Improved Photodynamic Therapy Based on Glutaminase Blockage via Tumor Membrane Coated CB-839/IR-780 Nanoparticles.

Photodynamic therapy (PDT) has promising applications. However, the lethal function of reactive oxygen species (ROS) produced during PDT is typically limited. This restriction is induced by oxygen shortage in the tumor microenvironment due to tumor cell hypermetabolism and reductive chemicals overexpression in tumor tissues. Glutamine (Gln) metabolism is crucial for malignancy development and is closely associated with redox. Herein, a novel nanoparticle (NP) named IRCB@M is constructed to boost PDT through dual effects. This NP simultaneously blocks aerobic respiration and inhibits cellular reduced substances by blocking the Gln metabolic pathway. Within the nanocomplex, a photosensitizer (IR-780) and a glutaminase inhibitor (CB-839) are self-assembled and then encapsulated by cancer cell membranes for homologous targeting. The Gln metabolism intervention relieves hypoxia and decreases the levels of nicotinamide adenine dinucleotide phosphate (NADPH) as well as reduced glutathione (GSH) in vitro and in vivo, which are the dual amplification effects on the IR-780-mediated lethal PDT. The antitumor effects against gastric cancer are ultimately evoked in vivo, thus offering a novel concept for enhancing PDT and other ROS-dependent therapeutic approaches.

Nasopharyngeal neutrophilic-retention signatures could predict disease progression in early SARS-CoV-2 infection.

The nasopharynx is the initial site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and neutrophils play a critical role in preventing viral transmission into the lower airways or lungs during the early phases of infection. However, neutrophil dynamics, functional signatures, and predictive roles in the nasopharynx of coronavirus disease 2019 (COVID-19) patients have not yet been elucidated. In this study, we carried out RNA sequencing of nasopharyngeal swabs from a cohort of COVID-19 patients with mild, moderate, severe outcomes and healthy donors as controls. Over 32.7% of the differentially expressed genes associated with COVID-19 severity were neutrophil-related, including those involved in migration, neutrophil extracellular traps formation, and inflammasome activation. Multicohort single-cell RNA sequencing analysis further confirmed these findings and identified a population of neutrophils expressing Vacuolar-type ATPase (V-ATPase) and the chemokine receptor CXCR4 in the nasopharynx. This population of neutrophils preferentially expressed pro-inflammatory genes relevant to phagosomal maturation as well as local reactive oxygen species and reactive nitrogen species production in the nasopharynx of patients with severe outcomes. A four-gene panel defined as a neutrophil signature associated with COVID-19 progression (NSAP) was identified as an early diagnostic predictor of severe COVID-19, which potentially distinguished severe patients from mild cases with influenza, respiratory syncytial virus, dengue virus, or hepatitis B virus infection. NSAP is mainly expressed on CXCR4high neutrophils and exhibits a significant association with the cell fraction of this neutrophil population. This study highlights novel potential therapeutic targets or diagnostic tools for predicting patients at a higher risk of severe outcomes.

Performance Evaluation of Newly-Developed Tumor Markers Assay Kit Based on Flow Fluorescence Assay.

BACKGROUND: The purpose of this study is to evaluate the performance of recently developed tumor marker clinical kits in China, with the aim of encouraging local medical technology innovation and thus narrowing the research and development gap with foreign kits. METHODS: The newly established reagent kits were analyzed on the TESMI F3999-Luminex200 flow lattice instrument to verify precision, sensitivity (blank limit), linearity, anti-interference ability, carry-over contamination rate, hook effect, and reference interval verification. Additionally, the newly established reagent kits were compared to other commercially available detection kits (reference reagent kits) to analyze the correlation between the two types of kits. RESULTS: The intra-assay and inter-assay precision had coefficients of variations (CVs) less than 3.50% and 6.91%, respectively. The tumor marker blank limits were lower than the manufacturer's statement. The newly established reagent kits demonstrated excellent linearity (r > 0.99). Rheumatoid factor, triglycerides, bilirubin, and hemoglobin did not have significant interference with the determination of tumor markers. The carry-over contamination rates were all much lower than 3%. At extremely high concentrations of AFP (277,335 ng/mL and 1,031,424 ng/mL), the measured tumor marker values were higher than the upper limit of the linear range and no hook effect occurred. The reference interval was suitable for use in clinical laboratory settings. Correlation analysis indicated a satisfactory relevance and consistency between the newly developed reagent kits and reference reagent kits, with correlation coefficients of r > 0.967 among 654 patients and healthy individuals. CONCLUSIONS: The newly developed reagent kits for tumor markers performed well in all evaluated parameters, having the potential for clinical promotion and application.

