Fluorescence determination of chloramphenicol in milk powder using carbon dot decorated silver metal-organic frameworks.

Carbon dot decorated silver metal-organic frameworks (CD-MOFs) were successfully synthesized at room temperature by adding CDs during the formation of Ag-MOFs. The CD-MOFs have excellent optical property, stability, and good fluorescence intensity in water compared with other solvents. The fluorescence intensity of CD-MOFs was relatively stable in the range of pH 5-9. It was used to construct a sensitive and reliable fluorescent sensor for the determination of chloramphenicol (CAP). When the CAP was introduced into the CD-MOFs, the fluorescence at 427 nm was quenched at the excitation wavelength of 332 nm. Wide linear relationships were established for CAP with a limit of detection of 44 nM. The fluorescent sensor has been applied to determine CAP in milk powder sample with satisfied recoveries (104 to 109%) and good precision (< 4%). The photoinduced electron-transfer is the most important mechanism contributing to the fluorescence quenching. The synthesized CD-MOFs provide a new orientation for fluorescence determination of chloramphenicol in real samples.

Development and Validation of a Nomogram Prognostic Model for Resected Limited-Stage Small Cell Lung Cancer Patients.

BACKGROUND: In this study, we developed and validated nomograms for predicting the survival in surgically resected limited-stage small cell lung cancer (SCLC) patients. METHODS: The SCLC patients extracted from the Surveillance, Epidemiology, and End Results database between 2000 and 2014 were reviewed. Significant prognostic factors were identified and integrated to develop the nomogram using multivariable Cox regression. The model was then validated internally by bootstrap resampling, and externally using an independent SCLC cohort diagnosed between 2000 and 2015 at our institution. The prognostic performance was measured by the concordance index (C-index) and calibration curve. RESULTS: A total of 1006 resected limited-stage SCLC patients were included in the training cohort. Overall, 444 cases from our institution constituted the validation cohort. Seven prognostic factors were identified and entered into the nomogram construction. The C-indexes of this model in the training cohort were 0.723, 0.722, and 0.746 for predicting 1-, 3-, and 5-year overall survival (OS), respectively, and 0.816, 0.710, and 0.693, respectively, in the validation cohort. The calibration curve showed optimal agreement between nomogram-predicted survival and actual observed survival. Additionally, significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed. The proposed nomogram was then deployed into a website server for convenient application. CONCLUSIONS: We developed and validated novel nomograms for individual prediction of survival for resected limited-stage SCLC patients. These models perform better than the previously widely used staging system and may offer clinicians instructions for strategy making and the design of clinical trials.

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state.

The tumor microenvironment (TME) is a vital component of tumor tissue. Increasing evidence suggests their significance in predicting outcomes and guiding therapies. However, no studies have reported a systematic analysis of the clinicopathologic significance of TME in lung adenocarcinoma (LUAD). Here, we inferred tumor stromal cells in 1184 LUAD patients using computational algorithms based on bulk tumor expression data, and evaluated the clinicopathologic significance of stromal cells. We found LUAD patients showed heterogeneous abundance in stromal cells. Infiltration of stromal cells was influenced by clinicopathologic features, such as age, gender, smoking, and TNM stage. By clustering stromal cells, we identified 2 clinically and molecularly distinct LUAD subtypes with immune active and immune repressed features. The immune active subtype is characterized by repressed metabolism and repressed proliferation of tumor cells, while the immune repressed subtype is characterized by active metabolism and active proliferation of tumor cells. Differentially expressed gene analysis of the two LUAD subtypes identified an immune activation signature. To diagnose TME subtypes practically, we constructed a TME score using principal component analysis based on the immune activation signature. The TME score predicted TME subtypes effectively in 3 independent datasets with areas under the receiver operating characteristic curves of 0.960, 0.812, and 0.819, respectively. In conclusion, we proposed 2 clinically and molecularly distinct LUAD subtypes based on tumor microenvironment that could be valuable in predicting clinical outcome and guiding immunotherapy.

Synthesis of Acid-Labile Poly(Doxazolidine) as a Polyprodrug with an Ultra-High Drug Content for Self-Delivery of High-Performance Chemotherapeutics.

