Volcanic contribution to the 1990s North Pacific climate shift in winter.

It is debatable whether external forcing can change the state of the climate. By investigating decadal changes with and without including the 1990s stratospheric volcanic aerosols, we explored the volcanic eruptions contribution to decadal climate regime shifts occurring in boreal winter over the North Pacific. The volcanic eruptions contribution can be characterized as a series of rapid changes, including the strengthening and poleward shift of the midlatitude westerly jet stream. In addition to the short-lived radiative effects primarily induced by the 1991 Mount Pinatubo eruption, the volcanically driven decadal change can be observed in the mid-to-late 1990s, suggesting a time-lagged characteristic of the volcanic climate impact. Compared with the decadal change irrelevant to volcanic eruption, the decadal state more dramatically enters into the next phase when volcanic forcing is included. The climate oscillation-related pattern shifts that occurred across the 1990s can provide insights into volcanically induced changes in decadal atmospheric circulation.

Tuning intramolecular charge transfer and spin-orbit coupling of AIE-active type-I photosensitizers for photodynamic therapy.

Development of photosensitizers (PSs) featuring type-I reactive oxygen species (ROS) with aggregation-induced emission (AIE) properties is a judicious approach to overcome the deficit of conventional photodynamic therapy (PDT). However, it remains a challenge to design AIE-active type-I ROS PSs using a simple theranostic scaffold paired with a delicate balance between intramolecular charge transfer (ICT) and large spin-orbit coupling (SOC) features to facilitate intersystem crossing (ISC) and hence to intensify triplet excitons for type-I ROS generation as well as to improve optical properties for the desired biomedical applications. In this work, a rationally designed series of PSs based on C-6-substituted tetraphenylethylene-fused benzothiazole-coumarin scaffolds, named TPE-nCUMs, were synthesized via a fused-ring-electron-acceptor (FREA) strategy, endowed with AIE properties in aqueous solution and thus self-monitoring type-I ROS generation under white-light irradiation to study the effects of diverse ICT and SOC potentials on their photochemical and optical properties. Both experimental and theoretical results revealed that the concomitantly increasing strengths of both ICT and SOC features promote type-I ROS generation by TPE-nCUMs. The key role of the SOC-promoting carbonyl group towards the ROS generation ability of TPE-nCUMs was then examined. Among TPE-nCUMs, gem-2OMe-TPE-2CUM displayed highly efficient type-I ROS generation. Importantly, gem-OMe-TPE-1CUM acts as a fluorescent indicator in HeLa cells (in vitro), revealing its excellent diffusion capability in both lysosomal and mitochondrial organelles with low dark toxicity, high cytotoxicity under white-light and remarkable PDT efficiency. Our study has thus elucidated a rationally designed strategy at the molecular level to fine-tune ICT and SOC features for the advance of AIE-active type-I ROS PSs, opening a new avenue for cancer treatment and image-guided therapy.

Role of eccentricity in early Holocene African and Asian summer monsoons.

The effect of precession on paleoclimate changes depends on eccentricity. However, whether and to what degree eccentricity relates to millennial-scale monsoonal changes remain unclear. By investigating climate simulations with a fixed precession condition of 9 ka before the present, we explored the potential influence of eccentricity on early-Holocene changes in the Afro-Asian summer monsoons. Compared with the lower eccentricity of the present day, higher eccentricity in the early Holocene strengthened the continental summer monsoons, Pacific anticyclone, and Hadley circulation, particularly over the ocean. Over Africa, the eccentricity-induced "dry-gets-wetter" condition could be related to the Green Sahara, suggesting a superimposed effect of precession. Over the western Pacific, the tropical response to eccentricity may have been competitive in terms of what an extremely high obliquity may have caused. A downscaled modulation of eccentricity in relation to precession and obliquity cannot be ignored when paleomonsoon records are studied. Regarding early-Holocene monsoonal changes in South Asia, however, a high eccentricity may have had only a secondary effect on enhancing the monsoonal precipitation in the southern edge of the Tibetan Plateau, exhibiting the weak power of candle-like heating. This suggested that sizable monsoonal changes over the northern Indian Ocean and India-Pakistan region are unrelated to early-Holocene eccentricity.

AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion.