Significance of High-Frequency Sonography for the Subclinical Progression of Rheumatoid Arthritis.

OBJECTIVES: This study aims to investigate the use of high-frequency sonography as a tool for detecting inflammatory and destructive changes in the hand and foot joints of patients with early and long-term RA. METHODS: This study employs a prospective cohort design involving 162 patients diagnosed with Rheumatoid arthritis (RA) who meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Patients were divided into two groups based on disease duration: Group 1 (n = 74) included patients with a disease duration of up to 2 years, or early РА (ERA;), Group 2 (n = 88) consisted of patients with a disease duration exceeding 2 years, or long-term persistent РА (LtRA). All patients underwent a clinical assessment of their joints, as well as radiography and arthrosonography, at the beginning of the study and again at 6 and 12 months later. RESULTS: In the general group of patients, ultrasound examination revealed signs of synovitis in the joints of the hands more frequently (66%) compared with clinical examination (56% by a number of swollen joints [NSJ] and 55% by a number of painful joints [NPJ], P < .01). After 6 months of treatment, 12% of the patients achieved full US remission and 24% achieved partial US remission. CONCLUSIONS: Within the scope of comprehensive RA diagnostics, arthrosonography of the joints of the hands and feet, utilizing a combination of greyscale and power Doppler, may surpass radiography in detecting early RA. This method allows for a more accurate assessment of disease activity and progression rates.

Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers.

OBJECTIVES: We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). METHODS: A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. RESULTS: A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. CONCLUSION: The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. KEY POINT: • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare.

Related factors of renal injury in primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a common chronic systemic autoimmune disorder which primarily affects the exocrine glands. Patients may have extraglandular disease involving multiple organs, including the kidneys. This study aimed at investigating the clinical data and laboratory markers which were associated with renal function damage or renal involvement. METHOD: One thousand two hundred eighty-eight adult pSS patients from the Department of Rheumatology and Clinical Immunology were enrolled in this retrospective cohort study. And there were 334 patients of them followed up for more than two years for analyzing demographic, clinical data and laboratory markers. Statistical analysis was performed by R software (Version 3.6.2). RESULT: Nearly 95% of 1288 pSS patients were women, and the positive rates of anti-SSA (Sjögren's syndrome A) and anti-SSB were 63% and 27% respectively. 12% of the pSS patients presented renal involvement with eGFR < 60 mL/min/1.73 m2, and the mean age of hospital presentation, serum creatinine and urea were the highest (P < 0.001), and ANA (antinuclear antibody)-positive, anti-SSB-positive and anti-scl-70-positive were more prevalent in this group. Multivariate analyses showed that age, urea, chlorine and anti-SSA indicate a significant association with renal dysfunction. Potassium, sodium and Jo-1 were also confirmed to be related with decreased renal function. The receiver operating characteristic (ROC) analysis including the above factors showed a good performance on the evaluation of renal injury including eGFR < 60 mL/min/1.73 m2 and eGFR 60 -90 mL/min/1.73 m2 in pSS, with area under curve (AUC) values of 0.957 and 0.821, and high sensitivity (71.1% and 84.4%) and specificity (95.5% and 70.5%). After a more than two years follow-up of anti-SSA positive patients, 34.14% of them developed decreased renal function, and 13.58% of them experienced a progression of renal injury with a 23.64% decrease in eGFR. CONCLUSION: Age, urea, chlorine, and anti-SSA were highly associated with renal injury in pSS. Early screening for autoantibodies would be meaningful for evaluation and prevention of renal injury in pSS.

