Combination of disulfiram and Copper-Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer.

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu3Cl(SR)2 (R[bond, double bond]CH2CH2NH2), showcases photodynamic effects and demonstrates significant anti-tumor potential under various conditions, including exposure to ultraviolet light, X-ray, microwave, and ultrasound. This study delves into exploring the synergistic anti-tumor effects and underlying mechanisms by utilizing copper-cysteamine in conjunction with DSF against endometrial cancer. The investigation involved comprehensive analyses encompassing in vitro experiments utilizing Ishikawa cells, in vivo studies, and transcriptomic analyses. Remarkably, the combined administration of both compounds at a low dose of 0.5 µM exhibited pronounced efficacy in impeding tumor growth, inhibiting blood vessel formation, and stimulating cell apoptosis. Notably, experiments involving transplanted tumors in nude mice vividly demonstrated the significant in vivo anti-tumor effects of this combination treatment. Detailed examination through transmission electron microscopy unveiled compelling evidence of mitochondrial damage, cellular swelling, and rupture, indicative of apoptotic changes in morphology due to the combined treatment. Moreover, transcriptomic analysis unveiled substantial downregulation of mitochondrial-related genes at the molecular level, coupled with a significant hindrance in the DNA repair pathway. These findings strongly suggest that the combined application of CuCy and DSF induces mitochondrial impairment in Ishikawa cells, thereby fostering apoptosis and ultimately yielding potent anti-tumor effects.

Complete mitogenomes and phylogenetic relationships of Haemaphysalis nepalensis and Haemaphysalis yeni.

The mitochondrial genome may include crucial data for understanding phylogenetic and molecular evolution. We sequenced the complete mitogenome of Haemaphysalis nepalensis and Haemaphysalis yeni for the first time. H. nepalensis and H. yeni's complete mitogenomes were 14,720 and 14,895 bp in size, respectively, and both contained two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes (PCG). Haemaphysalis nepalensis have one control region (D-loop). The adenine + thymine concentration of the genomes of H. nepalensis and H. yeni was 77.75 and 78.41%, respectively. The codon use pattern and amino acid content of proteins were both observed to be affected by the AT bias. Genes in the mitogenome were organized and located in a comparable manner to previously known genes from Haemaphysalis ticks. Mitochondrial PCGs were used to perform phylogenetic relationships based on the Minimum Evolution (ME) approach using MEGA 7.0 software, the results reveal that H. nepalensis has tight links with H. tibetensis, H. yeni and H. kolonini share a sister group relationship, and that H. nepalensis and H. yeni belong to Haemaphysalis. The results of this study include the following: (i) discovered and supplied new tick records (H. nepalensis) for China, (ii) provided the first complete mitochondrial genome for H. nepalensis and H. yeni and revealed their phylogenetic relationships, and (iii) the features of the mitochondrial genome of H. nepalensis and H. yeni provided more genetic reference for Phylogeography, systematics, and population genetics of the Haemaphysalis species.

Complete mitochondrial genome and phylogenetic analysis of Ixodes acutitarsus (Acari: Ixodidae).

Ixodes acutitarsus is regarded as the largest Ixodes tick around the world. I. acutitarsus is capable to transmit a wide range of animal and human pathogens. This research pioneered sequencing of the complete mitochondrial genome of I. acutitarsus. With a length of 14,475 bp, the complete mitochondrial genome encodes 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and one replication-initiating region. The phylogenetic relationship was established using the Maximum-likelihood method to indicate that I. acutitarsus and the others of the genus Ixodes fit into the same branch, which confirms the inclusion of I. acutitarsus in the genus Ixodes. The complete mitogenome of sequenced I. acutitarsus provides molecular evidence for the taxonomic status and phylogenetic position of several Ixodes species.

Multi-Omics Profiling to Assess Signaling Changes upon VHL Restoration and Identify Putative VHL Substrates in Clear Cell Renal Cell Carcinoma Cell Lines.

The inactivation of von Hippel-Lindau (VHL) is critical for clear cell renal cell carcinoma (ccRCC) and VHL syndrome. VHL loss leads to the stabilization of hypoxia-inducible factor α (HIFα) and other substrate proteins, which, together, drive various tumor-promoting pathways. There is inadequate molecular characterization of VHL restoration in VHL-defective ccRCC cells. The identities of HIF-independent VHL substrates remain elusive. We reinstalled VHL expression in 786-O and performed transcriptome, proteome and ubiquitome profiling to assess the molecular impact. The transcriptome and proteome analysis revealed that VHL restoration caused the downregulation of hypoxia signaling, glycolysis, E2F targets, and mTORC1 signaling, and the upregulation of fatty acid metabolism. Proteome and ubiquitome co-analysis, together with the ccRCC CPTAC data, enlisted 57 proteins that were ubiquitinated and downregulated by VHL restoration and upregulated in human ccRCC. Among them, we confirmed the reduction of TGFBI (ubiquitinated at K676) and NFKB2 (ubiquitinated at K72 and K741) by VHL re-expression in 786-O. Immunoprecipitation assay showed the physical interaction between VHL and NFKB2. K72 of NFKB2 affected NFKB2 stability in a VHL-dependent manner. Taken together, our study generates a comprehensive molecular catalog of a VHL-restored 786-O model and provides a list of putative VHL-dependent ubiquitination substrates, including TGFBI and NFKB2, for future investigation.