Drug self-delivery systems (DSDSs) have attracted intense attention due to their high drug content. However, their practical application still suffers from their premature drug leakage, slow drug release, and/or low antitumor efficacy of the released small molecular drugs. Here, acid-labile poly(Doxazolidine) (P(Doxaz)) is designed as a polyprodrug for the self-delivery of high antitumor chemotherapeutics (Doxazolidine (Doxaz)), with an ultrahigh Doxaz content of 92.45%. The P(Doxaz) nanoparticles could completely degrade into Doxaz within 10 h in the simulated tumor intracellular microenvironment, with a low drug leakage of 12.9% over 12 h in the normal physiological media. Owing to the ultrahigh drug content, fast acid-triggered degradation and drug release, and high antitumor efficacy of Doxaz, the proposed DSDS possesses an enhanced antiproliferation efficacy compared to the free DOX, demonstrating its potential in future tumor treatments.

Systematic Review and Meta-Analysis of -New-Generation Tyrosine Kinase Inhibitors versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia.

BACKGROUNDS: We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML). SUMMARY: We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. Key Messages: In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.

Comparison of indocyanine green and carbon nanoparticles in endoscopic techniques for central lymph nodes dissection in patients with papillary thyroid cancer.

BACKGROUND: Injection of carbon nanoparticle (CN) into the thyroid gland is used to stain CLNs in endoscopic surgery of patients with papillary thyroid cancer (PTC). The black-dye technique facilitates the central lymph nodes (CLNs) harvest and parathyroid protection, but improper handling of CN during injection leads to unwanted staining of surrounding tissues and increases the difficulty in anatomical identification. Therefore, a new method is needed to overcome this problem. METHODS: Forty-eight patients with PTC underwent endoscopic thyroidectomy via breast approach. Patients were randomized into the indocyanine green (ICG) group (Group ICG; n = 23) and CN group (Group CN; n = 25). After thyroid gland exposure, ICG was injected into the thyroid lobes. Fluorescent CLNs were identified and dissected in Group ICG. In Group CN, CN was used instead. Black dyed CLNs were harvested. The following was compared between groups: demographic characteristics, surgical time, drainage amount, hospital stay duration, number of CLNs harvested, frequency of postoperative hoarseness and hypothyroidism, and surgical cost. RESULTS: Group ICG showed decreased hypoparathyroidism frequency than Group CN (1/23 vs. 7/25, p = 0.028) and more harvested CLNs (4.6 ± 1.0 vs. 3.8 ± 1.2, p = 0.020). There was no difference between drainage amount, hospital stay duration, and frequency of postoperative hoarseness. The cost of Group ICG was less than that of Group CN (p = 0). CONCLUSION: Injection of ICG into the thyroid gland using fluorescence imaging in endoscopic surgery in patients with PTC is safer and more effective in identifying CLNs than injection with CN. This novel method can lead to improved identification and subsequent harvesting of CLNs.

Relationship between the 24-h variability of blood pressure, ocular perfusion pressure, intraocular pressure, and visual field defect in thyroid associated orbitopathy.

PURPOSE: To evaluate the relationship between the 24-h variability of blood pressure (BP), ocular perfusion pressure (OPP), intraocular pressure (IOP), and visual field (VF) defect in thyroid-associated orbitopathy (TAO). METHODS: Thirty patients (60 eyes) with TAO were clinically examined in the Eye Hospital of Wenzhou Medical University. Patients were divided into two groups: one with VF defect (A) and the other without (B). Clinical parameters measured include 24-h IOP, 24-h blood pressure, orbital computed tomography (CT) scan, optical coherence tomography (OCT), and VFs. The pulse pressure (PP), mean arterial pressure (MAP), mean ocular perfusion pressure (MOPP), and 24-h fluctuations were calculated by formula. RESULTS: The MOPP and MAP fluctuation were greater in group A than B (p < 0.05) and had significant negative correlation to mean deviation (MD) of VF (R = - 0.434 P = 0.001*). There was no statistical difference in the muscle index, medial rectus muscle thickness, and blood pressure between two groups. Although there were no significant differences in the mean IOP and IOP fluctuation between two groups, the incidence of IOP abnormalities has higher trend in group A. Patients with 24-h IOP fluctuation ≥8 mmHg and the mean IOP > 21 mmHg in the group A were more than group B. CONCLUSIONS: Dysthyroid optic neuropathy (DON) might have multiple pathogenic mechanisms. In this study, 24-h MOPP fluctuation and medial rectus maximal diameter were all the risk factors for DON. Higher mean IOP and 24-h IOP fluctuation might be risk factors for DON.

Survival-associated alternative splicing signatures in esophageal carcinoma.