Knowledge, attitude, and practice regarding sarcopenia: a survey between orthopedic and geriatric professionals in China.

BACKGROUND: In elderly patients with fractures, sarcopenia impairs recovery and even increases mortality. Both orthopedic and geriatric professionals are at the forefront of treating sarcopenic patients with fractures. However, it is not clear to what extent they have knowledge and skills to diagnose and treat sarcopenia. AIMS: This study aimed to analyze and compare knowledge, attitude, and practice regarding sarcopenia between orthopedic and geriatric professionals. METHODS: An online cross-sectional survey was conducted in June 2022 targeting professionals in orthopedic and geriatric departments in two largest tertiary general hospitals in Taizhou, southeastern China. Results on knowledge, attitude, and practice of sarcopenia were analyzed. Variables with significance were then included in a stepwise multiple linear regression analysis. RESULTS: A total of 220 professionals, 176 from orthopedic departments and 44 from geriatric departments, participated in this study. Orthopedic professionals scored lower than geriatrics in knowledge, attitude and practice (P < 0.001). The attitude score was high in both orthopedic and geriatric professionals. Stepwise multiple linear regression analysis showed that participants who had contact with sarcopenia patients had higher knowledge score (ß = 1.941, P < 0.001); participants who had attended sarcopenia training in the past 6 months (ß = 4.305, P < 0.001) had higher practice score. DISCUSSION: Orthopedic professionals have deficiencies in the screening and diagnosis of sarcopenia. Improving the knowledge and training of professionals can strengthen practice. It is necessary to formulate diagnostic criteria and improve practice of sarcopenia through training. CONCLUSION: Orthopedic professionals had limited knowledge and practice regarding sarcopenia compared with geriatric professionals. To improve sarcopenia practice, the use of diagnostic tools to formally diagnose sarcopenia and regular training on sarcopenia should be encouraged.

Fabrication of multifunctional g-C3N4-modified Au/Ag NRs arrays for ultrasensitive and recyclable SERS detection of bisphenol A residues.

Monolayer g-C3N4-modified Au/Ag nanorods (g-C3N4/Au/Ag NRs) array is fabricated as a dual-function platform with high surface-enhanced Raman scattering (SERS) response and excellent photocatalytic degradation ability for bisphenol A (BPA) residues. FDTD simulation results of Au/Ag NRs proves that the electromagnetic field intensity is significantly enhanced at the gap of Ag NRs and Au NPs and the protrusion of Au NPs, which endows the arrays with excellent SERS activity. The arrays exhibit high sensitivity for rhodamine 6G (R6G) (LOD = 1.1 × 10-11 mol/L) and high SERS enhancement (EF = 9.2 × 107). In addition, the g-C3N4/Au/Ag NRs could degrade ˃90% of BPA adsorbed on the substrate surface within 140 min under visible light irradiation, and maintains its SERS activity after repeated use for 4 times. The dual-function platform with high SERS response and excellent recycling capability is proved to be reliable and is very promising for monitoring of BPA residues in food.

Acute water intoxication in hysteroscopic myomectomy: a rare case report.

