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A metal-free visible-light-driven cascade cyclization reaction to synthesize 3-methyl-3-acetophenone-2-oxindoles and 3-methyl-3-(methylsulfonyl)benzene-2-oxindoles via benzoyl and phenylsulfinyl radicals has been reported.

BACKGROUND The aim of this study was to investigate the association between insulin resistance (IR) and vascular cognitive impairment (VCI) in patients with cerebral small vessel disease (CSVD). METHODS A total of 275 CSVD patients were enrolled in this retrospective case-control study. The homeostatic model assessment of insulin resistance (HOMA-IR) was used to measure the index of insulin resistance. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Spearman's correlation coefficient was used to evaluate the correlation between HOMA-IR and MoCA score. The variance inflation factor (VIF) was used to detect collinearity between variables. Multivariate logistic regression analysis was employed to confirm whether HOMA-IR is an independent risk factor for VCI in CVSD. Finally, receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic value of HOMA-IR in VCI. RESULTS Of the 275 patients, 164 displayed VCI. VCI patients showed a significantly higher level of HOMA-IR compared to non-VCI patients (P

Purpose The prognosis of nasopharyngeal carcinoma (NPC) patients with parotid lymph node (PLN) metastasis remains unclear. This study was performed to investigate the prognostic significance and optimal staging category of PLN metastasis and develop a nomogram for estimating individual risk.Materials and MethodsClinical data of 7,084 non-metastatic NPC patients were retrospectively reviewed. Overall survival (OS) was the primary endpoint. A nomogram was established based on the Cox proportional hazards regression model. The accuracy and calibration ability of this nomogram was evaluated by C-index and calibration curves with bootstrap validation.ResultTotally, 164/7,084 NPC patients (2.3%) presented with PLNs. Multivariate analyses showed that PLN metastasis was a negative prognostic factor for OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Patients with PLN metastasis had a worse prognosis than N3 disease. Five independent prognostic factors were included in the nomogram, which showed a C-index of 0.743. The calibration curves for probability of 3- and 5-year OS indicated satisfactory agreement between nomogram-based prediction and actual observation. All results were confirmed in the validation cohort.ConclusionNPC patient with PLN metastasis had poorer survival outcome (OS, PFS, DMFS, and LRFS) than N3 disease. We developed a nomogram to provide individual prediction of OS for patients with PLN metastasis.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18F-RWY, based on this integrin α6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin α6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin α6. 18F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin α6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18F-RWY for PET imaging of CRC.

Background: Hypertension and hyperhomocysteinemia (HHcy) are independent risk factors of stroke and are associated with each other. Although evidence suggests that they are related to cognitive impairment, the relationship between hypertension accompanied with HHcy and poststroke cognitive impairment (PSCI) is unclear. Objective: To define the relationship between hypertension with HHcy and early cognitive impairment after acute cerebral infarction. Materials and Methods: Our study enrolled 232 patients with acute first-ever ischemic stroke. Patients were assigned to 3 groups by blood pressure and homocysteine (Hcy) levels: hypertension with HHcy, simple hypertension, or control. Cognition was assessed by the Montreal cognitive assessment at admission and at 3- and 6-month follow-ups. Results: The hypertension with HHcy group exhibited the highest incidence of early cognitive impairment (simple hypertension: p = 0.000; control: p = 0.000). This group also had lower visual space/executive scores than the simple hypertension group (p = 0.000) and lower delayed recall scores than the control group (p = 0.011). Multivariate analysis showed that hypertension with HHcy (OR 7.797; 95% CI 2.917–20.843; p = 0.000), the level of serum Hcy (OR 1.063; 95% CI 1.109–1.109; p = 0.005), education years (OR 0.797; 95% CI 0.722–0.880; p = 0.000), and Fazekas scale of leukoaraiosis (OR 1.648; 95% CI 1.239–2.191; p = 0.001) were independent influencing factors of early PSCI; however, simple hypertension (OR 1.183, 95% CI 0.208–6.737; p = 0.850) and simple HHcy (OR 1.112, 95% CI 0.181–6.810; p = 0.909) were not. Conclusion: Patients with both hypertension and HHcy are at an increased risk of early cognitive impairment after acute first-ever ischemic stroke.