Breast cancer (BC) is a type of malignant tumor originating from the epithelial tissue of the mammary gland, and about 20% of breast cancers are human epidermal growth factor receptor 2 positive (HER2+), which is a subtype with more aggression. Recently, HER2-positive breast cancer is often accompanied by poor prognosis of patients, and targeted therapy showed a promising prospect. To combat this disease, novel therapeutic targets are still needed. Adenylate kinase 4 (AK4) is a member of the adenylate kinase family and is expressed in the mitochondrial matrix. AK4 is involved in multiple cellular functions such as energy metabolism homeostasis. Interestingly, AK4 was observed highly expressed in several tumor tissues, and the involvement of AK4 in cancer development was generally revealed. However, the possible role of AK4 on the growth and development of breast cancer is still unclear. Here, we investigated the possible functions of AK4 on the progression of HER2-positive breast cancer. We found the high expression of AK4 in HER2-positive breast cancer tissues from patients who received surgical treatment. Additionally, AK4 expression levels were obviously correlated with clinical-pathological features, including pTNM stage (P = 0.017) and lymph node metastasis (P = 0.046). We mechanically confirmed that AK4 depletion showed the obvious impairment of cell proliferation and invasion in MCF7 and MDA-MB-231 cells. AK4 also facilitates tumor growth and metastasis of HER2-positive breast cancer in vivo. In conclusion, we identified and mechanically confirmed that AK4 is a novel therapeutic target of HER2-positive breast cancer.

Paleoclimatic information recorded in fluid inclusions in halites from Lop Nur, Western China.

The homogenization temperature (Th) of primary fluid inclusions in halite can be used for paleoclimate interpretations. Lop Nur, in Central Asia, is an extremely arid zone where large amounts of glauberite were deposited from the late Middle to Late Pleistocene. This deposition was accompanied by formation of large-scale potash-bearing brines. However, quantitative paleotemperature data are still lacking, hindering reconstruction of Quaternary climate conditions and their control over potash formation. We measured the Th of inclusions in halite from the salt field and the top of Upper Pleistocene strata in Lop Nur. The maximum homogenization temperature (Th MAX) of inclusions in halite from the salt field was 41.1 °C, consistent with the maximum ambient temperature (43.4 °C) in the same period. The Th MAX of inclusions in halite from the Upper Pleistocene strata ranged from 35.6 °C to 43 °C, where maximum air temperatures may have reached 37.9 °C to 45.3 °C. The results show that a hot and arid climate prevailed in Lop Nur at the end of the Late Pleistocene. Furthermore, changes of the brine chemical composition due to supply variations instead of climate change, may have caused glauberite deposition to cease at the end of the Late Pleistocene.

Predictive model for contrast-enhanced ultrasound of the breast: Is it feasible in malignant risk assessment of breast imaging reporting and data system 4 lesions?

AIM: To build and evaluate predictive models for contrast-enhanced ultrasound (CEUS) of the breast to distinguish between benign and malignant lesions. METHODS: A total of 235 breast imaging reporting and data system (BI-RADS) 4 solid breast lesions were imaged via CEUS before core needle biopsy or surgical resection. CEUS results were analyzed on 10 enhancing patterns to evaluate diagnostic performance of three benign and three malignant CEUS models, with pathological results used as the gold standard. A logistic regression model was developed basing on the CEUS results, and then evaluated with receiver operating curve (ROC). RESULTS: Except in cases of enhanced homogeneity, the rest of the 9 enhancement appearances were statistically significant (P < 0.05). These 9 enhancement patterns were selected in the final step of the logistic regression analysis, with diagnostic sensitivity and specificity of 84.4% and 82.7%, respectively, and the area under the ROC curve of 0.911. Diagnostic sensitivity, specificity, and accuracy of the malignant vs benign CEUS models were 84.38%, 87.77%, 86.38% and 86.46%, 81.29% and 83.40%, respectively. CONCLUSION: The breast CEUS models can predict risk of malignant breast lesions more accurately, decrease false-positive biopsy, and provide accurate BI-RADS classification.

Contrast-enhanced ultrasound improved performance of breast imaging reporting and data system evaluation of critical breast lesions.

AIM: To determine whether contrast-enhanced ultrasound (CEUS) can improve the precision of breast imaging reporting and data system (BI-RADS) categorization. METHODS: A total of 230 patients with 235 solid breast lesions classified as BI-RADS 4 on conventional ultrasound were evaluated. CEUS was performed within one week before core needle biopsy or surgical resection and a revised BI-RADS classification was assigned based on 10 CEUS imaging characteristics. Receiver operating characteristic curve analysis was then conducted to evaluate the diagnostic performance of CEUS-based BI-RADS assignment with pathological examination as reference criteria. RESULTS: The CEUS-based BI-RADS evaluation classified 116/235 (49.36%) lesions into category 3, 20 (8.51%), 13 (5.53%) and 12 (5.11%) lesions into categories 4A, 4B and 4C, respectively, and 74 (31.49%) into category 5. Selecting CEUS-based BI-RADS category 4A as an appropriate cut-off gave sensitivity and specificity values of 85.4% and 87.8%, respectively, for the diagnosis of malignant disease. The cancer-to-biopsy yield was 73.11% with CEUS-based BI-RADS 4A selected as the biopsy threshold compared with 40.85% otherwise, while the biopsy rate was only 42.13% compared with 100% otherwise. Overall, only 4.68% of invasive cancers were misdiagnosed. CONCLUSION: This pilot study suggests that evaluation of BI-RADS 4 breast lesions with CEUS results in reduced biopsy rates and increased cancer-to-biopsy yields.