Water intoxication is rarely seen in forensic practice and is typically associated with excessive water consumption, amphetamine intake, and child abuse. Iatrogenic water intoxication is rare but usually related to medical disputes. Here, we report a 44-year-old female was admitted to the hospital due to a 3-month history of excessive menstrual bleeding. B-ultrasound revealed multiple substantial intrauterine masses, leading to a diagnosis of multiple uterine fibroids. After admission, she underwent submucous myomectomy, endometrial resection, and transcervical resection of endometrial polyps. During the procedure, the patient suffered dizziness and chest tightness, her blood pressure decreased to 89/52 mmHg, and moist rales were heard in her both lungs; she died despite medical efforts. A forensic autopsy was performed and revealed severe pulmonary edema. Considering the patient's clinical history, acute water intoxication was considered to be the cause of death. This highlights the need for forensic pathologists to be vigilant of postoperative water intoxication, a rare complication in obstetrics, to ensure accurate assessments.

Comparison of short-term outcomes between robotic-assisted and laparoscopic gastrectomy guided by carbon nanoparticle suspension injection in gastric cancer.

BACKGROUND: The clinical application of robotic-assisted gastrectomy remains controversial, especially as clinical studies of this operation navigated by carbon nanoparticle suspension injection (CNSI) have not been conducted. This study aims to assess the perioperative safety and efficacy of CNSI-guided robotic-assisted gastrectomy in patients with gastric cancer by focusing on short-term outcomes. METHODS: A retrospective analysis of patients who underwent CNSI-guided laparoscopic or robotic-assisted gastrectomy with a pathological diagnosis of gastric cancer was conducted. Data on demographics, surgical management, clinical-pathological results and short-term outcomes were compared among the groups. RESULTS: A total of 126 eligible patients were separated into the robotic-assisted gastrectomy (RAG) group (n = 16) and the laparoscopic gastrectomy (LG) group (n = 110) in total. The operation time of the RAG group is longer than the LG group (p = 0.0000). When it comes to perioperative and short-term complications, there exists no statistical difference between the two groups. CONCLUSION: The time required for CNSI-guided robotic-assisted gastrectomy is longer than that for CNSI-guided laparoscopic gastrectomy. CNSI-guided robotic-assisted gastrectomy is safe and effective.

Effect of radiofrequency therapy on HPV16-E7 lentivirus infection in the reproductive tract of mice and its effect on immune function of splenic lymphocytes.

OBJECTIVE: To investigate the effect of radiofrequency therapy (RFT) on HPV16-E7 lentivirus infection in the reproductive tract of mice and reveal its effect on immune function of splenic lymphocytes. MATERIALS AND METHODS: The mouse reproductive tract model was established by infection with HPV16-E7 lentivirus. Fluorescence microscope was used to evaluate successful injection. The expression of HPV16-E7 protein was detected by Western blotting test. The levels of CD4+ and CD8+ were determined by flow cytometry, and the ratio was calculated. The proliferation of splenic lymphocytes was detected by MTT assay. Expression of Interleukin (IL)-2 and interferon-γ (IFN-γ) messenger RNA (mRNA) in lymphocyte was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Fluorescence microscope determined the successful injection of HPV16-E7 lentivirus. Compared with model group, RFT treatment decreased HPV16-E7 protein, and increased CD4+/CD8+ ratio and the proliferation activity of splenic lymphocytes. Besides, RFT treatment increased the mRNA expression levels of IL-2 and IFN-γ compared to the model group. In particular, the proliferation activity of spleen lymphocytes and the expression levels of IL-2 mRNA and IFN-γ mRNA in RFT were higher at 12 days than at 6 days after treatment. CONCLUSION: RFT could eliminate HPV16-E7 lentivirus infection in the reproductive tract of mice, and the mechanism was related to the immune system.

Development of a nomogram model to predict survival outcomes in patients with primary hepatic neuroendocrine tumors based on SEER database.