The Discontinuous Elevational Distribution of an Ungulate at the Regional Scale: Implications for Speciation and Conservation.

The elevational range where montane species live is a key factor of spatial niche partitioning, because the limits of such ranges are influenced by interspecies interaction, abiotic stress, and dispersal barriers. At the regional scale, unimodal distributions of single species along the elevation gradient have often been reported, while discontinuous patterns, such as bimodal distributions, and potential ecological implications have been rarely discussed. Here, we used extensive camera trap records to reveal the elevation distribution of Himalaya blue sheep (Pseudois nayaur) and its co-existence with other ground animal communities along a slope of Baima Snow Mountain, southwest China. The results show that Himalaya blue sheep exhibited a distinctive bimodal distribution along the elevation gradient contrasting the unimodal distributions found for the other ungulates in Baima snow mountain. A first distributional peak was represented by a population habituating in scree habitat around 4100 m, and a second peak was found in the dry-hot valley around 2600 m. The two distinct populations co-existed with disparate animal communities and these assemblages were similar both in the dry and rainy seasons. The extremely low abundance of blue sheep observed in the densely forested belt at mid-elevation indicates that vegetation rather than temperature is responsible for such segregation. The low-elevation population relied highly on Opuntia ficus-indica, an invasive cactus species that colonized the region six hundred years ago, as food resource. Being the only animal that developed a strategy to feed on this spiky plant, we suggest invasive species may have formed new foraging niche to support blue sheep population in lower elevation hot-dry river valleys, resulting in the geographic separation from the original population and a potential morphological differentiation, as recorded. These findings emphasize the important conservation values of role of ecological functions to identify different taxa, and conservation values of apparent similar species of different ecological functions.

The ecological niche and terrestrial environment jointly influence the altitudinal pattern of aquatic biodiversity.

The altitudinal distribution of biodiversity in alpine ecosystems has captured academic attention, especially in streams because of their sensitivity to climate change. In the past years, research mainly focused on understanding the role played by alpine streams' internal factors such as aquatic environmental variables, as well as physical and hydrological conditions, on the shaping of benthic macroinvertebrate communities. More recently, external factors such as terrestrial environments were included in analyses worldwide. In particular, the inherent properties constituting the ecological niche of specific species were considered as factors regulating dispersal and influencing community construction. The objective of this study was to reveal the distribution pattern and the driving factors regulating aquatic biodiversity in alpine streams. We hypothesized that the altitudinal distribution of aquatic macroinvertebrates could be explained by the interaction of the aquatic environment with both species' ecological niche and the terrestrial environment surrounding their habitat, and that rare species display a more pronounced pattern than widespread dominant species. To test these hypotheses, samples were collected from two alpine streams situated on opposite slopes of Biluo Snow Mountain in Yunnan Province, China. Results of statistical analyses showed poor explanatory power from aquatic environmental factors, while the differences in vegetation type and the ecological niche of the species played an important role in determining the distribution pattern of aquatic biodiversity. Furthermore, we found that the altitudinal distribution pattern of aquatic biodiversity exhibits a bimodal type, with rare species fitting the bimodal peaks. These findings call for a better inclusion and further investigation on the effects of the terrestrial environment on aquatic ecosystems.

Comparative Transcriptome Analysis Reveals the Mechanism Related to Fluazinam Stress of Panonychus citri (Acarina: Tetranychidae).

The use of a large number of chemical acaricides to control these pest mites has led to an increasing problem of pesticide resistance, which has always been the difficulty in integrated pest management (IPM). Fluazinam has a good control effect on Panonychus citri, the serious pest on citrus; however, we only know the mechanism of action of fluazinam as a fungicide and its mechanism of action on mites remains unclear. Through analysis using Illumina high-throughput transcriptomic sequencing and differential expression genes in P. citri treated with fluazinam, 59 cytochrome P450 genes, 23 glutathione s-transferase genes, five carboxylate esterase genes, 11 superoxide dismutase genes and 15 catalase genes were identified. The Gene Ontology enrichment and the enrichment of KEGG results showed that the treatment were enrichment for redox enzyme pathways. Evaluating the efficacy of fluazinam, and analyzing the transcriptome data of P. citri under fluazinam stress, potentially provide a new agent for prevention and control of P. citri, and also preliminary research results for exploring the mechanism of action of fluazinam on P. citri. Given the up-regulated expression levels of genes for Mn-superoxide dismutase and catalase, we speculate that they play an important role in fluazinam-stress action on P. citri.

Sampling methods affect Nematode-Trapping Fungi biodiversity patterns across an elevational gradient.