PurposeBurkitt lymphoma (BL) is an invasive lymphoma subtype with FDG avid at 18F-FDG PET/CT, but there is currently no validated criterion in treatment evaluation and prognosis prediction. The aim of this study was to analyze the clinical accuracy of 18F-FDG PET/CT in Burkitt lymphoma in end of therapy PET/CT (EOT-PET) to assess the treatment response in BL and conduct a survival analysis with different Deauville 5-point score (DS) cutoff values.Materials and MethodsA total of 189 patients were retrospectively included: 97 underwent baseline PET/CT and all underwent EOT-PET. Survival curves were plotted according to the Kaplan-Meier method. Different DS cutoff values in EOT-PET were evaluated for risk stratification in Burkitt lymphoma.ResultsThe median progression free survival (PFS) and overall survival (OS) were 52 and 53 months, respectively. Applying the conventional DS 4 to 5, there was significant difference in outcome between EOT-PET negative and positive patients. However, the positive predictive value (PPV) (28.3% for PFS and 26.4% for OS) is low despite a high negative predictive value (NPV) (94.1% for OS and 94.9% for OS). When we moved the cutoff point to DS 5, the PPV was improved evidently (88.2% for PFS and 82.3% for OS) with the satisfactory NPV simultaneously (95.3% for PFS and 95.9% for OS).ConclusionsEOT-PET results using DS significantly related with PFS and OS. DS of 5 may be a better cutoff point at the end of treatment to determine whether patients have a significant risk of recurrence or progress.

Colorectal cancer (CRC) is the third most common diagnosed cancer of which risk factors include unhealthy diet, smoking, and chronic inflammation. Weakening the inflammatory response emerges as an effective therapeutic strategy to prevent the progression of CRC. Inflammatory macrophages produce substantial amounts of immunoregulatory metabolite itaconate, which is synthesized by the immune response gene 1 (Irg1). In this study, we use a membrane-permeable itaconate derivative, dimethyl itaconate (DI), for the protection against CRC in mouse model. DI decreased the high inflammatory state of ulcerative colitis and reduced the colitis-associated cancer (CAC) risk. Mechanistically, DI inhibited the secretion of the cytokines IL-1β and CCL2 from intestinal epithelial cells, and therefore reduced the recruitment of macrophages into tumor microenvironment. Meanwhile, the decrease of macrophage infiltration was accompanied by a decrease of myeloid-derived suppressor cell (MDSC) infiltration and the differentiation of T cell subsets into cytotoxic T cells. We showed that itaconate derivative limits inflammatory response, indicating a negative feedback loop that involves an inflammatory agent and itaconate. Our findings demonstrate the potential application of DI for the prevention of colitis-associated CRC. KEY MESSAGES: Dimethyl itaconate (DI) suppresses ulcerative colitis and colitis-associated colorectal cancer DI decreases infiltration of macrophages and myeloid-derived suppressor cells into tumor DI weakens the inflammatory response via inhibiting the secretion of IL-1β and CCL2.

A novel and efficient scandium-catalyzed oxidative reaction between ynamides and alcohols for the facile synthesis of various α-alkoxyl amides is reported in this paper. The reaction avoids the need for the use of α-diazo carbonyls which are unstable and may cause some safety concerns. Instead, by using alkynes as the starting materials, this protocol features readily available substrates, compatibility with a broad range of functional groups, simple procedure, mild reaction conditions, and high chemoselectivity.

Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer 18F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. 18F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide. We compared the integrin α6 targeted PET tracer 18F-RWY with the integrin αvβ3-targeted PET tracer 18F-3PRGD2 and the clinical PET tracer 18F-FDG in chemical induced HCC mice. Among 12 HCC identified by enhanced magnetic resonance imaging (MRI) with hepatocellular specific gadoxetate disodium Gd-EOB-DTPA, the sensitivities of 18F-RWY, 18F-3PRGD2 and 18F-FDG were approximately 92%, 73% and 50% while the tumor-to-liver ratios were 4.36 ± 1.41, 1.97 ± 0.43 and 1.63 ± 0.23 respectively. Additionally, PET imaging with the integrin α6 targeted 18F-RWY enabled to visualize small HCC lesions with diameters approximately 0.2 cm that was hard to be distinguished from surround hepatic vascular by enhanced MRI with Gd-EOB-DTPA. These findings potentiate the use of integrin α6 targeted PET tracer 18F-RWY for the detection of HCC.