BACKGROUND: Primary hepatic neuroendocrine tumors (PH-NETs) are extremely rare and unknown. Because of its rarity, its prognosis features and influencing factors are not well established. METHODS: Data of 140 patients with PH-NETs diagnosed in the SEER database from 1975 to 2016 were collected. The demographics and clinic-pathological features were described. By using propensity-score matching (PSM) analysis, three associated cohorts were selected to describe the malignancy of PH-NETs and univariate analysis was conducted. Then, multivariate Cox analyses were performed and a predicting nomograph was constructed. C-index, receiver operating characteristic (ROC) curve and calibration curves were used to evaluate the predictive value of nomogram. RESULTS: The overall survival outcomes of PH-NETs were superior to hepatocellular carcinoma (HCC) with a mean survival time 30.64 vs 25.11 months (p = 0.052), but inferior to gastrointestinal tract neuroendocrine tumors in situ (GI-NETs in situ) with a mean survival time 30.64 vs 41.62 months (p = 0.017). With reference to gastrointestinal neuroendocrine tumors with liver metastasis (GI-NETs-LM), GI-NETs-LM had better outcomes in short time (1-year survival rate: 64.75% vs 56.43%) but was worse in long time (5-year survival rate: 8. 63% vs 18.57%). Multivariate Cox analyses showed that tumor grade and surgery were two independent factors for prognosis of the patients (p < 0.00). Tumor grade and surgery were used to construct the predicting nomogram. The C-index was 0.79 (95%CI = 0.75-0.83). The area under curve (AUC) values in ROC were 0.868 in 1-year and 0.917 in 3-year survival and the calibration curves showed good consistency. CONCLUSIONS: The overall prognosis PH-NETs is generally favorable, better than HCC and GI-NETs-LM in long term. Preoperative biopsy and complete pathological diagnosis were recommended. Radical surgical intervention including transplantation was the first choice in PH-NETs therapy.

Diagnostic Value of Serum ELISA of Mycoplasma Pneumoniae IgM and IgG and Passive Particle Agglutination for Mycoplasma Pneumoniae Pneumonia in Children.

BACKGROUND: The study was aimed to compare ELISA results of Mycoplasma pneumoniae IgG (MP-IgG) and Mycoplasma pneumoniae IgM (MP-IgM) with the passive particle agglutination (PA) test, as well as to evaluate their application value in the diagnosis of Mycoplasma pneumoniae pneumonia (MPP) in children. METHODS: Serum MP antibodies were detected by ELISA for MP-IgM, MP-IgG, and PA for 292 patients in the MPP group and 89 patients in NMP group. The PA results were used as reference standards. These patients were treated in the respiratory department of Children's Hospital Capital Institute of Pediatrics, China, from July to December, 2019. RESULTS: In the MPP group, the positive rate for MP-IgM was 75% higher than that of the PA titer (73.97%), Pearson's coefficient was 0.711, and the Kappa coefficient was 0.662, p < 0.01, suggesting that both the correlation and the consistency of the two methods were high. In the PA-negative group (< 1:160), 22.38% of patients were MP-IgM positive, indicating that the sensitivity to MP-IgM was higher compared to PA, when the disease duration was less than 7 days. The diagnostic value for MP-IgG was lower than that for MP-IgM, and the high positive rate of MP-IgG (48.31%) in the NMP group suggested a high background value of MP-IgG in children. Testing of paired serum obtained a more accurate diagnosis. At admission, 47.57% of patients with paired serum who were negative for MP-IgM, converted to a net positive after 4 - 6 days, except for one patient. In the paired serum, 57.8% of patients had a 4-fold increase of MP-IgG. CONCLUSIONS: MP-IgM was a sensitive indicator of MP infection in children with a high consistency and correlation with the reference positive standard of PA titer ≥ 1:160. For a more accurate diagnosis, testing of paired serum is still necessary, and a 4-fold increase in MP-IgG could be the supplementary diagnosis method.

Antibody free ELISA-like assay for the detection of transcription factors based on double-stranded DNA thermostability.