Alternative splicing (AS), a major mechanism for the enhancement of transcriptome and proteome diversity, has been widely demonstrated to be involved in the full spectrum of oncogenic processes. High-throughput sequencing technology and the rapid accumulation of clinical data sets have provided an opportunity to systemically analyze the association between messenger RNA AS variants and patient clinical outcomes. Here, we compared differentially spliced AS transcripts between esophageal carcinoma (ESCA) and non-tumor tissues, profiled genome-wide survival-associated AS events in 87 patients with esophageal adenocarcinoma (EAC) and 79 patients with esophageal squamous cell carcinoma (ESCC) using The Cancer Genome Atlas (TCGA) RNA-seq data set, and constructed predictive models as well as splicing regulation networks by integrated bioinformatic analysis. A total of 2326 AS events in 1738 genes and 1812 AS events in 1360 genes were determined to be significantly associated with overall survival (OS) of patients in the EAC and ESCC cohorts, respectively, including some essential participants in the oncogenic process. The predictive model of each splice type performed reasonably well in distinguishing good and poor outcomes of patients with esophageal cancer, and values for the area under curve reached 0.942 and 0.815 in the EAC exon skip predictive model and the ESCC alternate acceptor site predictive model, respectively. The splicing regulation networks revealed an interesting correlation between survival-associated splicing factors and prognostic AS genes. In summary, we created prognostic models for patients with esophageal cancer based on AS signatures and constructed novel splicing correlation networks.

mTOR up-regulation of BEX4 promotes lung adenocarcinoma cell proliferation by potentiating OCT4.

Previously, BEX family members have been reported to participate in cancer development. However, little is known about the role of BEX4 in lung adenocarcinoma (LAC). Here, we found that BEX4 was over-expressed in LAC tissues compared with adjacent tissues. LAC tissues from metastatic patients exhibited higher expression of BEX4 comparing to those from non-metastatic ones. In vitro, BEX4 ectopic expression accelerated the proliferation of both A549 and H1975 cells. By contrast, knockdown of BEX4 suppressed the proliferation of A549 and H1975 cells. BEX4 positively regulated the expression of OCT4, silencing of which reduced the proliferation of A549 and H1975 cells with over-expressed BEX4. Additionally, mTOR activation, which is frequently observed in LAC, potentiated BEX4 depending on mTORC1 but not mTORC2. BEX4 abundance dictated the sensitivity of A549 and H1975 cells to rapamycin treatment. Our findings reveal that BEX4 is an oncogene in LAC and may contribute to the hyper-active mTOR-induced LAC development.

Microscale local strain gauges based on visible micro-disk lasers embedded in a flexible substrate.

Microscale local strain gauges with low-power consumption and large strain range were demonstrated by integrating microdisk lasers in a deformable and flexible polymer substrate. The lasing spectra of microdisk lasers were sensitive to substrate deformation and can be modulated by strains. The measured relative wavelength tuning under strains of the novel strain sensors illustrated a linear behavior with the gauge factor being ~4.0 nm and ~6.7 nm per stretching unit for microdisk lasers with the diameter of 1.2 µm and 1.5 µm, which corresponding to a smooth wavelength tuning of 1.5 nm and 2.6 nm under 36% strain, respectively. In addition, to being used as microscale strain gauges, the visible lasers on the deformable substrate can also function as a tunable light source for the photonic integrated circuits and flexible laser projection displays.

pH/Reduction Dual-Responsive Oxidized Alginate-Doxorubicin (mPEG-OAL-DOX/Cys) Prodrug Nanohydrogels: Effect of Complexation with Cyclodextrins.

Novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cys) prodrug nanohydrogels were designed for tumor-specific intracellular triggered release of anticancer drug DOX by conjugating DOX via acid-labile Schiff base linkage into the PEGylated oxidized alginate (mPEG-OAL) cross-linked with bioreducible disulfide bond. The effect of the complexation with cyclodextrins (α-CD and ß-CD) before or after the cross-linking of the mPEG-OAL on the DOX content and controlled release performance was investigated. It was found that the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(CD)-OAL-DOX/Cys, prepared by cross-linking of the mPEG-OAL after complexation with cyclodextrins, exhibited better pH/reduction dual-responsive controlled release performance than the mPEG-OAL-DOX/Cys(CD) ones prepared by cross-linking of the mPEG-OAL before complexation with cyclodextrins, owing to the supramolecular cross-linking of the adjacent pseudopolyrotaxanes. Especially for the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(α-CD)-OAL-DOX/Cys, DOX was released rapidly under lower pH media mimicking the tumor microenvironment and completely released within 48 h, while the premature leakage under the simulated physiological condition was ∼40%, without burst release in both cases. The cellular toxicity and uptake results demonstrated that the mPEG(α-CD)-OAL-DOX/Cys prodrug nanohydrogels possessed similar inhibition against cancer cell growth in comparison with the free DOX and enhanced drug intracellular accumulation.

pH/Reduction Dual-Triggered Degradable Poly(doxorubicin) Prodrug Nanoparticles for Leakage-Free Tumor-Specific Self-Delivery.

