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Two types of retrograded eclogite (phengite‐bearing eclogite and garnet pyroxenite) within eclogite‐facies granitic gneisses are reported for the first time from the Younusisayi area of the South Altyn high to ultrahigh pressure (HP–UHP) metamorphic belt. These eclogites were studied using petrology, mineral chemistry, phase equilibrium modelling, and geochronology. The phengite‐bearing eclogite records five stages of metamorphism: (1) early prograde (Grt + Cpx + Amp + Rt + Qz) at conditions of P = 11.50–17.5 kbar, T = 665–740°C; (2) peak eclogite‐facies (Grt + Omp + Ph + Rt + Qz) at conditions of P > 24.2 kbar, T = 710–1000°C; (3) overprinting during retrograde transition to HP granulite‐facies conditions (Grt + Cpx ± Kfs + Pl + Rt + Qz) at P = 12.1–16.9 kbar and T = 760–890°C; (4) retrogression at granulite‐facies conditions (Grt + Cpx + Amp + Pl + Ilm + Qz) of P = 9.1–11.4 kbar, T = 730–840°C; and (5) amphibolite‐facies metamorphism (Amp + Pl + Ilm + Qz) during cooling and decompression. The garnet pyroxenite records four stages of metamorphism: (1) eclogite‐facies at conditions of P > 23.2 kbar, T = 775–965°C; (2) HP granulite‐facies conditions of P = 13.2–17.8 kbar and T = 836–912°C; (3) granulite‐facies conditions of P = 8.6–9.7 kbar, T = 739–783°C; and (4) amphibolite‐facies metamorphism. Zircon U–Pb dating and trace element analysis constrain eclogite‐facies metamorphism to c. 500 Ma, consistent with the age of the surrounding eclogite‐facies granitic gneiss (497.8 ± 2.7 Ma). Retrograde metamorphism ages of c. 460 Ma are interpreted as recording zircon growth after granulite‐facies metamorphism. The P–T–t path defines the integrated process of deep subduction and multistage exhumation and places constraints on the early Palaeozoic geodynamics of the South Altyn belt. Well‐preserved major and trace element zoning of garnets in the Ph‐bearing eclogites lacks evidence of significant thermal diffusion and may record garnet growth during deep subduction, immediately followed by very rapid exhumation. [ABSTRACT FROM AUTHOR]

Summary: Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate ZHER2:V2-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using ZHER2:V2-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the 99mTc-labeled ZHER2:V2-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with 99mTc-ZHER2:V2-pemetrexed demonstrated that in HER2+ A549 models, ZHER2:V2-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that ZHER2:V2-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the ZHER2:V2-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the ZHER2:V2-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the ZHER2:V2-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

In this study, a series of chitosan films with different protonation degrees were prepared by deacidification with NaOH aqueous or ethanol solutions. The films were then used as a model to investigate the effects of the positive charge of chitosan on blood coagulation. The results showed that the positive charge of chitosan acted as a double-edged sword, in that it promoted erythrocyte adhesion, fibrinogen adsorption, and platelet adhesion and activation, but inhibited activation of the contact system. In contrast to prevailing views, we found that the positive charge of chitosan retarded thrombin generation and blood coagulation on these films. At least two reasons were responsible for this phenomenon. First, the positive charge inhibited the contact activation, and second, the positive charge could not significantly promote the activation of non-adherent platelets in the bulk phase during the early stage of coagulation. The present findings improve our understanding of the events leading to blood coagulation on chitosan films, which will be useful for the future development of novel chitosan-based hemostatic devices. [ABSTRACT FROM PUBLISHER]

Abstract: Mitochondrial malfunction and calcium dyshomeostasis are early pathological events considered as important features of the Alzheimer’s disease (AD) brain. Recent studies have suggested mitochondrion as an active regulator of Ca2+ signaling based on its calcium buffering capacity. Herein, we investigated the mitochondrial involvement in the modulation of store-operated calcium entry (SOCE) in neural 2a (N2a) transgenic AD model cells. Results showed that SOCE was significantly depressed in N2a cells transfected with wild-type human APP695 (N2a APPwt) compared with empty vector control (N2a WT) cells. Pharmacological manipulation with mitochondrial function blockers, such as FCCP, RuR, or antimycin A/oligomycin, could inhibit mitochondrial calcium handling, and then impair SOCE pathway in N2a WT cells. Furthermore, mitochondria of N2a APPwt cells exhibited more severe swelling in response to Ca2+, which is an indication of mitochondrial membrane permeability transition (MPT), than the wild-type controls. Additionally, treatment with cyclosporin A, a potent inhibitor of cyclophilin D, which can block MPT, could significantly restore the attenuated SOCE in N2a APPwt cells. Therefore, inhibition of cyclophilin D might be a therapeutic strategy for Alzheimer’s disease. [Copyright &y& Elsevier]

Objective To investigate the differences in energy spectrum CT findings between anterior mediastinal lymphoma and thymic carcinoma. Methods Twenty-two cases of anterior mediastinal lymphoma and 28 cases of thymic carcinoma confirmed by biopsy in Tangshan People's Hospital were selected.The CT values and changes of iodine content and water content in lesion sites were measured by energy spectrum analysis software.The differences between anterior mediastinal lymphoma and thymic carcinoma were compared. Results The single-energy CT value of 40-80 keV in thymus carcinoma was higher than that in anterior mediastinal lymphoma( P =0.001, P =0.037, P =0.042, P =0.034, P =0.002; P =0.016, P =0.013, P =0.018, P =0.024, P =0.012).The difference in the single-energy CT value of 90-110 keV between anterior mediastinal lymphoma and thymic carcinoma showed no statistical significance(all P >0.05).The concentrations of water in the arterial and venous stages of thymic carcinoma were significantly lower than those in the anterior mediastinal lymphoma( P =0.030, P =0.037),whereas the iodine concentrations were significantly higher( P =0.026, P =0.000). Conclusion Anterior mediastinal lymphoma and thymic carcinoma have remarkably different 40-80 keV single energy CT value and iodine concentration in arterial and venous phases,which may be helpful for the differential diagnosis of these two malignancies.

Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate Z HER2:V2 -pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using Z HER2:V2 -pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the 99m Tc-labeled Z HER2:V2 -pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with 99m Tc-Z HER2:V2 -pemetrexed demonstrated that in HER2+ A549 models, Z HER2:V2 -pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that Z HER2:V2 -pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the Z HER2:V2 -pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the Z HER2:V2 -pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the Z HER2:V2 -pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma.