Melt-quenched glass formation of a family of metal-carboxylate frameworks.

Metal-organic framework (MOF) glasses are an emerging class of glasses which complement traditional inorganic, organic and metallic counterparts due to their hybrid nature. Although a few zeolitic imidazolate frameworks have been made into glasses, how to melt and quench the largest subclass of MOFs, metal carboxylate frameworks, into glasses remains challenging. Here, we develop a strategy by grafting the zwitterions on the carboxylate ligands and incorporating organic acids in the framework channels to enable the glass formation. The charge delocalization of zwitterion-acid subsystem and the densely filled channels facilitate the coordination bonding mismatch and thus reduce the melting temperature. Following melt-quenching realizes the glass formation of a family of carboxylate MOFs (UiO-67, UiO-68 and DUT-5), which are usually believed to be un-meltable. Our work opens up an avenue for melt-quenching porous molecular solids into glasses.

Safety and efficacy of thoracic radiotherapy combined with chemo-immunotherapy in patients with extensive-stage small cell lung cancer: a multicenter retrospective analysis.

Background: Immunotherapy has greatly increased the survival time of patients with extensive-stage small cell lung cancer (ES-SCLC), and is now a standard first-line treatment for these patients. Increasing evidence suggests a possible synergistic effect between immunotherapy and radiotherapy, yet there is a paucity of evidence regarding the efficacy and safety of thoracic radiotherapy (TRT) combined with chemo-immunotherapy for ES-SCLC. Methods: The medical records of 78 consecutive patients with ES-SCLC who received TRT in combination with chemo-immunotherapy at Jinling Hospital and Jiangsu Cancer Hospital from January 2019 to January 2023 were retrospectively reviewed. The median overall survival (mOS) time and median progression-free survival (mPFS) time were used to evaluate efficacy, and the incidence of adverse events (AEs) was used to evaluate safety. Results: The median follow-up time was 31.9 months, the objective response rate (ORR) was 59%, and the disease control rate (DCR) was 89.8%. The mOS time was 20.0 months, and the 6-month OS rate was 95%. The mPFS time was 9.2 months, and the 6-month PFS rate was 78%. There were no treatment-related deaths. The incidence of pneumonitis was 23.1%, the incidence of radiation esophagitis was 5.1%, and 2 patients experienced high-grade pneumonitis. Primary liver metastasis was a predictor of poor OS and PFS. Patients who received consolidative TRT after chemo-immunotherapy experienced more benefit than those who received TRT as palliative or salvage treatment for superior vena cava syndrome or disease progression. Conclusions: TRT is a feasible treatment for patients who receive chemo-immunotherapy for the management of ES-SCLC in consideration of its considerable efficacy and tolerable safety risk. This treatment is especially useful for patients without primary liver metastasis and who receive consolidative TRT after chemo-immunotherapy. Large-scale prospective studies are needed to confirm the efficacy and safety of this treatment modality.

The effect of sperm DNA fragmentation on in vitro fertilization outcomes of unexplained infertility.

BACKGROUND: Infertility is caused by heterogeneous risks, but most of them are unexplained. The sperm DNA Fragmentation Index (DFI) was increasingly acknowledged as a parameter for the evaluation of male infertility. This study aimed to investigate the association between sperm DFI and laboratory and clinical outcomes in a population with unexplained infertility. METHODS: The clinical data of an infertile population was collected for the selection of reproductive patients with unexplained infertility. The authors classified the patients with normal sperm parameters in a control group (DFI < 25%) and an observation group (DFI ≥ 25%) and compared the difference in basal characteristics, laboratory, and clinical outcomes between the two groups. The authors conducted a correlation analysis to examine the relationship between DFI and the number of D3 good-quality embryos, as well as the clinical pregnancy rate and live birth rate. A total of 176 cases were enrolled in the retrospective study. RESULTS: The observation group (n = 88) showed advanced male age, lower sperm concentration, progressive motility, and morphology assessment than the control group. In addition, lower No. of D3 good-quality embryos, clinical pregnancy rate, and the live birth rate were shown in the observation group. A negative correlation between the DFI and No. of D3 good-quality embryos (rs = -0.347, p < 0.001) or live birth rate (rs = -0.185, p = 0.028) was shown. CONCLUSIONS: Sperm DFI was a good indicator for the prediction of D3 good-quality embryos in unexplained infertility couples, but it did not provide sufficient information regarding clinical pregnancy outcome but live pregnancy outcome.