Poly(doxorubicin) (PDOX) is synthesized with Mn of 1.66 × 104 and DOX content of 78% as prodrug for tumor-specific triggered release, via a facile condensation polymerization of DOX-SS-DOX and adipic dihydrazide. The PDOX nanoparticles (PDOX-NPs) could completely release DOX-SH within 1.5 days at the simulated tumor microenvironment, but no measurable leakage in the physiological media. The in vitro controlled release results show that the releasing rate is influenced by the dosage and independent of the particle size, while the solubility of the degraded products should be the main determining factor for the drug release from the PDOX-NPs. The PDOX-NPs are expected to be promising prodrug nanopharmaceutics for the on-demand self-delivery of DOX with enhanced anticancer efficacy in future tumor treatment.

fvs-Si48: a direct bandgap silicon allotrope.

A structurally stable silicon allotrope is predicted by means of first principles calculations. This new structure is composed of a six-membered ring, a five-membered ring and a three-membered ring with the space group PA3[combining macron] and fvs topology, which is named fvs-Si48. The calculations of geometrical, vibrational, and electronic and optical properties reveal that fvs-Si48 has good mechanical stability with a mass density of 1.86 g cm-3. More importantly, it is a semiconductor with a direct band gap of 2.15 eV. From the analysis of its optical properties, there is the possibility of its synthesis in theory. This fvs-Si48 could have a wide range of applications in photo catalysts, optoelectronics, hydrogen storage and aerospace engineering.

AIR-Chem: Authentic Intelligent Robotics for Chemistry.

The new era with prosperous artificial intelligence (AI) and robotics technology is reshaping the materials discovery process in a more radical fashion. Here we present authentic intelligent robotics for chemistry (AIR-Chem), integrated with technological innovations in the AI and robotics fields, functionalized with modules including gradient descent-based optimization frameworks, multiple external field modulations, a real-time computer vision (CV) system, and automated guided vehicle (AGV) parts. AIR-Chem is portable and remotely controllable by cloud computing. AIR-Chem can learn the parametric procedures for given targets and carry on laboratory operations in standalone mode, with high reproducibility, precision, and availability for knowledge regeneration. Moreover, an improved nucleation theory of size focusing on inorganic perovskite quantum dots (IPQDs) is theoretically proposed and experimentally testified to by AIR-Chem. This work aims to boost the process of an unmanned chemistry laboratory from the synthesis of chemical materials to the analysis of physical chemical properties, and it provides a vivid demonstration for future chemistry reshaped by AI and robotics technology.

Tunable Chiroptical Properties from the Plasmonic Band to Metal-Ligand Charge Transfer Band of Cysteine-Capped Molybdenum Oxide Nanoparticles.

Understanding the interactions between a semiconducting nanocrystal surface and chiral anchoring molecules could resolve the mechanism of chirality induction in nanoscale and facilitate the rational design of chiral semiconducting materials for chiroptics. Now, chiral molybdenum oxide nanoparticles are presented in which chirality is transferred via a bio-to-nano approach. With facile control of the amount of chiral cysteine molecules under redox treatment, circular dichroism (CD) signals are generated in the plasmon region and metal-ligand charge-transfer band. The obtained enhanced CD signals with tunable lineshapes illustrate the possibility of using chiral molybdenum oxide nanoparticles as potentials for chiral semiconductor nanosensors, optoelectronics, and photocatalysts.

Proposal and numerical study of a flexible visible photonic crystal defect cavity for nanoscale strain sensors.

A flexible photonic crystal cavity, consisting of a III-V active layer embedded in a flexible medium, with a line-defect by removing three air holes for nanoscale structural deformation detection is proposed and optimized. The cavity can hold the photonic band-gap modes with the fundamental mode located at approximately 686 nm, overlapping with the photoluminescence spectrum of the InGaP/InGaAlP quantum wells. Results of finite-difference time-domain simulations indicate that the L3 cavity features an ultra-compact mode volume of 10-3 µm3 and high quality factor of 104 at a sub-micron footprint within the studied visible wavelength. Theoretical optical strain sensitivities of approximately 4.5 and 3 nm per ε (1% strain for both) for the x and y directions are predicted, respectively. When the cavity is under large bending curvatures, the Q factor rapidly decreases from 8000 to 2000.

