Nano-energy interference: A novel strategy for blunting tumor adaptation and metastasis.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

LncRNA NKX2-1-AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR-2 signaling pathway in gastric cancer.

Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2-1-AS1 (NKX2-1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2-1-AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2-1-AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT-PCR). Using loss-of-function and gain-of-function experiments, the biological functions of NKX2-1-AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2-1-AS1 regulates angiogenic processes, tube formation and co-culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual-luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2-1-AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2-1-AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2-1-AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2-1-AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual-luciferase assays revealed that the microRNA miR-145-5p is a direct target of NKX2-1-AS1 and that NKX2-1-AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR-145-5p; besides, the NKX2-1-AS1/miR-145-5p axis induces the translation of SERPINE1, thus activating the VEGFR-2 signaling pathway to promote tumor progression and angiogenesis. NKX2-1-AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2-1-AS1 functions as a ceRNA to miR-145-5p and promotes tumor progression and angiogenesis by activating the VEGFR-2 signaling pathway via SERPINE1.

Characterization of a new male sterility-related gene Camf1 in Capsicum annum L.

For the sake of screening novel genes related to the male sterility in chili pepper for studying the molecular mechanism of plant male sterility, the gene differential expression analysis was performed by cDNA-amplified fragment length polymorphism (cDNA-AFLP) in the genic male sterile-fertile line 114AB of Capsicum annum L., and a variety of differentially expressed cDNA fragments were detected in fertile or sterility material. Camf1, a transcript-derived fragment (TDF) accumulated in fertile line flower buds was further investigated. The Camf1 has 1,854 bp in length with no introns containing a 1,707-bp open reading frame (ORF). The deduced amino acid sequence of Camf1 shares higher similarity to some members from a glyoxal oxidase-related protein family, and has a glyoxal oxidase conserved domain at the N-terminus and a domain of unknown function (DUF1929) at C-terminal end. Expression analysis showed that Camf1 expressed only in stage 3-7 flower buds of male fertile of C. annum L. 114AB, and no detection in all organs of male sterility. The peak of expression level of Camf1 appeared at stage 4 flower buds of fertile line. Furthermore, expression analysis of different organs revealed that Camf1 expressed only in anthers of male fertile material and there were no expression in sepals, petals, pistils, roots, stems, leaves and open flowers. These results suggested that Camf1 was an anther-specific gene and might be essential for the fertility of C. annum L.

[Lung protection of continuous pulmonary artery perfusion with oxygenated blood during cardiopulmonary bypass].

OBJECTIVE: To determine the lung protection of continuous pulmonary artery perfusion with oxygenated blood during cardiopulmonary bypass (CPB). METHODS: Thirty patients undergoing mitral valve replacement were randomly divided into the control group (n=15) and the lung perfusion group (n=15). The patients in the lung perfusion group were perfused oxygenated blood continuously to the pulmonary artery during CPB. The patients in the control group were performed the routine procedure of mitral valve replacement. Record the CPB time, aortic cross-clamp time, mechanical ventilation time and ICU monitoring time. The patients' oxygen index (OI) and lung static compliance (Cstat) were measured before the surgery, at 0 h after the CPB and at 0, 6 h after the surgery. Right lung biopsy specimens were obtained at 30 min after the CPB to observe the histological changes. Results The mechanical ventilation time and ICU monitoring time were shorter in the lung perfusion group than those in the control group (P < 0.05). The patients' OI and Cstat were higher after surgery in the lung perfusion group than those in the control group (P < 0.05). Tissue examination showed lung parenchyma edema and inflammatory cells accumulated in the control group, while no remarkable pathological changes occurred in the lung perfusion group. CONCLUSION: Lung injury exists after the surgery by CPB. Continuous pulmonary artery perfusion with oxygenated blood during CPB can decrease the lung injury.

[Development and application of geographic information system of Aedes vector in Chaozhou city, Guangdong province].

OBJECTIVE: To explore the spatial distribution character of dengue fever and the change of Aedes' population, so as to provide macroscopical decision-making evidences of prevention and supervision on dengue fever. METHODS: (1) Collecting data on morbidity of dengue and supervision on vector's population in the corresponding period. (2) Drawing digitized map of Chaozhou in scale of 1:50,000, including elements of boundary, residential areas, road and traffic, altitude, water systems etc. (3) Measuring the latitude and longitude of center position of surveillance safes on the scene. (4) Processing spatial analysis by the ArcGIS 8.5 software. RESULTS: Distribution of Aedes showed spatial cluster in Chaozhou, while its density was related to the distance to the watersides. The closer to the watersides, the higher the density was. Map on spatial distribution showed that although the Aedes epidemic situation changed yearly, but primarily be kept in high, middle, low regions. Cross-validation effects of the distribution maps were satisfactory. CONCLUSION: Geographic information system was promising in analyzing data on dengue fever, and better than other routine research methods.