Transcription factors (TFs) play critical roles in gene expression regulation and disease development. In this paper, we report an antibody free ELISA-like assay which could be used to analyze transcription factor NF-κB p50 with comparatively low cost and high throughput. This assay is based on the stabilization of a duplex DNA probe by binding with a transcription factor. The double-stranded DNA (dsDNA) probe immobilized on a 96-well plate was too short in length to stabilize its duplex structure at a relatively high temperature and would unwind into a single strand. In the presence of a target TF, the protein bound to a specific TF-binding site and prevented the specific dsDNA probe from being unzipped at the washing temperature, thus holding the chemiluminescence signal. This method could sensitively detect NF-κB p50 with a detection limit of 0.5 nM. The proposed strategy provides a convenient, cheap and high throughput detection method of TFs, which can potentially help the development of drug discovery and disease diagnosis.

Observations of N2O5 and NO3 at a suburban environment in Yangtze river delta in China: Estimating heterogeneous N2O5 uptake coefficients.

The nitrate radical (NO3) and dinitrogen pentoxide (N2O5) play an important role in the nocturnal atmosphere chemistry. Observations of NO3 radicals and N2O5 were performed in a semirural ground site at Tai'Zhou in polluted southern China using cavity ring down spectroscopy (CRDS) from 23 May to 15 June 2018. The observed NO3 and N2O5 concentrations were relatively low, with 1 min average value of 4.4 ± 2.2 and 26.0 ± 35.7 pptV, respectively. The N2O5 uptake coefficient was determined to be from 0.027 to 0.107 based on steady state lifetime method. Fast N2O5 hydrolysis was the largest contributor to the loss of NO3 and contributed to substantial nitrate formation, with an average value of 14.83 ± 6.01 µg/m3. Further analysis shows that the N2O5 heterogeneous reactions dominated the nocturnal NOx loss and the nocturnal NOx loss rate is 0.14 ± 0.02 over this region.

Chemical Deprenylation of N6 -Isopentenyladenosine (i6 A) RNA.

N6 -isopentenyladenosine (i6 A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i6 A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i6 A in nucleosides, oligonucleotides, and live cells. Importantly, other epigenetic modifications, amino acid residues, and natural products were not affected. Moreover, a significant phenotype difference in the Arabidopsis thaliana shoot and root development was observed with incubation of the cation. These results establish these small organic molecules as direct chemical regulators/artificial deprenylases of i6 A.

Neferine suppresses osteoclast differentiation through suppressing NF-κB signal pathway but not MAPKs and promote osteogenesis.

Osteoporosis is an ageing disease characterized by elevated osteoclastic bone resorption resulting in bone loss, decrease bone strength, and elevated incidence of fractures. Neferine, a natural compound isolated from the traditional Chinese medicine Nelumbo nucifera (Lotus), has been reported exhibit anti-inflammatory, antioxidant, and anticancer properties. However, its effect on bone remains to be determined. Here we showed that Neferine inhibits RANKL-induced osteoclast formation in a dose- and time-dependent manner. Furthermore, Neferine also demonstrated antiresorptive properties by effectively ameliorating the bone resorptive activity of mature osteoclasts. Mechanistically, Neferine suppressed RANKL-induced activation of NF-κB signaling pathway. This in turn hindered the induction and activation of NFATc1 resulting in downregulation of osteoclast marker genes closely related to differentiation, fusion as well as bone resorption. Interestingly, we found Neferine enhanced the differentiation and bone mineralization activity of MC3T3-E1 preosteoblast cells. Finally, mice treated with Neferine was protected against ovariectomy (OVX)-induced bone loss. The Neferine treatment improved bone volume following ovariectomy and also exhibited less TRAP-positive osteoclasts on bone surface. Collectively our data provide promising evidence that Neferine could be a potential therapeutic application for against osteolytic bone conditions such as osteoporosis.

Toward Anion-π Interactions Directed Self-Assembly with Predesigned Dual Macrocyclic Receptors and Dianions.