Azithromycin-induced torsade de pointes.

Although erythromycin frequently induces long QT interval and torsade de pointes, the newer drug, azithromycin, has rarely been reported to be associated with torsade de pointes. We report here the occurrence of a significant typical QT prolongation within a few hours after taking azithromycin which lead to torsade de pointes.

TT viral infection through blood transfusion: retrospective investigation on patients in a prospective study of post-transfusion hepatitis.

AIM:To investigate the role of blood transfusion in TT viral infection(TTV).METHODS:We retrospectively studied serum samples from 192 transfusion recipients who underwent cardiovascular surgery and blood transfusion between July 1991 and June 1992. All patients had a follow-up every other week for at least 6 months after transfusion. Eighty recipients received blood before screening donors for hepatitis C antibody (anti-HCV), and 112 recipients received screened blood. Recipients with alanine aminotransferase level > 2.5 times the upper normal limit were tested for serological markers for viral hepatitis A, B, C, G, Epstein-Barr virus and cytomegalovirus. TTV infection was defined by the positivity for serum TTV DNA using the polymerase chain reaction method.RESULTS: Eleven and three patients, who received anti-HCV unscreened and screened blood, respectively, had serum ALT levels > 90IU/L. Five patients (HCV and TTV 1; HCV, HGV, and TTV 1; TTV 2; and CMV and TTV 1) were positive for TTV DNA, and four of them had sero conversion of TTV DNA.CONCLUSION:TTV can be transmitted via blood transfusion.Two recipients infected by TTV alone may be associated with the hepatitis. However, whether TTV was the causal agent remains unsettled, and further studies are necessary to define the role of TTV infection in chronic hepatitis.

Nutritional status in non-alcoholic sub-clinical porto-systemic encephalopathy.

AIM:To understand the role of nutritional status in cirrhotic patients without clinical porto-systemic encephalopathy (PSE).METHODS:Fifty-one non-alcoholic patients with cirrhosis without PSE were studied prospectively and compared with 20 healthy volunteers. The nutritional evaluation included serum prealbumin, albumin, transferrin, body mass index (BMI), mid-arm muscle circumference (MAMC), and grip power. The occurrence of subclinical PSE (SPSE) was defined when N20-N65 inter-peak latencies of median nerve-stimulated somatosensory evoked potentials were > 2.5 standard deviations of control means. Blood chemistries were tested within 12h of somatosensory evoked potentials test and nutritional evaluation.RESULTS:Twenty-five, 17 and 9 cirrhotic patients were graded as Child-Pugh class A, B, and C, respectively. Twenty-four (47.1%) patients developed SPSE. Cirrhotic patients with SPSE had lower serum albumin (2.8g/dL ± 0.5g/dL vs 3.1g/dL ± 0.7g/dL, P < 0.001) levels than those without SPSE. Prealbumin (10.6mg/dL ± 5.7mg/dL vs 12.5mg/dL ± 5.8mg/dL), transferrin (164mg/dL ± 46mg/dL vs 178mg/dL ± 58mg/dL), BMI (23.7kg/m(2) ± 2.7kg/m(2) vs 25.3kg/m(2) ± 3.6kg/m(2)), MAMC (22.2cm ± 2.6cm vs 22.7cm ± 3.5cm), and grip power (26.3kg ± 6.4kg vs 26.9kg ± 6.8kg) were not different between cirrhotic patients with and without SPSE. N20-N65 inter-peak latencies were correlated with serum albumin levels (P =0.01) but not with prealbumin, transferrin, BMI, MAMC,or grip power. Serum albumin, prealbumin and transferrin levels were different among cirrhotic patients with Child-Pugh classes A, B, and C (P < 0.05). BMI, MAMC, and grip power were not different among Child-Pugh classes A, B and C.CONCLUSION:Our data suggest that serum albumin level is a simple test in the evaluation of nutritional status in patients with cirrhosis.