Objective To observe the characteristics of rat brain injury induced by shock wave propagation in solids resulting from underwater explosion and explore the related mechanism. Methods Explosion source outside the simulated ship cabin underwater was detonated for establishing a model of brain injury in rats by shock wave propagation in solid; 72 male SD rats were randomly divided into normal control group (n=8), injury group 1 (600mg RDX paper particle explosion source, n=32), injury group 2 (800mg RDX paper particle explosion source, n=32). The each injury group was randomly divided into 4 subgroups (n=8), 3, 6, 24 and 72h groups. The division plate as a whole and the head of 8 rats in each injury group were measured for the peak value of the solid shock wave, its rising time and the duration time of shock wave propagation in solid. To observe the physiological changes of animals after injury, plasma samples were collected for determination of brain damage markers, NSE and S-100β. All the animals were sacrificed, the right hemisphere of the brain was taken in each group of animals, weighting after baking, and the brain water content was calculated. Pathological examination was performed for left cerebral hemisphere in 24-h group. The normal pyramidal cells in the hippocampal CA1 region were counted. Results The peak value, rising time and duration time of shock wave propagation on the division plate and head were 1369.74±91.70g, 0.317±0.037ms and 24.85±2.53ms, 26.83±3.09g, 0.901±0.077ms and 104.21±6.26ms respectively in injury group 1, 1850.11±83.86g, 0.184±0.031ms and 35.61±2.66ms, 39.75±3.14g, 0.607±0.069ms and 132.44±7.17ms in injury group 2 (P

A Lewis acid-catalyzed alkyne oxidation strategy has been developed to produce diverse α-functionalized amides from readily and generally available ynamides. An efficient zinc(II)-catalyzed oxidative azidation and thiocyanation has been achieved, providing facile access to synthetically useful α-azido amides and α-thiocyanate amides, respectively. This chemistry can also be extended to oxidative halogenations by employing the 2-halopyridine N-oxide as both the oxidant and the halogen source, and its mechanistic rationale is also supported by density functional theory calculations. Moreover, NaBARF has been demonstrated to catalyze such an alkyne oxidation effectively, thus further excluding the metal carbene pathway in this cascade reaction.

A compact and high isolation microstrip six-channel diplexer has been proposed. The diplexer is formed by connecting two tri-band bandpass filters (BPFs) to a single feed with multiple coupling paths. By using the distributed coupling technique, the input matching circuit is not needed anymore, resulting in a smaller circuit size. In addition, by employing the multi-mode stepped-impedance resonators (SIRs), a diplexer with compact size and flexible frequency allocation can be implemented. For a demonstration, a six-channel diplexer with third-order Chybeshev bandpass response is designed and fabricated using microstrip technology. The size of the fabricated diplexer is only about $\pmb{0.69 \lambda_{\text{g}}\times 0.21\lambda_{\text{g}}}$ . Moreover, the isolation between the output channels is larger than 35 dB.

A novel and efficient scandium-catalyzed oxidative reaction between ynamides and alcohols for the facile synthesis of various α-alkoxyl amides is reported in this paper. The reaction avoids the need for the use of α-diazo carbonyls which are unstable and may cause some safety concerns. Instead, by using alkynes as the starting materials, this protocol features readily available substrates, compatibility with a broad range of functional groups, simple procedure, mild reaction conditions, and high chemoselectivity.

The title reaction of ynamides of type (I), (IV), and (VI) with benzylic azides (II) offers a highly regioselective access to 2-aminoindoles (III) and (V).

As a natural polymer, alginic acid is widely used in medical fields for its biodegradability, low toxicity and immunogenicity. In this paper, four kinds of cavernous calcium alginate wound dressings were prepared, and physical properties were tested, providing fundamental basis for further study. The results indicate that glycerin is not suitable as a plasticizer for this cavernous wound dressing; a relatively uniform structure of the calcium alginate wound dressing would be obtained as the solution temperature increased; the mechanical properties decrease with the increase of the pre-freezing time.

