The mitochondria-mediated caspase activation pathway is a major apoptotic pathway characterized by mitochondrial outer membrane permeabilization (MOMP) and subsequent release of cytochrome c into the cytoplasm to activate caspases. MOMP is regulated by the Bcl-2 family of proteins. This pathway plays important roles not only in normal development, maintenance of tissue homeostasis and the regulation of immune system, but also in human diseases such as immune disorders, neurodegeneration and cancer. In the past decades the molecular basis of this pathway and the regulatory mechanism have been comprehensively studied, yet a great deal of new evidence indicates that cytochrome c release from mitochondria does not always lead to irreversible cell death, and that caspase activation can also have non-death functions. Thus, many unsolved questions and new challenges are still remaining. Furthermore, the dysfunction of this pathway involved in cancer development is obvious, and targeting the pathway as a therapeutic strategy has been extensively explored, but the efficacy of the targeted therapies is still under development. In this review we will discuss the mitochondria-mediated apoptosis pathway and its physiological roles and therapeutic implications.

The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR). A total of 166 patients were included in the final analysis. Overall, the PFR was 68%, and objective response rate was 13% (95% confidence interval, 7.6%-18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR, median PFS and OS were: 58%, 4.1 and 11 months for UPS ( = 19); 63%, 5.6 and 13 months for LPS ( = 13); 75%, 11 and 15 months for LMS ( = 26); 75%, 7.7 and 12 months for SS ( = 47); 81%, 5.6 and 12 months for FS ( = 18); 77%, 21 and not reached for ASPS ( = 13); 54%, 11 and 16 months for CCS ( = 7); and 44%, 2.8 and 8.8 months for other sarcoma ( = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred. Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. .

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Background Osteosarcoma is the most common primary tumor of bone. It is a highly vascular and extremely destructive malignancy mainly affecting children and young adults. We performed microarray-based comparative genomic hybridization (aCGH) and carried out pathway analysis to gain a systemic view on the pathway alterations of the genetically altered genes. Methods Recurrent amplified and deleted genes detected by aCGH were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway analysis to identify the altered pathways. Among enriched pathways, vascular endothelial growth factor (VEGF) pathway genes were collectively amplified and the alterations of this pathway were validated by fluorescence in situ hybridization (FISH) and immunohistochemistry in 58 formalin-fixed and paraffin-embedded osteosarcoma archival tissues with clinical follow-up information. Results the pathway enrichment analyses of the aCGH data revealed that VEGF pathway genes, including vascular endothelial growth factor A(VEGFA) gene itself, were significantly amplified in osteosarcoma. Genetic amplification of the VEGFA gene, both focally and in larger fragment, was validated by FISH. Notably, amplification of VEGFA gene and elevated expression of the VEGFA protein were significantly associated with microvascular density (MVD) and adverse tumor-free survival in osteosarcoma. Conclusions We reported for the first time that VEGF pathway genes including VEGFA gene are amplified in osteosarcoma. Amplification of the VEGFA gene is not only an important mechanism for elevated VEGFA protein expression, but also a poor prognostic factor for tumor-free survival. Combined classification of VEGFA gene amplification and positive VEGFA protein expression might provide more accurate patient stratification method for selection of anti-VEGF therapy for osteosarcoma.

Direct cultivation of the first filial generation of gametophyte clones from different Laminaria species is a highly effective way of utilizing kelp heterozygous vigor (heterosis). A male gametophyte clone of L. longissima Miyabe and a female one of L. japonica Areschoug were hybridized, generating Dongfang No. 2 hybrid kelp. This hybrid kelp was used directly in trial cultivation, and its agronomical traits were evaluated. L. longissima and L. japonica are obviously different and complement each other in their morphological characteristics and ecological performances. The hybrid of their gametophyte clones, Dongfang No. 2, showed 56.8% heterozygous vigor in yield. It also showed increased yields of 41.0 and 76.4% compared to the widely used commercial kelps Variety 1 and Variety 2, respectively. In largescale cultivation trials at different locations and in different years, Dongfang No. 2 attained significantly higher yields than Varieties 1 and 2, increasing yield by 26.4% on average over Variety 1 and by 65.0% over the other. Dongfang No. 2 has a robust holdfast and a wide, long and deep-brown uniform blade, which shows a distinct middle groove. In addition to yield, Dongfang No. 2 also demonstrates obvious heterozygous vigor in other agronomic traits. It is resistant to strong irradiance, as the two commercial varieties are, has an appropriate vegetative maturation time, and adapts well to a range of different culture conditions. The parentage analysis using AFLP of total DNA and SNP of the ITS region of ribosomal RNA transcription unit showed that Dongfang No. 2 is the real hybrid of L. japonica and L. longissima.

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Photocatalysis is intensely employed to remove refractory organic pollutants in water but suffers from low efficiency due to the rapid recombination of photogenerated electrons and holes. Here, carbon-vacancy-modified g-C3N4 (VC-C3N4) is prepared via a handy two-step calcination method and first applied in the photocatalytic removal of bisphenol A (BPA). Compared to pristine g-C3N4, the photocatalytic degradation activity of VC-C3N4 for BPA is largely enhanced, in which the kinetic constant (k) of BPA degradation is 1.65 times that of pristine g-C3N4. The enhanced photocatalytic performance of VC-C3N4 is ascribed to the critical role of carbon vacancies. On the one hand, carbon vacancies serve as the reservoir of photogenerated electrons to inhibit the recombination of photogenerated holes and electrons. On the other hand, carbon vacancies as conversion centers transfer trapped photogenerated electrons to absorbed O2 for the generation of an abundant superoxide radical (•O2 –), which takes a dominant effect in the photocatalytic degradation process.

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