Exploration on the first-line treatment of ERBB2-altered advanced non-small cell lung cancer: A multicenter retrospective study.

BACKGROUND: Although the treatment of ERBB2-altered non-small cell lung cancer (NSCLC) has been studied for many years, there are no comprehensive studies to evaluate the benefits of various therapies as first-line treatment. Through the development of immunotherapy, more and more different combination treatments were applicated in clinical practice, therefore, we conducted a multicenter retrospective study to evaluate the efficacy of different treatments. METHODS: We enrolled patients with ERBB2-altered NSCLC who had undergone at least one-line systemic anticancer treatment to evaluate the efficacy of first-line chemotherapy alone (Chemo), anti-ERBB2 tyrosine kinase inhibitor (TKI), chemotherapy plus immunotherapy (Chemo + Immuno), chemotherapy plus anti-angiogenesis therapy (Chemo + Antiangio) and chemotherapy combined with immunotherapy and anti-angiogenesis therapy (Chemo + Immuno + Antiangio). The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), one-year and three-year survival rate. RESULTS: We enroll 36 patients harboring ERBB2 mutation and 29 with ERBB2 amplification. The overall ORR was 30.8%, DCR was 69.2% and mPFS was 5.7 months. Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (7.8 vs 3.6 months, HR: 0.24, 95 %CI: 0.09-0.64, P = 0.002; 5.9 vs 3.6 months, HR: 0.36, 95 %CI: 0.15-0.88, P = 0.019; respectively), while there was no significant difference in mPFS between Chemo + Immuno or Chemo + Antiangio and Chemo (both P > 0.05), the mPFS of the first two was longer. For ERBB2-mutant patients, the mPFS was 5.9 months, and Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (12.9 vs 2.9 months, HR: 0.15, 95 %CI: 0.03-0.68, P = 0.005; 7.1 vs 2.9 months, HR: 0.50, 95 %CI: 0.29-0.88, P = 0.009, respectively). In the same therapies, patients with ERBB2 mutation or ERBB2 amplification showed no statistical significance in PFS (both P > 0.05). CONCLUSIONS: In the first-line treatment of ERBB2-altered NSCLC, chemotherapy combined with immunotherapy or anti-angiogenesis therapy may have greater survival benefits than ERBB2-target therapy, but the efficacy may not be better than that of chemotherapy.

[Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus 
Disease 2019 Pneumonia in Lung Cancer Patients: 
A Single-center Retrospective Study].

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS: Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

The effect of sperm DNA fragmentation on in vitro fertilization outcomes of unexplained infertility

Abstract Background Infertility is caused by heterogeneous risks, but most of them are unexplained. The sperm DNA Fragmentation Index (DFI) was increasingly acknowledged as a parameter for the evaluation of male infertility. This study aimed to investigate the association between sperm DFI and laboratory and clinical outcomes in a population with unexplained infertility. Methods The clinical data of an infertile population was collected for the selection of reproductive patients with unexplained infertility. The authors classified the patients with normal sperm parameters in a control group (DFI < 25%) and an observation group (DFI ≥ 25%) and compared the difference in basal characteristics, laboratory, and clinical outcomes between the two groups. The authors conducted a correlation analysis to examine the relationship between DFI and the number of D3 good-quality embryos, as well as the clinical pregnancy rate and live birth rate. A total of 176 cases were enrolled in the retrospective study. Results The observation group (n = 88) showed advanced male age, lower sperm concentration, progressive motility, and morphology assessment than the control group. In addition, lower No. of D3 good-quality embryos, clinical pregnancy rate, and the live birth rate were shown in the observation group. A negative correlation between the DFI and No. of D3 good-quality embryos (rs = -0.347, p < 0.001) or live birth rate (rs = -0.185, p = 0.028) was shown. Conclusions Sperm DFI was a good indicator for the prediction of D3 good-quality embryos in unexplained infertility couples, but it did not provide sufficient information regarding clinical pregnancy outcome but live pregnancy outcome.

Ultrasound-Guided Dynamic Needle-Tip Positioning Method Is Superior to Conventional Palpation and Ultrasound Method in Arterial Catheterization.