Realizing anion-π interaction induced self-assembly with charge-neutral π receptors as building components is extremely challenging. We designed and synthesized a series of bisoxacalix[2]arene[2]triazines 7-11 in which two macrocyclic motifs are linked in diverse branching angle and rigidity. Crystal structures showed the use of rigid linkers is able to control the orientation of the two macrocyclic cavities. The interplay between the two cavities was revealed by binding studies of 8-11 with chloride in solution. Whereas 180°- and 120°-branched hosts 8 and 9 possess dual complexation ability, 60°-branched and flexibly linked hosts 10 and 11 only form 1:1 complex with chloride. Association and self-assembly of these bismacrocyclic building units with dianionic naphthalene-1,5-disulfonate were systematically investigated. The formation of oligomeric self-assemblies and large aggregates in solution was suggested by 1H NMR titrations, concentration- and temperature-variable 1H NMR, diffusion-ordered spectroscopy (DOSY), ESI-MS, and dynamic light scattering (DLS). The anion-π induced long-distance self-assembly with coherent particle formation was revealed by SEM, TEM, cryo-TEM, and AFM techniques. The systematic studies allowed us to draw the conclusion that the dianion served to bridge the initial host aggregates through anion-π interactions and was responsible for the coherent particle formation. The cavity orientation of the bismacrocycle components was found to have a significant influence on the coherent particle morphology.

Development of a field system for measurement of tropospheric OH radical using laser-induced fluorescence technique.

A ground-based system for measuring tropospheric OH radical based on laser-induced fluorescence (AIOFM-LIF) was developed in this work. In this system, ambient air is expanded through a 0.4 mm nozzle to low pressure in a detection chamber, where OH radical is irradiated by the 308 nm laser pulse at a repetition rate of 8.5 kHz. Then, the resultant fluorescence corresponding to the A2Σ+(υ'=0)←X2Πi(ν''=0) transition at 308 nm is detected using gated photon counting. The AIOFM-LIF system was integrated into a mobile observing platform for the field observation following the series of laboratory characterization. A portable standard OH radical source by water photolysis-ozone actinometry was established and optimized for accurate system calibration. The factors affecting the system sensitivity were quantified. It was shown that the ultimate system sensitivity is 9.9 × 10-8 cps (molecules cm-3)-1 mw-1; the minimum detection limits are (1.84 ± 0.26) × 105 cm-3 and (3.69 ± 0.52) × 105 cm-3 at night and noon, respectively; and the whole error of AIOFM-LIF system is about 16%. Then, the system was deployed in Shenzhen, China, during the "A comprehensive STudy of the Ozone foRmation Mechanism in Shenzhen" (STORM) campaign. Valid OH radical concentrations for 31 days were obtained, and the peak of the daily average concentration was 6.6 × 106 cm-3 around 12:00. And a high correlation (R2 = 0.77) between OH and j(O1D) was also observed in this field campaign. The relationship between OH concentration and NOx was attentively discussed. The deployment of AIOFM-LIF system in STORM campaign has demonstrated its capability of measuring tropospheric OH radical with high sensitivity and accuracy in a polluted environment.

Identification of novel peptidomimetics targeting the polo-box domain of polo-like kinase 1.

A series of new peptidomimetics targeting the polo-box domain (PBD) of polo-like kinase 1 (Plk1) was identified based on the potent and selective pentapeptide Plk1 PBD inhibitor PLHSpT. Unnatural amino acid residues were introduced to the newly designed compound and the N-terminal substituent of the peptidomimetic was investigated. The optimized compound 9 inhibited the Plk1 PBD with IC50 of 0.267 µM and showed almost no inhibition to Plk2 PBD or Plk3 PBD at 100 µM. Biolayer interferometry studies demonstrated that compound 9 showed potent binding affinity to Plk1 with a Kd value of 0.164 µM, while no Kd were detected against Plk2 and Plk3. Compound 9 showed improved stability in rat plasma compared to PLHSpT. Binding mode analysis was performed and in agreement with the observed experimental results. There are only two natural amino acids remained in the chemical structure of 9. This study may provide new information for further research on Plk1 PBD inhibitors.