Stair-Climbing Test Predicts Postoperative Cardiopulmonary Complications and Hospital Stay in Patients with Non-Small Cell Lung Cancer.

BACKGROUND There is currently no reliable method to predict major postoperative cardiopulmonary complications for patients with non-small cell lung cancer (NSCLC). In this study, we hypothesized that exercise oxygen desaturation (EOD) and heart rate change results in a stair-climbing test (SCT) would predict postoperative cardiopulmonary complications for patients with NSCLC. MATERIAL AND METHODS We examined 171 patients (41 females and 130 males) with NSCLC by preoperative SCT from January 2010 to July 2015. Among them, 27 underwent wedge resection, 122 underwent lobectomy, and 22 underwent pneumonectomy. The correlation between postoperative cardiopulmonary complications and parameters of SCT and pulmonary function test (PFT) parameters were analyzed retrospectively. RESULTS The overall 30-day postoperative morbidity of the patients was 46/171 (26.9%), with death occurring in 3/171(1.8%). The age, FEV1%, MVV, height of climbing, EOD, and heart rate change were found to be significantly different between the group with postoperative cardiopulmonary complications and those without. Binary logistic regression analysis showed that EOD and heart rate change were independently correlated with postoperative cardiopulmonary complications. In addition, a model predicting the probability of postoperative cardiopulmonary complication based on logistic regression for multivariable analysis was used to confirm our findings. CONCLUSIONS A symptom-limited SCT with oxygen saturation monitoring is a safe, simple, and low-cost method to evaluate cardiopulmonary function preoperatively.

The Efficacy of Rituximab Combined with 131I for Ophthalmic Outcomes of Graves' Ophthalmopathy Patients.

PURPOSE: The purpose of this study is to examine the effectiveness of introducing both rituximab (RTX) and 131I for active Graves' ophthalmopathy (GO) with hyperthyroidism. METHODS: In total, 217 patients suffering from active GO with hyperthyroidism were included in this research. All subjects were randomly assigned to 3 groups. Patients in group A solely received 131I treatment; group B1 underwent a methylprednisolone treatment in combination with 131I treatment; and group B2 received an RTX in combination with 131I treatment. Hyperthyroidism treatment outcomes, orbital volumetry, ophthalmic assessments, serum cytokine levels, and adverse effects were measured after treatment. RESULTS: The orbital volumetry principle was significantly different from 24 weeks after the start of treatment among all 3 groups, and improvements in most ophthalmic parameters were regarded significantly different among 3 groups (all p < 0.05). The expression levels of miR-146a and most serum cytokines were regarded significantly different from 24 weeks after the start of treatment among 3 groups (all p < 0.05). CONCLUSIONS: In comparison with other therapies, RTX treatment in combination with 131I treatment is considered to be more effective for hyperthyroidism with active GO.

Superparamagnetic Reduction/pH/Temperature Multistimuli-Responsive Nanoparticles for Targeted and Controlled Antitumor Drug Delivery.

Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a "gatekeeper" on the surface via two-stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the "triggered release" of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy.

Fluorescent Copolymer-Based Prodrug for pH-Triggered Intracellular Release of DOX.

A novel water-soluble pH stimuli-responsive fluorescent copolymer of P(PEGMA-b-(MAH-co-Rh6GEAm)) was synthesized by two-step sequential RAFT polymerization. The prodrug with drug content of 0.1560 mg/mg was prepared by coupling doxorubicin (DOX) onto the copolymer via acid-cleavable hydrazone bond, formed between the carbonyl group of DOX and abundant hydrazide functional groups in the copolymer. The amphiphilic DOX-conjugated prodrug (P(PEGMA-b-(MAH-DOX-co-Rh6GEAm))) could easily form a micelle in water with Dh of less than 100 nm. It could be transported into HepG2 cells and release DOX without burst release, while the leakage of DOX can be avoided in the simulated normal physiological media. Furthermore, its fluorescence intensity experienced a reversible change with the transformation of the media pH. The better biocompatibility, pH stimuli-responsiveness, and the strong fluorescence at low pH media make the nanoparticles a potential platform for the controlled release of anticarcinogens and real-time fluorescent imaging of tumor tissues.