Background: Dynamic needle-tip positioning (DNTP) was shown to improve arterial cannulation efficiency with fewer complications than conventional palpation and ultrasound methods by some studies. However, this is still controversial, and we performed this meta-analysis to comprehensively assess its value in arterial cannulation. Methods: A literature search of randomized controlled trials was conducted, and 11 studies were finally included. Efficiency outcomes (first-attempt success, overall success, and total cannulation time) and complications (hematoma, thrombosis, posterior wall puncture, and vasospasm) were separately analyzed. Subgroup analyses in different populations under cannulation were also performed. Results: DNTP was associated with increased first-attempt success (pooled RR = 1.792, p < 0.001), overall success (pooled RR = 1.368, p = 0.001), and decreased cannulation time (pooled SMD = −1.758, p = 0.001) than palpation. DNTP gained even more advantage in small children and infants. No significant difference in these outcomes between DNTP and conventional ultrasound method was detected. Fewer hematoma occurred in DNTP than palpation (pooled RR = 0.265, p < 0.001) or traditional ultrasound (pooled RR = 0.348, p < 0.001). DNPT was also associated with fewer posterior wall punctures (pooled RR = 0.495, p = 0.001) and vasospasm (pooled RR = 0.267, p = 0.007) than traditional ultrasound. Conclusions: DNTP was a better choice in artery cannulation than conventional palpation and ultrasound method, especially in small children and infants.

MOF-supported crystalline ionic liquid: new type of solid electrolyte for enhanced and high ionic conductivity.

Solid-state electrolyte (SSE) is crucial for a high-performance all-solid-state battery. Here, a new solid sodium electrolyte based on the ionic liquid EIMS-NaTFSI and one metal-organic framework (MOF) UiO-67-MIMS functionalized with zwitterion groups MIMS was obtained (UiO-67 and was assembled with 4,4'-biphenyldicarboxylate linker and cluster Zr6O4(OH)4) (EIMS = 1-(1-ethyl-3-imidazolio)propane-3-sulfonate, NaTFSI = sodium bis(trifluoromethanesulfonyl)imide, MIMS = 1-(1-mthyl-3-imidazolio)propane-3-sulfonate). By contacting and pairing EIMS-NaTFSI (abbreviated as EN-1) to the MIMS group on the framework, EN-1 was directed and arranged along the channels within UiO-67-MIMS, forming a solid composite EN-1@UiO-67-MIMS with Bragg scatter, i.e., a crystalline ionic liquid containing Na+ salts (NaTFSI). Such an ionic liquid EN-1@UiO-67-MIMS bearing crystalline MOF matrix showed and preserved fast ion conduction (1.02 × 10-2 S cm-1) at 150 °C even after 30 days, and exhibited 1-2 orders of magnitude higher conductivities than the bulk ionic liquid EN-1 within a wide temperature range, although the ion content in the latter was higher. The infinite pathway paved by the EN-1 arranged and contacted the MIMS along the channels within MOF well accounts for the fast ion transmission and the stability of the solid-state electrolyte. Such MOF-based crystalline ionic liquid provides a new strategy for developing high-performance solid-state electrolytes for ions.

Measuring self-efficacy in defecation: Validation and utilization of a Chinese version of the self-efficacy for functional constipation questionnaire (SEFCQ) in a pediatric population.

BACKGROUND: Self-efficacy in defecation plays an important role on behavioral therapy for functional constipation (FC). There is an unmet need for valid child self-report measures of task-specific self-efficacy for pediatric FC. Our aim was to cross-culturally validate the Self-Efficacy for Functional Constipation Questionnaire (SEFCQ) and to explore the salient factor(s) of self-efficacy in defecation that correlate with anxiety and constipation symptom severity among Chinese children. METHODS: The SEFCQ was adapted to Chinese version following the Rome Foundation guidelines for the translation of questionnaires. Two hundred and three children with FC were involved in psychometric testing. Confirmatory factor analysis was conducted to determine the structure of the SEFCQ. Construct validity was evaluated by testing the relationship between the SEFCQ and both anxiety and the Patient Assessment of Constipation Symptoms (PAC-SYM). Test-retest reliability, internal consistency, and interfactor correlation were used to evaluate reliability. Hierarchical multiple regression was used to identify salient self-efficacy for FC that correlates with anxiety and constipation symptom severity. KEY RESULTS: Confirmatory factor analysis supports the two-factor structure of the SEFCQ. Adequate test-retest reliability (r = 0.973, p<0.001) and internal consistency (Cronbach's α = 0.871) were obtained. Both self-efficacy factors were significantly associated with anxiety (r = -0.227 to -0.350, p<0.001) and PAC-SYM (r = -0.495 to -0.602, p<0.001), with emotional self-efficacy being the most salient factor for predicting the symptom severity of constipation after controlling for sex, age, quality of parents' marriage, and family history. CONCLUSION AND INFERENCES: The SEFCQ showed satisfactory psychometric properties. Low self-efficacy in defecation correlates with anxiety and may contribute to poor adherence to behavior change, which exacerbates the symptoms of constipation. Further study is needed to apply social cognitive intervention to increase children's self-efficacy in defecation and assess its effect on treatment outcomes.

