer analysis indicates the prognostic importance of long noncoding RNA SNHG17 in human cancers.

BACKGROUND: Cancer is one of the most widespread causes of death today. Early diagnosis can dramatically reduce cancer-related mortality. Studies have shown that the lncRNA Small Nucleolar RNA Host Gene 17 (SNHG17) is aberrantly expressed in various types of solid tumors. Nevertheless, its prognostic value remains to be elucidated. The main objective of this meta-analysis was to elucidate whether SNHG17 can be considered as a potential prognostic biomarker for a variety of cancers. METHODS: Correlational studies were screened from Cochrane, Embase, PubMed, and Web of Science. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled, and the role of SNHG17 in cancer was analyzed. The Cancer Genome Atlas (TCGA) database was employed to verify the results. RESULTS: Seventeen original papers including 1451 patients were included in the meta-analysis. SNHG17 expression was upregulated in various cancers. Overexpression of SNHG17 was significantly correlated with worse overall survival (OS) (HR = 1.92, 95% CI 1.55-2.37, P < 0.001) and relapse-free survival (RFS) (HR = 1.87, 95% CI 1.06-3.30, P = 0.030). Furthermore, overexpression of SNHG17 was predictive of earlier lymph node metastasis (LNM) (OR = 2.94, 95% CI 2.29-3.78, P < 0.001), more advanced tumor-node-metastases (TNM) stage (OR = 3.56, 95% CI 2.22-5.68, P < 0.001), larger tumor size (OR = 2.18, 95% CI 1.65-2.88, P < 0.001), worse differentiation grade (OR = 1.69, 95% CI 1.26-2.25, P < 0.001), and earlier distant metastasis (DM) (OR = 1.63, 95% CI 1.03-2.56, P = 0.033) in human cancers. Moreover, further inquiry based on TCGA dataset validated that SNHG17 was high expression in various tumors and foresaw unfavorable clinical prognosis. CONCLUSIONS: Overexpression of SNHG17 correlates with poor prognosis and advanced clinicopathological features in cancer patients and may be a potential prognostic indicator and a therapeutic target for cancer treatment.

The QICK (Quantum Instrumentation Control Kit): Readout and control for qubits and detectors.

We introduce a Xilinx RF System-on-Chip (RFSoC)-based qubit controller (called the Quantum Instrumentation Control Kit, or QICK for short), which supports the direct synthesis of control pulses with carrier frequencies of up to 6 GHz. The QICK can control multiple qubits or other quantum devices. The QICK consists of a digital board hosting an RFSoC field-programmable gate array, custom firmware, and software and an optional companion custom-designed analog front-end board. We characterize the analog performance of the system as well as its digital latency, important for quantum error correction and feedback protocols. We benchmark the controller by performing standard characterizations of a transmon qubit. We achieve an average gate fidelity of Favg=99.93%. All of the schematics, firmware, and software are open-source.

Curcumin increases crizotinib sensitivity through the inactivation of autophagy via epigenetic modulation of the miR-142-5p/Ulk1 axis in non-small cell lung cancer.

Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.

Cortactin is implicated in murine zygotic development.

Cortactin is a cortex-enriched protein implicated in Arp2/3 complex-mediated actin polymerization. However, the physiological role of cortactin remains unknown. We have generated a mouse strain in which the allele of murine cortactin was disrupted by a gene trapping vector. The resulting heterozygous mice developed normally and were fertile, but embryonic fibroblasts derived from heterozygous animals displayed partial impairment in PDGF-induced membrane ruffling. No homozygous offspring or early embryos even at the two-cell stage were detected. Analysis of oocytes revealed a gradual decrease in the detection of homozygous zygotes after fertilization. In normal oocytes arrested at meiotic metaphase II (MII), cortactin immunoreactivity was detected in an apical layer that overlies the maternal chromosome and overlaps with a polarized cortex enriched with actin. The formation of the polarized cortactin layer was diminished upon treatment with latrunculin B, an actin polymerization inhibitor. After resumption of meiosis II, the majority of cortactin protein was accumulated into the second polar body. Microinjection of MII-arrested eggs with either cortactin antibody or RNA encoding a cortactin mutant deficient in Arp2/3 complex binding disrupted the integrity of the actin cap and inhibited emission of the second polar body triggered by parthenogenesis. Our data suggest that cortactin plays an important role in the mechanics of asymmetric division in oocytes.

The N-classification for esophageal cancer staging: should it be based on number, distance, or extent of the lymph node metastasis?

BACKGROUND: The recently published AJCC-TNM staging system for esophageal carcinoma made an obvious modification on N-classification based on the number of metastatic regional lymph nodes (LN). However, this classification might ignore the site at which these LNs occur, a factor that might be even more important in reflecting patients' prognosis. METHODS: A retrospective study of 236 patients with carcinoma of thoracic esophagus who underwent esophagectomy between 1984 and 1989 with each at least six LNs removed was conducted, with a 10-year follow-up rate of 92.4%. The proposed scheme for N-classification according to the number (0, 1-2, 3-6, ≥7; N0-3), distance (0, 1, 2, 3 stations; S0-3), or extent (0, 1, and 2 fields; F0-2) of LN involvement was evaluated by univariate and multivariate survival analysis. RESULTS: The LN metastasis was identified in 112 patients, revealing a poorer 5-year survival in this patient group when compared to patients without node involvement. Cox regression analysis revealed that the number and distance of LN metastases and the number of metastasis fields were factors significantly influencing survival. When these factors were further analyzed by univariate log-rank test, no significant difference in survival existed between N2 and N3 patients, or among S1, S2, and S3 patients. When patients were grouped according to the extent of LN metastasis, significant differences in survival were observed overall and between each subgroup. CONCLUSIONS: Refining the current N-classification for esophageal cancer according to the extent of LN metastasis, rather than by number alone, might be a better means of staging that could subgroup patients more effectively and result in different rates of survival.