The cytotoxicity and anti-influenza virus (IFV) activity of calcium or zinc alginate fibers were investigated to explore the feasibility of them to be used as biomaterials. African Green Monkey kidney cell (Vero) and human cervical cancer cell (Hela) cultured with alginate fibres were used to screen cytotoxic effects. After 48 h, MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assays were performed. Then cytotoxicity was evaluated with six grades according to cell relative growth rate (RGR). In anti-IFV activity assay, IFV were added to all fibers and the Vero cell survival were detected by MTT assays with calculating the percentage of protection. The cytotoxity of calcium alginate fibers on Vero were grade 0 or 1 in contrast to zinc alginate fibers which was grade 0. The cytotoxity of calcium or zinc alginate fibers on Hela were grade 0. Furthermore, partial calcium or zinc alginate fibers could promote Vero or Hela cell growth. In antiviral assay the highest percentage of protection of calcium alginate fibers was 34.42%, while that of zinc alginate fibers was 59.42%. The results showed that calcium or zinc alginate fibers had a good cellular biocompatibility and the large weight zinc alginate fibers had a better anti-IFV activity than calcium alginate fibers, which is potential for tissue engineering.

In order to verify the transcription factor CBF2 gene can be induced to express in plant and improve the plant salt resistance, they were cloned from the Arabidopsis thaliana by PCR according to CBF2 gene sequence published on GenBank. The plant expression vector (pBI-rd29A-CBF2) with CBF2 gene was constructed. The CBF2 gene was transformed into soybean plants via Agrobacterium-mediated transformation. It approved that the CBF2 gene had been transformed and integrated into the genome of soybean by PCR and Southern blot. Through the physiological test of salt resistance, the relative electric conductivity of the transformed plants plasma membrane and the control were 36.84% and 59.35% respectively under salt stress. The content of chlorophyll of the transformed plants was 2.41 times as much as that of the control. The content of proline of the transformed plants was 2.49 times as much as that of the control. It showed that the CBF2 gene was induced to express in soybean plants. And it also indicated that the expression of the CBF2 gene increased the salt stress tolerance of the transgenic soybean plants. The results proved the CBF2 gene were functional gene.

To observe the effect of Quyu Jiedu Granules (祛瘀解毒颗粒, QJG) on the micro- microenvironment of ova in patients with endometriosis (EM). environment Twenty EM patients who received in vitro fertilization and embryo transfer (IVF-ET) were randomized equally into a treated group and a control group. Further, 20 patients who received IVF-ET due to oviduct factors were enrolled into a non-endometriosis group. The dosage of gonadotrophic hormone used, the number of ova attained, fertilization rate and clinical pregnancy rate were all observed, and the levels of tumor necrosis factor α (TNF-⇌) and interleukin 6 (IL-6) in follicular fluid as well as their mRNA expressions in ovarian granular cells were detected by RT-PCR on the very day of ovum attainment. The ova attainment (13.80±6.87) and fertilization rate (0.69±0.31) in the treated group were all higher than the corresponding values in the control group (9.80±5.32 and 0.47±0.22); the follicular fluid contents of TNF-α and IL-6 in the treated group were 1.38±0.21 ng/mL and 130.56±12.81 pg/mL, respectively, which were lower than those in the control group (1.98±0.34 ng/mL and 146.83±17.65 pg/mL, respectively). Further, the treated group showed much lower mRNA expressions of TNF-α and IL-6 in ovarian granular cells. The elevation of TNF-α and IL-6 contents in follicular fluid and their mRNA expressions in ovarian granular cells are possibly related to the low quality of ova in EM; QJG might raise the ova quality by reducing TNF-α and IL-6 levels to improve the living micro-environment for the ova.

The objective of this study was to investigate the effectiveness and specific effects of acupuncture on ischemic-induced damage in rats after permanent middle cerebral artery occlusion. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. The rats were divided into the following 4 groups: normal controls, ischemic, real acupuncture-treated (Shuigou, DU26), and non-acupoint-treated groups. On the third postoperative day, neurological deficit scores, cerebral blood flow, infarction volume, and neuronal cell death counts were measured. In the real acupuncture-treated group, the neurological deficit scores and cerebral blood flow were improved (p < 0.05) and the infarction volume and neuronal cell death counts were reduced (p < 0.01) compared to the ischemic and non-acupoint-treated groups. The present study demonstrated that real acupuncture was effective against focal ischemia-induced damage in rats after middle cerebral artery occlusion, and the effects were specifically related to the right needling location.Key words: specificity, real acupoint, non-acupoint, middle cerebral artery occlusion, animal experimentation