Analysis of M6A associated lncRNAs in prognosis and immune response of NSCLC patients.

Distinguishing between N6-methyladenosine (m6A)-associated long noncoding RNAs (lncRNAs) is crucial in non-small-cell lung cancer (NSCLC) patients. In this research, the prognosis and immunotherapeutic response of lncRNAs and m6A in NSCLC were examined. lncRNAs related to m6A were identified using co-expression analyses, and their prognostic impact on patients with NSCLC was assessed using univariate Cox regression analysis. Sixty-three m6A-associated lncRNAs were determined as prognostic lncRNAs, and on this basis, 25 m6A-associated lncRNAs were screened by least absolute shrinkage and selection operator (lasso) Cox regression. Multivariable Cox analysis obtained 14 m6A-associated lncRNAs for the construction of risk model. The NSCLC patients were grouped into different risk subgroups in accordance with the median of the risk fraction in each data, and we evaluated the differences of potential immunotherapeutic characteristics and drug sensitivity prediction between the two subgroups. By using this model to recombine patients, they can be effectively distinguished in terms of the immunotherapy response. Furthermore, candidate compounds for the differentiation of NSCLC subtypes were identified. The model based on 14 m6A-associated lncRNAs is a promising prognostic biomarker, which may help to predict the efficacy of immunotherapy in NSCLC patients and provide a theoretical basis for improving the outcome of patients.

Discovery of quality control ingredients in burdock root by combining anti-tumor effects and UHPLC-QqQ-MS/MS.

Burdock root is the root of Arctium lappa L., a plant of the Compositae family, which has the effects of dispersing wind and heat, detoxifying and reducing swelling. In order to better control the quality of burdock root, a screening study of quality control indicators was carried out. The current research combines biological activity evaluation with chemical analysis to screen and identify the biologically active compounds of burdock root as chemical components for the quality control of herbal medicine. The efficacy of 10 batches of ethanol extracts of burdock roots was evaluated by a tumor inhibition experiment in S180 tumor-bearing mice. The five main chemical components of these extracts were simultaneously quantitatively measured by ultra-high performance liquid chromatography combined with triple quadrupole mass spectrometry. Pearson correlation analysis was used to establish the relationship between these extracts' biological activity and chemical properties. The results showed that chlorogenic acid, caffeic acid and cynarin were positively correlated with the effect of inhibiting tumor growth, and further bioassays confirmed this conclusion. In conclusion, chlorogenic acid, caffeic acid and cynarin can be used as quality control markers for burdock root's antitumor effect.

Extracellular mitochondrial DNA promote NLRP3 inflammasome activation and induce acute lung injury through TLR9 and NF-κB.

BACKGROUND: Extracellular mitochondrial DNA (mtDNA) was demonstrated to be capable of inducing pulmonary inflammation through TLR9 while its role in NLRP3 inflammation activation remains unknown. METHODS: C57BL/6 mice were challenged intratracheally with mtDNA. Pulmonary pathology, the NLRP3 and caspase-1 p20 in lung tissues were assayed. PMA-primed THP-1 macrophages were incubated with mtDNA in vitro and cell-free medium were concentrated to detect caspase-1 p20 subunit and NLRP3 by Western blotting. Additionally, IL-1ß, L-18, TNF-α and caspase-1 activity in culture were also analyzed by ELISA kits and activity assay kit. RESULTS: Intratracheal administration of mtDNA increased NLRP3 and caspase-1 p20 subunit in lung together with excessive inflammation and damage. Inhibition of caspase-1 substantially diminished mtDNA-induced lung injury and inflammation. Exposed to mtDNA in THP-1 macrophages resulted in significant up-regulation of NLRP3 and increased caspase-1 p20 subunit release in culture. It also led to significant increased transcripts of NLRP3, ASC, caspase-1 and release of IL-1ß, IL-18 and TNF-α in culture media. Futhermore, mtDNA exposure resulted in significant up-regulation of phosho -p38 MAPK and nucleus translocation of NF-κB. mtDNA-induced Transcripts of NLRP3 and ASC were inhibited by p38 siRNA inhibitor or NF-κB inhibitor. CONCLUSIONS: Extracellular mtDNA promote NLRP3 inflammasome activation, acute pulmonary inflammation and injury through TLR9, p38 MAPK and NF-κB pathways.