BACKGROUND: Understanding the patterns of species richness across elevational gradients is a key concept for contemporary research in ecology and evolution, and critical to understanding large-scale trends in biodiversity, global change and conservation. However, patterns of elevational species richness between taxonomic groups, regions and latitudes are inconsistent, so that various, sometimes conflicting hypotheses exist. Several scholars have pointed out that research on elevational distribution patterns is often biased by the sampling design employed. To test this hypothesis, we analyzed species richness of Nematode-Trapping Fungi (NTF) across an elevation gradient at two mountainous sites in western Yunnan Province, P.R. China. We tested for potential differences in the results when using different sampling designs. RESULTS: A total of 3 genera, 17 species, 222 strains of NTF were isolated and identified from Gaoligongshan and Cangshan. Species accumulation curves for both sites and sampling modes had acceptable leveling, demonstrating sufficient sampling effort. At Gaoligongshan, the elevation distribution patterns of NTF were different under two sampling patterns. When reducing the analyzed altitude range in Gaoligongshan, the elevation distribution pattern of the NTF changed. A similar elevation distribution pattern was observed in Cangshan when testing the same altitude range. In general, when treating the same dataset using different sampling designs, the resulting distribution patterns of species richness and occurrence frequencies were clearly different. Moreover, after removal of the samples located within lower-altitude zones affected by anthropogenic interferences, the distribution pattern of NTF in the two sites tended to become uniform. CONCLUSION: The sampling design, and in particular the elevation interval between plots, has a significant effect on the assessment of species distribution in mountainous regions. Other factors such as human activities and the multi-dimensionality of biodiversity also contribute to result biases. It is recommended that sampling design is given careful consideration in future studies on the elevational gradients of species richness, using stratified approaches according to the most relevant factors.

The effective use of camera traps to document the northernmost distribution of the western black crested gibbon in China.

Gibbons represent a highly successful radiation of four genera and 20 species of Asian apes that, in response to recent habitat fragmentation and deforestation, are threatened with extinction. China has six species of gibbons, each of which is critically endangered. We present new biogeographical information on the distribution of the black crested gibbon (Nomascus concolor). Four subspecies of N. concolor have been described: three of them are present east of the Mekong River (Nomascus concolor jingdongensis, N. c. concolor and N. c. lu); and another is found west of the Mekong River (N. c. furvogaster). In addition, there has been speculation that gibbons exist in the Biluo Snow Mountains, between the Mekong and Salween basins. To clarify the biogeography of this species, from April 2011 to January 2012 and from January 2016 to September 2018, we conducted interviews with local villagers, completed line transect surveys, monitored gibbon calls, and placed 30 camera traps in the forest canopy. On October 30, 2016, we recorded gibbon's calls. On July 5, 2016, our camera traps obtained one image of a male gibbon, and on February 1 and 8, 2017, we captured two independent images of an adult female gibbon on Zhiben Mountains. Based on the black crest on the head, clearly visible in the photographs, the gibbons are N. c. furvogaster. Evidence from interviews and survey records indicate that N. c. furvogaster once was present in the Zhiben Mountains, at an altitude of between 2000 and 2700 m. Between 1990 and 2000, some 6-7 groups still existed in Caojian, Laowo and adjacent areas. Unfortunately, in the absence of an effective conservation strategy, the population was extirpated by hunters. The remaining forest in the Zhiben Mountains is highly fragmented, and most of the suitable habitat for gibbons has been lost. Therefore, we expect that this newly found gibbon population is under extreme anthropogenic pressure. It is imperative that further investigations of this gibbon population be conducted immediately, and that the local and national governments implement effective conservation plans, including educating the local communities to protect this critically endangered primate population.

Effects of reflective warning markers on wildlife.

Light pollution has become one of the top issues in environmental pollution, especially concerning how secondary light pollution, such as from traffic reflective materials, influences animal distribution and behavior. In this study, 15 camera traps were set up at sites with or without reflective warning markers (RWM) in coniferous forests on Cangshan Mountain located in Dali Prefecture, China. The results showed that the number of independent photographs and species at sites without RWMs were significantly higher than those at sites with RWMs. Significant differences were found between daytime and nighttime composition of bird species and non-flying mammals between two sites. This study found that RWMs had negative effects on wildlife, with the avoidance response of birds to RWMs being more obvious than that of animals at daytime. It is recommended that the use of reflective materials be carefully considered, especially in protected areas.

The optoelectronic role of chlorine in CH3NH3PbI3(Cl)-based perovskite solar cells.

Perovskite photovoltaics offer a compelling combination of extremely low-cost, ease of processing and high device performance. The optoelectronic properties of the prototypical CH3NH3PbI3 can be further adjusted by introducing other extrinsic ions. Specifically, chlorine incorporation has been shown to affect the morphological development of perovksite films, which results in improved optoelectronic characteristics for high efficiency. However, it requires a deep understanding to the role of extrinsic halide, especially in the absence of unpredictable morphological influence during film growth. Here we report an effective strategy to investigate the role of the extrinsic ion in the context of optoelectronic properties, in which the morphological factors that closely correlate to device performance are mostly decoupled. The chlorine incorporation is found to mainly improve the carrier transport across the heterojunction interfaces, rather than within the perovskite crystals. Further optimization according this protocol leads to solar cells achieving power conversion efficiency of 17.91%.