To observe the effect of human follicular fluid (HFF) from endometriosis (EM) patients treated with Quyu Jiedu Granule (QJG) on mouse embryonic development.Cultured 2-cell mouse embryos were divided into three groups. To the medium of Group A (70 embryos), HFF from endometriosis patients treated with QJG was added; to that of Group B (60 embryos), HFF from endometriosis patients untreated with QJG, and to Group C (59 embryos), HFF from patients with fallopian tube obstruction was added. The percentages of embryos developed to 8-cell stage, morula stage and blastula stage were counted, and the early stage number and rate of high-quality embryo were measured.Among the 70 embryos in Group A, 53 (75.71%) developed to 8-cell stage, 48 (68.57%) to morula stage and 45 (64.28%) to blastula stage; while in the 60 embryos of Group B, the corresponding number (percentage) were 34 (56.67%), 29 (48.33%), 21 (35.00%), respectively, showing significant differences between groups (P0.05). High-quality of embryo was 61 (87.14%) in Group A and 44 (73.3%) in Group B, the difference between groups also showed statistical significance (P0.05).HFF from endometriosis patients is toxic to 2-cell mouse embryos, but after treated by QJG, it could elevate the quality of cultured mouse embryo in the early stage.

To observe the effect of Quyu Jiedu Granules (, QJG) on the micro- microenvironment of ova in patients with endometriosis (EM). environmentTwenty EM patients who received in vitro fertilization and embryo transfer (IVF-ET) were randomized equally into a treated group and a control group. Further, 20 patients who received IVF-ET due to oviduct factors were enrolled into a non-endometriosis group. The dosage of gonadotrophic hormone used, the number of ova attained, fertilization rate and clinical pregnancy rate were all observed, and the levels of tumor necrosis factor alpha (TNF-right harpoon over left harpoon) and interleukin 6 (IL-6) in follicular fluid as well as their mRNA expressions in ovarian granular cells were detected by RT-PCR on the very day of ovum attainment.The ova attainment (13.80+/-6.87) and fertilization rate (0.69+/-0.31) in the treated group were all higher than the corresponding values in the control group (9.80+/-5.32 and 0.47+/-0.22); the follicular fluid contents of TNF-alpha and IL-6 in the treated group were 1.38+/-0.21 ng/mL and 130.56+/-12.81 pg/mL, respectively, which were lower than those in the control group (1.98+/-0.34 ng/mL and 146.83+/-17.65 pg/mL, respectively). Further, the treated group showed much lower mRNA expressions of TNF-alpha and IL-6 in ovarian granular cells.The elevation of TNF-alpha and IL-6 contents in follicular fluid and their mRNA expressions in ovarian granular cells are possibly related to the low quality of ova in EM; QJG might raise the ova quality by reducing TNF-alpha and IL-6 levels to improve the living micro-environment for the ova.

A field experiment was conducted to measure concentrations and size distributions of particle (10 nmD(p)487 nm) at four heights in an asymmetric street canyon on Beijing East Road in Shanghai, China. It shows that particle number size distributions are bimodal or trimodal lognormal in form. At a certain height in the range from 1.5 to 20 m, particle number concentrations and size distributions significantly vary with the height. Particle number concentrations in nuclei mode drop significantly and the mode diameters shift to the larger diameter. The variations of particle number concentration and size distribution in accumulation mode are less significant than that in nuclei mode. Particle number concentrations and size distributions slightly change with increasing the height in the range from 20 to 38 m. Concentrations of CO and PM(2.5) were also measured. Power laws are found to be well fitted for the concentration decay of total particle number, total particle volume, CO and PM(2.5). Due to the effect of the wind speed and direction, the total particle volume, PM(2.5) and CO concentrations are lower for Test I (high wind speed and step-up street canyon) than for test II (low wind speed and wind channeling along the canyon), at the meantime, the decay rates of the total particle number, the total particle volume, CO and PM(2.5) concentrations for test I are lower than for test II . No matter how the wind direction changes, the decay rates of the total particle number concentrations are larger than those of CO and PM(2.5), which clearly shows that coagulation and deposition besides dilution processes affect the total particle number concentration.