Diagnosis status and pathological diagnosis derived treatment of elderly lung cancer patients over 75 years old.

BACKGROUND: The number of lung cancer in the elderly is increasing. However, a disturbing number of elderly patients failed to get pathological diagnosis and therapeutic outcomes are worse than the young. This study is conducted to explore the diagnosis and treatment status of lung cancer in patients over 75 years old. METHODS: Patients diagnosed with lung cancer between September 1, 2010 and October 30, 2017 were continuously screened. The pathological diagnosis must be based on the cytology or histology diagnosis. The clinical diagnosis must be built on both typical imaging features and increased tumor markers. Clinical features and survival information were obtained and analyzed. RESULTS: A total of 338 primary lung cancer inpatients were finally included with an age of 78.02±2.94 years. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease (COPD) and cardiovascular disease; 290 of all these patients were pathologically diagnosed while the other 48 patients only got a clinical diagnosis. Among the pathological diagnosis, adenocarcinoma, squamous carcinoma and small cell lung cancer counted for 91.72%. Epidermal growth factor receptor (EGFR) detection was performed in 126 patients and 41 of them were sensitive mutated. Among all included patients, 150 were treated by the best supportive treatment (BST). Anti-cancer treatment is significantly associated with better survival than BST (P<0.001). Definite sensitive mutation is associated with improved survival than undetected patients in EGFR-tyrosine kinase inhibitors (TKIs) treatment patients (P=0.039). CONCLUSIONS: Pathological diagnosis of lung cancer in elderly patients is relatively deficient. Pathologic and molecular pathological diagnosis derived anti-cancer treatment is effective in improving survival.

Toward rapid analysis, forecast and discovery of bioactive compounds from herbs by jointly using thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy technique.

Conventional isolation and identification of active compounds from herbs have been extensively reported by using various chromatographic and spectroscopic techniques. However, how to quickly discover new bioactive ingredients from natural sources still remains a challenging task due to the interference of their similar structures or matrices. Here, we present a grand approach for rapid analysis, forecast and discovery of bioactive compounds from herbs based on a hyphenated strategy of thin layer chromatography and ratiometric surface-enhanced Raman spectroscopy. The performance of the hyphenated strategy is first evaluated by analyzing four protoberberine alkaloids, berberine (BER), coptisine (COP), palmatine (PAT) and jatrorrhizine (JAT), from a typical herb Coptidis Rhizoma as an example. It has been demonstrated that this coupling method can identify the four compounds by characteristic peaks at 728, 708, 736 and 732 cm-1, and especially discriminate BER and COP (with similar migration distances) by ratiometric Raman intensity (I708/I728). The corresponding limits of detection are 0.1, 0.05, 0.1 and 0.5 µM, respectively, which are about 1-2 orders of magnitude lower than those of direct observation method under 254 nm UV lamp. Based on these findings, the proposed method further guides forecast and discovery of unknown compounds from traditional Chinese herb Typhonii Rhizoma. Results infer that two trace alkaloids (BER and COP) from the n-butanol extract of Typhonii Rhizoma are found for the first time. Moreover, in vitro experiments manifest that BER can effectively decrease the viability of human glioma U87 cells by inducing cell cycle arrest in a concentration-dependent manner.

Ehrlich Reaction Evoked Multiple Spectral Resonances and Gold Nanoparticle Hotspots for Raman Detection of Plant Hormone.

Surface-enhanced Raman scattering (SERS) by use of noble metal nanoparticles has become a powerful tool to determine a low-concentration target by unique spectral fingerprints, but it is still limited to the Raman-inactive and nonresonant biomolecules such as amine acids, proteins, and hormones. Here, we report an Ehrlich reaction based derivative strategy in combination with gold nanoparticles (Au NPs) hotspots for the selective detection of indole-like plant hormones by SERS spectroscopy. Ehrlich reaction of p-(dimethylamino)benzaldehyde (PDAB) with the indole ring chemically transformed plant hormone indole-3-butyric acid (IBA) into a Raman-active and resonant derivative with an extended π-conjugated system in the form of a cation, which produced a new absorption band at 626 nm. On the other hand, cationic IBA-PDAB highly evoked the aggregation of Au NPs with negative citrate ligands to form the effective Raman hotspots and gave rise to the new absorption ranging from 600 to 800 nm. Significantly, the spectral overlap among IBA-PDAB, aggregated Au NPs, and the exciting laser initiated the multiple optical resonances to generate the ultrahigh Raman scattering with a sensitive limit of 2.0 nM IBA. The IBA in the whole sprouts and various parts of pea, mungbean, soybean, and black bean has been identified and quantified. The reported method opens a novel avenue for the SERS detection of Raman-inactive analyte by a proper derivation.

Neuroprotective Activity of Cerebrosides from Typhonium giganteum by Regulating Caspase-3 and Bax/Bcl-2 Signaling Pathways in PC12 Cells.

An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides E (1) and F (2), along with 11 known analogues (3-13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain. Among them, longan cerebroside II (11), with the longest fatty acyl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC50 value of 2.5 µM. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Bax, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.

Color-Multiplexing-Based Fluorescent Test Paper: Dosage-Sensitive Visualization of Arsenic(III) with Discernable Scale as Low as 5 ppb.

Fluorescent colorimetry test papers are promising for the assays of environments, medicines, and foods by the observation of the naked eye on the variations of fluorescence brightness and color. Unlike dye-absorption-based pH test paper, however, the fluorescent test papers with wide color-emissive variations with target dosages for accurate quantification remain unsuccessful even if the multicolorful fluorescent probes are used. Here, we report the dosage-sensitive fluorescent colorimetry test paper with a very wide/consecutive "from red to cyan" response to the presence and amount of arsenic ions, As(III). Red quantum dots (QDs) were modified with glutathione and dithiothreitol to obtain the supersensitivity to As(III) by the quenching of red fluorescence through the formation of dispersive QDs aggregates. A small amount of cyan carbon dots (CDs) with spectral blue-green components as the photostable internal standard were mixed into the QDs solution to produce a composited red fluorescence. Upon the addition of As(III) into the sensory solution, the fluorescence color could gradually be reversed from red to cyan with a detection limit of 1.7 ppb As(III). When the sensory solution was printed onto a piece of filter paper, surprisingly a serial of color evolution from peach to pink to orange to khaki to yellowish to yellow-green to final cyan with the addition of As(III) was displayed and clearly discerned the dosage scale as low as 5 ppb. The methodology reported here opens a novel pathway toward the real applications of fluorescent test papers.

Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation via LSD1 interaction and repression of NCALD in non-small-cell lung cancer.

Despite improvements in diagnostics and treatment of non-small cell lung cancer (NSCLC), it remains the leading causes of cancer-related mortality worldwide. In more recent years, mutiple lines of evidence have highlighted long noncoding RNAs (lncRNAs) serve as novel class of regulators of cancer biological processes, including proliferation, apoptosis and metastasis. LncRNAs serve as a novel class of regulators of cancer biological processes in cancer, but little is known of their expression and potential functions in NSCLC. We identified an oncogene, linc00673, whose expression level was upregulated by bioinformatics analyses and qRT-PCR analyses in NSCLC. The effects of linc00673 on tumor progression were investigated in vitro and in vivo. Linc00673 knockdown significantly inhibited cell proliferation and colony-forming ability, and suppressed S-phase entry in vitro and shRNA linc00673 mediated knockdown significantly inhibit tumor growth in vivo, meanwhile, linc00673 overexpression increased tumor cell growth. Analysis of RNAseq data revealed linc00673 could modulate the transcription of a large amount of genes including oncogene and tumor suppressor gene, so we investigated the role and regulatory mechanism of linc00673 in NSCLC proliferation. Further mechanistic analyses indicated that the oncogenic activity of linc00673 is partially attributable to its repression of NCALD through association with the epigenetic repressor LSD1. Taken together, these findings suggested that linc00673 could play crucial role in NSCLC progression and might be a potential therapeutic target for patients with NSCLC.

Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma.

p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC.